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Background and ObjectivesMultisystem inflammatory syndrome of children (MISC) carries a high attributable morbidity. We describe children aged MethodsAll were tested for SARS-CoV-2, infectious disease consultations performed, modified CDC criteria for MISC applied, charts reviewed and data analyzed.ResultsAmong 79 consecutive children with SARS-CoV-2, 41(52%) were hospitalised; with median age 10.5 years; Afro-Caribbean ethnicity 40(98%); males 21(51%); SARS-CoV-2 RT-PCR positivity 26 (63%), IgG/IgM positivity 7(17%), community exposures 8 (20%). MISC-cases 18 (44%) vs. non-MISC 23(56%) had fever (94% vs. 30%; pConclusionMISC was treated successfully with intravenous gammaglobulin, steroids and/or aspirin in 94% before cardiopulmonary decompensation, or need for inotropes, vasopressors, or invasive ventilation.

Background: Although the number of Zika virus (ZIKV) cases has substantially declined in Latin America and the Caribbean since the 2015-2016 outbreaks, the cohort of children born at that time and affected by congenital zika syndrome (CZS) are now around 4-5 years old and experiencing an ongoing impact on their health and development. Gaps in our understanding remain regarding the outcomes of ZIKV exposure in utero and congenital infection and the consequences of congenital zika syndrome (CZS) for health throughout childhood. Methods: The ZIKAction Paediatric Registry is an international multi-centre registry of infants and children with documented ZIKV exposure in utero (i.e. born to mother with confirmed infection in pregnancy) and/or with confirmed or suspected congenital ZIKV infection. Clinical teams at participating sites in Argentina, Brazil and Jamaica conduct retrospective case note reviews of children eligible for inclusion in the Registry and enter pseudonymised data into a central Registry database, with additional data collected prospectively on routine follow-up at some sites. Data collected will include sociodemographic, maternal and pregnancy information, delivery information and newborn assessment, paediatric clinical assessments (physical, neurological, developmental, ophthalmological, audiological), and laboratory results conducted as part of local standard of care. The ZIKAction Paediatric Registry network will conduct pooled analyses to address questions relating to characteristics, health and neurodevelopmental outcomes of this population. The Registry is embedded within a larger programme of research studies conducted by ZIKAction. Discussion: As the health outcomes of children affected by ZIKV continue to unfold, this paediatric registry will provide comprehensive data on their clinical and neurodevelopmental outcomes, growth and management, as well as on later sequelae. This will inform their support and care and provide potential insights on pathogenesis of the disease, of importance to currently affected families and for the response to possible future outbreaks. It will highlight the service needs of the affected populations in Latin America and the Caribbean and allow the identification of potential participants for future studies.

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.

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.

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.

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.

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. Children5 years (especially2) 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.

Summary Objectives We aimed to characterize neurological outcomes and determine the prevalence of HIV encephalopathy in a cohort of HIV-infected children in Jamaica. Methods Data for 287 HIV-infected children presenting between 2002 and 2008 were reviewed and neurological outcomes characterized. A nested case–control study was conducted between July and September 2009 used 15 randomly selected encephalopathic HIV-infected children aged 7–10 years and 15 matched controls (non-encephalopathic HIV-infected). Their neurocognitive functions were evaluated using clinical assessment and standardized tests for intelligence, short term memory (visuo-spatial and auditory), selective attention, and fine motor and coordination functions. Outcomes were compared using Fisher's exact test and the Mann–Whitney U -test. Results Sixty-seven (23.3%) children were encephalopathic. The median age at diagnosis of HIV encephalopathy was 1.6 years (interquartile range (IQR) 1.1–3.4 years). Predominant abnormalities were delayed milestones (59, 88.1%), hyperreflexia (59, 86.5%), spasticity (50, 74.6%), microcephaly (42, 61.7%), and quadriparesis (21, 31.3%). The median age of tested children was 8.7 years (IQR 7.6–10.8 years) in the encephalopathic group and 9 years (IQR 7.4–10.7 years) in the non-encephalopathic group. Encephalopathic children performed worse in all domains of neurocognitive function ( p Conclusions A high prevalence of HIV encephalopathy was noted, and significant neurocognitive dysfunction identified in encephalopathic children. Optimized management through the early identification of neurological impairment and implementation of appropriate interventions is recommended to improve quality of life.

