Bio

Clinical Focus


  • Infectious Diseases, Pediatric
  • Pediatric Infectious Diseases

Administrative Appointments


  • Fellowship Program Director, Pediatric Infectious Diseases (2006 - 2017)
  • Co-director, Pediatric Infectious Diseases Program for Immunocompromised Hosts, Children's Hospital at Stanford (2013 - Present)
  • Associate Fellowship Director, Pediatric Infectious Diseases, Stanford University Medical Center (2017 - Present)
  • Director, Fellowship Education, Department of Pediatrics, Stanford University Medical Center (2017 - Present)

Honors & Awards


  • Faculty Fellows Leader Program, Stanford University Medical Center (2011)
  • Certificate of Achievement, Stanford clinical Effectiveness Leadership Training, Stanford University School of Medicine (2017)
  • Fuji Apple Award in Recognition of Contribution to Fellowship Education and Mentorship, Department of Pediatrics, Stanford University Medical Center (2018)

Professional Education


  • Medical Education:State University of New York Syracuse Medical School Registrar (1991) NY
  • Board Certification: Pediatric Infectious Diseases, American Board of Pediatrics (1999)
  • Fellowship:Stanford University School of Medicine Registrar (1998) CA
  • Residency:Stanford University Medical Center (1994) CA
  • Internship:Stanford University Medical Center (1992) CA
  • M.D., SUNY at Syracuse, Medicine (1991)

Research & Scholarship

Current Research and Scholarly Interests


The focus of my laboratory is defining the immune response to viral vaccines evaluating the ontogeny of responses in infants and limitations in immunocompromised hosts. We have studied the memory effector T cells response in infants given an early two-dose measles vaccine regimen, measuring CD4+, CD4+CD45RO+ and CD4+CD45RO+CCR7-T cells that produce IFN;. We have also analyzed key markers of activation, using cell surface markers CD69 and CD40-ligand. In addition, we have studied innate immunity and the interactions with the adaptive immune system. We have measured dendritic cell and monocyte populations and function in infants and children and the effects on measles-specific CD4+ T cell responses. These analyses have also been applied to both term and preterm infants receiving polio vaccine, and children receiving varicella vaccination. Our findings have revealed relative limitations in both the innate and adaptive immune system of healthy infants and children as compared with adults. Currently, we are investigating mechanisms responsible for these restrictions. We are also examining the acquisition and persistence of viral immunity in two immunocompromised states, HIV infection and transplantation. The goals of these studies are to define immune profiles in populations where obstacles to vaccination exist to offer insights for the development of novel vaccine strategies.
In my role as Co-director of the Pediatric Infectious Diseases Program for Immunocompromised Hosts I am involved with research related to these populations, including outcome studies, epidemiologic studies focusing on respiratory illness in solid organ transplant, fever and neutropenia in Oncology, and risk factors for Post-transplant Lymphoproliferative Disease and cytomegalovirus disease in transplant recipients. In addition, we are studying the efficacy of vaccines and prophylactic measures, such as synagis, in these populations.

Clinical Trials


  • CMV T Cell Immunity in Pediatric Solid Organ Transplant Recipients Recruiting

    CMV infection and disease remain a significant clinical challenge for pediatric solid organ transplant (SOT) recipients. Current prevention strategies are limited to prophylaxis in which antiviral medication is administered for a period of several months or preemption in which close monitoring of CMV viral load from the peripheral blood is performed and treatment is initiated when CMV is detected. Each of these strategies has risks, costs, and limitations associated with it. Recently, assays for measurement of an individual patient's CMV immunity have been developed and are clinically available. One of these is the Viracor CMV T cell Immunity Panel. This flow cytometry based assay is performed on peripheral blood and measures cytokine release in response to CMV antigen stimulation by flow cytometry. The thresholds for this assay that confer protection against CMV infection in pediatric SOT recipients are not known. Defining CMV-specific cell mediated immune response thresholds that confer protection against CMV reactivation could inform patient specific durations of antiviral prophylaxis or pre-emptive surveillance testing. Therefore, the objective of this study is to quantify CMVresponsive T lymphocyte populations by flow cytometry (Viracor CMV T cell Immunity Panel) in pediatric heart, kidney, and liver transplant recipients within the first year of transplantation and to investigate potential threshold values that correlate with protection against CMV infection (DNAemia).

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  • Ontogeny of Measles Immunity in Infants Recruiting

    This is an immunogenicity study evaluating the development of the immune response of healthy infants following primary vaccination with Attenuvax at 6 or 9 months of age compared with responses in 12 month-old infants receiving MMR-II. Responses of infants receiving an early two dose measles vaccine regimen with the first dose given at 6 or 9 months followed by a second dose administered at 12 months will also be compared to infants given a single dose at 12 months of age (Table 2). The current approved regimen for measles vaccination is a first vaccination at 12-15 months and a subsequent vaccination at school entry. A secondary endpoint of this study will be to assess the safety of measles vaccine administered as Attenuvax at 6 or 9 months of age and in an early two dose measles vaccine regimen with Attenuvax administered at 6 or 9 months followed by MMR-II at 12 months of age.

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Teaching

2019-20 Courses


Graduate and Fellowship Programs


Publications

All Publications


  • Pneumocystis jiroveci in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice CLINICAL TRANSPLANTATION Fishman, J. A., Gans, H., AST Infect Dis Community Practice 2019

    View details for DOI 10.1111/ctr.13587

    View details for Web of Science ID 000474020400001

  • Risk Factors of Ambulatory Central Line-Associated Bloodstream Infection in Pediatric Short Bowel Syndrome. JPEN. Journal of parenteral and enteral nutrition Seddik, T. B., Tian, L., Nespor, C., Kerner, J., Maldonado, Y., Gans, H. 2019

    Abstract

    BACKGROUND: Children with short bowel syndrome (SBS) receiving home parenteral nutrition (HPN) are predisposed to ambulatory central line-associated bloodstream infection (A-CLABSI). Data describing risk factors of this infection in children are limited.METHODS: Retrospective cohort, single-center, case-crossover study of children ≤18 years old with SBS receiving HPN from January 2012 to December 2016. Univariate and multivariate mixed effect Poisson regression identified the relative risk (RR) of A-CLABSI with proposed risk factors.RESULTS: Thirty-five children were identified; median follow-up was 30 months. A-CLABSI rate was 4.2 per 1000 central line (CL) days. Univariate analysis identified younger age (RR: 0.92 per 12-month increase [95% confidence interval {CI}: 0.85-0.99; P = 0.036]), shorter small intestine length (RR: 0.96 per 10-cm increase [95% CI: 0.92-0.99; P = 0.008]), lower citrulline level (RR: 0.86 per 5-nmol/mL increase [95% CI: 0.75-0.99; P = 0.036]), and recent CL break (RR: 1.55 [95% CI: 1.06-2.28; P = 0.024]) as risk factors for A-CLABSI. Multivariate analysis showed increased A-CLABSI with clinical diagnosis of small intestine bacterial overgrowth (SIBO) (RR: 1.87 [95% CI: 1.1-3.17; P = 0.021]) and CL breaks (RR: 1.49 [95% CI: 1-2.22; P = 0.024]).CONCLUSIONS: Factors influencing gut integrity increase A-CLABSI rate, supporting translocation as an important mechanism and target for prevention. Clinical diagnosis of SIBO increases A-CLABSI rate, but whether dysbiosis or diarrhea is responsible is an area for future research. CL maintenance is crucial, and prevention of breaks would likely decrease A-CLABSI rate.

