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.

Hospitalized children with SARS-CoV-2 infection and MIS-C in Jamaica: A dive into the first 15 months of the novel pandemic.

Objectives: COVID-19 in children was initially mild until the emergence of Multisystem Inflammatory Syndrome in Children (MIS-C). We describe pediatric COVID-19 in a developing country within the Caribbean. Methods: Jamaican children who were hospitalized with SARS-CoV-2 infection, in one Caribbean regional academic referral center from April 2020 through June 2021 were included. Prospective surveillance and pediatric infectious disease consultations were performed using the CDC's MIS-C case definition. Data were extracted from patients' hospital charts using WHO's reporting form, entered into the RedCap database, and SPSS 28 was used for analysis. MIS-C and non-MIS-C patients were compared using independent sample t-tests for continuous variables and Fisher's exact test for categorical variables, p values < 0.05 were statistically significant. Results: Seventy-nine children with COVID-19 with/without MIS-C presented to UHWI. Thirty-eight (48%) were mild ambulatory cases. Hospitalizations occurred in 41 (52%) children, with median age of 10 1 2 years. SARS-CoV-2 RT-PCR positivity was present in 26 (63%), Immunoglobulin M, or Immunoglobulin G (IgM/IgG) positivity in 8 (20%), with community exposures in 7 (17%). Eighteen (44%) MIS-C positive patients were significantly more likely than 23 MIS-C negative patients (56%) to present with fever (94% vs. 30%; p < 0.001), fatigue/lethargy (41% vs. 4%; p = 0.006), lymphadenopathy (33% vs. 0%; p = 0.003), elevated neutrophils (100% vs. 87%; p = 0.024), and ESR (78% vs. 9%; p = 0.002). Involvement of > two organ systems occurred more frequently in MIS-C positive cases (100% vs. 34%; p < 0.001), including gastrointestinal (72% vs. 17%; p < 0.001); vomiting/nausea (39% vs. 9%; p < 0.028); hematological/coagulopathic (67% vs. 4%; p < 0.001); dermatologic involvement (56% vs. 0%; p < 0.001); and mucositis (28% vs. 0%; p = 0.001). MIS-C patients had Kawasaki syndrome (44%), cardiac involvement (17%), and pleural effusions (17%). MIS-C patients had >4 abnormal inflammatory biomarkers including D-dimers, C-reactive protein, ESR, ferritin, troponins, lactate dehydrogenase, neutrophils, platelets, lymphocytes, and albumen (72%). MIS-C patients were treated with intravenous immune gamma globulin (78%), aspirin (68%), steroids (50%), and non-invasive ventilation (11%). None required inotropes/vasopressors. MIS-C negative patients received standard care. All recovered except one child who was receiving renal replacement therapy and developed myocardial complications. Conclusions: In this first report of COVID-19 from the Caribbean, children and adolescents with and without MIS-C were not very severe. Critical care interventions were minimal and outcomes were excellent.

Severity and Outcomes of Dengue in Hospitalized Jamaican Children in 2018-2019 During an Epidemic Surge in the Americas.

Objective: In 2019, dengue was among the "top-ten threats to global health," with 3.1 million cases reported from the Americas, the highest ever. Simultaneously, Jamaica reported its largest dengue outbreak in 40 years, following Chikungunya and Zika virus epidemics, in 2014 and 2016-2017, respectively. We describe dengue in children admitted to five hospitals in Jamaica during August 2018 through September 2019. Methods: Hospitalized children and adolescents aged 0 to 15 years with dengue were managed using PAHO/WHO criteria. Data were extracted from questionnaires, entered into a dataset on Microsoft Excel version 2016, exported to SPSS version 20 and analyzed. Groups were compared using Student's t-test for normally distributed parametric data. Chi-square analysis, or Fisher's exact test was used for categorical variables. A p-value < 0.05 was considered statistically significant. Results: There were 339 children, 245 (72.3%) aged 1-10 years, males:females 1:1. Classification was "dengue without warning signs" 53 (15.3%), "dengue with warning signs" 218 (64.3%) and "severe dengue" 68 (20%). Co-morbidities were reported in 88 (26%). Hemoglobin SC disease was associated with severe dengue with hemorrhage (p = 0.005). Organ-system involvement occurred in 334 (98.5%) including gastrointestinal 317 (93.5%), hematologic 311 (91.7%) and musculoskeletal 180 (53.1%). Thirty-nine (11.5%) had 5-7 organ-systems involved. Metabolomics emphasized increased hepatic transaminases 245 (72.3%), lactate dehydrogenase 164 (48.4%) and creatine phosphokinase 84 (24.8%) approaching the high thousands (121,560 u/L), both were markers for severe disease (p < 0.002). Thirteen (3.8%) received intensive care. Dengue was laboratory-confirmed in 220 (78.9%): NS1 antigen-positive (218); RT-PCR-positive (23), with an overlap of NS1 antigen and RT-PCR positive (21); DENV-3 serotype (20). Seventeen (5%) died, 16 (94.1%) had severe dengue and 11 (64.7%) succumbed within 24 to 48 h of admission despite resuscitation and transfusion of blood products. Conclusion: Severe dengue with increased attributable mortality occurred in hospitalized children after Jamaica's maiden Zika epidemic.

