Bio

Clinical Focus


  • Infection as a trigger of chronic diseases
  • Infectious Disease
  • Chronic Fatigue Syndrome
  • Infection in the setting of solid organ transplantation
  • Toxoplasmosis

Academic Appointments


Administrative Appointments


  • Director, National Reference Laboratory for the Study and Diagnosis of Toxoplasmosis (2008 - Present)

Honors & Awards


  • Outstanding Senior Resident Awar, Department of Medicine, Tulane University School of Medicine (1990)
  • Outstanding Intern Award, Department of Medicine, Tulane University School of Medicine (1988)
  • The Owl Club Award for Outstanding Clinical Teaching, Tulane University School of Medicine (1990)
  • The Department of Medicine Outstanding Teaching Award, Tulane University School of Medicine (1990)
  • The Franklin G. Ebaugh, Jr. Award for Advising Medical Students, Stanford University School of Medicine (1995)
  • The Henry J. Kaiser Award for Excellence in Clinical Teaching, Stanford University School of Medicine (1995)
  • The Arthur L. Bloomfield Award for Excellence in the Teaching of Clinical Medicine, Stanford University School of Medicine (1997)
  • The David A. Rytand Teaching Award for Excellence in Clinical Teaching, Department of Medicine, Stanford University School of Medicine (1998)
  • The Kenneth Vosti Teaching Award for Excellence in Teaching, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine (2000)
  • The David A. Rytand Teaching Award for Excellence in Clinical Teaching., Department of Medicine, Stanford University School of Medicine (2001)
  • The Kenneth Vosti Teaching Award for Excellence in Teaching, Division of Infectious Diseases, Department of Medicine, Stanford University School of Medicine (2002)
  • Chief Residents Teaching Award for exemplary teaching at Stanford Resident's report, Department of Medicine, Stanford University School of Medicine (2003)
  • Fellow of the Infectious Diseases Society of America (FIDSA), Infectious Diseases Society of America (2011)
  • Fellow of the American College of Physicians (FACP), American College of Physicians (2011)
  • The Arthur L. Bloomfield Award for Excellence in the Teaching of Clinical Medicine, Stanford University School of Medicine (2011)

Boards, Advisory Committees, Professional Organizations


  • Member, Infectious Diseases Society of America (1993 - Present)
  • Member, American Society for Microbiology (2013 - 1993)
  • Member, American College of Physicians (1987 - Present)
  • Member, American Association for the Advancement of Science (1988 - Present)

Professional Education


  • Residency:Tulane University School of Medicine (1990) LA
  • Fellowship:Stanford University School of Medicine (1994) CA
  • Internship:Tulane University School of Medicine (1988) LA
  • Medical Education:Universidad Del Valle (1985) Colombia

Research & Scholarship

Clinical Trials


  • Valganciclovir (Valcyte) for Chronic Fatigue Syndrome Patients Who Have Elevated Antibody Titers Against Human Herpes Virus 6 (HHV-6)and Epstein-Barr Virus (EBV) Not Recruiting

    The purpose of this study determine whether the drug valganciclovir has a significant and real benefit on the central core of symptoms experienced by patients who have high titers to EBV and HHV-6 and are experiencing long-standing fatigue and cognitive impairment (CFS). In addition, to characterize a quantifiable biological marker in these patients that will facilitate the identification of those likely to respond to valganciclovir and will make it possible to assess response to treatment.

    Stanford is currently not accepting patients for this trial.

    View full details

  • A Multicenter, Randomized, Double-Blind, Comparative Study to Evaluate the Safety, Tolerability, and Efficacy of 2 Dosing Regimens of an Antifungal Drug in the Treatment of Fungal Infections in Adults (0991-801)(COMPLETED) Not Recruiting

    Comparison of the safety and effectiveness of standard drug dosing versus a daily dose 3 times higher than the standard dose in patients with invasive candidiasis (bloodstream and/or systemic yeast infections)

    Stanford is currently not accepting patients for this trial.

    View full details

Teaching

2013-14 Courses


Graduate and Fellowship Programs


Publications

Journal Articles


  • Polymerase Chain Reaction in Cerebrospinal Fluid for the Diagnosis of Congenital Toxoplasmosis. The Pediatric infectious disease journal Olariu, T. R., Remington, J. S., Montoya, J. G. 2014

    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

  • Acute Toxoplasma gondii Infection among Family Members in the United States EMERGING INFECTIOUS DISEASES Contopoulos-Ioannidis, D. G., Maldonado, Y., Montoya, J. G. 2013; 19 (12): 1981-1984

    Abstract

    We investigated 32 families of persons with acute toxoplasmosis in which > or = 1 other family member was tested for Toxoplasma gondii infection; 18 (56%) families had > or = 1 additional family member with acute infection. Family members of persons with acute toxoplasmosis should be screened for infection, especially pregnant women and immunocompromised persons.

    View details for DOI 10.3201/eid1912.121892

    View details for Web of Science ID 000327826600012

    View details for PubMedID 24274896

  • Randomized Clinical Trial to Evaluate the Efficacy and Safety of Valganciclovir in a Subset of Patients With Chronic Fatigue Syndrome JOURNAL OF MEDICAL VIROLOGY Montoya, J. G., Kogelnik, A. M., Bhangoo, M., Lunn, M. R., Flamand, L., Merrihew, L. E., Watt, T., Kubo, J. T., Paik, J., Desai, M. 2013; 85 (12): 2101-2109

    Abstract

    There is no known treatment for chronic fatigue syndrome (CFS). Little is known about its pathogenesis. Human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV) have been proposed as infectious triggers. Thirty CFS patients with elevated IgG antibody titers against HHV-6 and EBV were randomized 2:1 to receive valganciclovir (VGCV) or placebo for 6 months in a double-blind, placebo-controlled trial. Clinical endpoints aimed at measuring physical and mental fatigue included the Multidimensional Fatigue Inventory (MFI-20) and Fatigue Severity Scale (FSS) scores, self-reported cognitive function, and physician-determined responder status. Biological endpoints included monocyte and neutrophil counts and cytokine levels. VGCV patients experienced a greater improvement by MFI-20 at 9 months from baseline compared to placebo patients but this difference was not statistically significant. However, statistically significant differences in trajectories between groups were observed in MFI-20 mental fatigue subscore (P?=?0.039), FSS score (P?=?0.006), and cognitive function (P?=?0.025). VGCV patients experienced these improvements within the first 3 months and maintained that benefit over the remaining 9 months. Patients in the VGCV arm were 7.4 times more likely to be classified as responders (P?=?0.029). In the VGCV arm, monocyte counts decreased (P?

    View details for DOI 10.1002/jmv.23713

    View details for Web of Science ID 000325153400007

    View details for PubMedID 23959519

  • Persistent human herpesvirus-6 infection in patients with an inherited form of the virus. Journal of medical virology Pantry, S. N., Medveczky, M. M., Arbuckle, J. H., Luka, J., Montoya, J. G., Hu, J., Renne, R., Peterson, D., Pritchett, J. C., Ablashi, D. V., Medveczky, P. G. 2013; 85 (11): 1940-1946

    Abstract

    Human herpesvirus-6 (HHV-6)A and 6B are ubiquitous betaherpesviruses viruses with lymphotropic and neurotropic potential. As reported earlier, these viruses establish latency by integration into the telomeres of host chromosomes. Chromosomally integrated HHV-6 (CIHHV-6) can be transmitted vertically from parent to child. Some CIHHV-6 patients are suffering from neurological symptoms, while others remain asymptomatic. Four patients with CIHHV-6 and CNS dysfunction were treated with valganciclovir or foscarnet. HHV-6 replication was detected by reverse transcriptase polymerase chain reaction amplification of a late envelope glycoprotein. In this study we also compared the inherited and persistent HHV-6 viruses by DNA sequencing. The prevalence of CIHHV-6 in this cohort of adult patients from the USA suffering from a wide range of neurological symptoms including long-term fatigue were found significantly greater than the reported 0.8% in the general population. Long-term antiviral therapy inhibited HHV-6 replication as documented by loss of viral mRNA production. Sequence comparison of the mRNA and the inherited viral genome revealed that the transcript is produced by an exogenous virus. In conclusion, the data presented here document that some individuals with CIHHV-6 are infected persistently with exogenous HHV-6 strains that lead to a wide range of neurological symptoms; the proposed name for this condition is inherited herpesvirus 6 syndrome or IHS. J Med. Virol. 85:1940-1946, 2013. © 2013 Wiley Periodicals, Inc.

