- Pediatric Infectious Disease
- Infectious Diseases, Pediatric
Medical Director, Infection Control, LPCH (2006 - Present)
Board Certification: Pediatrics, American Board of Pediatrics (1986)
Fellowship:John Hopkins Hospital (1986) MD
Medical Education:Stanford University School of Medicine (1981) CA
Fellowship:Centers for Disease Control and Prevention (1988) GA
Fellowship, Johns Hopkins Hospital, Pediatric Infectious Diseases (1986)
Residency:John Hopkins Hospital (1984) MD
Internship:Stanford University School of Medicine (1982) CA
Current Research and Scholarly Interests
The research I have conducted has been focused on epidemiologic aspects of viral vaccine development and prevention of perinatal HIV transmission. A major project has been to identify the molecular epidemiology of factors affecting the immunogenicity of oral polio vaccine (OPV) among children living in developing areas of the world, where OPV immunogenicity is poor. We have identified several factors which affect the poor immunogenicity of OPV and will conduct clinical studies to attempt to improve immunogenicity. We are now working on ways to understand the transmission and circulation of polio vaccine derived viruses, which may cause polio, and how to use this information in global eradication of polio. I also work on perinatal HIV infection, including strategies to prevent breastfeeding transmission in developing settings as well as understanding how to maximize prevention strategies among pregnant women in developed countries.
A second recent project has been to define the ontogeny of the immune response to measles vaccine among young infants. The purpose is to identify specific humoral and cell-mediated immune responses to measles vaccine which affect vaccine immunogenicity and induce the immunosuppressive effects associated with measles vaccination.
A final project I have conducted since 1989 involves a long term natural history study of infants with perinatal HIV exposure and infection. This computer-based study involves following all HIV-exposed and infected infants living in the Northern California and defining factors associated with progression of HIV-related disease.
Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
The investigators hope to learn 1) if the addition of prophylaxis with vancomycin will decrease the rate of cefazolin non-susceptible SSI's, in high risk population 2) to develop better understanding of vancomycin and cefazolin pharmacokinetics in children undergoing cardiopulmonary bypass 3) to assess the barriers to vancomycin dosing peri-operatively 4) to assess side effects and risks associated with peri-operative vancomycin administration. This will allow us to improve patient care by better understanding the benefits or the risks of peri-operative vancomycin administration and potentially decrease cefazolin-resistant surgical site infections. In addition, this study gives us the opportunity to evaluate cefazolin and vancomycin pharmacokinetics on children on CPB. The investigators will take blood samples from 20 patients. In 10 patients the investigators will do Cefazolin pK analysis and in the other 10 the investigators will do pK Vancomycin analysis. For the remainder of 292 patients, only prospective chart review will be done to determine the incidence of SSI's. This data will be compared with 936 controls who received only Cefazolin pre-operatively as prophylaxis for SSI's. --------------------------------------------------------------------------------
Independent Studies (13)
- Directed Reading in Health Research and Policy
HRP 299 (Aut, Win, Spr, Sum)
- Directed Reading in Pediatrics
PEDS 299 (Aut, Win, Spr, Sum)
- Early Clinical Experience
PEDS 280 (Aut, Win, Spr, Sum)
- Graduate Research
HRP 399 (Aut, Win, Spr, Sum)
- Graduate Research
PEDS 399 (Aut, Win, Spr, Sum)
HUMBIO 194 (Win, Spr)
- Medical Scholars Research
HRP 370 (Aut, Win, Spr, Sum)
- Medical Scholars Research
PEDS 370 (Aut, Win, Spr, Sum)
- Out-of-Department Advanced Research Laboratory in Experimental Biology
BIO 199X (Aut, Win, Spr, Sum)
- Out-of-Department Graduate Research
BIO 300X (Win, Spr)
- Research in Human Biology
HUMBIO 193 (Aut, Win)
- Undergraduate Directed Reading/Research
PEDS 199 (Aut, Win, Spr, Sum)
- Undergraduate Research
HRP 199 (Aut, Win, Spr, Sum)
- Directed Reading in Health Research and Policy
- Prior Year Courses
Efficacy and Safety of an Extended Nevirapine Regimen in Infants of Breastfeeding Mothers With HIV-1 Infection for Prevention of HIV-1 Transmission (HPTN 046): 18-Month Results of a Randomized, Double-Blind, Placebo-Controlled Trial.
Journal of acquired immune deficiency syndromes (1999)
2014; 65 (3): 366-374
HPTN 046 compared the efficacy and safety of infant nevirapine (NVP) among HIV-exposed breastfed infants randomized at 6 weeks to 6 months to t NVP or placebo to prevent postnatal infection: we report final 18-month outcomes.Randomized, placebo-controlled trial in 4 African countries. Infant diagnostic HIV testing was performed regularly from birth through 18 months. Kaplan-Meier analysis was used to assess 18-month cumulative infant HIV infection, HIV infection/or death, and mortality rates.Between 6 weeks and 6 months, postnatal HIV infection rates were significantly lower among infants receiving daily NVP from 6 weeks to 6 months 1.1% [95% confidence interval (CI): 0.2% to 1.8%], compared with placebo 2.4% (95% CI: 1.3% to 2.6%), P = 0.049, but not significantly lower thereafter. Eighteen-month postnatal infection rates were low: 2.2% (95% CI: 1.1% to 3.3%) versus 3.1% (95% CI: 1.9% to 4.4%), respectively, P = 0.28. Mortality and HIV infection/death did not differ between arms at any age. Infants of women receiving antiretroviral therapy (ART) for their own health had the lowest 18-month postnatal infection rates (0.5%, 95% CI: 0.0% to 1.1%). However, HIV infection/death rates at 18 months were not significantly different for infants of mothers on ART (3.7%, 95% CI: 1.9% to 5.5%), and infants of mothers with CD4 counts of ≥350 cells per cubic millimeter not receiving ART (4.8%, 95% CI: 2.7% to 6.8%; P = 0.46). There were no differences in adverse events between study arms.This trial demonstrated early but not late differences in postnatal HIV transmission among infants randomized at age 6 weeks to extended NVP or placebo, underscoring the importance of continued prophylaxis throughout breastfeeding.
View details for DOI 10.1097/QAI.0000000000000052
View details for PubMedID 24189151
Temporal Trends in Otolaryngologic Findings among HIV-1-infected Children in a Population-based Cohort.
Pediatric infectious disease journal
2014; 33 (3): e76-80
Otolaryngologic conditions are common among HIV-1-infected children. In this study, we provide data regarding prevalence of pediatric HIV-1 otolaryngologic manifestations in the era of antiretroviral therapy (ART).We conducted population-based, prospective, multicenter pediatric HIV-1 surveillance among 276 children with perinatally acquired HIV-1 from 1988 to 2009. All Center for Disease Control (CDC) mild, moderate and severe otolaryngologic conditions were evaluated.CDC-defined, HIV-1-related otolaryngologic conditions among the 276 children were: 103, mild; 50, moderate and 20, severe. The majority [23.3% (24/103), 40.0% (20/50) and 50% (10/20)] of mild, moderate and severe diagnoses, respectively, occurred in the first year of life, with 53.4% (55/103), 66.0% (33/50) and 70% (14/20), respectively, occurring in the first 2 years of life. The most frequent diagnoses were otitis media [21% (58/276)] and oropharyngeal thrush [17.4% (48/276)]. There was a temporal decline by cohort in prevalence of mild and moderate otolaryngologic diagnoses which was significant for mild conditions: 90, pre-ART cohort and 13, ART cohort (P < 0.001) and moderate conditions: 47, pre-ART and 3, ART (P < 0.001).In our study, many CDC-defined, HIV-related otolaryngologic conditions occur in the first 2 years of life. Over 22 years of longitudinal follow up, there was a significant decline in prevalence of CDC-defined otolaryngologic conditions by temporal cohorts when comparing pre-ART and ART eras. This finding supports early ART administration to decrease morbidity in HIV-1-positive infants and children as well as current US and World Health Organization guidelines to prevent early HIV disease progression.
View details for DOI 10.1097/INF.0000000000000034
View details for PubMedID 23995587
HIV Disease Progression in the First Year After Delivery Among African Women Followed in the HPTN 046 Clinical Trial.
Journal of acquired immune deficiency syndromes
2013; 64 (3): 299-306
Starting lifelong antiretroviral therapy (ART) in HIV-infected pregnant women may decrease HIV progression and transmission, but adherence after delivery may be difficult, especially for asymptomatic women. We evaluated disease progression among HIV-infected women not on ART with CD4⁺ lymphocyte counts above 200 cells per microliter at delivery.We analyzed risk of death, progression to AIDS (stage IV or CD4 < 200 cells per microliter), or to CD4⁺ count <350 1 year after delivery among postpartum women enrolled to a prevention of breastfeeding transmission trial using the Kaplan-Meier method. In the primary analysis, women were censored if ART was initiated.Among 1285 women who were not WHO stage IV or less at 6 weeks postpartum, 49 (4.3%) progressed to stage IV/CD4 <200 cells per microliter or death by 1 year. Progression to CD4 <200 cells per microliter or death occurred among 16 (4.3%) of 441 women with CD4 count of 350-549 cells per microliter and 10 (1.6%) of 713 with CD4 counts >550 cells per microliter at delivery. CD4 <350 cells per microliter by 12 months postpartum occurred among 116 (37.0%) of 350 women with CD4 count 400-549 cells per microliter and 48 (7.4%) of 713 with CD4 count >550 cells per microliter at delivery.Progression to AIDS or CD4 count <350 cells per microliter is uncommon through 1 year postpartum for women with CD4 counts over 550 cells per microliter at delivery, but occurred in over one third of those with CD4 counts under 550 cells per microliter. ART should be continued after delivery or breastfeeding among women with CD4 counts <550 cells per microliter if follow-up and antiretroviral adherence can be maintained.
View details for DOI 10.1097/QAI.0b013e3182a2123a
View details for PubMedID 23846568
Vaccine Poliovirus Shedding and Immune Response to Oral Polio Vaccine in HIV-Infected and -Uninfected Zimbabwean Infants
JOURNAL OF INFECTIOUS DISEASES
2013; 208 (4): 672-678
Background. With prolonged replication, attenuated polioviruses used in oral polio vaccine (OPV) can mutate into vaccine-derived poliovirus (VDPV) and cause poliomyelitis outbreaks. Individuals with primary humoral immunodeficiencies can become chronically infected with vaccine poliovirus, allowing it to mutate into immunodeficiency-associated VDPV (iVDPV). It is unclear if children perinatally infected with the human immunodeficiency virus (HIV), who have humoral as well as cellular immunodeficiencies, might be sources of iVDPV. Methods. We conducted a prospective study collecting stool and blood samples at multiple time points from Zimbabwean infants receiving OPV according to the national schedule. Nucleic acid extracted from stool was analyzed by real-time polymerase chain reaction for OPV serotypes. Results. We analyzed 825 stool samples: 285 samples from 92 HIV-infected children and 540 from 251 HIV-uninfected children. Poliovirus shedding was similar after 0-2 OPV doses but significantly higher in the HIV-infected versus uninfected children after ≥3 OPV doses, particularly within 42 days of an OPV dose, independent of seroconversion status. HIV infection was not associated with prolonged or persistent poliovirus shedding. HIV infection was associated with significantly lower polio seroconversion rates. Conclusions. HIV infection is associated with decreased mucosal and humoral immune responses to OPV but not the prolonged viral shedding required to form iVDPV.
View details for DOI 10.1093/infdis/jit208
View details for Web of Science ID 000322412100017
View details for PubMedID 23661792
- 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
Temporal Trends in Mucocutaneous Findings Among Human Immunodeficiency Virus 1-Infected Children in a Population-Based Cohort
2013; 30 (4): 451-456
The objective of the study was to determine the prevalence of pediatric human immunodeficiency virus 1 (HIV-1) mucocutaneous manifestations in the era of highly active antiretroviral therapy (HAART). We conducted population-based, prospective, multicenter pediatric HIV-1 surveillance in 276 children with perinatally acquired HIV-1 from 1988 to 2009. Centers for Disease Control and Prevention (CDC)-defined HIV-1 related mucocutaneous conditions among the 276 children were: category A (n = 152), B (n = 60), and C (n = 1). Nearly half of the category A and B diagnoses (43.4% [66/152] and 35.0% [21/60], respectively) occurred in the first year of life, with 59.2% (90/152) and 61.7% (37/60), respectively, occurring in the first 2 years of life. The most frequent infectious diagnosis was oropharyngeal thrush (n = 117, 42.4%); the most common inflammatory diagnosis was diaper dermatitis (n = 71, 25.7%). There was a temporal decline in the prevalence of A (pre-HAART cohort, 123; post-HAART cohort, 29; p < 0.01) and B (pre-HAART, 55; post-HAART, 5; p < 0.01) mucocutaneous diagnoses. In children with perinatal HIV-1, there was a significant decline in CDC category A and B mucocutaneous diagnoses by temporal cohort, consistent with the introduction of antiretroviral medications and HAART. Clinical category A and B mucocutaneous diagnoses were most common in the first 2 years of life, emphasizing the importance of early HIV-1 testing and HAART initiation.