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.

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 3000copies/ml without antiretroviral therapy, and ‘treated progressors’ who had initiated HAART. Methods: Recognition of HIV optimal epitopes was assessed by interferon g (IFNg) enzyme-linked immunosorbent spot. Functional characterization of CD8 cells targeting B57 epitopes was performed by staining for cytokine production (intracellular IFNg, interleukin-2, tumor necrosis factor a) and degranulation. Sequencing of autologous RNA was performed to determine the prevalence of viral escape mutations within B57restricted 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. 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins AIDS 2010, 24:1425‐1435

Summary 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 ≥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.

Worldwide, rotaviruses have been a significant cause of dehydrating gastroenteritis. This contributed to increased infant morbidity and mortality in Jamaica. We enrolled 1804 Jamaican infants in the international randomized, placebo-controlled, pentavalent (G1, G2, G3, G4 and P1) rotavirus vaccine trial. This pentavalent vaccine was found to significantly reduce rotavirus gastroenteritis attributable emergency room visits and hospitalizations, without increasing the rates of intussusception, or other serious adverse events in Jamaican infants. It is recommended that the rotavirus vaccine be included in Jamaica's National Immunization Programme in accordance with recommendations from the World Health Organization.

Objective:To assess the risk of Mycobacterium tuberculosis infection and disease among patients and workers in a regional pediatric hospital.Design:Descriptive epidemiological study of the mandatory tuberculin skin testing program of hospital employees at hire and during annual reevaluation, pediatric patients with tuberculosis (TB), efficacy of hospital infection control measures, and community rates of TB.Setting:361-bed, university, pediatric hospital serving Cincinnati (1.7 million population).Results:During 1986 through 1994, 2,275 to 4,356 employees were compliant with Mantoux skin testing and screening each year. This represented >97% of the population who were eligible for screening. The cumulative rate of M tuberculosis infection from a previous positive tuberculin skin test was 10% to 12% per year during 1986 through 1994. Among new Mantoux skin-test converters in employees at annual reevaluation, the risk of TB infection was 0.3% in 1993 and 1994. There were no active cases of TB identified during new employee screening or annual reevaluation. Of 62 new Mantoux skin-test converters in 9 years, 23% were foreign-born, 13% were Asian, 23% were African American, 11% received the bacillus of Calmette-Guerin vaccine, and 60% had direct patient care or indirect patient contact. A cluster of five converters occurred in a department with no patient care or contact. Mantoux conversion rates were 1.9 per 1,000 employee patient-care or contact-years and 2.2 per 1,000 employee non-patient-contact years. Twenty pediatric patients with active TB were identified during 1991 to 1994, with ≤6 cases per year, placing this hospital in the low-risk category for M tuberculosis disease. Three children with pulmonary TB were admitted without immediate respiratory isolation, possibly exposing 9 patients and 42 employees; none converted their Mantoux skin tests on retesting. Rates of active TB in Cincinnati were stable during the period (eg, 8/100,000 population in 1994).Conclusions:Despite intense active surveillance among thousands of hospital employees with >97% annual compliance, tuberculin conversion rates were low, and no cases of active TB were identified during 9 years of follow-up. There was no evidence of transmission of M tuberculosis from infected patients to employees during uncontrolled exposures. Rates of TB in the community were low. These data suggest that rigorous application of the Centers for Disease Control and Prevention guidelines and Occupation Safety and Health Administration regulations for preventing nosocomial TB in pediatric hospitals may be excessive and costly. Special provisions should be made for pediatric hospitals with a proven low risk of transmission of M tuberculosis

We prospectively surveyed for rectal colonization with vancomycin-resistant Enterococcus among 93 high-risk pediatric patients who were hospitalized at least 5 (median, 20) days. Fifty-two patients (56%) had enterococcal colonization; none had active infection with Enterococcus. All enterococci were vancomycin-susceptible (minimum inhibitory concentration < or =4 microg/mL). Associated exposures included recent antibiotics (50, 96%), surgical procedures (26, 58%), and immunosuppression (15, 29%).