    View details for DOI 10.1002/jmv.23685

    View details for PubMedID 23893753

  • Utility of DNA Sequencing for Direct Identification of Invasive Fungi From Fresh and Formalin-Fixed Specimens AMERICAN JOURNAL OF CLINICAL PATHOLOGY Moncada, P. A., Budvytiene, I., Ho, D. Y., Deresinski, S. C., Montoya, J. G., Banaei, N. 2013; 140 (2): 203-208

    Abstract

    Objectives: To describe and discuss the utility and potential pitfalls of ribosomal RNA locus sequencing for direct identification of invasive fungi from fresh and formalin-fixed, paraffin-embedded specimens. Methods: DNA was extracted from fresh and formalin-fixed, paraffin-embedded tissue and subjected to real-time polymerase chain reaction (PCR) targeting ITS2 and D2 regions of fungal ribosomal RNA locus. Cycle sequencing was performed on PCR products, and the identity of sequences was determined using a public database. Results: Four clinical cases of invasive fungal infection are presented to illustrate the utility of DNA sequencing for determining etiology when microbiological culture is negative, for shortening the time to identification of slow-growing fungi, for guiding antifungal therapy, and for shedding light on the pathogenesis of disseminated fungal infection. Conclusions: Fungal ribosomal RNA locus sequencing from fresh or formalin-fixed, paraffin-embedded specimens is a powerful tool for rapid and accurate diagnosis of patients with culture-negative or uncultured invasive mycosis.

    View details for DOI 10.1309/AJCPNSU2SDZD9WPW

    View details for Web of Science ID 000322149600010

    View details for PubMedID 23897255

  • Otopathology in congenital toxoplasmosis. Otology & neurotology Salviz, M., Montoya, J. G., Nadol, J. B., Santos, F. 2013; 34 (6): 1165-1169

    Abstract

    OBJECTIVE: To describe the temporal bone histopathology in children with congenital toxoplasmosis. BACKGROUND: Toxoplasmosis is a parasitic infection caused by Toxoplasma gondii. If fetal infection occurs early in gestation, severe inflammation and necrosis can cause brain lesions, chorioretinitis, and hearing loss. Hearing loss in congenital toxoplasmosis may be preventable with early diagnosis and treatment. MATERIALS AND METHODS: The temporal bones of 9 subjects with congenital toxoplasmosis were removed at autopsy and studied under light microscopy. Cytocochleograms were constructed for hair cells, the stria vascularis, and cochlear neuronal cells. RESULTS: Three (33%) of 9 subjects were found to have parasites in the temporal bone. The organism was identified in the internal auditory canal, the spiral ligament, stria vascularis, and saccular macula. The cystic form of the parasite was not associated with the inflammatory response seen in the active tachyzoite form. CONCLUSION: We infer that the hearing loss of toxoplasmosis is likely the result of a postnatal inflammatory response to the tachyzoite form of T. gondii. Our findings have implications for the early identification and management of Toxoplasmosis.

    View details for DOI 10.1097/MAO.0b013e31828297b6

    View details for PubMedID 23598697

  • Risk factors and outcomes in lung transplant recipients with nodular invasive pulmonary aspergillosis JOURNAL OF INFECTION Singh, N., Suarez, J. F., Avery, R., Lass-Floerl, C., Geltner, C., Pasqualotto, A. C., Lyon, G. M., Barron, M., Husain, S., Wagener, M. M., Montoya, J. G. 2013; 67 (1): 72-78
  • Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: evidence of inflammatory pathology JOURNAL OF TRANSLATIONAL MEDICINE Stringer, E. A., Baker, K. S., Carroll, I. R., Montoya, J. G., Chu, L., Maecker, H. T., Younger, J. W. 2013; 11

    Abstract

    Chronic fatigue syndrome (CFS) is a debilitating disorder characterized by persistent fatigue that is not alleviated by rest. The lack of a clearly identified underlying mechanism has hindered the development of effective treatments. Studies have demonstrated elevated levels of inflammatory factors in patients with CFS, but findings are contradictory across studies and no biomarkers have been consistently supported. Single time-point approaches potentially overlook important features of CFS, such as fluctuations in fatigue severity. We have observed that individuals with CFS demonstrate significant day-to-day variability in their fatigue severity.Therefore, to complement previous studies, we implemented a novel longitudinal study design to investigate the role of cytokines in CFS pathophysiology. Ten women meeting the Fukuda diagnostic criteria for CFS and ten healthy age- and body mass index (BMI)-matched women underwent 25 consecutive days of blood draws and self-reporting of symptom severity. A 51-plex cytokine panel via Luminex was performed for each of the 500 serum samples collected. Our primary hypothesis was that daily fatigue severity would be significantly correlated with the inflammatory adipokine leptin, in the women with CFS and not in the healthy control women. As a post-hoc analysis, a machine learning algorithm using all 51 cytokines was implemented to determine whether immune factors could distinguish high from low fatigue days.Self-reported fatigue severity was significantly correlated with leptin levels in six of the participants with CFS and one healthy control, supporting our primary hypothesis. The machine learning algorithm distinguished high from low fatigue days in the CFS group with 78.3% accuracy.Our results support the role of cytokines in the pathophysiology of CFS.

    View details for DOI 10.1186/1479-5876-11-93

    View details for Web of Science ID 000318117400001

    View details for PubMedID 23570606

  • Response to valganciclovir in chronic fatigue syndrome patients with human herpesvirus 6 and Epstein-Barr virus IgG antibody titers JOURNAL OF MEDICAL VIROLOGY Watt, T., Oberfoell, S., Balise, R., Lunn, M. R., Kar, A. K., Merrihew, L., Bhangoo, M. S., Montoya, J. G. 2012; 84 (12): 1967-1974

    Abstract

    Valganciclovir has been reported to improve physical and cognitive symptoms in patients with chronic fatigue syndrome (CFS) with elevated human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV) IgG antibody titers. This study investigated whether antibody titers against HHV-6 and EBV were associated with clinical response to valganciclovir in a subset of CFS patients. An uncontrolled, unblinded retrospective chart review was performed on 61 CFS patients treated with 900 mg valganciclovir daily (55 of whom took an induction dose of 1,800 mg daily for the first 3 weeks). Antibody titers were considered high if HHV-6 IgG ? 1:320, EBV viral capsid antigen (VCA) IgG ? 1:640, and EBV early antigen (EA) IgG ? 1:160. Patients self-rated physical and cognitive functioning as a percentage of their functioning prior to illness. Patients were categorized as responders if they experienced at least 30% improvement in physical and/or cognitive functioning. Thirty-two patients (52%) were categorized as responders. Among these, 19 patients (59%) responded physically and 26 patients (81%) responded cognitively. Baseline antibody titers showed no significant association with response. After treatment, the average change in physical and cognitive functioning levels for all patients was +19% and +23%, respectively (P < 0.0001). Longer treatment was associated with improved response (P = 0.0002). No significant difference was found between responders and non-responders among other variables analyzed. Valganciclovir treatment, independent of the baseline antibody titers, was associated with self-rated improvement in physical and cognitive functioning for CFS patients who had positive HHV-6 and/or EBV serologies. Longer valganciclovir treatment correlated with an improved response.

    View details for DOI 10.1002/jmv.23411

    View details for Web of Science ID 000310339300020

    View details for PubMedID 23080504

  • Prevention and Treatment of Cancer-Related Infections JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Baden, L. R., Bensinger, W., Angarone, M., Casper, C., Dubberke, E. R., Freifeld, A. G., Garzon, R., Greene, J. N., Greer, J. P., Ito, J. I., Karp, J. E., Kaul, D. R., King, E., Mackler, E., Marr, K. A., Montoya, J. G., Morris-Engemann, A., Pappas, P. G., Rolston, K., Segal, B., Seo, S. K., Swaminathan, S., Naganuma, M., Shead, D. A. 2012; 10 (11): 1412-1445

    Abstract

    Patients with cancer are at increased risk for developing infectious complications during the course of their disease and treatment. The following sections of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prevention and Treatment of Cancer-Related Infections provide an overview of the risk factors for infectious complications, recommendations for infectious risk categorization, and strategies for prevention of infections in high-risk patient populations with cancer. Individualized risk evaluation for infections and incorporation of preventative measures are essential components of the overall spectrum of cancer care, and may contribute to optimizing treatment outcomes for patients.

    View details for Web of Science ID 000310822900011

    View details for PubMedID 23138169

  • Antiviral therapy of two patients with chromosomally-integrated human herpesvirus-6A presenting with cognitive dysfunction JOURNAL OF CLINICAL VIROLOGY Montoya, J. G., Neely, M. N., Gupta, S., Lunn, M. R., Loomis, K. S., Pritchett, J. C., Polsky, B., Medveczky, P. G. 2012; 55 (1): 40-45

    Abstract

    Human herpesvirus 6 (HHV-6) is a neurotropic virus implicated in central nervous system (CNS) dysfunction, multiple sclerosis, seizures and encephalitis. Inherited or "chromosomally integrated" HHV-6 (CIHHV-6) is a condition characterized by high DNA loads and germ line transmission of HHV-6 genomes, which are integrated into the telomere.We previously reported that integrated HHV-6 can be reactivated by trichostatin A in vitro. Therefore, we hypothesized that a broad array of neurological symptoms of CIHHV-6 patients may respond to antiviral drug treatment.The patients have been treated with antiviral drugs and monitored for viral load, late mRNA, and clinical improvement.Antiviral therapy of two CIHHV patients resulted in successful clinical resolution. However, both patients relapsed on multiple occasions within 4-6 months of cessation of antiviral therapy.Successful antiviral drug treatment suggests that clinical symptoms of these patients were due to symptomatic reactivation of CIHHV-6. Alternatively, some CIHHV-6 patients may have a reduced resistance to community-acquired HHV-6 strains due to tolerance leading to persistent infections.

