Bio

Academic Appointments


Honors & Awards


  • Distinguished Career Achievement Award, International Immunocompromised Host Society (ICHS) (2002)
  • Kenneth L. Vosti, M.D., Infectious Diseases Teaching Award, Stanford University School of Medicine (2002)
  • Albion Walter Hewlett Award, Stanford University (2002)
  • Infectious Diseases Divisional Teaching Award, Stanford University Department of Medicine (2002)
  • Fellow, American Academy of Microbiology (2000)
  • Fellow, American Association for the Advancement of Science (2000)
  • Ludwig Heilmeyer Society honorary membership, Ludwig Heilmeyer Society, Cologne, Germany (1998)
  • Bristol Award, Infectious Diseases Society of America (IDSA) (1996)
  • Diplomé de Docteur de L’Université Paul Sabatier de Toulouse DOCTEUR HONORIS CAUSA, l’Université Paul Sabatier, Toulouse, France (1992)
  • Harry A. Feldman Presidential Award, Infectious Diseases Society of America (IDSA) (1987-1988)
  • Alexander von Humboldt Scientific Award, Germany (1988)
  • MERIT Award, National Institutes of Health (1987)
  • James W. McLaughlin, MD Award, University of Texas (1985)
  • Maxwell Finland Award, Infectious Diseases Society of America (IDSA) (1982)
  • Osler Oration and Gold Medal, Royal College of Physicians, London, England (1999)
  • Award/Gold Medal, Dr.-Friedrich-Sasse-Foundation, Berlin, Germany (1999)
  • Fellowship, Royal College of Physicians, London, England (1999)
  • "Achievement in Medicine" Award, Santa Clara County Medical Association (1993)
  • Fellows Award for Clinical Excellence, Stanford University School of Medicine (1973)

Professional Education


  • Board Certif., ID, Amer. Brd. of Internal Med.
  • Fellowship, Harvard Medical School, Infectious Diseases (1962)
  • Resident, UCSF Medical Center, SF, Internal Medicine/ID (1960)
  • MD, Univers. of IL Coll. of Medicine, Internal Medicine (1956)

Research & Scholarship

Current Research and Scholarly Interests


Studies on the diagnosis, epidemiology, clinical features and prevention of toxoplasmosis in the pregnant woman, the fetus and newborn, in eye disease and in the immunocompromised patient.

Teaching

Publications

All Publications


  • Polymerase chain reaction in cerebrospinal fluid for the diagnosis of congenital toxoplasmosis. Pediatric infectious disease journal Olariu, T. R., Remington, J. S., Montoya, J. G. 2014; 33 (6): 566-570

    Abstract

    Congenital toxoplasmosis (CT) can result in visual impairment, hearing loss, serious neurologic sequelae and death in the infant. We studied the potential of the polymerase chain reaction (PCR) in cerebrospinal fluid (CSF) for diagnosis of congenital toxoplasmosis.For this purpose we studied both congenitally infected (diagnosed clinically and serologically) and non-infected infants born to untreated mothers.The infants ranged in age from 0 to 180 days. CSF PCR was positive in 27 of the 58 (46.5%) congenitally infected infants and was negative in each of the 103 infants without CT. The frequency of positive CSF PCR varied according to whether infants had major clinical signs of the disease; PCR was positive in 70.9%, 53.3% and 50.9% of those with hydrocephalus, cerebral calcifications and/or eye disease, respectively. Three of six infants who were negative for both IgM and IgA antibodies had a positive PCR in their CSF as the confirmatory test for diagnosis of congenital toxoplasmosis. IgM and IgA antibodies and CSF PCR, when combined, yielded a higher sensitivity for diagnosis of congenital toxoplasmosis when compared with the performance of each test alone.Our findings reveal that in infants with clinical and serologic findings suggestive of congenital toxoplasmosis and born to untreated mothers, CSF PCR has the potential to increase the frequency of cases in which the diagnosis is confirmed.

    View details for DOI 10.1097/INF.0000000000000256

    View details for PubMedID 24445828

  • Severe Congenital Toxoplasmosis in the United States Clinical and Serologic Findings in Untreated Infants PEDIATRIC INFECTIOUS DISEASE JOURNAL Olariu, T. R., Remington, J. S., McLeod, R., Alam, A., Montoya, J. G. 2011; 30 (12): 1056-1061

    Abstract

    Congenital toxoplasmosis can cause significant neurologic manifestations and other untoward sequelae.The Palo Alto Medical Foundation Toxoplasma Serology Laboratory database was searched for data on infants 0 to 180 days old, in whom congenital toxoplasmosis had been confirmed and who had been tested for Toxoplasma gondii-specific immunoglobulin G (IgG), IgM, and IgA antibodies, between 1991 and 2005. Their clinical findings were confirmed at the National Collaborative Chicago-based Congenital Toxoplasmosis Study center. We reviewed available clinical data and laboratory profiles of 164 infants with congenital toxoplasmosis whose mothers had not been treated for the parasite during gestation.One or more severe clinical manifestations of congenital toxoplasmosis were reported in 84% of the infants and included eye disease (92.2%), brain calcifications (79.6%), and hydrocephalus (67.7%). In 61.6% of the infants, eye disease, brain calcifications, and hydrocephalus were present concurrently. T. gondii-specific IgM, IgA, and IgE antibodies were demonstrable in 86.6%, 77.4%, and 40.2% of the infants, respectively. Testing for IgM and IgA antibodies increased the sensitivity of making the diagnosis of congenital toxoplasmosis to 93% compared with testing for IgM or IgA individually. IgM and IgA antibodies were still present in 43.9% of infants diagnosed between 1 and 6 months of life.Our study reveals that severe clinical signs of congenital toxoplasmosis including hydrocephalus, eye disease, or intracranial calcifications occurred in 85% infants whose sera were referred to our reference Toxoplasma Serology Laboratory during a period of 15 years. Laboratory tests, including serologic and polymerase chain reaction tests, were critical for diagnosis in the infants. Our results contrast remarkably with those of European investigators who rarely observe severe clinical signs in infants with congenital toxoplasmosis.

    View details for DOI 10.1097/INF.0b013e3182343096

    View details for Web of Science ID 000297406100012

    View details for PubMedID 21956696

  • Risk Factors for Toxoplasma gondii Infection in the United States CLINICAL INFECTIOUS DISEASES Jones, J. L., Dargelas, V., Roberts, J., Press, C., Remington, J. S., Montoya, J. G. 2009; 49 (6): 878-884

    Abstract

    Toxoplasmosis can cause severe ocular and neurological disease. We sought to determine risk factors for Toxoplasma gondii infection in the United States.We conducted a case-control study of adults recently infected with T. gondii. Case patients were selected from the Palo Alto Medical Foundation Toxoplasma Serology Laboratory from August 2002 through May 2007; control patients were randomly selected from among T. gondii-seronegative persons. Data were obtained from serological testing and patient questionnaires.We evaluated 148 case patients with recent T. gondii infection and 413 control patients. In multivariate analysis, an elevated risk of recent T. gondii infection was associated with the following factors: eating raw ground beef (adjusted odds ratio [aOR], 6.67; 95% confidence limits [CLs], 2.09, 21.24; attributable risk [AR], 7%); eating rare lamb (aOR, 8.39; 95% CLs, 3.68, 19.16; AR, 20%); eating locally produced cured, dried, or smoked meat (aOR, 1.97; 95% CLs, 1.18, 3.28; AR, 22%); working with meat (aOR, 3.15; 95% CLs, 1.09, 9.10; AR, 5%); drinking unpasteurized goat's milk (aOR, 5.09; 95% CLs, 1.45, 17.80; AR, 4%); and having 3 or more kittens (aOR, 27.89; 95% CLs, 5.72, 135.86; AR, 10%). Eating raw oysters, clams, or mussels (aOR, 2.22; 95% CLs, 1.07, 4.61; AR, 16%) was significant in a separate model among persons asked this question. Subgroup results are also provided for women and for pregnant women.In the United States, exposure to certain raw or undercooked foods and exposure to kittens are risk factors for T. gondii infection. Knowledge of these risk factors will help to target prevention efforts.

    View details for DOI 10.1086/605433

    View details for Web of Science ID 000269145100008

    View details for PubMedID 19663709

  • SOURCES OF TOXOPLASMA GONDII INFECTION IN THE UNITED STATES 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene Jones, J. L., Dargelas, V., Roberts, J., Press, C., Remington, J. S., Montoya, J. G. AMER SOC TROP MED & HYGIENE. 2008: 335–35
  • Longitudinal study of new eye lesions in children with toxoplasmosis who were not treated during the first year of life AMERICAN JOURNAL OF OPHTHALMOLOGY Phan, L., Kasza, K., Jalbrzikowski, J., Noble, A. G., Latkany, P., Kuo, A., Mieler, W., Meyers, S., Rabiah, P., Boyer, K., Swisher, C., Mets, M., Roizen, N., Cezar, S., Sautter, M., Remington, J., Meier, P., McLeod, R. 2008; 146 (3): 375-384

    Abstract

    To determine the incidence of new chorioretinal lesions in children with toxoplasmosis diagnosed after, and therefore not treated during, their first year.Prospective longitudinal cohort study.Thirty-eight children were evaluated in Chicago between 1981 and 2005 for new chorioretinal lesions. Thirty-eight children and mothers had serum IgG antibody to Toxoplasma gondii.Twenty-eight of 38 children had one of the following: diagnosis with serum antibody to T. gondii indicative of chronic infection at age 24 months, central nervous system calcifications, hydrocephalus, illness compatible with congenital toxoplasmosis perinatally but not diagnosed at that time. Twenty-five returned for follow-up during 1981 to 2005. Their mean (range) age at last exam was 10.9 +/- 5.7 (range, 3.5 to 27.2) years and mean follow-up was 5.7 +/- 2.9 years. Eighteen (72%) children developed at least one new lesion. Thirteen (52%) had new central lesions, 11 (44%) had new peripheral lesions, and six (24%) had both. Thirteen (52%) had new lesions diagnosed at age > or =10 years. New lesions were found at more than one visit in four (22%), and bilateral new lesions developed in seven (39%) of 18 children who developed new lesions. Of 10 additional children with eye findings and serologic tests indicative of chronic infection, six returned for follow-up, four (67%) developing new lesions at > or =10 years of age.More than 70% developed new chorioretinal lesions. New lesions were commonly diagnosed after the first decade of life.

    View details for DOI 10.1016/j.ajo.2008.04.033

    View details for Web of Science ID 000258883900010

    View details for PubMedID 18619570

    View details for PubMedCentralID PMC2747816

  • Management of Toxoplasma gondii infection during pregnancy CLINICAL INFECTIOUS DISEASES Montoya, J. G., Remington, J. S. 2008; 47 (4): 554-566

    Abstract

    Acute infection with Toxoplasma gondii during pregnancy and its potentially tragic outcome for the fetus and newborn continue to occur in the United States, as well as worldwide, despite the fact that it can be prevented. The infection can be acquired through ingestion of infected, undercooked meat or contaminated food or water. Transmission to the fetus occurs almost solely in women who acquire their primary infection during gestation and can result in visual and hearing loss, mental and psychomotor retardation, seizures, hematological abnormalities, hepatosplenomegaly, or death. Systematic education and serological screening of pregnant women are the most reliable and currently available strategies for the prevention, diagnosis, and early treatment of the infection in the offspring; this is largely because toxoplasmosis in pregnant women most often goes unrecognized. Treatment of the infection in the fetus and infant during the first year of life has been demonstrated to significantly improve the clinical outcome.

    View details for DOI 10.1086/590149

    View details for Web of Science ID 000257755700023

    View details for PubMedID 18624630

  • Prevalence of infection with Toxoplasma gondii among pregnant women in Cali, Colombia, South America AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE Rosso, F., Les, J. T., Agudelo, A., Villalobos, C., Chaves, J. A., Tunubala, G. A., Messa, A., Remington, J. S., Montoya, J. G. 2008; 78 (3): 504-508

    Abstract

    The aim of this study was to determine the prevalence of toxoplasma antibodies among pregnant women in Cali, Colombia. In 2005, 955 pregnant women were tested for IgG and IgM antibodies and sociodemographic information was collected. Their average age was 25.1 years, overall IgG seroprevalence 45.8% (95% CI: 41.8%, 48.2%), IgM 2.8% (95% CI: 1.5%, 3.6%). Seroprevalence increased significantly with age, 39.0% in 14 to 19 years to 55.3% in 30 to 39 years (P = 0.001). There was a significant trend toward a higher seroprevalence in the lower socioeconomic strata (SES) (low: 49.0%, high: 29%, P = 0.004). The increase in seroprevalence by age was more significant in the lower socioeconomic strata (P = 0.002). Our results suggest a higher prevalence when compared with those of the national 1980 (33-37.6%) survey. In contrast to reports from other regions of the world, Cali has not seen a decrease in T. gondii seroprevalence over the past 25 years.

    View details for Web of Science ID 000253928100027

    View details for PubMedID 18337350

  • Longitudinal study of new eye lesions in treated congenital toxoplasmosis 109th Annual Meeting of the American-Academy-of-Ophthalmology Phan, L., Kasza, K., Jalbrzikowski, J., Noble, A. G., Latkany, P., Kuo, A., Mieler, W., Meyers, S., Rabiah, P., Boyer, K., Swisher, C., Mets, M., Roizen, N., Cezar, S., Remington, J., Meier, P., McLeod, R. ELSEVIER SCIENCE INC. 2008: 553–59

    Abstract

    To determine the incidence of new chorioretinal lesions in patients with congenital toxoplasmosis who were treated throughout their first year of life.Prospective longitudinal observation of a cohort.One hundred thirty-two children were studied as part of the longitudinal observation.One hundred thirty-two children were treated during their first year of life with pyrimethamine, sulfadiazine, and leucovorin. They had eye examinations at prespecified intervals.New chorioretinal lesions on fundus examination and fundus photographs.The mean age (+/- standard deviation) is 10.8+/-5.1 years (range, 0.2-23). One hundred eight children have been evaluated for new chorioretinal lesions. Thirty-four (31%; 95% confidence interval, 23%-41%) of 108 children developed at least one chorioretinal lesion that was previously undetected. These occurred at varying times during their follow-up course. Fifteen children (14%) developed new central lesions, and 27 (25%) had newly detected lesions peripherally. Ten (9%) had more than one occurrence of new lesions developing, and 13 (12%) had new lesions in both eyes. Of those who developed new lesions, 14 children (41%) did so at age 10 or later.New central chorioretinal lesions are uncommon in children with congenital toxoplasmosis who are treated during their first year of life. This finding contrasts markedly with earlier reports in the literature for untreated children or those treated for only 1 month near birth, in whom new lesions were much more prevalent (>/=82%). Our observation that 14 (41%) of the 34 children with new chorioretinal lesions had occurrences when they were 10 years or older indicates that long-term follow-up into the second decade of life is important in assessing the efficacy of treating toxoplasmosis during infancy.

    View details for DOI 10.1016/j.ophtha.2007.06.022

    View details for Web of Science ID 000253798600023

    View details for PubMedID 17825418

  • The differential agglutination test as a diagnostic aid in cases of toxoplasmic lymphadenitis JOURNAL OF CLINICAL MICROBIOLOGY Montoya, J. G., Berry, A., Rosso, F., Remington, J. S. 2007; 45 (5): 1463-1468

    Abstract

    Lymphadenopathy (LN) is the most common clinical manifestation of acute acquired toxoplasma infection in humans. The diagnosis of toxoplasmic lymphadenitis (TL) is established by serological methods and/or lymph node biopsy. In the United States, the differential agglutination (of acetone [AC]-fixed versus that of formalin [HS]-fixed tachyzoites) test (AC/HS test) has primarily been used in assessments of pregnant women as a component of the toxoplasma serological profile to distinguish between recently acquired infections and infections acquired in the distant past. We studied the AC/HS test in patients with TL to define its usefulness in diagnosing individuals presenting with LN and to determine its kinetics after the onset of LN. One hundred nine consecutive patients (158 serum samples) diagnosed serologically and by lymph node biopsy as having TL were studied. Specific patterns in the AC/HS test were noted to be dependent on the time from the clinical onset of LN (COLN). Acute AC/HS patterns were observed for more than 75% of patients who according to their histories had developed their TL within 6 months after COLN. Acute patterns were not observed beyond the 12th month except for a single patient for whom an acute pattern (400/800) persisted to the 13th month after COLN. Equivocal patterns were observed up to 36 months after COLN. Nonacute patterns were observed only for serum samples drawn at least 13 months after COLN. A nonacute pattern in an individual at less than 12 months after COLN should suggest an etiology other than TL. In such cases, investigation for alternative causes, including malignancy, should be instigated.

    View details for DOI 10.1128/JCM.01781-06

    View details for Web of Science ID 000246600300013

    View details for PubMedID 17314220

  • Impact of visual impairment on measures of cognitive function for children with congenital toxoplasmosis: implications for compensatory intervention strategies PEDIATRICS Roizen, N., Kasza, K., Karrison, T., Mets, M., Noble, A. G., Boyer, K., Swisher, C., Meier, P., Remington, J., Jalbrzikowski, J., McLeod, R. 2006; 118 (2): E379-E390

    Abstract

    The purpose of this work was to determine whether visual impairment caused by toxoplasmic chorioretinitis is associated with impaired performance of specific tasks on standardized tests of cognitive function. If so, then we worked to determine whether there are patterns in these difficulties that provide a logical basis for development of measures of cognitive function independent of visual impairment and compensatory intervention strategies to facilitate learning for such children.Sixty-four children with congenital toxoplasmosis with intelligence quotient scores > or = 50 and visual acuity sufficient to cooperate with all of the intelligence quotient subscales had assessments of their vision, appearance of their retinas, and cognitive testing performed between 3.5 and 5 years of age. These evaluations took place between 1981 and 1998 as part of a longitudinal study to determine outcome of congenital toxoplasmosis. Children were evaluated at 3.5 or 5 (37 children) or both 3.5 and 5 (27 children) years of age. Cognitive function was measured using the Wechsler Preschool and Primary Scale of Intelligence-Revised. Wechsler Preschool and Primary Scale of Intelligence-Revised scale scores were compared for children grouped as those children who had normal visual acuity in their best eye (group 1), and those who had impaired vision in their best eye (acuity < 20/40) because of macular disease (group 2). Demographic characteristics were compared for children in the 2 groups. Test scores were compared between groups using all of the 3.5-year-old visits, all of the 5-year-old visits, and using each child's "last" visit (ie, using the 5-year-old test results when a child was tested at both 3.5 and 5 years of age or only at 5 years, otherwise using the 3.5-year-old test results). The results were similar and, therefore, only the results from the last analysis are reported here.There were 48 children with normal visual acuity in their best eye (group 1) and 16 children with impaired vision because of macular involvement in their best eye (group 2). Ethnicity and socioeconomic scores were similar. There was a significantly greater proportion of males in group 2 compared with group 1 (81% vs 46%). There was no significant diminution in Wechsler Preschool and Primary Scale of Intelligence-Revised test scores between 3.5 and 5 years of age for the 27 children tested at both of these ages. Verbal intelligence quotient, performance intelligence quotient, full-scale intelligence quotient scores, and all of the scaled scores except arithmetic and block design were significantly lower for children in group 2 compared with group 1. The majority of the differences remained statistically significant or borderline significant after adjusting for gender. However, the difference in overall verbal scores does not remain statistically significant. Mean +/- SD verbal (98 +/- 20) and performance (95 +/- 17) intelligence quotients were not significantly different for children in group 1. However, verbal (88 +/- 13) and performance intelligence quotients (78 +/- 17) were significantly different for children in group 2. For children in group 2, their lowest scale scores were in object assembly, geometric design, mazes, and picture completion, all timed tests that involved visual discrimination of linear forms with small intersecting lines. In the 2 scales scored that did not differ between groups 1 and 2, arithmetic and block design, timing and vision but not linear forms were components of the tasks. Children with monocular and binocular normal visual acuity did not differ in verbal, performance, or full-scale intelligence quotients or any of the subscale tests. Difficulty with sight or concomitant neurologic involvement also seemed to impact the ability to acquire information, comprehension skills, and vocabulary and performance in similarities testing. After controlling for gender, however, these differences were diminished, and there were no longer differences in overall verbal scores. As noted above, results were generally similar when all of the tests for 3.5-year-olds or 5-year-olds were analyzed separately. At the 3.5-year visit there were fewer significant differences between the 2 groups for the verbal components than at the 5-year visit.In children with congenital toxoplasmosis and bilateral macular disease (group 2) because of toxoplasmic chorioretinitis, scaled scores were lowest on timed tests that require discrimination of fine intersecting lines. Although the severity of ocular and neurologic involvement is often congruent in children with congenital toxoplasmosis, ophthalmologic involvement seems to account for certain specific limitations on tests of cognitive function. Children with such visual impairment compensate with higher verbal skills, but their verbal scores are still less than those of children with normal vision, and in some cases significantly so, indicating that vision impairment might affect other aspects of cognitive testing. Patterns of difficulties noted in the subscales indicate that certain compensatory intervention strategies to facilitate learning and performance may be particularly helpful for children with these impairments. These patterns also provide a basis for the development of measures of cognitive function independent of visual impairment.

    View details for DOI 10.1542/peds.2005-1530

    View details for Web of Science ID 000239440600095

    View details for PubMedID 16864640

  • Outcome of treatment for congenital toxoplasmosis, 1981-2004: The national collaborative Chicago-based, congenital toxoplasmosis study CLINICAL INFECTIOUS DISEASES McLeod, R., Boyer, K., Karrison, T., Kasza, K., Swisher, C., Roizen, N., Jalbrzikowski, J., Remington, J., Heydemann, P., Noble, A. G., Mets, M., Holfels, E., Withers, S., Latkany, P., MEIER, P. 2006; 42 (10): 1383-1394

    Abstract

    Without treatment, congenital toxoplasmosis has recurrent, recrudescent, adverse outcomes. Long-term follow-up of infants with congenital toxoplasmosis treated throughout their first year of life with pyrimethamine and sulfadiazine has not been reported.Between 1981 and 2004, one hundred twenty infants (current mean age +/- standard deviation, 10.5 +/- 4.8 years) with congenital toxoplasmosis were treated with 1 of 2 doses of pyrimethamine plus sulfadiazine; therapy was initiated shortly after birth and continued for 12 months. Children who received treatment were evaluated at birth and at predetermined intervals; the focus of the evaluations was on prespecified end points: motor abnormalities, cognitive outcome, vision impairment, formation of new eye lesions, and hearing loss.Treatment of infants without substantial neurologic disease at birth with pyrimethamine and sulfadiazine for 1 year resulted in normal cognitive, neurologic, and auditory outcomes for all patients. Treatment of infants who had moderate or severe neurologic disease (as defined in this article in the Treatments subsection of Methods) at birth resulted in normal neurologic and/or cognitive outcomes for >72% of the patients, and none had sensorineural hearing loss. Ninety-one percent of children without substantial neurologic disease and 64% of those with moderate or severe neurologic disease at birth did not develop new eye lesions. Almost all of these outcomes are markedly better than outcomes reported for children who were untreated or treated for 1 month in earlier decades (P<.01 to P<.001). Sex and severity of disease were comparable in our 2 treatment groups, and no significant differences in efficacy or toxicity were noted between the 2 treatment groups (P > .05).Although not all children did well with treatment, the favorable outcomes we noted indicate the importance of diagnosis and treatment of infants with congenital toxoplasmosis.

    View details for Web of Science ID 000237247400006

    View details for PubMedID 16619149

  • Serotyping of Toxoplasma gondii strains infecting pregnant women in the United States 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine Colon, I., Ramirez, R., Grigg, M., Montoya, J., Remington, J. MOSBY-ELSEVIER. 2005: S187–S187
  • Use of a single serum sample for diagnosis of acute toxoplasmosis in pregnant women and other adults JOURNAL OF CLINICAL MICROBIOLOGY Press, C., Montoya, J. G., Remington, J. S. 2005; 43 (7): 3481-3483

    Abstract

    Using a single serum sample for testing for immunoglobulin G (IgG) Toxoplasma antibodies, differences in sensitivity of the dye test (which measures primarily IgG antibodies) and an IgG enzyme immunoassay were found useful for very early diagnosis of acute Toxoplasma gondii infection.

