Hayley Gans

All Publications

• A Pilot Survey on the Perceptions of Pediatric Subspecialty Fellows and Program Directors on Virtual Compared with In-person Interview Experiences. The Journal of pediatrics Chiel, L., Gans, H. A., Bales, M., King, S., Mason, K., Schwartz, A., Kesselheim, J., Boyer, D. 2024: 114019

  Abstract

  Pediatric fellowship programs have conducted virtual interviews since the start of the COVID-19 pandemic in 2020. In this national survey of fellowship program directors (FPDs) and fellows interviewed in-person and virtually, FPDs and fellows formed accurate impressions, regardless of format, but our data did not clearly support one interview format over another.

  View details for DOI 10.1016/j.jpeds.2024.114019

  View details for PubMedID 38514003

• Vaccine Associated Measles Complicated by Suspected Measles Inclusion Body Encephalitis in a Pediatric Leukemia Patient and Stem Cell Transplant Recipient: A Focus on Clinical Evolution and Management. The Pediatric infectious disease journal Kushner, L. E., Kamens, J., Bertaina, A., Shyr, D., Gans, H. A. 2024

  Abstract

  Immunocompromised individuals are at increased risk for severe disease and complications from viral infections, highlighting the importance of vaccination. However, in extremely rare situations, vaccine associated viral infections can be associated with disseminated disease and complications in immunocompromised hosts.Herein, we present a case of a 1-year-old child diagnosed with acute myeloid leukemia less than 2 weeks after receiving live viral vaccines who developed acute vaccine-strain measles virus disease, later complicated by central nervous system involvement following hematopoietic stem cell transplantation. A brain biopsy specimen was positive for vaccine-strain measles virus detected by reverse transcriptase polymerase chain reaction.She was treated with intravenous ribavirin, inosine pranobex, intrathecal interferon-alpha and donor lymphocyte infusion following measles-mumps-rubella vaccine boost. Despite these measures, the patient suffered neurologic decline and dysautonomia, expiring after compassionate extubation. Management and ideal risk mitigation strategies are discussed within the context of existing literature for this rare complication.

  View details for DOI 10.1097/INF.0000000000004299

  View details for PubMedID 38380931

• Safety and Immunogenicity of Live Viral Vaccines in a Multicenter Cohort of Pediatric Transplant Recipients. JAMA network open Feldman, A. G., Beaty, B. L., Ferrolino, J. A., Maron, G., Weidner, H. K., Ali, S. A., Bitterfeld, L., Boulware, M. A., Campbell, K. M., Carr, E., Chapman, S., Chang, Y., Cunningham, R., Dallas, R. H., Dantuluri, K. L., Domenick, B. N., Ebel, N. H., Elisofon, S., Fawaz, R., Foca, M., Gans, H. A., Gopalareddy, V. V., Gu, C., Gupta, N. A., Harmann, K., Hollenbeck, J., Huppler, A. R., Jaramillo, C., Kasi, N., Kerkar, N., Lerret, S., Lobritto, S. J., Lopez, M. J., Marini, E., Mavis, A., Mehra, S., Moats, L., Mohandas, S., Munoz, F. M., Mysore, K. R., Onsan, C., Ovchinsky, N., Perkins, K., Postma, S., Pratscher, L., Rand, E. B., Rowe, R. K., Schultz, D., Sear, K., Sell, M. L., Sharma, T., Stoll, J., Vang, M., Villarin, D., Weaver, C., Wood, P., Woodford-Berry, O., Yanni, G., Danziger-Isakov, L. A. 2023; 6 (10): e2337602