    View details for DOI 10.1016/j.jcv.2012.05.016

    View details for Web of Science ID 000307997300009

    View details for PubMedID 22770640

  • A Multicenter Blinded Analysis Indicates No Association between Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and either Xenotropic Murine Leukemia Virus-Related Virus or Polytropic Murine Leukemia Virus MBIO Alter, H. J., Mikovits, J. A., Switzer, W. M., Ruscetti, F. W., Lo, S., Klimas, N., Komaroff, A. L., Montoya, J. G., Bateman, L., Levine, S., Peterson, D., Levin, B., Hanson, M. R., Genfi, A., Bhat, M., Zheng, H., Wang, R., Li, B., Hung, G., Lee, L. L., Sameroff, S., Heneine, W., Coffin, J., Hornig, M., Lipkin, W. I. 2012; 3 (5)

    Abstract

    The disabling disorder known as chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) has been linked in two independent studies to infection with xenotropic murine leukemia virus-related virus (XMRV) and polytropic murine leukemia virus (pMLV). Although the associations were not confirmed in subsequent studies by other investigators, patients continue to question the consensus of the scientific community in rejecting the validity of the association. Here we report blinded analysis of peripheral blood from a rigorously characterized, geographically diverse population of 147 patients with CFS/ME and 146 healthy subjects by the investigators describing the original association. This analysis reveals no evidence of either XMRV or pMLV infection. IMPORTANCE Chronic fatigue syndrome/myalgic encephalomyelitis has an estimated prevalence of 42/10,000 in the United States, with annual direct medical costs of $7 billion. Here, the original investigators who found XMRV and pMLV (polytropic murine leukemia virus) in blood of subjects with this disorder report that this association is not confirmed in a blinded analysis of samples from rigorously characterized subjects. The increasing frequency with which molecular methods are used for pathogen discovery poses new challenges to public health and support of science. It is imperative that strategies be developed to rapidly and coherently address discoveries so that they can be carried forward for translation to clinical medicine or abandoned to focus resource investment more productively. Our study provides a paradigm for pathogen dediscovery that may be helpful to others working in this field.

    View details for DOI 10.1128/mBio.00266-12

    View details for Web of Science ID 000310585000015

    View details for PubMedID 22991430

  • Toxoplasmosis in the fetus and newborn: an update on prevalence, diagnosis and treatment EXPERT REVIEW OF ANTI-INFECTIVE THERAPY Moncada, P. A., Montoya, J. G. 2012; 10 (7): 815-828

    Abstract

    Toxoplasma gondii is an unicellular coccidian parasite with worldwide distribution. It is estimated that more than a third of the world's population has been infected with the parasite, but seroprevalence is unevenly distributed across countries and different socioeconomic strata. The majority of newborns with congenital toxoplasmosis do not have any clinical signs of the disease at birth; however, 30-70% of those with clinical abnormalities were not detected initially, and are found to have new retinal lesions consistent with toxoplasmicchorioretinitis later in life. Congenital toxoplasmosis can also cause fetal death, stillbirths or long-term disabling sequelae, particularly among untreated infants. The disease appears to be more frequent and severe at certain latitudes. Congenital toxoplasmosis can be prevented and treated during gestation. Less severe disease is commonly reported in countries where prenatal screening and treatment have been systematically implemented. By contrast, severe disease appears to be observed primarily in infants born to untreated mothers. For definition purposes, it is best to use the term toxoplasma or Toxoplasma gondii infection when referring to asymptomatic patients with primary or chronic infection, and toxoplasmosis when referring to patients with symptoms or signs.

    View details for DOI 10.1586/ERI.12.58

    View details for Web of Science ID 000309854100016

    View details for PubMedID 22943404

  • Chromosomally integrated human herpesvirus 6: questions and answers REVIEWS IN MEDICAL VIROLOGY Pellett, P. E., Ablashi, D. V., Ambros, P. F., Agut, H., Caserta, M. T., Descamps, V., Flamand, L., Gautheret-Dejean, A., Hall, C. B., Kamble, R. T., Kuehl, U., Lassner, D., Lautenschlager, I., Loomis, K. S., Luppi, M., Lusso, P., Medveczky, P. G., Montoya, J. G., Mori, Y., Ogata, M., Pritchett, J. C., Rogez, S., Seto, E., Ward, K. N., Yoshikawa, T., Razonable, R. R. 2012; 22 (3): 144-155

    Abstract

    Chromosomally integrated human herpesvirus 6 (ciHHV-6) is a condition in which the complete HHV-6 genome is integrated into the host germ line genome and is vertically transmitted in a Mendelian manner. The condition is found in less than 1% of controls in the USA and UK, but has been found at a somewhat higher prevalence in transplant recipients and other patient populations in several small studies. HHV-6 levels in whole blood that exceed 5.5 log10 copies/ml are strongly suggestive of ciHHV-6. Monitoring DNA load in plasma and serum is unreliable, both for identifying and for monitoring subjects with ciHHV-6 due to cell lysis and release of cellular DNA. High HHV-6 DNA loads associated with ciHHV-6 can lead to erroneous diagnosis of active infection. Transplant recipients with ciHHV-6 may be at increased risk for bacterial infection and graft rejection. ciHHV-6 can be induced to a state of active viral replication in vitro. It is not known whether ciHHV-6 individuals are put at clinical risk by the use of drugs that have been associated with HHV-6 reactivation in vivo or in vitro. Nonetheless, we urge careful observation when use of such drugs is indicated in individuals known to have ciHHV-6. Little is known about whether individuals with ciHHV-6 develop immune tolerance for viral proteins. Further research is needed to determine the role of ciHHV-6 in disease.

    View details for DOI 10.1002/rmv.715

    View details for Web of Science ID 000303119600002

    View details for PubMedID 22052666

  • 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

  • Diagnostic Approach to Ocular Toxoplasmosis OCULAR IMMUNOLOGY AND INFLAMMATION Garweg, J. G., de Groot-Mijnes, J. D., Montoya, J. G. 2011; 19 (4): 255-261

    Abstract

    Toxoplasmic retinochoroiditis is deemed a local event, which may fail to evoke a detectable systemic immune response. A correct diagnosis of the disease is a necessary basis for estimating its clinical burden. This is not so difficult in a typical clinical picture. In atypical cases, further diagnostic efforts are to be installed. Although the aqueous humor may be analyzed for specific antibodies or the presence of parasitic DNA, the DNA burden therein is low, and in rare instances a confirmation would necessitate vitreous sampling. A laboratory confirmation of the diagnosis is frustrated by individual differences in the time elapsing between clinical symptoms and activation of specific antibody production, which may result in false negatives. In congenital ocular toxoplasmosis, a delay in the onset of specific local antibody production could reflect immune tolerance. Herein, the authors attempt to provide a simple and practicable algorithm for a clinically tailored diagnostic approach in atypical instances.

    View details for DOI 10.3109/09273948.2011.595872

    View details for Web of Science ID 000292915300008

    View details for PubMedID 21770803

  • Working formulation for the standardization of definitions of infections in patients using ventricular assist devices JOURNAL OF HEART AND LUNG TRANSPLANTATION Hannan, M. M., Husain, S., Mattner, F., Danziger-Isakov, L., Drew, R. J., Corey, G. R., Schueler, S., Holman, W. L., Lawler, L. P., Gordon, S. M., Mahon, N. G., Herre, J. M., Gould, K., Montoya, J. G., Padera, R. F., Kormos, R. L., Conte, J. V., Mooney, M. L. 2011; 30 (4): 375-384

    View details for DOI 10.1016/j.healun.2011.01.717

    View details for Web of Science ID 000288924200002

    View details for PubMedID 21419995

  • Yield of diagnostic procedures for invasive fungal infections in neutropenic febrile patients with chest computed tomography abnormalities MYCOSES Ho, D. Y., Lin, M., Schaenman, J., Rosso, F., Leung, A. N., Coutre, S. E., Sista, R. R., Montoya, J. G. 2011; 54 (1): 59-70

    Abstract

    Haematological patients with neutropenic fever are frequently evaluated with chest computed tomography (CT) to rule out invasive fungal infections (IFI). We retrospectively analysed data from 100 consecutive patients with neutropenic fever and abnormal chest CT from 1998 to 2005 to evaluate their chest CT findings and the yield of diagnostic approaches employed. For their initial CTs, 79% had nodular opacities, with 24.1% associated with the halo sign. Other common CT abnormalities included pleural effusions (48%), ground glass opacities (37%) and consolidation (31%). The CT findings led to a change in antifungal therapy in 54% of the patients. Fifty-six patients received diagnostic procedures, including 46 bronchoscopies, 25 lung biopsies and seven sinus biopsies, with a diagnostic yield for IFI of 12.8%, 35.0% and 83.3%, respectively. In conclusion, chest CT plays an important role in the evaluation of haematological patients with febrile neutropenia and often leads to a change in antimicrobial therapy. Pulmonary nodules are the most common radiological abnormality. Sinus or lung biopsies have a high-diagnostic yield for IFI as compared to bronchoscopy. Patients with IFI may not have sinus/chest symptoms, and thus, clinicians should have a low threshold for performing sinus/chest imaging, and if indicated and safe, a biopsy of the abnormal areas.