    View details for DOI 10.1002/jpen.1667

    View details for PubMedID 31179578

  • Adenovirus relationship to rejection: Two sides of the coin Mojica, C., Gans, H., Chen, S. F. WILEY. 2019
  • Pneumocystis jiroveci in Solid Organ Transplantation - Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clinical transplantation Fishman, J. A., Gans, H. 2019: e13587

    Abstract

    These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention and management of Pneumocystis jiroveci fungal infection transplant recipients. Pneumonia (PJP) may develop via airborne transmission or reactivation of prior infection. Nosocomial clusters of infection have been described among transplant recipients. PJP should not occur during prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX). Without prophylaxis, PJP risk is greatest in the first 6 months after organ transplantation but may develop later. Risk factors include low lymphocyte counts, cytomegalovirus infection (CMV), hypogammaglobulinemia, treated graft rejection or corticosteroids, and advancing patient age (> 65). Presentation typically includes fever, dyspnea with hypoxemia, and cough. Chest radiographic patterns generally reveal diffuse interstitial processes best seen by CT scans. Patients generally have PO2 <60 mmHg, elevated serum lactic dehydrogenase (LDH), and elevated serum (1→3) β-D-glucan assay. Specific diagnosis uses respiratory specimens with direct immunofluorescent staining; invasive procedures may be required. Quantitative PCR is a useful adjunct to diagnosis. TMP-SMX is the drug of choice for therapy; drug allergy should be documented before resorting to alternative therapies. Adjunctive corticosteroids may be useful early. Routine PJP prophylaxis is recommended for at least 6-12 months posttransplant, preferably with TMP-SMX. This article is protected by copyright. All rights reserved.

    View details for PubMedID 31077616

  • Preventing Measles among Immunosuppressed Cancer and Hematopoietic Cell Transplant Patients: A Position Statement by the American Society for Transplantation and Cellular Therapy. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation Pergam, S. A., Englund, J. A., Kamboj, M., Gans, H. A., Young, J. H., Hill, J. A., Savani, B., Chemaly, R. F., Dadwal, S. S., Storek, J., Duchin, J., Carpenter, P. A. 2019

    Abstract

    Until recently, measles exposures were relatively rare, and so consequently, were an afterthought for cancer and/or blood and marrow transplant recipients and their providers. Declines in measles herd immunity have reached critical levels in many communities throughout the US, due to increasing vaccine hesitancy, so that community-based outbreaks have occurred. The reemergence of measles as a clinical disease has raised serious concern among immunocompromised patients and those who work within the cancer and hematopoietic cell transplant (HCT) community. Since live attenuated vaccines such as measles mumps rubella (MMR) are contraindicated in immunocompromised patients and without approved antiviral therapies for measles, community exposures in these patients can lead to life-threatening infection. The lack of data regarding measles prevention in this population poses a number of clinical dilemmas. Herein, specialists in Infectious Diseases and HCT/cellular therapy endorsed by the American Society of Transplant and Cellular Therapy, address frequently asked questions about measles in these high-risk cancer and HCT patients, and provide their expert opinion based on the limited available data.

    View details for DOI 10.1016/j.bbmt.2019.07.034

    View details for PubMedID 31394271

  • Parental Risk Factors for Fever in their Children 7-10 Days After the First Dose of Measles-Containing Vaccines. Human vaccines & immunotherapeutics Zerbo, O., Modaressi, S., Goddard, K., Lewis, E., Bok, K., Gans, H., Klein, N. P. 2019

    Abstract

    We evaluated whether parental clinical conditions were associated with fever after a first dose of MCV in the child in a cohort study including 244125 children born in Kaiser Permanente Northern California between 2009 - 2016 who received MCV between ages 1 - 2 years. Each child was linked with his/her mother and father when possible. Parental clinical conditions present before and after their child's birth were identified. We defined fever in the children as clinic and emergency department visits with a fever code 7-10 days after a first dose of MCV ("MCV- associated fever"). We evaluated parental clinical conditions associated with MCV-associated fever using multivariate logistic regression analyses. After adjusting for multiple factors, including healthcare utilization, maternal fever (OR = 1.19, 95% CI 1.06 - 1.32), fever after MCV (OR = 5.90, 95% CI 1.35 - 25.78), respiratory infections (OR = 1.20, 95% CI 1.10 - 1.31), migraine (OR = 1.14, 95% CI 1.05 - 1.24), syncope (OR 1.14, 95% CI 1.01 - 1.27), and essential thrombocythemia (OR = 1.93, 95% CI 1.15 - 3.25) were significantly associated with MCV- associated fever. Paternal respiratory infections (OR = 1.15, 95% CI 1.05 - 1.27), fever associated with respiratory infections (OR = 1.47, 95% CI 1.23 - 1.76) and vitiligo (OR = 1.63, 95% CI 1.06 - 2.53) were significantly associated with MCV- associated fever. Parental clinical conditions, specifically fever alone and fever associated with respiratory infection, are associated with fever in their child 7-10 days after MCV.

    View details for DOI 10.1080/21645515.2019.1675458

    View details for PubMedID 31584845

  • Measles Maternal Antibodies With Low Avidity Do Not Interfere With the Establishment of Robust Quantity and Quality Antibody Responses After the Primary Dose of Measles, Mumps, and Rubella Vaccine Administered at 12-Months of Age. Journal of the Pediatric Infectious Diseases Society Collins, C. A., Gelinas, L., Yasukawa, L. L., Audet, S., Abu-Raya, B., Turvey, S. E., Beeler, J. A., Kollmann, T. R., Gans, H. A. 2019

    Abstract

    In this study, we illustrate, for the first time, that preexisting low-avidity neutralizing measles maternal antibodies do not interfere with the development of high concentrations of high-avidity measles antibodies in children immunized at age 12 months. This suggests that the quality of measles maternal antibodies, rather than the quantity, impacts immunogenicity of primary measles immunization.

