The impact of targeted malaria elimination with mass drug administrations on falciparum malaria in Southeast Asia: A cluster randomised trial

Abstract

Background The emergence and spread of multidrug-resistant Plasmodium falciparum in the Greater Mekong Subregion (GMS) threatens global malaria elimination efforts. Mass drug administration (MDA), the presumptive antimalarial treatment of an entire population to clear the subclinical parasite reservoir, is a strategy to accelerate malaria elimination. We report a cluster randomised trial to assess the effectiveness of dihydroartemisinin-piperaquine (DP) MDA in reducing falciparum malaria incidence and prevalence in 16 remote village populations in Myanmar, Vietnam, Cambodia, and the Lao People’s Democratic Republic, where artemisinin resistance is prevalent. Methods and findings After establishing vector control and community-based case management and following intensive community engagement, we used restricted randomisation within village pairs to select 8 villages to receive early DP MDA and 8 villages as controls for 12 months, after which the control villages received deferred DP MDA. The MDA comprised 3 monthly rounds of 3 daily doses of DP and, except in Cambodia, a single low dose of primaquine. We conducted exhaustive cross-sectional surveys of the entire population of each village at quarterly intervals using ultrasensitive quantitative PCR to detect Plasmodium infections. The study was conducted between May 2013 and July 2017. The investigators randomised 16 villages that had a total of 8,445 residents at the start of the study. Of these 8,445 residents, 4,135 (49%) residents living in 8 villages, plus an additional 288 newcomers to the villages, were randomised to receive early MDA; 3,790 out of the 4,423 (86%) participated in at least 1 MDA round, and 2,520 out of the 4,423 (57%) participated in all 3 rounds. The primary outcome, P . falciparum prevalence by month 3 (M3), fell by 92% (from 5.1% [171/3,340] to 0.4% [12/2,828]) in early MDA villages and by 29% (from 7.2% [246/3,405] to 5.1% [155/3,057]) in control villages. Over the following 9 months, the P . falciparum prevalence increased to 3.3% (96/2,881) in early MDA villages and to 6.1% (128/2,101) in control villages (adjusted incidence rate ratio 0.41 [95% CI 0.20 to 0.84]; p = 0.015). Individual protection was proportional to the number of completed MDA rounds. Of 221 participants with subclinical P . falciparum infections who participated in MDA and could be followed up, 207 (94%) cleared their infections, including 9 of 10 with artemisinin- and piperaquine-resistant infections. The DP MDAs were well tolerated; 6 severe adverse events were detected during the follow-up period, but none was attributable to the intervention. Conclusions Added to community-based basic malaria control measures, 3 monthly rounds of DP MDA reduced the...

Prevalence of asymptomatic malaria parasitaemia following mass testing and treatment in Pakro sub-district of Ghana

“…The protocol for this study was reviewed and approved by the Ghana Health Service Ethics Review Committee (GHS-ERC -01/03/17) and the Institutional Review Board of the Noguchi Memorial Institute for Medical Research, University of Ghana (054/ [16][17]. All participants signed an informed consent form prior to participating in the study.…”

“…MDA integrated with other approaches such as distribution of LLINs and strengthening community based health services and health workers, can accelerate malaria elimination ( [16][17][18][19]. MDA as an approach has shown mixed results in the history of malaria elimination [8,10,20] and depends upon i) the targeted region's epidemiology of malaria or transmission intensity; ii) geographical characteristics of the malaria endemic regions (islands where mobility of population is minimal have cleared malaria, such as Aneityum, Taiwan); iii) coverage of such an approach with effective community engagement [21,22]; and the challenges could be resistance to antimalarials [19,[23][24][25] as well as lack of support from local authorities.…”

Combining antimalarial drugs and vaccine for malaria elimination campaigns: a randomized safety and immunogenicity trial of RTS,S/AS01 administered with dihydroartemisinin, piperaquine, and primaquine in healthy Thai adult volunteers

“…In a recent series of MDA in Asia intense community engagement helped achieve MDA coverage above 80% which is thought to be the threshold for the interruption of malaria transmission. 24 The benefit of MVDA needs to be carefully communicated to target communities in order to reach adequate coverage. There is little reason to think that an intramuscular injection will reduce the uptake of the intervention substantially, on the contrary, it is possible that communities perceive injections more "powerful" than orally administered drugs and hence a desirable adjunct to drug administrations.…”

Tools to accelerate falciparum malaria elimination in Cambodia: a meeting report

“…To assess the impact of targeted malaria elimination project named "Targeted Malaria Elimination" (TME) including a cluster randomised trial with dihydroartemisinin-piperaquine (DHA/piperaquine) MDA was conducted between 2013 and 2017 in 16 rural communities in Cambodia, Myanmar, Vietnam, and the Lao People's Democratic Republic, where artemisinin resistance is prevalent. The results were presented during the meeting [45]. It is assumed that some mosquitoes, which ingested infected blood in the days prior to the MDA will survive until after the anti-malarial drug blood level is no longer high enough to clear a fresh P. falciparum inoculum.…”

“…MORU 2014 to 2017 [45]-Battambang province, western Cambodia and Binh Phuoc, Vietnam. The few, available data suggest a 100% clearance rate in the MSF studies in Cambodia, 90% clearance rate in MORU studies in Cambodia and Vietnam (no P. falciparum Pailin was detected in Myanmar and Laos) and 60% clearance rate in the USAFRIMS study in Cambodia.…”