    View details for DOI 10.1111/j.1439-0507.2009.01760.x

    View details for Web of Science ID 000284900600009

    View details for PubMedID 19793207

  • The latent human herpesvirus-6A genome specifically integrates in telomeres of human chromosomes in vivo and in vitro PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Arbuckle, J. H., Medveczky, M. M., Luka, J., Hadley, S. H., Luegmayr, A., Ablashi, D., Lund, T. C., Tolar, J., De Meirleir, K., Montoya, J. G., Komaroff, A. L., Ambros, P. F., Medveczky, P. G. 2010; 107 (12): 5563-5568

    Abstract

    Previous research has suggested that human herpesvirus-6 (HHV-6) may integrate into host cell chromosomes and be vertically transmitted in the germ line, but the evidence--primarily fluorescence in situ hybridization (FISH)--is indirect. We sought, first, to definitively test these two hypotheses. Peripheral blood mononuclear cells (PBMCs) were isolated from families in which several members, including at least one parent and child, had unusually high copy numbers of HHV-6 DNA per milliliter of blood. FISH confirmed that HHV-6 DNA colocalized with telomeric regions of one allele on chromosomes 17p13.3, 18q23, and 22q13.3, and that the integration site was identical among members of the same family. Integration of the HHV-6 genome into TTAGGG telomere repeats was confirmed by additional methods and sequencing of the integration site. Partial sequencing of the viral genome identified the same integrated HHV-6A strain within members of families, confirming vertical transmission of the viral genome. We next asked whether HHV-6A infection of naïve cell lines could lead to integration. Following infection of naïve Jjhan and HEK-293 cell lines by HHV-6, the virus integrated into telomeres. Reactivation of integrated HHV-6A virus from individuals' PBMCs as well as cell lines was successfully accomplished by compounds known to induce latent herpesvirus replication. Finally, no circular episomal forms were detected even by PCR. Taken together, the data suggest that HHV-6 is unique among human herpesviruses: it specifically and efficiently integrates into telomeres of chromosomes during latency rather than forming episomes, and the integrated viral genome is capable of producing virions.

    View details for DOI 10.1073/pnas.0913586107

    View details for Web of Science ID 000275898300054

    View details for PubMedID 20212114

  • Changing trends in infectious disease in heart transplantation JOURNAL OF HEART AND LUNG TRANSPLANTATION Haddad, F., Deuse, T., Pham, M., Khazanie, P., Rosso, F., Luikart, H., Valantine, H., Leon, S., Vu, T. A., Hunt, S. A., Oyer, P., Montoya, J. G. 2010; 29 (3): 306-315

    Abstract

    During the past 25 years, advances in immunosuppression and the use of selective anti-microbial prophylaxis have progressively reduced the risk of infection after heart transplantation. This study presents a historical perspective of the changing trends of infectious disease after heart transplantation.Infectious complications in 4 representative eras of immunosuppression and anti-microbial prophylaxis were analyzed: (1) 38 in the pre-cyclosporine era (1978-1980), (2) 72 in the early cyclosporine era (1982-1984), where maintenance immunosuppression included high-dose cyclosporine and corticosteroid therapy; (3) 395 in the cyclosporine era (1988-1997), where maintenance immunosuppression included cyclosporine, azathioprine, and lower corticosteroid doses; and (4) 167 in the more recent era (2002-2005), where maintenance immunosuppression included cyclosporine and mycophenolate mofetil.The overall incidence of infections decreased in the 4 cohorts from 3.35 episodes/patient to 2.03, 1.35, and 0.60 in the more recent cohorts (p < 0.001). Gram-positive bacteria are emerging as the predominant cause of bacterial infections (28.6%, 31.4%, 51.0%, 67.6%, p = 0.001). Cytomegalovirus infections have significantly decreased in incidence and occur later after transplantation (88 +/- 77 days, pre-cyclosporine era; 304 +/- 238 days, recent cohort; p < 0.001). Fungal infections also decreased, from an incidence of 0.29/patient in the pre-cyclosporine era to 0.08 in the most recent era. A major decrease in Pneumocystis jiroveci and Nocardia infections has also occurred.The overall incidence and mortality associated with infections continues to decrease in heart transplantation and coincides with advances in immunosuppression, the use of selective anti-microbial prophylaxis, and more effective treatment regimens.

    View details for DOI 10.1016/j.healun.2009.08.018

    View details for Web of Science ID 000276005200013

    View details for PubMedID 19853478

  • 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

  • Trends in invasive disease due to Candida species following heart and lung transplantation TRANSPLANT INFECTIOUS DISEASE Schaenman, J. M., Rosso, F., Austin, J. M., Baron, E. J., Gamberg, P., Miller, J., Oyer, P. E., Robbins, R. C., Montoya, J. G. 2009; 11 (2): 112-121

    Abstract

    Although invasive candidiasis (IC) causes significant morbidity and mortality in patients who undergo heart, lung, or heart-lung transplantation, a systematic study in a large cohort of thoracic organ transplant recipients has not been reported to date. Clinical and microbiological data were reviewed for 1305 patients who underwent thoracic organ transplantation at Stanford University Medical Center between 1980 and 2004. We identified and analyzed 76 episodes of IC in 68 patients (overall incidence 5.2% per patient).The incidence of IC was higher in lung (LTx) and heart-lung transplant (HLTx) recipients as compared with heart transplant (HTx) recipients (risk ratio [RR] 1.7, 95% confidence interval [CI] 1.1-2.7).The incidence of IC decreased over time in all thoracic organ transplant recipients, decreasing from 6.1% in the 1980-1986 time period to 2.1% in the 2001-2004 era in the HTx recipients, and from 20% in the 1980-1986 period to 1.8% in the 2001-2004 period in the LTx and HLTx recipients.The most common site of infection differed between the HTx and LTx cohorts, with bloodstream or disseminated disease in the former and tracheobronchitis in the latter. IC in the first year after transplant was significantly associated with death in both HTx (RR 2.9, 95% CI 1.8-4.6, P=0.001) and LTx and HLTx patients (RR 3.0, 95% CI 1.9-4.6, P<0.001). The attributable mortality from IC decreased during the 25-year period of observation, from 36% to 20% in the HTx recipients and from 39% to 15% in the LTx and HLTx recipients. There were a significant number of cases caused by non-albicans Candida species in all patients, with a trend toward higher mortality in the HTx group. In conclusion, the incidence and attributable mortality of IC in thoracic organ transplant recipients has significantly declined over the past 25 years.The use of newer antifungal agents for prophylaxis and treatment, the decrease in the incidence of cytomegalovirus disease, and the use of more selective immunosuppression, among other factors, may have been responsible for this change.

    View details for DOI 10.1111/j.1399-3062.2009.00364.x

    View details for Web of Science ID 000265015600004

    View details for PubMedID 19254327

  • Challenges and Pitfalls of Morphologic Identification of Fungal Infections in Histologic and Cytologic Specimens A Ten-Year Retrospective Review at a Single Institution AMERICAN JOURNAL OF CLINICAL PATHOLOGY Sangoi, A. R., Rogers, W. M., Longacre, T. A., Montoya, J. G., Baron, E. J., Banaei, N. 2009; 131 (3): 364-375

    Abstract

    Despite the advantages of providing an early presumptive diagnosis, fungal classification by histopathology can be difficult and may lead to diagnostic error. To assess the accuracy of histologic diagnosis of fungal infections vs culture ("gold standard"), we performed a 10-year retrospective review at our institution. Of the 47 of 338 positive mold and yeast cultures with concurrent surgical pathology evaluation without known history of a fungal infection, 37 (79%) were correctly identified based on morphologic features in histologic and/or cytologic specimens. The 10 discrepant diagnoses (21%) included misidentification of septate and nonseptate hyphal organisms and yeast forms. Errors resulted from morphologic mimics, use of inappropriate terminology, and incomplete knowledge in mycology. The accuracy did not correlate with preceding antifungal therapy (P = .14) or use of special stains (P = .34) and was not operator-dependent. Among 8 discrepancies with clinical follow-up available, 2 potential adverse clinical consequences resulted. While histopathologic identification of fungi in tissue sections and cytologic preparations is prone to error, implementation of a standardized reporting format should improve diagnostic accuracy and prevent adverse outcomes.

