Dengue, chikungunya and zika arbovirus infections in Caribbean children.

PURPOSE OF REVIEW: Dengue, chikungunya and zika have caused significant epidemics in the Caribbean in recent years. This review highlights their impact in Caribbean children. RECENT FINDINGS: Dengue has been increasingly intense and severe, seroprevalence is 80-100% in the Caribbean, children have increased attributable morbidity and mortality. Severe dengue, especially dengue with haemorrhage was significantly associated with haemoglobin SC disease and multiple organ-systems involved. These included the gastrointestinal and haematologic systems with extremely high lactate dehydrogenases and creatinine phosphokinases and severely abnormal bleeding indices. Despite appropriate interventions, mortality was highest within the first 48 h of admission. Chikungunya, a togavirus, affected 80% of some Caribbean populations. Paediatric presentations included high fever, skin, joint and neurological manifestations. Children less than 5 years of age had the highest morbidity and mortality. This maiden chikungunya epidemic was explosive and overwhelmed public health systems. Zika, another flavivirus, has a seroprevalence of 15% in pregnancy, so the Caribbean remains susceptible. Paediatric complications include pregnancy losses, stillbirths, Congenital Zika syndrome, Guillain-Barre syndrome, acute disseminated encephalomyelitis and transverse myelitis. Neurodevelopment stimulation programs for zika-exposed infants have been effective in improving language and positive behaviour scores. SUMMARY: Caribbean children remain at risk for dengue, chikungunya and zika, with high attributable morbidity and mortality.

Detection of Potential Arbovirus Infections and Pregnancy Complications in Pregnant Women in Jamaica Using a Smartphone App (ZIKApp): Pilot Evaluation Study.

BACKGROUND: There is growing evidence of the benefits of mobile health technology, which include symptom tracking apps for research, surveillance, and prevention. No study has yet addressed arbovirus symptom tracking in pregnancy. OBJECTIVE: This study aimed to evaluate the use of a smartphone app (ZIKApp) to self-report arbovirus symptoms and pregnancy complications and to assess compliance with daily symptom diaries during pregnancy in a cohort of women in an arbovirus-endemic, subtropical, middle-income country (Jamaica). METHODS: Pregnant women aged ≥16 years, having a smartphone, and planning on giving birth at the recruiting center were enrolled between February 2020 and July 2020. ZIKApp comprised a daily symptom diary based on algorithms to identify potential episodes of arbovirus infection and pregnancy complications. Sociodemographic, epidemiological, and obstetric information was collected at enrollment, with additional review of medical records, and users' perception was collected through an exit survey. Descriptive analyses and logistic regression analysis of possible factors associated with diary adherence were performed. RESULTS: Of the 173 women enrolled, 157 (90.8%) used ZIKApp for a median duration of 155 (IQR 127-173) days until pregnancy end, 6 (3.5%) used the app for <7 days, and 10 (5.8%) exited the study early. For each successive 30-day period from enrollment up to 150 days after enrollment, of these 157 women, 121 (77.1%) to 129 (82.2%) completed their daily symptom diary; 50 (31.8%) to 56 (35.7%) did so on the same day. Overall, 31.8% (50/157) of the women had good adherence to diary reporting (ie, they completed the task on the same day or 2 to 3 days later for ≥80% of the days enrolled). There were 3-fold higher odds of good adherence for participants aged >34 years versus those aged 25 to 29 years (adjusted odds ratio 3.14, 95% CI 1.10-8.98) and 2-fold higher odds for women with tertiary versus secondary education (adjusted odds ratio 2.26, 95% CI 1.06-4.83). Of the 161 women who ever made a diary entry, 5454 individual symptom reports were made (median 17 per woman; IQR 4-42; range 0-278); 9 (5.6%) women reported symptom combinations triggering a potential arbovirus episode (none had an adverse pregnancy outcome) and 55 (34.2%) reported painful uterine contractions or vaginal bleeding, mainly in the month before delivery. Overall, 51.8% (71/137) of the women rated the app as an excellent experience and were less likely to be poor diary adherers (P=.04) and 99.3% (138/139) reported that the app was easy to understand and use. CONCLUSIONS: This pilot found a high adherence to ZIKApp. It demonstrated the feasibility and usability of the app in an arbovirus-endemic region, supporting its future development to contribute to surveillance and diagnosis of arbovirus infections in pregnancy and to optimize maternal care.