View details for DOI 10.1111/pde.12020
View details for Web of Science ID 000321206100022
View details for PubMedID 23131130
Antiretroviral Drugs to Prevent Mother-to-Child Transmission of HIV During Breastfeeding
CURRENT HIV RESEARCH
2013; 11 (2): 102-125
In low and middle-income countries (LMIC), transmission of HIV during breastfeeding represents a major public health challenge. Several viral, maternal clinical, immunological and genetic factors, as well as maternal-infant host factors and type of infant feeding may influence the risk of breastfeeding transmission of HIV. The mechanisms of breast milk HIV transmission are poorly understood. For mothers who are healthy and do not need combination antiretroviral therapy for their own health, randomized controlled trials have proven that administration of extended maternal triple-drug antiretroviral (ARV) prophylaxis or extended infant ARV prophylaxis can significantly reduce the risk of HIV transmission during breastfeeding. Based on this evidence, the World Health Organization (WHO) published new guidance in 2010 on the use of ARVs for treating pregnant women, and preventing mother-to-child HIV transmission (PMTCT). Although, remarkable advances have occurred in prevention of postnatal transmission during breastfeeding using antiretroviral strategies, a number of challenges remain. Future research must focus on field studies to evaluate programmatic implementation of new WHO PMTCT regimens, monitor long-term safety of ART exposure during pregnancy and lactation, and study emergence of ARV resistance (in mothers and infected infants despite prophylaxis).
View details for Web of Science ID 000317098500004
View details for PubMedID 23432487
Reproductive Health and Family Planning Needs Among HIV-Infected Women in Sub-Saharan Africa
CURRENT HIV RESEARCH
2013; 11 (2): 160-168
Review key topics and recent literature regarding reproductive health and family planning needs for HIV-infected women in Sub-Saharan Africa.Electronic searches performed in PubMed, JSTOR, and Web of Science; identified articles reviewed for inclusion.Most HIV-infected women in Sub-Saharan Africa bear children, and access to antiretroviral therapy may increase childbearing desires and/or fertility, resulting in greater need for contraception. Most contraceptive options can be safely and effectively used by HIV-infected women. Unmet need for contraception is high in this population, with 66- 92% of women reporting not wanting another child (now or ever), but only 20-43% using contraception. During pregnancy and delivery, HIV-infected women need access to prevention of mother-to-child transmission (PMTCT) services, a skilled birth attendant, and quality post-partum care to prevent HIV infection in the infant and maximize maternal health. Providers may lack resources as well as appropriate training and support to provide such services to women with HIV. Innovations in biomedical and behavioral interventions may improve reproductive healthcare for HIV-infected women, but in Sub-Saharan Africa, models of integrating HIV and PMTCT services with family planning and reproductive health services will be important to improve reproductive outcomes.HIV-infected women in Sub-Saharan Africa have myriad needs related to reproductive health, including access to high-quality family planning information and options, high-quality pregnancy care, and trained providers. Integrated services that help prevent unintended pregnancy and optimize maternal and infant health before, during and after pregnancy will both maximize limited resources as well as provide improved reproductive outcomes.
View details for Web of Science ID 000317098500008
View details for PubMedID 23432491
Staphylococcal infections in children, California, USA, 1985-2009.
Emerging infectious diseases
2013; 19 (1): 10-20
We conducted a retrospective, observational, population-based study to investigate the effect of staphylococcal infections on the hospitalization of children in California during 1985-2009. Hospitalized children with staphylococcal infections were identified through the California Office of Statewide Health Planning and Development discharge database. Infections were categorized as community onset, community onset health care-associated, or hospital onset. Infection incidence was calculated relative to all children and to those hospitalized in acute-care facilities. A total of 140,265 records were analyzed. Overall incidence increased from 49/100,000 population in 1985 to a peak of 83/100,000 in 2006 and dropped to 73/100,000 in 2009. Staphylococcal infections were associated with longer hospital stays and higher risk for death relative to all-cause hospitalizations of children. The number of methicillin-resistant Staphylococcus aureus infections increased, and the number of methicillin-susceptible S. aureus infections remained unchanged. Children <3 years of age, Blacks, and those without private insurance were at higher risk for hospitalization.
View details for DOI 10.3201/eid1901.111740
View details for PubMedID 23260060
Communicating About Vaccines and Vaccine Safety: What Are Medical Residents Learning and What Do They Want to Learn?
JOURNAL OF PUBLIC HEALTH MANAGEMENT AND PRACTICE
2013; 19 (1): 40-46
Physicians spend significant amounts of time discussing vaccine safety concerns with patients and parents. This study aimed to better understand the educational needs of US residents regarding vaccine safety communication, primarily by quantifying the vaccine safety communication training that residents currently receive and elucidating residents' preferences around education about vaccines and vaccine safety communication.A mixed-methods needs assessment consisting of focus groups and a survey.A convenience sample of 303 medical residents in pediatrics, family medicine, and internal medicine from across the United States participated in an online, anonymous survey from March through June 2010. In addition, 9 focus groups with 47 resident participants were held. MAIN OUTCOME MEASURES/RESULTS: The sample included residents in pediatrics (239, 80.2%), internal or family medicine (30, 10.1%), and dual medicine-pediatrics (29, 9.7%); 20.6% of the residents reported "not learning" about vaccine safety communication in their residency programs. Preferred learning methods, which were also the most commonly used methods, included didactic lectures and role-modeling/cases. Electronic teaching method were not only less desired but also very rarely utilized. More than 95% of residents reported thinking that vaccine safety communication would be very or somewhat important in their careers.Improving education on vaccine safety communication within US residency programs, as well as offering self-learning opportunities, can better prepare physicians for their careers.
View details for DOI 10.1097/PHH.0b013e3182495776
View details for Web of Science ID 000311830300011
View details for PubMedID 23169402
Cultural adaptation of a survey to assess medical providers' knowledge of and attitudes towards HIV/AIDS in Albania.
2013; 8 (3)
Though the HIV/AIDS epidemic in Southeastern Europe is one of low reported prevalence, numerous studies have described the pervasiveness of medical providers' lack of knowledge of HIV/AIDS in the Balkans. This study sought to culturally adapt an instrument to assess medical providers' knowledge of and attitudes towards HIV/AIDS in Albania. Cultural adaptation was completed through development of a survey from previously validated instruments, translation of the survey into Albanian, blinded back translation, expert committee review of the draft instrument, focus group pre-testing with community- and University Hospital Center of Tirana-based physicians and nurses, and test-retest reliability testing. Blinded back translation of the instrument supported the initial translation with slight changes to the idiomatic and conceptual equivalences. Focus group pre-testing generally supported the instrument, yet some experiential and idiomatic changes were implemented. Based on unweighted kappa and/or prevalence adjusted bias adjusted kappa (PABAK), 20 of the 43 questions were deemed statistically significant at kappa and/or PABAK ?0.5, while 12 others did not cross zero on the 95% confidence interval for kappa, indicating their probable significance. Subsequently, an instrument to assess medical providers' knowledge of and attitudes toward HIV/AIDS for an Albanian population was developed which can be expanded within Albania and potentially to other countries within the Balkans, which have an Albanian-speaking population.
View details for DOI 10.1371/journal.pone.0059816
View details for PubMedID 23544101
- Measles Vaccine, HIV Infection, and Antiretroviral Therapy-A Window of Opportunity JOURNAL OF INFECTIOUS DISEASES 2012; 206 (4): 466-468
Hematologic and Immunologic Parameters in Zimbabwean Infants: A Case for Using Local Reference Intervals to Monitor Toxicities in Clinical Trials
JOURNAL OF TROPICAL PEDIATRICS
2012; 58 (1): 59-62
Studies investigating novel therapies in African infants report laboratory adverse events based on reference intervals from white Western infants. However, prior studies have shown that reference intervals differ based on ethnicity and geographic location. We calculated reference intervals for Zimbabwean infants by analyzing the hematologic and immunologic values found in 542 blood samples from 269 HIV-uninfected, black, Zimbabwean infants at 3, 5 and 9 months of age. Substantial proportions of the platelet counts (44%), hemoglobins (19%) and mean corpuscular volumes (41%) were outside published normal ranges. The majority (65%) of hemoglobin values qualified as a United States National Institutes of Health Division of AIDS adverse events. The majority (71%) of CD4% values indicated immunodeficiency by World Health Organization criteria. Hematologic and immunologic reference intervals used to evaluate toxicities in pediatric trials in sub-Saharan Africa need to be reevaluated to account for differences in ethnicity, geographic location, nutrition and socioeconomic status.
View details for DOI 10.1093/tropej/fmr031
View details for Web of Science ID 000299646700011
View details for PubMedID 21504989
Immunologic Response to Oral Polio Vaccine in Human Immunodeficiency Virus-infected and Uninfected Zimbabwean Children
PEDIATRIC INFECTIOUS DISEASE JOURNAL
2012; 31 (2): 176-180
Poliovirus eradication is dependent on maintaining adequate community-wide levels of serologic protection. Many African countries with conditions that favor continued wild poliovirus propagation also have a high prevalence of pediatric human immunodeficiency virus (HIV) infection. Data are limited regarding the degree of serologic immunity conferred on HIV-infected children after immunization with oral polio vaccine (OPV).This was a cross-sectional study correlating HIV infection and neutralizing antibodies against poliovirus serotypes 1, 2, and 3 in 95 Zimbabwean children 2 months to 2 years of age, born to HIV-infected mothers, who received OPV according to the national schedule.HIV-infected children had significantly lower rates of seroconversion to all 3 poliovirus serotypes than HIV-uninfected children (60%, 67%, and 47% vs. 96%, 100%, and 82%, P = 0.001, 0.0003, and 0.015 for serotypes 1, 2, and 3 in HIV-infected and uninfected children, respectively, after ?3 OPV doses). Among poliovirus seroconverters, HIV-infected children also had significantly lower geometric mean titers against serotypes 1 and 2 than HIV-uninfected children (geometric mean titers: 198 and 317 vs. 1193 and 1056, P = 0.032 and 0.050, for serotypes 1 and 2, respectively, after ?3 OPV doses). In addition, HIV-infected children had significantly higher levels of total IgG and significantly lower CD4% and mean weight than HIV-uninfected children. Of note, none of the HIV-infected children were receiving antiretroviral therapy, and 71% had a CD4% indicating severe immunodeficiency.Pediatric HIV infection is associated with a poor serologic response to OPV, which could pose an obstacle to global polio eradication.
View details for DOI 10.1097/INF.0b013e31823faa5f
View details for Web of Science ID 000299316500016
View details for PubMedID 22146742
Efficacy and safety of an extended nevirapine regimen in infant children of breastfeeding mothers with HIV-1 infection for prevention of postnatal HIV-1 transmission (HPTN 046): a randomised, double-blind, placebo-controlled trial
2012; 379 (9812): 221-228
Nevirapine given once-daily for the first 6, 14, or 28 weeks of life to infants exposed to HIV-1 via breastfeeding reduces transmission through this route compared with single-dose nevirapine at birth or neonatally. We aimed to assess incremental safety and efficacy of extension of such prophylaxis to 6 months.In our phase 3, randomised, double-blind, placebo-controlled HPTN 046 trial, we assessed the incremental benefit of extension of once-daily infant nevirapine from age 6 weeks to 6 months. We enrolled breastfeeding infants born to mothers with HIV-1 in four African countries within 7 days of birth. Following receipt of nevirapine from birth to 6 weeks, infants without HIV infection were randomly allocated (by use of a computer-generated permuted block algorithm with random block sizes and stratified by site and maternal antiretroviral treatment status) to receive extended nevirapine prophylaxis or placebo until 6 months or until breastfeeding cessation, whichever came first. The primary efficacy endpoint was HIV-1 infection in infants at 6 months and safety endpoints were adverse reactions in both groups. We used Kaplan-Meier analyses to compare differences in the primary outcome between groups. This study is registered with ClinicalTrials.gov, number NCT00074412.Between June 19, 2008, and March 12, 2010, we randomly allocated 1527 infants (762 nevirapine and 765 placebo); five of whom had HIV-1 infection at randomisation and were excluded from the primary analyses. In Kaplan-Meier analysis, 1·1% (95% CI 0·3-1·8) of infants who received extended nevirapine developed HIV-1 between 6 weeks and 6 months compared with 2·4% (1·3-3·6) of controls (difference 1·3%, 95% CI 0-2·6), equating to a 54% reduction in transmission (p=0·049). However, mortality (1·2% for nevirapine vs 1·1% for placebo; p=0·81) and combined HIV infection and mortality rates (2·3%vs 3·2%; p=0·27) did not differ between groups at 6 months. 125 (16%) of 758 infants given extended nevirapine and 116 (15%) of 761 controls had serious adverse events, but frequency of adverse events, serious adverse events, and deaths did not differ significantly between treatment groups.Nevirapine prophylaxis can safely be used to provide protection from mother-to-child transmission of HIV-1 via breastfeeding for infants up to 6 months of age.US National Institutes of Health.