    View details for DOI 10.1309/AJCP99OOOZSNISCZ

    View details for Web of Science ID 000263427400008

    View details for PubMedID 19228642

  • Severe Encephalomyelitis in an Immunocompetent Adult with Chromosomally Integrated Human Herpesvirus 6 and Clinical Response to Treatment with Foscarnet plus Ganciclovir CLINICAL INFECTIOUS DISEASES Troy, S. B., Blackburn, B. G., Yeom, K., Caulfield, A. K., Bhangoo, M. S., Montoya, J. G. 2008; 47 (12): E93-E96

    Abstract

    Human herpesvirus 6 has rarely been identified as a cause of encephalitis in immunocompetent adults. We describe a patient who had severe encephalomyelitis, hypoglycorrhachia, and human herpesvirus 6 identified in his cerebrospinal fluid and serum and who recovered after treatment with foscarnet and ganciclovir. Human herpesvirus 6 should be considered in immunocompetent patients with encephalitis.

    View details for DOI 10.1086/593315

    View details for Web of Science ID 000261163600035

    View details for PubMedID 18991511

  • 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

  • Prevention and treatment of cancer-related infections. Journal of the National Comprehensive Cancer Network Segal, B. H., Freifeld, A. G., Baden, L. R., Brown, A. E., Casper, C., Dubberke, E., Gelfand, M., Greene, J. N., Ison, M. G., Ito, J. I., Karp, J. E., Kaul, D. R., King, E., Mackler, E., Marcucci, G., Montoya, J. G., Engemann, A. M., Rolston, K., The, A. S. 2008; 6 (2): 122-174

    View details for PubMedID 18319048

  • Improving the tools in the fight against cytomegalovirus or strengthening David to defeat Goliath CURRENT OPINION IN INFECTIOUS DISEASES Montoya, J. G. 2007; 20 (4): 397-398

    View details for Web of Science ID 000248074100008

    View details for PubMedID 17609599

  • 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

  • Treating disseminated fusariosis: amphotericin B, voriconazole or both? MYCOSES Ho, D. Y., Lee, J. D., Rosso, F., Montoya, J. G. 2007; 50 (3): 227-231

    Abstract

    Disseminated Fusarium infection can cause significant morbidity and mortality in immunocompromised patients. We present a case of disseminated fusariosis in a patient with neutropenic fever successfully treated using both liposomal amphotericin B and voriconazole. Combination anti-fungal therapy may be considered for such patients, particularly for those failing single-drug therapy.

    View details for DOI 10.1111/j.0933-7407.2006.2006.01346.x

    View details for Web of Science ID 000246151400013

    View details for PubMedID 17472622

  • A case of successful treatment of cutaneous Acanthamoeba infection in a lung transplant recipient TRANSPLANT INFECTIOUS DISEASE Walia, R., Montoya, J. G., Visvesvera, G. S., Booton, G. C., Doyle, R. L. 2007; 9 (1): 51-54

    Abstract

    Acanthamoeba species are known to cause 2 well-described entities: (1) granulomatous amoebic encephalitis (GAE), which usually affects immunocompromised hosts, and (2) keratitis, which typically follows trauma associated with contamination of water or contact lenses. Less common manifestations include pneumonitis and a subacute granulomatous dermatitis. We describe a case of granulomatous dermatitis secondary to Acanthamoeba infection in a lung transplant recipient and a successful outcome following treatment with lipid formulation of amphotericin B and voriconazole. We believe this is the second case report describing disseminated Acanthamoeba infection in a lung transplant recipient. We also describe successful outcome with a combination of lipid formulation of amphotericin B and voriconazole, drugs that have not been previously reported to treat Acanthamoeba.

    View details for DOI 10.1111/j.1399-3062.2006.00159.x

    View details for Web of Science ID 000244957300011

    View details for PubMedID 17313473

  • Pulmonary nocardiosis in a heart transplant patient: Case report and review of the literature JOURNAL OF HEART AND LUNG TRANSPLANTATION Haddad, F., Hunt, S. A., Perlroth, M., Valantine, H., Doyle, R., Montoya, J. 2007; 26 (1): 93-97

    Abstract

    Pulmonary infection with Nocardia is an uncommon but serious infection found in immunocompromised patients. We describe a rapidly progressive pulmonary nocardiosis in a heart transplant patient. We then review the common clinical features of Nocardia infection in transplant recipients, outlining the challenges in its diagnosis and management. We also review the differences between Pneumocystis jiroveci prophylaxis regimens with respect to concomitant prophylaxis of Nocardia and other opportunistic infections.

    View details for DOI 10.1016/j.healun.2006.11.002

    View details for Web of Science ID 000243950900015

    View details for PubMedID 17234524

  • Use of valganciclovir in patients with elevated antibody titers against Human Herpesvirus-6 (HHV-6) and Epstein-Barr Virus (EBV) who were experiencing central nervous system dysfunction including long-standing fatigue JOURNAL OF CLINICAL VIROLOGY Kogelnik, A. M., Loomis, K., Hoegh-Petersen, M., Rosso, F., Hischier, C., Montoya, J. G. 2006; 37: S33-S38

    Abstract

    Twelve patients with long-standing symptoms of central nervous system (CNS) dysfunction were found to have elevated antibody titres to human herpesvirus-6 (HHV-6) and Epstein-Barr virus (EBV). All patients had four or more of the following neurocognitive symptoms: impaired cognitive functioning, slowed processing speed, sleep disturbance, short-term memory deficit, fatigue and symptoms consistent with depression.We sought to determine whether elevated antibodies to EBV and HHV-6 indicated chronic viral activation in patients with CNS dysfunction and if their symptoms could be improved by suppressing viral activity with oral valganciclovir.Patients with high IgG antibody titers against HHV-6 and EBV who were suffering from central nervous system dysfunction and debilitating fatigue for more than one year (median 3 years, range 1-8 years) were treated with 6 months of valganciclovir in an open label study.Nine out of 12 (75%) patients experienced near resolution of their symptoms, allowing them all to return to the workforce or full time activites. In the nine patients with a symptomatic response to treatment, EBV VCA IgG titers dropped from 1:2560 to 1:640 (p = 0.008) and HHV-6 IgG titers dropped from a median value of 1:1280 to 1:320 (p = 0.271). Clinically significant hematological toxicity or serious adverse events were not observed among the 12 patients.These preliminary clinical and laboratory observations merit additional studies to establish whether this clinical response is mediated by an antiviral effect of the drug, indirectly via immunomodulation or by placebo effect.

    View details for Web of Science ID 000243845000009

    View details for PubMedID 17276366

  • Is combination therapy indicated for invasive fungal infections? Yes and no CURRENT OPINION IN INFECTIOUS DISEASES Montoya, J. G., Rosso, F. 2006; 19 (4): 357-359

    View details for Web of Science ID 000239417200007

    View details for PubMedID 16804383

  • Late-onset invasive aspergillosis in organ transplant recipients in the current era MEDICAL MYCOLOGY Singh, N., Limaye, A. P., Forrest, G., Safdar, N., Munoz, P., Pursell, K., Houston, S., Rosso, F., Montoya, J. G., Patton, P. R., del Busto, R., Aguado, J. M., Wagener, M. M., Husain, S. 2006; 44 (5): 445-449

    Abstract

    We assessed predictive factors and characteristics of patients with late-onset invasive aspergillosis in the current era of novel immunosuppressive agents. Forty transplant recipients with invasive aspergillosis were included in this prospective, observational study initiated in 2003 at our institutions. In 50% (20/40) of these patients, the infections were late-occurring. Receipt of sirolimus in conjunction with tacrolimus for refractory rejection or cardiac allograft vasculopathy (P=0.047) was significantly associated with late-onset infection. The use of depleting or non-depleting T or B-cell antibodies, either as induction or as antirejection therapy did not correlate with time to onset of invasive aspergillosis. Mortality at 90 days was 20% (4/20) for the patients with early-onset infection and 45% (9/20) for those with late-onset infection (P=0.17). Thus, nearly one-half of the Aspergillus infections in transplant recipients in the current era are late-occurring. These data have implications relevant for prophylactic strategies and guiding clinical management of transplant recipients presenting with pulmonary infiltrates.

    View details for DOI 10.1080/13693780600684494

    View details for Web of Science ID 000240494500007

    View details for PubMedID 16882611

  • Combination of voriconazole and caspofungin as primary therapy for invasive aspergillosis in solid organ transplant recipients: A prospective, multicenter, observational study TRANSPLANTATION Singh, N., Limaye, A. P., Forrest, G., Safdar, N., Munoz, P., Pursell, K., Houston, S., Rosso, F., Montoya, J. G., Patton, P., del Busto, R., Aguado, J. M., Fisher, R. A., Klintmalm, G. B., Miller, R., Wagener, M. M., Lewis, R. E., Kontoyiannis, D. P., Husain, S. 2006; 81 (3): 320-326

    Abstract

    : The efficacy of the combination of voriconazole and caspofungin when used as primary therapy for invasive aspergillosis in organ transplant recipients has not been defined.: Transplant recipients who received voriconazole and caspofungin (n=40) as primary therapy for invasive aspergillosis (proven or probable) in a prospective multicenter study between 2003 and 2005 were compared to a control group comprising a cohort of consecutive transplant recipients between 1999 and 2002 who had received a lipid formulation of AmB as primary therapy (n=47). In vitro antifungal testing of Aspergillus isolates to combination therapy was correlated with clinical outcome.: Survival at 90 days was 67.5% (27/40) in the cases, and 51% (24/47) in the control group (HR 0.58, 95% CI, 0.30-1.14, P=0.117). However, in transplant recipients with renal failure (adjusted HR 0.32, 95% CI: 0.12-0.85, P=0.022), and in those with A. fumigatus infection (adjusted HR 0.37, 95% CI: 0.16-0.84, P=0.019), combination therapy was independently associated with an improved 90-day survival in multivariate analysis. No correlation was found between in vitro antifungal interactions of the Aspergillus isolates to the combination of voriconazole and caspofungin and clinical outcome.: Combination of voriconazole and caspofungin might be considered preferable therapy for subsets of organ transplant recipients with invasive aspergillosis, such as those with renal failure or A. fumigatus infection.