    View details for DOI 10.1093/jpids/piz074

    View details for PubMedID 31644795

  • Response to editor regarding "Improvement of psychiatric symptoms in youth following resolution of sinusitis". International journal of pediatric otorhinolaryngology Frankovich, J., Sidell, D., Gans, H., Brown, K., Mahony, T., Thienemann, M. 2018; 112: 208–9

    View details for PubMedID 29050812

  • Central line replacement following infection does not improve reinfection rates in pediatric pulmonary hypertension patients receiving intravenous prostanoid therapy PULMONARY CIRCULATION McCarthy, E. K., Ogawa, M. T., Hopper, R. K., Feinstein, J. A., Gans, H. A. 2018; 8 (1): 2045893218754886

    Abstract

    Treatment of pediatric pulmonary hypertension (PH) with IV prostanoids has greatly improved outcomes but requires a central line, posing inherent infection risk. This study examines the types of infections, infection rates, and importantly the effect of line management strategies on reinfection in children receiving IV prostanoids for PH. This study is a retrospective review of all pediatric PH patients receiving intravenous epoprostenol (EPO) or treprostinil (TRE) at one academic tertiary care center between 2000 and 2014. No patients declined participation in the study or were otherwise excluded. Infectious complications were characterized by organism(s), infection rates, time to next infection, and line management decisions (salvage vs. replace). Of the 40 patients followed, 13 sustained 38 infections involving 49 pathogens, with a predominance of gram-positive (GP) organisms (n = 35). The pooled infection rate was 1.06 per 1000 prostanoid days with no difference between EPO and TRE. No significant difference in reinfection rate was observed when comparing line salvage to replacement, regardless of organism type. Both overall and organism-type comparisons suggest longer time between line infections following line salvage compared with line replacement (732 vs. 410 days overall; 793 vs. 363 days for GP; 611 vs. 581 days for gram-negative [GN]; P > 0.05 for all comparisons). Central line replacement following blood stream infections in pediatric PH patients does not improve subsequent infection rates or time to next infection, and may lead to unnecessary risks associated with line replacement, including potential loss of vascular access. A revised approach to central line infections in pediatric PH is proposed.

    View details for PubMedID 29309237

    View details for PubMedCentralID PMC5826011

  • Palatal Petechiae in the Absence of Group A Streptococcus in Pediatric Patients with Acute-Onset Neuropsychiatric Deterioration: A Cohort Study. Journal of child and adolescent psychopharmacology Mahony, T., Sidell, D., Gans, H., Cooperstock, M., Brown, K., Cheung, J. M., Farhadian, B., Gustafson, M., Thienemann, M., Frankovich, J. 2017

    Abstract

    Palatal petechiae are 95% specific for streptococcal pharyngitis. Despite this, and despite prior research demonstrating that Group A Streptococcus (GAS) is a common antecedent to pediatric acute-onset neuropsychiatric syndrome (PANS) episodes, we anecdotally observed a low rate of documented GAS in patients with PANS and palatal petechiae. This retrospective chart review was conducted to formally report the rate of palatal petechiae and concurrent GAS in a cohort of patients with PANS and investigate other etiologic factors.The clinical notes of 112 patients seen at the Stanford PANS Clinic who met PANS research criteria were reviewed for mention of palatal petechiae. The medical records of patients who demonstrated palatal petechiae on physical examination were reviewed for signs of infection, a clinical history of trauma, and laboratory results that could indicate other causes of petechiae.Twenty-three patients had documented palatal petechiae on physical examination (ages 5-16, 13/23 [57%] male). Fifteen patients had a rapid GAS test and GAS culture in the Stanford PANS clinic, all with negative results. Evidence of recent GAS infection was found in 8/23 (32%) patients (elevated GAS titers [n = 6] or documentation of a positive rapid GAS test at another facility [n = 2]), one of whom also had potential herpes simplex virus (HSV) infection. One patient had potential HSV infection and recent palatal trauma. No patients had thrombocytopenia. 14/23 (61%) of patients with palatal petechiae had no discernable cause of petechiae. 10/19 (53%) of patients had antihistone antibodies.Despite the established relationship between palatal petechiae and GAS, no patient with palatal petechiae in our clinic tested positive for GAS and only 32% had evidence of recent GAS. Most did not have an identifiable cause for the palatal lesions. This finding suggests the potential for alternative causes of palatal petechiae or undetectable GAS in our patient population. The high prevalence of palatal petechiae without GAS infection suggests that the pathogenesis of PANS is multifactorial and may involve disruption or inflammation of the microvasculature. Additional research is needed to further elucidate these findings.

    View details for DOI 10.1089/cap.2016.0153

    View details for PubMedID 28387528

  • Improvement of psychiatric symptoms in youth following resolution of sinusitis INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY Mahony, T., Sidell, D., Gans, H., Brown, K., Farhadian, B., Gustafson, M., Sherr, J., Thienemann, M., Frankovich, J. 2017; 92: 38-44

    Abstract

    Accumulating evidence supports a role for inflammation in psychiatric illness, and the onset or exacerbation of psychiatric symptoms may follow non-CNS infections. Here, we provide the first detailed description of obsessive-compulsive and related psychiatric symptoms arising concurrently with sinusitis.We reviewed the charts of 150 consecutive patients evaluated in our Pediatric Acute-onset Neuropsychiatric Syndromes clinic for documented sinusitis as defined by the American Academy of Pediatrics guidelines. Sinusitis treatments, sinonasal imaging, and neuropsychiatric symptoms before, during, and after sinusitis onset were noted. Patients were included in the final review if they had a clear diagnosis of isolated sinusitis (without concurrent illness and/or immunodeficiency), and were evaluated during an episode of sinusitis.10/150 (6.6%) patients had isolated sinusitis at the time of their neuropsychiatric deterioration. Eight patients received antibiotics to treat sinusitis, three of whom also received sinus surgery. Neuropsychiatric symptoms improved in all eight patients concurrent with resolution of sinusitis per parent report and clinician assessment. One patient did not follow through with recommended sinus surgery or antibiotics and her psychiatric symptoms persisted. One patient was lost to follow-up.Improvement of psychiatric symptoms correlated with resolution of sinus disease in this retrospective study. Identification, treatment, and resolution of underlying infections, including sinusitis, may have the potential to change the trajectory of some neuropsychiatric illnesses. Randomized clinical trials are needed.

