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Seasonal malaria chemoprevention in an area of extended seasonal transmission in Ashanti, Ghana: an individually randomised clinical trial.

ABSTRACT: To investigate the effectiveness of seasonal malaria chemoprevention (SMC) and community case management with long-acting artemisinin-based combination therapies (ACTs) for the control of malaria in areas of extended seasonal malaria transmission.Individually randomised, placebo-controlled trial in the Ashanti Region of Ghana. A total of 2400 children aged 3-59 months received either: (i) a short-acting ACT for case management of malaria (artemether-lumefantrine, AL) plus placebo SMC, or (ii) a long-acting ACT (dihydroartemisinin-piperaquine, DP) for case management plus placebo SMC or (iii) AL for case management plus active SMC with sulphadoxine-pyrimethamine and amodiaquine. SMC or placebo was delivered on five occasions during the rainy season. Malaria cases were managed by community health workers, who used rapid diagnostic tests to confirm infection prior to treatment.The incidence of malaria was lower in children given SMC during the rainy season. Compared to those given placebo SMC and AL for case management, the adjusted hazard ratio (aHR) was 0.62 (95% CI: 0.41, 0.93), P = 0.020 by intention to treat and 0.53 (95% CI: 0.29, 0.95), P = 0.033 among children given five SMC courses. There were no major differences between groups given different ACTs for case management (aHR DP vs. AL 1.18 (95% CI 0.83, 1.67), P = 0.356).SMC may have an important public health impact in areas with a longer transmission season, but further optimisation of SMC schedules is needed to maximise its impact in such settings.

SUBMITTER: Tagbor H

PROVIDER: S-EPMC4982104 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Seasonal malaria chemoprevention in an area of extended seasonal transmission in Ashanti, Ghana: an individually randomised clinical trial.

Tagbor Harry H Antwi Gifty Dufie GD Acheampong Princess Ruhama PR Bart Plange Constance C Chandramohan Daniel D Cairns Matthew M

Tropical medicine & international health : TM & IH 20151216 2

<h4>Objective</h4>To investigate the effectiveness of seasonal malaria chemoprevention (SMC) and community case management with long-acting artemisinin-based combination therapies (ACTs) for the control of malaria in areas of extended seasonal malaria transmission.<h4>Method</h4>Individually randomised, placebo-controlled trial in the Ashanti Region of Ghana. A total of 2400 children aged 3-59 months received either: (i) a short-acting ACT for case management of malaria (artemether-lumefantrine, ...[more]

PMID: 26578353

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Project description:Introduction: Plasmodium falciparum induced antibodies are key components of anti-malarial immunity in malaria endemic areas, but their antigen targets can be polymorphic. Induction of a high proportion of strain-specific antibodies will limit the recognition of a broad diversity of parasite strains by these responses. There are indications that circulating parasite diversity varies with malaria transmission intensity, and this may affect the specificity of elicited anti-malarial antibodies. This study therefore assessed the effect of varying malaria transmission patterns on the specificity of elicited antibody responses and to identify possible antibody correlates of naturally acquired immunity to malaria in children in an area of Ghana with seasonal malaria transmission.Methods: This retrospective study utilized plasma samples collected longitudinally at six time points from children aged one to five years. Multiplex assays were used to measure antibody levels against four P. falciparum AMA 1 variants (from the 3D7, FVO, HB3 and CAMP parasite strains) and the 3D7 variant of the EBA 175 region II antigen and the levels compared between symptomatic and asymptomatic children. The relative proportions of cross-reactive and strain-specific antibodies against the four AMA 1 variants per sampling time point were assessed by Bland-Altman plots. The levels of antibodies against allelic AMA1 variants, measured by singleplex and multiplex luminex assays, were also compared.Results: The data show that increased transmission intensity is associated with higher levels of cross-reactive antibody responses, most likely a result of a greater proportion of multiple parasite clone infections during the high transmission period. Anti-AMA1 antibodies were however associated with a history of infection rather than protection in this age group.Conclusion: The data contribute to understanding the underlying mechanism of the acquisition of strain-transcending antibody immunity following repeated exposure to diverse parasite strains.