    View details for DOI 10.1128/JCM.43.7.3481-3483.2005

    View details for Web of Science ID 000230614900075

    View details for PubMedID 16000484

  • Risk factors for Toxoplasma gondii infection in mothers of infants with congenital toxoplasmosis: Implications for prenatal management and screening AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Boyer, K. M., Holfels, M., Roizen, N., Swisher, C., Mack, D., Remington, J., Withers, S., MEIER, P., McLeod, R. 2005; 192 (2): 564-571

    Abstract

    The purpose of this study was to determine whether demographic characteristics, history of exposure to recognized transmission vehicles, or illness that was compatible with acute toxoplasmosis during gestation identified most mothers of infants with congenital toxoplasmosis.Mothers of 131 infants and children who were referred to a national study of treatment for congenital toxoplasmosis were characterized demographically and questioned concerning exposure to recognized risk factors or illness.No broad demographic features identified populations that were at risk. Only 48% of mothers recognized epidemiologic risk factors (direct or indirect exposure to raw/undercooked meat or to cat excrement) or gestational illnesses that were compatible with acute acquired toxoplasmosis during pregnancy.Maternal risk factors or compatible illnesses were recognized in retrospect by fewer than one half of North American mothers of infants with toxoplasmosis. Educational programs might have prevented acquisition of Toxoplasma gondii by those mothers who had clear exposure risks. However, only systematic serologic screening of all pregnant women at prenatal visits or of all newborn infants at birth would prevent or detect a higher proportion of these congenital infections.

    View details for DOI 10.1016/j.ajog.2004.07.031

    View details for Web of Science ID 000226989000040

    View details for PubMedID 15696004

  • Evaluation of the immunoglobulin G avidity test for diagnosis of toxoplasmic lymphadenopathy JOURNAL OF CLINICAL MICROBIOLOGY Montoya, J. G., Huffman, H. B., Remington, J. S. 2004; 42 (10): 4627-4631

    Abstract

    Toxoplasmic lymphadenopathy (TL) is the most common clinical manifestation of acute acquired toxoplasma infection in normal individuals. The diagnosis is established by serologic methods and lymph node biopsy. Recently, tests for avidity of toxoplasma immunoglobulin G (IgG) antibodies have been introduced to help discriminate between recently acquired and distant infection with the parasite. We studied an avidity test to define the usefulness of this method and to determine the evolution of the IgG avidity in TL. Seventy-three consecutive patients diagnosed as having TL were studied. IgG avidity test titers were noted to be time dependent from the clinical onset of lymphadenopathy. Low IgG avidity test results were observed in patients who had developed lymphadenopathy from <1 month to 17 months prior to the sampling of sera, emphasizing that low IgG avidity test results are not reliable for diagnosis of recently acquired infection. In contrast, high IgG avidity test results were observed only in patients who had developed lymphadenopathy at least 4 months earlier. Thus, a high IgG avidity test result in an individual who has recent onset of lymphadenopathy (e.g., within 2 to 3 months of sera sampling) suggests a cause other than toxoplasmosis. In such cases, further workup is warranted in order to determine the cause of the lymphadenopathy.

    View details for DOI 10.1128/JCM.42.10.4627-4631.2004

    View details for Web of Science ID 000224473000033

    View details for PubMedID 15472320

  • Management of community-acquired respiratory tract infections CLINICAL INFECTIOUS DISEASES Remington, J. S. 2004; 39: S141-S141

    View details for Web of Science ID 000223367700001

    View details for PubMedID 15546108

  • Recent developments for diagnosis of toxoplasmosis JOURNAL OF CLINICAL MICROBIOLOGY Remington, J. S., Thulliez, P., Montoya, J. G. 2004; 42 (3): 941-945
  • Gemifloxacin inhibits cytokine secretion by lipopolysaccharide stimulated human monocytes at the post-transcriptional level CLINICAL MICROBIOLOGY AND INFECTION Araujo, F., Slifer, T., Li, S., Kuver, A., Fong, L., Remington, J. 2004; 10 (3): 213-219

    Abstract

    The fluroquinolone gemifloxacin was examined for its capacity to modulate secretion of cytokines by human monocytes stimulated with lipopolysaccharide (LPS). Monocytes from six male and two female healthy volunteers were stimulated with LPS, exposed to gemifloxacin and the amounts of secreted IL-1 alpha, IL-1 beta, IL-6, IL-10 and TNF-alpha measured at 3, 6 and 24 h. The results revealed that LPS alone increased secretion of each cytokine significantly. Treatment of the LPS-stimulated monocytes with gemifloxacin resulted in a significant inhibition (p < 0.01) of secretion of each of the cytokines from monocytes of the eight volunteers. Nuclear extracts of the human monocyte cell line, THP-1, were used in the electrophoretic mobility shift assay to determine whether gemifloxacin affects nuclear factor-kappa B (NF-kappa B) activation. In addition, RNA from THP-1 cells was used in Northern blots to determine whether inhibition of secretion of IL-1 beta and TNF-alpha by gemifloxacin occurred at the transcription or translation level. Whereas LPS induced a rapid increase in NF-kappa B activation, gemifloxacin alone did not. Gemifloxacin did not affect the kinetics or decrease the extent of activation. Northern blots indicated that the inhibitory activity of gemifloxacin occurred post-transcription. Thus, gemifloxacin may modulate the immune response by altering secretion of cytokines by human monocytes. Although the concentrations of gemifloxacin used were higher than those observed in the serum of human volunteers treated with the dose under clinical development, it should be taken into consideration that concentrations at tissue and intracellular levels may be considerably higher than serum concentrations.

    View details for DOI 10.1111/j.1198-743X.2004.00824.x

    View details for Web of Science ID 000189395800003

    View details for PubMedID 15008941

  • TCR V beta 8(+) T cells prevent development of toxoplasmic encephalitis in BALB/c mice genetically resistant to the disease JOURNAL OF IMMUNOLOGY Kang, H., Liesenfeld, O., Remington, J. S., Claflin, J., Wang, X. S., Suzuki, Y. 2003; 170 (8): 4254-4259

    Abstract

    BALB/c are genetically resistant to development of toxoplasmic encephalitis (TE) when infected with Toxoplasma gondii, whereas CBA/Ca mice are susceptible. We compared TCR Vbeta chain usage in lymphocytes infiltrated into brains between these animals following infection. TCR Vbeta8(+) cells were the most frequent T cell population in brains of infected, resistant BALB/c mice, whereas TCR Vbeta6(+) T cells were more prevalent than Vbeta8(+) T cells in brains of infected, susceptible CBA/Ca mice. Adoptive transfer of Vbeta8(+) immune T cells, obtained from infected BALB/c mice, prevented development of TE and mortality in infected athymic nude mice that lack T cells. In contrast, adoptive transfer of Vbeta6(+) immune T cells did not prevent development of TE or mortality in the nude mice. The protective activity of Vbeta8(+) immune T cells was greater than that of the total Vbeta8(-) population. In addition, Vbeta8(+) immune T cells produced markedly greater amounts of IFN-gamma than did the Vbeta8(-) population after stimulation with tachyzoite lysate Ags in vitro. Thus, Vbeta8(+) T cells appear to play a crucial role in the genetic resistance of BALB/c mice against development of TE.

    View details for Web of Science ID 000182171100040

    View details for PubMedID 12682259

  • Trimethoprim-sulfamethoxazole as toxoplasmosis prophylaxis for heart transplant recipients - Reply CLINICAL INFECTIOUS DISEASES Montoya, J. G., Remington, J. S. 2003; 36 (7): 933-933
  • Inhibition of secretion of interleukin-1 alpha and tumor necrosis factor alpha by the ketolide antibiotic telithromycin ANTIMICROBIAL AGENTS AND CHEMOTHERAPY Araujo, F. G., Slifer, T. L., Remington, J. S. 2002; 46 (10): 3327-3330

    Abstract

    The antibiotic telithromycin was examined for its effect on secretion of interleukin-1alpha (IL-1alpha), IL-1beta, IL-6, IL-10, and tumor necrosis factor alpha (TNF-alpha) by lipopolysaccharide (LPS)-stimulated monocytes of eight human donors. Secretion of each cytokine was significantly increased by LPS alone, whereas treatment with telithromycin significantly inhibited secretion of IL-1alpha and TNF-alpha but not secretion of IL-1beta, IL-6, and IL-10. Telithromycin had immunomodulatory effects as a result of alteration of secretion of IL-1alpha and TNF-alpha by monocytes.

    View details for DOI 10.1128/AAC.46.10.3327-3330.2002

    View details for Web of Science ID 000178150700042

    View details for PubMedID 12234873

    View details for PubMedCentralID PMC128773

  • VIDAS test for avidity of Toxoplasma-specific immunoglobulin G for confirmatory testing of pregnant women JOURNAL OF CLINICAL MICROBIOLOGY Montoya, J. G., Liesenfeld, O., Kinney, S., Press, C., Remington, J. S. 2002; 40 (7): 2504-2508

    Abstract

    Because congenital toxoplasmosis is almost solely the result of maternal infection acquired during gestation, it is critical to determine whether infection during pregnancy has occurred. In the United States, definitive diagnosis of the acute infection and the time of its occurrence have been compromised by a lack of systematic screening and the fact that only a single serum sample is submitted for testing. In studies in Europe, and depending on the method used, the demonstration of high-avidity immunoglobulin G (IgG) toxoplasma antibodies has been shown to exclude infection having occurred in the first 3 to 5 months of pregnancy. We investigated the usefulness of determining the avidity of IgG toxoplasma antibodies with a VIDAS kit (herein referred to as the VIDAS Toxo-IgG avidity kit, the VIDAS kit essentially rules out acute infection having occurred within the 4 prior months) in the setting of a reference serology laboratory in the United States. Sera (132 samples) from 132 women in the first 16 weeks of pregnancy were chosen because at least one test in the toxoplasma serological profile (TSP) suggested or was equivocal for a recently acquired infection. High-avidity antibodies were demonstrated in 75% of 99 sera positive with the IgM enzyme-linked immunosorbent assay (ELISA) and 31.3% of 16 sera with acute TSP results. A significant percentage of sera with equivocal results wtih the IgM ELISA or TSP also had high-avidity test results. Of 39 women for whom treatment with spiramycin had been suggested to attempt to prevent congenital transmission, 19 (48.7%) had high-avidity antibodies. These findings highlight the value of the VIDAS IgG avidity kit when used in combination with the TSP to exclude recent infection, especially when only a single serum sample is available.

    View details for DOI 10.1128/JCM.40.7.2504-2508.2002

    View details for Web of Science ID 000176605800030

    View details for PubMedID 12089270

  • Effect of moxifloxacin on secretion of cytokines by human monocytes stimulated with lipopolysaccharide CLINICAL MICROBIOLOGY AND INFECTION Araujo, F. G., Slifer, T. L., Remington, J. S. 2002; 8 (1): 26-30

    Abstract

    To determine the effect of moxifloxacin on secretion of cytokines by human monocytes stimulated with lipopolysaccharide (LPS) or Pansorbin.Monocytes obtained from 10 healthy volunteer donors were stimulated with LPS or Pansorbin and exposed or not to different concentrations of the fluoroquinolone antibiotic moxifloxacin. At 3, 6 and 24 h, the amounts of interleukin-1alpha (IL-1alpha), IL-1beta, IL-6, IL-10, IL-12 (p70) and tumour necrosis factor-alpha (TNF-alpha) were measured in the supernatants of the monocyte cultures using enzyme-linked immunosorbent assay.Stimulation of human monocytes with either LPS or Pansorbin resulted in a significant increase in secretion of each of the cytokines examined. Treatment of LPS-stimulated monocytes with moxifloxacin significantly inhibited (P < 0.01) secretion of IL-1alpha by monocytes of each of 10 human donors; the secretion of TNF-alpha was significantly inhibited (P < 0.01) in monocytes from six of 10 donors. In general there was a trend towards inhibition of secretion of IL-6, IL-10 and IL-12 (p70), but the inhibitory effect was not statistically significant. Secretion of cytokines by Pansorbin-stimulated monocytes was not significantly inhibited by moxifloxacin.Moxifloxacin has immunomodulatory activity through its capacity to alter the secretion of IL-1alpha and TNF-alpha by human monocytes.

    View details for Web of Science ID 000174688800003

    View details for PubMedID 11906497

  • Diagnostic value of IgG avidity in Toxoplasma infection: Comparison of 3 commercial kits - Reply JOURNAL OF INFECTIOUS DISEASES Liesenfeld, O., Montoya, J. G., Remington, J. S. 2001; 184 (7): 944-946
  • Infectious complications among 620 consecutive heart transplant patients at Stanford University Medical Center 10th International Symposium on Infections in the Immunocompromised Montoya, J. G., Giraldo, L. F., Efron, B., Stinson, E. B., Gamberg, P., Hung, S., Giannetti, N., Miller, J., Remington, J. S. OXFORD UNIV PRESS INC. 2001: 629–40

    Abstract

    A total of 1073 infectious episodes (IEs) that occurred in 620 consecutive heart transplantation patients at Stanford Medical Center between 16 December 1980 and 30 June 1996 were reviewed. Infectious complications were a major cause of morbidity and mortality, second only to rejection as the cause of early deaths and the most common cause of late deaths. Of the IEs, 468 (43.6%) were caused by bacteria, 447 (41.7%) by viruses, 109 (10.2%) by fungi, 43 (4.0%) by Pneumocystis carinii, and 6 (0.6%) by protozoa. The largest number of IEs occurred in the lungs (301 [28.1%]). A significant reduction in the incidence of IEs and a delay in presentation after transplantation were observed; these were most likely related to the introduction of new chemoprophylactic regimens during the study period and prevention of significant disease caused by cytomegalovirus.

    View details for Web of Science ID 000170271200007

    View details for PubMedID 11486285

  • Infectious complications among 620 consecutive heart transplant patients at Stanford University Medical Center 10th International Symposium on Infection in the Immunocompromised Host Montoya, J. G., Giraldo, L. F., Efron, B., Stinson, E. B., Gamberg, P., Hunt, S., Giannetti, N., Miller, J., Remington, J. S. CELL PRESS. 2001: 629–U6
  • Simple and efficient method for measuring anti-toxoplasma immunoglobulin antibodies in human sera using complement-mediated lysis of transgenic tachyzoites expressing beta-galactosidase JOURNAL OF CLINICAL MICROBIOLOGY Dando, C., Gabriel, K. E., Remington, J. S., Parmley, S. F. 2001; 39 (6): 2122-2125

    Abstract

    A simple and efficient method using transgenic Toxoplasma gondii tachyzoites expressing beta-galactosidase was developed for detection of specific antibodies against the parasite in sera of patients. The titers obtained with the new test were similar to those obtained with the Sabin-Feldman dye test run in parallel. Although significant changes in endpoint titers were not observed when sera drawn sequentially at 2- to 3-week intervals were tested with both procedures, apparent differences in antibody affinity were observed with the new test which were not perceptible with the Sabin-Feldman dye test. Like the Sabin-Feldman dye test, the new test is based on complement lysis of tachyzoites, but it is much easier to perform and the reaction is read colorimetrically instead of visually.

    View details for Web of Science ID 000169097100014

    View details for PubMedID 11376045

  • Animal models for Toxoplasma gondii infection. Current protocols in immunology / edited by John E. Coligan ... [et al.] Subauste, C., Remington, J. 2001; Chapter 19: Unit 19 3-?

    Abstract

    Toxoplasma gondii is an obligate intracellular protozoan that commonly infects mammals and birds throughout the world. This unit describes murine models of acute T. gondii infection and toxoplasmic encephalitis. T. gondii infection in severe combined immunodeficient (SCID) mice, which lack T and B cells, has allowed for the study of T cell-independent mechanisms of defense against intracellular organisms, as described here. The establishment of temperature-sensitive mutant strains of T. gondii has allowed adoptive-transfer experiments without the concern for the transfer of the parasite at the same time. The temperature-sensitive mutant ts-4 strain disappears from tissues of immunocompetent mice without forming tissue cysts and induces protection against challenge with virulent strains of the parasite, and a protocol is provided for infection with this mutant strain. Support protocols present methodology for evaluation of progression of infection and immune response to the parasite, maintenance of T. gondii tissue cysts and tachyzoites, as well as preparation of T. gondii lysate antigens.

    View details for DOI 10.1002/0471142735.im1903s28

    View details for PubMedID 18432754

  • Effect of testing for IgG avidity in the diagnosis of Toxoplasma gondii infection in pregnant women: Experience in a US reference laboratory JOURNAL OF INFECTIOUS DISEASES Liesenfeld, O., Montoya, J. G., Kinney, S., Press, C., Remington, J. S. 2001; 183 (8): 1248-1253

    Abstract

    The usefulness of testing for IgG avidity in association with Toxoplasma gondii was evaluated in a US reference laboratory. European investigators have reported that high-avidity IgG toxoplasma antibodies exclude acute infection in the preceding 3 months. In this US study, 125 serum samples taken from 125 pregnant women in the first trimester were chosen retrospectively, because either the IgM or differential agglutination (AC/HS) test in the Toxoplasma serologic profile suggested or was equivocal for a recently acquired infection. Of 93 (74.4%) serum samples with either positive or equivocal results in the IgM ELISA, 52 (55.9%) had high-avidity antibodies, which suggests that the infection probably was acquired before gestation. Of 87 (69.6%) serum samples with an acute or equivocal result in the AC/HS test, 35 (40.2%) had high-avidity antibodies. Forty women were given spiramycin, to prevent congenital transmission, and 7 (17.5%) had high-avidity antibodies. These findings highlight the value of testing a single serum sample obtained in the first trimester of pregnancy for IgG avidity.

    View details for Web of Science ID 000167674600010

    View details for PubMedID 11262207

  • Confirmatory serologic testing for acute toxoplasmosis and rate of induced abortions among women reported to have positive Toxoplasma immunoglobulin M antibody titers 35th Annual Meeting of the Infectious-Diseases-Society-of-America Liesenfeld, O., Montoya, J. G., Tathineni, N. J., Davis, M., Brown, B. W., Cobb, K. L., Parsonnet, J., Remington, J. S. MOSBY-ELSEVIER. 2001: 140–45

    Abstract

    Results obtained with commercial testing kits for immunoglobulin M Toxoplasma antibodies may be inaccurate or may be inaccurately interpreted, which may influence whether a woman decides to terminate the pregnancy. This study was undertaken to determine whether confirmatory testing at a reference laboratory and communication of the results and an expert interpretation to the patient's physician would affect the rate of induced abortions among pregnant women with positive results of testing for immunoglobulin M Toxoplasma antibodies in outside laboratories.This was a retrospective cohort study of 811 consecutive pregnant women for whom the toxoplasma serologic profile was performed at a reference laboratory. Almost all the patients had been informed by their physicians that a result of a test for immunoglobulin M Toxoplasma antibodies performed in an outside laboratory was positive. Women were separated into those with a toxoplasma serologic profile result suggestive of a recently acquired infection (group 1) and those with a result suggestive of an infection acquired in the more distant past (group 2). Physician reports of induced abortions were used to determine rates of induced abortion in groups 1 and 2.Of the 811 women 321 (39.6%) were considered likely to have a recent infection (group 1) and 490 (60.4%) were considered likely to have a past infection (group 2). Physicians reported pregnancy outcomes for 433 (53.4%) of 811 women (65.1% and 45.7% in groups 1 and 2, respectively). Whereas 36 of 209 women in group 1 (17.2%) terminated the pregnancy, only 1 of 224 women in group 2 (0.4%) chose abortion (P <.001).Confirmatory serologic testing in a reference laboratory and communication of the results and their correct interpretation by an expert to the patient's physician decreased the rate of unnecessary abortions by approximately 50% among women for whom positive immunoglobulin M Toxoplasma test results had been reported by outside laboratories.

    View details for Web of Science ID 000166679700023

    View details for PubMedID 11174493

  • Activity of gatifloxacin alone or in combination with pyrimethamine or gamma interferon against Toxoplasma gondii ANTIMICROBIAL AGENTS AND CHEMOTHERAPY Khan, A. A., Slifer, T. R., Araujo, F. G., Remington, J. S. 2001; 45 (1): 48-51

    Abstract

    The activity of gatifloxacin against Toxoplasma gondii, either alone or in combination with pyrimethamine or gamma interferon (IFN-gamma), was examined in vitro and in vivo. In vitro, gatifloxacin significantly inhibited intracellular replication of tachyzoites of the RH strain with a 50% inhibitory concentration of 0.21 microg/ml at 48 h after addition of the drug to the cultures. Toxicity for host cells was not observed at this concentration. A synergistic effect (combination indices < 0.5) was demonstrated in vitro following 48 h of treatment with the combination of gatifloxacin and pyrimethamine (1:1 ratio). Doses of gatifloxacin of 100 and 200 mg/kg of body weight/day administered orally to mice for 10 days resulted in significant (P values of 0.056 and <0.0001, respectively) prolongation in time to death following infection with a lethal inoculum of tachyzoites. A dose of 400 mg/kg resulted in 20% survival (P = 0.0001). Mortality was 100% in untreated control mice and in mice treated with 25 or 50 mg/kg/day. Treatment of infected mice with a combination of gatifloxacin at 200 mg/kg/day and pyrimethamine at 12.5 mg/kg/day resulted in 85% survival, whereas 100 and 80% of mice treated with gatifloxacin alone or pyrimethamine alone, respectively, died (P < 0.0001). Moreover, a gatifloxacin dose of 200 mg/kg/day administered orally for 10 days plus 2 microg of recombinant murine IFN-gamma/day administered intraperitoneally for 10 days resulted in significant survival compared with IFN-gamma alone (P < 0.0001) or gatifloxacin alone (P < 0.007).

    View details for Web of Science ID 000165952500007

    View details for PubMedID 11120943

    View details for PubMedCentralID PMC90238

  • Human peripheral blood lymphocyte severe combined immunodeficiency (hu-PBL SCID) models of toxoplasmosis IMMUNOLOGY AND CELL BIOLOGY Beaman, M. H., Remington, J. S., Meyer, D. J. 2000; 78 (6): 608-615

    Abstract

    Toxoplasmosis is a potentially fatal opportunistic infection of immunocompromised hosts. Improved animal models of toxoplasmosis are needed to more nearly approximate conditions that occur in immunocompromised humans. The development of models of toxoplasmosis using human peripheral blood lymphocytes (hu-PBL) transplanted into severe combined immunodeficiency (SCID) mice is described here. Transplantation of hu-PBL into SCID mice without prior conditioning of the mice resulted in detectable differences in quantitative histological scores of brain inflammation due to Toxoplasma gondii infection, but did not alter mortality when compared to SCID mouse controls. The lack of detectable differences in survival were due to inadequate engraftment of hu-PBL, as assessed by flow cytometry. Unconditioned hu-PBL SCID mice had low titre T. gondii-specific antibody detectable after infection. When pretransplantation conditioning with irradiation and antiasialo GM 1 (n-glucolyl neuraminic acid) antibody was used, prolonged hu-PBL engraftment was observed in SCID mice, which was associated with worsened histopathology and usually impaired survival when compared with SCID mouse controls. When pretransplantation conditioning with irradiation, antiasialo GM antibody and polyethylene glycol-conjugated IL-2 was used, prolonged hu-PBL engraftment was also documented, but this did not affect survival from T. gondii infection when compared with similarly conditioned SCID mouse controls. The latter conditioning protocol resulted in hu-PBL SCID mice producing high titre T. gondii-specific antibody after infection. Conditioned hu-PBL SCID mice had evidence of increased T. gondii-induced inflammatory scores when compared with conditioned SCID mice. These models show promise for the study of the pathogenesis of toxoplasmosis and conditioned hu-PBL SCID mice may have applications for the evaluation of novel therapies for toxoplasmosis in immunocompromised humans.

    View details for Web of Science ID 000165662800006

    View details for PubMedID 11114971

  • Detection of immunoglobulin m antibodies to p35 antigen of Toxoplasma gondii for serodiagnosis of recently acquired infection in pregnant women JOURNAL OF CLINICAL MICROBIOLOGY Suzuki, Y., Ramirez, R., Press, C., Li, S. L., Parmley, S., Thulliez, P., Remington, J. S. 2000; 38 (11): 3967-3970

    Abstract

    We examined the efficiency of detection of immunoglobulin M (IgM) antibodies to a 35-kDa antigen (P35) of Toxoplasma gondii for serodiagnosis of acute infection in pregnant women. A double-sandwich enzyme-linked immunosorbent assay (ELISA) with recombinant P35 antigen (P35-IgM-ELISA) was used for this purpose. On the basis of the clinical history and the combination of results from the toxoplasma serological profile (Sabin-Feldman dye test, conventional IgM and IgA ELISAs, and the differential agglutination test), the patients were classified into three groups: group I, status suggestive of recently acquired infection; group II, status suggestive of infection acquired in the distant past; group III, status suggestive of persisting IgM antibodies. Eighteen (90.0%) of 20 serum samples from group I patients were positive by the P35-IgM-ELISA, whereas none of the 33 serum samples from group II patients were positive. Only 4 (25.0%) of 16 serum samples from group III patients were positive by the P35-IgM-ELISA, whereas all these serum samples were positive by the conventional IgM ELISA. These results indicate that demonstration of IgM antibodies against P35 by the P35-IgM-ELISA is more specific for the acute stage of the infection than demonstration of IgM antibodies by the ELISA that uses a whole-lysate antigen preparation. Studies with sera obtained from four pregnant women who seroconverted (IgG and IgM antibodies) during pregnancy revealed that two of them became negative by the P35-IgM-ELISA between 4 and 6 months after seroconversion, whereas the conventional IgM ELISA titers remained highly positive. The P35-IgM-ELISA appears to be useful for differentiating recently acquired infection from those acquired in the distant past in pregnant women.