  Abstract

  Importance: Live vaccines (measles-mumps-rubella [MMR] and varicella-zoster virus [VZV]) have not been recommended after solid organ transplant due to concern for inciting vaccine strain infection in an immunocompromised host. However, the rates of measles, mumps, and varicella are rising nationally and internationally, leaving susceptible immunocompromised children at risk for life-threating conditions.Objective: To determine the safety and immunogenicity of live vaccines in pediatric liver and kidney transplant recipients.Design, Setting, and Participants: This cohort study included select pediatric liver and kidney transplant recipients who had not completed their primary MMR and VZV vaccine series and/or who displayed nonprotective serum antibody levels at enrollment between January 1, 2002, and February 28, 2023. Eligibility for live vaccine was determined by individual US pediatric solid organ transplant center protocols.Exposures: Exposure was defined as receipt of a posttransplant live vaccine. Transplant recipients received 1 to 3 doses of MMR vaccine and/or 1 to 3 doses of VZV vaccine.Main Outcome and Measure: Safety data were collected following each vaccination, and antibody levels were obtained at 0 to 3 months and 1 year following vaccination. Comparisons were performed using Mann-Whitney U test, and factors associated with development of postvaccination protective antibodies were explored using univariate analysis.Results: The cohort included 281 children (270 [96%] liver, 9 [3%] kidney, 2 [1%] liver-kidney recipients) from 18 centers. The median time from transplant to enrollment was 6.3 years (IQR, 3.4-11.1 years). The median age at first posttransplant vaccine was 8.9 years (IQR, 4.7-13.8 years). A total of 202 of 275 (73%) children were receiving low-level monotherapy immunosuppression at the time of vaccination. The majority of children developed protective antibodies following vaccination (107 of 149 [72%] varicella, 130 of 152 [86%] measles, 100 of 120 [83%] mumps, and 124 of 125 [99%] rubella). One year post vaccination, the majority of children who initially mounted protective antibodies maintained this protection (34 of 44 [77%] varicella, 45 of 49 [92%] measles, 35 of 42 [83%] mumps, 51 of 54 [94%] rubella). Five children developed clinical varicella, all of which resolved within 1 week. There were no cases of measles or rubella and no episodes of graft rejection within 1 month of vaccination. There was no association between antibody response and immunosuppression level at the time of vaccination.Conclusions and Relevance: The findings suggest that live vaccinations may be safe and immunogenic after solid organ transplant in select pediatric recipients and can offer protection against circulating measles, mumps, and varicella.

  View details for DOI 10.1001/jamanetworkopen.2023.37602

  View details for PubMedID 37824141

• A Visiting Rotation for Underrepresented in Medicine Pediatric Residents Is Valuable for Recruitment Into Pediatric Fellowships. Journal of graduate medical education Okorie, C. U., Kibrom, S., Rotandi, C. L., Guerin, A., Gans, H. A., Blankenburg, R. 2023; 15 (3): 397-399

  View details for DOI 10.4300/JGME-D-22-00793.1

  View details for PubMedID 37363674

• National Pediatric Subspecialty Recruitment Sessions Increase Program Visibility and Impact Candidate Application Choices. Journal of graduate medical education Gans, H. A., Boyer, D., Bales, M., Fussell, J. 2023; 15 (3): 399-400

  View details for DOI 10.4300/JGME-D-22-00749.1

  View details for PubMedID 37363682

• Benefits and Limitations of Virtual Recruitment: Perspectives From Subspeciality Directors. Pediatrics Petersen, T. L., King, J. C., Fussell, J. J., Gans, H. A., Waggoner-Fountain, L. A., Castro, D., Green, M. L., Hamilton, M. F., Marcdante, K., Mink, R., Nielsen, K. R., Turner, D. A., Watson, C. M., Zurca, A. D., Boyer, D. L. 2022

