Mass drug administration for malaria

Background Studies evaluating mass drug administration (MDA) in malarious areas have shown reductions in malaria immediately following the intervention. However, these eGects vary by endemicity and are not sustained. Since the 2013 version of this Cochrane Review on this topic, additional studies have been published. Objectives Primary objectives To assess the sustained eGect of MDA with antimalarial drugs on: - the reduction in malaria transmission in moderate- to high-transmission settings; - the interruption of transmission in very low- to low-transmission settings. Secondary objective To summarize the risk of drug-associated adverse eGects following MDA. Search methods We searched several trial registries, citation databases, conference proceedings, and reference lists for relevant articles up to 11 February 2021. We also communicated with researchers to identify additional published and unpublished studies. Selection criteria Randomized controlled trials (RCTs) and non-randomized studies comparing MDA to no MDA with balanced co-interventions across study arms and at least two geographically distinct sites per study arm. Data collection and analysis Two review authors independently assessed trials for eligibility and extracted data. We calculated relative risk (RR) and rate ratios with corresponding 95% confidence intervals (CIs) to compare prevalence and incidence, respectively, in MDA compared to no-MDA groups. We stratified analyses by malaria transmission and by malaria species. For cluster-randomized controlled trials (cRCTs), we adjusted standard errors using the intracluster correlation coeGicient. We assessed the certainty of the evidence using the GRADE approach. For non-randomized controlled before-and-aLer (CBA) studies, we summarized the data using diGerence-in-diGerences (DiD) analyses. Main results Thirteen studies met our criteria for inclusion. Ten were cRCTs andthree were CBAs. Cluster-randomized controlled trials Moderate- to high-endemicity areas (prevalence >= 10%) We included data from two studies conducted in The Gambia and Zambia. At one to three months aLer MDA, the Plasmodium falciparum (hereaLer, P falciparum) parasitaemia prevalence estimates may be higher compared to control but the CIs included no eGect (RR 1.76, 95% CI 0.58 to 5.36; Zambia study; low-certainty evidence); parasitaemia incidence was probably lower (RR 0.61, 95% CI 0.40 to 0.92; The Gambia study; moderate-certainty evidence); and confirmed malaria illness incidence may be substantially lower, but the CIs included no eGect (rate ratio 0.41, 95% CI 0.04 to 4.42; Zambia study; low-certainty evidence). At four to six months aLer MDA, MDA showed little or no eGect on P falciparum parasitaemia prevalence (RR 1.18, 95% CI 0.89 to 1.56; The Gambia study; moderate-certainty evidence) and, no persisting eGect was demonstrated with parasitaemia incidence (rate ratio 0.91, 95% CI 0.55 to 1.50; The Gambia study). Very low- to low-endemicity areas (prevalence < 10%) Seven studies from Cambodia, Laos, Myanmar (two studies), Vietnam, Zambia, and Zanzibar evaluated the eGects of multiple rounds of MDA on P falciparum. Immediately following MDA (less than one month aLer MDA), parasitaemia prevalence was reduced (RR 0.12, 95% CI 0.03 to 0.52; one study; low-certainty evidence). At one to three months aLer MDA, there was a reduction in both parasitaemia incidence (rate ratio 0.37, 95% CI 0.21 to 0.55; 1 study; moderate-certainty evidence) and prevalence (RR 0.25, 95% CI 0.15 to 0.41; 7 studies; lowcertainty evidence). For confirmed malaria incidence, absolute rates were low, and it is uncertain whether MDA had an eGect on this outcome (rate ratio 0.58, 95% CI 0.12 to 2.73; 2 studies; very low-certainty evidence). For P falciparum prevalence, the relative diGerences declined over time, from RR 0.63 (95% CI 0.36 to 1.12; 4 studies) at four to six months aLer MDA, to RR 0.86 (95% CI 0.55 to 1.36; 5 studies) at 7 to 12 months aLer MDA. Longer-term prevalence estimates showed overall low absolute risks, and relative eGect estimates of the eGect of MDA on prevalence varied from RR 0.82 (95% CI 0.20 to 3.34) at 13 to 18 months aLer MDA, to RR 1.25 (95% CI 0.25 to 6.31) at 31 to 36 months aLer MDA in one study. Five studies from Cambodia, Laos, Myanmar (2 studies), and Vietnam evaluated the eGect of MDA on Plasmodium vivax (hereaLer, P vivax). One month following MDA, P vivax prevalence was lower (RR 0.18, 95% CI 0.08 to 0.40; 1 study; low-certainty evidence). At one to three months aLer MDA, there was a reduction in P vivax prevalence (RR 0.15, 95% CI 0.10 to 0.24; 5 studies; low-certainty evidence). The immediate reduction on P vivax prevalence was not sustained over time, from RR 0.78 (95% CI 0.63 to 0.95; 4 studies) at four to six months aLer MDA, to RR 1.12 (95% CI 0.94 to 1.32; 5 studies) at 7 to 12 months aLer MDA. One of the studies in Myanmar provided estimates of longer-term eGects, where overall absolute risks were low, ranging from RR 0.81 (95% CI 0.44 to 1.48) at 13 to 18 months aLer MDA, to RR 1.20 (95% CI 0.44 to 3.29) at 31 to 36 months aLer MDA. Non-randomized studies Three CBA studies were conducted in moderate- to high-transmission areas in Burkina Faso, Kenya, and Nigeria. There was a reduction in P falciparum parasitaemia prevalence in MDA groups compared to control groups during MDA (DiD range: -15.8 to -61.4 percentage points), but the eGect varied at one to three months aLer MDA (DiD range: 14.9 to -41.1 percentage points). Authors' conclusions In moderate- to high-transmission settings, no studies reported important eGects on P falciparum parasitaemia prevalence within six months aLer MDA. In very low- to low-transmission settings, parasitaemia prevalence and incidence were reduced initially for up to three months for both P falciparum and P vivax; longer-term data did not demonstrate an eGect aLer four months, but absolute risks in both intervention and control groups were low. No studies provided evidence of interruption of malaria transmission.

Automated summary

Studies evaluating mass drug administration in malarious areas have shown reductions in malaria immediately following the intervention, but these effects are not sustained and vary by endemicity. The sustained effect of MDA on malaria transmission differs between moderate-to-high transmission settings and very low-to-low transmission settings. The risk of drug-associated adverse effects following MDA needs further investigation.