Antenatal Seroprevalence of Zika and Chikungunya Viruses, Kingston Metropolitan Area, Jamaica, 2017-2019.

To determine the extent of exposure to Zika virus (ZIKV) and chikungunya virus (CHIKV) in Jamaica, we collected serum from 584 pregnant women during 2017-2019. We found that 15.6% had antibodies against ZIKV and 83.6% against CHIKV. These results indicate potential recirculation of ZIKV but not CHIKV in the near future.

Zika virus infection in pregnancy: a protocol for the joint analysis of the prospective cohort studies of the ZIKAlliance, ZikaPLAN and ZIKAction consortia.

INTRODUCTION: Zika virus (ZIKV) infection in pregnancy has been associated with microcephaly and severe neurological damage to the fetus. Our aim is to document the risks of adverse pregnancy and birth outcomes and the prevalence of laboratory markers of congenital infection in deliveries to women experiencing ZIKV infection during pregnancy, using data from European Commission-funded prospective cohort studies in 20 centres in 11 countries across Latin America and the Caribbean. METHODS AND ANALYSIS: We will carry out a centre-by-centre analysis of the risks of adverse pregnancy and birth outcomes, comparing women with confirmed and suspected ZIKV infection in pregnancy to those with no evidence of infection in pregnancy. We will document the proportion of deliveries in which laboratory markers of congenital infection were present. Finally, we will investigate the associations of trimester of maternal infection in pregnancy, presence or absence of maternal symptoms of acute ZIKV infection and previous flavivirus infections with adverse outcomes and with markers of congenital infection. Centre-specific estimates will be pooled using a two-stage approach. ETHICS AND DISSEMINATION: Ethical approval was obtained at each centre. Findings will be presented at international conferences and published in peer-reviewed open access journals and discussed with local public health officials and representatives of the national Ministries of Health, Pan American Health Organization and WHO involved with ZIKV prevention and control activities.

Researching Zika in pregnancy: lessons for global preparedness.

Our understanding of congenital infections is based on prospective studies of women infected during pregnancy. The EU has funded three consortia to study Zika virus, each including a prospective study of pregnant women. Another multi-centre study has been funded by the US National Institutes of Health. This Personal View describes the study designs required to research Zika virus, and questions whether funding academics in the EU and USA to work with collaborators in outbreak areas is an effective strategy. 3 years after the 2015-16 Zika virus outbreaks, these collaborations have taught us little about vertical transmission of the virus. In the time taken to approve funding, agree contracts, secure ethics approval, and equip laboratories, Zika virus had largely disappeared. By contrast, prospective studies based on local surveillance and standard-of-care protocols have already provided valuable data. Threats to fetal and child health pose new challenges for global preparedness requiring support for the design and implementation of locally appropriate protocols. These protocols can answer the key questions earlier than externally designed studies and at lower cost. Local protocols can also provide a framework for recruitment of unexposed controls that are required to study less specific outcomes. Other priorities include accelerated development of non-invasive tests, and longer-term storage of neonatal and antenatal samples to facilitate retrospective reconstruction of cohort studies.

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

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.

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 / 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.

New Delhi metallo-ß-lactamase in Jamaica.

INTRODUCTION: The global dissemination of the New Delhi metallo-beta-lactamase (NDM) gene among certain strains of bacteria has serious implications since the infections caused by such organisms pose a therapeutic challenge. Although the NDM gene has been detected in various parts of the world, this is the first report of its detection in the English-speaking Caribbean. The NDM producing Klebsiella pneumoniae was isolated from an Indian patient who had recently relocated to Jamaica. METHODOLOGY: Identification and susceptibility testing of the K. pneumoniae isolate was performed using the Vitek 2 automated system) in keeping with Clinical and Laboratory Standards Institute (CLSI) standards. It was identified as a metallobetalactamase producer using the Rosco KPC+MBL kit. Genotypic screening for common betalactamase (including carbapenemase) genes, was carried out  using two multiplex PCRs: one for SHV-, TEM-, CTX-M-, OXA-1-, and CMY-2-types, and one for VIM-, KPC-, IMP-, OXA-48, GES-, and NDM-types. Strain typing was conducted by pulsed-field gel electrophoresis (PFGE) using XbaI and multi-locus sequencing (MLS). Plasmid isolation and analysis was also performed. RESULTS: K. pneumoniae (N11-02395), not previously associated with the dissemination of the NDM in India, Sweden or the UK, was found to harbor the NDM-1 gene on plasmid pNDM112395. CONCLUSION: The identification of the NDM-1 gene underscores the need for effective surveillance and infection control measures to identify and prevent spread of multidrug resistant Gram negative bacilli. Strict infection control measures implemented for this patient helped to prevent the spread of this organism to other patients.