    View details for Web of Science ID 000166892900010

    View details for PubMedID 11060053

  • Protection against lipopolysaccharide-induced death by fluoroquinolones ANTIMICROBIAL AGENTS AND CHEMOTHERAPY Khan, A. A., Slifer, T. R., Araujo, F. G., Suzuki, Y., Remington, J. S. 2000; 44 (11): 3169-3173

    Abstract

    Because fluoroquinolones have an immunomodulatory effect on cytokine production by lipopolysaccharide (LPS)-treated human monocytes, we examined the effect of fluoroquinolones on the survival of mice injected with a lethal dose of LPS. Trovafloxacin (100 mg/kg), ciprofloxacin (250 mg/kg), and tosufloxacin (100 mg/kg) protected 75% (P = 0.0001), 25% (P = 0.002), and 50% (P = 0.002), respectively, of mice against death. The fluoroquinolones significantly reduced serum levels of interleukin-6 and tumor necrosis factor alpha in LPS-treated mice. The protective effects of fluoroquinolones in LPS-induced shock in mice may also occur in humans.

    View details for Web of Science ID 000090029200043

    View details for PubMedID 11036044

  • Strain typing of Toxoplasma gondii: Comparison of antigen-coding and housekeeping genes JOURNAL OF PARASITOLOGY Lehmann, T., Blackston, C. R., Parmley, S. F., Remington, J. S., Dubey, J. P. 2000; 86 (5): 960-971

    Abstract

    Molecular characterization of Toxoplasma gondii isolates is central for understanding differences in disease transmission and manifestations. Only 3 subgroups (lineages) have been discerned with subtle within-lineage variation, permitting low-resolution classification of isolates. Because proteins, coding sequences, and especially antigen-coding genes have been used extensively in previous studies, we focused on sequence variation in introns of housekeeping genes, which may be more informative for phylogenetic analysis because they evolve under lower selection. We compared sequence variation in introns of 5 housekeeping genes with 2 antigen-coding genes. Introns of housekeeping genes were slightly more polymorphic than coding and noncoding regions of antigen-coding genes and only the former showed intralineage variation. Intragenic linkage disequilibrium was complete, but intergenic linkage, although highly significant, was incomplete, suggesting that genes are partially uncoupled. Six of 7 substitutions found within the region coding for the tachyzoite surface antigen, SAG2, were nonsynonymous, indicating that diversifying selection acts on this locus. Typing isolates on the basis of housekeeping and antigen-coding genes was consistent, but the phylogenetic relationships among the resulting groups was inconsistent. A cougar isolate typed as lineage II using a restriction fragment length polymorphism assay possessed multiple unique polymorphisms, suggesting that it represents a new lineage. We concluded that introns of housekeeping genes are preferred markers for phylogenetic study, and that multilocus genotyping is preferred for typing parasites, especially from feral or unstudied environments.

    View details for Web of Science ID 000089957700014

    View details for PubMedID 11128519

  • Ketolide ABT-773 is active against Toxoplasma gondii JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY Khan, A. A., Araujo, F. G., Craft, J. C., Remington, J. S. 2000; 46 (3): 489-492

    Abstract

    ABT-773 is active in vitro and in vivo against Toxoplasma gondii. It inhibited replication of RH strain tachyzoites in human foreskin fibroblasts. Mice infected intraperitoneally with tachyzoites and treated orally with 25, 50 or 100 mg/kg/day of ABT-773 for 10 days had 20% (P: = 0.016), 50% (P: = 0.003) and 100% (P: = 0.001) survival, respectively. Remarkable and highly significant survival was also noted in mice infected orally with strain C56 cysts and treated with ABT-773. Thus, ABT-773 may be useful for therapy of human toxoplasmosis.

    View details for Web of Science ID 000089299600023

    View details for PubMedID 10980181

  • Serodiagnosis of recently acquired Toxoplasma gondii infection using an enzyme-linked immunosorbent assay with a combination of recombinant antigens CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY Li, S. L., Galvan, G., Araujo, F. G., Suzuki, Y., Remington, J. S., Parmley, S. 2000; 7 (5): 781-787

    Abstract

    An enzyme-linked immunosorbent assay (ELISA) using four recombinant antigens of Toxoplasma gondii (rP22, rP25, rP29, and rP35) was used in an attempt to differentiate pregnant women with toxoplasma serologic profiles (TSPs) indicative of recently acquired infections (acute profile) from those with TSPs indicative of infections acquired in the distant past (chronic profile). In general, immunoglobulin G antibodies in sera from women with the acute profile reacted more strongly with the recombinant antigens than did those in sera from women with the chronic profile. However, reactivities differed significantly between antigens that reacted with a single serum and between sera that reacted with a single antigen. Because of these variations, we employed a combination of the four antigens in an ELISA (Comb-ELISA) and evaluated its ability to distinguish pregnant women with the acute profile from those with the chronic profile. Eighteen of 20 (90%) sera from acute-profile women were positive in the Comb-ELISA, whereas 69 of 70 (98.6%) sera from the chronic-profile women were negative. Thus, the Comb-ELISA may be useful for diagnosis of toxoplasmosis in pregnant women and for differentiation between recently acquired infections and infections acquired in the more distant past.

    View details for Web of Science ID 000089235400013

    View details for PubMedID 10973455

  • Strategies for the successful treatment of gram-positive bacterial infections CLINICAL INFECTIOUS DISEASES Remington, J. S. 2000; 31: S150-S151

    View details for Web of Science ID 000090150600006

    View details for PubMedID 11017865

  • Effect of quinupristin/dalfopristin on production of cytokines by human monocytes JOURNAL OF INFECTIOUS DISEASES Khan, A. A., Slifer, T. R., Araujo, F. G., Remington, J. S. 2000; 182 (1): 356-358

    Abstract

    The effect of the novel streptogramin antibiotic quinupristin/dalfopristin (synercid) on cytokine production in vitro was examined in monocytes obtained from healthy human volunteers and stimulated with either lipopolysaccharide or heat-killed Staphylococcus aureus (Pansorbin). Synercid at concentrations that are achievable in humans (1, 5, and 10 microgram/mL) significantly suppressed production of interleukin (IL)-1alpha, IL-1beta, IL-6, IL-10, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor-alpha in a concentration-dependent manner. Thus, synercid possesses significant immunomodulatory activity, in addition to its antimicrobial activity.

    View details for Web of Science ID 000088522300051

    View details for PubMedID 10882624

  • Decreased resistance of B cell-deficient mice to infection with Toxoplasma gondii despite unimpaired expression of IFN-gamma, TNF-alpha, and inducible nitric oxide synthase JOURNAL OF IMMUNOLOGY Kang, H., Remington, J. S., Suzuki, Y. 2000; 164 (5): 2629-2634

    Abstract

    The role of B cells in resistance against Toxoplasma gondii was studied using B cell-deficient (muMT) mice. Following peroral infection with 10 cysts of the ME49 strain, all muMT mice survived the acute stage of the infection but died between 3 and 4 wk after infection. In contrast, all control mice were alive at 8 wk after infection. At the stage during which muMT animals succumbed to the infection, parasite replication and pathology were most evident in their brains; small numbers of tachyzoites were also detectable in their lungs. Significantly greater numbers of T. gondii cysts and areas of inflammation associated with tachyzoites were observed in brains of muMT than in control mice. Large areas of necrosis associated with numerous tachyzoites were observed only in brains of muMT mice. Anti-T. gondii IgG Abs were detected only in sera of control mice, whereas similar levels of IFN-gamma were detected in sera of both strains of mice. Amounts of mRNA for IFN-gamma, IL-10, and inducible NO synthase in the brain did not differ between infected muMT and control mice. Expression of mRNA for TNF-alpha was increased in brains of muMT mice. Administration of polyclonal rabbit anti-T. gondii IgG Ab prevented early mortality and pathology associated with tachyzoites in the brain in the infected muMT mice. These results indicate that B cells play an important role, most likely through their production of specific Abs, in resistance to persistent active (tachyzoite) infection with T. gondii in mice, especially in the brain and lung.

    View details for Web of Science ID 000085477100044

    View details for PubMedID 10679102

  • Introduction Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Remington, J. S. 2000; 31 Suppl 4: S123

    View details for DOI 10.1086/314076

    View details for PubMedID 11017860

  • Serodiagnosis of recently acquired Toxoplasma gondii infection with a recombinant antigen JOURNAL OF CLINICAL MICROBIOLOGY Li, S. L., Maine, G., Suzuki, Y., Araujo, F. G., Galvan, G., Remington, J. S., Parmley, S. 2000; 38 (1): 179-184

    Abstract

    A portion of a cDNA encoding a 35-kDa antigen from Toxoplasma gondii was cloned into the CKS expression vector and expressed in Escherichia coli. By using the enzyme-linked immunosorbent assay (ELISA), the recombinant protein (rP35 antigen) was examined for reactivity with immunoglobulin G (IgG) antibodies in the sera of pregnant women. Of these women, 41 had a toxoplasma serologic profile suggestive of recently acquired T. gondii infection (Sabin-Feldman dye test [DT] titers from 1:256 to 1:32,000, positive IgM ELISA titers from 2.3 to 9.7, positive IgA ELISA from 1 to >28, and acute patterns in the differential agglutination [AC/HS] test) (group I), and 50 women had a toxoplasma serologic profile suggestive of infection acquired in the distant past (low DT titers from 1:16 to 1:512, negative IgM ELISA titers from 0 to 0.8, and chronic patterns in the AC/HS test) (group II). The classification of acute or chronic profile was based on the individual's clinical history as well as the combination of the results of the toxoplasma serological profile. An additional group (group III) was composed of sera from 50 women who were seronegative for T. gondii antibodies in the DT. The results revealed that whereas 85.3% of women in group I had IgG antibodies that reacted with the rP35 antigen, only 8% of women in group II had IgG antibodies that reacted with the same antigen. In immunoblots, the rP35 antigen was recognized by IgG antibodies in a pool of sera from individuals with a toxoplasma serologic profile compatible with acute infection but not in a pool of sera from individuals with a serologic profile characteristic of a chronic infection. These results reveal that IgG antibodies against the P35 antigen are produced during the acute stage of the infection but are uncommon in the latent or chronic phase of the infection. Thus, the rP35 antigen may be a useful serologic marker to differentiate between recently acquired infection and that acquired in the more distant past.

    View details for Web of Science ID 000084689800032

    View details for PubMedID 10618084

    View details for PubMedCentralID PMC88692

  • Immunopathogenesis of CNS toxoplasmosis Conference on New Concepts in the Immunopathogenesis of CNS Infections Suzuki, Y., Remington, J. S. BLACKWELL SCIENCE PUBL. 2000: 143–162
  • Quinupristin-dalfopristin is active against Toxoplasma gondii ANTIMICROBIAL AGENTS AND CHEMOTHERAPY Khan, A. A., Slifer, T. R., Araujo, F. G., Remington, J. S. 1999; 43 (8): 2043-2045

    Abstract

    Synercid and each of its components (quinupristin and dalfopristin) were examined for their activities against Toxoplasma gondii. In vitro, intracellular replication of tachyzoites was inhibited by synercid and each of its two components. The 50% inhibitory concentrations of synercid, quinupristin, and dalfopristin were 1.6, 2.7, and 6.3 microg/ml, respectively. Thus, synercid was markedly more active than its components. Treatment of acutely infected mice with 100 or 200 mg of synercid per kg of body weight per day administered intraperitoneally for 10 days resulted in survival of 50% (P = 0.0002) and 100% (P < 0.0001) of infected mice, respectively, whereas all control mice died by day 18. In contrast, treatment with 200 mg of either quinupristin and dalfopristin per kg per day alone resulted in only 20% survival; treatment with 50 mg of either drug per kg per day resulted only in the prolongation of time to death. These results suggest that synercid may be useful for treatment of toxoplasmosis in humans.

    View details for Web of Science ID 000081789200036

    View details for PubMedID 10428933

    View details for PubMedCentralID PMC89411

  • Use of the polymerase chain reaction for diagnosis of ocular toxoplasmosis 35th Annual Meeting of the Infectious-Diseases-Society-of-America Montoya, J. G., Parmley, S., Liesenfeld, O., JAFFE, G. J., Remington, J. S. ELSEVIER SCIENCE INC. 1999: 1554–63

    Abstract

    To report a cohort of patients in whom polymerase chain reaction (PCR) was performed on vitreous samples and to place in perspective the current role of PCR in the diagnosis of ocular toxoplasmosis.Noncomparative case series.Fifteen patients in whom toxoplasmic retinochoroiditis was considered in the differential diagnosis and in whom the clinical presentation was not diagnostic and/or response to treatment was inadequate.Examination of vitreous fluid by PCR and of serum for the presence of Toxoplasma-specific antibodies.Presence of Toxoplasma gondii DNA, serologic test results, clinical findings, treatment, and outcome.In 7 of 15 patients, vitreous fluid examination results by PCR were positive for the presence of T. gondii DNA. Five of these seven patients had serologic test results consistent with Toxoplasma infection acquired in the distant past; the other two patients had serologic test results consistent with retinochoroiditis in the setting of acute toxoplasmosis. The PCR results influenced the management of these patients in six of the seven positive cases. In the eight patients in whom vitreous examination results were negative by PCR, either Toxoplasma serology was negative (6), the retinal lesions were caused by cytomegalovirus (1), or, on further consideration, the eye signs were not consistent with those of toxoplasmic retinochoroiditis (1).In patients in whom toxoplasmosis is considered in the differential diagnosis but in whom the presentation is atypical, PCR was frequently a useful diagnostic aid.

    View details for Web of Science ID 000081732300032

    View details for PubMedID 10442904

  • Anti-Toxoplasma gondii activities and structure-activity relationships of novel fluoroquinolones related to trovafloxacin ANTIMICROBIAL AGENTS AND CHEMOTHERAPY Khan, A. A., Araujo, F. G., Brighty, K. E., Gootz, T. D., Remington, J. S. 1999; 43 (7): 1783-1787

    Abstract

    Eleven novel fluoroquinolones closely related to trovafloxacin were evaluated for their in vitro activity against Toxoplasma gondii, and their structure-activity relationships were examined. The 50% inhibitory concentration (IC50) of trovafloxacin against T. gondii was 2.93 microM; the IC50 of the 11 analogs ranged from 0.53 to 14. 09 microM. Six analogs had IC50s lower than that of trovafloxacin. Examination of the structure-activity relationships of the compounds revealed that addition of a -CH3 at C-5 of the 1,8-naphthyridone ring, at C-2 of the azabicyclohexane ring, or on the -NH2 at the 6 position of the azabicyclohexane ring resulted in a four- to sixfold increase in activity. Moreover, replacement of 2,4-difluorophenyl by cyclopropyl at N-1 of the 1,8-naphthyridone ring increased activity twofold, and moving the -NH2 one atom further away from the azabicyclohexane ring decreased activity. There was no difference between the naphthyridone and quinolone analogs. These results indicate that structure-activity studies of compounds related to drugs active against T. gondii may be useful in producing compounds with more potent activities against the parasite.

    View details for Web of Science ID 000081210800047

    View details for PubMedID 10390245

    View details for PubMedCentralID PMC89366

  • TNF-alpha, nitric oxide and IFN-gamma are all critical for development of necrosis in the small intestine and early mortality in genetically susceptible mice infected perorally with Toxoplasma gondii PARASITE IMMUNOLOGY Liesenfeld, O., Kang, H., Park, D., Nguyen, T. A., Parkhe, C. V., Watanabe, H., Abo, T., Sher, A., Remington, J. S., Suzuki, Y. 1999; 21 (7): 365-376

    Abstract

    We previously reported that genetic susceptibility of mice to peroral infection with T. gondii is associated with CD4+ T cell-dependent, interferon (IFN)-gamma-mediated necrosis of their small intestine. We examined the role of tumour necrosis factor (TNF)-alpha and nitric oxide (NO), in addition to IFN-gamma. At 7 days after infection, a marked increase in CD4+ T cells was observed in lamina propria mononuclear cells (LPC) of the small intestine as compared with normal mice, and significantly greater amounts of mRNA for IFN-gamma, TNF-alpha, and inducible NO synthase (iNOS) were detected in LPC of the small intestine of infected than uninfected animals. Treatment of infected mice with anti-TNF-alpha monoclonal antibody (mAb) or the iNOS inhibitor, aminoguanidine, prevented necrosis and prolonged time to death. Infected iNOS-targeted mutant mice did not develop the disease whereas infected, control mice did. Treatment with anti-TNF-alpha mAb did not affect the expression of IFN-gamma in the LPC but inhibited expression of iNOS in the infected mice, indicating the role of TNF-alpha in the induction of iNOS. These results suggest that NO induced by a combination of IFN-gamma and TNF-alpha through activation of iNOS is a critical mediator of intestinal pathology and contributes to early mortality in genetically susceptible mice.

    View details for Web of Science ID 000081827500005

    View details for PubMedID 10417671

  • Recombinant bactericidal/permeability-increasing protein (rBPI(21)) in combination with sulfadiazine is active against Toxoplasma gondii ANTIMICROBIAL AGENTS AND CHEMOTHERAPY Khan, A. A., Lambert, L. H., Remington, J. S., Araujo, F. G. 1999; 43 (4): 758-762

    Abstract

    The activity of recombinant bactericidal/permeability-increasing protein (rBPI21), alone or in combination with sulfadiazine, on the intracellular replication of Toxoplasma gondii was assessed in vitro and in mice with acute toxoplasmosis. rBPI21 markedly inhibited the intracellular growth of T. gondii in human foreskin fibroblasts (HFFs). Following 72 h of exposure, the 50% inhibitory concentration of rBPI21 for T. gondii was 2.6 micrograms/ml, whereas only slight cytotoxicity for HFF cells was observed at the concentrations tested. Subsequent mathematical analyses revealed that the combination of rBPI21 with sulfadiazine yielded slight to moderate synergistic effects against T. gondii in vitro. Infection of mice orally with C56 cysts or intraperitoneally (i.p.) with RH tachyzoites resulted in 100% mortality, whereas prolongation of the time to death or significant survival (P = 0.002) was noted for those animals treated with 5 to 20 mg of rBPI21 per kg of body weight per day. Treatment with rBPI21 in combination with sulfadiazine resulted in significant (P = 0.0001) survival of mice infected i.p. with tachyzoites but not of mice infected orally with T. gondii cysts. These results indicate that rBPI21 is active in vitro and in vivo against T. gondii and that its activity is significantly enhanced when it is used in combination with sulfadiazine. To our knowledge, this is the first report of the activity of rBPI21 against a protozoan parasite.

    View details for Web of Science ID 000079555400005

    View details for PubMedID 10103177

    View details for PubMedCentralID PMC89203

  • Antibiotics modulate in vitro production of IL-12 in stimulated human monocytes. Khan, A. A., Slifer, T. R., Araujo, F. G., Remington, J. S. LIPPINCOTT WILLIAMS & WILKINS. 1999: 99A–99A
  • Mesenteric lymph node T cells but not splenic T cells maintain their proliferative response to Concanavalin-A following peroral infection with Toxoplasma gondii PARASITE IMMUNOLOGY Neyer, L. E., Kang, H., Remington, J. S., Suzuki, Y. 1998; 20 (12): 573-581

    Abstract

    The suppression of T cell responsiveness which occurs after infection with Toxoplasma gondii in mice has been widely studied using spleen cells. Because the natural route of infection with T. gondii is the peroral route, we examined the proliferative responses of mesenteric lymph node (MLN) cells, in addition to spleen cells, to Concanavalin-A (Con-A) in mice perorally infected with T. gondii. Proliferative responses of spleen cells were significantly suppressed seven and ten days after infection when compared with spleen cells from uninfected mice (62% and 91% reduction, respectively). In contrast, proliferative responses of MLN cells from these infected mice did not differ from those of normal MLN cells. Since IFN-gamma-induced reactive nitrogen intermediate (RNI) production has been reported to play a major role in suppression of proliferative responses in spleen cells of infected mice, we compared production of IFN-gamma and RNI by spleen and MLN cells following infection. MLN cells produced as much IFN-gamma as did spleen cells, but produced 70% less nitrite (as a measure of RNI) after Con-A stimulation. Proliferative responses of MLN cells were suppressed when co-cultured with spleen cells from infected mice, and addition of an inhibitor of RNI to these co-culture inhibited this suppression, suggesting that reduced RNI production by MLN cells contributes to their maintenance of higher proliferative responses. These results demonstrated a clear difference in activity of T cells in the MLN and spleen during the acute stage of the infection.

    View details for Web of Science ID 000081826800001

    View details for PubMedID 9990642

  • Use of ketolides in combination with other drugs to treat experimental toxoplasmosis JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY Araujo, F. G., Khan, A. A., Bryskier, A., Remington, J. S. 1998; 42 (5): 665-667

    Abstract

    Because combination therapy is required to treat human toxoplasmosis, we examined combinations of the ketolides HMR 3004 and HMR 3647 with atovaquone, clindamycin or sulphadiazine in a murine model of toxoplasmosis. An oral dose of 50 mg/kg/day of HMR 3004 protected 30% of mice lethally infected with Toxoplasma gondii. The same dose protected 100% of infected mice when administered in combination with non-protective doses of atovaquone, clindamycin or sulphadiazine. Similar results were noted with 25 mg/kg/day of HMR 3647. These results demonstrate that these drug combinations are highly effective for treating toxoplasmosis in mice.

    View details for Web of Science ID 000077186400017

    View details for PubMedID 9848454

  • Effect of trovafloxacin on production of cytokines by human monocytes ANTIMICROBIAL AGENTS AND CHEMOTHERAPY Khan, A. A., Slifer, T. R., Remington, J. S. 1998; 42 (7): 1713-1717

    Abstract

    Antibiotics have previously been shown to have immunomodulatory effects. We examined the effect of the broad-spectrum fluoroquinoline antibiotic trovafloxacin on cytokine synthesis by monocytes obtained from healthy human volunteers and stimulated with either lipopolysaccharide or gram-positive cells (heat-killed Staphylococcus aureus [Pansorbin]). Trovafloxacin levels achievable in humans suppressed in vitro synthesis of each of the cytokines analyzed, viz., interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-6, IL-10, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor alpha. This effect was not due to direct effects of the drug on cellular viability; at these concentrations, trovafloxacin did not have demonstrable cytotoxicity for the monocytes, as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. Although similar patterns of suppression of cytokine synthesis were observed in samples obtained from the same volunteers on different days, there were significant day-to-day variations. These results reveal that trovafloxacin possesses significant immunomodulatory activity in vitro and suggest that suppression of acute-phase inflammatory responses may occur in vivo, elicited through trovafloxacin's effect on cytokine synthesis by human monocytes.

    View details for Web of Science ID 000074535500032

    View details for PubMedID 9661009

    View details for PubMedCentralID PMC105671

  • alpha beta T cell response to Toxoplasma gondii in previously unexposed individuals JOURNAL OF IMMUNOLOGY Subauste, C. S., Fuh, F., Malefyt, R. D., Remington, J. S. 1998; 160 (7): 3403-3411

    Abstract

    The mechanisms by which T cells from previously unexposed hosts respond in vitro to certain intracellular pathogens remain to be fully understood. We report and characterize the in vitro reactivity to Toxoplasma gondii of human alpha beta T cells from T. gondii-seronegative individuals. Resting alpha beta T cells from these individuals proliferated in response to PBMC infected with T. gondii or pulsed with T. gondii lysate Ags. This was accompanied by an increase in the percentage of CD4+ alpha beta T cells. Purified CD4+ alpha beta T cells but not CD8+ alpha beta T cells proliferated in response to these T. gondii preparations. Both CD4+ alpha beta T cells with naive (CD45RA+) and memory (CD45RO+) phenotypes from adults as well as alpha beta T cells from T. gondii-seronegative newborns proliferated after incubation with T. gondii. This alpha beta T cell response to the parasite was inhibited by anti-HLA-DR mAb and to a lesser degree by anti-HLA-DQ mAb. Use of paraformaldehyde-fixed PBMC completely abrogated the proliferation of alpha beta T cells, indicating the need for processing of T. gondii Ags. Analysis of the TCR V beta expression did not show evidence for restriction in TCR V beta usage during T. gondii stimulation of alpha beta T cells. Alpha beta T cells secreted significant amounts of IFN-gamma after incubation with T. gondii-infected monocytes. This rapid and remarkable alpha beta T cell response may play an important role in the early events of the immune response to T. gondii.