  Abstract

  BACKGROUND AND OBJECTIVES: Because of the coronavirus disease 2019 pandemic and recommendations from a range of leaders and organizations, the pediatrics subspecialty 2020 recruitment season was entirely virtual. Minimal data exist on the effect of this change to guide future strategies. The aim of this study was to understand the effects of virtual recruitment on pediatric subspecialty programs as perceived by program leaders.METHODS: This concurrent, triangulation, mixed-methods study used a survey that was developed through an iterative (3 cycles), consensus-building, modified Delphi process and sent to all pediatric subspecialty program directors (PSPDs) between April and May 2021. Descriptive statistics and thematic analysis were used, and a conceptual framework was developed.RESULTS: Forty-two percent (352 of 840) of PSPDs responded from 16 of the 17 pediatric (94%) subspecialties; 60% felt the virtual interview process was beneficial to their training program. A majority of respondents (72%) reported cost savings were a benefit; additional benefits included greater efficiency of time, more applicants per day, greater faculty involvement, and perceived less time away from residency for applicants. PSPDs reported a more diverse applicant pool. Without an in-person component, PSPDs worried about programs and applicants missing informative, in-person interactions and applicants missing hospital tours and visiting the city. A model based upon theory of change was developed to aid program considerations for future application cycles.CONCLUSIONS: PSPDs identified several benefits to virtual recruitment, including ease of accommodating increased applicants with a diverse applicant pool and enhanced faculty involvement. Identified limitations included reduced interaction between the applicant and the larger institution/city.

  View details for DOI 10.1542/peds.2022-056735

  View details for PubMedID 36082609

• Pediatric Solid Organ Transplant Recipients Demonstrate Robust Cell-Mediated and Humoral Responses to 3 Doses of mRNA SARS-CoV-2 Vaccine. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons Bratic, J. S., Gans, H. A., Chen, S. F., Banaei, N., Johnston, E. M., Sear, K., Samreth, S., Nadimpalli, S. S. 2022

  Abstract

  Pediatric solid organ transplant recipients (pSOTR) often demonstrate suboptimal vaccine responses and are not included in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccine efficacy trials. This population has shown variable humoral immunity following SARS-CoV-2 vaccination, and no studies have assessed cell-mediated responses after SARS-CoV-2 vaccination in pSOTR. SARS-CoV2-specific interferon-gamma release assay (IGRA), immunoglobulin G (IgG), and receptor-binding domain (RBD)-ACE2 blocking antibody (Ab), were measured in pSOTR aged 5-17years after 2-3 doses of SARS-CoV-2 mRNA vaccine. Thirty-three subjects were included, with 25 tested after the 2nd dose of mRNA vaccine (V2) and 21 tested after the 3rd dose of mRNA vaccine (V3). Of the 19 subjects who had IgG testing after V3, 100.0% (19/19) had a positive IgG response. Of the 17 subjects who had IGRA testing after V3, 94.1% (16/17) had a positive IGRA response. RBD-ACE2 blocking antibody increased significantly from V2 to V3 (p=0.007). Subjects <1 year from transplant demonstrated a significantly larger increase in RBD-ACE2 blocking Ab from V2 to V3 than did those >1 year from transplant (p=0.05). SARS-CoV-2 vaccination induces humoral and cell-mediated responses in the majority of pSOTR, with improved quantitative humoral response after 3 doses.

  View details for DOI 10.1111/ajt.17195

  View details for PubMedID 36083190

• Immunizing pediatric liver transplant recipients against varicella virus using live-attenuated vaccination Harmann, K., Sear, K., Nadimpalli, S., Chen, S. F., Gans, H., Bensen, R. WILEY. 2022

  View details for Web of Science ID 000783167500005

• Vaccine-Associated Measles Encephalitis in Immunocompromised Child, California, USA. Emerging infectious diseases Costales, C., Sahoo, M. K., Huang, C., Guimaraes, C. V., Born, D., Kushner, L., Gans, H. A., Doan, T. A., Pinsky, B. A. 2022; 28 (4): 906-908

  Abstract

  We report a fatal case of vaccine-associated measles encephalitis in an immunocompromised child in California, USA. The infection was confirmed by whole-genome RNA sequencing of measles virus from brain tissue. We observed biased matrix-gene hypermutation consistent with persistent measles virus central nervous system infection.