An apparent increase in the incidence of enterococcal bacteremias from 7 to 48/1000 bacteremias during 1986 to 1991 (p < 0.01) prompted this descriptive clinical and molecular epidemiologic study of 83 episodes occurring in 80 children between 1986 and 1992. Most community-acquired cases were in infants, in comparison with nosocomial episodes (24/26 and 34/57; p < 0.01); many of them were neonates (10/26 and 6/57; p < 0.01). Nosocomial cases were associated with underlying conditions including major surgery 56%, immunosuppression 49%, organ and tissue transplants 30%, and cardiac 32%, pulmonary 25%, renal 21%, and hepatic 21% disorders. Nosocomial episodes developed after a median of 32 days. There were 58 primary and 25 secondary bacteremias. Thirty-two episodes were polymicrobial and 44 organisms were involved. Twenty-six percent of the patients died. In 15%, death was preceded by septic shock, disseminated intravascular coagulation, and polymicrobial bacteremia (p < 0.01). Of 75 isolates, 82% were Enterococcus faecalis and 14% were Enterococcus faecium. Fourteen E. faecalis strains produced hemolysin; none produced beta-lactamase. Three had high-level resistance to gentamicin and 13 to streptomycin; two E. faecium and none of the E. faecalis strains were vancomycin resistant at a low level (p < 0.01) and one was ampicillin resistant. Pulsed-field gel electrophoresis of whole-cell DNA digested with restriction enzymes Sma I and Eag I showed five isolates with a homogeneous pattern, two with another homogeneous pattern, and 68 with distinct heterogeneous patterns. The increase in enterococcal bacteremias was not due to a clonal strain dissemination but to an increase in cases of heterogeneous enterococcal strains. We conclude that enterococcal septicemia is now an important cause of serious morbidity and death in critically ill 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.

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.

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.

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-γ, TNF-α, 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.

Measles antibody titres were determined by haemagglutination inhibition and by neutralization in 221 sets of serum collected from delivering mothers, umbilical cords, and infants when about six months of age. Radio-immunoassay was also used to measure antibody in 120 sera. Total IgG concentration was determined in the infant sera. All mothers had measles antibody and the mean titre was high. At the time of birth, measles antibody had been further concentrated in the infant. Nevertheless, many children lost protective titres before six months of age. The rate of loss was correlated with the infant's total serum IgG so that high IgG levels at six months correlated with rapid loss of measles-specific antibody. It is suggested that in homes where sanitation is poor, antibody is made to many agents at an early age. To maintain physiological balance, homeostatic mechanisms then increase the rate of catabolism of all IgG, including that passively acquired. In keeping with its stage of sanitary development, vaccination in Jamaica can profitably be given earlier than in the United States, but it must be later than in many African countries.

The subtypes of 141 isolates of human immunodeficiency virus type-1 (HIV-1) from Jamaica were determined by a combination of env and gag heteroduplex mobility analysis (HMA) genotyping. The majority of HIV-1 isolates were subtype B (131/141, 93.0%); one (0.8%) isolate each of subtypes C, D and E was found and 7 (4.9%) were indeterminate. These results and the failure of the sets of primers used to amplify some of the HIV-1 isolates provide strong evidence of genetic diversity of the HIV/AIDS epidemic in Jamaica. Surveillance of the circulating HIV-1 genetic subtypes is a pre-requisite for developing regional vaccine strategies and understanding the transmission patterns of the virus. This is the first study of its kind in Jamaica and the findings complement data from other Caribbean countries. This work supports the view of colleagues from the French and Spanish-speaking Caribbean that an epidemiological network supported by regional laboratories will help track this epidemic accurately with positive outcomes for the public.

Long-term backyard smelting of lead in a district known as Mona Commons, Kingston, Jamaica, has produced lead burdens as high as 30 000 mg/kg in soils near to the smelter, and indoor dust loadings of 373 microg/f2 in the residents' home. The blood lead levels (BPb) of 107 children from the district were in the range 2.2-202 microg/dL. Fifty-nine per cent of these had BPb levels above 10 microg/dL and the population mean was an unacceptably high 25.1 microg/dL. The highest levels were observed for five siblings, two of whom presented with lead encephalopathy. This severe chronic exposure to lead was exacerbated by a significant history of pica, and chronic nutritional anaemia. Chelation therapy significantly reduced the BPb levels but due to lead storage in other organs, the values after several months were still higher than desirable. This study emphasizes the importance of reducing the exposure of children to lead.

