Adaptation of WHO COVID-19 guidelines by Caribbean countries and territories.

The normative role of the World Health Organization (WHO) involves creating evidence-based, principled guidelines to guide its Member States in making well-informed public health decisions. While these guidelines often need to be adapted to ensure contextual relevance, foster better implementation and adherence, adapting existing guidelines is more efficient than creating new ones. Here we describe the adaptation of the WHO coronavirus disease 2019 (COVID-19) living guideline on pharmacological interventions for the Caribbean using the grading of recommendations, assessment, development and evaluation (GRADE)-ADOLOPMENT method. The Caribbean Public Health Agency and the Pan American Health Organization led the effort, assembling a diverse panel of 16 experts from seven Caribbean countries and territories. The adaptation process, involving 15 steps, was guided by an experienced methodologist and included selecting relevant clinical questions and prioritizing them based on regional needs. The panel evaluated the latest WHO guidelines and integrated additional local data. They adjusted the direction and strength of several recommendations to better fit the Caribbean context, considering local values and preferences, resources, accessibility, feasibility and impact on health equity. Ultimately, we changed the direction of two recommendations and the strength of five, tailoring them to regional realities. This effort highlights the importance of adapting global guidelines to local settings, improving their applicability and effectiveness. The adaptation process also serves as a valuable opportunity for skill transfer and capacity-building in guideline development. Continued research is needed to assess the impact of these adaptations on health-care outcomes in the Caribbean.

Le rôle normatif de l'Organisation mondiale de la santé (OMS) consiste à élaborer des lignes directrices fondées sur des données scientifiques et sur des principes afin d'aider ses États membres à prendre des décisions éclairées en matière de santé publique. Bien qu'elles nécessitent souvent des adaptations pour garantir leur pertinence par rapport à des contextes précis et pour favoriser une meilleure mise en œuvre et adhésion, il est plus efficace d'adapter les lignes directrices existantes que d'en créer de nouvelles. La présente publication décrit l'adaptation de la ligne directrice évolutive de l'OMS sur les interventions pharmacologiques dans le cadre de la maladie à coronavirus (COVID-19) pour les Caraïbes en appliquant la méthodologie GRADE (classement des recommandations, de l'appréciation, du développement et de l'évaluation)-ADOLOPMENT. L'Agence de santé publique des Caraïbes et l'Organisation panaméricaine de la Santé ont dirigé les travaux en réunissant un groupe diversifié de 16 experts issus de sept pays et territoires des Caraïbes. Le processus d'adaptation, comptant 15 étapes et encadré par un méthodologiste expérimenté, a consisté à sélectionner des questions cliniques pertinentes et à les classer par ordre de priorité selon les besoins régionaux. Ce groupe a évalué les dernières lignes directrices de l'OMS et a intégré des données locales supplémentaires. Il a ensuite ajusté l'orientation et le poids de plusieurs recommandations afin de mieux les adapter au contexte des Caraïbes, en tenant compte des valeurs et des préférences locales, des ressources, de l'accessibilité, de la faisabilité et de l'impact sur l'équité en matière de santé. En fin de compte, l'orientation de deux recommandations et le poids de cinq autres ont été modifiés, en les adaptant aux réalités régionales. Cet effort souligne l'importance d'adapter des lignes directrices mondiales aux contextes locaux, afin d'en améliorer l'applicabilité et l'efficacité. Le processus d'adaptation représente également une occasion précieuse de transfert de compétences et de renforcement des capacités en matière d'élaboration de lignes directrices. Des recherches continues s'imposent pour évaluer l'impact de ces adaptations sur les résultats des soins de santé dans les Caraïbes.

La función normativa de la Organización Mundial de la Salud (OMS) consiste en elaborar directrices basadas en pruebas y principios para orientar a sus Estados Miembros en la toma de decisiones de salud pública bien fundamentadas. Aunque con frecuencia es necesario adaptar estas directrices para garantizar su pertinencia contextual y fomentar una mejor implementación y observancia, la adaptación de directrices existentes es más eficiente que la creación de otras nuevas. Aquí describimos la adaptación de la directriz vigente de la OMS sobre la enfermedad por coronavirus (COVID-19) relativa a las intervenciones farmacológicas para el Caribe utilizando el método de clasificación de valoración, elaboración y evaluación de las recomendaciones (GRADE)-ADOLOPMENT. La Agencia de Salud Pública del Caribe y la Organización Panamericana de la Salud lideraron la iniciativa, que reunió a un variado grupo de 16 expertos de siete países y territorios caribeños. El proceso de adaptación, que comprendió 15 pasos y fue guiado por un metodólogo experimentado, incluyó la selección de preguntas clínicas pertinentes y su priorización en función de las necesidades regionales. El grupo evaluó las últimas directrices de la OMS e integró datos locales adicionales. Ajustaron la orientación y la fuerza de varias recomendaciones para adaptarlas mejor al contexto caribeño, teniendo en cuenta los valores y preferencias locales, los recursos, la accesibilidad, la viabilidad y el impacto en la equidad sanitaria. Finalmente, cambiamos la orientación de dos recomendaciones y la fuerza de cinco para adaptarlas a las realidades regionales. Esta iniciativa destaca la importancia de adaptar las directrices mundiales a los contextos locales, lo que mejora su aplicabilidad y eficacia. El proceso de adaptación también constituye una valiosa oportunidad para la transferencia de conocimientos y el desarrollo de capacidades en la elaboración de directrices. Es necesario seguir investigando para evaluar el impacto de estas adaptaciones en los resultados de la atención sanitaria en el Caribe.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Maternal transmission of human immunodeficiency virus escape mutations subverts HLA-B57 immunodominance but facilitates viral control in the haploidentical infant.

Expression of HLA-B57 is associated with restricted replication of human immunodeficiency virus (HIV), but the mechanism for its protective effect remains unknown. If this advantage depends upon CD8 T-cell recognition of B57-restricted epitopes, mother-to-child transmission of escape mutations within these epitopes could nullify its protective effect. However, if the B57 advantage is largely mediated by selection for fitness-attenuating viral mutations within B57-restricted epitopes, such as T242N in TW10-Gag, then the transmission of such mutations could facilitate viral control in the haploidentical infant. We assessed the consequences of B57-associated mutations on replication capacity, viral control, and clinical outcome after vertical transmission in 13 mother-child pairs. We found that expression of HLA-B57 was associated with exceptional control of HIV during infancy, even when mutations within TW10 and most other B57-restricted epitopes were transmitted, subverting the natural immunodominance of HLA-B57. In contrast, most B57-negative infants born to B57-positive mothers progressed rapidly to AIDS. The presence of T242N led to a reproducible reduction in viral fitness, as demonstrated by in vitro assays using NL4-3 constructs encoding p24 sequences from individual mothers and infants. Associated compensatory mutations within p24-Gag were observed to reverse this impairment and to influence the propensity of T242N to revert after transmission to B57-negative hosts. Moreover, primary failure to control viremia was observed in one infant to whom multiple compensatory mutations were transmitted along with T242N. These parallel in vivo and in vitro data suggest that HLA-B57 confers its advantage primarily by driving and maintaining a fitness-attenuating mutation in p24-Gag.

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.

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.

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.

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.)

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.

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.

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.

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.