Project description:BackgroundSeasonal Malaria Chemoprevention (SMC) is currently recommended for children under five in areas where malaria transmission is highly seasonal. We explored children's caregivers' and community health workers' (CHWs) responses to an extended 5-month SMC programme.MethodsThirteen in-depth interviews and eight focus group discussions explored optimal and suboptimal 'uptake' of SMC to examine facilitators and barriers to caregivers' uptake.ResultsThere did not appear to be major differences between caregivers of children with optimal and sub-optimal SMC uptake in terms of their knowledge of malaria, their perceptions of the effect of SMC on a child's health, nor their understanding of chemoprevention. Caregivers experienced difficulty in prioritising SMC for well children, perceiving medication being for treatment rather than prevention. Prior to the study, caregivers had become accustomed to rapid diagnostic testing (RDT) for malaria, and therefore blood testing for malaria during the baseline survey at the start of the SMC programme may have positively influenced uptake. Facilitators of uptake included caregivers' trust in and respect for administrators of SMC (including CHWs), access to medication and supportive (family) networks. Barriers to uptake related to poor communication of timings of community gatherings, travel distances, absence during SMC home deliveries, and limited demand for SMC due to lack of previous experience. Future delivery of SMC by trained CHWs would be acceptable to caregivers.ConclusionA combination of caregivers' physical access to SMC medication, the drug regimen, trust in the medical profession and perceived norms around malaria prevention all likely influenced caregivers' level of uptake. SMC programmes need to consider: 1) developing supportive, accessible and flexible modes of drug administration including home delivery and village community kiosks; 2) improving demand for preventive medication including the harnessing of learnt trust; and 3) developing community-based networks for users to support optimal uptake of SMC.

Project description:BackgroundSeasonal malaria chemoprevention (SMC) is now widely deployed in the Sahel, including several countries that are major contributors to the global burden of malaria. Consequently, it is important to understand whether SMC continues to provide a high level of protection and how SMC might be improved. SMC was evaluated using data from a large, household-randomised trial in Houndé, Burkina Faso and Bougouni, Mali.Methods and findingsThe parent trial evaluated monthly SMC plus either azithromycin (AZ) or placebo, administered as directly observed therapy 4 times per year between August and November (2014-2016). In July 2014, 19,578 children aged 3-59 months were randomised by household to study group. Children who remained within the age range 3-59 months in August each year, plus children born into study households or who moved into the study area, received study drugs in 2015 and 2016. These analyses focus on the approximately 10,000 children (5,000 per country) under observation each year in the SMC plus placebo group. Despite high coverage and high adherence to SMC, the incidence of hospitalisations or deaths due to malaria and uncomplicated clinical malaria remained high in the study areas (overall incidence rates 12.5 [95% confidence interval (CI): 11.2, 14.1] and 871.1 [95% CI: 852.3, 890.6] cases per 1,000 person-years, respectively) and peaked in July each year, before SMC delivery began in August. The incidence rate ratio comparing SMC within the past 28 days with SMC more than 35 days ago-adjusted for age, country, and household clustering-was 0.13 (95% CI: 0.08, 0.20), P < 0.001 for malaria hospitalisations and deaths from malaria and 0.21 (95% CI 0.20, 0.23), P < 0.001 for uncomplicated malaria, indicating protective efficacy of 87.4% (95% CI: 79.6%, 92.2%) and 78.3% (95% CI: 76.8%, 79.6%), respectively. The prevalence of malaria parasitaemia at weekly surveys during the rainy season and at the end of the transmission season was several times higher in children who missed the SMC course preceding the survey contact, and the smallest prevalence ratio observed was 2.98 (95% CI: 1.95, 4.54), P < 0.001. The frequency of molecular markers of sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) resistance did not increase markedly over the study period either amongst study children or amongst school-age children resident in the study areas. After 3 years of SMC deployment, the day 28 PCR-unadjusted adequate clinical and parasitological response rate of the SP + AQ regimen in children with asymptomatic malaria was 98.3% (95% CI: 88.6%, 99.8%) in Burkina Faso and 96.1% (95% CI: 91.5%, 98.2%) in Mali. Key limitations of this study are the potential overdiagnosis of uncomplicated malaria by rapid diagnostic tests and the potential for residual confounding from factors related to adherence to the monthly SMC schedule.ConclusionDespite strong evidence that SMC is providing a high level of protection, the burden of malaria remains substantial in the 2 study areas. These results emphasise the need for continuing support of SMC programmes. A fifth monthly SMC course is needed to adequately cover the whole transmission season in the study areas and in settings with similar epidemiology.Trial registrationThe AZ-SMC trial in which these data were collected was registered at clinicaltrials.gov: NCT02211729.

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Seasonal malaria chemoprevention in an area of extended seasonal transmission in Ashanti, Ghana: an individually randomised clinical trial.

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Seasonal malaria chemoprevention in an area of extended seasonal transmission in Ashanti, Ghana: an individually randomised clinical trial.

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