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.

Severe eosinophilic meningitis owing to Angiostrongylus cantonensis in young Jamaican children: case report and literature review.

Eosinophilic meningitis caused by Angiostrongylus cantonensis is an endemic and emerging disease that affects adults and children in Jamaica. Most cases resolve without sequelae, but young children are at high risk of neurological damage and death. Treatment with corticosteroids and albendazole is considered safe for adults and children, but protocols for its use in children have not been established. A 19-month-old infant with permanent neurological sequlae caused by Angiostrongylus cantonensis meningitis is reported, and five other Jamaican cases are summarized. A review of the literature of children with permanent neurological sequlae and death is presented. Children <5 years (especially <2) were at increased risk of incomplete recovery and death if they presented with bulbar signs, flaccid paresis and coma. None of the severe or fatal cases received early intervention with anthelminthics, and disease progression was not altered with corticosteroids. In view of the pathophysiology, necropsy reports and animal studies, it seems that the early use of larvicidals may change the course of severe presentations.

Asking the right questions: developing evidence-based strategies for treating HIV in women and children.

In July 2010, the World Health Organization (WHO) issued formal revisions of its guidelines on the use of highly active antiretroviral therapy for HIV. The new guidelines greatly expand eligibility for treatment of adults and children, as well as for pregnant women seeking prophylaxis for vertical HIV transmission. WHO's new recommendations bring the guidelines closer to practices in developed countries, and its shift to earlier treatment alone will increase the number of treatment-eligible people by 50% or more.Scaling up access to HIV treatment is revealing important gaps in our understanding of how best to provide for all those in need. This knowledge gap is especially significant in developing countries, where women and children comprise a majority of those living with HIV infection. Given the magnitude and significance of these populations, the International AIDS Society, through its Industry Liaison Forum, prioritized HIV treatment and prophylaxis of women and children. In March 2010, the International AIDS Society and 15 partners launched a Consensus Statement outlining priority areas in which a relative lack of knowledge impedes delivery of optimal prevention of mother to child transmission (PMTCT) and treatment to women and children.The Consensus Statement, "Asking the Right Questions: Advancing an HIV Research Agenda for Women and Children", makes a special appeal for a more gender-sensitive approach to HIV research at all stages, from conception to design and implementation. It particularly emphasizes research to enhance the understanding of sex-based differences and paediatric needs in treatment uptake and response. In addition to clinical issues, the statement focuses on programmatic research that facilitates access and adherence to antiretroviral regimens. Better coordination of HIV management with sexual and reproductive healthcare delivery is one such approach.We discuss here our knowledge gaps concerning effective, safe PMTCT and treatment for women and children in light of the expansion envisioned by WHO's revised guidelines. The guideline's new goals present an opportunity for advancing the women and children's agenda outlined in the Consensus Statement.

Pentavalent rotavirus vaccine in developing countries: safety and health care resource utilization.

OBJECTIVE: In the international, placebo-controlled, Rotavirus Efficacy and Safety Trial, the pentavalent rotavirus vaccine reduced the rate of rotavirus-attributable hospitalizations and emergency department visits by 95%. This study investigated the effect in Jamaica. METHODS: The vaccine effect on rates of hospitalizations and emergency department visits in Jamaica was evaluated in both modified intention-to-treat and per-protocol analyses. Rates of serious adverse events, including intussusception, also were compared between groups. RESULTS: A total of 1804 Jamaican infants, 6 to 12 weeks of age at entry and primarily from low/middle-income families of African heritage, received ≥1 dose. During the first year after dose 1, there were 2 and 11 hospitalizations or emergency department visits attributable to rotavirus gastroenteritis involving any serotype among 831 evaluable vaccine recipients and 809 evaluable placebo recipients, respectively (rate reduction: 82.2% [95% confidence interval: 15.1%-98.0%]). In the per-protocol analysis, all 8 G1 to G4 rotavirus-attributable events that occurred ≥2 weeks after dose 3 were in the placebo group (rate reduction: 100% [95% confidence interval: 40.9%-100%]). Of the 1802 subjects included in the safety analyses, intussusception was confirmed for 1 vaccine recipient (115 days after the third dose) and 3 placebo recipients. One vaccine recipient and 3 placebo recipients died during the follow-up period, but none of the deaths was considered to be vaccine-related. CONCLUSIONS: In this posthoc subgroup analysis, the vaccine reduced health care resource utilization attributable to rotavirus gastroenteritis, without increased risk of intussusception or other serious adverse events, among infants in a resource-limited country.