View details for DOI 10.1016/S0140-6736(11)61653-X
View details for Web of Science ID 000299316100036
View details for PubMedID 22196945
Intradermal fractional dose inactivated polio vaccine: A review of the literature
2012; 30 (2): 121-125
Oral polio vaccine (OPV) will likely be insufficient to completely eradicate polio due to its propensity to mutate into neurovirulent forms and its inability to produce adequate immunity in certain areas of the world. Inactivated polio vaccine (IPV), a killed vaccine which therefore cannot mutate, may be more effective than OPV in certain populations, and will likely be required for global polio eradication. However, the high cost of IPV is prohibitive in many areas of the world. Intradermal administration has the potential to lower the dose, and thus the cost, of IPV. This article reviews the clinical studies to date on intradermal fractional dose polio vaccination. We conclude that intradermal IPV vaccination shows potential as a means to reduce the cost and increase the ease of administration of IPV, but that additional research is needed to determine the optimal fractional dose, timing, and role of adjuvants in intradermal IPV vaccination as well as the clinical significance of different antibody titers above the threshold for seroconversion.
View details for DOI 10.1016/j.vaccine.2011.11.018
View details for Web of Science ID 000299971800006
View details for PubMedID 22100886
Timing of Antiretroviral Therapy Initiation and its Impact on Disease Progression in Perinatal Human Immunodeficiency Virus-1 Infection
PEDIATRIC INFECTIOUS DISEASE JOURNAL
2012; 31 (1): 53-60
Treatment with highly active antiretroviral therapy (HAART) reduces overall perinatal human immunodeficiency virus (HIV) type 1-related mortality. The effect of timing of HAART initiation on reduction of morbidity is not well defined. We evaluated the association of timing of HAART initiation on progression to moderate or severe disease.Retrospective, population-based study of 196 perinatally HIV-infected children followed from birth in northern California from 1988 to 2009.Of 196 children, 58% received HAART and were followed for a median of 6.2 years after HAART initiation. HAART use was associated with improved survival to the age of 5 years: no HAART, 50% versus HAART, 88%; P < 0.0001. However, the advantage of initial HAART over mono or dual therapy transitioning to HAART was small and not statistically significant (P = 0.23). Starting HAART before the development of moderate or severe disease delayed the median age of diagnosis of moderate disease from 0.4 years (interquartile range, [0.3-0.8]) without HAART to 3.0 years ([interquartile range, 1.9-5.8]; P < 0.0001) with HAART. HAART initiation after progression to moderate or severe disease was associated with decreased progression to severe disease or death, respectively (moderate to severe: 8% [3/36] with HAART vs. 84% [70/83] with no HAART, P < 0.0001; severe to death: 9% [6/68] with HAART vs. 73% [49/67] with no HAART, P < 0.0001).In perinatal HIV infection, HAART is associated with delayed progression and reduced mortality regardless of disease severity at HAART initiation. This finding reinforces US guidelines regarding HAART initiation at >1 year of age if children present with most clinical category B diagnoses, regardless of CD4 measurements or plasma HIV RNA level.
View details for DOI 10.1097/INF.0b013e31823515a2
View details for Web of Science ID 000299050100016
View details for PubMedID 21979798
Real-time Polymerase Chain Reaction Analysis of Sewage Samples to Determine Oral Polio Vaccine Circulation Duration and Mutation After Mexican National Immunization Weeks.
Journal of the Pediatric Infectious Diseases Society
2012; 1 (3): 223-229
Oral polio vaccine (OPV) can mutate and cause outbreaks of paralytic poliomyelitis with prolonged replication. After poliovirus eradication, global use of inactivated polio vaccine (IPV) may be needed until all OPV stops circulating. Mexico, where children receive routine IPV but where OPV is given only during biannual national immunization weeks (NIWs), provides a natural setting to study duration of OPV circulation in a community primarily vaccinated with IPV.One-liter sewage samples from four separate arroyos (creeks) near Orizaba, Mexico, were collected monthly for 12 months. Concentrated sewage underwent RNA extraction, reverse transcription, and real-time polymerase chain reaction (PCR) to detect OPV serotypes 1, 2, and 3 and their variants containing the serotype-specific point mutation in the 5' untranslated region associated with neurovirulence.OPV was detected 3, 4, 5, and 7 months after the May 2010 NIW, but was not detected at 6 or 8 months. A second and third NIW occurred in February 2011 and May 2011, and OPV was detected in the sewage monthly after both of these NIW through July 2011 when collection stopped. The OPV detected was primarily serotype 2 and predominantly contained the point mutations in the 5' untranslated region associated with increased neurovirulence.OPV was detected in sewage as late as 7 months after an NIW in a Mexican community primarily vaccinated with IPV, but was not detected at 8 months, suggesting that OPV circulation may have ceased. These data suggest that in communities with high vaccination rates, 1 or 2 years of IPV administration after OPV cessation could be sufficient to prevent outbreaks of paralytic poliomyelitis from vaccine-derived strains.
View details for PubMedID 23667738
Levels of self-reported depression and anxiety among HIV-positive patients in Albania: a cross-sectional study
CROATIAN MEDICAL JOURNAL
2011; 52 (5): 622-628
To gain an initial perspective of mental health issues facing the Human Immunodeficiency Virus (HIV)-positive population at the University Hospital Center of Tirana (UHCT) HIV/AIDS Ambulatory Clinic.From June-August 2009, we conducted semi-structured interviews with 79 patients (93% response rate) at the UHCT HIV/AIDS Ambulatory Clinic. The interviews assessed patient-reported histories of mental health diagnoses, patients' demographics, and current emotional health status.The percentage of patients who reported a history of diagnosis of depression or anxiety was high - 62.3% and 82.3%, respectively. Factors associated with a history of depression included having been diagnosed with anxiety (P<0.001), having a higher number of barriers to care (P<0.001), having a higher number of current medical and social needs (P<0.001), or having not obtained antiretroviral therapy (ART) abroad (P=0.004). Factors associated with a history of anxiety included having been on first-line ART (P=0.008), having been diagnosed with HIV for shorter periods of time (P=0.043), having been diagnosed with depression (P<0.001), having a higher number of current medical and social needs (P=0.035), or having not obtained ART abroad (P=0.003).Mental health problems are widespread among the known HIV-positive patient population in Albania. The high prevalences of anxiety and depression and of dual diagnoses of these conditions suggest the need for more mental health care for HIV-positive patients in Albania.
View details for DOI 10.3325/cmj.2011.52.622
View details for Web of Science ID 000297080000006
View details for PubMedID 21990080
Trends in Hospitalization for Pediatric Pyelonephritis: A Population Based Study of California From 1985 to 2006
JOURNAL OF UROLOGY
2011; 186 (3): 1028-1034
We examined trends in pediatric hospitalization for pyelonephritis from 1985 to 2006 and identified factors associated with admission.We performed a population based analysis of hospital discharges using the Office of Statewide Health Planning and Development database to evaluate trends in California regarding pediatric hospitalizations for pyelonephritis from 1985 to 2006. Multivariable logistic regression was performed to identify factors associated with admission for pyelonephritis.A total of 46,300 children were hospitalized for pyelonephritis in California from 1985 to 2006. The overall rate of hospitalization for pyelonephritis increased by greater than 80%, from 17 per 100,000 children in the California population in 1985 to 31 per 100,000 in 2005. This change was primarily due to the nearly ninefold increase in pyelonephritis hospitalizations observed in children younger than 1 year, from 28 per 100,000 in 1985 to 238 per 100,000 in 2005. Among children younger than 1 year males without private insurance and of nonwhite race had increased odds of hospitalization, while females with private insurance and of Asian race had increased odds of hospitalization, compared with nonprivate insurance and white race, respectively.A significant increase in hospital admissions for pyelonephritis, primarily in children younger than 1 year, occurred in California between 1985 and 2006. Further studies are needed to establish the cause of this striking increase and to determine why certain pediatric populations are at increased risk for hospitalization.
View details for DOI 10.1016/j.juro.2011.04.101
View details for Web of Science ID 000293688300095
View details for PubMedID 21784477
Epidemiologic trends in penile anomalies and hypospadias in the state of California, 1985-2006
JOURNAL OF PEDIATRIC UROLOGY
2011; 7 (3): 294-298
Using statewide data, we evaluated whether the changing incidence of penile anomalies and hypospadias is reflected in the diverse California population of newborn males over the past 20 years.Discharge data from all California hospitals, prepared by the OSHPD (Sacramento, CA) was reviewed for the years 1985-2006 for male infant births with an ICD-9 code (752.6) for hypospadias, epispadias or other penile anomalies. Trends were examined by Generalized Estimation Equations for Poisson regression.From 1985 to 2006, the birth incidence of newborn penile anomalies increased in California from 47 to 57 cases per 10,000 newborn discharges, yet the trend for hypospadias alone appears stable from 1997. The rates for penile anomalies in newborns increased 1.4% annually (p < 0.001). All racial/ethnic groups analyzed showed this increase (p < 0.001 for each). During the study period there was a 2% increase per year in plural births (p < 0.001). Interestingly, the rate of change in penile anomaly incidence was greater in males of plural births compared to their singleton cohorts (2% vs 1% annually) (p < 0.001). The birth incidence of cleft palate, another congenital anomaly known to be stable over time, remained unchanged over this period.From 1985 to 2006 in California the incidence of penile anomalies increased in a statistically significant manner, but the incidence of hypospadias appears stable for the last decade. Our data support the notion that different racial/ethnic groups have distinct incidences of penile anomaly formation and that an association with plural births appears to be present.
View details for DOI 10.1016/j.jpurol.2011.03.006
View details for Web of Science ID 000292666200014
View details for PubMedID 21527236
BARRIERS TO CARE AND CURRENT MEDICAL AND SOCIAL NEEDS OF HIV-POSITIVE PATIENTS IN ALBANIA
CENTRAL EUROPEAN JOURNAL OF PUBLIC HEALTH
2011; 19 (2): 91-97
As HIV/AIDS prevalence rises in Eastern Europe, assessment of local epidemics in the bordering Central European region, especially South Eastern Europe, is vital in order to meet treatment and prevention needs. Understanding current medical and social needs and barriers to care experienced by HIV-positive patients in these regions may provide insight into how to best respond to the local epidemics, increase patients' access to treatment, and reduce loss to follow-up.This study assesses the patient characteristics, barriers to care, and current medical and social needs of HIV-positive patients in Albania. Semi-structured interviews were used in this cross-sectional study.We interviewed 79 of 85 patients (93% response rate) followed at the University Hospital Center of Tirana (UHCT) HIV/AIDS Ambulatory Clinic, which represented the majority of patients under HIV care in Albania during 2009.The local HIV epidemic seems to be comprised mainly of heterosexual men who have spent an average of 3.6 years abroad. The vast majority of patients under care at UHCT HIV/AIDS Ambulatory Clinic had experienced barriers to care associated with social stigma (97.4%), lack of knowledge of HIV medical care (76.6%), and medical provider's lack of knowledge of HIV (70.9%). Social needs of the patients were also overwhelmingly unmet (90.0-95.7%).In addressing HIV/AIDS in Albania, it will be crucial to educate the healthcare sector in ways to identify and address barriers to care and current medical and social needs of HIV-positive patients.
View details for Web of Science ID 000291919600008
View details for PubMedID 21739899
Factors Associated With Repeat Pregnancy Among Women in an Area of High HIV Prevalence in Zimbabwe
WOMENS HEALTH ISSUES
2011; 21 (3): 222-229
This study examined predictors of repeat pregnancy among women from the Prevention of Mother-to-Child Transmission of HIV (PMTCT) program in Zimbabwe.The study was conducted at urban antenatal clinics in Chitungwiza, a high HIV prevalence urban town on the outskirts of Harare, Zimbabwe. Using a cross-sectional design, 79 HIV-positive and 80 HIV-negative women who had participated in a PMTCT program in their index pregnancy were interviewed in Shona using a standardized questionnaire 24 months after delivery of their index pregnancy. Logistic regression was used to determine whether a relationship exists between repeat pregnancy and HIV status, socioeconomic status, age, Fertility Attitude Score, and previous pregnancy outcomes.In multivariate analysis, factors associated with an increased likelihood of repeat pregnancy were death of a child (odds ratio [OR], 3.9; 95% confidence interval [CI], 1.25-12.52; p = .0019), miscarriage (OR, 3.4; 95% CI, 1.23-9.34; p = .019), and each additional child (OR, 4.6; 95% CI, 1.89-11.52; p = .001). Decreased likelihood of repeat pregnancy was associated with decreased rank order of living conditions (OR, -0.75; 95% CI, 0.55-0.95; p = .021), each additional year of age (OR, -0.86; 95% CI, 0.77-0.97; p = .012), and higher Fertility Attitude Score (OR, -0.76; 95% CI, 0.64-0.91; p = .002).HIV status alone was not significant as a predictor of repeat pregnancy. Women's childbearing intentions are not influenced by the risk of mother-to-child transmission of HIV (MTCT) in this population. Future research is needed to address the cultural attitudes and sexual practices of HIV-positive women in order to minimize the threat of MTCT.
