A cluster-randomized trial of mass drug administration with a gametocytocidal drug combination to interrupt malaria transmission in a low endemic area in Tanzania.

Seif A Shekalaghe,Seif A Shekalaghe,Seif A Shekalaghe,Seif A Shekalaghe,Wouter Van Den Bijllaardt,Wouter Van Den Bijllaardt,Roel Ter Braak,Roly Gosling,Charles Mwanziva,Alutu Masokoto,Robert Sauerwein,Robert Sauerwein,Chris Drakeley,Lucy Okell,Teun Bousema,Teun Bousema,Teun Bousema,Sven Van Den Bosch,Sven Van Den Bosch,Karina Teelen,Karina Teelen,Frank Mosha,Rob Hermsen,Salimu Semvua

doi:10.1186/1475-2875-10-247

Abstract

BackgroundEffective mass drug administration (MDA) with anti-malarial drugs can clear the human infectious reservoir for malaria and thereby interrupt malaria transmission. The likelihood of success of MDA depends on the intensity and seasonality of malaria transmission, the efficacy of the intervention in rapidly clearing all malaria parasite stages and the degree to which symptomatic and asymptomatic parasite carriers participate in the intervention. The impact of MDA with the gametocytocidal drug combination sulphadoxine-pyrimethamine (SP) plus artesunate (AS) plus primaquine (PQ, single dose 0.75 mg/kg) on malaria transmission was determined in an area of very low and seasonal malaria transmission in northern Tanzania.MethodsIn a cluster-randomized trial in four villages in Lower Moshi, Tanzania, eight clusters (1,110 individuals; cluster size 47- 209) were randomized to observed treatment with SP+AS+PQ and eight clusters (2,347 individuals, cluster size 55- 737) to treatment with placebo over three days. Intervention and control clusters were 1km apart; households that were located between clusters were treated as buffer zones where all individuals received SP+AS+PQ but were not selected for the evaluation. Passive case detection was done for the entire cohort and active case detection in 149 children aged 1-10 year from the intervention arm and 143 from the control arm. Four cross-sectional surveys assessed parasite carriage by microscopy and molecular methods during a five-month follow-up period.ResultsThe coverage rate in the intervention arm was 93.0% (1,117/1,201). Parasite prevalence by molecular detection methods was 2.2-2.7% prior to the intervention and undetectable during follow-up in both the control and intervention clusters. None of the slides collected during cross-sectional surveys had microscopically detectable parasite densities. Three clinical malaria episodes occurred in the intervention (n = 1) and control clusters (n = 2).ConclusionsThis study illustrates the possibility to achieve high coverage with a three-day intervention but also the difficulty in defining suitable outcome measures to evaluate interventions in areas of very low malaria transmission intensity. The decline in transmission intensity prior to the intervention made it impossible to assess the impact of MDA in the chosen study setting.Trial RegistrationClinicalTrials.gov: NCT00509015

Highlights

Effective mass drug administration (MDA) with anti-malarial drugs can clear the human infectious reservoir for malaria and thereby interrupt malaria transmission
This is because the impact of treatment on transmission intensity is greatly influenced by the proportion of parasite carriers that carry the infection asymptomatically and that are unlikely to seek anti-malarial treatment [18]
Submicroscopic parasite carriage may be most relevant for malaria transmission in areas of low endemicity, where the relative proportion of parasite carriers that are missed by microscopy is greatest [30]

Summary

Introduction

Effective mass drug administration (MDA) with anti-malarial drugs can clear the human infectious reservoir for malaria and thereby interrupt malaria transmission. Even at very low levels of transmission intensity, the employment of ACT in the first-line treatment of malaria may not result in the elimination of malaria [15] This is because the impact of treatment on transmission intensity is greatly influenced by the proportion of parasite carriers that carry the infection asymptomatically and that are unlikely to seek anti-malarial treatment [18]. Submicroscopic parasite carriage may be most relevant for malaria transmission in areas of low endemicity, where the relative proportion of parasite carriers that are missed by microscopy is greatest [30] These low-density infections should be included in interventions that aim to target the human infectious reservoir

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