  View details for DOI 10.3201/eid2804.212357

  View details for PubMedID 35318930

• Live Virus Vaccination of Pediatric Solid-Organ Transplant Candidates Within One Month Prior to Transplantation: A Multi-Center Experience. Transplant infectious disease : an official journal of the Transplantation Society Rosenthal, A., Madigan, T., Chen, S. F., Gans, H., Nadimpalli, S. 2021: e13667

  Abstract

  BACKGROUND: Solid organ transplant (SOT) recipients are at increased risk of vaccine preventable illness due to the high degree of immunosuppression required following transplantation. The current recommendation is to vaccinate with live attenuated vaccines, including Measles, Mumps and Rubella (MMR) and Varicella (VAR) vaccines, at least 4 weeks prior to transplant. However, data to support the time interval between vaccine and transplant is limited.METHODS: We conduct a literature review of the natural history of the viruses and length of viremia following live-attenuated viral vaccines and we describe a series of five cases from two pediatric transplant centers in which live attenuated viral vaccines were administered within 21 days prior to SOT.RESULTS: None of the 5 children who received MMR or VAR 8 to 21 days prior to liver (2) and heart (3) transplant suffered from vaccine related viral illness after transplant, even in the presence of significant immunosuppression with T-cell-depleting agents.CONCLUSION: These cases support that shorter intervals of live vaccine administration prior to transplant may be safe, allowing the vaccination of a larger cohort of SOT candidates. Increasing pre-transplant vaccinations is crucial since, in most cases, live viral vaccines are contraindicated post-transplantation, and the most effective vaccine approaches utilize prime-boost strategies, priming before and boosting after transplant.

  View details for DOI 10.1111/tid.13667

  View details for PubMedID 34145665

• Using Speed Mentoring to Expand Scholarship Perspectives and Opportunities for Fellows. Journal of graduate medical education Guerin, A., Okamura, E., Rotandi, C. L., Halpern-Felsher, B., Blankenburg, R., Gans, H. A. 2021; 13 (3): 423-424

  View details for DOI 10.4300/JGME-D-20-01284.1

  View details for PubMedID 34178272

• Improving Pediatric Subspecialty Recruitment Using an Interdivisional Department Session. Journal of graduate medical education Okamura, E., Rotandi, C. L., Guerin, A., Halpern-Felsher, B., Blankenburg, R., Gans, H. A. 2021; 13 (3): 424-426

  View details for DOI 10.4300/JGME-D-20-01302.1

  View details for PubMedID 34178273

• Varicella zoster immune globulin (human) (VARIZIG) in immunocompromised patients: a subgroup analysis for safety and outcomes from a large, expanded-access program. BMC infectious diseases Gans, H., Chemaly, R. F. 2021; 21 (1): 46

  Abstract

  BACKGROUND: Immunocompromised children and adults are at increased risk for severe disease and death following varicella zoster virus infection. Varicella zoster immune globulin (human) (VARIZIG) is recommended for post-exposure prophylaxis to prevent or attenuate varicella infection in high-risk individuals.METHODS: An open-label, expanded-access program provided VARIZIG to high-risk individuals exposed to varicella or herpes zoster. Immunocompromised participants were stratified by type of immunocompromising condition ("oncologic immunodeficiency", "primary immunodeficiency", "solid organ transplant" [SOT], "hematopoietic cell transplant" [HCT], and "other"). Patient characteristics, type of exposure and varicella outcome, and safety data were assessed.RESULTS: This analysis included 40 adults (primary [n=6] or oncologic [n=10] immunodeficiencies, history of SOT [n=5] or HCT [n=6], and other [n=13]), and 263 children (primary [n=13] or oncologic [n=152] immunodeficiencies, history of SOT [n=36] or HCT [n=17], and other [n=45]). Among adults and children, 48% vs 72% were exposed to varicella, 38% vs 16% were exposed to herpes zoster, and 15% vs 12% had an unspecified exposure. Overall incidence of varicella infection in adults after VARIZIG use was 6%; incidence of varicella infection in children after VARIZIG use was 7%. Similar rates were noted in each subgroup. Most cases of varicella were mild, with two children developing >100 lesions and no cases of varicella-related pneumonia or encephalitis. Varicella-related hospitalizations occurred primarily in children with oncologic immunodeficiencies. One serious adverse event (serum sickness) was considered related to VARIZIG and occurred in a child with oncologic immunodeficiency. There were no varicella- or VARIZIG-related deaths.CONCLUSIONS: These data indicate that VARIZIG may reduce severity of varicella in immunocompromised children and adults.TRIAL REGISTRATION: This study was retrospectively registered with the public clinical trial identification NCT00338442 at https://www.clinicaltrials.gov on 20 June 2006.

