Appropriate targeting of artemisinin-based combination therapy by community health workers using malaria rapid diagnostic tests: Findings from randomized trials in two contrasting areas of high and low malaria transmission in south western Uganda.


Ndyomugyenyi, R; Magnussen, P; Lal, S; Hansen, K; Clarke, SE; (2016) Appropriate targeting of artemisinin-based combination therapy by community health workers using malaria rapid diagnostic tests: Findings from randomized trials in two contrasting areas of high and low malaria transmission in south western Uganda. Tropical medicine & international health . ISSN 1360-2276 DOI: 10.1111/tmi.12748

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Abstract

: HIV infection, and potentially its treatment, increases the risk of an arterial ischemic stroke. Multiple etiologies and lack of clear case definitions inhibit progress in this field. Several etiologies, many treatable, are relevant to HIV-related stroke. To fully understand the mechanisms and the terminology used, a robust classification algorithm to help ascribe the various etiologies is needed. This consensus paper considers the strengths and limitations of current case definitions in the context of HIV infection. The case definitions for the major etiologies in HIV-related strokes were refined (e.g., varicella zoster vasculopathy and antiphospholipid syndrome) and in some instances new case definitions were described (e.g., HIV-associated vasculopathy). These case definitions provided a framework for an algorithm to help assign a final diagnosis, and help classify the subtypes of HIV etiology in ischemic stroke.<br/> OBJECTIVES: An increasing proportion of people living with HIV are older adults, who may require specialized care. Adverse physical and psychological effects of HIV infection may be greatest among older people or those who have lived longer with HIV.<br/> METHODS: The ASTRA study is a cross-sectional questionnaire study of 3258 HIV-diagnosed adults (2248 men who have sex with men, 373 heterosexual men and 637 women) recruited from UK clinics in 2011-2012. Associations of age group with physical symptom distress (significant distress for at least one of 26 symptoms), depression and anxiety symptoms (scores ≥ 10 on PHQ-9 and GAD-7, respectively), and health-related functional problems (problems on at least one of three domains of the Euroqol 5D-3L)) were assessed, adjusting for time with diagnosed HIV infection, gender/sexual orientation and ethnicity.<br/> RESULTS: The age distribution of participants was: < 30 years, 5%; 30-39 years, 23%; 40-49 years, 43%; 50-59 years, 22%; and ≥ 60 years, 7%. Overall prevalences were: physical symptom distress, 56%; depression symptoms, 27%; anxiety symptoms, 22%; functional problems, 38%. No trend was found in the prevalence of physical symptom distress with age [adjusted odds ratio (OR) for trend across age groups, 0.96; 95% confidence interval (CI) 0.89, 1.04; P = 0.36]. The prevalence of depression and anxiety symptoms decreased with age [adjusted OR 0.86 (95% CI 0.79, 0.94; P = 0.001) and adjusted OR 0.85 (95% CI 0.77, 0.94; P = 0.001), respectively], while that of functional problems increased (adjusted OR 1.28; 95% CI 1.17, 1.39; P < 0.001). In contrast, a longer time with diagnosed HIV infection was strongly and independently associated with a higher prevalence of symptom distress, depression symptoms, anxiety symptoms, and functional problems (P < 0.001 for trends, adjusted analysis).<br/> CONCLUSIONS: Among people living with HIV, although health-related functional problems were more common with older age, physical symptom distress was not, and mental health was more favourable. These results suggest that a longer time with diagnosed HIV infection, rather than age, is the dominating factor contributing to psychological morbidity and lower quality of life.<br/> BACKGROUND: The epidemiology of oral human papillomavirus (HPV) infection in men who have sex with men (MSM) differs from anogenital HPV infection. The impact of HPV vaccination has, to date, largely focussed on anogenital outcomes. Vaccination of MSM in the UK has been recommended and, if implemented, baseline estimates of oral HPV prevalence will be useful.