Correlates of spontaneous viral control among long-term survivors of perinatal HIV-1 infection expressing human leukocyte antigen-B57.

OBJECTIVE: We sought to identify immunologic and virologic correlates of spontaneous viral control among long-term survivors of perinatal HIV infection expressing the protective human leukocyte antigen (HLA)-B57 allele. DESIGN: The frequency, epitope specificity, and functional attributes of HIV-specific T cells and sequence variation within B57-restricted epitopes were compared between 'spontaneous controllers' who maintained normal CD4 percentages and viral loads less than 3000 copies/ml without antiretroviral therapy, and 'treated progressors' who had initiated HAART. METHODS: Recognition of HIV optimal epitopes was assessed by interferon gamma (IFNgamma) enzyme-linked immunosorbent spot. Functional characterization of CD8 cells targeting B57 epitopes was performed by staining for cytokine production (intracellular IFNgamma, interleukin-2, tumor necrosis factor alpha) and degranulation. Sequencing of autologous RNA was performed to determine the prevalence of viral escape mutations within B57-restricted epitopes and associated compensatory mutations. RESULTS: HLA-B57 remained immunodominant during chronic infection in both controllers and progressors, but controllers recognized fewer epitopes and targeted epitopes within Gag and reverse transcriptase only, whereas progressors demonstrated a broader response targeting additional proteins. No individual epitope was targeted more frequently by spontaneous controllers. CD8 cytokine production patterns were heterogeneous among individuals and even among different epitopes in the same individual and did not correlate with spontaneous viral control. Extensive sequence variation within B57 epitopes was observed in both groups, but only progressors displayed additional capsid mutations that are known to offset the viral fitness cost of B57-driven immune escape. CONCLUSION: Among HLA-B57-positive long-term survivors, spontaneous control of viremia is not associated with a qualitatively or quantitatively superior T-cell response, but with uncompensated fitness-attenuating mutations in the viral capsid.

Lower respiratory tract infections among human immunodeficiency virus-exposed, uninfected infants.

OBJECTIVES: To evaluate whether maternal HIV disease severity during pregnancy is associated with an increased likelihood of lower respiratory tract infections (LRTIs) in HIV-exposed, uninfected infants. METHODS: HIV-exposed, uninfected, singleton, term infants enrolled in the NISDI Perinatal Study, with birth weight >2500g were followed from birth until 6 months of age. LRTI diagnoses, hospitalizations, and associated factors were assessed. RESULTS: Of 547 infants, 103 (18.8%) experienced 116 episodes of LRTI (incidence=0.84 LRTIs/100 child-weeks). Most (81%) episodes were bronchiolitis. Forty-nine (9.0%) infants were hospitalized at least once with an LRTI. There were 53 hospitalizations (45.7%) for 116 LRTI episodes. None of these infants were breastfed. The odds of LRTI in infants whose mothers had CD4% <14 at enrollment were 4.4 times those of infants whose mothers had CD4% ≥29 (p=0.003). The odds of LRTI in infants with a CD4+ count (cells/mm(3)) <750 at hospital discharge were 16.0 times those of infants with CD4+ ≥750 (p=0.002). Maternal CD4+ decline and infant hemoglobin at the 6-12 week visit were associated with infant LRTIs after 6-12 weeks and before 6 months of age. CONCLUSIONS: Acute bronchiolitis is common and frequently severe among HIV-exposed, uninfected infants aged 6 months or less. Lower maternal and infant CD4+ values were associated with a higher risk of infant LRTIs. Further understanding of the immunological mechanisms of severe LRTIs is needed.

Deficiency of HIV-Gag-specific T cells in early childhood correlates with poor viral containment.