  View details for DOI 10.1186/s12879-020-05656-6

  View details for PubMedID 33430796

• Do I Belong Here? Confronting Imposter Syndrome at an Individual, Peer, and Institutional Level in Health Professionals. MedEdPORTAL : the journal of teaching and learning resources Rivera, N., Feldman, E. A., Augustin, D. A., Caceres, W., Gans, H. A., Blankenburg, R. 2021; 17: 11166

  Abstract

  Introduction: Imposter syndrome (IS) is a feeling of being an intellectual fraud and is common among health professionals, particularly those underrepresented in medicine. IS is accompanied by burnout, self-doubt, and beliefs of decreased success. This workshop aims to discuss the impact of IS and develop strategies to confront IS at the individual, peer, and institutional levels.Methods: During the 75-minute interactive workshop, participants listened to didactics and engaged in individual reflection, small-group case discussion, and large-group instruction. Workshop participants and facilitators included medical students, residents, fellows, faculty, staff, and program leadership. Anonymous postworkshop evaluations exploring participants' satisfaction and intentions to change their behavior were collected. Descriptive statistics were used to analyze the quantitative data, and content analysis was used to analyze participants' intentions to change their behavior.Results: The workshop was presented at three local academic conferences and accepted at one national conference. Data were collected from 92 participants. Ninety-two percent of participants felt the workshop met its objectives, and 90% felt the workshop was a valuable use of their time. Furthermore, 90% of participants stated they would apply information learned at the workshop in the future. The participants indicated an intent to change behavior on individual, peer, and institutional levels, while recognizing that barriers exist at all those levels.Discussion: This workshop proved to be an effective means to discuss strategies on how to address IS at the individual, peer, and institutional levels. The materials can be adapted for relevance to various audiences.

  View details for DOI 10.15766/mep_2374-8265.11166

  View details for PubMedID 34277932

• Standardization of Post-operative Antimicrobials Reduced Exposure While Maintaining Good Outcomes in Pediatric Liver Transplant Recipients. Transplant infectious disease : an official journal of the Transplantation Society Bio, L. L., Schwenk, H. T., Chen, S. F., Conlon, S., Gallo, A., Andy Bonham, C., Gans, H. A. 2020: e13538

  Abstract

  Infections following orthotopic liver transplant (OLT) result in significant morbidity and mortality, warranting careful consideration of risks associated with antibiotic overuse and benefits of infection prevention. In the absence of specific guidelines for antimicrobial prophylaxis in pediatric OLT, we developed a standardized approach to post-operative (post-op) antimicrobial therapy including 48 hours of antibiotics, no vancomycin for post-op fever within the first 48 hours, and caspofungin only for certain situations. The goal was to reduce antimicrobial utilization and adverse outcomes associated with longer duration of and broader treatment while maintaining good outcomes. The impact of this standardization on antimicrobial utilization and clinical outcomes at the largest pediatric liver transplant center in the United States is described. All individuals receiving an OLT from 1/1/17-9/30/17 (N=38) and 3/14/18-12/13/18 (N=27) were included in the pre-intervention (PreI) and post-intervention (PostI) groups, respectively. The intervention resulted in a significant reduction in individuals receiving post-op broad-spectrum gram-negative antibiotics for > 48 hours (76% PreI vs 44% PostI OLT recipients, P = 0.01) and post-op vancomycin use (50% PreI, vs 7.4% PostI, P < 0.001). There were no statistically significant differences between groups for post-op fever, positive pre-/post-operative cultures, receipt of massive transfusion, or hospital length of stay. In conclusion, following the implementation of a standardized approach to post-op prophylaxis, antimicrobial exposure was significantly reduced without affecting OLT recipient outcomes.