    View details for Web of Science ID 000072700100041

    View details for PubMedID 9531300

  • Scedosporium apiospermum (Pseudallescheria boydii) infection in a heart transplant recipient: A case of mistaken identity JOURNAL OF HEART AND LUNG TRANSPLANTATION Lopez, F. A., Crowley, R. S., Wastila, L., Valantine, H. A., Remington, J. S. 1998; 17 (3): 321-324

    Abstract

    We report a case of fatal central nervous system infection with Scedosporium apiospermum (Pseudallescheria boydii) in a heart transplant recipient. This ubiquitous fungus is known to cause mycetoma and localized infections in patients with otherwise normal conditions. Disseminated infections occur rarely and are seen primarily in patients who are receiving immunosuppressive medications or who have neutropenia. Often life-threatening when infection is disseminated and involves the central nervous system, this diagnosis is difficult to make rapidly because S. apiospermum (P. boydii) mimics Aspergillus spp. and Fusarium spp., both clinically and histopathologically. Imidazoles such as miconazole, but not amphotericin B, are considered the therapeutic compounds of choice. Improved diagnostic and treatment options are needed to optimize management of infections with S. apiospermum (P. boydii).

    View details for Web of Science ID 000072988500013

    View details for PubMedID 9563611

  • Evaluation of six commercial kits for detection of human immunoglobulin M antibodies to Toxoplasma gondii. The FDA Toxoplasmosis Ad Hoc Working Group. Journal of clinical microbiology Wilson, M., Remington, J. S., Clavet, C., Varney, G., Press, C., Ware, D. 1997; 35 (12): 3112-3115

    Abstract

    As a result of reports received by the Food and Drug Administration (FDA) of false-positive results obtained with FDA-cleared in vitro diagnostic kits for the detection of Toxoplasma-specific human immunoglobulin M (IgM) antibodies, an FDA-sponsored evaluation of six kits was performed. A battery of 258 serum specimens, including 30 specimens drawn 1 to 5 months after initial Toxoplasma infection and 228 specimens from Toxoplasma IgG-positive individuals, Toxoplasma IgG-negative individuals, rheumatoid factor-positive persons, and persons determined to be Toxoplasma IgM positive by commercially available assays, was assembled, randomly assorted, and coded. The battery was tested at the FDA with six commercially available kits, at the Palo Alto Medical Foundation (PAMF) by the PAMF double-sandwich IgM enzyme-linked immunosorbent assay (PAMF IgM ELISA), and at the Centers for Disease Control and Prevention (CDC) by the CDC EIA IgM. The results of the PAMF IgM ELISA that were obtained with the battery were considered to be the "gold standard" for this study; specificity rates were computed by considering the PAMF results to be 100% specific. Sensitivity and specificity rates were found to be as follows: CDC EIA IgM, 100 and 99.1%, respectively; Abbott IMx Toxo IgM, version 1, 100 and 77.5%, respectively; Abbott IMx Toxo IgM, version 2, 93.3 and 97.3%, respectively; Abbott Toxo-M EIA, 100 and 84.2%, respectively; BioMérieux Vitek VIDAS Toxo IgM, 100 and 98.6%, respectively; BioWhittaker Toxocap-M, 100 and 95.9%, respectively; Gull Toxo IgM, 97 and 85.6%, respectively; and Sanofi Diagnostics Pasteur Platelia Toxo IgM, 100 and 96.8%, respectively. Although the extent of false-positive reactions with these kits cannot be calculated because the study was retrospective and sample choices were biased, the results may be useful as an indicator of the relative specificities of these kits.

    View details for PubMedID 9399504

    View details for PubMedCentralID PMC230132

  • Evaluation of six commercial kits for detection of human immunoglobulin M antibodies to Toxoplasma gondii JOURNAL OF CLINICAL MICROBIOLOGY Wilson, M., Remington, J. S., Clavet, C., Varney, G., Press, C., Ware, D., HERMAN, C. L., SHIVELY, R. G., SIMMS, T. E., Hansen, S., GAFFEY, C. M., Nutter, C. D., Langone, J. J., McCracken, J., Staples, B. 1997; 35 (12): 3112-3115
  • The ketolide antibiotics HMR 3647 and HMR 3004 are active against Toxoplasma gondii in vitro and in murine models of infection ANTIMICROBIAL AGENTS AND CHEMOTHERAPY Araujo, F. G., Khan, A. A., Slifer, T. L., Bryskier, A., Remington, J. S. 1997; 41 (10): 2137-2140

    Abstract

    Ketolides are a new class of macrolide antibiotics that have been shown to be active against a variety of bacteria including macrolide-resistant bacteria and mycobacteria. We examined two ketolides, HMR 3647 and HMR 3004, for their in vitro and in vivo activities against the protozoan parasite Toxoplasma gondii. In vitro, both ketolides at concentrations as low as 0.05 microg/ml markedly inhibited replication of tachyzoites of the RH strain within human foreskin fibroblasts. HMR 3004 demonstrated some toxicity for host cells after they were exposed to 5 microg of the drug per ml for 72 h. In contrast, HMR 3647 did not show any significant toxicity even at concentrations as high as 25 microg/ml. In vivo, both ketolides provided remarkable protection against death in mice lethally infected intraperitoneally with tachyzoites of the RH strain or orally with tissue cysts of the C56 strain of T. gondii. A dosage of 100 mg of HMR 3647 per kg of body weight per day administered for 10 days protected 50% of mice infected with tachyzoites. The same dosage of HMR 3004 protected 100% of the mice. In mice infected with cysts, a dosage of 30 mg of HMR 3647 per kg per day protected 100% of the mice, whereas a dosage of 40 mg of HMR 3004 per kg per day protected 75% of the mice. These results demonstrate that HMR 3647 and HMR 3004 possess excellent activities against two different strains of T. gondii and may be useful for the treatment of toxoplasmosis in humans.

    View details for Web of Science ID A1997XY74700012

    View details for PubMedID 9333038

    View details for PubMedCentralID PMC164083

  • Type I interferons enhance production of IFN-gamma by NK cells IMMUNOLOGY LETTERS Hunter, C. A., Gabriel, K. E., Radzanowski, T., Neyer, L. E., Remington, J. S. 1997; 59 (1): 1-5

    Abstract

    In murine models, challenge with different viral and parasitic infection is closely associated with the production of type I interferons (IFN-alpha/beta) and NK cell production of interferon-gamma (IFN-gamma). Therefore, we wished to determine if IFN-alpha/beta had a role in the regulation of NK cell production of IFN-gamma. IFN-alpha/beta alone stimulated low levels of IFN-gamma production by purified populations of IL-2 activated NK cells but in combination with IL-12 resulted in the production of significant levels of IFN-gamma. Interestingly, maximal production of IFN-gamma by NK cells stimulated with IL-2 plus IFN-alpha/beta was dependent on endogenous tumor necrosis factor-alpha (TNF-alpha). Further studies revealed that TNF-alpha enhanced the ability of IFN-alpha/beta to stimulate production of IFN-gamma by NK cells. In contrast to the stimulatory effect of IFN-alpha/beta on NK cell production of IFN-gamma, IFN-alpha/beta inhibited IL-2 induced proliferation of NK cells. This inhibitory effect was not reversed by the addition of neutralizing antibodies specific for IFN-gamma or TNF-alpha. These data demonstrate that the type I interferons enhance NK cell production of IFN-gamma and suggest that they may be important in the regulation of NK cell production of IFN-gamma during infection.

    View details for Web of Science ID A1997XY36200001

    View details for PubMedID 9334850

  • Impaired resistance to the development of toxoplasmic encephalitis in interleukin-6-deficient mice INFECTION AND IMMUNITY Suzuki, Y., Rani, S., Liesenfeld, O., Kojima, T., Lim, S., Nguyen, T. A., Dalrymple, S. A., Murray, R., Remington, J. S. 1997; 65 (6): 2339-2345

    Abstract

    The role of interleukin-6 (IL-6) in the pathogenesis of toxoplasmic encephalitis (TE) was examined by using IL-6-targeted mutant (IL-6(-/-)) mice. At 4 and 8 weeks after infection with the ME49 strain of Toxoplasma gondii, significantly greater numbers of T. gondii cysts and areas of inflammation associated with tachyzoites were observed in brains of IL-6(-/-) mice than in those of control mice. Large areas of necrosis were observed only in brains of IL-6(-/-) mice. Tachyzoites were frequently detected in the areas of necrosis, suggesting that necrosis was caused by proliferation of the parasite. These results indicate that IL-6 is protective against development of TE by preventing formation of T. gondii cysts and proliferation of tachyzoites in brains of infected mice. Whereas in brains of control mice, large numbers of inflammatory cells were always observed in areas where tachyzoites were detected, in brains of IL-6(-/-) mice, only small numbers of inflammatory cells were observed in many areas with tachyzoites. Lymphocyte preparations isolated from brains of infected control mice had significantly higher ratios of gamma/delta T cells and CD4+ alpha/beta T cells but lower ratios of CD8+ alpha/beta T cells compared to those of infected IL-6(-/-) mice. There were no differences in the ratios of these T-cell subsets in spleens between these mice. The amounts of mRNA for gamma interferon (IFN-gamma) detected by reverse transcriptase PCR were significantly smaller in brains of IL-6(-/-) mice than in those of control mice, whereas amounts of IL-10 mRNA were greater in the former than in the latter. IL-6 mRNA was detected only in infected control mice. The protective activity of IL-6 against development of TE appears to be through its ability to stimulate IFN-gamma production and induce infiltration and accumulation of different T-cell subsets in brains of infected mice.

    View details for Web of Science ID A1997XB56200050

    View details for PubMedID 9169772

    View details for PubMedCentralID PMC175324

  • Activity of trovafloxacin in combination with other drugs for treatment of acute murine toxoplasmosis ANTIMICROBIAL AGENTS AND CHEMOTHERAPY Khan, A. A., Slifer, T., Araujo, F. G., Polzer, R. J., Remington, J. S. 1997; 41 (5): 893-897

    Abstract

    Current therapy for toxoplasmosis with a synergistic combination of pyrimethamine plus sulfadiazine or pyrimethamine plus clindamycin is not always efficacious and is frequently discontinued due to intolerable toxic effects in immunocompromised individuals, particularly those with AIDS. Trovafloxacin, a new fluoroquinolone with potent activity against Toxoplasma gondii, was examined for potential synergistic activity when combined with other drugs used for treatment of human toxoplasmosis. Combinations of trovafloxacin with clarithromycin, pyrimethamine, or sulfadiazine demonstrated significantly enhanced activities compared to those observed with each drug alone. Our results suggest that combinations of trovafloxacin and other anti-toxoplasma drugs should be further explored for treatment of toxoplasmosis in humans.

    View details for Web of Science ID A1997WX58300003

    View details for PubMedID 9145840

    View details for PubMedCentralID PMC163821

  • Role of interleukin-10 in regulation of T-cell-dependent and T-cell-independent mechanisms of resistance to Toxoplasma gondii INFECTION AND IMMUNITY Neyer, L. E., Grunig, G., Fort, M., Remington, J. S., Rennick, D., Hunter, C. A. 1997; 65 (5): 1675-1682

    Abstract

    Interleukin-10 (IL-10) is a cytokine which can inhibit T-cell and natural killer (NK) cell functions associated with cell-mediated immunity to intracellular infections. The production of IL-10 by mice infected with Toxoplasma gondii has been implicated in the suppression of lymphocyte proliferation observed during acute toxoplasmosis, as well as susceptibility to infection with this parasite. We have used C57BL/6 mice which lack a functional IL-10 gene (IL-10(-/-) mice) to investigate the role of IL-10 in acute toxoplasmosis. Intraperitoneal infection of IL-10(-/-) mice with T. gondii resulted in 100% mortality by day 13, whereas wild-type C57BL/6 (WT) mice survived acute infection. IL-10(-/-) mice infected with T. gondii had significantly higher serum levels of IL-12 and gamma interferon (IFN-gamma) than WT mice. Early mortality of infected IL-10(-/-) mice was prevented by treatment with IL-10 and significantly delayed by neutralizing antibodies to IL-12 and IFN-gamma. Further studies revealed that SCID/IL-10(-/-) mice infected with T. gondii had delayed time to death compared to IL-10(-/-) mice, indicating that lymphocytes contributed to death of IL-10(-/-) mice. In addition, infected SCID/IL-10(-/-) mice survived longer than infected SCID mice. These latter data indicate that in mice lacking lymphocytes, endogenous IL-10 is associated with increased susceptibility to T. gondii. However, the lack of IL-10 does not alter the infection-induced suppression of T cell and NK cell functions. Our experiments reveal that IL-10 is associated with protection or increased susceptibility to infection with T. gondii, depending on whether mice possess lymphocytes, and demonstrate the important roles of IL-12 and IFN-gamma in the early infection-induced mortality observed in the IL-10(-/-) mice.

    View details for Web of Science ID A1997WW39800015

    View details for PubMedID 9125546

    View details for PubMedCentralID PMC175195

  • Toxoplasmic myocarditis and polymyositis in patients with acute acquired toxoplasmosis diagnosed during life CLINICAL INFECTIOUS DISEASES Montoya, J. G., Jordan, R., Lingamneni, S., Berry, G. J., Remington, J. S. 1997; 24 (4): 676-683

    Abstract

    The presence of both toxoplasmic myocarditis and myositis in the same individual has been reported only at autopsy. We report the first case of biopsy-proven toxoplasmic myocarditis and polymyositis simultaneously occurring in the same individual that was diagnosed during life. Results of her toxoplasmic serology were consistent with acute toxoplasmosis. She subsequently developed visual symptoms consistent with toxoplasmic chorioretinitis. She had a positive clinical response to therapeutic agents specific against Toxoplasma gondii. Her toxoplasmic serological profile established the diagnosis of acute toxoplasmosis. A toxoplasmic serological profile should be obtained for patients with myocarditis and/or polymyositis of unclear etiology. Endomyocardial or skeletal muscle tissue biopsies may establish the definitive diagnosis of toxoplasmic myocarditis or polymyositis, respectively. Examination of blood by polymerase chain reaction analysis before antitoxoplasmic treatment and early in the course of primary infection with T. gondii may prove useful.

    View details for Web of Science ID A1997WT72500020

    View details for PubMedID 9145743

  • Vertical transmission of toxoplasma by human immunodeficiency virus-infected women AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Minkoff, H., Remington, J. S., HOLMAN, S., Ramirez, R., Goodwin, S., Landesman, S. 1997; 176 (3): 555-559

    Abstract

    Our goal was to determine the frequency of mother-to-child transmission of Toxoplasma gondii from human immunodeficiency virus-infected mothers who are also chronically infected with T. gondii.One hundred thirty-eight women were entered into a prospective study of human immunodeficiency virus infection in pregnancy. The women were seen at enrollment, during the third, sixth, and eighth months of pregnancy (except those enrolled later in pregnancy or at delivery), at 2 and 6 months post partum, and at 6-month intervals thereafter through 4 years after delivery. Standardized interviews and physical examinations were performed, and blood was drawn at each visit. Toxoplasma serologic testing was performed on the sample drawn earliest in pregnancy; the Sabin-Feldman dye test for immunoglobulin G antibodies and enzyme-linked immunoassays for immunoglobulins M, A, and E were used. Univariate analysis for categoric variables was performed with chi2 and two-tailed Fisher exact tests, and for continuous variables the Student t test was used. Statistical Analysis System procedures were followed.Twenty-eight of 138 (20.2%) women who had positive test results for human immunodeficiency virus had positive findings of the Sabin-Feldman dye test. Serologic status for T. gondii did not correlate with age, immune status, parity, or drug use. One of 27 children born to women who were seropositive for both human immunodeficiency virus and T. gondii (one child's serologic status for T. gondii was unknown) had Sabin-Feldman dye test antibodies beyond age 6 months (3.7%, 95% confidence interval 0.09% to 18.9%). Among the cohort of human immunodeficiency virus-infected mothers the rate of mother-to-child human immunodeficiency virus transmission did not vary with maternal Toxoplasma status. However, with sample sizes of 28 and 110, respectively, for the mothers who were T. gondii seropositive and seronegative, the power to detect a difference in the human immunodeficiency virus transmission rate between these groups would be relatively small.Transmission of T. gondii from a chronically infected mother can occur in the setting of a human immunodeficiency virus infection, but this is not a common phenomenon. In a small cohort of human immunodeficiency virus-infected women we did not observe its occurrence among those without severe immunocompromise.

    View details for Web of Science ID A1997WR88600012

    View details for PubMedID 9077606

  • Macrolides, azalides, and streptogramins in treatment of opportunistic infections in immunocompromised patients 3rd International Conference on the Macrolides, Azalides, and Streptogramins Remington, J. S. MARCEL DEKKER. 1997: 189–204
  • Eye manifestations of congenital toxoplasmosis AMERICAN JOURNAL OF OPHTHALMOLOGY Mets, M. B., Holfels, E., Boyer, K. M., SWISHER, C. N., Roizen, N., Stein, L., Stein, M., Hopkins, J., Withers, S., Mack, D., Luciano, R., Patel, D., Remington, J. S., MEIER, P., McLeod, R. 1997; 123 (1): 1-16

    Abstract

    To determine the natural history of treated and untreated congenital toxoplasmosis and impact of this infection on vision.In this prospective, longitudinal study, 76 newborns were treated with pyrimethamine and sulfadiazine for approximately one year, and 18 individuals not treated during their first year of life entered the study after age 1 year (historical patients).Chorioretinal scars were the most common eye finding in all patients and were most common in the periphery (58% of treated and 82% of historical patients). Macular scars were present in 54% of the treated patients; 41% were bilateral. Macular scars were present in 76% of the historical patients; 23% were bilateral. Visual acuity in the presence of macular lesions ranged from 20/20 to 20/400. Of the patients followed up from the newborn period and treated, 29% had bilateral visual impairment, with visual acuity for the best eye of less than 20/40. Causes for this visual impairment in eyes with quiescent lesions included macular scars, dragging of the macula secondary to a peripheral lesion, retinal detachment, optic atrophy, cataract, amblyopia, and phthisis. There were recurrences in both treated (13%, 7/54) and previously untreated historical patients (44%, 8/18). The total, median, and range of years of follow-up during which recurrences were observed were, for treated patients, 189 years (total), five years (median) and three to ten years (range) and, for historical, untreated patients, 160 years (total), 11 years (median), and three to 24 years (range). New lesions occurred in previously normal retinas and also contiguous to older scars. Active lesions appeared to become quiescent within ten to 14 days after beginning pyrimethamine and sulfadiazine therapy.Many children with congenital toxoplasmosis have substantial retinal damage at birth and consequent loss of vision. Nonetheless, vision may be remarkably good in the presence of large macular scars. Active lesions become quiescent with treatment.

    View details for Web of Science ID A1997WB82200001

    View details for PubMedID 9186091

  • False-positive results in immunoglobulin M (IgM) Toxoplasma antibody tests and importance of confirmatory testing: The Platelia Toxo IgM test JOURNAL OF CLINICAL MICROBIOLOGY Liesenfeld, O., Press, C., Montoya, J. G., Gill, R., ISAACRENTON, J. L., HEDMAN, K., Remington, J. S. 1997; 35 (1): 174-178

    Abstract

    Although tests for detection of immunoglobulin M (IgM) toxoplasma antibodies have been reported to have a high degree of accuracy, it is well recognized by investigators in the United States and Europe that false-positive results may occur with many of these tests, at times to an alarming degree. Unfortunately, this information is not well documented in the literature. Studies on various toxoplasma IgM test kits are frequently flawed. The investigators often use reference tests which have not previously been carefully evaluated as well as sera that were not appropriate to answer the question of how often false-positive results might occur. We recently had the unique opportunity to evaluate the accuracy of the Platelia Toxo IgM test in 575 serum samples obtained during an outbreak of toxoplasmosis which occurred in 1995 in the Capital Regional District of British Columbia, Canada. When compared with results obtained in a reference IgM enzyme-linked immunosorbent assay (ELISA), the Platelia Toxo IgM test had a sensitivity of 99.4%, specificity of 49.2%, positive predictive value of 51.9%, negative predictive value of 99.3%, and an overall agreement of 67.0%. In an attempt to resolve discrepancies between these two tests, a serological profile (Sabin-Feldman dye test, IgA and IgE antibody tests, differential agglutination [AC/HS] test, and IgG avidity method) was performed. Of 153 serum samples that were positive in the Platelia Toxo IgM test and negative in the IgM ELISA, 71 (46.4%) were negative in the Sabin-Feldman dye test. Of the serum samples that were positive in the dye test, 77 (93.9%) had a serological profile most compatible with an infection acquired in the distant past. These results reveal high numbers of false-positive results in the Platelia Toxo IgM test and highlight the importance of appropriate evaluation of commercial tests that are currently being marked. Our results also emphasize the importance of confirmatory testing to determine whether the results of an IgM antibody test reflect the likelihood of a recently acquired infection.

    View details for Web of Science ID A1997VY56600031

    View details for PubMedID 8968902

    View details for PubMedCentralID PMC229533

  • Treatment with interleukin 12 in combination with atovaquone or clindamycin significantly increases survival of mice with acute toxoplasmosis ANTIMICROBIAL AGENTS AND CHEMOTHERAPY Araujo, F. G., Hunter, C. A., Remington, J. S. 1997; 41 (1): 188-190

    Abstract

    The capacity of interleukin 12 (IL-12) to potentiate drugs in the treatment of murine toxoplasmosis was examined. IL-12 (100 ng/injection), atovaquone (10 mg/kg of body weight/day), or clindamycin (5 mg/kg/day) administered alone caused delayed time to death or minimal survival rates. In contrast, significant survival rates resulted when the same dose of IL-12 was used in combination the same doses of atovaquone (P=0.01) or clindamycin (P=0.001). Infected mice treated with IL-12 plus drug produced significantly higher levels of gamma interferon than controls. Although IL-12 was effective only when administered before infection, these results suggest that this cytokine may be a useful adjunct in the therapy of human toxoplasmosis in situations when cysts reactivate and tachyzoites start multiplying in immunocompromised patients.

    View details for Web of Science ID A1997WA65600034

    View details for PubMedID 8980778

  • Congenital toxoplasmosis transmitted from an immunologically competent mother infected before conception CLINICAL INFECTIOUS DISEASES Vogel, N., Kirisits, M., Michael, E., Bach, H., Hostetter, M., Boyer, K., Simpson, R., Holfels, E., Hopkins, J., Mack, D., Mets, M. B., SWISHER, C. N., Patel, D., Roizen, N., Stein, L., Stein, M., Withers, S., Mui, E., Egwuagu, C., Remington, J., Dorfman, R., McLeod, R. 1996; 23 (5): 1055-1060

    Abstract

    Congenital transmission of Toxoplasma gondii from a mother who was apparently immunologically competent and who had toxoplasmic lymphadenitis 2 months before conception is described. Since no T. gondii-specific serological data were available for this mother from the time her lymph node biopsy specimen was obtained, the specimen was studied by polymerase chain reaction (PCR) to determine whether the T. gondii B1 gene was present. The predictive diagnostic value of histologic findings previously considered to be classic signs of T. gondii lymphadenitis also was studied. This was done by correlation of serological tests diagnostic of acute acquired T. gondii infection and presence of characteristic findings in biopsy specimens from persons without known immunocompromise. Both PCR and review of the characteristic features of her lymph node biopsy specimen confirmed the diagnosis of preconceptual infection in the mother. We also discuss two other cases in which apparently immunologically competent mothers with preconceptually acquired infection transmitted this parasite to their fetuses.

    View details for Web of Science ID A1996VQ90600019

    View details for PubMedID 8922802

  • Tularemia presenting as community-acquired pneumonia - Implications in the era of managed care ARCHIVES OF INTERNAL MEDICINE Fredricks, D. N., Remington, J. S. 1996; 156 (18): 2137-2140

    Abstract

    A case of pleuropulmonary tularemia was diagnosed by sputum culture and serologic studies in a patient who did not have classic epidemiological risks for tularemia. The patient had atypical pneumonia when initially seen and his condition slowly improved with antibiotic therapy that included erythromycin lactobionate. The diagnosis of tularemia was delayed because the gram-negative rod isolated from the patient's sputum was initially not speciated in an effort to reduce laboratory costs.

    View details for Web of Science ID A1996VL78200015

    View details for PubMedID 8862107

  • Study of Abbott Toxo IMx system for detection of immunoglobulin G and immunoglobulin M toxoplasma antibodies: Value of confirmatory testing for diagnosis of acute toxoplasmosis JOURNAL OF CLINICAL MICROBIOLOGY Liesenfeld, O., Press, C., Flanders, R., Ramirez, R., Remington, J. S. 1996; 34 (10): 2526-2530

    Abstract

    We compared the Abbott Toxo immunoglobulin G (IgG) and IgM IMx assays with the Sabin-Feldman dye test and an IgM enzyme-linked immunosorbent assay (ELISA) in 398 serum samples previously tested in our laboratory (retrospective group) and 1,000 consecutive serum samples, tested as they were received in our laboratory in 1995 (prospective group). In the retrospective group, the IgG IMx had a sensitivity of 100%, specificity of 99.0%, positive predictive value of 99.0%, negative predictive value of 100%, and overall agreement of 99.5%. The percentages for the IgM IMx were 97.8, 99.0, 98.9, 98, and 98.4%, respectively. In the prospective group, the IgG IMx had a sensitivity of 97.8%, specificity of 98.7%, positive predictive value of 97.8%, negative predictive value of 98.7%, and overall agreement of 98.4%. The percentages for the IgM IMx were 88.3, 95.9, 74.7, 98.3, and 95%. A serological profile (IgA and IgE antibodies and the differential agglutination [AC/HS] test) was performed in an attempt to resolve discrepancies. Of 21 serum samples that were positive in the IgM IMx and negative in the IgM ELISA, 19 had serological profiles which were most compatible with an infection acquired in the distant past. Of 8 serum samples which were positive in the IgM ELISA and negative in the IgM IMx, 5 had serological profiles which were most compatible with an infection acquired in the distant past. Of the 55 serum samples that were positive in both IgM tests, 21 were from patients who had serological profiles which were most compatible with an infection acquired in the distal past. In conclusion, our data highlight the importance of confirmatory testing for the diagnosis of recently acquired infection with Toxoplasma gondii. When compared with the dye test and IgM ELISA, the Toxo IgG and IgM IMx assays, respectively, revealed high overall agreement in the retrospective and prospective study.

