Immunity After Childhood Vaccinations in Perinatally HIV-exposed Children With and Without HIV Infection in Latin America.

BACKGROUND: Perinatally HIV-infected (PHIV) children are at risk for under-vaccination and poor vaccine response at 4 years of age. Childhood vaccine coverage and immune response were compared between PHIV and HIV-exposed uninfected (HEU) children in Latin America and the Caribbean. METHODS: PHIV and HEU children were enrolled prospectively at 15 sites from 2002 to 2009. Full vaccination by age 4 years was defined as: 3 hepatitis B virus vaccine doses; 4 tetanus toxoid-containing vaccine doses; 3 doses of Haemophilus influenzae type b vaccine by age 12 months or ≥1 dose given after age 12 months; one measles-containing vaccine dose; one rubella-containing vaccine dose. Immunity was defined by serum antibody titer. Fisher exact test (for categorical measures) and t test (for continuous measures) were used for comparisons. RESULTS: Among 519 children seen at age 4 years, 191 had serum specimens available (137 PHIV, 54 HEU). Among those with specimens available, 29.3% initiated combination antiretroviral therapy (cART) <12 months of age, 30.9% initiated at ≥12 months of age, and 39.8% had not received cART by the time they were seen at 4 years of age. At 4 years of age, 59.9% were on PI-containing cART (cART/PI), and 20.4% were on no ART. PHIV children were less likely than HEU children to be fully vaccinated for tetanus (55.5% vs. 77.8%, P = 0.005) and measles and rubella (both 70.1% vs. 94.4%, P < 0.001). Among those fully vaccinated, immunity was significantly lower among PHIV than HEU for all vaccines examined: 20.9% versus 37.8% for hepatitis B virus (P = 0.04), 72.0% versus 90.5% for tetanus (P = 0.02), 51.4% versus 68.8% for H. influenzae type b (P = 0.05), 80.2% versus 100% for measles (P < 0.001) and 72.9% versus 98.0% for rubella (P < 0.001) vaccine, respectively. CONCLUSIONS: Compared with HEU, PHIV children were significantly less likely to be immune to vaccine-preventable diseases when fully vaccinated. Strategies to increase immunity against vaccine-preventable diseases among PHIV require further study.

Infectious disease morbidity and growth among young HIV-exposed uninfected children in Jamaica / Morbilidad por enfermedades infecciosas y crecimiento en niños pequeños no infectados pero expuestos al VIH en Jamaica

ABSTRACT Objective There is a growing body of data that demonstrates increased infectious disease outcomes for HIV-exposed uninfected (HIV-EU) infants as compared to their HIV-unexposed (HU) counterparts. We hypothesized that these HIV-EU infants are at greater risk for infectious morbidity and mortality when compared to the general childhood population. We therefore aimed to characterize infections and growth outcomes among HIV-EU infants in Jamaica during their first two years of life. By identifying these outcomes, specific interventions could be implemented to mitigate this risk of morbidity and mortality. Methods HIV-EU infants born between 1 January 2004 and 31 December 2006 in Kingston, Jamaica, were enrolled and followed in multicenter health facilities, using standardized protocols. HIV status was determined by RNA/DNA polymerase chain reaction (PCR) and confirmatory HIV enzyme-linked immunoassay (ELISA). Data were collected on demographic and anthropometric characteristics, infectious morbidity and mortality, and hospitalizations. Outcomes (incidence of infections and hospitalizations; growth (z scores for weight)) were determined, using univariate analyses. Results Of 195 HIV-EU infants followed for 25.9 months (standard deviation, 10.9 months), 102 (52%) were male, 185 (95%) were non-breast-fed, 161 (83%) experienced at least one infection, and 58 (30%) were hospitalized at least once. Infectious disease incidence per 1 000 child-weeks included upper respiratory tract infection of 7.25 (95% confidence interval (CI): 5.92–8.90), otitis media of 4.12 (3.21–5.20), and acute gastroenteritis (AGE) of 1.92 (1.35–2.65). Hospitalization incidence per 1 000 child-weeks included lower respiratory tract infections (LRTIs) of 0.89 (0.53–1.40), sepsis of 0.48 (0.23–0.89), and AGE of 0.43 (0.20–0.81). These infection incidence rates among the HIV-EU infants were higher than those for published community controls. Among the HIV-EU infants, the low-birthweight ones and those born via cesarean section had significantly higher hospitalization rates from LRTI and sepsis than did published community controls. The mean z score for weight during the infants’ first 6 months ranged from -0.06 to 0.78 in this predominantly non-breast-fed population. That score trended upwards to 24 months of age. Conclusions Infectious disease morbidity was higher but growth was normal in this cohort of HIV-EU non-breast-fed infants, in comparison to published community controls. Specific interventions should be implemented to mitigate the risk in this setting.

