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

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 1 km 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.

Figures

Figure 1
Figure 1
The study villages of Kiruani, Majengo, Magadini and Korongo. Each village is presented separately. The north-south arrow relates to the position of households within a village, not to the relative location of villages. Each dot represents a household, dark dots represent intervention households; open dots control households. Buffer zones are depicted in transparent grey. The intervention (I) and control (C) clusters are numbered.
Figure 2
Figure 2
Seasonality, entomology and timing of the intervention. Rainfall data is given in the dashed line in mm/week; the average number of female anophelines caught per night in five sentinel houses in Kiruani is represented by solid diamonds; the average number of female anophelines caught per night in ten sentinel houses in Magadini and Korongo is represented by open diamonds. The drug intervention was completed 3-5 weeks before the start of the rains in early April.
Figure 3
Figure 3
Participant flow chart.

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