    View details for Web of Science ID A1996VK78700038

    View details for PubMedID 8880514

    View details for PubMedCentralID PMC229310

  • IL-4 is protective against development of toxoplasmic encephalitis JOURNAL OF IMMUNOLOGY Suzuki, Y., Yang, Q., Yang, S. M., Nguyen, N., Lim, S., Liesenfeld, O., Kojima, T., Remington, J. S. 1996; 157 (6): 2564-2569

    Abstract

    IFN-gamma is critical for prevention of development of toxoplasmic encephalitis (TE). Since IL-4 down-regulates production of IFN-gamma, we examined its role in the pathogenesis of TE in IL-4-targeted mutant (IL-4-/-) mice. IL-4-/- mice all died from 6 to 20 wk after peroral infection with cysts of the ME49 strain of Toxoplasma gondii; control mice survived. At 4 and 8 wk after infection, significantly greater numbers of T. gondii cysts and foci of acute inflammation, and greater amounts of tachyzoite-specific mRNA (by reverse-transcriptase PCR) were in brains of IL-4-/- mice than controls. Toxoplasma IgG2b and IgG3 Ab levels were slightly but significantly higher in sera of IL-4-/- than control mice, whereas IgM and IgG2a levels did not differ between these mice. Toxoplasma IgG1 and IgE Abs were not detected in sera of either strain. Amounts of IFN-gamma, TNF-alpha, IL-6, and IL-10 mRNA detected by reverse-transcriptase PCR did not differ between brains of infected IL-4-/- and controls, although brains of the former mice had greater numbers of inflammatory mononuclear cell infiltrates. IL-4 mRNA was detected only in infected control mice. Spleen cells of control mice at 8 wk after infection produced significantly greater amounts of IFN-gamma following stimulation in vitro with soluble T. gondii Ags than did those from IL-4-/- mice. These results indicate that IL-4 is protective against development of TE by preventing formation of T. gondii cysts and proliferation of tachyzoites in the brain. The impaired ability of IL-4-/- mice in the late stage of T. gondii infection to produce IFN-gamma most likely contributes to their susceptibility for development of severe TE.

    View details for Web of Science ID A1996VL10300042

    View details for PubMedID 8805658

  • Eye manifestations of congenital toxoplasmosis AMERICAN JOURNAL OF OPHTHALMOLOGY Mets, M. B., Holfels, E., Boyer, K. M., SWISHER, C. N., Roizen, N., Stein, L., Stein, M., Hopkins, J., Withers, S., Mack, D., Luciano, R., Patel, D., Remington, J. S., MEIER, P., McLeod, R. 1996; 122 (3): 309-324

    Abstract

    To determine the natural history of treated and untreated congenital toxoplasmosis and impact of this infection on vision.In this prospective, longitudinal study, 76 newborns were treated with pyrimethamine and sulfadiazine for approximately one year, and 18 individuals not treated during their first year of life entered the study after age 1 year (historical patients).Chorioretinal scars were the most common eye finding in all patients and were most common in the periphery (58% of treated and 82% of historical patients). Macular scars were present in 54% of the treated patients; 41% were bilateral. Macular scars were present in 76% of the historical patients; 23% were bilateral. Visual acuity in the presence of macular lesions ranged from 20/20 to 20/400. Of the patients followed up from the newborn period and treated, 29% had bilateral visual impairment, with visual acuity for the best eye of less than 20/40. Causes for this visual impairment in eyes with quiescent lesions included macular scars, dragging of the macula secondary to a peripheral lesion, retinal detachment, optic atrophy, cataract, amblyopia, and phthisis. There were recurrences in both treated (13%, 7/54) and previously untreated historical patients (44%, 8/18). The total, median, and range of years of follow-up during which recurrences were observed were, for treated patients, 189 years (total), five years (median), and three to ten years (range) and, for historical, untreated patients, 160 years (total), 11 years (median), and three to 24 years (range). New lesions occurred in previously normal retinas and also contiguous to older scars. Active lesions appeared to become quiescent within ten to 14 days after beginning pyrimethamine and sulfadiazine therapy.Many children with congenital toxoplasmosis have substantial retinal damage at birth and consequent loss of vision. Nonetheless, vision may be remarkably good in the presence of large macular scars. Active lesions become quiescent with treatment.

    View details for Web of Science ID A1996VF62000002

    View details for PubMedID 8794703

  • Toxoplasmic chorioretinitis in the setting of acute acquired toxoplasmosis CLINICAL INFECTIOUS DISEASES Montoya, J. G., Remington, J. S. 1996; 23 (2): 277-282

    Abstract

    Ocular toxoplasmosis is considered to be the most commonly recognized cause of chorioretinitis in the United States. It is commonly believed that the majority of cases of acute toxoplasmic chorioretinitis involving adults in the United States are late sequelae of congenital infection and that the condition is rarely associated with acute postnatally acquired infection. We report here the clinical and serological test findings for 22 adults with acute toxoplasmic chorioretinitis that occurred in the setting of acute postnatally acquired toxoplasmosis. The initial serum specimen from each adult yielded an acute toxoplasmic serological profile, on the basis of the following positive results: 95.5%, Sabin-Feldman dye test [titer of > or = 1:1,024]; 95.5%, IgM ELISA; 90.9%, IgA ELISA; 77.3%, IgE ELISA; 95.5%, IgE immunosorbent agglutination assay; and 86.4%, differential agglutination (AC/HS) test (acute pattern). Detection of IgA or IgE antibodies or an acute pattern in the AC/HS test was particularly helpful in diagnosis for those patients whose ELISA IgM titers at presentation were negative or lowly positive. Thus, acute toxoplasmic chorioretinitis occurring with a recently acquired Toxoplasma gondii infection would appear to be more common in the United States than previously recognized, and a toxoplasmic serological profile is useful in diagnosing this entity.

    View details for Web of Science ID A1996VA55400011

    View details for PubMedID 8842263

  • Association of CD4(+) T cell-dependent, interferon-gamma-mediated necrosis of the small intestine with genetic susceptibility of mice to peroral infection with Toxoplasma gondii JOURNAL OF EXPERIMENTAL MEDICINE Liesenfeld, O., Kosek, J., Remington, J. S., Suzuki, Y. 1996; 184 (2): 597-607

    Abstract

    Since there is a remarkable difference in susceptibility to peroral infection with Toxoplasma gondii among inbred strains of mice, we performed studies to examine the mechanism(s) of this difference in susceptibility. After peroral infection with the ME49 strain of T. gondii, C57BL/6 (B6) mice all died whereas BALB/c mice all survived. At day 7 of infection (when B6 mice began dying), massive necrosis of the villi and mucosal cells in the ilea were observed in B6 but not in BALB/c mice. To analyze the role of T cells in resistance against death and development of necrosis in the ilea after infection, studies were performed using athymic nude and euthymic control B6 and BALB/c mice. Athymic B6 mice all died after infection, but surprisingly, they survived significantly longer than control B6 mice, indicating that T cells predispose to early death in these mice. Necrosis in the ilea was observed in control B6 but not in athymic B6 mice; however, significantly less numbers of tachyzoites were observed in the ilea of the former than the latter mice. These results indicate that necrosis in the ilea of the B6 mice was not due to destruction of tissue by tachyzoites but was mediated by T cells. This deleterious effect of T cells appears to contribute to early death in these mice. In contrast, T cells conferred resistance against death in BALB/c mice but did not cause necrosis in their ilea. To analyze the T cell subset(s) that induces necrosis of the ilea in B6 mice, we examined histological changes of the small intestines after infection of mutant mice deficient in different T cell subsets (with the same H-2b haplotype as B6 mice). Mice deficient in alpha/beta or CD4+ T cells did not develop necrosis in the ilea, whereas wild-type control mice and mice deficient in gamma/delta or CD8+ T cells did, suggesting that the cells that induce necrosis in the ilea after infection are CD4+ alpha/beta T cells. Since interferon (IFN)-gamma has been shown to be critical for survival of BALB/c mice after infection with T. gondii, we examined the role of this cytokine in resistance/susceptibility of infected B6 mice. Treatment of B6 mice with anti-IFN-gamma monoclonal antibody shortly before they developed illness prolonged time to death and prevented necrosis in the ilea in these mice. These results indicate that IFN-gamma mediates necrosis in the ilea of B6 mice after infection. This CD4+ T cell-dependent, IFN-gamma-mediated necrosis of the small intestines appears to be a mechanism that underlies the genetic susceptibility of B6 mice to peroral infection with T. gondii, whereas the same cytokine plays a critical role in the resistance of genetically resistant BALB/c mice.

    View details for Web of Science ID A1996VC33700031

    View details for PubMedID 8760813

    View details for PubMedCentralID PMC2192709

  • Trovafloxacin is active against Toxoplasma gondii ANTIMICROBIAL AGENTS AND CHEMOTHERAPY Khan, A. A., Slifer, T., Araujo, F. G., Remington, J. S. 1996; 40 (8): 1855-1859

    Abstract

    Drugs currently used for treatment of toxoplasmosis in pregnant women, congenital infections, immunocompromised patients, and patients with the ocular disease are not always effective or may be dangerous to use; therefore, there is a need for more-effective and less-toxic drugs. Recently, we examined a group of fluoroquinolones for in vitro and in vivo activities against Toxoplasma gondii. Among those examined in vitro (ciprofloxacin, fleroxacin, ofloxacin, temafloxacin, and trovafloxacin), only trovafloxacin significantly inhibited intracellular replication of T. gondii without significant toxicity for host cells. In a murine model of acute toxoplasmosis, 100 or 200 mg of trovafloxacin per kg of body weight per day for 10 days protected 100% of infected mice against death. A dose of 50 mg/kg/day protected 90% of the mice, and a dose of 25 mg/kg/day effected prolongation of time to death. The other fluoroquinolones did not have such in vivo activities. These results indicate that trovafloxacin may be useful for treatment of toxoplasmosis in humans.

    View details for Web of Science ID A1996VA86500016

    View details for PubMedID 8843293

    View details for PubMedCentralID PMC163429

  • Rifapentine is active in vitro and in vivo against Toxoplasma gondii ANTIMICROBIAL AGENTS AND CHEMOTHERAPY Araujo, F. G., Khan, A. A., Remington, J. S. 1996; 40 (6): 1335-1337

    Abstract

    Rifapentine, a derivative of rifamycin, was examined for its in vitro and in vivo activities against the protozoan parasite Toxoplasma gondii. The drug inhibited the intracellular replication of parasites and was not cytotoxic for the host cells at inhibitory concentrations. Mice infected either intraperitoneally with tachyzoites of the RH strain or orally with tissue cysts of the C56 strain were protected against death by treatment with rifapentine. The degree of protection was similar to that induced by atovaquone and apparently higher than that induced by rifabutin. Rifapentine may be a useful drug for the treatment of toxoplasmosis in immunocompromised individuals.

    View details for Web of Science ID A1996UP10700002

    View details for PubMedID 8725996

  • Use of rifabutin in combination with atovaquone, clindamycin, pyrimethamine, or sulfadiazine for treatment of toxoplasmic encephalitis in mice EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES Araujo, F. G., Suzuki, Y., Remington, J. S. 1996; 15 (5): 394-397

    Abstract

    The effectiveness of combinations of rifabutin with atovaquone, clindamycin, pyrimethamine, or sulfadiazine in the treatment of toxoplasmic encephalitis in a murine model was investigated. Doses of each drug that were not effective in reducing inflammation in the brain of mice with toxoplasmic encephalitis when used alone were used in combination with a dose of rifabutin which was minimally effective. At the end of each period of therapy (15 or 30 days), brains of mice were examined histopathologically and the severity of the inflammatory lesions scored. Treatment with rifabutin in combination with pyrimethamine or sulfadiazine did not reduce brain inflammation significantly when compared to treatment with each drug alone. In contrast, treatment with rifabutin plus atovaquone for 15 or 30 days or with rifabutin plus clindamycin for 15 days resulted in statistically significant reduction in the inflammation. These results suggest that combining rifabutin with certain drugs that are active against Toxoplasma gondii may be useful for the treatment of toxoplasmic encephalitis in humans and may allow for a reduction in dosage of either or both drugs with a resulting reduction in untoward side effects.

    View details for Web of Science ID A1996UR49300007

    View details for PubMedID 8793398

  • Resolution of intracranial calcifications in infants with treated congenital toxoplasmosis RADIOLOGY Patel, D. V., Holfels, E. M., Vogel, N. P., Boyer, K. M., Mets, M. B., SWISHER, C. N., ROIZEN, N. J., Stein, L. K., Stein, M. A., Hopkins, J., Withers, S. E., Mack, D. G., LUCIANO, R. A., MEIER, P., Remington, J. S., McLeod, R. L. 1996; 199 (2): 433-440

    Abstract

    To determine the natural history of intracranial calcifications in infants with treated congenital toxoplasmosis.Between January 1982 and March 1994, cranial computed tomography was performed in 56 infants with treated congenital toxoplasmosis when they were newborns and approximately 1 year old. Locations and sizes of intracranial calcifications were noted.Forty newborns had intracranial calcifications. By 1 year of age, calcifications diminished or resolved in 30 (75%) and remained stable in 10 (25%) of these treated infants. Ten (33%) of the 30 infants whose calcifications diminished versus seven (70%) of the 10 infants with stable calcifications received less intensive antimicrobial treatment than the other treated infants. In contrast, a small number of infants who were untreated or treated 1 month or less had intracranial calcifications that increased or remained stable during their 1st year of life.Diminution or resolution of intracranial calcifications was an unexpected and remarkable finding in infants with treated, congenital toxoplasmosis, consonant with their improved neurologic functioning.

    View details for Web of Science ID A1996UG01100023

    View details for PubMedID 8668790

  • Human CD4(+) and CD8(+) T lymphocytes are both cytotoxic to Toxoplasma gondii-infected cells INFECTION AND IMMUNITY Montoya, J. G., Lowe, K. E., CLAYBERGER, C., Moody, D., Do, D., Remington, J. S., Talib, S., Subauste, C. S. 1996; 64 (1): 176-181

    Abstract

    Studies to determine if Toxoplasma gondii-specific human T cells lyse parasite-infected cells have yielded conflicting results. Furthermore, attempts to obtain human cytotoxic CD8+ T lymphocytes have been difficult because of the lack of a reproducible system for their generation. By using paraformaldehyde-fixed, T. gondii-infected peripheral blood mononuclear cells as antigen-presenting cells, we developed a method whereby T. gondii-specific T-cell lines can be reproducibly generated. Six T. gondii-specific T-cell lines were generated from an individual chronically infected with T. gondii. Cytofluorometric analysis of these lines revealed > 99% CD3+, 85 to 95% CD3+ alpha beta T-cell-receptor-positive (TCR+), 5 to 9% CD3+ gamma delta TCR+, 50 to 70% CD4+, and 20 to 40% CD8+ cells when cells were examined during the first 3 weeks of stimulation and >99% CD3+, >99% CD3+ alpha beta TCR+, < 1% CD3+ gamma delta TCR+, 20 to 40% CD4+, and 60 to 80% CD8+ cells when cells were examined between 5 and 11 weeks. Both CD4+ and CD8+ T cells had remarkable cytotoxic activity against T. gondii-infected target cells (30 to 50% specific Cr release at an effector-to-target ratio of 30:1) but not against uninfected target cells ( < 10% at an effector-to-target ratio of 30:1). Cytotoxic activity by the whole T-cell lines was not T. gondii strain specific. Whole T-cell lines were cytotoxic for target cells infected with the C56 and ME49 strains and the RH strain (which was used to infect peripheral blood mononuclear cells). T. gondii-specific T-cell lines displayed the predominant expression of V beta 7 TCR. The CDR3 regions of the V beta 7 TCRs of these T-cell lines showed a striking degree of sequence identity (oligoclonality). T-cell lines obtained by the method reporter here can be used to characterize functional activity of T-lymphocyte subsets in humans infected with T. gondii.

    View details for Web of Science ID A1996TM71800025

    View details for PubMedID 8557337

  • Evidence for genetic regulation of susceptibility to toxoplasmic encephalitis in AIDS patients JOURNAL OF INFECTIOUS DISEASES Suzuki, Y., Wong, S. Y., GRUMET, F. C., Fessel, J., Montoya, J. G., Zolopa, A. R., PORTMORE, A., SCHUMACHERPERDREAU, F., Schrappe, M., Koppen, S., Ruf, B., Brown, B. W., Remington, J. S. 1996; 173 (1): 265-268

    Abstract

    The frequency of HLA-DQ antigens in AIDS patients with toxoplasmic encephalitis (TE) were examined. HLA-DQ3 was significantly more frequent in white North American AIDS patients with TE (85.0%) than in the general white population (51.8%; P = .007, corrected P = .028) or randomly selected control AIDS patients who had not developed TE (40.0%; P = .016). In contrast, the frequency of HLA-DQ1 was lower in TE patients than in healthy controls (40.0% vs. 66.5%, P = .027), but this difference did not reach statistical significance when corrected for the number of variables tested (corrected P = .108 for the general white population). HLA-DQ3 thus appears to be a genetic marker of susceptibility to development of TE in AIDS patients, and DQ1 may be a resistance marker. These HLA associations with disease indicate that development of TE in AIDS patients is affected by a gene or genes in the HLA complex and that HLA-DQ typing may help in decisions regarding TE prophylaxis.

    View details for Web of Science ID A1996TM34300042

    View details for PubMedID 8537674

  • Cells and cytokines in resistance to Toxoplasma gondii TOXOPLASMA GONDII Hunter, C. A., Suzuki, Y., Subauste, C. S., Remington, J. S. 1996; 219: 113-125

    View details for Web of Science ID A1996BJ59J00011

    View details for PubMedID 8791694

  • Genetic resistance against acute toxoplasmosis depends on the strain of Toxoplasma gondii JOURNAL OF PARASITOLOGY Suzuki, Y., Yang, Q., Remington, J. S. 1995; 81 (6): 1032-1034

    Abstract

    The role of the strain of Toxoplasma gondii in genetic control of resistance against acute infection with T. gondii was studied with 2 strains of T. gondii, which differ in their virulence and genotype. Following peroral infection with 10 cysts of the C56 strain, C57BL/6 (H-2b) and C3H/HeN (H-2k) mice died significantly earlier than BALB/c mice (H-2d) mice, although all of the mice eventually died of acute toxoplasmosis from 10 to 23 days after infection. There was no significant difference in time to death between C57BL/6 mice and C3H/HeN mice. In peroral infection with 100 cysts of the less virulent ME49 strain, all C57BL/6 mice died of acute toxoplasmosis from 7 to 10 days after infection. C57BL/6 mice died significantly earlier following infection with the ME49 strain than with the C56 strain, whereas all C3H/HeN mice infected with the ME49 strain survived as did BALB/c mice. These results indicate that genetic control of resistance against acute infection with T. gondii differs depending on the strain of T. gondii.

    View details for Web of Science ID A1995TL74600042

    View details for PubMedID 8544050

  • IL-1-BETA IS REQUIRED FOR IL-12 TO INDUCE PRODUCTION OF IFN-GAMMA BY NK-CELLS - A ROLE FOR IL-1-BETA IN THE T-CELL-INDEPENDENT MECHANISM OF RESISTANCE AGAINST INTRACELLULAR PATHOGENS JOURNAL OF IMMUNOLOGY Hunter, C. A., Chizzonite, R., Remington, J. S. 1995; 155 (9): 4347-4354

    Abstract

    Mice with the severe combined immunodeficiency (SCID) possess an IFN-gamma-dependent mechanism of resistance to the intracellular pathogens Toxoplasma gondii and Listeria monocytogenes that is dependent on IL-12-induced production of IFN-gamma by NK cells. In this report we demonstrate that IL-1 beta is required for IL-12 to stimulate production of IFN-gamma by NK cells, and that IL-1 is important in IL-12-mediated resistance to T. gondii in vivo. Stimulation of SCID mouse splenocytes with tachyzoites of T. gondii resulted in production of IFN-gamma. Addition of neutralizing Ab specific for IL-1 beta to these cultures inhibited completely the production of IFN-gamma. Similar results were obtained when LPS or L. monocytogenes were used to stimulate production of IFN-gamma by SCID mouse splenocytes. Addition of a neutralizing Ab to IL-1 alpha did not affect production of IFN-gamma by SCID mouse splenocytes stimulated with T. gondii, L. monocytogenes, or LPS. Stimulation of SCID mouse splenocytes with IL-1 beta or IL-1 alpha did not result in production of IFN-gamma but enhanced remarkably the ability of T. gondii or IL-12 to stimulate production of IFN-gamma. Furthermore, production of IFN-gamma by SCID mouse splenocytes stimulated with IL-12 plus TNF-alpha was completely ablated by anti-IL-1 beta, but not by anti-IL-1 alpha. Analysis of the culture supernatants of spleen cells from SCID mice stimulated with T. gondii or IL-12 plus TNF-alpha detected low levels of IL-1 beta; addition of a neutralizing Ab to IFN-gamma resulted in a 5- to 10-fold increase in levels of IL-1 beta. Furthermore, stimulation of SCID mouse splenocytes with IL-12, in the presence of anti-IFN-gamma, resulted in an increase in detectable levels of IL-1 beta. To determine the in vivo relevance of our in vitro data, SCID mice were infected with T. gondii and treated with IL-12 alone or IL-12 in combination with an Ab specific for the type I IL-1 receptor. This Ab reduced production of IFN-gamma by SCID mouse splenocytes stimulated with either T. gondii, LPS, L. monocytogenes, or IL-12 plus IL-1 beta. In vivo administration of this Ab antagonized significantly the ability of exogenous IL-12 to delay the time to death of SCID mice infected with T. gondii.(ABSTRACT TRUNCATED AT 400 WORDS)

    View details for Web of Science ID A1995TB46800029

    View details for PubMedID 7594594

  • The role of IL12 in toxoplasmosis RESEARCH IN IMMUNOLOGY Hunter, C. A., Remington, J. S. 1995; 146 (7-8): 546-551

    View details for Web of Science ID A1995TW31300076

    View details for PubMedID 8839160

  • DEFINITIVE IDENTIFICATION OF A GENE THAT CONFERS RESISTANCE AGAINST TOXOPLASMA CYST BURDEN AND ENCEPHALITIS IMMUNOLOGY Brown, C. R., Hunter, C. A., Estes, R. G., Beckmann, E., Forman, J., David, C., Remington, J. S., McLeod, R. 1995; 85 (3): 419-428

    Abstract

    Control of resistance to cyst burden following per-oral infection with Toxoplasma gondii has been mapped previously to a region of mouse chromosome 17 of approximately 140 kb. This region is contiguous with and contains the class I gene, Ld. Resistance to development of toxoplasmic encephalitis has also been reported to be controlled by genes in this region of H-2. TNF-alpha, D and L genes, as well as unidentified genes, are also in this region. The work described here was performed to identify definitively the gene(s) in this 140 kb region that confers resistance to cysts and encephalitis. The study demonstrates that relative resistance to T. gondii organisms and cyst burden in brain, and toxoplasmic encephalitis, 30 days following per-oral T. gondii infection is correlated absolutely with the presence of the Ld gene in inbred, recombinant, mutant and C3H.Ld transgenic mice. Mice with the Ld gene had lower cyst burdens and less encephalitis than those without the Ld gene. Specifically, 30 days after infection mice with the Ld gene had minimal perivascular inflammation and meningeal inflammation and very few Toxoplasma cysts or organisms in immunoperoxidase-stained preparations of their brains. Mice without the Ld gene had a similar pattern of inflammation, but in addition they had collections of inflammatory cells in the brain parenchyma. Free tachyzoites were found within these foci of inflammation and cysts were present in these areas as well as in contiguous areas without inflammatory cells. There were CD4+ and CD8+ T lymphocytes in the areas of inflammation and throughout the brain parenchyma. Mice that were resistant to cysts and encephalitis had little detectable brain cytokine mRNA expression, while mice that were susceptible had elevated levels of mRNA for a wide range of cytokines, consistent with their greater amounts of inflammation. The present work definitively demonstrates that a Ld-restricted response decreases the number of organisms and cysts within the brain and thereby limits toxoplasmic encephalitis and levels of interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2), IL-6, IL-10, transforming growth factor-beta (TGF-beta), IL-1 alpha, IL1 beta and macrophage inhibiting protein (MIP) mRNA in the brain 30 days after per-oral infection.