  View details for DOI 10.1111/tid.13538

  View details for PubMedID 33252820

• Kinetics of SARS-CoV-2 positivity of infected and recovered patients from a single center. Scientific reports Huang, J. n., Zheng, L. n., Li, Z. n., Hao, S. n., Ye, F. n., Chen, J. n., Gans, H. A., Yao, X. n., Liao, J. n., Wang, S. n., Zeng, M. n., Qiu, L. n., Li, C. n., Whitin, J. C., Tian, L. n., Chubb, H. n., Hwa, K. Y., Ceresnak, S. R., Zhang, W. n., Lu, Y. n., Maldonado, Y. A., McElhinney, D. B., Sylvester, K. G., Cohen, H. J., Liu, L. n., Ling, X. B. 2020; 10 (1): 18629

  Abstract

  Recurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive detection in infected but recovered individuals has been reported. Patients who have recovered from coronavirus disease 2019 (COVID-19) could profoundly impact the health care system. We sought to define the kinetics and relevance of PCR-positive recurrence during recovery from acute COVID-19 to better understand risks for prolonged infectivity and reinfection. A series of 414 patients with confirmed SARS-Cov-2 infection, at The Second Affiliated Hospital of Southern University of Science and Technology in Shenzhen, China from January 11 to April 23, 2020. Statistical analyses were performed of the clinical, laboratory, radiologic image, medical treatment, and clinical course of admission/quarantine/readmission data, and a recurrence predictive algorithm was developed. 16.7% recovered patients with PCR positive recurring one to three times, despite being in strict quarantine. Younger patients with mild pulmonary respiratory syndrome had higher risk of PCR positivity recurrence. The recurrence prediction model had an area under the ROC curve of 0.786. This case series provides characteristics of patients with recurrent SARS-CoV-2 positivity. Use of a prediction algorithm may identify patients at high risk of recurrent SARS-CoV-2 positivity and help to establish protocols for health policy.

  View details for DOI 10.1038/s41598-020-75629-x

  View details for PubMedID 33122706

• A 10-Month-Old Female With Complicated Mastoiditis Due to Fusobacterium necrophorum: A Case Report and Literature Review. Journal of the Pediatric Infectious Diseases Society Rosenthal, A. n., Gans, H. n., Schwenk, H. T. 2020

  View details for DOI 10.1093/jpids/piaa059

  View details for PubMedID 32531061

• Genetic associations with a fever after measles-containing vaccines. Human vaccines & immunotherapeutics Klein, N. P., Zerbo, O. n., Goddard, K. n., Wang, W. n., Fohner, A. E., Wiesner, A. n., Shokoohi, V. n., Coller, J. n., Bok, K. n., Gans, H. A. 2020: 1–7