RESUMEN Objetivo Existe un volumen cada vez mayor de datos que muestran un aumento de casos de enfermedades infecciosas en lactantes no infectados pero expuestos al VIH en comparación con lactantes no expuestos al virus. Formulamos la hipótesis de que los lactantes no infectados pero expuestos presentan mayor riesgo de morbilidad y mortalidad por enfermedades infecciosas comparados con la población general de niños. Por consiguiente, nos propusimos caracterizar las infecciones y los resultados de crecimiento en lactantes no infectados pero expuestos al VIH en Jamaica durante sus dos primeros años de vida. Al determinarse estos resultados, podrían ejecutarse intervenciones específicas para mitigar este riesgo de morbilidad y mortalidad. Métodos Se inscribieron lactantes no infectados pero expuestos al HIV nacidos entre el 1 de enero del 2004 y el 31 de diciembre del 2006 en Kingston (Jamaica), y se les hizo seguimiento en establecimientos multicéntricos de salud, con protocolos estandarizados. El estado con respecto a la infección por el VIH se determinó mediante la reacción en cadena de la polimerasa (PCR) para ARN/ADN y prueba confirmatoria de inmunoadsorción enzimática (ELISA). Se recopilaron datos sobre características demográficas y antropométricas, morbilidad y mortalidad por infecciones y hospitalizaciones. Los resultados (incidencia de infecciones y hospitalizaciones; crecimiento [puntuaciones z para el peso]) se determinaron usando un análisis de una sola variable. Resultados De 195 lactantes no infectados pero expuestos a los que se les dio seguimiento durante 25,9 meses (desviación estándar, 10,9 meses), 102 (52%) eran de sexo masculino, 185 (95%) no fueron amamantados, 161 (83%) presentaron al menos una infección y 58 (30%) fueron hospitalizados por lo menos una vez. La incidencia de enfermedades infecciosas por 1 000 niño-semanas incluyó infecciones de las vías respiratorias superiores de 7,25 (intervalo de confianza [IC] de 95%: 5,92–8,90), otitis media de 4,12 (3,21–5,20) y gastroenteritis aguda (AGE) de 1,92 (1,35–2,65). La incidencia de hospitalización por 1 000 niño-semanas incluyó infecciones de las vías respiratorias inferiores de 0,89 (0,53–1,40), septicemia de 0,48 (0,23–0,89) y gastroenteritis aguda de 0,43 (0,20–0,81). Estas tasas de incidencia de infecciones en los lactantes no infectados pero expuestos fueron más altas que las de los controles comunitarios publicados. En los lactantes no infectados pero expuestos, aquellos con peso bajo al nacer y aquellos nacidos por cesárea registraron tasas de hospitalización significativamente más altas por infecciones de las vías respiratorias inferiores y septicemia que los controles comunitarios publicados. La media de la puntuación z para el peso durante los 6 primeros meses de los lactantes se ubicó entre -0,06 y 0,78 en esta población que en su mayoría no fue amamantada. Esa puntuación mostró una tendencia ascendente a los 24 meses de edad. Conclusiones La morbilidad por enfermedades infecciosas fue mayor, pero el crecimiento fue normal en esta cohorte de lactantes no infectados pero expuestos al VIH y no amamantados, en comparación con los controles comunitarios publicados. Deben realizarse intervenciones específicas para mitigar el riesgo en este entorno.

Infectious disease morbidity and growth among young HIV-exposed uninfected children in Jamaica.

OBJECTIVE: There is a growing body of data that demonstrates increased infectious disease outcomes for HIV-exposed uninfected (HIV-EU) infants as compared to their HIV-unexposed (HU) counterparts. We hypothesized that these HIV-EU infants are at greater risk for infectious morbidity and mortality when compared to the general childhood population. We therefore aimed to characterize infections and growth outcomes among HIV-EU infants in Jamaica during their first two years of life. By identifying these outcomes, specific interventions could be implemented to mitigate this risk of morbidity and mortality. METHODS: HIV-EU infants born between 1 January 2004 and 31 December 2006 in Kingston, Jamaica, were enrolled and followed in multicenter health facilities, using standardized protocols. HIV status was determined by RNA/DNA polymerase chain reaction (PCR) and confirmatory HIV enzyme-linked immunoassay (ELISA). Data were collected on demographic and anthropometric characteristics, infectious morbidity and mortality, and hospitalizations. Outcomes (incidence of infections and hospitalizations; growth (z scores for weight)) were determined, using univariate analyses. RESULTS: Of 195 HIV-EU infants followed for 25.9 months (standard deviation, 10.9 months), 102 (52%) were male, 185 (95%) were non-breast-fed, 161 (83%) experienced at least one infection, and 58 (30%) were hospitalized at least once. Infectious disease incidence per 1 000 child-weeks included upper respiratory tract infection of 7.25 (95% confidence interval (CI): 5.92-8.90), otitis media of 4.12 (3.21-5.20), and acute gastroenteritis (AGE) of 1.92 (1.35-2.65). Hospitalization incidence per 1 000 child-weeks included lower respiratory tract infections (LRTIs) of 0.89 (0.53-1.40), sepsis of 0.48 (0.23-0.89), and AGE of 0.43 (0.20-0.81). These infection incidence rates among the HIV-EU infants were higher than those for published community controls. Among the HIV-EU infants, the low-birthweight ones and those born via cesarean section had significantly higher hospitalization rates from LRTI and sepsis than did published community controls. The mean z score for weight during the infants' first 6 months ranged from -0.06 to 0.78 in this predominantly non-breast-fed population. That score trended upwards to 24 months of age. CONCLUSIONS: Infectious disease morbidity was higher but growth was normal in this cohort of HIV-EU non-breast-fed infants, in comparison to published community controls. Specific interventions should be implemented to mitigate the risk in this setting.