    View details for DOI 10.1097/01.tp.0000202421.94822.f7

    View details for Web of Science ID 000235377800005

    View details for PubMedID 16477215

  • Practice guidelines for the diagnosis and management of skin and soft-tissue infections CLINICAL INFECTIOUS DISEASES Stevens, D. L., BISNO, A. L., Chambers, H. F., Everett, E. D., Dellinger, P., Goldstein, E. J., Gorbach, S. L., Hirschmann, J. V., Kaplan, E. L., Montoya, J. G., Wade, J. C. 2005; 41 (10): 1373-1406

    View details for Web of Science ID 000232670400001

    View details for PubMedID 16231249

  • Diagnosis and management of toxoplasmosis CLINICS IN PERINATOLOGY Montoya, J. G., Rosso, F. 2005; 32 (3): 705-?

    Abstract

    This article discusses the diagnosis and management of toxoplasmosis. Congenital toxoplasmosis continues to be a tragic outcome of a preventable and treatable infection. Education of patients, physicians and health policy makers on the primary and secondary preventive measures of the disease, and their execution, will undoubtedly result in lower incidence, morbidity, and mortality rates from congenital disease due to Toxoplasma gondii.

    View details for DOI 10.1016/j.clp.2005.04.011

    View details for Web of Science ID 000231553500011

    View details for PubMedID 16085028

  • Molecular mycological diagnosis and correct antimycotic treatments JOURNAL OF CLINICAL MICROBIOLOGY Mancini, N., Ossi, C. M., Perotti, M., Clementi, M. 2005; 43 (7): 3584-3584
  • 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

  • Scedosporium apiospermum soft tissue infection successfully treated with voriconazole: Potential pitfalls in the transition from intravenous to oral therapy JOURNAL OF CLINICAL MICROBIOLOGY Schaenman, J. M., DiGiulio, D. B., Mirels, L. F., McClenny, N. M., Berry, G. J., Fothergill, A. W., Rinaldi, M. G., Montoya, J. G. 2005; 43 (2): 973-977

    Abstract

    An immunocompromised patient with an invasive soft tissue infection due to Scedosporium apiospermum was successfully treated with voriconazole and surgical debridement. After transition from intravenous to oral therapy, successive adjustments of the oral dose were required to achieve complete resolution. For soft tissue infections due to molds characterized by thin, septate hyphae branching at acute angles, voriconazole should be considered a first-line antifungal agent. The potential usefulness of plasma voriconazole levels for guiding optimal therapy should be investigated.

    View details for DOI 10.1128/JCM.43.2.973-977.2005

    View details for Web of Science ID 000227045600082

    View details for PubMedID 15695722

  • 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

  • Successes and limitations of antimicrobial interventions in the setting of organ transplantation CURRENT OPINION IN INFECTIOUS DISEASES Montoya, J. G. 2004; 17 (4): 341-345
  • Toxoplasmosis LANCET Montoya, J. G., Liesenfeld, O. 2004; 363 (9425): 1965-1976

    Abstract

    Toxoplasma gondii is a protozoan parasite that infects up to a third of the world's population. Infection is mainly acquired by ingestion of food or water that is contaminated with oocysts shed by cats or by eating undercooked or raw meat containing tissue cysts. Primary infection is usually subclinical but in some patients cervical lymphadenopathy or ocular disease can be present. Infection acquired during pregnancy may cause severe damage to the fetus. In immunocompromised patients, reactivation of latent disease can cause life-threatening encephalitis. Diagnosis of toxoplasmosis can be established by direct detection of the parasite or by serological techniques. The most commonly used therapeutic regimen, and probably the most effective, is the combination of pyrimethamine with sulfadiazine and folinic acid. This Seminar provides an overview and update on management of patients with acute infection, pregnant women who acquire infection during gestation, fetuses or infants who are congenitally infected, those with ocular disease, and immunocompromised individuals. Controversy about the effectiveness of primary and secondary prevention in pregnant women is discussed. Important topics of current and future research are presented.

    View details for Web of Science ID 000221962800019

    View details for PubMedID 15194258

  • Recent developments for diagnosis of toxoplasmosis JOURNAL OF CLINICAL MICROBIOLOGY Remington, J. S., Thulliez, P., Montoya, J. G. 2004; 42 (3): 941-945
  • Invasive aspergillosis in the setting of cardiac transplantation CLINICAL INFECTIOUS DISEASES Montoya, J. G., Chaparro, S. V., Celis, D., Cortes, J. A., Leung, A. N., Robbins, R. C., Stevens, D. A. 2003; 37: S281-S292

    Abstract

    Among patients undergoing heart transplantation, Aspergillus is the opportunistic pathogen with the highest attributable mortality. The median time of onset from transplantation for invasive pulmonary aspergillosis (IPA) was 46 days, but the median time to first positive culture result was 104 days among patients with Aspergillus colonization but no invasive disease. Most patients with IPA presented with fever and cough within the first 90 days of transplantation and with single or multiple pulmonary nodules. None of the heart transplant recipients with either IPA or invasive extrapulmonary aspergillosis (IEPA) had associated neutropenia. Human leukocyte antigen A1 locus was found significantly more frequently among patients colonized with Aspergillus than among patients with IPA (P<.006) or IEPA (P<.001). Even in the absence of neutropenia, IPA should be suspected for heart transplant recipients who have fever and respiratory symptoms within the first 3 months of transplantation, have a positive result of culture of respiratory secretions, and have abnormal radiological findings (particularly nodules).

    View details for Web of Science ID 000186262900006

    View details for PubMedID 12975755

  • Post-transplantation lymphoproliferative disease in heart and heart-lung transplant recipients: 30-year experience at Stanford University JOURNAL OF HEART AND LUNG TRANSPLANTATION Gao, S. Z., Chaparro, S. V., Perlroth, M., Montoya, J. G., Miller, J. L., DiMiceli, S., Hastie, T., Oyer, P. E., Schroeder, J. 2003; 22 (5): 505-514

    Abstract

    Post-transplantation lymphoproliferative disease (PTLD) is an important source of morbidity and mortality in transplant recipients, with a reported incidence of 0.8% to 20%. Risk factors are thought to include immunosuppressive agents and viral infection. This study attempts to evaluate the impact of different immunosuppressive regimens, ganciclovir prophylaxis and other potential risk factors in the development of PTLD.We reviewed the records of 1026 (874 heart, 152 heart-lung) patients who underwent transplantation at Stanford between 1968 and 1997. Of these, 57 heart and 8 heart-lung recipients developed PTLD. During this interval, 4 different immunosuppressive regimens were utilized sequentially. In January 1987, ganciclovir prophylaxis for cytomegalovirus serologic-positive patients was introduced. Other potential risk factors evaluated included age, gender, prior cardiac diagnoses, HLA match, rejection frequency and calcium-channel blockade.No correlation of development of PTLD was found with different immunosuppression regimens consisting of azathioprine, prednisone, cyclosporine, OKT3 induction, tacrolimus and mycophenolate mofetil. A trend suggesting an influence of ganciclovir on the prevention of PTLD was not statistically significant (p = 0.12). Recipient age and rejection frequency, as well as high-dose cyclosporine immunosuppression, were significantly (p < 0.02) associated with PTLD development. The prevalence of PTLD at 13.3 years was 15%.The overall incidence of PTLD was 6.3%. It was not altered by sequential modifications in treatment regimens. Younger recipient age and higher rejection frequency were associated with increased PTLD occurrence. The 15% prevalence of PTLD in 58 long-term survivors was unexpectedly high.

