Short-term Impact of Mass Drug Administration With Dihydroartemisinin Plus Piperaquine on Malaria in Southern Province Zambia: A Cluster-Randomized Controlled Trial

Thomas P Eisele, Adam Bennett, Kafula Silumbe, Timothy P Finn, Victor Chalwe, Mulakwa Kamuliwo, Busiku Hamainza, Hawela Moonga, Emmanuel Kooma, Elizabeth Chizema Kawesha, Joshua Yukich, Joseph Keating, Travis Porter, Ruben O Conner, Duncan Earle, Richard W Steketee, John M Miller, Thomas P Eisele, Adam Bennett, Kafula Silumbe, Timothy P Finn, Victor Chalwe, Mulakwa Kamuliwo, Busiku Hamainza, Hawela Moonga, Emmanuel Kooma, Elizabeth Chizema Kawesha, Joshua Yukich, Joseph Keating, Travis Porter, Ruben O Conner, Duncan Earle, Richard W Steketee, John M Miller

Abstract

Background: Mass drug administration (MDA) using dihydroartemisinin plus piperaquine (DHAp) represents a potential strategy to clear Plasmodium falciparum infections and reduce the human parasite reservoir.

Methods: A cluster-randomized controlled trial in Southern Province, Zambia, was used to assess the short-term impact of 2 rounds of community-wide MDA and household-level (focal) MDA with DHAp compared with no mass treatment. Study end points included parasite prevalence in children, infection incidence, and confirmed malaria case incidence.

Results: All end points significantly decreased after intervention, irrespective of treatment group. Parasite prevalence from 7.71% at baseline to 0.54% after MDA in lower-transmission areas, resulting in an 87% reduction compared with control (adjusted odds ratio, 0.13; 95% confidence interval, .02-.92; P = .04). No difference between treatment groups was observed in areas of high transmission. The 5-month cumulative infection incidence was 70% lower (crude incidence rate ratio, 0.30; 95% confidence interval, .06-1.49; P = .14) and 58% lower (0.42; .18-.98; P = .046) after MDA compared with control in lower- and higher-transmission areas, respectively. No significant impact of focal MDA was observed for any end point.

Conclusions: Two rounds of MDA with DHAp rapidly reduced infection prevalence, infection incidence, and confirmed case incidence rates, especially in low-transmission areas.

Clinical trials registration: NCT02329301.

Keywords: elimination; malaria; mass drug administration.

© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

Figures

Figure 1.
Figure 1.
Map of the study area, divided into 60 health facility catchment areas that served as the unit of randomization. Abbreviations: fMDA, focal mass drug administration; MDA, mass drug administration; N, north.
Figure 2.
Figure 2.
Trial profile. Sixty health facility catchment areas (HFCAs) served as the unit of randomization. After matching for transmission stratum and HFCA population size, HFCAs were randomly assigned to either mass drug administration (MDA), focal MDA (fMDA), or control groups, using the random allocation rule. As a result, 10 HFCAs per transmission stratum were assigned to MDA, fMDA, and control groups. All eligible participants in MDA and fMDA HFCAs each received 2 rounds of these mass treatment interventions. The primary end point of infection prevalence was measured before and after the mass treatment rounds with a parasite survey. The secondary end point of cumulative infection incidence was measured with a prospective cohort, with 5 months of follow-up after round 1 of the mass treatment rounds. Individuals in control HFCAs did not receive any mass treatment but were eligible to participate in the parasite surveys and cohort. Abbreviation: DHAp, dihydroartemisinin plus piperaquine.

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Source: PubMed

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