  Abstract

  Children have elevated fever risk 1 to 2 weeks after the first dose of a measles-containing vaccine (MCV), which is likely affected by genetic, immunologic, and clinical factors. Fever after MCV is associated with febrile seizures, though may also be associated with higher measles antibody titers. This exploratory study investigated genetic and immunologic associations with a fever after MCV. Concurrent with a randomized Phase 3 clinical trial of 12-15-month-olds who received their first measles-mumps-rubella (MMR) vaccine in which parents recorded post-vaccination temperatures daily, we consented a subset to collect additional blood and performed human leukocyte antigens (HLA) typing. Association between fever 5-12 days after MMR ("MMR-associated") and HLA type was assessed using logistic regression. We compared 42-day post-vaccination geometric mean titers (GMT) to measles between children who did and did not have fever using a t-test. We enrolled 86 children and performed HLA typing on 82; 13 (15.1%) had MMR-associated fever. Logistic regressions identified associations between MMR-associated fever and HLA Class I loci A-29:02 (P = .036), B-57:01 (P = .018), C-06:02 (P = .006), C-14:02 (P = .022), and Class II loci DRB1-15 (P = .045). However, Bonferroni's adjustment for multiple comparisons suggests that these associations could have been due to chance. Ninety-eight percent of children had protective antibody titers to measles; however, GMT was higher among those with fever compared with children without fever (P = .006). Fever after the measles vaccine correlated with genetic factors and higher immune response. This study suggests a possible genetic susceptibility to MMR-associated fever.

  View details for DOI 10.1080/21645515.2020.1849520

  View details for PubMedID 33351701

• 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

  View details for Web of Science ID 000485482200093

• 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. n. 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. n., Gans, H. A., Young, J. H., Hill, J. A., Savani, B. n., Chemaly, R. F., Dadwal, S. S., Storek, J. n., Duchin, J. n., 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. n., Modaressi, S. n., Goddard, K. n., Lewis, E. n., Bok, K. n., Gans, H. n., 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. n., Yasukawa, L. L., Audet, S. n., Abu-Raya, B. n., 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

• Clinical Management of Pediatric Acute-Onset Neuropsychiatric Syndrome: Part II-Use of Immunomodulatory Therapies. Journal of child and adolescent psychopharmacology Frankovich, J., Swedo, S., Murphy, T., Dale, R. C., Agalliu, D., Williams, K., Daines, M., Hornig, M., Chugani, H., Sanger, T., Muscal, E., Pasternack, M., Cooperstock, M., Gans, H., Zhang, Y., Cunningham, M., Bernstein, G., Bromberg, R., Willett, T., Brown, K., Farhadian, B., Chang, K., Geller, D., Hernandez, J., Sherr, J., Shaw, R., Latimer, E., Leckman, J., Thienemann, M. 2017; 27 (7): 574-593

  Abstract

  Introduction: Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) is a clinically heterogeneous disorder with a number of different etiologies and disease mechanisms. Inflammatory and postinfectious autoimmune presentations of PANS occur frequently, with some clinical series documenting immune abnormalities in 75%-80% of patients. Thus, comprehensive treatment protocols must include immunological interventions, but their use should be reserved only for PANS cases in which the symptoms represent underlying neuroinflammation or postinfectious autoimmunity, as seen in the PANDAS subgroup (Pediatric Autoimmune Neuropsychiatric Disorders associated with Streptococcal infections). Methods: The PANS Research Consortium (PRC) immunomodulatory task force is comprised of immunologists, rheumatologists, neurologists, infectious disease experts, general pediatricians, psychiatrists, nurse practitioners, and basic scientists with expertise in neuroimmunology and PANS-related animal models. Preliminary treatment guidelines were created in the Spring of 2014 at the National Institute of Health and refined over the ensuing 2 years over conference calls and a shared web-based document. Seven pediatric mental health practitioners, with expertise in diagnosing and monitoring patients with PANS, were consulted to create categories in disease severity and critically review final recommendations. All authors played a role in creating these guidelines. The views of all authors were incorporated and all authors gave final approval of these guidelines. Results: Separate guidelines were created for the use of immunomodulatory therapies in PANS patients with (1) mild, (2) moderate-to-severe, and (3) extreme/life-threatening severity. For mildly impairing PANS, the most appropriate therapy may be "tincture of time" combined with cognitive behavioral therapy and other supportive therapies. If symptoms persist, nonsteroidal anti-inflammatory drugs and/or short oral corticosteroid bursts are recommended. For moderate-to-severe PANS, oral or intravenous corticosteroids may be sufficient. However, intravenous immunoglobulin (IVIG) is often the preferred treatment for these patients by most PRC members. For more severe or chronic presentations, prolonged corticosteroid courses (with taper) or repeated high-dose corticosteroids may be indicated. For PANS with extreme and life-threatening impairment, therapeutic plasma exchange is the first-line therapy given either alone or in combination with IVIG, high-dose intravenous corticosteroids, and/or rituximab. Conclusions: These recommendations will help guide the use of anti-inflammatory and immunomodulatory therapy in the treatment of PANS.