    View details for DOI 10.1016/S1053-2498(02)01229-9

    View details for Web of Science ID 000182805100002

    View details for PubMedID 12742411

  • 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

  • Evolution of primary protease inhibitor resistance mutations during protease inhibitor salvage therapy ANTIMICROBIAL AGENTS AND CHEMOTHERAPY Kantor, R., Fessel, W. J., Zolopa, A. R., Israelski, D., Shulman, N., Montoya, J. G., Harbour, M., Schapiro, J. M., Shafer, R. W. 2002; 46 (4): 1086-1092

    Abstract

    In order to track the evolution of primary protease inhibitor (PI) resistance mutations in human immunodeficiency virus type 1 (HIV-1) isolates, baseline and follow-up protease sequences were obtained from patients undergoing salvage PI therapy who presented initially with isolates containing a single primary PI resistance mutation. Among 78 patients meeting study selection criteria, baseline primary PI resistance mutations included L90M (42% of patients), V82A/F/T (27%), D30N (21%), G48V (6%), and I84V (4%). Despite the switching of treatment to a new PI, primary PI resistance mutations present at the baseline persisted in 66 of 78 (85%) patients. D30N persisted less frequently than L90M (50% versus 100%, respectively; P < 0.001) and V82A/F/T (50% versus 81%, respectively; P = 0.05). HIV-1 isolates from 38 (49%) patients failing PI salvage therapy developed new primary PI resistance mutations including L90M, I84V, V82A, and G48V. Common combinations of primary and secondary PI resistance mutations after salvage therapy included mutations at amino acid positions 10, 82, and 46 and/or 54 in 16 patients; 10, 90, and 71 and/or 73 in 14 patients; 10, 73, 84, 90, and 46 and/or 54 in 5 patients; 10, 48, and 82 in 5 patients; and 30, 88 and 90 in 5 patients. In summary, during salvage PI therapy, most HIV-1 isolates with a single primary PI resistance mutation maintained their original mutations, and 49% developed additional primary PI resistance mutations. The persistence of L90M, V82A/F/T, G48V, and I84V during salvage therapy suggests that these mutations play a role in clinical resistance to multiple PIs.

    View details for DOI 10.1128/AAC.46.4.1086-1092.2002

    View details for Web of Science ID 000174597000022

    View details for PubMedID 11897594

  • Infectious complications among 620 consecutive heart transplant patients at Stanford University Medical Center AMERICAN JOURNAL OF HUMAN GENETICS Montoya, J. G., Giraldo, L. F., Efron, B., Stinson, E. B., Gamberg, P., Hunt, S., Giannetti, N., Miller, J., Remington, J. S. 2001; 69 (3): 629-U6
  • 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

  • Paclitaxel-induced hypersensitivity pneumonitis: radiographic and CT findings. AJR. American journal of roentgenology Wong, P., Leung, A. N., Berry, G. J., Atkins, K. A., Montoya, J. G., Ruoss, S. J., Stockdale, F. E. 2001; 176 (3): 718-720

    View details for PubMedID 11222212

  • Posttransplantation lymphoproliferative disease in heart and heart-lung transplant recipients: thirty years experience at our hospital. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Chaparro, S., Gao, S., Perlroth, M., Montoya, J., Hastie, T., Miller, J. L., Oyer, P. E., Schroeder, J. 2001; 20 (2): 258

    View details for PubMedID 11250519

  • Highly active antiretroviral therapy results in HIV type 1 suppression in lymph nodes, increased pools of naive T cells, decreased pools of activated T cells, and diminished frequencies of peripheral activated HIV type 1-specific CD8(+) T cells AIDS RESEARCH AND HUMAN RETROVIRUSES Gray, C. M., Lawrence, J., Ranheim, E. A., Vierra, M., Zupancic, M., Winters, M., Altman, J., Montoya, J., Zolopa, A., Schapiro, J., Haase, A. T., Merigan, T. C. 2000; 16 (14): 1357-1369

    Abstract

    This study examines sequential lymph nodes from 13 drug-naive patients before and after 24 weeks of highly active antiretroviral therapy (HAART). A multipronged approach was used to study changes in HIV-1 RNA in each paired lymph node in relation to tissue architecture and frequency of naive T cells. After 24 weeks, all patients showed significant suppression of plasma viral load and 12 of 13 showed concordant viral suppression in the lymph node (p = 0.001). Using in situ hybridization and quantitative image analysis, we showed that HIV-1 RNA was reduced to below detectable levels (two copies per cell) in follicular dendritic cell (FDC) and mononuclear cell pools. Independent immunohistochemical analysis of lymph node sections revealed that 5 of 13 patients displayed increased FDC networks and 6 of 13 showed no change and all patients showed increases in tissue-resident CD4+ cells. All lymph node biopsies at 24 weeks showed increased proportions of CD4+ and CD8+ cells coexpressing the naive markers CD45RA and CD62L when compared with baseline values. Significant correlations existed between viral load suppression and loss of activated CD8+ T cells after 24 weeks in both lymph node and blood, which was mirrored by significantly lowered frequencies of activated peripheral Gag peptide/MHC tetramer+ CD8+ cells. Overall, these data show that a potent and successful treatment strategy that significantly suppresses and removes FDC-resident HIV-1 results in improvements in lymphoid architecture and by so doing provides the structures available for increased numbers of naive cells to interact with cognate antigen. In addition, our article shows that suppression of HIV-1 replication results in diminished frequencies of peripherally activated antigen-specific CD8+ cells.

    View details for Web of Science ID 000089593100004

    View details for PubMedID 11018855

  • HIV-1 genotypic resistance patterns predict response to saquinavir-ritonavir therapy in patients in whom previous protease inhibitor therapy had failed ANNALS OF INTERNAL MEDICINE Zolopa, A. R., Shafer, R. W., Warford, A., Montoya, J. G., Hsu, P., KATZENSTEIN, D., Merigan, T. C., Efron, B. 1999; 131 (11): 813-?

    Abstract

    Tests for resistance to HIV drugs are available for clinical use; however, their predictive value has not been fully assessed.To determine HIV-1 genotypic predictors of a virologic response to saquinavir-ritonavir therapy in patients in whom at least one previous protease inhibitor-containing regimen had failed and to compare the predictive value of baseline genotype with that of standard clinical evaluation.Retrospective clinical cohort study.University-based HIV clinic.54 HIV-1-infected adults treated with saquinavir-ritonavir who had experienced virologic failure while receiving a protease inhibitor-containing regimen for at least 3 months.HIV-1 reverse transcriptase and protease gene sequences, CD4 cell counts, clinical characteristics, detailed antiretroviral treatment history, and plasma HIV-1 RNA levels at baseline and at three follow-up time points (median, 4, 12, and 26 weeks). Virologic failure was defined as a plasma HIV RNA level greater than 1000 copies/mL.In 22 patients (41%), a plasma HIV-1 RNA level less than 500 copies/mL was achieved by week 12; in 15 patients (28%), this response was maintained through week 26. Clinical characteristics predicting a poorer response included a diagnosis of AIDS, lower CD4 cell count, and higher plasma HIV RNA level (P<0.03). Number of previous nucleoside reverse transcriptase inhibitors, previous protease inhibitor therapy, and duration of previous protease inhibitor therapy were predictors of poorer response (P<0.01). Multivariate regression models revealed that protease mutations present at the initiation of saquinavir-ritonavir therapy were the strongest predictors of virologic response. A model of clinical features explained up to 45% of the variation in virologic outcomes by week 12, whereas the explained variance was 71% when genotypic predictors were included.In patients in whom protease inhibitor-containing antiretroviral therapy fails, HIV-1 genotype is predictive of virologic response to subsequent therapy. This predictive capacity adds to that of standard clinical evaluation.

    View details for Web of Science ID 000084053200002

    View details for PubMedID 10610625

  • Invasive fungal sinusitis due to Scedosporium apiospermum in a patient with AIDS CLINICAL INFECTIOUS DISEASES Eckburg, P. B., Zolopa, A. R., Montoya, J. G. 1999; 29 (1): 212-213

    View details for Web of Science ID 000081685300042

    View details for PubMedID 10433595

  • Risk of tuberculosis in tuberculin skin test-positive liver transplant patients CLINICAL INFECTIOUS DISEASES Chaparro, S. V., Montoya, J. G., Keeffe, E. B., Rhee, J. T., Small, P. M. 1999; 29 (1): 207-208

    View details for Web of Science ID 000081685300037

    View details for PubMedID 10433590

  • 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

  • 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

  • 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

  • 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

  • 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

  • PERIPHERAL-BLOOD MONONUCLEAR CELL HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 PROVIRAL DNA QUANTIFICATION BY POLYMERASE CHAIN-REACTION - RELATIONSHIP TO IMMUNODEFICIENCY AND DRUG EFFECT JOURNAL OF CLINICAL MICROBIOLOGY Montoya, J. G., Wood, R., KATZENSTEIN, D., HOLODNY, M., Merigan, T. C. 1993; 31 (10): 2692-2696

    Abstract

    Human immunodeficiency virus type 1 (HIV-1) proviral DNA from peripheral blood mononuclear cells (PBMCs) was quantitated in 61 HIV-1-seropositive individuals by a nonisotopic polymerase chain reaction assay. Primers from the gag region (SK38, SK39) were used to determine the log10 HIV-1 proviral copy number per 10(6) CD4+ T lymphocytes (peripheral blood proviral load). A standard curve was generated for each assay by using ACH-2 cell DNA. The peripheral blood proviral load was followed in 15 individuals in a longitudinal study and was measured in 45 individuals in a cross-sectional analysis. Three of four untreated patients who were followed for 14 months had stable PBMC proviral loads and CD4+ T lymphocyte counts; one untreated patient had a sustained increase in PBMC proviral load followed 5 months later by a significant decline in the CD4+ T lymphocyte count. Eleven previously untreated individuals were monitored for 1 year following initiation of zidovudine and/or 2',3'-dideoxyinosine therapy. The mean log10 number of proviral HIV-1 copies per 10(6) CD4+ T cells decreased from 4.3 +/- 0.4 at the baseline to 3.5 +/- 0.6 after 2 to 4 months of therapy (P < 0.01). This initial 0.8 log10 fall in the PBMC proviral load after the initiation of therapy was followed by a rise in the PBMC proviral load by the sixth month of therapy. The PBMC proviral load in 45 subjects, both treated (n = 25) and untreated (n = 20), correlated inversely with the CD4+ T lymphocyte count (P < 0.01, R = 0.49). PBMC proviral DNA quantification by a nonisotopic polymerase chain reaction assay correlates with HIV-1 disease progression and could be used to monitor the effect of antiretroviral therapy.