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.

Sexual Abuse and Sexually-Transmitted HIV/AIDS in Jamaican Children and Adolescents Aged 6-19 Years.

INTRODUCTION: Risk factors and outcomes of sexually-acquired human immunodeficiency virus infection were characterized in Jamaican children and adolescents. METHODOLOGY: Management was carried out by multidisciplinary teams in Infectious Diseases clinics during August 2003 through February 2019 using modified World Health Organization HIV criteria. RESULTS: There were 78 clients, aged 6 to 19 years, with females:males = 4:1 (p < 0.05). Sexual-initiation occurred in 60%, 47 before < 16 years (median 13 years, with four < 10 years; females:males = 7:1). Sexual-initiation preceded HIV diagnosis in all cases (median 2 years). Secondary education 93% (69/77) and living with non-parental relatives 17% (13/78) were associated with early sexual-initiation (p < 0.042); as was later imprisonment in 6% (3/52). Other sexually transmitted infections 36% (19/53) were associated with sexual-initiation ≥ 16 years (p < 0.01). Risks for ongoing HIV-transmission included infrequent condom use 74% (39/53), body-piercings 50% (24/48), illicit drug use 37% (28/76), tattoos 36% (19/52), transactional sex 14% (7/53) and pregnancy 56% of girls. 77% (59/77) had Centres for Diseases Control's Category A HIV infection; 82% (61/75) initiated anti-retroviral therapy; 75% (56/75) had first-line drugs, with helper T lymphocyte counts ≥ 500 cells/µL in 61% (48/78) and HIV viral load of < 1,000 copies/µL in 63% (40/64). Complications included dermatological 39% (20/52), respiratory 25% (13/52) and neurological 15% (8/52). Early sexual initiation was associated with depression 43% (33/76; p < 0.004) and suicidal attempt or ideation 23% (18/77; p < 0.096). Four (5%) died. CONCLUSIONS: Sexually transmitted HIV/AIDS in children and adolescents should preempt prompt medical, legal and psychosocial interventions.

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.

Transfer is not a transition - voices of Jamaican adolescents with HIV and their health care providers.

Increasing access to antiretroviral therapy in resource-limited settings (RLS) has resulted in the survival of perinatally HIV-infected children into adulthood. We characterized the transition process from pediatric to adult care by conducting semi-structured interviews of HIV-infected adolescents and health care providers in Jamaica. Using an inductive content analytic approach, four themes emerged: (1) Transition should be holistic and a process; (2) Pediatric clinics were like families; (3) Rootedness in the pediatric clinic; and (4) Need for adolescent-centered services to bridge the gap between pediatric and adult-centered services. Adolescent informed- and centered-transition approach may result in better outcomes for HIV-infected adolescents.

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.

Seroepidemiology of human bocavirus infection in Jamaica.

BACKGROUND: Human bocavirus (HBoV) is a newly identified human parvovirus. HBoV is associated with upper and lower respiratory tract infections and gastroenteritis in children. Little is known about the seroepidemiology of HBoV in populations in the Caribbean. METHODS: In a cross-sectional study conducted at the University Hospital of the West Indies in Kingston, Jamaica, 287 blood samples were collected from pediatric patients and tested for the presence of HBoV-specific antibody using a virus-like-particle based enzyme-linked immunosorbent assay (ELISA). RESULTS: HBoV-specific antibodies were found to be present in 220/287 (76.7%) of samples collected from the pediatric population. Seroprevalence of HBoV was highest in those ≥2 years old. The seroepidemiological profile suggests that most children are exposed to HBoV during the first two years of life in Jamaica. CONCLUSION: HBoV infection is common in children in Jamaica. HBoV seroprevalence rates in the Caribbean are similar to those previously reported in other areas of the world.

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.

Sequence evolution of HIV-1 following mother-to-child transmission.

The genetic heterogeneity of HIV-1 poses a major obstacle to vaccine development. Although most horizontally acquired HIV-1 infections are initiated by a single homogeneous virus, marked genetic diversification and evolution occur following transmission. The relative contribution of the antiviral immune response to intrahost viral evolution remains controversial, in part because the sequence of the transmitted virus and the array of T-cell epitopes targeted by both donor and recipient are seldom known. We directly compared predominant viral sequences derived from 52 mother-child transmission pairs following vertical infection and identified 1,475 sites of mother-infant amino acid divergence within Nef, Gag, and Pol. The cumulative number of mutations away from the consensus subtype B sequence increased linearly with time since transmission, whereas reversions toward the consensus sequence accumulated more slowly with increasing duration of infection. Comprehensive mapping of T-cell epitopes targeted by these mothers and infants revealed that 14% of nonsynonymous mutations away from the consensus sequence were located within regions targeted by the infant, whereas 24% of nonsynonymous mutations toward the consensus sequence were located in regions targeted by the mother. On the basis of analysis of optimal epitopes listed in the HIV Molecular Immunology Database, fewer than 10% of epitopes containing maternal escape mutations reverted to the consensus sequence following transmission to an infant lacking the restricting HLA allele. This surprisingly low reversion rate of mutated epitopes following transmission suggests that the fitness cost associated with many CD8 epitope mutations may be modest.

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.