    View details for Web of Science ID A1995RK30100011

    View details for PubMedID 7558130

  • PREFERENTIAL ACTIVATION AND EXPANSION OF HUMAN PERIPHERAL-BLOOD GAMMA-DELTA T-CELLS IN RESPONSE TO TOXOPLASMA GONDII IN VITRO AND THEIR CYTOKINE PRODUCTION AND CYTOTOXIC ACTIVITY AGAINST T-GONDII-INFECTED CELLS JOURNAL OF CLINICAL INVESTIGATION Subauste, C. S., Chung, J. Y., Do, D., Koniaris, A. H., Hunter, C. A., Montoya, J. G., Porcelli, S., Remington, J. S. 1995; 96 (1): 610-619

    Abstract

    Studies were conducted to determine if gamma delta T cells participate in the immune response to Toxoplasma gondii. Preferential expansion of human gamma delta T cells occurred when peripheral blood T cells from either T. gondii-seronegative or seropositive individuals were incubated with autologous PBMC infected with the parasite. That gamma delta T cells proliferated after incubation with infected cells was confirmed using purified of gamma delta T cells. These T. gondii-induced gamma delta T cell responses did not require prior exposure to the parasite since T cells obtained from umbilical cord blood from seronegative newborns also exhibited preferential expansion of gamma delta T cells. Cytofluorometric analysis of T cells obtained from either umbilical cord blood or peripheral blood from adults revealed that V gamma 9+ and V delta 2+ gamma delta T cells responded to stimulation with infected cells. Preferential expansion of gamma delta T cells was not restricted by polymorphic determinants of MHC molecules. PBMC that had internalized killed parasites but not PBMC incubated with T. gondii lysate antigens also stimulated preferential expansion and activation of gamma delta T cells as assessed by expression of CD25 and HLA-DR molecules. V gamma 9+V delta 2+ gamma delta T cells were cytotoxic for T. gondii-infected cells in an MHC-unrestricted manner, and produced IFN-gamma, IL-2, TNF-alpha, but not IL-4 when incubated with cells infected with the parasite. These results suggest that rapid induction of a remarkable primary gamma delta T cell response may be important in the early protective immune response to T. gondii.

    View details for Web of Science ID A1995RH89400073

    View details for PubMedID 7615835

  • STUDIES ON THE SERODIAGNOSIS OF TOXOPLASMIC LYMPHADENITIS CLINICAL INFECTIOUS DISEASES Montoya, J. G., Remington, J. S. 1995; 20 (4): 781-789

    Abstract

    The purpose of this study was to determine the value of conventional and newer serological tests (toxoplasmic serological profile) in the diagnosis of toxoplasmic lymphadenitis (TL). We studied 40 consecutive patients with biopsy-proven TL. Cervical, axillary, or occipital adenopathy was present in 72.5%, 20%, and 7.5% of the patients, respectively. Low-grade fever, fatigue, general malaise, or sore throat were present in only 6 (15%) of the 40 patients. A positive result for all serological tests was time dependent from the clinical onset of lymphadenopathy. The initial serum samples were positive for antibody for each patient, as shown by a Sabin-Feldman dye test. Between 3 and 6 months after clinical onset of TL, all of the patients had antibody titers of > or = 1:1,024. The ELISA was positive for IgM antibodies in all of the patients in the first 3 months. Detection of IgA or IgE antibodies or an acute pattern in the differential agglutination test was helpful in diagnosing TL in those patients who had negative, low-positive, or equivocal titers of IgM antibodies (as measured by ELISA) after 3 months. A toxoplasmic serological profile on the first serum specimen drawn after clinical onset of TL had a sensitivity of 100%. It is advisable to obtain such a serological profile in cases of asymptomatic lymphadenopathy before biopsy is carried out, especially for those individuals who have negative or equivocal IgM antibody titers.

    View details for Web of Science ID A1995QP66200008

    View details for PubMedID 7795074

  • TRANSFORMING GROWTH-FACTOR-BETA INHIBITS INTERLEUKIN-12-INDUCED PRODUCTION OF INTERFERON-GAMMA BY NATURAL-KILLER-CELLS - A ROLE FOR TRANSFORMING GROWTH-FACTOR-BETA IN THE REGULATION OF T-CELL-INDEPENDENT RESISTANCE TO TOXOPLASMA-GONDII EUROPEAN JOURNAL OF IMMUNOLOGY Hunter, C. A., Bermudez, L., BEERNINK, H., Waegell, W., Remington, J. S. 1995; 25 (4): 994-1000

    Abstract

    Severe-combined immune deficient (SCID) mice have been found to resist infection with the intracellular protozoan parasite Toxoplasma gondii via interleukin (IL)-12 stimulation of interferon (IFN)-gamma production by natural killer (NK) cells. Previously, we demonstrated the presence of increased levels of transcripts for transforming growth factor-beta (TGF-beta) in the brains and lungs of SCID mice infected with T. gondii, leading us to investigate the role of TGF-beta in the mechanism of resistance to T. gondii in these mice. Stimulation of splenocytes from SCID mice with heat-killed T. gondii resulted in production of low levels of IFN-gamma and a two to threefold increase in levels of TGF-beta in the culture supernatants. Production of IFN-gamma in these cultures was increased three to fourfold by addition of anti-TGF-beta antibody. Stimulation of splenocytes from SCID mice with IL-12 in combination with either TNF-alpha or IL-1 beta resulted in production of high levels of IFN-gamma. Addition of TGF-beta to these cultures inhibited production of IFN-gamma in a dose-dependent manner. Immunohistochemical studies revealed increased levels of TGF-beta protein in the spleens of SCID mice 5 days after oral infection with the ME49 strain of T gondii, and brains of SCID mice at 18 days post-infection. However, no difference was detected in the levels of TGF-beta transcripts in the spleens of uninfected mice or mice infected for 5 days. To test whether TGF-beta could antagonize IL-12 mediated resistance to T. gondii in vivo, we administered TGF-beta to SCID mice infected with T. gondii. This treatment resulted in earlier mortality of infected mice and significantly reduced the ability of exogenous IL-12 to delay time-to-death. Administration of anti-TGF-beta to SCID mice, beginning 24 h prior to infection and every 2 days thereafter, delayed significantly time-to-death. Together, our data demonstrate that TGF-beta antagonizes the ability of IL-12 to stimulate production of IFN-gamma by splenocytes from SCID mice, and suggest a role for TGF-beta in regulation of T cell-independent resistance to T. gondii.

    View details for Web of Science ID A1995QY50800018

    View details for PubMedID 7737303

  • ROLES OF GAMMA-INTERFERON AND OTHER CYTOKINES IN SUPPRESSION OF THE SPLEEN-CELL PROLIFERATIVE RESPONSE TO CONCANAVALIN-A AND TOXOPLASMA ANTIGEN DURING ACUTE TOXOPLASMOSIS INFECTION AND IMMUNITY Candolfi, E., Hunter, C. A., Remington, J. S. 1995; 63 (3): 751-756

    Abstract

    Suppressed splenocyte proliferation in response to mitogen and toxoplasma lysate antigen (TLA) is observed in mice acutely infected with Toxoplasma gondii. Recently, we reported that NG-monomethyl-L-arginine (NMMA), an inhibitor of reactive nitrogen intermediate (RNI) production, partially restored proliferative responses of splenocytes from infected mice. In the present study we have examined the effect of NMMA on production of cytokines by splenocytes from mice acutely infected with T. gondii and assessed the role of gamma interferon (IFN-gamma) and interleukin-10 (IL-10) in the RNI-mediated suppression. Stimulation with concanavalin A (ConA) or TLA of splenocytes from CBA/Ca mice infected for 7 days resulted in increased production of IFN-gamma, IL-4, and IL-10 but reduced levels of IL-2 when compared with cultures of splenocytes from uninfected mice. Whereas addition of NMMA did not alter levels of cytokines produced by splenocytes from uninfected mice, splenocytes from infected mice stimulated with ConA produced significantly higher levels of IL-10 and reduced levels of IL-2 and IL-4. Addition of anti-IFN-gamma monoclonal antibodies to cultures of spleen cells from mice infected for 7 or 14 days remarkably decreased the levels of nitrite and resulted in a 47- and 4-fold increase in proliferation induced by stimulation with ConA or TLA, respectively. Anti-IL-10 did not reduce levels of nitrite produced in culture but did result in a fourfold increase in the proliferative response of splenocytes from mice infected for 14 days. In vivo administration of anti-IFN-gamma or anti-IL-10 monoclonal antibodies to infected mice partially restored ex vivo spleen cell proliferative responses by approximately 40 and 15%, respectively. Our data indicate that IFN-gamma is important in inducing the RNI-mediated immunosuppression, which, in turn, affects production of cytokines by splenocytes. Our data also demonstrate that IL-10 is involved in the suppression observed but that this activity is independent of RNI.

    View details for Web of Science ID A1995QJ52400002

    View details for PubMedID 7868243

    View details for PubMedCentralID PMC173066

  • IL-1b is required for IL-12 to induce production of IFN-j by NK cells. J. Immun. Remington J.S., Hunter C.A., Chizzonite R. 1995: 4347-4354
  • STUDIES ON THE ROLE OF INTERLEUKIN-12 IN ACUTE MURINE TOXOPLASMOSIS IMMUNOLOGY Hunter, C. A., Candolfi, E., Subauste, C., VANCLEAVE, V., Remington, J. S. 1995; 84 (1): 16-20

    Abstract

    Interleukin-12 (IL-12) is important in the regulation of resistance to Toxoplasma gondii in mice with severe combined immunodeficiency (SCID). The protective ability of IL-12 in SCID mice appears to be through its activity on natural killer (NK) cells to induce production of interferon-gamma (IFN-gamma). In this study we assessed the role of IL-12 in the acute stage of toxoplasmosis in immunocompetent mice. Administration of IL-12 to BALB/c mice infected with the virulent C56 strain of T. gondii remarkably delayed time to death. The protective activity of IL-12 was abrogated by administration of monoclonal antibodies to IFN-gamma or tumour necrosis factor-alpha (TNF-alpha), and by depletion of NK cells using an antisera against asialoGM1. Whereas BALB/c mice infected with the ME49 strain of T. gondii survived infection, administration of anti-IL-12 to infected mice resulted in 100% mortality accompanied by decreased serum levels of IFN-gamma. Furthermore, this treatment significantly reversed the suppression of spleen cell proliferation to concanavalin A (Con A), which is associated with the acute stage of infection, and resulted in decreased ex vivo production of IFN-gamma, IL-2, IL-4 and IL-10 in response to Con A. Our results indicate an important role for IL-12 in mediating resistance to T. gondii during acute infection in immunocompetent mice, that NK cells are required for this protective activity, and that IL-12 is involved in the immunosuppression which accompanies this infection.

    View details for Web of Science ID A1995PZ44600004

    View details for PubMedID 7890300

    View details for PubMedCentralID PMC1415199

  • NEUROLOGIC AND DEVELOPMENTAL OUTCOME IN TREATED CONGENITAL TOXOPLASMOSIS PEDIATRICS Roizen, N., SWISHER, C. N., Stein, M. A., Hopkins, J., Boyer, K. M., Holfels, E., Mets, M. B., Stein, L., Patel, D., MEIER, P., Withers, S., Remington, J., Mack, D., Heydemann, P. T., Patton, D., McLeod, R. 1995; 95 (1): 11-20

    Abstract

    Earlier studies have shown that infants with untreated congenital toxoplasmosis and generalized or neurologic abnormalities at presentation almost uniformly develop mental retardation, seizures, and spasticity. Children with untreated subclinical disease at birth have developed seizures, significant cognitive and motor deficits, and diminution in cognitive function over time.To determine neurologic, cognitive, and motor outcomes for children with congenital toxoplasmosis who were treated for approximately 1 year with pyrimethamine and sulfadiazine.Systematic, prospective, and longitudinal neurologic, cognitive, and motor evaluations were performed for 36 individuals with congenital toxoplasmosis. These infants were born between December 1981 and January 1991 and were treated with pyrimethamine and sulfadiazine for approximately 1 year beginning in the first months of life. Compliance with medications was documented. These individuals were evaluated in a standardized manner in a single center in the first months of life and at approximately 1, 3.5, 5, 7.5, and 10 years of age. Their cognitive function was compared with the cognitive function of a nearest-age, same-sex sibling when such siblings older than 3.5 years were available for study.Signs of active central nervous system infection (eg, cerebrospinal fluid [CSF] pleiocytosis, hypoglycorrhachia, elevated CSF protein, and, in some instances, seizures and motor abnormalities) resolved during therapy. Six of the 36 children had perinatal seizures. Four had their anticonvulsant therapy discontinued successfully within the first months of life, and two additional children developed new seizures at 3 and 5 years of age. Tone and motor abnormalities resolved by 1 year of age in 12 of 20 infants who exhibited abnormalities of tone and motor function at their initial neonatal evaluation. By February 1992, 29 of the 36 children had been evaluated when they were 1 year old, and 23 (79%) had a mean +/- standard deviation Mental Developmental Index (MDI) of 102 +/- 22 (range, 59 to 140). Six (21%) had a measure of their cognitive function that was less than 50. Results of sequential IQ tests, performed at 1.5 year intervals or greater, did not differ significantly over time (P > .05). Seven children with MDIs greater than 50 were compared with sibling controls; they had scores of 87 +/- 11 (range, 68 to 97) and their siblings had scores of 112 +/- 15 (range, 85 to 132) (P = .008). Seventeen of 18 children without hydrocephalus and six of eight children with obstructive hydrocephalus responsive to shunting had normal or near-normal neurologic and developmental outcomes. Children with hydrocephalus ex vacuo present at birth, with high CSF protein, and with lack of response to shunting have done less well.Neurologic and developmental outcomes were significantly better for most of these treated children than outcomes reported for untreated children or those treated for only 1 month (P < .001). Although the level of cognitive function for treated children was less than for their uninfected siblings (P < .008), there was no significant deterioration in neurologic and cognitive function of the treated children tested sequentially. These favorable treatment outcomes justify systematic identification and treatment of pregnant women with acute gestational Toxoplasma infection and young infants with congenital toxoplasmosis.

    View details for Web of Science ID A1995PZ72900003

    View details for PubMedID 7770286

  • Transforming growth factor-b inhibits interleukin-12 induced production of interferon-g by natural killer cells: a role for transforming growth factor-b in the regulation of T cell-independent resistance to Toxoplasma gondii. Eur. J. Immun. Remington J.S., Hunter C.A., Bermudez L.E., Beernink H., Waegell W. 1995: 994-1000
  • MHC CLASS-I GENE(S) IN THE D/L REGION BUT NOT THE TNF-ALPHA GENE DETERMINES DEVELOPMENT OF TOXOPLASMIC ENCEPHALITIS IN MICE JOURNAL OF IMMUNOLOGY Suzuki, Y., Joh, K., Kwon, O. C., Yang, Q., CONLEY, F. K., Remington, J. S. 1994; 153 (10): 4649-4654

    Abstract

    Previous studies revealed that mice with the b or k allele at the H-2D region are susceptible to toxoplasmic encephalitis (TE); those with the d allele are resistant. To determine whether the b or d allele is dominant, F1 hybrids between susceptible C57BL/6 (H-2b) and resistant BALB/c (H-2d) mice were infected with T. gondii. TE was not observed in the F1 hybrids, indicating that the d allele is dominant for protection against development of TE. Mice with a mutation in the D/L region were used to determine whether the D gene or the L gene of MHC class I Ags of the H-2D region is most critical for resistance against development of TE. B10.D2-H2dm1 (dm1) mice that have the mutant D/L hybrid gene formed by fusion of the 5' part of the Dd gene and the 3' part of the Ld gene developed TE in contrast to their background B10.D2 mice. BALB/c-H-2dm2 (dm2) mice, which have a complete deletion of the Ld gene, had significantly more T. gondii cysts in their brains than did dm1 mice and developed large areas of necrosis in their brains that were not observed in dm1 mice. These results indicate that a gene(s) in the D/L region determines whether TE will occur and that the Ld gene plays a critical role in the resistance against development of TE. Polymorphisms in the TNF-alpha gene (located in the H-2D region) have been reported to correlate with resistance against the development of TE. When development of TE was studied in BALB/c and dm2 mice that have the same TNF-alpha gene, only dm2 mice developed TE. This indicates that the TNF-alpha gene is not a determining factor for the development of TE. Transcripts for TNF-alpha were detected in brains of infected dm2 mice but not in BALB/c mice. Injection of neutralizing Abs against TNF-alpha resulted in worsening of the TE in infected dm2 mice but did not induce TE in infected BALB/c mice. Thus, TNF-alpha appears to be produced in the brain after TE has developed and is responsible for preventing the progression of TE.

    View details for Web of Science ID A1994PR22200032

    View details for PubMedID 7963536

  • ENHANCEMENT OF INTRACELLULAR REPLICATION OF TOXOPLASMA-GONDII BY IL-6 - INTERACTIONS WITH IFN-GAMMA AND TNF-ALPHA JOURNAL OF IMMUNOLOGY Beaman, M. H., Hunter, C. A., Remington, J. S. 1994; 153 (10): 4583-4587

    Abstract

    Toxoplasma gondii is a major pathogen of immunocompromised hosts, and one defense mechanism against the parasite is activation of macrophages (M phi) for toxoplasmacidal activity by IFN-gamma after triggering by TNF-alpha. IL-6, IFN-gamma, and TNF-alpha are cytokines involved in inflammatory responses and are induced by T. gondii infection. We studied the interaction of these three cytokines using an in vitro model of T. gondii infection. Pretreatment (but not post-treatment) of unelicited murine peritoneal M phi with IL-6 enhanced T. gondii replication in a dose-dependent manner. Pretreatment with IFN-gamma resulted in active killing of parasites whereas the addition of IL-6 to IFN-gamma pretreatment resulted in a reversal of IFN-gamma-mediated toxoplasmacidal activity. Combining TNF-alpha with IL-6 and IFN-gamma pretreatment resulted in restoration of toxoplasmacidal activity. Addition of a polyclonal anti-TNF-alpha Ab to IL-6 and IFN-gamma pretreatment resulted in enhancement in the IL-6-mediated impairment of IFN-gamma function. These data taken together suggest that IL-6 enhances intracellular replication of T. gondii and reverses IFN-gamma mediated activation of murine peritoneal M phi, and that certain of the interactions between these two cytokines may be at the level of TNF-alpha triggering.

    View details for Web of Science ID A1994PR22200025

    View details for PubMedID 7963530

  • IMMUNOPATHOGENESIS OF TOXOPLASMIC ENCEPHALITIS JOURNAL OF INFECTIOUS DISEASES Hunter, C. A., Remington, J. S. 1994; 170 (5): 1057-1067

    Abstract

    The incidence of toxoplasmic encephalitis (TE) has increased with the increasing numbers of patients with immunodeficiencies, in whom reactivation of latent Toxoplasma infection may occur. This highlights the important role of the immune response in maintaining infection with Toxoplasma gondii in a latent form. Because the brain is the most commonly affected site of latent infection and because it is anatomically unique in regard to the immune system, understanding the systemic immune response to infection within the brain is important. Murine models have proven useful for the study of the immune response to T. gondii and identified the importance of cytokines and NK and T cells in the regulation of protective immunity to T. gondii. Further studies on the development of TE have indicated the possible importance of the interactions of glial cells, such as microglia and astrocytes, with infiltrating T cells to mediate immunity to T. gondii within the brain.

    View details for Web of Science ID A1994PN66800001

    View details for PubMedID 7963693

  • IMMUNOCYTOCHEMICAL DETECTION OF CYTOKINES IN THE LYMPH-NODES AND BRAINS OF MICE RESISTANT OR SUSCEPTIBLE TO TOXOPLASMIC ENCEPHALITIS JOURNAL OF INFECTIOUS DISEASES Hunter, C. A., Litton, M. J., Remington, J. S., Abrams, J. S. 1994; 170 (4): 939-945

    Abstract

    BALB/c mice develop toxoplasmic encephalitis (TE) but the pathology resolves; in contrast, CBA/Ca mice develop progressive TE. Immunohistochemical analysis revealed peak staining for interferon-gamma (IFN-gamma) and tumor necrosis factor (TNF) in lymph nodes of both strains on day 7 of infection, with elevated levels of IFN-gamma and TNF persisting in CBA/Ca mice. TNF was present in the central nervous systems (CNS) of both strains of mice and correlated with severity of pathology. Interleukin (IL)-2 was detected in lymph nodes and CNS of CBA/Ca mice after day 52 of infection and only in the lymph nodes of BALB/c mice between days 14 and 21 after infection. Highest levels of IL-10 were observed in lymph nodes and CNS of infected CBA/Ca mice. Variations in cytokine levels in lymph nodes and CNS of these mouse strains may account for differences in their susceptibility to TE.

    View details for Web of Science ID A1994PJ69400029

    View details for PubMedID 7930739

  • A MORPHOLOGICAL-STUDY OF CHRONIC CEREBRAL TOXOPLASMOSIS IN MICE - COMPARISON OF 4 DIFFERENT STRAINS OF TOXOPLASMA-GONDII PARASITOLOGY RESEARCH Ferguson, D. J., HUSKINSONMARK, J., Araujo, F. G., Remington, J. S. 1994; 80 (6): 493-501

    Abstract

    The pathological changes, host-parasite relationship and structure of the tissue cysts in the brains of mice chronically infected with four different strains of Toxoplasma gondii were examined by light and electron microscopy. In mice infected with the mouse-adapted ME49 strain for 4, 8, 12, 16 and 25 weeks, the pathological changes consisted of moderate to severe meningitis and cuffing of blood vessels by inflammatory cells. At 4 weeks post-infection (p.i.), lymphocytes were the major cell type, but at later time points, plasma cells predominated. Large numbers of cysts were observed at between 4 and 12 weeks p.i., with a decrease being seen at 16 weeks p.i. Microglial nodules, many containing tachyzoites or bradyzoites, were present at all time points. In contrast, the three strains isolated from patients with the acquired immune deficiency syndrome (AIDS) resulted in no meningitis in two cases (DEY, DAG) and in mild meningitis in one case (WIL), although all three showed some cuffing of blood vessels. In addition, only very low numbers of cysts and nodules were observed. Ultrastructurally, the cysts of all four strains were seen to be located within host cells. The cysts of the ME49 strain differed from those of the other strains in that a proportion contained immature and dividing bradyzoites at all time points, whereas those of the other strains contained only mature bradyzoites. From the observation of nodules with parasites and cysts with immature zoites, it would appear that the ME49 strain may result in an unstable chronic infection with a continuous turnover of cysts, a feature that should be taken into consideration when this strain is used as an experimental model of chronic toxoplasmosis.

    View details for Web of Science ID A1994PC41300008

    View details for PubMedID 7808999

  • MOLECULAR CHARACTERIZATION OF A 65-KILODALTON TOXOPLASMA-GONDII ANTIGEN EXPRESSED ABUNDANTLY IN THE MATRIX OF TISSUE CYSTS MOLECULAR AND BIOCHEMICAL PARASITOLOGY Parmley, S. F., Yang, S. M., Harth, G., Sibley, L. D., Sucharczuk, A., Remington, J. S. 1994; 66 (2): 283-296

    Abstract

    We describe the cloning and characterization of a novel antigen expressed in the bradyzoite stage of Toxoplasma gondii. A cDNA library was constructed in bacteriophage lambda gt11 Sfi-Not using messenger RNA molecules isolated from cysts of the ME49 strain of T. gondii. The recombinant phage library was subjected to screening with polyclonal antibodies against bradyzoite antigens. This screening identified a recombinant antigen that was recognized strongly by polyclonal antibodies against bradyzoite antigens as well as by sera from mice chronically infected with T. gondii. The native antigen is a protein of 65 kDa that localized to the matrix of the cyst and the cyst wall surrounding the bradyzoites. The antigen was found to be expressed abundantly in cysts but could not be detected in tachyzoites or within the parasitophorous vacuole of tachyzoite infected host cells. Genomic and cDNA sequence of the gene revealed an open reading frame encoding 452 amino acids interrupted by 2 introns: a 503-bp intron located in the 5' untranslated region preceding the protein coding sequence and a 110-bp intron located 95 bp downstream of the first ATG.