    View details for Web of Science ID A1993LY05900024

    View details for PubMedID 7902845

  • MEASUREMENT OF HIV VIRUS LOAD AND GENOTYPIC RESISTANCE BY GENE AMPLIFICATION IN ASYMPTOMATIC SUBJECTS TREATED WITH COMBINATION THERAPY JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES Holodniy, M., KATZENSTEIN, D., Winters, M., Montoya, J., Shafer, R., Kozal, M., Ragni, M., Merigan, T. C. 1993; 6 (4): 366-369

    Abstract

    Quantification of viral load in HIV disease has become increasingly important as a marker of antiviral efficacy. We applied gene amplification techniques in vivo to asses antiretroviral activity of combination therapy. Five HIV-infected subjects, four of whom were drug naive, were administered combination therapy with zidovudine (ZDV) and didanosine (ddI). Plasma and peripheral blood mononuclear cells (PBMC) were obtained twice at baseline and then at 1, 3, 6, 9, and 12 months after the initiation of therapy. Results show that plasma HIV RNA copy number fell from 2,170 +/- 660/ml to undetectable at 1 month, with continued suppression at 12 months. HIV proviral DNA copy number decreased from 3.9 to 3.0 log10/10(6) CD4+ T cells at 12 months. Cell dilution cultures were positive in 4 of 5 subjects at baseline and in only 1 of 5 after 12 months. CD4+ T-cell count increased from 390 +/- 30/mm3 pretherapy, to 505 +/- 66/mm3 after 6 months of therapy, but returned to baseline levels after 12 months of therapy. No mutations were detected from PBMC DNA for codon 215 and 74 in the HIV pol gene from the drug-naive subjects. These findings suggest that gene amplification techniques can be used to study changes in viral load or genotype and can be applied in real time to samples from patients involved in clinical trials.

    View details for Web of Science ID A1993KU22100007

    View details for PubMedID 8095981

  • SAFETY AND EFFICACY OF POLYETHYLENE-GLYCOL MODIFIED INTERLEUKIN-2 AND ZIDOVUDINE IN HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION - A PHASE I-II STUDY JOURNAL OF INFECTIOUS DISEASES Wood, R., Montoya, J. G., Kundu, S. K., Schwartz, D. H., Merigan, T. C. 1993; 167 (3): 519-525

    Abstract

    The safety and efficacy of combined therapy with polyethylene glycolated (PEG) interleukin (IL)-2 and zidovudine was assessed in 19 human immunodeficiency virus type 1 (HIV-1)-seropositive subjects in a phase I/II open-label dose-ranging study. During courses of three weekly infusions of PEG IL-2, dose-limiting side effects were seen at 5 x 10(6) IU/m2 and reversible encephalopathy in 1 subject at 3 x 10(6) IU/m2. Significant increases were seen in CD4 cell counts (P < .01), NK cell activity (P < .05), and HIV-specific cytotoxicity (P < .01). Virologic monitoring (quantitative DNA polymerase chain reaction and p24 antigen assay) showed no evidence of increased HIV activation. Patients with CD4 cells < 200/mm3 were entered into a chronic dosing phase. PEG IL-2 was given at 14-day intervals at doses of 10(6) IU/m2 for 8 weeks and 3 x 10(6) IU/m2 for up to 16 weeks, resulting in mean CD4 cell count elevations of 16% and 33%, respectively. PEG IL-2 appears to warrant further investigation, especially in subjects with CD4 cell counts < 200/mm3, to determine whether increased lymphocyte numbers will translate into improved clinical outcome.

    View details for Web of Science ID A1993KN15200001

    View details for PubMedID 8095058

  • [Community practice in units of primary care at the rural level: an experience with medical students]. Educación médica y salud de Bedoya, Y. A., Casas, L. A., Grill, H., Hoyos, J., Jiménez, F., Montoya, J. G., Torres, C. H. 1984; 18 (2): 164-181

    Abstract

    During the three weeks of vacation from the sixth semester of medical school in May 1982, a group of six students and a professor in the Department of Social Medicine of Valle University, Colombia, conducted a voluntary experimental exercise in some of the rural primary care units of Tuluá Regional Hospital in Valle del Cauca department, using the hospital's Administration as their operational center. The purpose of the exercise, called "Ruralito," was to compile a health census of the general characteristics of the rural communities constituting the primary health care service area. The teaching process employed was designed to encourage the students to act on their own initiative and in their own way and to exchange experiences and plan measures even after completion of the three years of the exercise. The article describes the salient features of the relationship between teaching practice and public health practice in this first exercise, in which a new instructional framework was introduced for the area of medicine; the students' highly favorable reaction to this exercise and the substantial gains made justify the expectation that it will serve as an example for future student exercises in similar processes.

    View details for PubMedID 6745159

Conference Proceedings


  • Clinical risk factors for development of nonlymphoma cancer post-heart and heart-lung transplantation: Analysis of 30-year follow-up in 1,026 patients Gao, S. Z., Perlroth, M. G., Montoya, J. G., Miller, J. L., DiMiceli, S., Brown, B., Oyer, P. E., Schroeder, J. S. ELSEVIER SCIENCE INC. 2002: 146A-146A
  • Hemolytic uremic syndrome after E. coli O157 : H7 infection in a patient with HIV infection: Clinical implications Cortes, J. A., Parsonnet, J., Chaparro, S. V., Montoya, J. G. OXFORD UNIV PRESS INC. 2001: 1113-1113
  • Brain abscess due to Listeria monocytogenes - Five cases and a review of the literature Eckburg, P. B., Montoya, J. G., Vosti, K. L. LIPPINCOTT WILLIAMS & WILKINS. 2001: 223-235

    View details for Web of Science ID 000170114800001

    View details for PubMedID 11470983

  • Brain abscess due to Listeria monocytogenes in cardiac transplant recipients Eckburg, P. B., Montoya, J. G., Vosti, K. L. OXFORD UNIV PRESS INC. 2000: 254-254
  • Clinical resistance patterns and responses to two sequential protease inhibitor regimens in saquinavir and reverse transcriptase inhibitor-experienced persons Lawrence, J., Schapiro, J., Winters, M., Montoya, J., Zolopa, A., Pesano, R., Efron, B., Winslow, D., Merigan, T. C. UNIV CHICAGO PRESS. 1999: 1356-1364

    Abstract

    The efficacy of sequential protease inhibitor therapy was studied in 16 human immunodeficiency virus (HIV) 1-infected persons in whom saquinavir with multiple nucleoside reverse transcriptase (RT) inhibitors (NRTI) had failed. Nelfinavir plus two NRTIs (new or continued) resulted in minimal (0.59 log RNA copies/mL) and transient (8 weeks) suppression of plasma HIV RNA levels. Rapid failure was surprisingly associated with baseline presence of protease gene mutation L90M (P=.04) in the absence of D30N and with RT mutations D67N (P<.01), K70R/S (P=.02), and K219Q/W/R/E (P<.01). Ten patients were subsequently switched to indinavir plus nevirapine and 2 NRTIs, resulting in a median 1.62 log reduction in plasma HIV RNA, with 3 patients maintaining 400 copies/mL for 24 weeks. These results suggest that nelfinavir may have limited utility after saquinavir failure, particularly without potent concomitant therapy. Combining an NRTI with a new protease inhibitor for rescue may improve response.

    View details for Web of Science ID 000080561100007

    View details for PubMedID 10228055

  • Association between non-bacterial infections and cardiac allograft atherosclerosis Giannetti, N., Montoya, J., Behr, M., Remmington, J., Valantine, H. A., Hunt, S. A. LIPPINCOTT WILLIAMS & WILKINS. 1998: 692-692
  • SERODIAGNOSIS OF TOXOPLASMIC LYMPHADENOPATHY (TL) Montoya, J. G., Remington, J. S. SLACK INC. 1994: A285-A285

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