Objective: The objective structured clinical examination (OSCE) has been recognized not only as a useful assessment tool but also as a valuable method of promoting student learning. Student selfassessment is also seen as a means of helping students recognize their strengths and weaknesses, understand the relevance of core learning objectives and to take more responsibility for each stage of their work. The authors sought to evaluate the accuracy of medical student self-assessment of their performance in the paediatric clerkship OSCE and thus obtain preliminary data for use in programme strengthening. Design and Methods: A self-administered questionnaire was completed by successive groups of students immediately after the OSCE at the end of each clerkship rotation. Students assessed their performance at each station, using a performance rating scale. Performance data were summarized using descriptive and non-parametric tests. Basic statistical analysis of the Likert items was conducted by calculating frequencies, means and standard deviations. Regression analysis was used to correlate selfreported rating and actual performance in each station. A p value of < 0.05 was considered significant. Eighty-one students (92%) completed the questionnaire. Results: Fifty-eight (72%) of the students achieved greater than minimum competence in their overall scores. Significant positive correlation (p < 0.05) between student self-rating and actual score was noted among the following stations: technical skills, cardiovascular examination, assessment of dysmorphism, dermatology, communication and photographic interpretation stations. Students overestimated their performance in the gastrointestinal examination, radiological and arterial blood gas interpretation. Students underestimated their performance in the following: respiratory system, examination of the head, developmental and nutritional assessment. Conclusions: The findings highlight the perceived strengths and weaknesses in clinical competence and self-assessment skills and provide direction for programme training needs.

We present a case of Kawasaki syndrome complicated by coronary aneurysm in a 6-year-old boy with laboratory evidence of group A streptococcal infection and infectious mononucleosis. The case demonstrates that evidence of acute infection in a patient with features suggestive of Kawasaki syndrome should not exclude a diagnosis of the latter. Immunoglobulin therapy should be considered seriously in highly suggestive cases, even if diagnostic criteria are not fulfilled.

The safety and immunogenicity of acellular pertussis (AP) vaccine in outbreak control was determined in a randomized, double-blind, controlled trial. Participants received AP vaccine (n=102), which contained 25 microg of pertussis toxoid (PT) and 3 microg of filamentous hemagglutinin (FHA), or licensed meningococcal vaccine (MN; n=97). Local reactions (pain or tenderness, redness, swelling, and induration) and systemic reactions (fever, sleepiness or lethargy, and irritability) were similar among AP and MN vaccinees. One month after AP vaccination, the geometric mean level of IgG anti-PT was 33.1 microg/mL, with 2-fold increases in 85% of patients and 4-fold increases in 73% of patients; for IgG anti-FHA, the respective values were 34.7 microg/mL, 92%, and 63%. After 6 months of follow-up, no serological evidence of pertussis was seen among symptomatic or asymptomatic subjects. However, recent evidence of Bordetella pertussis infection before immunization was shown. Thus, AP vaccine was safe and immunogenic in adults.

Objective. To describe the clinical characteristics of complicated parapneumonic effusions (CPE) in children caused by Streptococcus pneumoniae nonsusceptible to penicillin (PCN-N) and compare their clinical outcome with CPE caused by penicillin-susceptible (PCN-S) organisms.Design. Children with parapneumonic effusions were identified retrospectively between July 1992 and June 1996. Charts of patients with CPE were reviewed for data obtained at the time of hospital admission. In addition, outpatient charts and/or the families of children with CPE caused by PCN-N S pneumoniae were reviewed to identify specific risk factors associated with PCN-N organisms.Results. Sixty-four cases of CPE were identified during the 4-year period. In 26 cases a bacterial pathogen was recovered, withS pneumoniae accounting for 23 of these isolates (88%). Of the 23 S pneumoniae cases, 17 were PCN-S and 6 cases were nonsusceptible. Complicated parapneumonic effusions caused by PCN-NS pneumoniae occurred in significantly younger patients than CPE that were PCN-S (2.1 years vs 7.9 years). Nonsusceptible effusions also had a higher incidence of bacteremia than PCN-S effusions (100% vs 29%). There were no significant differences between the two groups for duration of chest tube drainage, febrile days, oxygen use, and hospital stay.Conclusion. CPE caused by PCN-N S pneumoniaeis associated with a younger age and higher rate of bacteremia than CPE caused by PCN-S strains. However, there were no significant differences in outcome measures between patients infected with susceptible or nonsusceptible organisms.