    View details for DOI 10.1016/j.ijporl.2016.10.034

    View details for Web of Science ID 000393245100008

    View details for PubMedID 28012531

  • Fever and Renal Failure in a Child With DiGeorge Syndrome and Tetralogy of Fallot. Journal of the Pediatric Infectious Diseases Society Itoh, M., Kann, D. C., Schwenk, H. T., Gans, H. A. 2015; 4 (4): 373-375

    View details for DOI 10.1093/jpids/piv029

    View details for PubMedID 26407263

  • Pleural Effusion and Fever in an Immunocompromised Patient. Journal of the Pediatric Infectious Diseases Society Kay, A. W., Itoh, M., Valdez, J., Chen, S. F., Mathew, R., Gans, H. A. 2015; 4 (1): e6-9

    View details for DOI 10.1093/jpids/piu018

    View details for PubMedID 26407371

  • Loss of passively acquired maternal antibodies in highly vaccinated populations: an emerging need to define the ontogeny of infant immune responses. journal of infectious diseases Gans, H. A., Maldonado, Y. A. 2013; 208 (1): 1-3

    View details for DOI 10.1093/infdis/jit144

    View details for PubMedID 23661801

  • The status of live viral vaccination in early life. Vaccine Gans, H. A. 2013; 31 (21): 2531-2537

    Abstract

    The need for neonatal vaccines is supported by the high disease burden during the first year of life particularly in the first month. Two-thirds of childhood deaths are attributable to infectious diseases of which viruses represent key pathogens. Many infectious diseases have the highest incidence, severity and mortality in the first months of life, and therefore early life vaccination would provide significant protection and life savings. For some childhood viral diseases successful vaccines exist, such as against measles, mumps, rubella, varicella, influenza poliovirus, and rotavirus, but their use in the first year particularly at birth is not yet practiced. Vaccines against other key pathogens continue to elude scientists such as against respiratory syncytial virus. The obstacles for early and neonatal vaccination are complex and include host factors, such as a developing immune system and the interference of passively acquired antibodies, as well vaccine-specific issues, such as optimal route of administration, titer and dosing requirements. Importantly, additional host and infrastructure barriers also present obstacles to neonatal vaccination in the developing world where morbidity and mortality rates are highest. This review will highlight the current live viral vaccines and their use in the first year of life, focusing on efficacy and entertaining the barriers that exist. It is important to understand the successes of current vaccines and use this knowledge to determine strategies that are successful in young infants and for the development of new vaccines for use in early life.

    View details for DOI 10.1016/j.vaccine.2012.09.043

    View details for PubMedID 23026688

  • Measles humoral and cell-mediated immunity in children aged 5-10 years after primary measles immunization administered at 6 or 9 months of age. journal of infectious diseases Gans, H. A., Yasukawa, L. L., Sung, P., Sullivan, B., Dehovitz, R., Audet, S., Beeler, J., Arvin, A. M. 2013; 207 (4): 574-582

    Abstract

    Given the high infant measles mortality rate, there is interest in whether a measles immunization regimen beginning at <12 months of age provides lasting immunity.Measles-specific immune responses were evaluated in 70 children aged 5-10 years after primary measles vaccine administered at 6, 9, or 12 months.At 5-10 years of age, the stimulation index for measles T-cell proliferation was 11.4 (SE, 1.3), 10.9 (SE, 1.5), and 14.4 (SE 2.1) when the first measles dose was given at 6, 9, or 12 months, respectively. Neutralizing antibody concentration (geometric mean titer [GMT]) in those immunized at 6 months of age was 125 mIU/mL (95% confidence interval [CI], 42-377) in the presence of passive antibodies (PAs) and 335 mIU/mL (95% CI, 211-531) in those without PAs; in those immunized at 9 months, GMTs were 186 mIU/mL (95% CI, 103-335) and 1080 mIU/mL (95% CI, 642-1827) in the presence and absence of PAs, respectively. The GMT was 707 mIU/mL (95% CI, 456-1095) when vaccine was administered at 12 months (P ≤ .04).Measles-specific T-cell responses were sustained at 5-10 years of age regardless of age at time of primary measles immunization. Neutralizing antibody concentrations were lower in cohorts given the first vaccine dose at 6 months of age and in the presence of PAs; however, responses could be boosted by subsequent doses. Starting measles vaccination at <12 months of age may be beneficial during measles outbreaks or in endemic areas.

    View details for DOI 10.1093/infdis/jis719

    View details for PubMedID 23300162

    View details for PubMedCentralID PMC3549597

  • Innate Immune Dysfunction is Associated with Enhanced Disease Severity In Infants with Severe Respiratory Syncytial Virus Bronchiolitis JOURNAL OF INFECTIOUS DISEASES Gans, H. A., Yasukawa, L. L., Sung, P., Sullivan, B., Dehovitz, R., Audet, S., Beeler, J., Arvin, A. M. 2013; 207 (4): 574-582

    Abstract

    Given the high infant measles mortality rate, there is interest in whether a measles immunization regimen beginning at <12 months of age provides lasting immunity.Measles-specific immune responses were evaluated in 70 children aged 5-10 years after primary measles vaccine administered at 6, 9, or 12 months.At 5-10 years of age, the stimulation index for measles T-cell proliferation was 11.4 (SE, 1.3), 10.9 (SE, 1.5), and 14.4 (SE 2.1) when the first measles dose was given at 6, 9, or 12 months, respectively. Neutralizing antibody concentration (geometric mean titer [GMT]) in those immunized at 6 months of age was 125 mIU/mL (95% confidence interval [CI], 42-377) in the presence of passive antibodies (PAs) and 335 mIU/mL (95% CI, 211-531) in those without PAs; in those immunized at 9 months, GMTs were 186 mIU/mL (95% CI, 103-335) and 1080 mIU/mL (95% CI, 642-1827) in the presence and absence of PAs, respectively. The GMT was 707 mIU/mL (95% CI, 456-1095) when vaccine was administered at 12 months (P ≤ .04).Measles-specific T-cell responses were sustained at 5-10 years of age regardless of age at time of primary measles immunization. Neutralizing antibody concentrations were lower in cohorts given the first vaccine dose at 6 months of age and in the presence of PAs; however, responses could be boosted by subsequent doses. Starting measles vaccination at <12 months of age may be beneficial during measles outbreaks or in endemic areas.

    View details for DOI 10.1093/infdis/jis719

    View details for Web of Science ID 000314121800005

    View details for PubMedCentralID PMC3549597

  • IMP-Producing Carbapenem-Resistant Klebsiella pneumoniae in the United States JOURNAL OF CLINICAL MICROBIOLOGY Limbago, B. M., Rasheed, J. K., Anderson, K. F., Zhu, W., Kitchel, B., Watz, N., Munro, S., Gans, H., Banaei, N., Kallen, A. J. 2011; 49 (12): 4239-4245

    Abstract

    The emergence and spread of carbapenem-resistant Enterobacteriaceae (CRE) producing acquired carbapenemases have created a global public health crisis. In the United States, CRE producing the Klebsiella pneumoniae carbapenemase (KPC) are increasingly common and are endemic in some regions. Metallo-β-lactamase (MBL)-producing CRE have recently been reported in the United States among patients who received medical care in countries where such organisms are common. Here, we describe three carbapenem-resistant K. pneumoniae isolates recovered from pediatric patients at a single U.S. health care facility, none of whom had a history of international travel. The isolates were resistant to carbapenems but susceptible to aztreonam, trimethoprim-sulfamethoxazole, and fluoroquinolones. The three isolates were closely related to each other by pulsed-field gel electrophoresis and contained a common plasmid. PCR and sequence analysis confirmed that these isolates produce IMP-4, an MBL carbapenemase not previously published as present among Enterobacteriaceae in the United States.