View details for DOI 10.1016/j.whi.2010.11.005
View details for Web of Science ID 000290358900006
View details for PubMedID 21411336
Use of a Novel Real-Time PCR Assay To Detect Oral Polio Vaccine Shedding and Reversion in Stool and Sewage Samples after a Mexican National Immunization Day
JOURNAL OF CLINICAL MICROBIOLOGY
2011; 49 (5): 1777-1783
During replication, oral polio vaccine (OPV) can revert to neurovirulence and cause paralytic poliomyelitis. In individual vaccinees, it can acquire specific revertant point mutations, leading to vaccine-associated paralytic poliomyelitis (VAPP). With longer replication, OPV can mutate into vaccine-derived poliovirus (VDPV), which causes poliomyelitis outbreaks similar to those caused by wild poliovirus. After wild poliovirus eradication, safely phasing out vaccination will likely require global use of inactivated polio vaccine (IPV) until cessation of OPV circulation. Mexico, where children receive routine IPV but where OPV is given biannually during national immunization days (NIDs), provides a natural setting to study the duration of OPV circulation in a population primarily vaccinated with IPV. We developed a real-time PCR assay to detect and distinguish revertant and nonrevertant OPV serotype 1 (OPV-1), OPV-2, and OPV-3 from RNA extracted directly from stool and sewage. Stool samples from 124 children and 8 1-liter sewage samples from Orizaba, Veracruz, Mexico, collected 6 to 13 weeks after a NID were analyzed. Revertant OPV-1 was found in stool at 7 and 9 weeks, and nonrevertant OPV-2 and OPV-3 were found in stool from two children 10 weeks after the NID. Revertant OPV-1 and nonrevertant OPV-2 and -3 were detected in sewage at 6 and 13 weeks after the NID. Our real-time PCR assay was able to detect small amounts of OPV in both stool and sewage and to distinguish nonrevertant and revertant serotypes and demonstrated that OPV continues to circulate at least 13 weeks after a NID in a Mexican population routinely immunized with IPV.
View details for DOI 10.1128/JCM.02524-10
View details for Web of Science ID 000289941000012
View details for PubMedID 21411577
Rural HIV-infected women's access to medical care: ongoing needs in California
AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV
2011; 23 (7): 792-796
HIV-infected women living in rural areas often have considerably less access to care than their urban and suburban counterparts. In much of the USA, little is known about HIV care among rural populations. This study elucidated barriers to care for rural women in California. Methods included retrospective structured interviews conducted with 64 women living in rural areas and receiving HIV care at 11 California healthcare facilities. Facilities were randomly sampled and all HIV-infected female patients seeking care at those facilities during a specified time period were eligible. The most commonly cited barriers to accessing care included physical health problems that prevented travel to care (32.8%), lack of transportation (31.2%), and lack of ability to navigate the healthcare system (25.0%). Being divorced/separated/widowed (compared to being either married or single) was associated with reporting physical health as a barrier to care (p=0.03); being unemployed (p=0.003) or having to travel 31-90 minutes (p=0.007, compared to less than 31 or greater than 90) were both associated with transportation as a barrier; and speaking English rather than Spanish was associated with reporting "difficulty navigating the system" (p=0.04). Twenty-nine women (45.3%) reported difficulty in traveling to appointments. Overall, 24 (37.5%) women missed an HIV medical appointment in the previous 12-month period, primarily due to their physical health and transportation limitations. Physical health and transportation problems were both the major barriers to accessing health services and the primary reasons for missing HIV care appointments among this population of HIV-infected women living in rural areas. Providing transportation programs and/or mobile clinics, as well as providing support for patients with physical limitations, may be essential to improving access to HIV care in rural areas.
View details for DOI 10.1080/09540121.2010.516345
View details for Web of Science ID 000299479300002
View details for PubMedID 21287418
How Racial and Ethnic Groupings May Mask Disparities: The Importance of Separating Pacific Islanders From Asians in Prenatal Care Data
MATERNAL AND CHILD HEALTH JOURNAL
2010; 14 (4): 635-641
To understand racial/ethnic differences in prenatal care receipt among Pacific Islanders and Asians, who are often combined into a single A/PI category.Retrospective, population-based data were collected by the Vital Statistics branch of the California Department of Health Services. Approximately 2.6 million records of all live California births with a birth certificate in 2000-2004 were included. Analysis focused on prenatal care receipt and population characteristics associated with lack of adequate prenatal care, especially among Asian and Pacific Islander groups.Pacific Islanders (n = 11,962) were the most likely, compared to any other racial/ethnic group, to have inadequate prenatal care (OR = 2.9, 95% CIs 2.8-3.1), even when controlling for factors known to affect care receipt, specifically maternal age, educational attainment, parity, insurance, geographical region of residence, and maternal place of birth. In contrast, Asian women (n = 295,741) received care closer to that of the White reference group (OR = 1.5, 95% CIs 1.5-1.5). Among Pacific Islanders, Samoans (OR = 3.0, 95% CIs 2.7-3.4) were at particular risk of inadequate care compared to other PI sub-groups.Pacific Islander women received less adequate prenatal care than women of other racial/ethnic groups. The common practice of combining Asians and Pacific Islanders into a single A/PI category may mask needs in the Pacific Islander community. Therefore, in order to continue to reduce health disparities, it may be necessary to collect separate data on these two distinct populations in order to be able to appropriately direct programs and resources.
View details for DOI 10.1007/s10995-009-0494-x
View details for Web of Science ID 000279477400017
View details for PubMedID 19582560
Validation of the Edinburgh Postnatal Depression Scale among women in a high HIV prevalence area in urban Zimbabwe
ARCHIVES OF WOMENS MENTAL HEALTH
2010; 13 (3): 201-206
Despite the significant burden of common mental disorders (CMD) among women in sub Saharan Africa, data on postnatal depression (PND) is very limited, especially in settings with a high HIV prevalence. The Edinburgh Postnatal Depression Scale (EPDS), a widely used screening test for PND has been validated in many countries, but not in Zimbabwe. We assessed the validity of the EPDS scale among postpartum women compared with Diagnostic Manual of Mental Disorders (DSM-IV) criteria for major depression. Six trained community counselors administered the Shona version of the EPDS to a random sample of 210 postpartum HIV-infected and uninfected women attending two primary care clinics in Chitungwiza. All women were subsequently subjected to mental status examination using DSM IV criteria for major depression by 2 psychiatrists, who were blinded to the subject's EPDS scores. Data were analyzed using receiver operating characteristic (ROC) curve analysis. Of the 210 postpartum mothers enrolled, 64 (33%) met DSM IV criteria for depression. Using a cut-off score of 11/12 on the Shona version of the EPDS for depression, the sensitivity was 88%, and specificity was 87%, with a positive predictive value of 74%, a negative predictive value of 94%, and an area under the curve of 0.82. Cronbach's alpha coefficient for the whole scale was 0.87. Conclusion: The Shona version of the EPDS is a reliable and valid tool to screen for PND among HIV-infected and un-infected women in Zimbabwe. Screening for PND should be integrated into routine antenatal and postnatal care in areas with high HIV prevalence.
View details for DOI 10.1007/s00737-009-0073-6
View details for Web of Science ID 000277935600004
View details for PubMedID 19760051
Prenatal Screening for Infectious Diseases: An Analysis of Disparities and Adherence to Policy in California
MATERNAL AND CHILD HEALTH JOURNAL
2009; 13 (2): 260-267
Prenatal infectious diseases are a major cause of mortality and morbidity among newborns, but many are preventable with proper maternal screening and treatment. METHODS; Adherence to prenatal infectious disease screening guidelines and demographic factors that influence adherence were determined utilizing existing data on 1837 live births from 1999-2003.We found higher rates of testing for syphilis (94.54%), rubella (92.69%) and hepatitis B (94.23%) than for HIV (73.82%) and GBS (69.05%). Adherence to testing guidelines varied by both disease and maternal factors. Lack of insurance, geographic location, inadequate prenatal care and incarceration were the main maternal factors associated with lack of testing.Disease screening rates may be improved by reducing socioeconomic barriers to prenatal testing, supporting access to insurance, eliminating provider biases and providing adequate prenatal care.
View details for DOI 10.1007/s10995-008-0341-5
View details for Web of Science ID 000263081300012
View details for PubMedID 18446431
- Increased Uptake of HIV Testing With the Integration of Nurse-Initiated HIV Testing Into Routine Prenatal Care JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES 2008; 49 (5): 571-573
Patient acceptance of and satisfaction with rapid HIV testing in a labor and delivery setting
JOURNAL OF WOMENS HEALTH
2008; 17 (3): 465-471
To evaluate women's acceptance of and satisfaction with rapid human immunodeficiency virus (HIV) testing in a labor and delivery (L&D) setting.We conducted a cross-sectional survey of pregnant women who underwent counseling for rapid HIV testing in an L&D unit at a university-affiliated urban hospital from April 1, 2005, to July 15, 2006. Medical chart abstractions were performed for all 158 eligible women, and a convenience sample of 46 women also completed a survey evaluating their satisfaction using a validated decisional conflict scale.Uptake of rapid HIV testing was 98.1% (155 of 158). Overall, 89.1% of the 46 surveyed women reported feeling satisfied with their testing experience, and 82.6% of women reported no decisional conflict in making decisions for rapid testing; 9% of women reported decisional conflict. The median decisional conflict score on a scale of 0-100 was 5 (mean 11.6, SD 16). In addition, most women reported feeling certain about their decision to test (87.0%), feeling informed about testing (76.1%), having high levels of clarity about their values regarding testing (76.1%), and feeling supported in their decision-making process (76.1%).In this study population, there was a high level of acceptance and satisfaction with rapid HIV testing in the L&D setting. Rapid HIV testing is a vital component of perinatal HIV transmission prevention, as well as being an opportunity for women, some of whom have little contact with the healthcare system, to learn their HIV status.
View details for DOI 10.1089/jwh.2007.0545
View details for Web of Science ID 000254734800015
View details for PubMedID 18373491
The feasibility of preventing mother-to-child transmission of HIV using peer counselors in Zimbabwe.
AIDS research and therapy
2008; 5: 17-?
Prevention of mother-to-child transmission of HIV (PMTCT) is a major public health challenge in Zimbabwe.Using trained peer counselors, a nevirapine (NVP)-based PMTCT program was implemented as part of routine care in urban antenatal clinics.Between October 2002 and December 2004, a total of 19,279 women presented for antenatal care. Of these, 18,817 (98%) underwent pre-test counseling; 10,513 (56%) accepted HIV testing, of whom 1986 (19%) were HIV-infected. Overall, 9696 (92%) of women collected results and received individual post-test counseling. Only 288 men opted for HIV testing. Of the 1807 HIV-infected women who received posttest counseling, 1387 (77%) collected NVP tablet and 727 (40%) delivered at the clinics. Of the 1986 HIV-infected women, 691 (35%) received NVPsd at onset of labor, and 615 (31%) infants received NVPsd. Of the 727 HIV-infected women who delivered in the clinics, only 396 women returned to the clinic with their infants for the 6-week follow-up visit; of these mothers, 258 (59%) joined support groups and 234 (53%) opted for contraception. By the end of the study period, 209 (53%) of mother-infant pairs (n = 396) came to the clinic for at least 3 follow-up visits.Despite considerable challenges and limited resources, it was feasible to implement a PMTCT program using peer counselors in urban clinics in Zimbabwe.
View details for DOI 10.1186/1742-6405-5-17
View details for PubMedID 18673571
Impact of fetal and neonatal viral (and parasitic) infections on later development and disease outcome
WINDOW OF OPPORTUNITY: PRE-PREGNANCY TO 24 MONTHS OF AGE
2008; 61: 225-242
It is estimated that there are 4 million neonatal deaths and an equal number of stillbirths annually, the majority in the developing world. Neonatal deaths account for one third of deaths in children less than 5 years of age, and at least one third of neonatal deaths are related to infections. Infections also account for 80% of deaths in the postneonatal period through 5 years of age. There are several viral and parasitic infections which produce fetal and neonatal morbidity and mortality. Neonatal infections occur during one or more perinatal periods: in utero (congenital), intrapartum (during labor and delivery), and early or late postpartum. Here the term perinatal refers to all of these stages of fetal or neonatal infections. The mechanisms of perinatal viral and parasitic infections vary depending on the specific pathogen, however, all begin with maternal infection. Following maternal infection, organisms may produce indirect placental infection with or without fetal infection, direct fetal or neonatal infection, or primary maternal infection and subsequent perinatal sequelae without either placental or fetal infection. Some pathogens may produce infections by more than one mechanism. This brief report will provide an overview of the pathogenesis, general outcomes, and known pathogens associated with perinatal viral and parasitic infections.
