BackgroundClinical laboratory reference intervals have not been established in many African countries, and non-local intervals are commonly used in clinical trials to screen and monitor adverse events (AEs) among African participants. Using laboratory reference intervals derived from other populations excludes potential trial volunteers in Africa and makes AE assessment challenging. The objective of this study was to establish clinical laboratory reference intervals for 25 hematology, immunology and biochemistry values among healthy African adults typical of those who might join a clinical trial.Methods and FindingsEqual proportions of men and women were invited to participate in a cross sectional study at seven clinical centers (Kigali, Rwanda; Masaka and Entebbe, Uganda; two in Nairobi and one in Kilifi, Kenya; and Lusaka, Zambia). All laboratories used hematology, immunology and biochemistry analyzers validated by an independent clinical laboratory. Clinical and Laboratory Standards Institute guidelines were followed to create study consensus intervals. For comparison, AE grading criteria published by the U.S. National Institute of Allergy and Infectious Diseases Division of AIDS (DAIDS) and other U.S. reference intervals were used. 2,990 potential volunteers were screened, and 2,105 (1,083 men and 1,022 women) were included in the analysis. While some significant gender and regional differences were observed, creating consensus African study intervals from the complete data was possible for 18 of the 25 analytes. Compared to reference intervals from the U.S., we found lower hematocrit and hemoglobin levels, particularly among women, lower white blood cell and neutrophil counts, and lower amylase. Both genders had elevated eosinophil counts, immunoglobulin G, total and direct bilirubin, lactate dehydrogenase and creatine phosphokinase, the latter being more pronounced among women. When graded against U.S.-derived DAIDS AE grading criteria, we observed 774 (35.3%) volunteers with grade one or higher results; 314 (14.9%) had elevated total bilirubin, and 201 (9.6%) had low neutrophil counts. These otherwise healthy volunteers would be excluded or would require special exemption to participate in many clinical trials.ConclusionsTo accelerate clinical trials in Africa, and to improve their scientific validity, locally appropriate reference ranges should be used. This study provides ranges that will inform inclusion criteria and evaluation of adverse events for studies in these regions of Africa.
Background HIV-1 incidence estimates and correlates of HIV-1 acquisition in African men who have sex with men are largely unknown. Methods Since 2005, HIV-1-uninfected men who reported sex with men and women (MSMW) or sex with men exclusively (MSME) were followed at scheduled visits for collection of behavioural and clinical examination data and plasma for HIV-1 testing. Urethral or rectal secretions were collected from symptomatic men to screen for gonorrhoea. Poisson regression methods were used to estimate adjusted incidence rate ratios (aIRR) to explore associations between risk factors and incident HIV-1 infection. Plasma viral loads (PVL) were assessed over two years following seroconversion. Results Overall HIV-1 incidence in 449 men was 8.6 (95% confidence interval [CI]: 6.7–11.0) per 100 person-years (py). Incidence was 5.8 (95% CI: 4.2–7.9) per 100 py among MSMW, and 35.2 (95% CI: 23.8–52.1) per 100 py among MSME. Unprotected sex, receptive anal intercourse, exclusive sex with men, group sex, and gonorrhoea in the past 6 months were strongly associated with HIV-1 acquisition, adjusted for confounders. PVL in seroconverters was >4 log10 copies/mL at 230 (73.4%) of 313 visits in MSMW and 153 (75.0%) of 204 visits in MSME. Conclusions HIV-1 incidence is very high among MSM in coastal Kenya, and many seroconverters maintain high PVL for up to two years after infection. Effective HIV-1 prevention interventions, including treatment as prevention, are urgently needed in this population.
To characterize WHO-defined transmitted HIV drug resistance mutation (TDRM) data from recently HIVinfected African volunteers, we sequenced HIV ( pol) and evaluated for TDRM the earliest available specimens from ARV-naive volunteers diagnosed within 1 year of their estimated date of infection at eight research centers in sub-Saharan Africa. TDRMs were detected in 19/408 (5%) volunteers. The prevalence of TDRMs varied by research center, from 5/26 (19%) in Entebbe, 6/78 (8%) in Kigali, 2/49 (4%) in Kilifi, to 3/106 (3%) in Lusaka. One of five volunteers from Cape Town (20%) had TDRMs. Despite small numbers, our data suggest an increase in DRMs by year of infection in Zambia ( p ¼ 0.004). The prevalence observed in Entebbe was high across the entire study. ARV history data from 12 (63%) HIV-infected sexual partners were available; 3 reported ARV use prior to transmission. Among four partners with sequence data available, transmission linkage was confirmed and two had the same TDRMs as the newly infected volunteer (both K103N). As ARV therapy continues to increase in availability throughout Africa, monitoring incident virus strains for the presence of TDRMs should be a priority. Early HIV infection cohorts provide an excellent and important platform to monitor the development of TDRMs to inform treatment guidelines, drug choices, and strategies for secondary prevention of TDRM transmission.
Background: Severe acute malnutrition (SAM) is currently defined by the WHO as either a low mid-upper arm circumference (i.e. MUAC <115 mm), a low weight-for-height z-score (i.e. WHZ <− 3), or bilateral pitting oedema. MUAC and WHZ do not always identify the same children as having SAM. This has generated broad debate, as illustrated by the recent article by Grellety & Golden (BMC Nutr. 2016;2:10). Discussion: Regional variations in the proportion of children selected by each index seem mostly related to differences in body shape, including stuntedness. However, the practical implications of these variations in relation to nutritional status and also to outcome are not clear. All studies that have examined the relationship between anthropometry and mortality in representative population samples in Africa and in Asia have consistently showed that MUAC is more sensitive at high specificity levels than WHZ for identifying children at high risk of death. Children identified as SAM cases by low MUAC gain both weight and MUAC in response to treatment. The widespread use of MUAC has brought enormous benefits in terms of the coverage and efficiency of programs. As a large high-risk group responding to treatment, children with low MUAC should be regarded as a public health priority independently of their WHZ. Conclusion: While a better understanding of the mechanism behind the discrepancy between MUAC and WHZ is desirable, research in this area should not delay the implementation of programs aiming at effectively reducing malnutrition-related deaths by prioritising the detection and treatment of children with low MUAC.
Finding, enrolling, and retaining risk populations for HIV prevention trials is challenging in Africa. African MSM are not frequently engaged for research, have high HIV incidence, need urgent risk reduction counseling, and may represent a suitable population for future HIV prevention trials.
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