    View details for DOI 10.1128/JCM.05297-11

    View details for Web of Science ID 000298113400036

    View details for PubMedID 21998425

  • Challenges in infant immunity: implications for responses to infection and vaccines NATURE IMMUNOLOGY PrabhuDas, M., Adkins, B., Gans, H., King, C., Levy, O., Ramilo, O., Siegrist, C. 2011; 12 (3): 189-194

    View details for DOI 10.1038/ni0311-189

    View details for Web of Science ID 000287354400002

    View details for PubMedID 21321588

  • Preterm Infants' T Cell Responses to Inactivated Poliovirus Vaccine JOURNAL OF INFECTIOUS DISEASES Klein, N. P., Gans, H. A., Sung, P., Yasukawa, L. L., Johnson, J., Sarafanov, A., Chumakov, K., Hansen, J., Black, S., Dekker, C. L. 2010; 201 (2): 214-222

    Abstract

    The antigen-specific T cell responses of preterm infants to immunization are not well understood. The aim of the present study was to compare the T cell responses of preterm infants after inactivated poliovirus vaccination with those of term infants.We prospectively enrolled 2-month-old preterm (gestational age, 33 weeks) and term (gestational age, 37 weeks) infants to receive 3 doses of diphtheria-tetanus toxoids-acellular pertussis-hepatitis B virus-inactivated poliovirus vaccine. Whole blood and peripheral blood mononuclear cells (PBMCs) were stimulated with poliovirus vaccine, and memory T cell activation was analyzed by flow cytometry and lymphoproliferation, respectively. Levels of poliovirus neutralizing antibodies were measured in serum.We enrolled 33 preterm and 50 term infants. Preterm infants had fewer circulating CD4(+)CD45RO(+) memory (P = .005) and CD4(+)CD69(+)IFN-gamma(+) cells activated by staphylococcus enterotoxin B at 2 (P = .015) and 7 (P = .05) months of age. After immunization, preterm and term infants had comparable frequencies of poliovirus-specific CD4(+)CD45RO(+)CD69(+)IFN-gamma(+) memory T cells (P = .79). PBMCs from preterm infants had diminished poliovirus-specific lymphoproliferation (P<.001). Although all infants developed seroprotective poliovirus antibody titers, serotype 1 titers were lower among preterm infants (P = .03).Preterm infants develop poliovirus-specific T cell responses that are comparable to those of term infants. However, they demonstrate nonspecific and poliovirus-specific functional T cell limitations, suggesting that investigations into whether T cell differences remain as preterm infants mature are warranted.

    View details for DOI 10.1086/649590

    View details for Web of Science ID 000273051200008

    View details for PubMedID 20017631

  • Age-Related Increase in the Frequency of CD4(+) T Cells That Produce Interferon-gamma in Response to Staphylococcal Enterotoxin B during Childhood JOURNAL OF INFECTIOUS DISEASES Hanna-Wakim, R., Yasukawa, L. L., Sung, P., Fang, M., Sullivan, B., Rinki, M., Dehovitz, R., Arvin, A. M., Gans, H. A. 2009; 200 (12): 1921-1927

    Abstract

    The susceptibility of infants to infections is well defined clinically, and immunologic abnormalities have been described. Immune maturation is complex, however, and the interval during which changes occur during childhood has not been identified.To assess age-related differences in the CD4(+) T cell responses, we evaluated the frequency of CD4(+) T cells that produced interferon (IFN) gamma in response to staphylococcal enterotoxin B (SEB) stimulation in 382 healthy infants and children (2 months to 11 years of age) and 66 adults. Flow cytometry was used to assess SEB-induced CD69 and CD40 ligand (CD40-L) expression and IFN-gamma production by CD4(+) and CD45RO(+)CD4(+) T cells.CD69 and CD40-L expression by CD4(+) and CD45RO(+)CD4(+) T cells were similar to adult levels from infancy, but the frequency of activated T cells that produced IFN-gamma remained lower than adult responses until children were 10 years of age.These observations indicate that the IFN-gamma response of CD4(+) T cells to SEB remains limited for a much longer interval than was reported elsewhere, extending to the second decade of life. Observed differences in CD45RO(+)CD4(+) T cell function indicate that CD4(+) T cells with the same phenotypes do not possess equivalent functional capabilities.

    View details for DOI 10.1086/648375

    View details for Web of Science ID 000271874000016

    View details for PubMedID 19909079

  • Immune responses to mumps vaccine in adults who were vaccinated in childhood Annual Meeting of the Pediatric-Academic-Societies/Society-of-Pediatric-Research Hanna-Wakim, R., Yasukawa, L. L., Sung, P., Arvin, A. M., Gans, H. A. UNIV CHICAGO PRESS. 2008: 1669–75

    Abstract

    In a mumps outbreak in the United States, many infected individuals were adults who had received 2 doses of mumps vaccine. The persistence of cellular immunity to mumps vaccine has not been defined.This was an observational, nonrandomized cohort study evaluating cell-mediated and humoral immunity to mumps in 10 vaccinated and 10 naturally immune adults. Mumps-specific T cell activation and interferon (IFN)-gamma production were measured using lymphoproliferative and flow cytometry assays, and mumps immunoglobulin (Ig) G was measured using enzyme-linked immunosorbent assay.T cell immunity to mumps was high in both groups; 70% of vaccinated and 80% of naturally immune individuals had a positive (> or =3) stimulation index (SI) (P = 1.0). The mean percentages of mumps-specific CD4+ T cells that expressed CD69 and produced IFN-gamma were equivalent in the 2 groups: 0.06% and 0.12%, respectively (P = .11). The mean SIs in the groups were also equivalent, although IFN-gamma concentrations from cultures stimulated with mumps antigen were higher in naturally immune adults than in vaccinated adults (P < or = .01). All adults were positive for mumps IgG.T and B cell immunity to mumps was detected in adults at least 10 years after immunization. Except for IFN-gamma release, responses in vaccinated adults paralleled those observed in naturally immune individuals.