Empyema rarely complicates pneumonia. In a 361-bed regional pediatric hospital, 50 pleural empyemas were identified from 1988 through 1994; 17 (34%) occurred in the last 12 months of this period, for which the incidence was 3.3 per 100,000 of the population aged < or = 18 years (P < .05, chi 2 test). A significant seasonal prevalence was observed: 50% of cases occurred in the winter (P < .001, chi 2 test). In contrast with the findings of previous studies, in which empyemas predominantly occurred in infants, the median age of our patients was 7 years; underlying illnesses were present in only 10%, and all had community-acquired disease. Eighty-two percent had chest tubes inserted, 56% required a thoracotomy with pleural decortication, and 2% had a lobectomy. There were no deaths. Streptococcus pneumoniae was isolated in 40% of the cases; specimens in 44% of the cases were sterile. None of the empyemas were associated with Staphylococcus aureus or Haemophilus influenzae type b, and only one was caused by group A streptococcus. Among 13 S. pneumoniae isolates, the rate of resistance to penicillin was 15%; to erythromycin, 15%; to chloramphenicol, 31%; and to cefotaxime, 23%. The penicillin-resistance rate among blood and cerebrospinal fluid pneumococcal isolates was 17% during 1993-1994. Drug-resistant S. pneumoniae is now a recognized cause of pleural empyemas in children.

Objective:To study the epidemiology of Acinetobacter baumanii during a period of increased seasonal prevalence.Design:Descriptive molecular and clinical epidemiologic study of A baumanii isolates from 1990 through 1992.Setting:A 770-bed urban, acute, tertiary-care university hospital.Results:During 1990 through 1992, the rate of A baumanii isolations was 30.4 per 1,000 culture isolations during the summer, compared to 12.6 per 1,000 culture isolations during the fall, winter, and spring (P

Objective: To describe methods of preventing nosocomial pertussis in patients, employees, and visitors to a hospital during a communitywide epidemic in Greater Cincinnati. Design: Six-month descriptive study of the methods, effectiveness, and cost of a program to prevent nosocomial pertussis. Setting: Three hundred sixty-one bed, tertiary-care, university, pediatric hospital. Results: We educated 3,764 hospital employees about pertussis. We evaluated 206 employees with respiratory illnesses, based on clinical presentation, pertussis exposure, and work setting. Eighty-seven had pertussis: 84 coughed for > or = 2 weeks (outbreak clinical case definition), 65 had paroxysms, 27 whooped, 22 had posttussive emesis, and 13 were positive by direct fluorescent antibody or culture for Bordetella pertussis. Seventy-nine employees were sent on 5-day furloughs. Six hundred twenty-two employees received 14 days of erythromycin (579) or trimethoprim-sulfamethoxazole (43). Symptomatic patients were identified at triage in the emergency department and placed in respiratory isolation. Suspect pertussis cases were admitted in respiratory isolation. Among 49 toddlers who were given erythromycin and managed in "coughing respiratory cohorts," eight had proven pertussis. Inpatients were restricted to assigned nursing units. Respiratory masks were required for those entering the test referral center, where more than 3,500 pertussis cultures were performed. Hospitalwide visitor restriction was enforced for those aged 14 years or younger and for those with respiratory symptoms. Only parents and guardians were permitted to visit the newborn intensive care unit. A child-care service managed 488 inpatient sibling visitors. Four symptomatic children in the employees' child-care center were excluded pending physician evaluation; one had pertussis. Conclusions: Control measures appeared effective. Pertussis occurred in 87 (2%) employees. Among 102 children hospitalized with pertussis, respiratory isolation was delayed in nine cases, and one case was nosocomial. Program expenses totalled $85,400. Adult booster immunization with acellular pertussis vaccine might represent the safest and least expensive strategy for preventing epidemic pertussis, and controlled trials of acellular pertussis vaccine in hospital employees are needed.

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.

