CCR5 deficiency increases risk of symptomatic West Nile virus infection

West Nile virus (WNV) is a reemerging pathogen that causes fatal encephalitis in several species, including mouse and human. Recently, we showed that the chemokine receptor CCR5 is critical for survival of mice infected with WNV, acting at the level of leukocyte trafficking to the brain. To test whether this receptor is also protective in man, we determined the frequency of CCR5Δ32, a defective CCR5 allele found predominantly in Caucasians, in two independent cohorts of patients, one from Arizona and the other from Colorado, who had laboratory-confirmed, symptomatic WNV infection. The distribution of CCR5Δ32 in a control population of healthy United States Caucasian random blood donors was in Hardy-Weinberg equilibrium and CCR5Δ32 homozygotes represented 1.0% of the total group (n = 1,318). In contrast, CCR5Δ32 homozygotes represented 4.2% of Caucasians in the Arizona cohort (odds ratios [OR] = 4.4 [95% confidence interval [CI], 1.6–11.8], P = 0.0013) and 8.3% of Caucasians in the Colorado cohort (OR = 9.1 [95% CI, 3.4–24.8], P < 0.0001). CCR5Δ32 homozygosity was significantly associated with fatal outcome in the Arizona cohort (OR = 13.2 [95% CI, 1.9–89.9], P = 0.03). We conclude that CCR5 mediates resistance to symptomatic WNV infection. Because CCR5 is also the major HIV coreceptor, these findings have important implications for the safety of CCR5-blocking agents under development for HIV/AIDS

Rapid Training and Implementation of the Pollock Technique, a Safe, Effective Newborn Circumcision Procedure, in a Low-Resource Setting

Male circumcision is highly protective against urinary tract infections, inflammatory conditions of the penis, sexually transmitted infections, and urogenital cancers. We aimed to reintroduce newborn male circumcision through the creation of a training program in Port-au-Prince, Haiti?an area with a considerable burden of preventable urogenital infections, sexually transmitted infections, and low circumcision rate?after an earlier study reported that a majority of Haitian medical providers were in need of and wanted newborn circumcision training. The program was conducted at the GHESKIO Health Centers, a large, non-governmental clinic offering comprehensive pediatric and adult health services. Two Haitian obstetricians and seven nurses learned circumcision procedures. On training completion, one of two obstetricians achieved surgical competence. Introduction of a newborn male circumcision training program was feasible, achieving an acceptable rate of procedural competency and high-quality services. Permanent resources now exist in Haiti to train additional providers to perform newborn male circumcisions

Tuberculosis in the aftermath of the 2010 earthquake in Haiti.

PROBLEM: In 2010, Haiti sustained a devastating earthquake that crippled the health-care infrastructure in the capital city, Port-au-Prince, and left 1.5 million people homeless. Subsequently, there was an increase in reported tuberculosis in the affected population. APPROACH: We conducted active tuberculosis case finding in a camp for internally displaced persons and a nearby slum. Community health workers screened for tuberculosis at the household level. People with persistent cough were referred to a physician. The National Tuberculosis Program continued its national tuberculosis reporting system. LOCAL SETTING: Even before the earthquake, Haiti had the highest tuberculosis incidence in the Americas. About half of the tuberculosis cases occur in the Port-au-Prince region. RELEVANT CHANGES: The number of reported tuberculosis cases in Haiti has increased after the earthquake, but data are too limited to determine if this is due to an increase in tuberculosis burden or to improved case detection. Compared to previous national estimates (230 per 100,000 population), undiagnosed tuberculosis was threefold higher in a camp for internally displaced persons (693 per 100,000) and fivefold higher in an urban slum (1165 per 100,000). With funding from the World Health Organization (WHO), active case finding is now being done systematically in slums and camps. LESSONS LEARNT: Household-level screening for prolonged cough was effective in identifying patients with active tuberculosis in this study. Without accurate data, early detection of rising tuberculosis rates is challenging; data collection should be incorporated into pragmatic disease response programmes

CYP2B6 Variants and Plasma Efavirenz Concentrations during Antiretroviral Therapy in Port‐au‐Prince, Haiti

Polymorphisms in CYP2B6 are known to predict increased steady-state plasma concentrations of efavirenz. We characterized relationships between genetic polymorphisms and plasma efavirenz concentrations among 45 Haitians who initiated antiretroviral therapy in Port-au-Prince

