Human IgG subclass antibodies to the 19 kilodalton carboxy terminal fragment of Plasmodium Falciparum merozoite surface protein 1 (MSP119) and predominance of the MAD20 allelic type of MSP1 in Uganda

Objective: To determine the natural human humoral immune responses to the 19 kilodalton carboxy terminal fragment of Plasmodium falciparum merozoite surface protein 1 (MSP119), a malaria candidate vaccine antigen and to determine the prevalence of MAD20 and K1 alleles of P. falciparum MSP1.Design: Community based cross-sectional study.Setting: Atopi Parish, Apac District, Uganda, 1995.Subjects: Three hundred and seventy four Ugandans betwee

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

The cardiotonic effect of the crude ethanolic extract of Nerium oleander in the isolated guinea pig hearts

Cardiovascular diseases are increasingly becoming one of the leading diseases causing morbidity and mortality in Uganda. Ethnographic evidence suggests that these diseases are often first managed by indigenous and related herbs before patients are referred for allopathic forms of management. One such herb of interest is Nerium oleander. Therefore the crude ethanolic extracts of the dried leaves of this herb were tested against the following parameters in the isolated guinea pig hearts: force of contraction, heart rate and cardiac flow. The extracts brought about dose-dependent increases in all these parameters from their baseline readings. Compared with graded doses of digoxin the effects closely mirrored the activities in a dose dependent manner. At the mechanism of action level, it would appear the extract works in the same as digoxin since their dose-contraction-reponse curves are parallel. This finding would tend to provide a strong rationale for the herb's traditional use in cardiovascular illness

Ethnomedicinal plants used for malaria treatment in Rukungiri District, Western Uganda

Abstract Background Malaria remains a major global health challenge and a serious cause of morbidity and mortality in sub-Saharan Africa. In Uganda, limited access to medical facilities has perpetuated the reliance of indigenous communities on herbal medicine for the prevention and management of malaria. This study was undertaken to document ethnobotanical knowledge on medicinal plants prescribed for managing malaria in Rukungiri District, a meso-endemic malaria region of Western Uganda. Methods An ethnobotanical survey was carried out between May 2022 and December 2022 in Bwambara Sub-County, Rukungiri District, Western Uganda using semi-structured questionnaire. A total of 125 respondents (81 females and 44 males) were randomly selected and seven (7) key informants were engaged in open interviews. In all cases, awareness of herbalists on malaria, treatment-seeking behaviour and herbal treatment practices were obtained. The ethnobotanical data were analyzed using descriptive statistics, informant consensus factor and preference ranking. Results The study identified 48 medicinal plants belonging to 47 genera and 23 families used in the treatment of malaria and its symptoms in the study area. The most frequently cited species were Vernonia amygdalina, Aloe vera and Azadirachta indica. Leaves (74%) was the most used plant organ, mostly for preparation of decoctions (41.8%) and infusions (23.6%) which are administered orally (89.6%) or used for bathing (10.4%). Conclusions Indigenous knowledge of medicinal plants used as prophylaxis and for treatment of malaria still exist among the local communities of Bwambara Sub-County. However, there is a need to investigate the antimalarial efficacy, phytochemical composition and safety of species (such as Digitaria abyssinica and Berkheya barbata) with high percentage use values to validate their use

Aneurisma micotico cerebral bilateral em criança: registro de um caso e revisão da literatura

Os autores relatam caso de paciente masculino, de 6 anos de idade, hospitalizado com diagnóstico de meningite purulenta. A pneumencefalografia mostrou processo expansivo fronto-temporal esquerdo. A arteriografia carotídea bilateral demonstrou presença de aneurisma da artéria frontal ascendente, com hematoma circundante, à esquerda e, aneurisma da artéria temporal posterior, à direita. Cirurgia para evacuação do hematoma e clipagem do aneurisma foi realizada. O paciente piorou no pós-operatório e faleceu. A autópsia demonstrou a presença de hemorragia subaracnóide, hematoma fronto-temporal esquerdo e para-capsular direito. No interior do hematoma, à direita, evidencia-se massa arredondada, cujo exame histopatológico demonstrou tratar-se de paredes arteriais dilatadas, com intenso processo inflamatório supurativo. Os autores tecem considerações a respeito da frequência de aneurismas micóticos na infância, a multiplicidade dos mesmos, a sua etiopatogenia, a localização dos mesmos na árvore arterial intracraniana, do valor diagnóstico da angiografia carotídea e da indicação cirúrgica

Dataset: Assessing the daily natural history of asymptomatic Plasmodium infections in adults and older children in Katakwi, Uganda: a longitudinal cohort study

Data fields: Column 1: Row identifier Column 2: id (subject identifier) Column 3: sex (male/female) Column 4: age_category (adult or older child) Column 5: study_day (by day) Colum 6: Pf_parasites_per_mL_va (P. falciparum parasites/mL of blood by 18S rRNA RT-PCR) Column 7: Pan_parasites_per_mL_va (pan-Plasmodium parasites/mL of blood by 18S rRNA RT-PCR) Column 8: infection_type (category of infection: Negative, Pf, Pan, or Mixed)This is the dataset accompanying Hergott et al. publications related to this field study conducted in Katakwi District, Uganda in March-May 2021. This dataset contains line listings of sample-by-sample data for Plasmodium RT-PCR results by subject.U.S. National Institutes of Health (R21AI146763) Bill and Melinda Gates Foundation INV-00931