Assessing the effectiveness of household-level focal mass drug administration and community-wide mass drug administration for reducing malaria parasite infection prevalence and incidence in Southern Province, Zambia: study protocol for a community randomized controlled trial

Abstract

BackgroundMass drug administration (MDA) and focal MDA (fMDA) using dihydroartemisinin plus piperaquine (DHAp), represent two strategies to maximize the use of existing information to achieve greater clearance of human infection and reduce the parasite reservoir, and provide longer chemoprophylactic protection against new infections. The primary aim of this study is to quantify the relative effectiveness of MDA and fMDA with DHAp against no mass treatment (standard of care) for reducing Plasmodium falciparum prevalence and incidence.Methods/designThe study will be conducted along Lake Kariba in Southern Province, Zambia; an area of low to moderate malaria transmission and high coverage of vector control. A community randomized controlled trial (CRCT) of 60 health facility catchment areas (HFCAs) will be used to evaluate the impact of two rounds of MDA and fMDA interventions, relative to a control of no mass treatment, stratified by high and low transmission. Community residents in MDA HFCAs will be treated with DHAp at the end of the dry season (round one: November to December 2014) and the beginning of the rainy season (round two: February to March 2015). Community residents in fMDA HFCAs will be tested during the same two rounds for malaria parasites with a rapid diagnostic test; all positive individuals and all individuals living in their household will be treated with DHAp. Primary outcomes include malaria parasite prevalence (n = 5,640 children aged one month to under five-years-old), as measured by pre- and post-surveys, and malaria parasite infection incidence (n = 2,250 person-years among individuals aged three months and older), as measured by a monthly longitudinal cohort. The study is powered to detect approximately a 50 % relative reduction in these outcomes between each intervention group versus the control.DiscussionStrengths of this trial include: a robust study design (CRCT); cross-sectional parasite surveys as well as a longitudinal cohort; and stratification of high and low transmission areas. Primary limitations include: statistical power to detect only a 50 % reduction in primary outcomes within high and low transmission strata; potential for contamination; and potential for misclassification of exposure.Trial registrationIdentifier: Clinicaltrials.gov: NCT02329301. Registration date: 30 December 2014.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-015-0862-3) contains supplementary material, which is available to authorized users.

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

“…As a result, the expected detectable differences in these end points for comparing the mass treatment interventions to control was much lower than expected, resulting in lower statistical power than expected to detect significant differences [16]. It is unclear why such large declines in control areas occurred, but there are several potential explanations.…”

“…Second, because of the relatively small number of clusters (10 HFCAs in each treatment group in each transmission stratum), there was the potential for imbalance across treatment groups. However, all analyses of study end points also included models with potential confounders, stipulated a priori in the protocol [16]. It should be noted that effect estimates between crude and adjusted models were very similar, suggest that important confounding factors were balanced across treatment groups.…”

“…The full protocol for this trial has been published elsewhere [16]. Ethical approval was obtained from Tulane University, Western Institutional Review Board, the University of Zambia, and the Zambia Medicines Regulatory Authority.…”

“…A sample size of 2820 children at each survey round was required to detect a 50% reduction in infection prevalence with 80% power taking into account the cluster randomization, as described elsewhere [16]. RDTs and microscopy were used to assess the malaria parasite infection status among included children.…”

“…A target sample size of 2250 individuals was sought to detect a 50% reduction in infection incidence between either mass treatment group and control, with 80% statistical power taking into account the cluster randomization, as described elsewhere [16]. Cohort participants were drawn from a simple random sample within each HFCA (39 persons within 13 households in each HFCA).…”