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Open Access Highly Accessed Research

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 Shekalaghe123*, Chris Drakeley4, Sven van den Bosch2, Roel ter Braak2, Wouter van den Bijllaardt2, Charles Mwanziva1, Salimu Semvua1, Alutu Masokoto1, Frank Mosha1, Karina Teelen2, Rob Hermsen2, Lucy Okell5, Roly Gosling4, Robert Sauerwein2 and Teun Bousema24

Author Affiliations

1 Kilimanjaro Christian Medical College-Kilimanjaro Clinical Research Institute, Moshi, Tanzania

2 Department of Medical Microbiology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands

3 Ifakara Health Institute, Bagamoyo Research and Training Centre, Bagamoyo, Tanzania

4 Department of Immunology & Infection; Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK

5 MRC Centre for Outbreak Analysis & Modelling, Department of Infectious Disease Epidemiology, Imperial College London, London, UK

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Malaria Journal 2011, 10:247  doi:10.1186/1475-2875-10-247

Published: 24 August 2011

Abstract

Background

Effective 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.

Methods

In 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.

Results

The 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).

Conclusions

This 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 Registration

ClinicalTrials.gov: NCT00509015