View details for Web of Science ID 000253942500015
View details for PubMedID 18196955
Routine offer of antenatal HIV testing ( "opt-out" approach) to prevent mother-to-child transmission of HIV in urban Zimbabwe
BULLETIN OF THE WORLD HEALTH ORGANIZATION
2007; 85 (11): 843-850
To assess the impact of routine antenatal HIV testing for preventing mother-to-child transmission of HIV (PMTCT) in urban Zimbabwe.Community counsellors were trained in routine HIV testing policy using a specific training module from June 2005 through November 2005. Key outcomes during the first 6 months of routine testing were compared with the prior 6-month "opt-in" period, and clients were interviewed.Of the 4551 women presenting for antenatal care during the first 6 months of routine HIV testing, 4547 (99.9%) were tested for HIV compared with 3058 (65%) of 4700 women during the last 6 months of the opt-in testing (P < 0.001), with a corresponding increase in the numbers of HIV-infected women identified antenatally (926 compared with 513, P < 0.001). During routine testing, more HIV-infected women collected results compared to the opt-in testing (908 compared with 487, P < 0.001) resulting in a significant increase in deliveries by HIV-infected women (256 compared with 186, P = 0.001); more mother/infant pairs received antiretroviral prophylaxis (n = 256) compared to the opt-in testing (n = 185); and more mother/infant pairs followed up at clinics (105 compared with 49, P = 0.002). Women were satisfied with counselling services and most (89%) stated that offering routine testing is helpful. HIV-infected women reported low levels of spousal abuse and other adverse social consequences.Routine antenatal HIV testing should be implemented at all sites in Zimbabwe to maximize the public health impact of PMTCT.
View details for DOI 10.2471/BLT.06.035188
View details for Web of Science ID 000250858300011
View details for PubMedID 18038074
Shedding and reversion of oral polio vaccine type 3 in Mexican vaccinees: Comparison of mutant analysis by PCR and enzyme cleavage to a real-time PCR assay
JOURNAL OF CLINICAL MICROBIOLOGY
2007; 45 (8): 2419-2425
A uracil-to-cytosine mutation at nucleotide position 472 of oral poliovirus vaccine type 3 (OPV3) contributes to the development of vaccine-associated paralytic poliomyelitis (VAPP). To analyze OPV3 shedding patterns, we previously used the multistep method of mutant analysis by PCR and enzyme cleavage (MAPREC). This involves conventional reverse transcription-PCR to detect OPV3, followed by a restriction digest to quantify position 472 reversion. Real-time PCR detects and quantifies nucleic acid as PCR occurs and avoids postreaction processing. The goal of this study was to compare a real-time PCR method to MAPREC. Seventy-three stool samples from Mexican OPV recipients underwent the reverse transcription-PCR step of MAPREC and real-time PCR. Real-time PCR identified 23% more OPV3-positive samples than conventional reverse transcription-PCR. When reversion was compared, the revertant proportion (RP), defined as the percentage of revertants in a sample, differed by < or =10% in 21/25 (84%) samples. The four samples differing by >10% were obtained within 5 days of OPV administration. The real-time PCR assay identified samples with an RP of > or =85% with 94% sensitivity and 86% specificity compared to MAPREC. The mean difference in RP between the two methods was 3.6% (95% confidence interval, -0.3 to 7.5%). Real-time PCR methods reliably detect OPV3, and reversion estimates correlate more consistently with MAPREC when OPV3 reversion rates are high. Detecting VAPP-related mutations by real-time PCR is rapid and efficient and can be useful in monitoring ongoing global polio eradication efforts.
View details for DOI 10.1128/JCM.02268-06
View details for Web of Science ID 000248793300011
View details for PubMedID 17581940
The effectiveness of state and national policy on the implementation of perinatal HIV prevention interventions
AMERICAN JOURNAL OF PUBLIC HEALTH
2007; 97 (6): 1041-1046
The 1994 and 1995 US Public Health Service Guidelines regarding HIV testing and treatment for pregnant women and the resulting 1995 California law mandating an HIV test and treatment offer to every pregnant woman aim to reduce perinatal HIV transmission. However, the effectiveness of such policies after implementation is often unclear. We analyzed the association between these policies and offers of HIV tests and treatment to HIV-infected women in California.Data from active, population-based surveillance of 496 HIV-infected women and their infants, collected from 1987 to 2002, were analyzed to compare rates of offers of HIV tests and treatment before and after 1996.We found significant increases in offers of HIV tests (P<.001) and offers of treatment (P<.001) when we compared women who delivered between 1987 and 1995 with those who delivered between 1996 and 2002. Receipt of prenatal care was the major predictor of both test and treatment offer. A significant shift in reported HIV risk factors was also evident between the 2 groups.Our findings of increased offers of HIV tests and treatment to HIV-infected pregnant women suggest that the national guidelines and the 1996 California law improved health care for these women, which may lessen the risk of perinatal HIV transmission.
View details for DOI 10.2105/AJPH.2005.072371
View details for Web of Science ID 000246867200016
View details for PubMedID 17463383
Disease progression among HIV-infected children who receive perinatal zidovudine prophylaxis
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
2007; 44 (1): 106-111
Studies of perinatal HIV infection have reported mixed results regarding the prognosis of HIV-infected infants exposed to perinatal zidovudine prophylaxis (PZP).We have followed a population-based cohort of children with perinatal HIV infection to evaluate whether early HIV disease progression was more common among those who received PZP and whether subsequent antiretroviral therapy (ART) was less effective in preventing early disease progression.We identified 73 children with perinatal HIV infection born between 1994 and 2001 with at least 3 years of follow-up and with information concerning PZP administration. Children who received PZP started subsequent ART at an earlier age than those who did not receive PZP (median age at starting treatment: 2 months for PZP vs. 6 months for no PZP; P = 0.0002). PZP was associated with decreased early HIV progression: 21% (7 of 33) of children who received PZP progressed to a category C diagnosis by 3 years compared with 45% (18 of 40) of children who did not receive PZP (P = 0.047). Children who did not receive PZP progressed to a category C diagnosis at a younger age than children who received PZP (median: 4 vs. 11 months; P = 0.061). ART was as effective in preventing early HIV progression in children who received PZP as in children who did not receive PZP.In our population-based cohort of perinatally HIV-infected children, those who received PZP started ART at a significantly earlier age than those who did not receive PZP and also demonstrated decreased HIV disease progression by the age of 3 years.
View details for Web of Science ID 000243189400016
View details for PubMedID 17075392
A comparison of perinatal HIV prevention opportunities for Hispanic and non-Hispanic women in California
AIDS EDUCATION AND PREVENTION
2006; 18 (5): 430-443
Using a semi-structured survey and convenience sample of pregnant/recently delivered Hispanic (n = 453) and non-Hispanic (n = 904) women in four California counties, this study compared rates of timely prenatal care (PNC) initiation, HIV test counseling, test offering, and test acceptance in PNC between Hispanic and non-Hispanic women. Hispanic women were less likely to report timely PNC initiation (69.3% vs. 80.4%, p < .0001), receiving test offer (69.5% vs. 76.7%, p = .002), and ever having been tested (77.3% vs. 87.9%, p < .0001) than non-Hispanic women. Hispanic women were more likely to report not knowing where to go (p = .04) and having no insurance (p < .001), transportation (p = .001), and child care (p = .007) as reasons for late PNC start. Both Hispanic and non-Hispanic women most commonly accepted a test offer for their health/health of their baby; Hispanic women were more likely to accept based on doctor/nurse recommendation (80.1% vs. 62.7%, p < .001). A quarter of Hispanic and non-Hispanic women reported they didn't feel they had a choice or that test was done automatically. Efforts to improve perinatal HIV prevention opportunities for all women in California are required. Furthermore, Hispanic women may have disparities in receipt of prenatal care and HIV test offer that need additional attention.
View details for Web of Science ID 000241078100005
View details for PubMedID 17067254
Range of normal neutrophil counts in healthy Zimbabwean infants: Implications for monitoring antiretroviral drug toxicity
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
2006; 42 (4): 460-463
Mother-to-child HIV prevention trials in sub-Saharan Africa use the US National Institutes of Health Division of AIDS (DAIDS) grading scale to monitor hematologic toxicity. A recent study of nevirapine prophylaxis given for 6 months in breast-feeding Zimbabwean infants reported several cases of relative neutropenia in clinically well infants, raising concerns of drug toxicity. However, the DAIDS tables are based on normal blood counts for white infants, although there is evidence that black African infants may have lower absolute neutrophil counts (ANCs) than white infants. To establish normal hematologic values in black Zimbabwean infants and to quantify the apparent prevalence of relative neutropenia in this population, we evaluated HIV-uninfected healthy infants born to HIV-uninfected women at birth, 10 days, 6 weeks, 3, and 4 months of life. A physical examination and blood count were performed at each visit, and an HIV test was performed at the final visit. The ANC values were graded using the DAIDS table. A total of 145 healthy term infants satisfied the inclusion criteria. The mean ANC values for Zimbabwean infants were less than half of the corresponding standard values at all 5 time points (P < 0.0001). Using the DAIDS table in use at the time that the blood was collected, 57% of these healthy infants had relative neutropenia of any grade at birth, followed by 29% at day 10, 53% at 6 weeks, 32% at 3 months, and 37% at 4 months of life. Our data indicate that relative neutropenia exists in healthy black Zimbabwean infants. The guidelines for identifying toxicity were changed in December 2004. However, even by the new DAIDS tables, 43%, 23%, 24%, 42%, and 43% of these healthy babies had relative neutropenia at the time of the 5 visits. Future HIV prevention and treatment trials in sub-Saharan Africa should use normal hematologic values derived from African infants to avoid the overestimation of antiretroviral drug toxicity.
View details for Web of Science ID 000239129100011
View details for PubMedID 16810112
Immunogenicity of aerosol measles vaccine given as the primary measles immunization to nine-month-old Mexican children
2006; 24 (5): 683-690
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
Screening for psychological morbidity in HIV-infected and HIV-uninfected pregnant women using community counselors in Zimbabwe.
Journal of the International Association of Physicians in AIDS Care (Chicago, Ill. : 2002)
2005; 4 (4): 83-88
To examine the prevalence of psychological morbidity in HIV-infected and uninfected pregnant women seeking antenatal care in Zimbabwe.Pregnant women were screened for psychological morbidity at the initial antenatal care visit using the 14-item Shona Symptom Questionnaire (SSQ) before voluntary HIV counseling and testing (VCT). The primary outcome measure was "cases," as determined by a SSQ score of >or= 8. Demographic characteristics and HIV status were compared between cases and noncases to determine the risk factors for psychological morbidity.Of the 437 participants, psychological morbidity was detected in 73 (17%) women before undergoing VCT. Risk factors for psychological morbidity included having a spouse older than 35 years of age. HIV infection by itself was not a risk factor for psychological morbidity for women.There is a high burden of psychological morbidity among pregnant women in Zimbabwe. Mental health services should be integrated into antenatal care to improve psychological health for all women in Zimbabwe.
View details for PubMedID 16533796
The feasibility of voluntary counselling and HIV testing for pregnant women using community volunteers in Zimbabwe
INTERNATIONAL JOURNAL OF STD & AIDS
2005; 16 (11): 755-759
The purpose of this pilot project was to assess the feasibility and acceptability of voluntary counselling and HIV testing (VCT) by pregnant women using community volunteers in Zimbabwe to prevent mother to child transmission (MTCT) of HIV. From July 1999 to June 2001, a short-course zidovudine (ZDV)-based perinatal HIV prevention programme was initiated in two antenatal clinics. Community volunteers, recruited from local community organizations, underwent a two-week training course in VCT, which included HIV/AIDS facts, systematic counselling approach, and practical counselling techniques using scripts and role-play. Rapid HIV testing was performed after informed consent. Lay counsellors conducted individual pre- and post-test counselling for HIV. A total of 35 women community volunteers were trained in VCT; 34 graduated and committed to work four hours per week in the clinic. Of the 6051 pregnant women presenting for antenatal clinics (ANC), 1824 (30%) underwent pre-test counselling and 1547 (26%) were tested, and 429 (28%) were HIV infected. Overall, 1283 (83%) returned for their test results including 406 (95%) of HIV-infected women. Of the 406 HIV-infected women who collected their test results, only 203 (50%) opted for ZDV prophylaxis to prevent MTCT of HIV. Over the two-year study period, two counsellors died and three sought employment at other organizations. Adherence to duty roster was 97% and no breach of confidentiality was reported. Despite many challenges, VCT delivered by community volunteers is feasible and acceptable for pregnant women aiming to reduce their risk of transmitting HIV to their infants. This programme is being implemented at several urban and rural MTCT sites in Zimbabwe and can serve as a model for other resource-poor countries.