    View details for DOI 10.1086/588195

    View details for Web of Science ID 000256315300006

    View details for PubMedID 18419345

    View details for PubMedCentralID PMC2561204

  • Effects of interleukin-12 and interleukin-15 on measles-specific T-cell responses in vaccinated infants VIRAL IMMUNOLOGY Gans, H. A., Yasukawa, L. L., Zhang, C. Z., Wakim, R. H., Rinki, M., Dehovitz, R., Arvin, A. M. 2008; 21 (2): 163-172

    Abstract

    Understanding the infant host response to measles vaccination is important because of their increased mortality from measles and the need to provide effective protection during the first year of life. Measles-specific T and B-cell responses are lower in infants after measles vaccination than in adults. To define potential mechanisms, we investigated age-related differences in measles-specific T-cell proliferation, CD40-L expression, and IFN-gamma production after measles immunization, and the effects of rhIL-12 and rhIL-15 on these responses. Measles-specific T-cell proliferation and mean IFN-gamma release from infant PBMCs were significantly lower when compared with responses of vaccinated children and adults. Infant responses increased to ranges observed in children and adults when both rhIL-12 and rhIL-15 were added to PBMC cultures. Furthermore, a significant rise in T-cell proliferation and IFN-gamma release was observed when infant PBMCs were stimulated with measles antigen in the presence of rhIL-12 and rhIL-15 compared to measles antigen alone. CD40-L expression by infant and adult T cells stimulated with measles antigen was comparable, but fewer infant CD40-L(+) T cells expressed IFN-gamma. These observations suggest that lower measles-specific T-cell immune responses elicited by measles vaccine in infants may be due to diminished levels of key cytokines.

    View details for DOI 10.1089/vim.2007.0113

    View details for Web of Science ID 000257494700008

    View details for PubMedID 18419254

    View details for PubMedCentralID PMC2599809

  • Primary vaccine failure after 1 dose of varicella vaccine in healthy children 44th Annual Meeting of the Infectious-Diseases-Society-of-America Michalik, D. E., Steinberg, S. P., LaRussa, P. S., Edwards, K. M., Wright, P. F., Arvin, A. M., Gans, H. A., Gershon, A. A. UNIV CHICAGO PRESS. 2008: 944–49

    Abstract

    Universal immunization of young children with 1 dose of varicella vaccine was recommended in the United States in 1995, and it has significantly decreased the incidence of chickenpox. Outbreaks of varicella, however, are reported among vaccinated children. Although vaccine effectiveness has usually been 85%, rates as low as 44% have been observed. Whether this is from primary or secondary vaccine failure-or both-is unclear. We tested serum samples from 148 healthy children immunized against varicella in New York, Tennessee, and California to determine their seroconversion rates, before and after 1 dose of Merck/Oka varicella vaccine. The median age at vaccination was 12.5 months; postvaccination serum samples were obtained on average 4 months later. Serum was tested for antibodies against varicella-zoster virus (VZV) by use of the previously validated sensitive and specific fluorescent antibody to membrane antigen (FAMA) assay. Of 148 healthy child vaccinees, 113 (76%) seroconverted, and 24% had no detectable VZV FAMA antibodies. Our data contrast with reported seroconversion rates of 86%-96% by other VZV antibody tests and suggest that many cases of varicella in immunized children are due to primary vaccine failure. A second dose of varicella vaccine is expected to increase seroconversion rates and vaccine effectiveness.

    View details for DOI 10.1086/529043

    View details for Web of Science ID 000254249500004

    View details for PubMedID 18419532

    View details for PubMedCentralID PMC2657090

  • EOSINOPHILIC MENINGOENCEPHALITIS: PSYCHIATRIC PRESENTATION AND TREATMENT INTERNATIONAL JOURNAL OF PSYCHIATRY IN MEDICINE Hong, D. S., Bernstein, M., Smith, C., Gans, H., Shaw, R. J. 2008; 38 (3): 287-295

    Abstract

    Eosinophilic meningoencephalitis (EM) is usually a self-limited neurological illness commonly accompanied by a variety of neurological symptoms. The presence of acute psychotic symptoms in EM, however, has not previously been reported, and there is no literature to guide its treatment and management. In this case report, the onset of psychotic symptoms in a hypoactive delirium and their significant improvement following the administration of atypical antipsychotics are described in a boy with EM. This case report demonstrates the efficacy and safety of antipsychotic agents during the acute phase of meningoencephalitis.

    View details for DOI 10.2190/PM.38.3.e

    View details for Web of Science ID 000261315400005

    View details for PubMedID 19069573

  • Age-dependent differences in IgG isotype and avidity induced by measles vaccine received during the first year of life JOURNAL OF INFECTIOUS DISEASES Nair, N., Gans, H., Lew-Yasukawa, L., Long-Wagar, A. C., Arvin, A., Griffin, D. E. 2007; 196 (9): 1339-1345

    Abstract

    Measles remains an important cause of death worldwide, and vaccinating individuals at an earlier age could lead to better control of the disease. However, persistence of maternal antibody and young age affect the quantity of vaccine-induced neutralizing antibody and may also affect antibody quality.Enzyme immunoassay was used to analyze measles virus-specific IgG levels, avidity maturation, and isotype changes, using serum samples from infants who received measles vaccine at 6 months of age and measles-mumps-rubella (MMR)-II at 12 months of age (n=26), measles vaccine at 9 months of age and measles-mumps-rubella (MMR)-II at 12 months of age (n=48), or only MMR-II at 12 months of age (n=27).The median IgG level was lower among infants with maternal antibody than among those without maternal antibody. Compared with median avidity indices for infants aged 12 months, median values were lower for 6-month-old infants with maternal antibody (P=.0001), 6-month-old infants without maternal antibody (P=.001), 9-month-old infants with maternal antibody (P=.03), and 9-month-old infants without maternal antibody (P=.006). The median IgG3 level was highest at 6 months of age. IgG1 was predominant at 12 months. Low avidity responses at 6 or 9 months of age did not hinder higher avidity responses or the switch to IgG1 after secondary vaccination. The 2-dose regimen did not augment the response, compared with the response in infants who received 1 dose at 12 months of age.Avidity and isotype maturation of measles vaccine-induced antibody are affected by age, providing insight into the ontogeny of the immune response to measles vaccine.

