Arbovirus circulation, epidemiology and spatiotemporal distribution in Uganda

BackgroundArboviruses are endemic in Uganda; however, little is known about their epidemiology, seasonality, and spatiotemporal distribution. This study sought to provide information on arbovirus outbreaks from acute clinical presentations.MethodsA retrospective analysis of IgM and confirmatory Plaque Reduction Neutralization Test (PRNT)and results for arbovirus diagnosis of samples collected from 2016 to 2019 was carried out. Demographic data were used to determine the epidemiology and spatiotemporal distribution of arboviruses using the SaTScan and SPSS software.ResultsArbovirus activity peaked consistently during March-May rainy seasons. The overall arbovirus seroprevalence was 9·5% (137/1441). Of the 137 IgM positives, 72 (52·6%) were confirmed by PRNT, of which the central region (53/72; 73·6%) and YFV (20/72; 27·8%) had the highest prevalence. The 5-14 age group were four times more likely to be infected with an arbovirus p=0·003, 4·1 (1·3- 12·3 CI). Significant arboviral activity was observed among indoor (p=0·003) and outdoor (p=0·05) patients. Spatiotemporal analysis indicated arboviral activity in 23 districts with five distinct clusters in 6 districts. Masaka, in the Central region, was the most affected among the districts, with a significant YFV cluster (p˂0·001) from March to May 2016.InterpretationThis study shows that arbovirus activity peak during the March-May rainy season and highlights the need for YFV mass vaccination to reduce the clinical burden of arboviruses transmitted within the region

B cell sub-types following acute malaria and associations with clinical immunity.

BACKGROUND: Repeated exposure to Plasmodium falciparum is associated with perturbations in B cell sub-set homeostasis, including expansion atypical memory B cells. However, B cell perturbations immediately following acute malaria infection have been poorly characterized, especially with regard to their relationship with immunity to malaria. METHODS: To better understand the kinetics of B cell sub-sets following malaria, the proportions of six B cell sub-sets were assessed at five time points following acute malaria in four to 5 years old children living in a high transmission region of Uganda. B cell sub-set kinetics were compared with measures of clinical immunity to malaria-lower parasite density at the time of malaria diagnosis and recent asymptomatic parasitaemia. RESULTS: Atypical memory B cell and transitional B cell proportions increased following malaria. In contrast, plasmablast proportions were highest at the time of malaria diagnosis and rapidly declined following treatment. Increased proportions of atypical memory B cells were associated with greater immunity to malaria, whereas increased proportions of transitional B cells were associated with evidence of less immunity to malaria. CONCLUSIONS: These findings highlight the dynamic changes in multiple B cell sub-sets following acute, uncomplicated malaria, and how these sub-sets are associated with developing immunity to malaria

The use of common bean (Phaseolus vulgaris ) traditional varieties and their mixtures with commercial varieties to manage bean fly (Ophiomyia spp .) infestations in Uganda

The bean fly (Ophiomyia spp.) is considered the most economically damaging field insect pest of common beans in Uganda. Despite the use of existing pest management approaches, reported damage has remained high. Forty-eight traditional and improved common bean varieties currently grown in farmers’ fields were evaluated for resistance against bean fly. Data on bean fly incidence, severity and root damage from bean stem maggot were collected. Generalized linear mixed model (GLMM) revealed significant resistance to bean fly in the Ugandan traditional varieties. A popular resistant traditional variety and a popular susceptible commercial variety were selected from the 48 varieties and evaluated in pure and mixed stands. The incidence of bean fly infestation on both varieties in mixtures with different arrangements (systematic random versus rows), and different proportions within each of the two arrangements, was measured and analysed using GLMMs. The proportion of resistant varieties in a mixture and the arrangement type significantly decreased bean fly damage compared to pure stands, with the highest decrease in damage registered in the systematic random mixture with at least 50 % of resistant variety. The highest reduction in root damage, obvious 21 days after planting, was found in systematic random mixtures with at least 50 % of the resistant variety. Small holder farmers in East Africa and elsewhere in the world have local preferences for growing bean varieties in genetic mixtures. These mixtures can be enhanced by the use of resistant varieties in the mixtures to reduce bean fly damage on susceptible popular varieties

Mapping the medical outcomes study HIV health survey (MOS-HIV) to the EuroQoL 5 Dimension (EQ-5D-3L) utility index

10.1186/s12955-019-1135-8Health and Quality of Life Outcomes1718

The cost‐effectiveness of prophylaxis strategies for individuals with advanced HIV starting treatment in Africa