View details for Web of Science ID 000233349700010
View details for PubMedID 16303072
Breast-milk shedding of drug-resistant HIV-1 subtype C in women exposed to single-dose nevirapine
JOURNAL OF INFECTIOUS DISEASES
2005; 192 (7): 1260-1264
Single-dose nevirapine reduces intrapartum human immunodeficiency virus 1 type (HIV-1) transmission but may also select for nonnucleoside reverse-transcriptase inhibitor (NNRTI) resistance in breast milk (BM) and plasma. Among 32 Zimbabwean women, median 8-week postpartum plasma and BM HIV-1 RNA levels were 4.57 and 2.13 log(10) copies/mL, respectively. BM samples from women with laboratory-diagnosed mastitis (defined as elevated BM Na(+) levels) were 5.4-fold more likely to have HIV-1 RNA levels above the median. BM RT sequences were not obtained for 12 women with BM HIV-1 RNA levels below the lower limit of detection of the assay used. In 20 paired BM and plasma samples, 65% of BM and 50% of plasma RT sequences had NNRTI-resistance mutations, with divergent mutation patterns.
View details for Web of Science ID 000231623700019
View details for PubMedID 16136470
Temporal trends in early clinical manifestations of perinatal HIV infection in a population-based cohort
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
2005; 293 (18): 2221-2231
The effect of early antiretroviral therapy (ART) on the early progression of perinatal human immunodeficiency virus (HIV) infection is not well defined.To examine early disease progression and survival in a population-based cohort with perinatal HIV infection in relation to year of birth and use of ART.Retrospective study of temporal trends in early progression of perinatal HIV infection among 205 HIV-infected children in Northern California born between January 1, 1988, and December 31, 2001, and followed up through age 3 years.Prevalence of and age at progression to a first US Centers for Disease Control and Prevention category C diagnosis relative to year of birth, type of ART, and age at initiation of therapy.Of 205 children, 134 (65%) received ART and/or Pneumocystis jiroveci pneumonia prophylaxis. By age 3 years, 81 (40%) progressed to a category C diagnosis, 41 (51%) of whom died. Untreated children were significantly more likely to progress to a category C diagnosis (62% [44/71] untreated vs 28% [37/134] treated children, P<.001); none of 23 infants who received triple ART progressed to category C. However, even without triple ART, very early mono/dual ART (by age 2 months vs 3-4 months) was associated with delayed and decreased progression to category C (P = .02). Of 33 children born between January 1, 1996, and December 31, 2001, only 7 (21%) progressed to category C (P = .02 compared with 1988-1995), 6 of 7 of whom received no therapy. More recent year of birth and more advanced therapy were associated with improved survival.This population-based cohort demonstrated decreased early HIV progression and improved survival at age 3 years, associated with more advanced therapy. Although limited by small sample size, the findings suggest that very early treatment, even without triple ART, was associated with improved outcome.
View details for Web of Science ID 000228981100023
View details for PubMedID 15886377
Unique challenges to preventing perinatal HIV transmission among Hispanic women in California: Results of a needs assessment
AIDS EDUCATION AND PREVENTION
2005; 17 (1): 22-40
To identify rates and factors associated with timely prenatal care (PNC) initiation, HIV test counseling, test offering, and test offer acceptance, we conducted a semistructured survey of a convenience sample of pregnant/recently delivered Hispanic women (n=453, 418 with analyzable data) in four California counties in 2000. Only 68.4% and 43.5% of Hispanic women reported receiving an HIV test offer and counseling, respectively, though 88.8% of those offered a test accepted. After controlling for the effects of age, education, years lived in the United States, health insurance coverage, delivery status, and parity, Hispanic women who initiated prenatal care in the first trimester were 1.7 times more likely to be offered an HIV test and almost 3 times more likely to receive counseling than women with a later prenatal care start or no prenatal care. Factors associated with timely PNC initiation on multivariate analysis were private/HMO insurance (OR=10.7, p < .001), Medi-Cal insurance (OR = 4.32, p < .001), being 25-30 years old (OR = 3.0, p = .008), and completion of high school (OR = 2.07, p = .01). Key opportunities to prevent perinatal HIV transmission are being lost for Hispanic women in California. Interventions to increase timely PNC initiation, and to improve test offering by health care providers, may help to improve counseling and testing rates for this population.
View details for Web of Science ID 000227275300003
View details for PubMedID 15843108
Shedding of Sabin poliovirus type 3 containing the nucleotide 472 uracil-to-cytosine point mutation after administration of oral poliovirus vaccine
JOURNAL OF INFECTIOUS DISEASES
2004; 190 (2): 409-416
A uracil-to-cytosine point mutation at nucleotide (nt) 472 of Sabin oral poliovirus vaccine (OPV) type 3 is found in conjunction with vaccine-associated paralytic poliomyelitis (VAPP). Direct RNA extraction and mutant analysis by polymerase chain reaction and restriction enzyme cleavage were used to identify this point mutation in clinical samples. A total of 238 stool samples were obtained from 28 healthy infants for 6 weeks after OPV vaccination. More than 25% of infants shed OPV3 in the week after vaccination, with a decrease on day 6. A second wave of OPV3 shedding occurred beginning the second week after vaccination and was maintained through the end of the study period. During the first week after vaccination, the proportion of nt 472 mutants in the shed OPV3 increased from undetectable to almost 100%. During the second shedding period, the proportion of nt 472 mutants remained close to 100%. These results suggest that selective mutation drives the VAPP-associated nt 472 point mutation for OPV3 in the human gastrointestinal tract.
View details for Web of Science ID 000222254800028
View details for PubMedID 15216480
Humoral and cell-mediated immune responses to an early 2-dose measles vaccination regimen in the United States
JOURNAL OF INFECTIOUS DISEASES
2004; 190 (1): 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 Web of Science ID 000222002700010
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 Web of Science ID 000222411500014
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
Safety and Trough Concentrations of Nevirapine Prophylaxis Given Daily, Twice Weekly, or Weekly in Breast-Feeding Infants From Birth to 6 Months
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
2003; 34 (5): 482-490
Despite the success of antiretroviral prophylaxis in reducing mother-to-child HIV-1 transmission, postpartum transmission through breast milk remains a problem. Antiretroviral administration to the infant during the period of breast-feeding could protect against postnatal transmission. An open-label phase 1/2 study was designed to assess the safety and trough concentrations of nevirapine (NVP) given once weekly (OW), twice weekly (TW), or once daily (OD) to HIV-exposed breast-feeding infants for 24 weeks. Following maternal dosing with 200 mg NVP orally at onset of labor, breast-feeding infants were randomized within 48 hours of birth to 1 of 3 regimens: arm 1, NVP given OW (4 mg/kg from birth to 14 days, upward arrow to 8 mg/kg from 15 days to 24 weeks), arm 2, NVP given TW (4 mg/kg from birth to 14 days, upward arrow to 8 mg/kg from 15 days to 24 weeks), and arm 3, NVP given OD (2 mg/kg from birth to 14 days, upward arrow to 4 mg/kg from 15 days to 24 weeks). Trough NVP concentrations and clinical and laboratory abnormalities were monitored. Of the 75 infants randomized (26 to OW, 25 to TW, and 24 to OD dosing), 63 completed the 32-week follow-up visit. No severe skin, hepatic, or renal toxicity related to NVP was observed. Neutropenia occurred in 8 infants. Trough NVP levels were lower than the therapeutic target (100 ng/mL) in 48 of 75 (64.0%) samples from infants in the OW arm, 3 of 65 (4.6%) samples in the TW arm, and 0 of 72 samples in the OD arm. Median (range) trough NVP concentrations were 64 ng/mL (range: <25-1519 ng/mL) with OW dosing; 459 (range: <25-1386 ng/mL) with TW dosing; and 1348 (range: 108-4843 ng/ml) with OD dosing. Our data indicate that NVP prophylaxis for 6 months was safe and well tolerated in infants. OD NVP dosing resulted in all infants with trough concentration greater than the therapeutic target and maintenance of high drug concentrations. A phase 3 study is planned to assess the efficacy of OD infant NVP regimen to prevent breast-feeding HIV-1 transmission.
View details for Web of Science ID 000206324300006
View details for PubMedID 14657758
Measles and mumps vaccination as a model to investigate the developing immune system: passive and active immunity during the first year of life
2003; 21 (24): 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 Web of Science ID 000184402300012
View details for PubMedID 12850348
Direct extraction of Sabin poliovirus genomes from human fecal samples using a guanidine thiocyanate extraction method
JOURNAL OF VIROLOGICAL METHODS
2003; 110 (2): 193-200
To permit rapid and efficient detection of Sabin poliovirus type 3 from human fecal samples, we developed a guanidine thiocyanate (GuSCN) extraction and reverse transcriptase polymerase chain reaction (RT-PCR) method. Using 10-fold serial dilutions from stock Sabin-Leon 12 a1b poliovirus type 3 at 10(7) TCID(50) per 0.1 ml, genome was detected to a dilution of 10(3) TCID(50) per 0.1 ml. A total of 40 archived fecal samples were examined using this GuSCN extraction method followed by RT-PCR. Fourteen of 20 poliovirus type 3 tissue culture-positive specimens (70%) and two of 20 tissue culture-negative specimens (10%) were detected by GuSCN extraction and RT-PCR. All positive and negative extraction and RT-PCR controls were identified accurately. This GuSCN extraction and RT-PCR technique is rapid, inexpensive, and can be readily adapted to identify genome sequences of other enterovirus types in large numbers of fecal samples. Moreover, the GuSCN technique extracts viral RNA directly from fecal samples, allowing observation of in vivo alterations of genome sequences. Further studies are underway to examine the development of revertant point mutations in the Sabin poliovirus type 3 genome following oral administration of trivalent Sabin Oral Poliovirus Vaccine to humans.
View details for DOI 10.1016/S0166-0934(03)00133-2
View details for Web of Science ID 000183669500011
View details for PubMedID 12798248
- Current controversies in vaccination - Vaccine safety JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION 2002; 288 (24): 3155-3158
Group A streptococcal meningitis: Report of a case and review of literature since 1976
PEDIATRIC EMERGENCY CARE
2001; 17 (6): 430-434
Group A streptococcal (GAS) invasive disease has become increasingly common in recent years. However, acute bacterial meningitis caused by this pathogen is unusual. We report a case of GAS meningitis in a previously healthy 21/2-year-old child associated with a dramatically rapid course and fatal outcome. A literature review of previously reported cases is presented. This case serves as a reminder that GAS can cause severe meningitis in otherwise healthy hosts.
View details for Web of Science ID 000173001500007
View details for PubMedID 11753187
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
Patterns of health seeking behavior during episodes of childhood diarrhea: a study of Tzotzil-speaking Mayans in the highlands of Chiapas, Mexico
SOCIAL SCIENCE & MEDICINE
1999; 48 (4): 489-495
In Chiapas, Mexico, diarrheal disease causes the majority of all deaths in children under the age of five. Treatment of childhood diarrhea may be influenced by local beliefs and cultural practices. Few studies have attempted to quantitatively evaluate health seeking behavior (HSB) for diarrheal diseases in indigenous communities, while controlling for potential confounding factors such as parental education or socioeconomic status. A rapid ethnographic survey was conducted in Nabenchauc, Chiapas, to determine hypothetical HSB patterns for each of four major types of childhood diarrhea. Additionally, we examined the actual HSB for the last episode of childhood diarrheal illness within the household. One hundred households participated in the survey; 94 households with children < 5 years old reported a mean of 1.9 diarrheal episodes during the preceding month. Households reported using a mean of 1.3 types of in-home remedies. Oral rehydration therapy (ORT) was used in <2% of the 368 HSB patterns elicited for the four types of diarrhea. HSB patterns utilized an eclectic combination of traditional, allopathic, local and distant health care options. A mean of 2.5 outside-the-home health care options were reported for each diarrheal type; the local grocery store was reported in 245 (67%) of the hypothetical HSB patterns and as a first option in 199 (54%). Maternal and/or paternal education had little impact on hypothetical HSB. Households with lower SES were more likely to report using local grocery stores as a first option and were less likely to use options outside the village. The rapid ethnographic survey approach allows for assessment of changes in the approach to health care option utilization in cultures incorporating new health care paradigms. Public health interventions targeting local stores may lead to increased use of ORT, thereby potentially reducing early morbidity and mortality due to childhood diarrhea.