    View details for DOI 10.1086/522519

    View details for Web of Science ID 000250010800012

    View details for PubMedID 17922398

  • Immunogenicity of aerosol measles vaccine given as the primary measles immunization to nine-month-old Mexican children 42nd Annual Meeting of the Infectious-Diseases-Society-of-America Wong-Chew, R. M., Islas-Romero, R., Garcia-Garcia, M. D., Beeler, J. A., Audet, S., Santos-Preciado, J. I., Gans, H., Lew-Yasukawa, L., Maldonado, Y. A., Arvin, A. M., Valdespino-Gomez, J. L. ELSEVIER SCI LTD. 2006: 683–90

    Abstract

    Aerosol measles vaccination has been found to be more immunogenic than subcutaneous administration as a booster in school aged children, and immunogenic in 12-month-old children as a primary dose. The objective of the study was to evaluate immunogenicity to aerosol measles vaccine in 9-month-old children.Nine-months-old infants received Edmonston-Zagreb measles vaccine by aerosol (10(3.58) CCID50/0.1 mL, estimated retained dose 10(2.81) CCID50 or subcutaneous route (10(4.28) CCID50/0.5 mL); cellular and humoral immunity and adverse events were assessed.Measles-specific T cell proliferative responses developed in 42% of children given aerosolized vaccine compared with 67% of those who received subcutaneous vaccine (p = 0.01); the mean stimulation index (SI) was 4.4+/-0.7 versus 6.9+/-1, respectively, (p = 0.05). Seroconversion rates were 33 and 92% after aerosol or subcutaneous immunization (p < 0.001). Among infants who developed serologic responses, measles geometric mean titers (GMT; 95% CI) by neutralizing antibody assay were 215 mIU/mL (115-400) in aerosol vaccine recipients and 411 mIU/mL (345-490) in those given subcutaneous vaccine (p = 0.06).The proportion of 9-month-old infants who developed cellular and/or humoral immunity to measles was lower in the aerosol group but measles antibody and T cell responses were comparable among those who developed measles immunity. Differences in response rates are attributable to the lower aerosol dose. Improving aerosol delivery or increasing the dose may enhance immunogenicity of primary aerosol measles vaccination in this age group.

    View details for DOI 10.1016/j.vaccine.2005.08.045

    View details for Web of Science ID 000235273900017

    View details for PubMedID 16154241

  • T cell immunity to measles viral proteins in infants and adults after measles immunization VIRAL IMMUNOLOGY Gans, H. A., Yasukawa, L. L., Alderson, A., Rinki, M., DeHovitz, R., Maldonado, Y., Arvin, A. M. 2004; 17 (2): 298-307

    Abstract

    Vaccination of infants against measles remains of global importance, and proposed new vaccine strategies include the use of measles proteins or synthetic peptides as immunogens. We studied cell-mediated immunity to whole measles antigen and measles proteins in immune adults and infants after measles vaccine. Further, we measured CD8+ T cell responses to peptide pools corresponding to the nucelocapsid (N) measles protein in adults given measles vaccine. Cell-mediated immune responses to three of four measles proteins were equivalent to those against whole measles antigen in immune adults. Responses to the fusion (F) protein were lower in infants compared to whole measles antigen (p < or = 0.03). Infant responses to both whole measles antigen and the F protein were lower compared with these responses in adults (p < or = 0.001). CD8+ T cell responses to N peptide pools varied, and differed between immune HLA-A2-positive individuals compared with naive and HLA-A2-negative subjects after measles vaccination. The measles-specific T cell adaptive response of infants is limited compared to adults, including responses to the F protein.

    View details for PubMedID 15279707

  • Induction of cellular and humoral immunity after aerosol or subcutaneous administration of Edmonston-Zagreb measles vaccine as a primary dose to 12-month-old children JOURNAL OF INFECTIOUS DISEASES Wong-Chew, R. M., Islas-Romero, R., Garcia-Garcia, M. D., Beeler, J. A., Audet, S., Santos-Preciado, J. I., Gans, H., Lew-Yasukawa, L., Maldonado, Y. A., Arvin, A. M., Valdespino-Gomez, J. L. 2004; 189 (2): 254-257

    Abstract

    Infants were immunized by aerosol (10(3.6) plaque-forming units [pfu]/dose) or subcutaneous (sc) (10(4.27) pfu/dose) administration of Edmonston-Zagreb measles vaccine. Measles-specific T cell proliferative responses with a stimulation index of > or =3 developed in 72% of children given aerosol-administered vaccine, compared with 87% given s.c.-administered vaccine (P =.06). Seroconversion rates were 90% after aerosol-administered vaccine and 100% after s.c.-administered vaccine (P=.01), and measles geometric mean titers were 237 milli-international units (mIU) (95% confidence interval [CI], 146-385 mIU) and 487 mIU (95% CI, 390-609 mIU) in each group, respectively (P=.01). Measles-specific T and B cell responses were weaker after aerosol than after sc vaccination, indicating a need to use a higher aerosol dose to achieve optimal immunogenicity.

    View details for Web of Science ID 000188097900012

    View details for PubMedID 14722890

  • Measles and mumps vaccination as a model to investigate the developing immune system: passive and active immunity during the first year of life International Symposium on Protection of Newborns through Maternal Immunization Gans, H., DeHovitz, R., Forghani, B., Beeler, J., Maldonado, Y., Arvin, A. M. ELSEVIER SCI LTD. 2003: 3398–3405

    Abstract

    Evaluations of neutralizing antibody responses in 6-, 9- and 12-month-old infants given measles or mumps vaccine indicated that 6-month-old infants had diminished humoral immune responses associated with passive antibody effects, but also had an intrinsic deficiency in antiviral antibody production, which was independent of passive antibody effects. In contrast, lower neutralizing antibody titers in 9-month-olds were related only to passive antibody effects. Measles and mumps-specific T-cell proliferation and interferon-gamma (IFNgamma) production were induced by vaccination at 6, 9 or 12 months, regardless of passive neutralizing antibodies or age. These observations suggest a need to refine concepts about passive antibody interference and primary vaccine failure, taking into account the sensitization of antiviral T-cells, which occurs in the presence of passive antibodies and is observed in infants who do not develop active humoral immunity. A second dose of measles vaccine given at 12-15 months enhanced antiviral T-cell responses to measles in infants who were vaccinated at 6 or 9 months, and produced higher seroconversion rates. Since T-cell immunity is elicited under the cover of passive antibodies, the youngest infants benefit from the synergistic protection mediated by maternal antibodies and their own capacity to develop sensitized antiviral T-cells, which prime for subsequent exposures to the viral antigens. Conceptually, maternal immunization approaches with vaccines that can be given to women of child-bearing age before pregnancy, or that are safe for administration during pregnancy, should enhance passive antibody protection. Rather than being detrimental to infant adaptive immune responses, maternal vaccination can be coupled effectively with vaccine regimens that elicit priming of antiviral immune responses in infants during the first year of life.

    View details for DOI 10.1016/S0264-410X(03)00341-4

    View details for PubMedID 12850348

  • Jarisch-Herxheimer reaction associated with ciprofloxacin administration for tick-borne relapsing fever PEDIATRIC INFECTIOUS DISEASE JOURNAL Webster, G., Schiffman, J. D., Dosanjh, A. S., Amieva, M. R., Gans, H. A., Sectish, T. C. 2002; 21 (6): 571-573

    Abstract

    A 14-year-old girl was seen at a community clinic with a chief complaint of abdominal pain and fevers and was treated with oral ciprofloxacin for presumed pyelonephritis. She became tachycardic and hypotensive after her first dose of antibiotic, and she developed disseminated intravascular coagulation. She was admitted to our hospital for presumed sepsis. Her outpatient peripheral blood smear was reviewed, revealing spirochetes consistent with Borrelia sp. To our knowledge this is the first reported case of the Jarisch-Herxheimer reaction to ciprofloxacin.