Analysis of reverse transcriptase and protease genes of HIV for antiretroviral drug resistance in treatment-exposed Jamaican pediatrics.

This study reports on the drug resistance profiles for HIV-infected pediatrics in Jamaica who have been exposed to antiretroviral therapy (ART). The genetic diversity of HIV-1 found in these patients was also determined using phylogenetic analysis. The protease-reverse transcriptase (Pro-RT) region of the genome was amplified from 40 samples, sequenced, and analyzed for the identification of antiretroviral resistance-associated mutations (RAMs). All isolates belonged to subtype B and 39 possessed multiple RAMs in the reverse transcriptase genes that would compromise the efficacy of drugs being used to treat these patients. Four isolates possessed RAMs in the protease genes. The overall frequency of HIV drug resistance was 95%. The high frequency of drug resistance is supported by epidemiological data that revealed an equally high frequency of treatment failure (98%) among the study participants. The results of this study indicate the urgent need for greater access to drug resistance testing in Jamaica.

Undervaccination of perinatally HIV-infected and HIV-exposed uninfected children in Latin America and the Caribbean.

BACKGROUND: Perinatally HIV-infected (PHIV) children may be at risk of undervaccination. Vaccination coverage rates among PHIV and HIV-exposed uninfected (HEU) children in Latin America and the Caribbean were compared. METHODS: All PHIV and HEU children born from 2002 to 2007 who were enrolled in a multisite observational study conducted in Latin America and the Caribbean were included in this analysis. Children were classified as up to date if they had received the recommended number of doses of each vaccine at the appropriate intervals by 12 and 24 months of age. Fisher's exact test was used to analyze the data. Covariates potentially associated with a child's HIV status were considered in multivariable logistic regression modeling. RESULTS: Of 1156 eligible children, 768 (66.4%) were HEU and 388 (33.6%) were PHIV. HEU children were significantly (P < 0.01) more likely to be up to date by 12 and 24 months of age for all vaccines examined. Statistically significant differences persisted when the analyses were limited to children enrolled before 12 months of age. Controlling for birth weight, sex, primary caregiver education and any use of tobacco, alcohol or illegal drugs during pregnancy did not contribute significantly to the logistic regression models. CONCLUSIONS: PHIV children were significantly less likely than HEU children to be up to date for their childhood vaccinations at 12 and 24 months of age, even when limited to children enrolled before 12 months of age. Strategies to increase vaccination rates in PHIV are needed.

Student evaluation of an OSCE in paediatrics at the University of the West Indies, Jamaica.

BACKGROUND: The Faculty of Medical Sciences, University of the West Indies first implemented the Objective Structured Clinical Examination (OSCE) in the final MB Examination in Medicine and Therapeutics during the 2000-2001 academic year. Simultaneously, the Child Health Department initiated faculty and student training, and instituted the OSCE as an assessment instrument during the Child Health (Paediatric) clerkship in year 5. The study set out to explore student acceptance of the OSCE as part of an evaluation of the Child Health clerkship. METHODS: A self-administered questionnaire was completed by successive groups of students immediately after the OSCE at the end of each clerkship rotation. Main outcome measures were student perception of examination attributes, which included the quality of instructions and organisation, the quality of performance, authenticity and transparency of the process, and usefulness of the OSCE as an assessment instrument compared to other formats. RESULTS: There was overwhelming acceptance of the OSCE in Child Health with respect to the comprehensiveness (90%), transparency (87%), fairness (70%) and authenticity of the required tasks (58-78%). However, students felt that it was a strong anxiety-producing experience. And concerns were expressed regarding the ambiguity of some questions and inadequacy of time for expected tasks. CONCLUSION: Student feedback was invaluable in influencing faculty teaching, curriculum direction and appreciation of student opinion. Further psychometric evaluation will strengthen the development of the OSCE.