Perinatal HIV infection is characterized by a sustained high-level viremia and a high risk of rapid progression to AIDS, indicating a failure of immunologic containment of the virus. We hypothesized that age-related differences in the specificity or function of HIV-specific T cells may influence HIV RNA levels and clinical outcome following perinatal infection. In this study, we defined the HIV epitopes targeted by 76 pediatric subjects (47 HIV infected and 29 HIV exposed, but uninfected), and assessed the ability of HIV-specific CD8 and CD4 T cells to degranulate and produce IFN-gamma, TNF-alpha, and IL-2. No responses were detected among HIV-uninfected infants, whereas responses among infected subjects increased in magnitude and breadth with age. Gag-specific responses were uncommon during early infancy, and their frequency was significantly lower among children younger than 24 mo old (p = 0.014). Importantly, Gag responders exhibited significantly lower HIV RNA levels than nonresponders (log viral load 5.8 vs 5.0; p = 0.005). Both the total and Gag-specific T cell frequency correlated inversely with viral load after correction for age, whereas no relationship with targeting of other viral proteins was observed. Functional assessment of HIV-specific T cells by multiparameter flow cytometry revealed that polyfunctional CD8 cells were less prevalent in children before 24 mo of age, and that HIV-specific CD4 cell responses were of universally low frequency among antiretroviral-naive children and absent in young infants. These cross-sectional data suggest that qualitative differences in the CD8 response, combined with a deficiency of HIV-specific CD4 cells, may contribute to the inability of young infants to limit replication of HIV.

Efficacy of a pentavalent rotavirus vaccine in reducing rotavirus-associated health care utilization across three regions (11 countries).

OBJECTIVE: To evaluate the effect of a human-bovine reassortant pentavalent rotavirus vaccine (PRV) on health care encounters in nearly 70 000 subjects randomized in three regions - Europe, the United States, and Latin America/the Caribbean - in the Rotavirus Efficacy and Safety Trial (REST). METHODS: Healthy 6- to 12-week-old infants received 3 doses of PRV or placebo at 4- to 10-week intervals. The exact binomial method for ratios of Poisson counts was used to evaluate the effect of PRV on the rate of rotavirus-related hospitalizations and emergency department (ED) visits involving rotavirus G-types 1-4 occurring > or =14 days after the third dose of vaccine for up to 2 years. RESULTS: In fully vaccinated infants, reductions in rotavirus-associated hospitalizations and ED visits were 94.7% (95% CI: 90.9, 96.9) in Europe, 94.9% (95% CI: 84.0, 98.9) in the United States, and 90.0% (95% CI: 29.4, 99.8) in the Latin American/Caribbean regions. CONCLUSIONS: PRV reduced hospitalizations and ED visits within each region in REST. Results were consistent across regions and across the overall study cohort.

Safety and efficacy of a pentavalent human-bovine (WC3) reassortant rotavirus vaccine.

BACKGROUND: Rotavirus is a leading cause of childhood gastroenteritis and death worldwide. METHODS: We studied healthy infants approximately 6 to 12 weeks old who were randomly assigned to receive three oral doses of live pentavalent human-bovine (WC3 strain) reassortant rotavirus vaccine containing human serotypes G1, G2, G3, G4, and P[8] or placebo at 4-to-10-week intervals in a blinded fashion. Active surveillance was used to identify subjects with serious adverse and other events. RESULTS: The 34,035 infants in the vaccine group and 34,003 in the placebo group were monitored for serious adverse events. Intussusception occurred in 12 vaccine recipients and 15 placebo recipients within one year after the first dose including six vaccine recipients and five placebo recipients within 42 days after any dose (relative risk, 1.6; 95 percent confidence interval, 0.4 to 6.4). The vaccine reduced hospitalizations and emergency department visits related to G1-G4 rotavirus gastroenteritis occurring 14 or more days after the third dose by 94.5 percent (95 percent confidence interval, 91.2 to 96.6 percent). In a nested substudy, efficacy against any G1-G4 rotavirus gastroenteritis through the first full rotavirus season after vaccination was 74.0 percent (95 percent confidence interval, 66.8 to 79.9 percent); efficacy against severe gastroenteritis was 98.0 percent (95 percent confidence interval, 88.3 to 100 percent). The vaccine reduced clinic visits for G1-G4 rotavirus gastroenteritis by 86.0 percent (95 percent confidence interval, 73.9 to 92.5 percent). CONCLUSIONS: This vaccine was efficacious in preventing rotavirus gastroenteritis, decreasing severe disease and health care contacts. The risk of intussusception was similar in vaccine and placebo recipients. (ClinicalTrials.gov number, NCT00090233.)

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.