In 1993 there was a resurgence of pertussis in the United States. Altogether, 6335 cases were reported, the most in 26 years.Using active microbiologic surveillance, we investigated the epidemic of pertussis in Greater Cincinnati in 1993. The population of 1.7 million in this area is served by a single children's hospital and pertussis laboratory. We prospectively followed patients given a new diagnosis of pertussis in July through September 1993 to determine the characteristics of the epidemic.From 1979 to 1992, there was a cumulative total of 542 cases of pertussis. In 1993, 352 cases were diagnosed, an increase of 259 percent over the 1992 total. Sixty-three percent of the cases had positive cultures for Bordetella pertussis, 18 percent were positive on direct fluorescent-antibody testing only, and 19 percent were diagnosed clinically. The outbreak began in the suburbs during the summer and spread through Greater Cincinnati. Of 255 total cases diagnosed in July through September (195 excess cases over the maximal base-line level of 20 per month in the previous 14 years), 75 percent were in white patients and 67 percent of the patients had private insurance or paid for care out of pocket. In 1993, as compared with 1979 through 1992, there was a shift in incidence from younger infants to older children; the percentages of cases according to age group were as follows: 0 to 6 months, 53 percent from 1979 through 1992 and 35 percent in 1993 (P0.001); 7 months to 5 years, 33 percent and 43 percent (P0.002); 6 to 12 years, 5 percent and 11 percent (P0.001); and more than 12 years, 5 percent and 11 percent (P0.003). Immunization records revealed that 74 percent (75 of 101) of the children with pertussis who were 19 months to 12 years old had received four or five doses of the combined diphtheria-pertussis-tetanus (DPT) vaccine, and that 82 percent (103 of 126) of those 7 to 71 months old had received at least three doses of DPT vaccine. The whole-cell vaccines used came from both of the major manufacturers (Connaught Laboratories and Lederle Laboratories). Disease was not severe, but 80 of the 255 children (31 percent) given diagnoses during the three epidemic months were hospitalized. There were no deaths.Since the 1993 pertussis epidemic in Cincinnati occurred primarily among children who had been appropriately immunized, it is clear that the whole-cell pertussis vaccine failed to give full protection against the disease.

NICHD 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 >2500 g 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% = 29 (p = 0.003). the odds of LRTI in infants with a CD4+ count (cells/ mm(3)) = 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. (C) 2010 International Society for Infectious Diseases. Published by Elsevier B.V. All rights reserved. Univ São Paulo, Fac Med Ribeirao Preto, BR-14049900 Ribeirao Preto, SP, Brazil WESTAT Corp, Rockville, MD 20850 USA Univ Caxias Sul, Rio Grande Do Sul, Brazil Hosp Diego Paroissien, Buenos Aires, DF, Argentina Universidade Federal de São Paulo, São Paulo, Brazil Univ W Indies, Kingston 7, Jamaica Hosp Juan Fernandez, Buenos Aires, DF, Argentina Hosp Agudos Dra Cecilia Grierson, Buenos Aires, DF, Argentina NICHD, Pediat Adolescent & Maternal AIDS Branch, CRMC, NIH,DHHS, Bethesda, MD USA Universidade Federal de São Paulo, EPM, São Paulo, Brazil NICHD: N01-HD-3-3345 NICHD: HHSN267200800001C NICHD: N01-DK-8-0001 Web of Science

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.

Medical records of 60 patients with bacteremia caused by group A streptococci who were treated at the Yale-New Haven (Conn) Hospital from 1973 to 1986 and the Boston Children's Hospital Medical Center from 1977 to 1984 were reviewed. Seven children (12%) were immunocompromised, seven (12%) had varicella, and two (3%) had cavernous hemangiomas. Fifty-two children (87%) had an identifiable focus of infection. The most commonly documented sources of bacteremia were in the skin (22 children) and the respiratory tract (19 children). Metastatic foci of infection included osteomyelitis (nine children), septic arthritis (eight children), and meningitis (three children). Seven episodes were nosocomial (four were catheter related and three occurred postoperatively). Four patients (7%) died: two were severely immunocompromised, one of whom had extensive hemorrhagic varicella; the third had widespread hemorrhage into a large cavernous hemangioma of the skin; the fourth had an initial diagnosis of sudden infant death syndrome. Bacteremia with group A streptococci, although uncommon, continues to cause serious infections in children during the antibiotic era.