BackgroundMass drug administration (MDA) using dihydroartemisinin plus piperaquine (DHAp) represents a potential strategy to clear Plasmodium falciparum infections and reduce the human parasite reservoir.MethodsA 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.ResultsAll 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.ConclusionsTwo rounds of MDA with DHAp rapidly reduced infection prevalence, infection incidence, and confirmed case incidence rates, especially in low-transmission areas.Clinical Trials RegistrationNCT02329301.

Reducing the human reservoir of malaria parasites is critical for elimination. We conducted a community randomized controlled trial in Southern Province, Zambia to assess the impact of three rounds of a mass test and treatment (MTAT) intervention on malaria prevalence and health facility outpatient case incidence using random effects logistic regression and negative binomial regression, respectively. Following the intervention, children in the intervention group had lower odds of a malaria infection than individuals in the control group (adjusted odds ratio = 0.47, 95% confidence interval [CI] = 0.24–0.90). Malaria outpatient case incidence decreased 17% in the intervention group relative to the control group (incidence rate ratio = 0.83, 95% CI = 0.68–1.01). Although a single year of MTAT reduced malaria prevalence and incidence, the impact of the intervention was insufficient to reduce transmission to a level approaching elimination where a strategy of aggressive case investigations could be used. Mass drug administration, more sensitive diagnostics, and gametocidal drugs may potentially improve interventions targeting the human reservoir of malaria parasites.

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.

BackgroundTo assess progress in the scale-up of rapid diagnostic tests and artemisinin-based combination therapies (ACTs) across Africa, malaria control programs have increasingly relied on standardized national household surveys to determine the proportion of children with a fever in the past 2 wk who received an effective antimalarial within 1–2 d of the onset of fever. Here, the validity of caregiver recall for measuring the primary coverage indicators for malaria diagnosis and treatment of children <5 y old is assessed.Methods and FindingsA cross-sectional study was conducted in five public clinics in Kaoma District, Western Provence, Zambia, to estimate the sensitivity, specificity, and accuracy of caregivers' recall of malaria testing, diagnosis, and treatment, compared to a gold standard of direct observation at the health clinics. Compared to the gold standard of clinic observation, for recall for children with fever in the past 2 wk, the sensitivity for recalling that a finger/heel stick was done was 61.9%, with a specificity of 90.0%. The sensitivity and specificity of caregivers' recalling a positive malaria test result were 62.4% and 90.7%, respectively. The sensitivity and specificity of recalling that the child was given a malaria diagnosis, irrespective of whether a laboratory test was actually done, were 76.8% and 75.9%, respectively. The sensitivity and specificity for recalling that an ACT was given were 81.0% and 91.5%, respectively.ConclusionsBased on these findings, results from household surveys should continue to be used for ascertaining the coverage of children with a fever in the past 2 wk that received an ACT. However, as recall of a malaria diagnosis remains suboptimal, its use in defining malaria treatment coverage is not recommended. Please see later in the article for the Editors' Summary

BackgroundReactive case detection could be a powerful tool in malaria elimination, as it selectively targets transmission pockets. However, field operations have yet to demonstrate under which conditions, if any, reactive case detection is best poised to push a region to elimination. This study uses mathematical modelling to assess how baseline transmission intensity and local interconnectedness affect the impact of reactive activities in the context of other possible intervention packages.MethodsCommunities in Southern Province, Zambia, where elimination operations are currently underway, were used as representatives of three archetypes of malaria transmission: low-transmission, high household density; high-transmission, low household density; and high-transmission, high household density. Transmission at the spatially-connected household level was simulated with a dynamical model of malaria transmission, and local variation in vectorial capacity and intervention coverage were parameterized according to data collected from the area. Various potential intervention packages were imposed on each of the archetypical settings and the resulting likelihoods of elimination by the end of 2020 were compared.ResultsSimulations predict that success of elimination campaigns in both low- and high-transmission areas is strongly dependent on stemming the flow of imported infections, underscoring the need for regional-scale strategies capable of reducing transmission concurrently across many connected areas. In historically low-transmission areas, treatment of clinical malaria should form the cornerstone of elimination operations, as most malaria infections in these areas are symptomatic and onward transmission would be mitigated through health system strengthening; reactive case detection has minimal impact in these settings. In historically high-transmission areas, vector control and case management are crucial for limiting outbreak size, and the asymptomatic reservoir must be addressed through reactive case detection or mass drug campaigns.ConclusionsReactive case detection is recommended only for settings where transmission has recently been reduced rather than all low-transmission settings. This is demonstrated in a modelling framework with strong out-of-sample accuracy across a range of transmission settings while including methodologies for understanding the most resource-effective allocations of health workers. This approach generalizes to providing a platform for planning rational scale-up of health systems based on locally-optimized impact according to simplified stratification.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-017-1903-z) contains supplementary material, which is available to authorized users.