    View details for DOI 10.1097/01.inf.0000015641.27909.b6

    View details for Web of Science ID 000176194400018

    View details for PubMedID 12182387

  • Quanitation of CD4+responder T cell frequencies to measles in vaccinated infants and adults Gans, H. A., Alderson, A., Lew-Yasukawa, L., Rinki, M., DeHovitz, R., Arvin, A. M. OXFORD UNIV PRESS INC. 2001: 1152–52
  • Developmental maturation of the immune response to measles and mumps live viral vaccines. Gans, H. A., Maldonado, Y., Yasukawa, L. L., Beeler, J., Audet, S., Forghani, B., Rinki, M. M., DeHovitz, R., Hammer, L., Arvin, A. M. OXFORD UNIV PRESS INC. 2000: 223–23
  • Intravenous ribavirin therapy for adenovirus pneumonia PEDIATRIC PULMONOLOGY Shetty, A. K., Gans, H. A., So, S., Millan, M. T., Arvin, A. M., Gutierrez, K. M. 2000; 29 (1): 69-73

    Abstract

    We report on the effectiveness of intravenous ribavirin for severe adenoviral pneumonia in a 10-month-old male following orthotopic liver transplantation. On day 20 post-transplantation, he developed high fever, marked respiratory compromise, and hypoxemia. The chest radiograph showed bilateral pulmonary infiltrates. Samples of bronchoalveolar lavage fluid grew adenovirus, serotype 1. Marked clinical and radiological improvement was noted after intravenous ribavirin therapy. A prospective clinical trial is needed to determine the efficacy of ribavirin therapy for severe adenovirus disease.

    View details for Web of Science ID 000084587800011

    View details for PubMedID 10613789

  • IL-12, IFN-gamma, and T cell proliferation to measles in immunized infants JOURNAL OF IMMUNOLOGY Gans, H. A., Maldonado, Y., Yasukawa, L. L., Beeler, J., Audet, S., Rinki, M. M., DeHovitz, R., Arvin, A. M. 1999; 162 (9): 5569-5575

    Abstract

    Measles infection in infants is associated with severe complications, and secondary infections are attributed to generalized immunosuppression. Measles binding to its monocyte receptor down-regulates IL-12 which is expected to diminish Th1-like cytokine responses, including IFN-gamma. Whether young infants can be immunized effectively against measles is an important public health issue. We evaluated Ag-specific IL-12, IFN-gamma, and T cell responses of infants at 6 (n = 60), 9 (n = 46), or 12 mo (n = 56) of age and 29 vaccinated adults. IL-12 and IFN-gamma release by PBMC stimulated with measles Ag increased significantly after measles immunization in infants. IL-12 and IFN-gamma concentrations were equivalent in younger and older infants, but IL-12 concentrations were significantly lower in infants than in adults (p = 0.04). IL-12 production by monocytes was down-regulated by measles; the addition of recombinant human IL-12 enhanced IFN-gamma production by PBMC stimulated with measles Ag, but infant T cells released significantly less IFN-gamma than adult T cells under this condition. Of particular interest, the presence of passive Abs to measles had no effect on the specific T cell proliferation or IFN-gamma production after measles stimulation. Cellular immunity to measles infection and vaccination may be limited in infants compared with adults as a result of less effective IFN-gamma and IL-12 production in response to measles Ags. These effects were not exaggerated in younger infants compared with effects in infants who were immunized at 12 mo. In summary, infant T cells were primed with measles Ag despite the presence of passive Abs, but their adaptive immune responses were limited compared with those of adults.

    View details for Web of Science ID 000079892600073

    View details for PubMedID 10228039

  • Immune responses of 6, 9 and 12 month old infants immunized with measles or mumps vaccine and the effects of passive antibodies on these responses Gans, H. A., Lew-Yasukawa, L., Beeler, J., DeHovitz, R., Maldonado, Y., Arvin, A. M. NATURE PUBLISHING GROUP. 1999: 161A–161A
  • Deficiency of the humoral immune response to measles vaccine in infants immunized at age 6 months JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Gans, H. A., Arvin, A. M., Galinus, J., Logan, L., DeHovitz, R., Maldonado, Y. 1998; 280 (6): 527-532

    Abstract

    Measles causes serious morbidity in infants, with the highest risk among those who are 6 to 12 months of age. In the United States, measles vaccine has been given at age 12 to 15 months to minimize interference by passive antibodies and to achieve the high seroprevalence required for herd immunity. Infants of mothers with vaccine-induced immunity may lose passively acquired antibodies before 12 months, leaving them susceptible to measles infection.To assess the immunogenicity of measles vaccine in infants younger than 12 months.Cohort study conducted before and after measles immunization.Pediatric clinic in Palo Alto, Calif.Infants 6 (n = 27), 9 (n = 26), and 12 (n = 34) months of age were enrolled; 72 provided both initial and follow-up samples.Evaluation of immunogenicity before and 12 weeks after measles vaccination, including measles neutralizing antibody titers, measles-specific T-cell proliferation, and cytokine profiles.Measles neutralizing antibodies were present before vaccination in 52% (12/23), 35% (7/20), and 0% (0/22) of 6-, 9-, and 12-month-old infants, respectively. In the absence of detectable passive antibodies, geometric mean titers after vaccination were significantly lower in 6-month-old infants compared with 9-month-old infants (27 vs 578, P = .01) and 12-month-old infants (27 vs 972, P=.001). The seroconversion rate, defined as a 4-fold rise in antibody titer, in these 6-month-old infants was only 67%, and only 36% of these infants achieved seroprotective neutralizing antibody titers of 120 or higher after vaccination compared with 100% of 9- and 12-month-old infants lacking detectable passive antibody prior to vaccination. T-cell proliferation and cytokine responses to measles did not differ with age.Humoral immunity was deficient in 6-month-old infants given measles vaccine, even in the absence of detectable passively acquired neutralizing antibodies. Comparison of their responses with those of 9- and 12-month-old infants indicates that a developmental maturation of the immune response to measles may occur during the first year of life, which affects the immunogenicity of measles vaccine.

    View details for Web of Science ID 000075244900028

    View details for PubMedID 9707142

  • Comparison of T-cell responses to measles antigen in infants immunized at 6, 9, and 12 months of age. Gans, H., Galinus, J., DeHovitz, R., Arvin, A., Maldonado, Y. OXFORD UNIV PRESS INC. 1996: 269–69