View details for Web of Science ID 000077986300005
View details for PubMedID 10075174
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
Population-based prevalence of symptomatic and asymptomatic astrovirus infection in rural Mayan infants
JOURNAL OF INFECTIOUS DISEASES
1998; 178 (2): 334-339
Symptomatic and asymptomatic astrovirus infection was prospectively determined in a 3-year birth cohort of Mayan infants. Stool samples from 271 infants and 268 older siblings were tested for astrovirus, adenovirus 40/41, rotavirus and Salmonella, Shigella and Campylobacter species. Concurrent diarrhea, vomiting, fever, or anorexia were noted. Astrovirus was detected in 164 infants (61%) and 20 siblings (7%). Rotavirus (4%) and adenovirus 40/41 (13%) were isolated less frequently. Of all diarrheal episodes reported at a visit, 26% (78/305) were associated with astrovirus; 17% (78/452) of astrovirus infections were associated with diarrhea and 9% with other symptoms. Only diarrhea was associated with astrovirus infection (odds ratio, 1.4; 95% confidence interval [CI], 1.07-1.92; P = .01). Of infants with astrovirus, 70% shed at multiple visits over a period of 2-17 weeks (median, 5). The point prevalence of astrovirus infection was significantly higher among infants than siblings (relative risk, 6.18; 95% CI, 3.93-9.72; P < .0001, chi2). Astrovirus was identified throughout the year, peaked in March and May, and decreased in September. In this population, astrovirus was the most common enteric pathogen isolated; symptomatic infection was prevalent among infants.
View details for Web of Science ID 000075153000007
View details for PubMedID 9697712
Mortality in the first 2 years among infants born to human immunodeficiency virus-infected women in Harare, Zimbabwe
JOURNAL OF INFECTIOUS DISEASES
1998; 178 (1): 109-113
Transmission of human immunodeficiency virus (HIV) and mortality was studied among infants of infected women in Zimbabwe. Of 367 infants born to HIV-infected women, 72 (19.6%) died compared with 20 (5.4%) of 372 infants of uninfected women (P < .01). Infection by HIV DNA polymerase chain reaction among infants who survived >7 days and died within 2 years could be assessed in 87% (58/67) of infants of infected women and 83% (5/6) of infants of uninfected women; transmission occurred in 40 of 58 infants. Among 27 infected infants tested at birth, 19 (70%), 5 (19%), and 3 (11%) were apparently infected via in utero, intrapartum or early postpartum, and late postpartum transmission, respectively. The majority of HIV-infected infants who died in the first 2 years of life were likely to have acquired in utero infection.
View details for Web of Science ID 000074357900014
View details for PubMedID 9652429
Pneumocystis carinii pneumonia prophylaxis and early clinical manifestations of severe perinatal human immunodeficiency virus type 1 infection
PEDIATRIC INFECTIOUS DISEASE JOURNAL
1998; 17 (5): 398-402
Some children with perinatal HIV infection develop early progression to severe symptoms (Category C) within the first 4 years of life. Prophylactic therapy with trimethoprim-sulfamethoxazole (TMP/SMX) may affect progression by decreasing the incidence of Pneumocystis carinii pneumonia (PCP).HIV progression to Category C in the first 3 years of life was retrospectively analyzed in a population-based cohort of children with perinatal HIV infection followed for > or = 3 years from birth. Time to development of Category C and clinical patterns of new Category C diagnoses were examined in relation to patterns of PCP prophylaxis before diagnosis.Fifty-eight of 147 children developed 67 initial category C diseases by 3 years of age: PCP (n=24), encephalopathy (n=22), other opportunistic infections (n=19) and wasting (n=2). Before diagnosis therapy included TMP/ SMX and zidovudine (ZDV) (n=11), TMP/SMX alone (n=7), ZDV alone (n=1) and neither (n= 39). The probability of developing a Category C diagnosis after 2 years was significantly lower among children who received TMP/SMX compared with those who did not (29%, TMP/SMX vs. 45%, no TMP/SMX; 30%, TMP and ZDV vs. 45%, no therapy; P < 0.01). The frequency of PCP was significantly lower and that of HIV encephalopathy was significantly higher among children receiving TMP/SMX +/- ZDV before Category C diagnosis than among children receiving neither.In this study PCP prophylaxis was associated with longer time to Category C diagnoses in the first 3 years of life. This association was related to a decreased incidence of PCP and an increased incidence of encephalopathy as the first Category C diagnosis among children who received TMP/SMX.
View details for Web of Science ID 000073634500009
View details for PubMedID 9613653
Neutrophil CD11b expression as a diagnostic marker for early-onset neonatal infection
JOURNAL OF PEDIATRICS
1998; 132 (3): 445-451
To determine whether neutrophil surface expression of CD11b predicts early-onset infection or suspected infection in at-risk infants.CD11b expression on peripheral blood neutrophils was determined by flow cytometry of whole blood samples. Blood (0.1 ml) was obtained from a convenience sample of at-risk infants admitted to the neonatal intensive care unit, stained with antibodies detecting CD11b and CD15, chilled, and analyzed within 8 hours. Blood for culture, blood counts, and C-reactive protein (CRP) determination was obtained simultaneously. Subjects were grouped on the basis of culture results and clinical signs, and investigators were blinded to CD11b level.Of 106 subjects, seven had positive bacterial or viral cultures ("confirmed infection"), 17 had clinical signs of infection but negative cultures ("suspected infection"), and 82 had negative cultures and no clinical signs ("no infection"). Neutrophil CD11b was elevated in all infants with confirmed infection, 94% with suspected infection, and none with no infection. The negative and positive predictive values, sensitivity, and specificity were 100%, 99%, 96%, and 100%, respectively, for diagnosis of neonatal infection at initial evaluation. CD11b levels correlated with peak CRP (r2 = 0.76, p < 0.0001); however, CD11b was elevated at the time of admission in all five infants with proven bacterial infection, whereas CRP was normal until the second day in the neonatal intensive care unit in three of these five. Both infants with positive viral cultures had elevated CD11b, but the CRP levels remained within normal limits. The negative predictive value of neutrophil CD11b for identifying suspected or confirmed infection was 99%.This assay for neutrophil CD11b is a promising test for exclusion of early-onset neonatal infection. If validated prospectively, this assay may reduce hospital and antibiotic use in the population of neonates at risk for early-onset infection.
View details for Web of Science ID 000072877800018
View details for PubMedID 9544899
Development of chemiluminescent probe hybridization, RT-PCR and nucleic acid cycle sequencing assays of Sabin type 3 isolates to identify base pair 472 Sabin type 3 mutants associated with vaccine associated paralytic poliomyelitis
JOURNAL OF VIROLOGICAL METHODS
1997; 68 (2): 109-118
Sabin type 3 polio vaccine virus is the most common cause of poliovaccine associated paralytic poliomyelitis. Vaccine associated paralytic poliomyelitis cases have been associated with Sabin type 3 revertants containing a single U to C substitution at bp 472 of Sabin type 3. A rapid method of identification of Sabin type 3 bp 472 mutants is described. An enterovirus group-specific probe for use in a chemiluminescent dot blot hybridization assay was developed to identify enterovirus positive viral lysates. A reverse transcription-polymerase chain reaction (RT-PCR) assay producing a 319 bp PCR product containing the Sabin type 3 bp 472 mutation site was then employed to identify Sabin type 3 isolates. Chemiluminescent nucleic acid cycle sequencing of the purified 319 bp PCR product was then employed to identify nucleic acid sequences at bp 472. The enterovirus group probe hybridization procedure and isolation of the Sabin type 3 PCR product were highly sensitive and specific; nucleic acid cycle sequencing corresponded to the known sequence of stock Sabin type 3 isolates. These methods will be used to identify the Sabin type 3 reversion rate from sequential stool samples of infants obtained after the first and second doses of oral poliovirus vaccine.
View details for Web of Science ID A1997YB42500001
View details for PubMedID 9389400
Clinical and laboratory characteristics of a large cohort of symptomatic, human immunodeficiency virus-infected infants and children
PEDIATRIC INFECTIOUS DISEASE JOURNAL
1996; 15 (11): 1025-1036
View details for Web of Science ID A1996VT45000010
Natural history of human immunodeficiency virus disease in perinatally infected children: An analysis from the pediatric spectrum of disease project
1996; 97 (5): 710-716
To describe the progression of human immunodeficiency virus (HIV) disease through clinical stages from birth to death among a large number of perinatally infected children.The Pediatric Spectrum of Disease (PSD) project, coordinated by the Centers for Disease Control and Prevention (CDC), has conducted active surveillance for HIV disease since 1988 in seven geographic regions. PSD data are collected from medical and social service records every 6 months through practitioners at each participating hospital clinic. We analyzed data from perinatally HIV-infected children born between 1982 and 1993. The natural history of HIV disease was divided into five progressive stages using the clinical categories in the CDC 1994 pediatric HIV classification system: stage N, no signs or symptoms; stage A, mild signs or symptoms; stage B, moderate signs or symptoms; stage C, severe signs or symptoms; and stage D, death. A five-stage Markov model was fitted to the PSD data. To compare the estimates from the PSD project with the published estimates, we also fitted an alternative Markov model using acquired immunodeficiency syndrome (AIDS; 1987 case definition) in place of stage C and also calculated standard Kaplan-Meier estimates.A total of 2148 perinatally HIV-infected children were included in the analysis. The estimated mean times spent in each stage were: N, 10 months; A, 4 months; B, 65 months; and C, 34 months. We estimated that a child born with HIV infection has a 50% (95% confidence interval [CI], 40%-60%) chance of severe signs or symptoms developing by 5 years of age and a 75% (95% CI, 68%-82%) chance of surviving to 5 years of age. For a child in stage B, there is a 60% (95% CI, 49%-71%) chance of severe signs or symptoms developing within the next 5 years and a 65% (95% CI, 56%-73%) chance of surviving 5 more years. The estimated mean time from birth to stage C was 6.6 (95% CI, 5.7-7.5) years, and the estimated mean survival time from birth was 9.4 (95% CI, 8.1-10.7) years. From the alternative Markov model, the estimated mean time from birth to AIDS was 4.8 (95% CI, 4.5-5.2) years.Markov modeling using the revised pediatric classification system allowed us to describe the natural history of HIV disease in children before diagnosis of AIDS. On average, children progress to moderate symptoms in the second year of life and then remain moderately symptomatic for more than half of their expected lives, underscoring their need for clinical care before the onset of AIDS. The results from the Markov model are useful in family counseling, health care planning, and clinical trial designs.
View details for Web of Science ID A1996UH75800018
View details for PubMedID 8628612
Disease patterns and survival after acquired immunodeficiency syndrome diagnosis in human immunodeficiency virus-infected children
PEDIATRIC INFECTIOUS DISEASE JOURNAL
1996; 15 (4): 321-328
The clinical manifestations of HIV infection in children involve a broad spectrum of conditions ranging from mild symptoms to AIDS. Knowledge of the disease and survival patterns of these children are needed to plan for future needs and develop baseline information to evaluate newer prophylactic or therapeutic management options.To identify AIDS-defining conditions and estimate post-AIDS diagnosis survival among HIV-infected children.Disease patterns and survival after the diagnosis of AIDS-defining conditions were studied in 126 children who were identified through a multisite university-based active surveillance system in California from January, 1989, through August, 1993. Hospital medical records were periodically reviewed and data were abstracted onto standardized forms designed for pediatric HIV surveillance. We determined the length of survival between AIDS diagnosis and death and evaluated the impact of disease patterns on survival using Kaplan-Meier's product-limit method and Cox proportional hazards regression.The median age at diagnosis was 13 months for children with perinatally acquired infection and 101.5 months for children infected through other routes of transmission. Pneumocystis carinii pneumonia and lymphoid interstitial pneumonia were the most common AIDS-defining conditions among perinatal cases, whereas the disease patterns observed among nonperinatal cases were more varied. The median postdiagnosis survival for the cohort was 26 months.Survival time did not differ significantly by race/ethnicity, sex or route of transmission. Respiratory candidiasis and wasting syndrome had significant negative impact on survival but P. carinii pneumonia was not associated with shorter survival. Zidovudine or other antiviral therapies was associated with increased survival.
View details for Web of Science ID A1996UE89200007
View details for PubMedID 8866801
EARLY LOSS OF PASSIVE MEASLES ANTIBODY IN INFANTS OF MOTHERS WITH VACCINE-INDUCED IMMUNITY
1995; 96 (3): 447-450
Maternally derived passive measles antibody may interfere with vaccine-induced immunity in infants less than 12 months of age. However, early loss of passive measles antibody may occur in infants of women who received measles vaccine because measles vaccine induces lower antibody titers than does natural infection.Persistence of passive neutralizing measles antibody was studied longitudinally in a group of normal infants as a function of maternal measles titer at birth and maternal date of birth. Maternal serum and cord blood specimens were tested from 162 women and their newborns, from 51 of these infants at 9 months of age and from 63 at 12 months of age.Seventy-one percent of sera from 9-month-old infants (36 of 51, 95% confidence interval 68% to 84%) and 95% of samples from 12-month-old infants (60 of 63, 95% confidence interval 89% to 101%) had no detectable neutralizing measles antibody. Measles geometric mean titers were significantly higher at delivery in mothers whose infants were seropositive at 9 and 12 months compared with mothers whose infants were seronegative at 9 and 12 months. All infants with detectable measles antibody at 9 or 12 months had mothers born before 1963, before the vaccine era, and both material and cord blood measles geometric mean titers decreased significantly with decreasing maternal age.Persistence of passive measles antibody is uncommon by 12 months of age; earlier antibody loss is related to lower maternal age and maternal measles titer.