  View details for DOI 10.1089/cap.2016.0148

  View details for PubMedID 36358107

• 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

• Humoral and cell-mediated immune responses to an early 2-dose measles vaccination regimen in the United States 41st Annual Meeting of the Infectious-Diseases-Society-of-America Gans, H. A., Yasukawa, L. L., Alderson, A., Rinki, M., DeHovitz, R., Beeler, J., Audet, S., Maldonado, Y., Arvin, A. M. UNIV CHICAGO PRESS. 2004: 83–90

  Abstract

  Shifts in peak measles incidence to children <12 months old and the associated high mortality support the study of an early 2-dose measles vaccine regimen.Fifty-five infants were vaccinated with measles vaccine at age 6 (n=32) or 9 (n=23) months, followed by measles-mumps-rubella (MMR)-II vaccine at age 12 months. A control group received MMR-II only at age 12 months. Measles-specific humoral and cell-mediated immunity were evaluated before, 12 weeks after measles immunization, and 24 weeks after MMR-II.Measles-specific T cell proliferation after both doses of vaccine was equivalent, regardless of age or the presence of passive antibodies. Seroconversion rates, geometric mean titers, and the percentage of infants with antibody titers >120 mIU after the first measles vaccine were lower in infants vaccinated at age 6 months, regardless of the presence of passive antibodies, but measles humoral responses increased after the administration of MMR-II vaccine in children initially vaccinated at age 6 or 9 months.Measles vaccination elicits T cell responses in infants as young as 6 months old, which may prime the humoral response to the second dose. Initiating measles vaccination as an early 2-dose regimen results in an immunologic response that is likely to have clinical benefits in developed and developing countries.

  View details for PubMedID 15195246

• 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

• Immune responses to measles and mumps vaccination of infants at 6, 9, and 12 months 38th Annual Meeting of the Infectious-Diseases-Society-of-America Gans, H., Yasukawa, L., Rinki, M., DeHovitz, R., Forghani, B., Beeler, J., Audet, S., Maldonado, Y., Arvin, A. M. UNIV CHICAGO PRESS. 2001: 817–26

  Abstract

  Immunizing infants against measles at the youngest age possible has the potential to reduce morbidity and mortality. The ability of infants at 6, 9, or 12 months to respond to measles and mumps vaccines was evaluated by measuring T cell proliferation, interferon-gamma production, and neutralizing antibody titers before and after vaccination. Infants in all age groups had equivalent cellular immune responses to measles or mumps viruses, with or without passive antibodies when immunized. In contrast, 6-month-old infants without passive antibodies had low geometric mean titers of antibody to measles or mumps viruses and low seroconversion rates. Geometric mean titers of antibody to measles virus increased if infants were revaccinated at 12 months. Six-month-old infants had limited humoral responses to paramyxovirus vaccines, whereas cellular immunity was equivalent to that of older infants. T cell responses can be established by immunization with these live attenuated virus vaccines during the first year, despite the presence of passive antibodies.

  View details for Web of Science ID 000171228400002

  View details for PubMedID 11528592

• 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

  View details for Web of Science ID 000171226900400

• 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

  View details for Web of Science ID 000088950900107

• 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

  View details for Web of Science ID 000079476700940

• 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

  View details for Web of Science ID A1996VN24600315