    View details for Web of Science ID A1994PE32100010

    View details for PubMedID 7808478

  • ANTIBODY AGAINST INTERLEUKIN-6 REDUCES INFLAMMATION AND NUMBERS OF CYSTS IN BRAINS OF MICE WITH TOXOPLASMIC ENCEPHALITIS INFECTION AND IMMUNITY Suzuki, Y., Yang, Q., CONLEY, F. K., Abrams, J. S., Remington, J. S. 1994; 62 (7): 2773-2778

    Abstract

    Treatment of toxoplasmic encephalitis in C57BL/6 mice with monoclonal antibody (MAb) against interleukin-6 (IL-6) resulted in a remarkable decrease in the number of foci of acute inflammation in their brains caused by proliferation of tachyzoites. In brains of mice treated with isotype control MAb and those treated with anti-IL-6 MAb, tachyzoites were observed only in foci of acute inflammation. Immunoperoxidase staining revealed a greatly diminished frequency of tachyzoites in brains of mice treated with anti-IL-6 MAb. Of interest, treatment with MAb against IL-6 was also associated with reduced numbers of Toxoplasma gondii cysts in the brains and with higher serum levels of gamma interferon than in control mice. Paradoxically, the mice treated with anti-IL-6 MAb had higher serum levels of IL-6 as measured by an enzyme-linked immunosorbent assay than controls. These results revealed the importance of IL-6 in the immunopathogenesis of murine toxoplasmic encephalitis.

    View details for Web of Science ID A1994NU01400016

    View details for PubMedID 8005667

    View details for PubMedCentralID PMC302880

  • THE VITEK IMMUNODIAGNOSTIC ASSAY FOR DETECTION OF IMMUNOGLOBULIN-M TOXOPLASMA ANTIBODIES CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY Candolfi, E., Ramirez, R., HADJU, M. P., Shubert, C., Remington, J. S. 1994; 1 (4): 401-405

    Abstract

    We compared the Vitek immunodiagnostic assay for detection of immunoglobulin M (IgM) toxoplasma antibodies (VIDAS TXM) with an IgM enzyme-linked immunosorbent assay (ELISA) which we developed. A total of 407 serum samples from 391 adults were used for this study. We also examined 17 serial serum samples from four women who had seroconverted during gestation. We observed a sensitivity of 99.5%, a specificity of 93%, a positive predictive value of 93.6%, a negative predictive value of 99.5%, and a global agreement of 96.3%. In each case of seroconversion the VIDAS TXM became positive at the same time as did the IgM ELISA.

    View details for Web of Science ID A1994PT56500007

    View details for PubMedID 8556476

    View details for PubMedCentralID PMC368275

  • TOXOPLASMOSIS IN PREGNANCY CLINICAL INFECTIOUS DISEASES Wong, S. Y., Remington, J. S. 1994; 18 (6): 853-861

    View details for Web of Science ID A1994NQ82600001

    View details for PubMedID 8086543

  • MITOGEN-SPECIFIC AND ANTIGEN-SPECIFIC PROLIFERATION OF T-CELLS IN MURINE TOXOPLASMOSIS IS INHIBITED BY REACTIVE NITROGEN INTERMEDIATES INFECTION AND IMMUNITY Candolfi, E., Hunter, C. A., Remington, J. S. 1994; 62 (5): 1995-2001

    Abstract

    Acute and chronic infections with Toxoplasma gondii result in a nonspecific suppression of immunologic function in mice and humans. Proliferation of spleen cells in response to concanavalin A (ConA) and toxoplasma lysate antigen (TLA) was studied during the course of infection in mice susceptible (CBA/Ca) and resistant (BALB/c) to development of toxoplasmic encephalitis to determine if reactive nitrogen intermediates (RNI) are involved in the suppression of the proliferative responses. Maximal suppression of proliferation of spleen cells in response to ConA and TLA was observed on days 7 and 14 after infection and correlated with elevated levels of nitrite in spleen cell culture supernatants. By day 68 postinfection in BALB/c mice, proliferative responses returned to normal levels, whereas in CBA/Ca mice, they remained suppressed. The addition of an inhibitor of production of RNI (NG-monomethyl-L-arginine) increased proliferation of spleen cells in response to both ConA and TLA at days 7, 14, and 21 after infection. Depletion of adherent cells from spleen cell preparations obtained from acutely infected mice followed by their repletion with adherent spleen cells from uninfected mice resulted in increased proliferation of spleen cells from infected mice and a significant decrease in nitrite in the cultures. These results indicate that production of RNI by macrophages contributes significantly to the suppression of the spleen cell proliferation observed in the acute stage of toxoplasmosis.

    View details for Web of Science ID A1994NH31300068

    View details for PubMedID 8168967

    View details for PubMedCentralID PMC186459

  • AN ULTRASTRUCTURAL-STUDY OF THE EFFECT OF TREATMENT WITH ATOVAQUONE IN BRAINS OF MICE CHRONICALLY INFECTED WITH THE ME49 STRAIN OF TOXOPLASMA-GONDII INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY Ferguson, D. J., HUSKINSONMARK, J., Araujo, F. G., Remington, J. S. 1994; 75 (2): 111-116

    Abstract

    The morphological effects of drug treatment with atovaquone in the brains of mice chronically infected with Toxoplasma gondii was examined by light and electron microscopy. As early as 1 and 2 weeks of treatment there appeared to be fewer tissue cysts compared to untreated controls and this reduction was more significant after 4 weeks treatment. There also appeared to be a decrease in the number of inflammatory nodules and the severity of the meningitis. Ultrastructurally, the cysts of both treated and control animals were located within host cells. There was a marked increase in both the number of cysts with lysed bradyzoites and the number of degenerate bradyzoites after 4 weeks treatment. It is probable that the drug is more active against the metabolically active immature bradyzoites than the mature organisms. Drug treatment does not appear to result in rupture of tissue cysts or release of Toxoplasma antigens since there is a reduction rather than an increase in the inflammatory response. This drug may be useful in treating chronic toxoplasmosis since it appears to be active against the bradyzoites reducing the parasite burden (cyst number) without initiating a destructive inflammatory response.

    View details for Web of Science ID A1994NG79200007

    View details for PubMedID 8199003

    View details for PubMedCentralID PMC2002108

  • SERODIAGNOSIS OF TOXOPLASMIC LYMPHADENOPATHY (TL) Montoya, J. G., Remington, J. S. SLACK INC. 1994: A285–A285
  • 2 ALLELES OF THE GENE ENCODING SURFACE-ANTIGEN P22 IN 25 STRAINS OF TOXOPLASMA-GONDII JOURNAL OF PARASITOLOGY Parmley, S. F., Gross, U., Sucharczuk, A., Windeck, T., Sgarlato, G. D., Remington, J. S. 1994; 80 (2): 293-301

    Abstract

    A group of 25 strains of Toxoplasma gondii (4 mouse-virulent strains and 21 mouse-avirulent strains) were tested by immunoblot with 4 monoclonal antibodies (MAb) against surface antigen P22. Parasite lysates from only 12 strains were recognized by all 4 MAbs, while lysates from the remaining 13 strains (all avirulent) were not recognized by any of the 4 MAbs. Strains not recognized by the 4 MAbs were found to express an altered form of the P22 antigen. Sequencing of the P22 genes from 10 strains revealed only 2 alleles. One allele is identical to the gene from the virulent RH strain. The second allele carries 5 single nucleotide substitutions and an insertion of a GGT triplet when compared to the allele from the RH strain. Four of the 5 nucleotide changes result in amino acid substitutions and the triplet insertion results in an extra glycine residue. Four of the single base changes also result in restriction fragment length polymorphisms (RFLP). RFLP analysis of the P22 gene revealed only 2 patterns among the 25 strains. The allele of the P22 gene correlated with reactivity of the 4 MAbs to lysates of each strain. However, the allele of the P22 gene did not correlate with the virulence of each strain for mice.

    View details for Web of Science ID A1994NF44300018

    View details for PubMedID 7908967

  • RIFABUTIN IS ACTIVE IN MURINE MODELS OF TOXOPLASMOSIS ANTIMICROBIAL AGENTS AND CHEMOTHERAPY Araujo, F. G., Slifer, T., Remington, J. S. 1994; 38 (3): 570-575

    Abstract

    Rifabutin, a semisynthetic derivative of rifamycin S, was examined alone and in combination with other drugs for activity in treatment of systemic toxoplasmosis and toxoplasmic encephalitis in murine models. One hundred percent of the mice infected with a lethal inoculum of tachyzoites or cysts of Toxoplasma gondii were protected against death by treatment with doses of 400 or 300 mg of rifabutin per kg administered alone for 10 days. Doses of 200 mg/kg protected at least 80% of the mice, and doses of 100 mg/kg protected 10 to 40% of the infected mice against death. Doses of 50 mg/kg were not protective but caused a delay in time to death. Combination of nonprotective (50-mg/kg) or slightly protective (100-mg/kg) doses of rifabutin with doses of sulfadiazine, pyrimethamine, clindamycin, or atovaquone that did not confer any protection against death from toxoplasmosis when administered alone resulted in remarkable enhancement of the in vivo activities of all of these drugs. Seventy-five percent of the infected mice survived when treated with 100 mg of rifabutin per kg per day combined with the ineffective dose of 10 mg of pyrimethamine per kg. A dose of 50 mg of rifabutin per kg in combination with the ineffective dosages of clindamycin (25 mg/kg/day), atovoquone (5 mg/kg/day), and sulfadiazine (80 mg per liter of drinking water) protected at least 80, 60, and 60% of the mice against death, respectively. The inflammatory responses in the brains of mice treated for 30 days with 200 mg of rifabutin per kg per day were significantly reduced compared with those in the brains of untreated controls. These observations suggest that clinical trials with rifabutin for treatment and prevention of human toxoplasmosis may be justified, particularly when the drug is used in combination with other drugs with activity against T. gondii.

    View details for Web of Science ID A1994MZ31200028

    View details for PubMedID 8203856

    View details for PubMedCentralID PMC284499

  • Toxoplasma-macrophage interactions. Immunology series Beaman, M. H., Subauste, C. S., Wong, S. Y., Remington, J. S. 1994; 60: 475-493

    View details for PubMedID 8251588

  • THE ROLE OF CYTOKINES IN TOXOPLASMOSIS BIOTHERAPY Hunter, C. A., Subauste, C. S., Remington, J. S. 1994; 7 (3-4): 237-247

    Abstract

    Infection with Toxoplasma gondii is normally asymptomatic, but as a consequence of the AIDS epidemic the incidence of symptomatic disease and especially toxoplasmic encephalitis (TE) has grown in frequency. The high frequency of adverse reactions to conventional therapeutic regimens for toxoplasmosis highlight the need to develop new strategies for the management of this disease. The importance of cytokines in resistance against T. gondii has been shown primarily in murine models of toxoplasmosis and a number of cytokines (e.g., IFN-gamma, TNF-alpha, IL-2 and IL-12) have been proposed for trials in patients with TE. One mechanism by which these cytokines produce their effects is through stimulation of macrophages and/or NK cells. However, there are problems with immunological intervention in immunocompromised patients with TE since the infection is present primarily in the central nervous system (CNS), an immunoprivileged site, and because certain cytokines may down regulate the immune response. While much valuable information has been obtained from studies conducted in immunocompetent strains of mice their relevance to an immunocompromised host is unknown. The development of genetically altered mice with immune deficiencies offers promising new models that may allow for more rational development of new treatment regimens.

    View details for Web of Science ID A1994PQ40500010

    View details for PubMedID 7865354

  • TOXOPLASMOSIS IN PATIENTS WITH CANCER CLINICAL INFECTIOUS DISEASES Israelski, D. M., Remington, J. S. 1993; 17: S423-S435

    Abstract

    The unusual occurrence, protein manifestations, and often devastating consequences of toxoplasmosis in patients with cancer emphasize the need for clinical acumen in the diagnosis and management of this disorder. Toxoplasmosis in patients with cancer has most commonly been described in association with Hodgkin's disease. It has also been reported, usually in the setting of treatment with antineoplastic agents, in patients with other lymphoproliferative disorders, hematologic malignancies, and solid tumors. In this review, among patients for whom the diagnosis was made early enough to begin specific treatment, conditions of 68% improved; this finding was in marked contrast to the severe morbidity and mortality observed for untreated individuals. The high mortality in the untreated group reflects the general debilitation and severe immunocompromise of these patients. Therefore, although toxoplasmosis contributed to a poor prognosis, it was not necessarily always the proximate cause of death.

    View details for Web of Science ID A1993MF18700022

    View details for PubMedID 8274608

  • CYTOKINE MESSENGER-RNA IN THE CENTRAL-NERVOUS-SYSTEM OF SCID MICE INFECTED WITH TOXOPLASMA-GONDII - IMPORTANCE OF T-CELL-INDEPENDENT REGULATION OF RESISTANCE TO TOXOPLASMA-GONDII INFECTION AND IMMUNITY Hunter, C. A., Abrams, J. S., Beaman, M. H., Remington, J. S. 1993; 61 (10): 4038-4044

    Abstract

    Levels of cytokine mRNA were studied in the central nervous system (CNS) of SCID mice infected with Toxoplasma gondii. This infection led to 100% mortality by day 23 postinfection. Inflammation was observed in the lungs on day 7 and in the heart, liver, and kidneys on days 14 and 18 of infection. In the CNS, necrotic, acellular lesions that contained numerous parasites, accompanied by a localized astrocyte activation, were evident on day 14. Polymerase chain reaction-assisted amplification of RNA revealed that, although transcripts for interleukin-1 alpha (IL-1 alpha) and IL-1 beta were present in the brains of uninfected mice, increased levels of these transcripts were detected on day 7 of infection. Transcripts for macrophage inflammatory protein 1 and transforming growth factor beta were also detected in brains of infected mice at this time point. On days 14 and 18, levels of these transcripts had increased and transcripts for IL-6, IL-10, gamma interferon (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were also detected. Transcripts for IL-2 or IL-4 were not detected at any of the time points. Detection of locally produced cytokine transcripts may reflect involvement of the cytokines in the immunopathogenesis of this infection or involvement in mediating antitoxoplasma activity. To assess the possible role of endogenous IFN-gamma, TNF-alpha, IL-10, IL-6, and GM-CSF, cytokine-neutralizing monoclonal antibodies were administered to infected SCID mice. Neutralization of IFN-gamma or TNF-alpha led to earlier mortality than that in controls. In contrast, treatment with antibody to IL-10 and IL-6 increased survival time. Treatment with anti-GM-CSF did not alter the time to death. These results indicate that TNF-alpha and IFN-gamma are both involved in T-cell-independent mechanisms of resistance to T. gondii in SCID mice and that IL-10 and IL-6 may downregulate the immune response to this pathogen.

    View details for Web of Science ID A1993LZ26400003

    View details for PubMedID 8406791

  • IMMUNITY TO TOXOPLASMA-GONDII CURRENT OPINION IN IMMUNOLOGY Subauste, C. S., Remington, J. S. 1993; 5 (4): 532-537

    Abstract

    Recent advances in our understanding of the immunological mechanisms involved during infection with Toxoplasma gondii include evidence for the role of different subsets of lymphocytes and cytokines in acute infection as well as in reactivation of chronic infection. The mechanisms of presentation of T. gondii antigen have been clarified recently, and animal models of toxoplasmosis that mimic disease observed in AIDS patients developed.

    View details for Web of Science ID A1993LU97500010

    View details for PubMedID 8216929

  • PREVALENCE OF TOXOPLASMA INFECTION IN A COHORT OF HOMOSEXUAL MEN AT RISK OF AIDS AND TOXOPLASMIC ENCEPHALITIS JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES Israelski, D. M., Chmiel, J. S., POGGENSEE, L., Phair, J. P., Remington, J. S. 1993; 6 (4): 414-418

    Abstract

    The purpose of this study was to characterize the epidemiologic, clinical, and laboratory parameters of a cohort of men at risk of AIDS-associated toxoplasmic encephalitis. One hundred seventeen (11%) of the 1,073 participants at the time of enrollment into the Chicago Multicenter AIDS Cohort Study (MACS) were seropositive for Toxoplasma antibodies. Significant differences in prevalence of antibodies between African-American, Hispanic, or white men were not observed (p = 0.49). One hundred one (86%) of the 117 antibody-positive participants had at least one follow-up serology performed and 6 (6%) of the 101 had a significant rise in IgG antibody titer on subsequent visits. Five of six participants with a significant rise in titer were also seropositive for HIV-1 at entry or seroconverted during the study. A trend toward higher IgG Toxoplasma titers and prevalence of IgM antibodies in participants seropositive for HIV-1 was observed, but the differences did not reach statistical significance. There was no evidence that the presence of Toxoplasma infection predisposed to development of CD4+ depletion or AIDS. None of the 183 individuals in the cohort who developed AIDS and who were seronegative for Toxoplasma antibodies developed toxoplasmic encephalitis. In contrast, of the 13 persons who developed AIDS and who were positive for Toxoplasma antibodies, 5 (38%) developed toxoplasmic encephalitis. Prevalence of Toxoplasma antibodies in the MACS population was independent of HIV-1 serostatus. Toxoplasma infection does not appear to predispose to progression of HIV-1 infection. The risk of development of toxoplasmic encephalitis in persons with AIDS and chronic Toxoplasma infection may have been underestimated by previous retrospective studies.

    View details for Web of Science ID A1993KU22100015

    View details for PubMedID 8455146

  • VACCINATION OF MICE WITH THE PROTECTIVE F3G3 ANTIGEN OF TOXOPLASMA-GONDII ACTIVATES CD4+ BUT NOT CD8+ T-CELLS AND INDUCES TOXOPLASMA SPECIFIC IGG ANTIBODY MOLECULAR IMMUNOLOGY Brinkmann, V., Remington, J. S., Sharma, S. D. 1993; 30 (4): 353-358

    Abstract

    A major cytoplasmic Toxoplasma gondii (T. gondii) antigen recognized by monoclonal antibody F3G3 (F3G3-Ag), as well as two surface antigens recognized by monoclonal antibodies 2G11 and 1E11 respectively (2G11-Ag; 1E11-Ag), were isolated from crude Toxoplasma sonicates using affinity chromatography. Purified F3G3-Ag induced long term protection against Toxoplasma infection in mice and induced Toxoplasma specific IgG antibody. CD4+ but not CD8+ T cells from immune animals proliferated and produced IL-2 upon restimulation with either Toxoplasma sonicate or F3G3-Ag in vitro. Furthermore, CD4+ T cells from mice immunized with F3G3-Ag responded to purified 2G11- and 1E11-Ag. In contrast, CD4+ T cells from mice immunized with 2G11-Ag responded to Toxoplasma sonicate and 2G11-Ag, but not to F3G3- or 1E11-Ag. The results may indicate that the protective F3G3-Ag shares immunogenic epitopes present also on 2G11- and 1E11-Ag, since the F3G3-Ag used for the vaccination did not contain detectable amounts of 2G11- or 1E11-Ag, and none of the antigens displayed any mitogenicity. Taken together the results show that the cytoplasmic F3G3-Ag of T. gondii induces CD4+ T helper cells, Toxoplasma specific IgG antibodies and long term protection against Toxoplasma infection, but does not induce detectable sensitization of the CD8+ T cell compartment.

    View details for Web of Science ID A1993KT20300003

    View details for PubMedID 8096062

  • THE ACTIVITY OF ATOVAQUONE-(566C80) IN MURINE TOXOPLASMOSIS IS MARKEDLY AUGMENTED WHEN USED IN COMBINATION WITH PYRIMETHAMINE OR SULFADIAZINE JOURNAL OF INFECTIOUS DISEASES Araujo, F. G., Lin, T., Remington, J. S. 1993; 167 (2): 494-497

    Abstract

    The activity of atovaquone in the treatment of murine toxoplasmosis was greatly enhanced when administered in combination with pyrimethamine or sulfadiazine. Mice infected with lethal inocula of tachyzoites or cysts of Toxoplasma gondii and treated with doses of atovaquone, pyrimethamine, or sulfadiazine that were ineffective when administered alone had 70% survival when pyrimethamine plus atovaquone and 100% survival when sulfadiazine plus atovaquone was used. Of interest, doses of pyrimethamine and, particularly, sulfadiazine far below the doses that would induce any protection in infected mice were active when combined with atovaquone. These results suggest that clinical trials for treatment of toxoplasmosis in AIDS patients using the combination of atovaquone with sulfadiazine or pyrimethamine are justified.

    View details for Web of Science ID A1993KJ48700040

    View details for PubMedID 8421189

  • Toxoplasmosis in the non-AIDS immunocompromised host. Current clinical topics in infectious diseases Israelski, D. M., Remington, J. S. 1993; 13: 322-356

    View details for PubMedID 8397917

  • TOXOPLASMIC ENCEPHALITIS IN AIDS PATIENTS AND EXPERIMENTAL-MODELS FOR STUDY OF THE DISEASE AND ITS TREATMENT RESEARCH IN IMMUNOLOGY Suzuki, Y., Remington, J. S. 1993; 144 (1): 66-67

    View details for Web of Science ID A1993KK61300015

    View details for PubMedID 8451522

  • TOXOPLASMIC ENCEPHALITIS IN AIDS CLINICAL INFECTIOUS DISEASES Luft, B. J., Remington, J. S. 1992; 15 (2): 211-222

    Abstract

    Involvement of the central nervous system (CNS) is common in patients with advanced disease due to human immunodeficiency virus (HIV). Symptoms range from lethargy and apathy to coma, incoordination and ataxia to hemiparesis, loss of memory to severe dementia, and focal to major motor seizures. Involvement may be closely associated with HIV infection per se, as in the AIDS dementia complex, but is frequently caused by opportunistic pathogens such as Toxoplasma gondii and Cryptococcus neoformans or malignancies such as primary lymphoma of the CNS. The clinical presentations of attendant and direct CNS involvement are remarkably non-specific and overlapping, yet a correct diagnosis is critical to successful intervention. Toxoplasmic encephalitis is one of the most common and most treatable causes of AIDS-associated pathology of the CNS. A great deal has been learned in the last 10 years about its unique presentation in the HIV-infected patient with advanced disease. Drs. Benjamin J. Luft of the State University of New York at Stony Brook and Jack S. Remington of the Stanford University School of Medicine and Palo Alto Medical Foundation's Research Institute have studied T. gondii for many years and are two of the leading experts in the field. This commentary comprises an update of their initial review (J Infect Dis 1988;157:1-6) and a presentation of the current approaches to diagnosing and managing toxoplasmic encephalitis in HIV-infected patients.

    View details for Web of Science ID A1992JF19000002

    View details for PubMedID 1520757

  • CYTOKINES, TOXOPLASMA AND INTRACELLULAR PARASITISM IMMUNOLOGICAL REVIEWS Beaman, M. H., Wong, S. Y., Remington, J. S. 1992; 127: 97-117

    View details for Web of Science ID A1992JD81800005

    View details for PubMedID 1506009

  • MURINE CD8+ CYTOTOXIC LYMPHOCYTES-T LYSE TOXOPLASMA-GONDII-INFECTED CELLS JOURNAL OF IMMUNOLOGY Subauste, C. S., Koniaris, A. H., Remington, J. S. 1991; 147 (11): 3955-3959

    Abstract

    Studies were performed to determine whether CTL against Toxoplasma gondii-infected cells could be induced in a murine model of T. gondii infection in which CD8+ T lymphocytes have been shown to play a major role in resistance against this parasite. In 51Cr release assays, nylon wool nonadherent spleen cells from BALB/c (H-2d) mice immunized with the temperature-sensitive (ts-4) mutant strain of T. gondii were cytotoxic for T. gondii-infected P815 (H-2d) mastocytoma cells but not for uninfected cells. This cytotoxic activity was remarkably increased after in vitro stimulation with T. gondii-infected syngeneic spleen cells. The effector cells were shown to be CD8+ T lymphocytes, because the cytotoxicity was significantly inhibited by depletion of CD8+ T lymphocytes but not by depletion of CD4+ T lymphocytes. This cytotoxic activity was genetically restricted. Spleen cells from T. gondii-immune BALB/c mice were not cytotoxic for T. gondii-infected EL4 (H-2b) thymoma cells, whereas spleen cells from T. gondii-immune C57B1/6 (H-2b) mice were cytotoxic for T. gondii-infected EL4 cells but not for T. gondii-infected P815 cells. The cytolytic activity of CD8+ T lymphocytes against T. gondii-infected cells might be a mechanism whereby these cells confer resistance against T. gondii.

