A multiphase program for malaria elimination in southern Mozambique (the Magude project): A before-after study

Abstract

Background Malaria eradication remains the long-term vision of the World Health Organization (WHO). However, whether malaria elimination is feasible in areas of stable transmission in sub-Saharan Africa with currently available tools remains a subject of debate. This study aimed to evaluate a multiphased malaria elimination project to interrupt Plasmodium falciparum malaria transmission in a rural district of southern Mozambique. Methods and findings A before-after study was conducted between 2015 and 2018 in the district of Magude, with 48,448 residents living in 10,965 households. Building on an enhanced surveillance system, two rounds of mass drug administrations (MDAs) per year over two years (phase I, August 2015-2017), followed by one year of reactive focal mass drug administrations (rfMDAs) (phase II, September 2017-June 2018) were deployed with annual indoor residual spraying (IRS), programmatically distributed long-lasting insecticidal nets (LLINs), and standard case management. The four MDA rounds covered 58%-72% of the population, and annual IRS reported coverage was >70%. Yearly parasite surveys and routine surveillance data were used to monitor the primary outcomes of the study-malaria prevalence and incidence-at baseline and annually since the onset of the project. Parasite prevalence by rapid diagnostic test (RDT) declined from 9.1% (95% confidence interval [CI] 7.0-11.8) in May 2015 to 2.6% (95% CI 2.0-3.4), representing a 71.3% (95% CI 71.1-71.4, p < 0.001) reduction after

Shifts in P. falciparum genetic structure and gametocyte markers in the transition to elimination

“…Importantly, less than 100 samples per group were enough to detect signals of a bottleneck in the parasite population driven by a 71% drop in Pf prevalence. 12 Moreover, the enhanced genetic similarity after the bottleneck in the parasite population may increase the performance of genetic tools to identify imported infections with unrelated haplotypes. 22 The reduction in Pf within-host genetic diversity and the enhanced between-infection similarity of infections after the drastic drop in transmission were coincident with an increase in the detectability and levels of Pf transcripts speci cally expressed by female gametocytes (pfs25), sexually committed (pfap2g) and recently formed gametocytes (pfgexp02).…”

“…As a result, all-age Pf prevalence by rapid diagnostic test decreased from 9.1% in May 2015 to 2.6% in May 2017. 12 50 µL dried blood spots (DBS) were collected onto Whatman 3 mm lter paper from a random selection of individuals included in an age-strati ed community-based cross-sectional survey conducted at the end of the transmission season at baseline (May 2015; n = 1035) and three months after the last MDA round (May 2017; n = 3752), 12 as well as among consenting participants prior to rst MDA round (November 2015, n = 1322). DBS collected in May 2015 and 2017 were also preserved in 250 µl RNAprotect (Qiagen, Hilden, Germany) and stored in -80ºC.…”

“…Here we employed parasites collected before and after the deployment of an intensive combination of interventions in Magude district (southern Mozambique) 12 to interrogate for shifts in population structure and gametocyte carriage. We hypothesized that reductions in genetic variation, as a result of drastic reductions in transmission intensity, would lead to increases in gametocyte production due to lower within-host competition.…”

Effect of mass dihydroartemisinin–piperaquine administration in southern Mozambique on the carriage of molecular markers of antimalarial resistance

“…Two MDA rounds separated by a period of 4–6 weeks were deployed at the beginning of the rainy seasons of 2015–16 (November and January-February) and 2016–17 (December and January-February) in Magude District (Southern Mozambique). The MDAs were targeted to the entire population of Magude (48,488 residents, 10965 households in 2015) and reached 72.3%, 58%, 66.6% and 64.8% of the population in each of the four rounds, respectively [ 27 ].…”

“…A before-after study was conducted in southern Mozambique to evaluate the impact of a package of interventions with the aim to interrupt Plasmodium falciparum ( Pf ) malaria transmission [ 27 ]. Two rounds of MDA with DHAp per year over 2015 and 2017, together with annual indoor residual spraying (IRS), programmatically distributed long-lasting insecticide treated nets (LLINs) and standard case management, lead to a 71.3% reduction of all-age parasite prevalence by rapid diagnostic test (from 9.1% to 2.6%), and a 61.5% reduction in case incidence at health facility level (from 195 to 75 cases per 1000).…”