HIV-1 Epidemic in the Caribbean Is Dominated by Subtype B

The molecular epidemiology of HIV-1 in the Caribbean has been described using partial genome sequencing; subtype B is the most common subtype in multiple countries. To expand our knowledge of this, nearly full genome amplification, sequencing and analysis was conducted.Virion RNA from sera collected in Haiti, Dominican Republic, Jamaica and Trinidad and Tobago were reverse transcribed, PCR amplified, sequenced and phylogenetically analyzed. Nearly full genomes were completed for 15 strains; partial pol was done for 67 strains. All but one of the 67 strains analyzed in pol were subtype B; the exception was a unique recombinant of subtypes B and C collected in the Dominican Republic. Of the nearly full genomes of 14 strains that were subtype B in pol, all were subtype B from one end of the genome to the other and not inter-subtype recombinants. Surprisingly, the Caribbean subtype B strains clustered significantly with each other and separate from subtype B from other parts of the pandemic.The more complete analysis of HIV-1 from 4 Caribbean countries confirms previous research using partial genome analysis that the predominant subtype in circulation was subtype B. The Caribbean strains are phylogenetically distinct from other subtype B strains although the biological meaning of this finding is unclear

A Second Look at the Association between Gender and Mortality on Antiretroviral Therapy

Objective: We assessed the association between gender and mortality on antiretroviral therapy (ART) using identical models with and without sex-specific categories for weight and hemoglobin. Design: Cohort study of adult patients on ART. Setting: GHESKIO Clinic in Port-au-Prince, Haiti. Participants: 4,717 ART-naïve adult patients consecutively enrolled on ART at GHESKIO from 2003 to 2008. Main Outcome Measure: Mortality on ART; multivariable analyses were conducted with and without sex-specific categories for weight and hemoglobin. Results: In Haiti, male gender was associated with mortality (OR 1.61; 95% CI: 1.30–2.00) in multivariable analyses with hemoglobin and weight included as control variables, but not when sex-specific interactions with hemoglobin and weight were used. Conclusions: If sex-specific categories are omitted, multivariable analyses indicate a higher risk of mortality for males vs. females of the same weight and hemoglobin. However, because males have higher normal values for weight and hemoglobin, the males in this comparison would generally have poorer health status than the females. This may explain why gender differences in mortality are sometimes observed after controlling for differences in baseline variables when gender-specific interactions with weight and hemoglobin are omitted

Adapting and Implementing a Community Program to Improve Retention in Care among Patients with HIV in Southern Haiti: “Group of 6”

Objective. In Mozambique, a patient-led Community ART Group model developed by Médecins Sans Frontières improved retention in care and adherence to antiretroviral therapy (ART) among persons with HIV. We describe the adaptation and implementation of this model within the HIV clinic located in the largest public hospital in Haiti’s Southern Department. Methods. Our adapted model was named Group of 6. Hospital staff enabled stable patients with HIV receiving ART to form community groups with 4–6 members to facilitate monthly ART distribution, track progress and adherence, and provide support. Implementation outcomes included recruitment success, participant retention, group completion of monthly monitoring forms, and satisfaction surveys. Results. Over one year, 80 patients from nine communities enrolled into 15 groups. Six participants left to receive HIV care elsewhere, two moved away, and one died of a non-HIV condition. Group members successfully completed monthly ART distribution and returned 85.6% of the monthly monitoring forms. Members reported that Group of 6 made their HIV management easier and hospital staff reported that it reduced their workload. Conclusions. We report successful adaptation and implementation of a validated community HIV-care model in Southern Haiti. Group of 6 can reduce barriers to ART adherence, and will be integrated as a routine care option

External validation of the RISC, RISC-Malawi, and PERCH clinical prediction rules to identify risk of death in children hospitalized with pneumonia

From Crossref journal articles via Jisc Publications RouterBackground Existing scores to identify children at risk of hospitalized pneumonia-related mortality lack broad external validation. Our objective was to externally validate three such risk scores. Methods We applied the Respiratory Index of Severity in Children (RISC) for HIV-negative children, the RISC-Malawi, and the Pneumonia Etiology Research for Child Health (PERCH) scores to hospitalized children in the Pneumonia REsearch Partnerships to Assess WHO REcommendations (PREPARE) data set. The PREPARE data set includes pooled data from 41 studies on pediatric pneumonia from across the world. We calculated test characteristics and the area under the curve (AUC) for each of these clinical prediction rules. Results The RISC score for HIV-negative children was applied to 3574 children 0-24 months and demonstrated poor discriminatory ability (AUC = 0.66, 95% confidence interval (CI) = 0.58-0.73) in the identification of children at risk of hospitalized pneumonia-related mortality. The RISC-Malawi score had fair discriminatory value (AUC = 0.75, 95% CI = 0.74-0.77) among 17 864 children 2-59 months. The PERCH score was applied to 732 children 1-59 months and also demonstrated poor discriminatory value (AUC = 0.55, 95% CI = 0.37-0.73). Conclusions In a large external application of the RISC, RISC-Malawi, and PERCH scores, a substantial number of children were misclassified for their risk of hospitalized pneumonia-related mortality. Although pneumonia risk scores have performed well among the cohorts in which they were derived, their performance diminished when externally applied. A generalizable risk assessment tool with higher sensitivity and specificity to identify children at risk of hospitalized pneumonia-related mortality may be needed. Such a generalizable risk assessment tool would need context-specific validation prior to implementation in that setting.11pubpub