Introduction Many HIV‐positive individuals in Africa have advanced disease when initiating antiretroviral therapy (ART) so have high risks of opportunistic infections and death. The REALITY trial found that an enhanced‐prophylaxis package including fluconazole reduced mortality by 27% in individuals starting ART with CD4 <100 cells/mm3. We investigated the cost‐effectiveness of this enhanced‐prophylaxis package versus other strategies, including using cryptococcal antigen (CrAg) testing, in individuals with CD4 <200 cells/mm3 or <100 cells/mm3 at ART initiation and all individuals regardless of CD4 count. Methods The REALITY trial enrolled from June 2013 to April 2015. A decision‐analytic model was developed to estimate the cost‐effectiveness of six management strategies in individuals initiating ART in the REALITY trial countries. Strategies included standard‐prophylaxis, enhanced‐prophylaxis, standard‐prophylaxis with fluconazole; and three CrAg testing strategies, the first stratifying individuals to enhanced‐prophylaxis (CrAg‐positive) or standard‐prophylaxis (CrAg‐negative), the second to enhanced‐prophylaxis (CrAg‐positive) or enhanced‐prophylaxis without fluconazole (CrAg‐negative) and the third to standard‐prophylaxis with fluconazole (CrAg‐positive) or without fluconazole (CrAg‐negative). The model estimated costs, life‐years and quality‐adjusted life‐years (QALY) over 48 weeks using three competing mortality risks: cryptococcal meningitis; tuberculosis, serious bacterial infection or other known cause; and unknown cause. Results Enhanced‐prophylaxis was cost‐effective at cost‐effectiveness thresholds of US$300 and US$500 per QALY with an incremental cost‐effectiveness ratio (ICER) of US$157 per QALY in the CD4 <200 cells/mm3 population providing enhanced‐prophylaxis components are sourced at lowest available prices. The ICER reduced in more severely immunosuppressed individuals (US$113 per QALY in the CD4 <100 cells/mm3 population) and increased in all individuals regardless of CD4 count (US$722 per QALY). Results were sensitive to prices of the enhanced‐prophylaxis components. Enhanced‐prophylaxis was more effective and less costly than all CrAg testing strategies as enhanced‐prophylaxis still conveyed health gains in CrAg‐negative patients and savings from targeting prophylaxis based on CrAg status did not compensate for costs of CrAg testing. CrAg testing strategies did not become cost‐effective unless the price of CrAg testing fell below US$2.30. Conclusions The REALITY enhanced‐prophylaxis package in individuals with advanced HIV starting ART reduces morbidity and mortality, is practical to administer and is cost‐effective. Efforts should continue to ensure that components are accessed at lowest available prices

Late Presentation With HIV in Africa: Phenotypes, Risk, and Risk Stratification in the REALITY Trial.

This article has been accepted for publication in Clinical Infectious Diseases Published by Oxford University PressBackground: Severely immunocompromised human immunodeficiency virus (HIV)-infected individuals have high mortality shortly after starting antiretroviral therapy (ART). We investigated predictors of early mortality and "late presenter" phenotypes. Methods: The Reduction of EArly MortaLITY (REALITY) trial enrolled ART-naive adults and children ≥5 years of age with CD4 counts .1). Results: Among 1711 included participants, 203 (12%) died. Mortality was independently higher with older age; lower CD4 count, albumin, hemoglobin, and grip strength; presence of World Health Organization stage 3/4 weight loss, fever, or vomiting; and problems with mobility or self-care at baseline (all P < .04). Receiving enhanced antimicrobial prophylaxis independently reduced mortality (P = .02). Of five late-presenter phenotypes, Group 1 (n = 355) had highest mortality (25%; median CD4 count, 28 cells/µL), with high symptom burden, weight loss, poor mobility, and low albumin and hemoglobin. Group 2 (n = 394; 11% mortality; 43 cells/µL) also had weight loss, with high white cell, platelet, and neutrophil counts suggesting underlying inflammation/infection. Group 3 (n = 218; 10% mortality) had low CD4 counts (27 cells/µL), but low symptom burden and maintained fat mass. The remaining groups had 4%-6% mortality. Conclusions: Clinical and laboratory features identified groups with highest mortality following ART initiation. A screening tool could identify patients with low CD4 counts for prioritizing same-day ART initiation, enhanced prophylaxis, and intensive follow-up. Clinical Trials Registration: ISRCTN43622374.REALITY was funded by the Joint Global Health Trials Scheme (JGHTS) of the UK Department for International Development, the Wellcome Trust, and Medical Research Council (MRC) (grant number G1100693). Additional funding support was provided by the PENTA Foundation and core support to the MRC Clinical Trials Unit at University College London (grant numbers MC_UU_12023/23 and MC_UU_12023/26). Cipla Ltd, Gilead Sciences, ViiV Healthcare/GlaxoSmithKline, and Merck Sharp & Dohme donated drugs for REALITY, and ready-to-use supplementary food was purchased from Valid International. A. J. P. is funded by the Wellcome Trust (grant number 108065/Z/15/Z). J. A. B. is funded by the JGHTS (grant number MR/M007367/1). The Malawi-Liverpool–Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine (grant number 101113/Z/13/Z) and the Kenya Medical Research Institute (KEMRI)/Wellcome Trust Research Programme, Kilifi (grant number 203077/Z/16/Z) are supported by strategic awards from the Wellcome Trust, United Kingdom. Permission to publish was granted by the Director of KEMRI. This supplement was supported by funds from the Bill & Melinda Gates Foundation