- Infectious Diseases, Pediatric
- Pediatric Infectious Diseases
Clinical Professor, Pediatrics - Infectious Diseases
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)
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)
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.
Ontogeny of Measles Immunity in Infants
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.
- Independent Studies (5)
Graduate and Fellowship Programs
- 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 2013; 208 (1): 1-3
The status of live viral vaccination in early life.
2013; 31 (21): 2531-2537
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
2013; 207 (4): 574-582
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
IMP-Producing Carbapenem-Resistant Klebsiella pneumoniae in the United States
JOURNAL OF CLINICAL MICROBIOLOGY
2011; 49 (12): 4239-4245
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 2011; 12 (3): 189-194
Preterm Infants' T Cell Responses to Inactivated Poliovirus Vaccine
JOURNAL OF INFECTIOUS DISEASES
2010; 201 (2): 214-222
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
2009; 200 (12): 1921-1927
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
UNIV CHICAGO PRESS. 2008: 1669–75
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
2008; 21 (2): 163-172
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
UNIV CHICAGO PRESS. 2008: 944–49
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
2008; 38 (3): 287-295
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
2007; 196 (9): 1339-1345
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
ELSEVIER SCI LTD. 2006: 683–90
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
UNIV CHICAGO PRESS. 2004: 83–90
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
2004; 17 (2): 298-307
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
2004; 189 (2): 254-257
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
ELSEVIER SCI LTD. 2003: 3398–3405
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
2002; 21 (6): 571-573
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
UNIV CHICAGO PRESS. 2001: 817–26
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
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.
OXFORD UNIV PRESS INC. 2000: 223–23
View details for Web of Science ID 000088950900107
Intravenous ribavirin therapy for adenovirus pneumonia
2000; 29 (1): 69-73
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
1999; 162 (9): 5569-5575
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
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
1998; 280 (6): 527-532
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.
OXFORD UNIV PRESS INC. 1996: 269–69
View details for Web of Science ID A1996VN24600315