    View details for Web of Science ID A1991GQ83700041

    View details for PubMedID 1940378

  • RAPID PRENATAL-DIAGNOSIS OF CONGENITAL TOXOPLASMA INFECTION BY USING POLYMERASE CHAIN-REACTION AND AMNIOTIC-FLUID JOURNAL OF CLINICAL MICROBIOLOGY GROVER, C. M., Thulliez, P., Remington, J. S., Boothroyd, J. C. 1990; 28 (10): 2297-2301

    Abstract

    Infection of pregnant women with Toxoplasma gondii places the developing fetus at risk for congenital infection. We report a prospective study of 43 documented cases of acute maternal Toxoplasma infections acquired during gestation in which the polymerase chain reaction (PCR) was evaluated for diagnosis of fetal infection and compared with the current standard methods. On the basis of direct lysis of pelleted amniotic fluid cells followed by amplification of a gene sequence specific for T. gondii, PCR correctly identified the presence of T. gondii in five of five samples of amniotic fluid from four proven cases of congenital infection. PCR also detected three of five positive cases from a nonprospective group. The two diagnostic methods of comparable speed, detection of specific immunoglobulin M from fetal blood and and inoculation of amniotic fluid into tissue culture, correctly identified only 3 and 4 of the 10 positive samples, respectively. The considerably more time-consuming methods of mouse inoculation of amniotic fluid and fetal blood both detected 7 of 10 positive samples. There were no false-positive diagnoses by any of the methods. Therefore, detection of T. gondii by PCR appears to be the most promising method for prenatal diagnosis of congenital Toxoplasma infection, since it is both extremely rapid and highly sensitive.

    View details for Web of Science ID A1990DZ42500028

    View details for PubMedID 2229355

  • THE TRAGEDY OF TOXOPLASMOSIS SYMP ON PERINATAL INFECTIOUS DISEASES : UPDATE 1990 Remington, J. S. LIPPINCOTT WILLIAMS & WILKINS. 1990: 762–63

    View details for Web of Science ID A1990EC31500022

    View details for PubMedID 2235157

  • DIFFERENTIAL AGGLUTINATION-TEST FOR DIAGNOSIS OF RECENTLY ACQUIRED INFECTION WITH TOXOPLASMA-GONDII JOURNAL OF CLINICAL MICROBIOLOGY DANNEMANN, B. R., Vaughan, W. C., Thulliez, P., Remington, J. S. 1990; 28 (9): 1928-1933

    Abstract

    We evaluated the recently described differential agglutination test (HS/AC test) to differentiate recently acquired toxoplasma infections from those acquired in the more distant past in sera obtained from 38 patients with carefully defined symptomatic and asymptomatic infections. AC antigens detect acute-phase-specific immunoglobulin G (IgG) antibodies against Toxoplasma gondii tachyzoites that are formed only during the acute stage of infection in humans. The HS/AC test correctly identified recently acquired infections in patients with toxoplasmic lymphadenopathy or asymptomatic infections (including infections in 7 women who seroconverted during gestation) in 31 of 33 patients. We also studied 15 individuals who had been infected for at least 2 years. In that group, only 13% had an acute pattern in the HS/AC test. However, the wide range in times from infection (from 2 to 14 years) did not allow for an estimate of when the pattern in the HS/AC test changed from acute to not acute. These results reveal that in the appropriate clinical situation, when both IgG and IgM tests are positive and a question still remains about the acuteness of infection, the HS/AC test may be useful for differentiating between toxoplasma infections acquired recently and those acquired in the more distant past.

    View details for Web of Science ID A1990DU74100011

    View details for PubMedID 2229374

    View details for PubMedCentralID PMC268080

  • THE EFFECT OF ANTI-IFN-GAMMA ANTIBODY ON THE PROTECTIVE EFFECT OF LYT-2+ IMMUNE T-CELLS AGAINST TOXOPLASMOSIS IN MICE JOURNAL OF IMMUNOLOGY Suzuki, Y., Remington, J. S. 1990; 144 (5): 1954-1956

    Abstract

    The effect of an IFN-gamma mAb on the protective activity of immune T cells against Toxoplasma infection was examined in a murine model of toxoplasmosis. Mice that received anti-IFN-gamma antibody and immune spleen cells all died of toxoplasmosis after challenge with Toxoplasma tachyzoites. In contrast, mice that received normal IgG and immune spleen cells all survived the infection. The protective activity of Lyt-2+ immune T cells, previously shown to be the principal mediators of resistance against Toxoplasma in mice was completely ablated by the anti-IFN-gamma mAb. These results suggest that IFN-gamma is the major mediator of the resistance against Toxoplasma infection in mice which is conferred by immune T cells.

    View details for Web of Science ID A1990CR42900055

    View details for PubMedID 2106557

  • EFFECT OF RECOMBINANT TUMOR NECROSIS FACTOR ON ACUTE INFECTION IN MICE WITH TOXOPLASMA-GONDII OR TRYPANOSOMA-CRUZI IMMUNOLOGY Black, C. M., Israelski, D. M., Suzuki, Y., Remington, J. S. 1989; 68 (4): 570-574

    Abstract

    Recombinant tumor necrosis factor (rTNF) has been shown to protect mice against lethal bacterial infections. We previously reported that in in vitro experiments with mouse peritoneal macrophages, rTNF inhibited intracellular multiplication of Trypanosoma cruzi but not of Toxoplasma gondii. These disparate results led us to study the effect of rTNF on the in vivo infection with these parasites. Daily administration of 0.5 and 5.0 micrograms rTNF resulted in a dose-dependent, significantly decreased time to death (p less than 0.05) in mice infected with lethal doses of T. cruzi. The same effect was found in mice infected with T. gondii and given a daily dose of 5.0 micrograms rTNF. Lower doses of rTNF did not significantly affect time to death of mice infected with either parasite.

    View details for Web of Science ID A1989CC37000023

    View details for PubMedID 2514141

    View details for PubMedCentralID PMC1385548

  • TOXOPLASMIC ENCEPHALITIS IN AIDS HOSPITAL PRACTICE DANNEMANN, B. R., Remington, J. S. 1989; 24 (3): 139-?

    View details for Web of Science ID A1989T757700015

    View details for PubMedID 2493464

  • ZIDOVUDINE ANTAGONIZES THE ACTION OF PYRIMETHAMINE IN EXPERIMENTAL-INFECTION WITH TOXOPLASMA-GONDII ANTIMICROBIAL AGENTS AND CHEMOTHERAPY Israelski, D. M., Tom, C., Remington, J. S. 1989; 33 (1): 30-34

    Abstract

    The effect of zidovudine (azidothymidine; AZT) on the action of pyrimethamine against Toxoplasma gondii was investigated. Zidovudine was found to antagonize the toxoplasmacidal effect of low concentrations of pyrimethamine in vitro, and in vitro synergism of pyrimethamine and sulfadiazine against T. gondii was reversed by zidovudine. Zidovudine also antagonized the therapeutic effect of pyrimethamine in mice acutely infected with T. gondii.

    View details for Web of Science ID A1989R638700007

    View details for PubMedID 2712547

    View details for PubMedCentralID PMC171416

  • DIAGNOSIS OF TOXOPLASMIC ENCEPHALITIS IN PATIENTS WITH ACQUIRED IMMUNODEFICIENCY SYNDROME BY USING A NEW SEROLOGIC METHOD JOURNAL OF CLINICAL MICROBIOLOGY Suzuki, Y., Israelski, D. M., DANNEMANN, B. R., STEPICKBIEK, P., Thulliez, P., Remington, J. S. 1988; 26 (12): 2541-2543

    Abstract

    The present study was performed to develop a serological method for diagnosing toxoplasmic encephalitis in patients with acquired immunodeficiency syndrome (AIDS). The trophozoite form of Toxoplasma gondii, fixed with either Formalin or acetone, was used in a modification of an agglutination method previously shown to differentiate between the acute and the chronic (latent) stages of infection with toxoplasma in immunologically normal persons. By using these antigens in separate tests and evaluating the data for statistical significance, 70% of patients with AIDS with biopsy-proven toxoplasmic encephalitis were distinguished from control, ambulatory patients with AIDS with toxoplasma antibodies but without signs or symptoms of central nervous system involvement. In a separate study, the agglutination tests identified from controls 84% of patients with AIDS with two or more brain lesions detected by computed-tomographic or magnetic-resonance-imaging scans and suspected of having toxoplasmic encephalitis. Thus, these agglutination tests should prove valuable for the noninvasive diagnosis of toxoplasmic encephalitis in patients with AIDS.

    View details for Web of Science ID A1988R033900015

    View details for PubMedID 3230132

    View details for PubMedCentralID PMC266941

  • TREATMENT OF TOXOPLASMIC ENCEPHALITIS WITH INTRAVENOUS CLINDAMYCIN ARCHIVES OF INTERNAL MEDICINE DANNEMANN, B. R., Israelski, D. M., Remington, J. S. 1988; 148 (11): 2477-2482

    Abstract

    At present, therapy for toxoplasmic encephalitis (TE) is the combination of pyrimethamine with sulfadiazine or trisulfapyrimidines. Unfortunately, due to adverse reactions to sulfonamides, many patients with acquired immunodeficiency syndrome (AIDS) are unable to receive a complete course of therapy. The promising results with clindamycin phosphate therapy in a mouse model of TE prompted us to seek further information about patients with AIDS with TE who had been treated with clindamycin. Fifteen such patients were identified in whom clindamycin was used to treat 18 episodes of TE. Eleven patients showed clinical or radiologic improvement after receiving clindamycin therapy, either alone or in combination with pyrimethamine. Twelve received oral clindamycin as suppressive therapy after discharge from the hospital. Adverse reactions possibly related to clindamycin therapy included diarrhea, reversible granulocytopenia, and skin reactions. The results of this retrospective study suggest that clindamycin, either alone or in combination with pyrimethamine, may represent an effective alternative therapy for TE in patients with AIDS. Whether this supposition can be substantiated by appropriately designed studies is presently being determined.

    View details for Web of Science ID A1988Q934000022

    View details for PubMedID 3190380

  • Toxoplasmic encephalitis in patients with AIDS. Infectious disease clinics of North America Israelski, D. M., Remington, J. S. 1988; 2 (2): 429-445

    Abstract

    Toxoplasmic encephalitis has been recognized as a major CNS complication in patients with AIDS and is the most frequent cause of focal intracerebral lesions in these patients. This complication of AIDS is almost always observed in patients who have a chronic (latent) infection with Toxoplasma gondii. Therefore, patients who from the outset of their HIV infection or AIDS are known to have antibodies to T. gondii should be considered at risk for development of toxoplasmic encephalitis. Although serologic tests cannot distinguish active from latent infection, a patient who is seronegative for Toxoplasma antibodies is unlikely to have toxoplasmic encephalitis. Neuroradiologic studies may be highly suggestive of toxoplasmic encephalitis, but, at present, the definitive diagnosis can be made only by demonstration of Toxoplasma in brain tissue. The unique pathogenesis of toxoplasmic encephalitis in patients with AIDS makes intensive primary therapy followed by a lifelong suppressive regimen necessary. We recommend 6 weeks of high doses of pyrimethamine and sulfadiazine (or trisulfapyrimidines) as primary therapy for the acute disease followed by daily administration of reduced doses of these drugs. The use of clindamycin as an alternative drug for primary therapy, at least at present, must be regarded as investigational and should be reserved for patients who suffer severe reactions to the sulfonamides. As most patients will respond to their primary therapy, those who fail to improve clinically and radiologically to therapy within 10 days should be evaluated for additional or alternative causes of their intracerebral pathology. This will often necessitate brain biopsy.

    View details for PubMedID 3060527

  • INTERFERON-GAMMA - THE MAJOR MEDIATOR OF RESISTANCE AGAINST TOXOPLASMA-GONDII SCIENCE Suzuki, Y., Orellana, M. A., Schreiber, R. D., Remington, J. S. 1988; 240 (4851): 516-518

    Abstract

    Mice were injected with a monoclonal antibody to interferon-gamma to examine the importance of endogenous production of this lymphokine in resistance against infection with the sporozoan parasite Toxoplasma gondii. Mice with intraperitoneal infections of T. gondii that received no antibody survived and developed chronic T. gondii infection, whereas the infected mice that received the monoclonal antibody died of toxoplasmosis. The activation of macrophages, which kill T. gondii in vivo, was inhibited by administration of the monoclonal antibody, but the production of antibodies to T. gondii was not suppressed. The fact that an antibody to interferon-gamma can eliminate resistance to acute Toxoplasma infection in mice suggests that this lymphokine is an important mediator of host resistance to this parasite.

    View details for Web of Science ID A1988N019200038

    View details for PubMedID 3128869

  • ROLE OF SEROLOGY IN THE DIAGNOSIS OF TOXOPLASMIC LYMPHADENOPATHY REVIEWS OF INFECTIOUS DISEASES Brooks, R. G., McCabe, R. E., Remington, J. S. 1987; 9 (4): 775-782
  • CLINICAL SPECTRUM IN 107 CASES OF TOXOPLASMIC LYMPHADENOPATHY REVIEWS OF INFECTIOUS DISEASES McCabe, R. E., Brooks, R. G., Dorfman, R. F., Remington, J. S. 1987; 9 (4): 754-774

    Abstract

    Lymphadenopathy is the most frequent clinical manifestation of acute acquired infection with Toxoplasma in the immunocompetent individual. One hundred seven cases of histologically verified toxoplasmic lymphadenitis were reviewed in an effort to determine the usual modes of clinical presentation and the incidence of extranodal disease. Toxoplasmic lymphadenitis most frequently involved a solitary lymph node in the head and neck regions, without systemic symptoms or extranodal disease and with a benign clinical course. However, serious extranodal disease did occur in some patients and included myocarditis, pneumonitis, encephalitis, chorioretinitis, and transmission of the infection to the fetus. Case histories are presented to illustrate important points with respect to clinical presentation, complications, and diagnosis.

    View details for Web of Science ID A1987J296600008

    View details for PubMedID 3326123

  • LABORATORY-ACQUIRED CHAGAS-DISEASE TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE HOFFLIN, J. M., SADLER, R. H., Araujo, F. G., PAGE, W. E., Remington, J. S. 1987; 81 (3): 437-440

    Abstract

    A laboratory technician developed fever, malaise, headache and non-tender erythematous swelling proximal to the site of accidental inoculation of his thumb, 24 days earlier, with a needle contaminated with Trypanosoma cruzi. Findings included a characteristic rash, remarkable fever, relative bradycardia and leukopaenia--T lymphopaenia with maintenance of a normal helper/suppressor ratio. Trypanosomes were not detected in blood concentrates or in biopsies of an enlarged lymph node and a skin lesion. T. cruzi antibody was first detected 33 days after the laboratory accident, when parasites were first isolated. Therapy with nifurtimox was well tolerated and the patient's serology became negative 9 months after the accident.

    View details for Web of Science ID A1987J645200026

    View details for PubMedID 3120369

  • KETOCONAZOLE PROMOTES PARASITOLOGICAL CURE OF MICE INFECTED WITH TRYPANOSOMA-CRUZI TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE McCabe, R. E., Remington, J. S., Araujo, F. G. 1987; 81 (4): 613-615

    Abstract

    Administration of 120 mg/kg/day of ketoconazole for 9 weeks resulted in parasitological cure of at least 78.5% of mice infected with 10(5) blood trypanosomes of Trypanosoma cruzi, strain Y. These results and the fact that ketoconazole is widely used in humans for prolonged therapy of fungal infections without significant side effects strongly suggest that further evaluation of ketoconazole for treatment of Chagas disease is highly desirable.

    View details for Web of Science ID A1987K029400030

    View details for PubMedID 3127963

  • PULMONARY TOXOPLASMOSIS AMERICAN REVIEW OF RESPIRATORY DISEASE Catterall, J. R., HOFFLIN, J. M., Remington, J. S. 1986; 133 (4): 704-705

    View details for Web of Science ID A1986A740600035

    View details for PubMedID 3963635

  • CELL FREE SYNTHESIS OF TOXOPLASMA-GONDII ANTIGENS MOLECULAR AND BIOCHEMICAL PARASITOLOGY Prince, J. B., KOVENQUINN, M. A., Remington, J. S., Sharma, S. D. 1985; 17 (2): 163-170

    Abstract

    Functionally active poly(A)-containing mRNA was isolated from tachyzoites of the RH strain of Toxoplasma gondii. The T. gondii mRNA was capable of directing the synthesis of proteins in a wheat germ in vitro translation system, but not in a cell free system derived from rabbit reticulocyte lysate. Efficient translation in the wheat germ system required spermine and exogenous tRNA. Amino acid incorporation was maximal at 110 mM K+ and 1.8 mM Mg2+. Tachyzoite antigens synthesized in vitro were immunoprecipitated with T. gondii antibodies from rabbits, mice and humans. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of immunoprecipitated polypeptides yielded patterns that differed according to antibody source, but all T. gondii antibody preparations reacted with a translation product with an apparent molecular weight of 24 000.

    View details for Web of Science ID A1985ATV2400004

    View details for PubMedID 2866444

  • PNEUMOCYSTIS-CARINII PNEUMONIA IN THE PATIENT WITH AIDS CHEST Catterall, J. R., Potasman, I., Remington, J. S. 1985; 88 (5): 758-762

    View details for Web of Science ID A1985ATP7200028

    View details for PubMedID 3931990

  • MECHANISMS OF INTRACELLULAR KILLING OF TOXOPLASMA-GONDII MEDECINE ET MALADIES INFECTIEUSES Remington, J. S. 1985; 15 (11BI): 681-682
  • DETECTION OF TOXOPLASMA-GONDII ANTIGENS BY A DOT-IMMUNOBINDING TECHNIQUE JOURNAL OF CLINICAL MICROBIOLOGY Brooks, R. G., Sharma, S. D., Remington, J. S. 1985; 21 (1): 113-116

    Abstract

    A sensitive assay for the detection of antigens of Toxoplasma gondii by spotting samples directly onto nitrocellulose paper was developed. The sensitivity ranged from 10 to 40 pg of antigen diluted in phosphate-buffered saline and 40 to 130 pg of antigen diluted in normal mouse serum, normal human serum, or human cerebrospinal fluid. T. gondii antigen in serum samples taken from mice infected with T. gondii was detectable by day 2 of infection. Antigen was also detectable in cerebrospinal fluid samples taken from four of six infants congenitally infected with T. gondii and in serum samples from two of these infants.

    View details for Web of Science ID A1985TX69200020

    View details for PubMedID 3968198

    View details for PubMedCentralID PMC271586

  • Q-FEVER ENDOCARDITIS WESTERN JOURNAL OF MEDICINE Gallagher, J. G., Remington, J. S. 1984; 140 (6): 943-945

    View details for Web of Science ID A1984SW69400024

    View details for PubMedID 6741132

    View details for PubMedCentralID PMC1011147

  • ANTIGENIC SIMILARITY BETWEEN THE COCCIDIAN PARASITES TOXOPLASMA-GONDII AND HAMMONDIA-HAMMONDI JOURNAL OF PROTOZOOLOGY Araujo, F. G., Dubey, J. P., Remington, J. S. 1984; 31 (1): 145-147

    Abstract

    The antigens that are present in the coccidian parasites Toxoplasma gondii and Hammondia hammondi were demonstrated and defined by using SDS-PAGE and immunoenzymatic techniques with 125I-labeled and unlabeled antigens of T. gondii and sera of mice infected orally or intraperitoneally with H. hammondi . All cell surface antigens of T. gondii that were labeled with 125I were recognized by antibodies in the sera of the mice infected with H. hammondi except the antigen of approximate molecular weight of 21.5 Kd. This suggests that this antigen is specific for T. gondii. Various antigens in the T. gondii-lysed antigen preparations were recognized by antibodies to H. hammondi . The number of recognized antigens increased as the infection of the mice with H. hammondi progressed. Oral infection with H. hammondi appeared to induce the formation of antibodies that recognized more T. gondii antigens than infection by intraperitoneal inoculation.

    View details for Web of Science ID A1984SQ48200027

    View details for PubMedID 6204042

  • THE DIAGNOSIS AND TREATMENT OF TOXOPLASMOSIS EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES McCabe, R. E., Remington, J. S. 1983; 2 (2): 95-104

    View details for Web of Science ID A1983QP14200002

    View details for PubMedID 6861739

  • INTRAVENOUS SULFAMETHOXAZOLE AND TRIMETHOPRIM FOR SERIOUS GRAM-NEGATIVE BACILLARY INFECTION ARCHIVES OF INTERNAL MEDICINE Sattler, F. R., Remington, J. S. 1983; 143 (9): 1709-1712

    Abstract

    Intravenous therapy with sulfamethoxazole and trimethoprim cured seven patients with serious gram-negative infection. Three patients had bacteremia, three had pneumonia, and one each had meningitis, peritonitis, pyogenic liver abscesses, and urinary tract infection. Sulfamethoxazole and trimethoprim was selected in three patients with renal failure to avoid aminoglycoside-induced nephrotoxicity, in three patients because of penicillin allergy, and in two cases because of bacterial resistance to other readily available antibiotics. Adverse drug reactions occurred in three cases and included oral monilia, transient leukopenia, and fluid overload. In contrast to the new broad-spectrum cephalosporin antibiotics, sulfamethoxazole and trimethoprim costs two to 2 1/2 times less and has not been associated with the emergence of bacterial resistance during therapy. This may favor the use of parenteral sulfamethoxazole and trimethoprim for some patients with serious gram-negative infection.

    View details for Web of Science ID A1983RF40100011

    View details for PubMedID 6615092

  • DETECTION OF TOXOPLASMAL ANTIGEN AND ANTIBODY IN OCULAR FLUIDS IN EXPERIMENTAL OCULAR TOXOPLASMOSIS ARCHIVES OF OPHTHALMOLOGY Rollins, D. F., Tabbara, K. F., OCONNOR, G. R., Araujo, F. G., Remington, J. S. 1983; 101 (3): 455-457

    Abstract

    Enzyme-linked immunosorbent assays were used to detect intraocular toxoplasmal antigen and antitoxoplasmal IgG antibodies in a rabbit model of experimental ocular toxoplasmosis. Toxoplasmal antigen could be detected in the vitreous humor of the infected eye at the height of clinical activity of the lesion. Antitoxoplasmal IgG antibodies were detected in the aqueous and vitreous humors of the infected eyes five weeks following the onset of toxoplasmic retinochoroiditis.

    View details for Web of Science ID A1983QF21600023

    View details for PubMedID 6830502

  • KETOCONAZOLE PROTECTS AGAINST INFECTION WITH TRYPANOSOMA-CRUZI IN A MURINE MODEL AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE McCabe, R. E., Araujo, F. G., Remington, J. S. 1983; 32 (5): 960-962

    Abstract

    The oral administration of ketoconazole to mice protected them against death caused by infection with Trypanosoma cruzi. The addition of ketoconazole to cultures of macrophages infected with the organism markedly inhibited the intracellular multiplication of amastigotes. These observations suggest that ketoconazole may be a potent agent against T. cruzi and should be evaluated more extensively as a chemotherapeutic agent for Chagas' disease.

    View details for Web of Science ID A1983RM77500010

    View details for PubMedID 6312824

  • EFFECT OF AMPHOTERICIN-B ON NATURAL-KILLER CELL-ACTIVITY INVITRO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY HAUSER, W. E., Remington, J. S. 1983; 11 (3): 257-262

    Abstract

    Incubation of murine peritoneal and spleen natural killer cells with amphotericin B at concentrations of 2.5, 5 and 10 mg/l in vitro, resulted in depression of their tumoricidal activity which had been augmented in vivo by infection with Toxoplasma gondii. In contrast, amphotericin B at the same concentrations had little or no effect on spontaneous natural killer cell activity in vitro. These in-vitro data suggest amphotericin B may have adverse effects on natural killer cell function in vivo.

    View details for Web of Science ID A1983QH29400009

    View details for PubMedID 6841308

  • NATURAL-KILLER CELLS INDUCED BY ACUTE AND CHRONIC TOXOPLASMA INFECTION CELLULAR IMMUNOLOGY HAUSER, W. E., Sharma, S. D., Remington, J. S. 1982; 69 (2): 330-346

    View details for Web of Science ID A1982NT87000010

    View details for PubMedID 6980721

  • EFFECT OF ANTI-MICROBIAL AGENTS ON CHEMI-LUMINESCENCE OF HUMAN POLYMORPHONUCLEAR LEUKOCYTES IN RESPONSE TO PHAGOCYTOSIS JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY Siegel, J. P., Remington, J. S. 1982; 10 (6): 505-515

    View details for Web of Science ID A1982PV43300006

    View details for PubMedID 7161229

  • IGM AND IGG ANTIBODY-RESPONSE IN 2 IMMUNOSUPPRESSED PATIENTS WITH LEGIONNAIRES-DISEASE - EVIDENCE OF REACTIVATION OF LATENT INFECTION AMERICAN JOURNAL OF MEDICINE Naot, Y., Brown, A., Elder, E. M., SHONNARD, J., Luft, B. J., Remington, J. S. 1982; 73 (6): 791-794

    Abstract

    Two patients in whom pneumonia due to Legionella pneumophila developed while they were receiving immunosuppressive therapy had serologic evidence of prior infection with the same serogroup of L. pneumophila two and eight months prior to their clinical pneumonia. This suggests that the pneumonia in these patients may have been due to the reactivation of a latent infection, possibly due to their immunosuppressed state. A new enzyme-linked immunosorbent assay (ELISA) was developed to detect IgG and IgM antibodies to L. pneumophila, and the kinetics of these antibody responses were useful diagnostically.

    View details for Web of Science ID A1982PU43000004

    View details for PubMedID 6756135