View details for Web of Science ID A1995RT95400007
View details for PubMedID 7651776
ALTERED REPRESENTATION OF NAIVE AND MEMORY CD8 T-CELL SUBSETS IN HIV-INFECTED CHILDREN
JOURNAL OF CLINICAL INVESTIGATION
1995; 95 (5): 2054-2060
CD8 T cells are divided into naive and memory subsets according to both function and phenotype. In HIV-negative children, the naive subset is present at high frequencies, whereas memory cells are virtually absent. Previous studies have shown that the overall number of CD8 T cells does not decrease in HIV-infected children. In studies here, we use multiparameter flow cytometry to distinguish naive from memory CD8 T cells based on expression of CD11a, CD45RA, and CD62L. With this methodology, we show that within the CD8 T cell population, the naive subset decreases markedly (HIV+ vs. HIV-, 190 vs. 370 cells/microliter; P < or = 0.003), and that there is a reciprocal increase in memory cells, such that the total CD8 T cell counts remained unchanged (800 vs. 860 cells/microliter; P < or = 0.76). In addition, we show that for HIV-infected children, the naive CD8 T cell and total CD4 T cell counts correlate (chi 2 P < or = 0.001). This correlated loss suggests that the loss of naive CD8 T cells in HIV infection may contribute to the defects in cell-mediated immunity which become progressively worse as the HIV disease progresses and CD4 counts decrease.
View details for Web of Science ID A1995QW20500014
View details for PubMedID 7738172
Factors associated with early clinical recognition of children with perinatal human immunodeficiency virus infection. Northern California Pediatric HIV Consortium.
journal of infectious diseases
1995; 171 (3): 689-692
Surveillance of children born to women with human immunodeficiency virus (HIV) infection at five pediatric regional centers assessed times and patterns of clinical recognition in these children. Regional HIV seroprevalences among childbearing women were used to assess the proportion of identified children born to HIV-infected women. In total, 415 children with perinatal HIV exposure were identified. Early age at first HIV evaluation was significantly associated with maternal intravenous drug use (3.2 vs. 7.2 months for other or unknown maternal risk, P = .01), birth county with population > 500,000 (3.5 vs. 8.2 months for population < or = 500,000, P = .003), and hospital with routine HIV screening of pregnant women (0.1 vs. 8.8 months for no screening, P = .006). Race did not correlate with age at first evaluation. Using maternal HIV seroprevalence rates for 1988-1991, 34%-50% of the expected number of infants born to HIV-infected women were in clinical care. Perception of increased maternal risk for HIV infection was associated with early clinical recognition of infants of HIV-infected women.
View details for PubMedID 7876619
BIOLOGIC, FOSTER, AND ADOPTIVE PARENTS - CAREGIVERS OF CHILDREN EXPOSED PERINATALLY TO HUMAN-IMMUNODEFICIENCY-VIRUS IN THE UNITED-STATES
1992; 90 (4): 603-607
Children born to human immunodeficiency virus (HIV)-infected mothers often do not live with a biologic parent because of drug use, illness, or death of the mother. Public health officials need to know the number and proportion of children who will require care by someone other than a biologic parent (alternative care giver). The Pediatric Spectrum of Disease project, conducted in six different geographic regions in the United States, assesses issues specific to HIV in children. Among the information being collected in this study are data regarding the primary care giver. Of 1683 children born to HIV-infected mothers and enrolled through 1990, 55% (937) were living with a biologic parent, 10% (169) with another relative, 28% (455) were in foster care, 3% (55) had been adopted, and 4% (67) lived in group settings or with other care givers. In all locations and for all racial/ethnic groups, children of mothers who used intravenous drugs were more likely to be living with an alternative care giver than were children of mothers who had not used intravenous drugs (odds ratio 4.15). However, there were striking variations by study location (odds ratio range 1.4 to 7.2). The data suggest that maternal drug use may be the most important factor determining whether a child lives with a biologic parent and that there are also regional differences in alternative care placement.
View details for Web of Science ID A1992JT86300018
View details for PubMedID 1408516
BAILLIERES CLINICAL GASTROENTEROLOGY
1990; 4 (3): 609-625
Since their discovery in the 1970s, the human rotaviruses have been recognized as the most important cause of acute infectious gastroenteritis among infants and children worldwide. Rotavirus has been found to infect almost all mammalian and avian species tested, and is primarily a disease of the young. In humans, rotavirus is the most frequent gastrointestinal pathogen in infants and children less than 2 years of age. In developing countries, the attack rate peaks at 6 months of age, whereas in developed areas of the world the virus is most commonly found among children 6-12 months of age. Rotavirus displays a marked seasonality in temperate climates, with the number of cases peaking in the colder winter months. In tropical climates, this seasonality is not as apparent, and infection may occur year round. Symptoms of rotavirus infection are non-specific and include vomiting and diarrhoea, occasionally accompanied by a low grade fever. Dehydration is more common with rotavirus infection than with most bacterial pathogens, and is the most common cause of death related to rotavirus infection. Treatment is non-specific and includes the use of oral rehydration therapy, especially in developing countries where malnutrition is common. Strategies for the prevention of rotavirus infection are dependent on advances in the understanding of the molecular biology of the rotavirus. The genetic structure of the virus has been extensively studied, and a number of the structural proteins have been identified. The neutralization antigens, located on VP4 and VP7, may be important in conferring immunity to rotavirus in vivo. Two animal-derived and several reassortant rotavirus vaccines are currently being evaluated in field studies, and a number of other candidate vaccines are being tested in vitro and in animal studies.
View details for Web of Science ID A1990EN54900003
View details for PubMedID 1962726
EPITOPE-SPECIFIC IMMUNE-RESPONSES TO ROTAVIRUS VACCINATION
1987; 93 (5): 941-950
Rotavirus gastroenteritis is a leading cause of infant mortality in developing countries and an important cause of morbidity in children under 2 yr of age in the United States. Vaccine programs have evaluated animal rotavirus strains that are attenuated in humans but antigenically similar to some human strains. Whether a single vaccine strain can elicit protective immunity in humans to rotaviruses of the same or different serotypes is an important question in determining vaccine efficacy. We used characterized serotype-specific monoclonal antibodies directed at VP7 in a competitive solid-phase immunoassay to measure epitope-specific immune responses to serotypes 1, 2, and 3 in sera of children who received a candidate serotype-3 rotavirus vaccine. Antibodies to serotype 3 were detected in 72% of sera samples, and to serotype 1 and 2 in only 11% each. Also, a VP3-specific monoclonal antibody which neutralizes three serotypically distinct strains of rotavirus was used to detect the presence of similar antibodies in 56% of the test sera. This finding suggests a mechanism of heterotypic immunity.
View details for Web of Science ID A1987K557000004
View details for PubMedID 2443417
SAFETY AND IMMUNOGENICITY OF BOVINE ROTAVIRUS VACCINE RIT-4237 IN 3-MONTH-OLD INFANTS
JOURNAL OF PEDIATRICS
1986; 109 (6): 931-935
To assess the safety and immunogenicity of bovine rotavirus vaccine, we administered attenuated strain RIT 4237 to 54 inner-city infants randomized to one of three groups in a double-blind fashion to receive a dose at 3 and 5 months of age of either placebo, vaccine virus at 10(7) TCID50/ml, or vaccine virus at 10(8) TCID50/ml. Vaccination began in early fall 1984, and continued through spring 1985. Forty-nine infants received one dose of vaccine or placebo; 43 received both doses of vaccine or placebo. At 2 and 3 months after vaccination, homologous geometric mean neutralizing antibody titers were significantly higher in children who received either dose of vaccine compared with placebo recipients. Cumulative seroconversion to bovine rotavirus after either dose of vaccine virus was 87% at 6 months of age. Seroconversion was significantly higher (P less than 0.01) in both vaccine groups compared with the placebo group. No ill effects were associated with vaccine administration. RIT 4237 vaccine appears to be safe and immunogenic when administered to young infants living in the United States.
View details for Web of Science ID A1986F117800003
View details for PubMedID 3537248
Rapid flux in non-nucleoside reverse transcriptase inhibitor resistance mutations among subtype CHIV-1-infected women after single dose nevirapine
INT MEDICAL PRESS LTD. 2003: U78-U79
View details for Web of Science ID 000231265900090
Immune responses to measles and mumps vaccination of infants at 6, 9, and 12 months
UNIV CHICAGO PRESS. 2001: 817-826
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
Developmental maturation of the immune response to measles and mumps live viral vaccines.
OXFORD UNIV PRESS INC. 2000: 223-223
View details for Web of Science ID 000088950900107
The epidemiology of neonatal herpes simplex virus infections in California from 1985 to 1995
OXFORD UNIV PRESS INC. 1999: 199-202
Comprehensive hospital discharge data completed by the California Office of Statewide Health Planning and Development was used to determine whether the proportion of infants =6 weeks of age who were hospitalized with a diagnosis of herpes simplex virus (HSV) infection changed between 1985 and 1995. During 1985, 1990, and 1995, respectively, 11.7, 11.3, and 11.4 infants per 100,000 live births had a diagnosis of HSV (P=.98). The proportion of infants 1-42 days of age who were discharged from the hospital with a diagnosis of HSV infection did not change over this time period despite a decrease in deliveries by cesarean section and an increase in the proportion of women with a diagnosis of genital HSV infection who gave birth to infants by vaginal delivery. From 1985 to 1995 there was no decrease in the rate of secondary diagnosis of genital HSV in delivering women.
View details for Web of Science ID 000081132100027
View details for PubMedID 10353880
Serum level of maternal human immunodeficiency virus (HIV) RNA, infant mortality, and vertical transmission of HIV in Zimbabwe
UNIV CHICAGO PRESS. 1999: 1382-1387
Maternal human immunodeficiency virus (HIV) RNA load, vertical transmission of subtype C HIV, and infant mortality were examined in 251 HIV-seropositive women and their infants in Zimbabwe. Demographic characteristics, health and medical histories, serum HIV RNA loads, and CD4+ lymphocyte counts for mothers were examined by logistic regression analysis to determine significant risk factors and their odds ratios for transmission and infant mortality. Tenfold (1 log10) incremental increases in maternal HIV RNA were associated with a 1.9-fold increase (95% confidence interval [CI], 1.2-2.9) in transmission and a 2.1-fold increase (95% CI, 1.3-3.5) in infant mortality (P<.01). Maternal CD4 cell counts and demographic and medical characteristics were not significant predictors of transmission. However, maternal CD4 cell counts below the median (400/mm3) were significantly associated with infant mortality (P=. 035, Fisher's exact test). The maternal level of serum HIV is an important determinant of vertical transmission and infant mortality in subtype C infection in Zimbabwe.
View details for Web of Science ID 000080561100010
View details for PubMedID 10228058
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
Host and viral factors affecting the decreased immunogenicity of Sabin type 3 vaccine after administration of trivalent oral polio vaccine to rural Mayan children
UNIV CHICAGO PRESS. 1997: 545-553
Factors affecting immunogenicity of the first 2 doses of oral poliovirus vaccine (OPV) among unimmunized Mayan infants were prospectively evaluated. The relative impact of multiple variables, including mass or routine vaccination, concurrent enteric bacterial (salmonella, shigella, and campylobacter) and viral (adenovirus 40/41, astrovirus, nonpolio enteroviruses, and rotavirus) infections, interference among Sabin vaccine viruses, and preexisting poliovirus antibodies were studied. Sera were available from 181 infants after 2 OPV doses. Seroresponses were 86% to Sabin type 1, 97% to Sabin type 2, and 61% to Sabin type 3 vaccines. Mass versus routine vaccination and preexisting poliovirus antibodies did not affect immunogenicity. By multiple logistic regression analysis, fecal shedding of homologous Sabin strains was associated with increased seroresponses to all Sabin types, especially to Sabin type 3. Decreased OPV immunogenicity was primarily attributable to interference of Sabin type 3 by Sabin type 2. OPV formulations with higher doses of Sabin type 3 could improve immunogenicity among infants in developing countries.
View details for Web of Science ID A1997WK41100006
View details for PubMedID 9041324
Comparison of T-cell responses to measles antigen in infants immunized at 6, 9, and 12 months of age.
OXFORD UNIV PRESS INC. 1996: 269-269
View details for Web of Science ID A1996VN24600315