<br/> METHODS: We searched Medline, Embase and psycINFO databases for studies reporting prevalence, incidence, and clearance of oral HPV infection in MSM. We performed a random-effects meta-analysis and meta-regression on prevalence estimates and summarised within-study risk factors for oral HPV DNA detection and incidence/clearance rates. We also performed a meta-analysis of the effect of MSM on oral HPV prevalence compared to heterosexual men.<br/> RESULTS: 26 publications were identified. The pooled prevalence of oral HPV16 from twelve estimates was 3.0% (95%CI 0.5-5.5) in HIV-negative and 4.7% (95%CI 2.1-7.3) in HIV-positive MSM. Median age of study participants explained 38% of heterogeneity (p<0.01) in HPV prevalence estimates (pooled = 17% and 29% in HIV-negative and HIV-positive, respectively; 22 estimates). Nine studies compared MSM to heterosexual men and found no difference in oral HPV prevalence (pooled OR 1.07 (95%CI 0.65-1.74)). The clearance rate was higher than incidence within studies. Type-specific concordance between oral and anogenital sites was rare.<br/> CONCLUSION: There was substantial heterogeneity between estimates of oral HPV prevalence in MSM populations that was partly explained by HIV status and median age.<br/> OBJECTIVE: To compare the impact of malaria rapid diagnostic tests (mRDTs), used by Community Health Workers (CHWs), on the proportion of children < 5 years of age receiving appropriately targeted treatment with ACT, to presumptive treatment.<br/> METHODS: Cluster-randomized trials were conducted in two contrasting areas of moderate-high and low malaria transmission in rural Uganda. Each trial examined the effectiveness of mRDTs in the management of malaria and targeting of ACTs by CHWs comparing two diagnostic approaches: (1) presumptive clinical diagnosis of malaria [control arm], and (2) confirmatory diagnosis with mRDTs followed by ACT treatment for positive patients [intervention arm]; with village as the unit of randomisation. Treatment decisions by CHWs were validated by microscopy on a reference blood slide collected at the time of consultation, to compare the proportion of children <5 years receiving appropriately targeted ACT treatment, defined as patients with microscopically confirmed presence of parasites in a peripheral blood smear receiving ACT or rectal artesunate, and patients with no malaria parasites not given ACT.<br/> RESULTS: In the moderate-high transmission area, ACT treatment was appropriately targeted in 79.3% (520/656) of children seen by CHWs using mRDTs to diagnose malaria, vs. 30.8% (215/699) of children seen by CHWs using presumptive diagnosis (P<0.001). In the low transmission area, 90.1% (363/403) children seen by CHWs using mRDTs received appropriately targeted ACT treatment vs. 7.8% (64/817) seen by CHWs using presumptive diagnosis (P<0.001). Low mRDT sensitivity in children with low density parasitaemia (<200 parasites/μl) was identified as a potential concern.<br/> CONCLUSION: When equipped with mRDTs, ACT treatments delivered by CHWs are more accurately targeted to children with malaria parasites. mRDT use could play an important role in reducing overdiagnosis of malaria and improving fever case management within iCCM, in both moderate-to-high and low transmission areas. Nonetheless, missed treatments due to the low sensitivity of current mRDTs in patients with low parasite density are a concern. For community-based treatment in areas of low transmission and/or non-immune populations, presumptive treatment of all fevers as malaria may be advisable, until more sensitive diagnostic assays, suitable for routine use by CHWs in remote settings, become available. This article is protected by copyright. All rights reserved.<br/>

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Disease Control
Faculty of Public Health and Policy > Dept of Global Health and Development
Faculty of Infectious and Tropical Diseases > Dept of Clinical Research
Research Centre: Antimicrobial Resistance Centre (AMR)
Malaria Centre
Neglected Tropical Diseases Network
PubMed ID: 27383558
Web of Science ID: 387144800011
URI: http://researchonline.lshtm.ac.uk/id/eprint/2728837

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