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

Lorenz von Seidlein 1, 2, * Thomas Peto 1, 2 Jordi Landier 3, 4, * Thuy-Nhien Nguyen 5 Rupam Tripura 1, 2, 6 Koukeo Phommasone 7, 8 Tiengkham Pongvongsa 9, 10 Khin Lwin 4 Lilly Keereecharoen 4 Ladda Kajeechiwa 4 May Thwin 4 Daniel Parker 4, 11 Jacher Wiladphaingern 4 Suphak Nosten 4 Stephane Proux 4 Vincent Corbel 12 Nguyen Tuong-Vy 5 Truong Le Phuc-Nhi 5 Do Son 5 Pham Nguyen Huong-Thu 5 Nguyen Thi Kim Tuyen 5 Nguyen Tien 5 Le Dong 13 Dao van Hue 14 Huynh Hong Quang 15 Chea Nguon 16 Chan Davoeung 17 Huy Rekol 16 Bipin Adhikariid 1, 2 Gisela Henriques 1, 18 Panom Phongmany 9 Preyanan Suangkanarat 7 Atthanee Jeeyapant 1 Benchawan Vihokhern 1 Rob van der Pluijm 1, 2 Yoel Lubell 1, 2 Lisa White 1, 2 Ricardo Aguas 1, 2 Cholrawee Promnarate 1, 19 Pasathorn Sirithiranont 1 Benoit Malleret 20, 21 Laurent Rénia 21 Carl Onsjö 1, 22 Xin Chan 1, 2 Jeremy Chalk 1 Olivo Miotto 1, 23 Krittaya Patumrat 24 Kesinee Chotivanich 1, 25 Borimas Hanboonkunupakarn 1, 10 Podjanee Jittmala 1, 10 Nils Kaehler 1 Phaik Cheah 1, 2 Christopher Pell 8 Mehul Dhorda 1 Mallika Imwong 1, 24 Georges Snounou 26 Mavuto Mukaka 1, 2 Pimnara Peerawaranun 1 Sue Lee 1, 2 Julie Simpson 27 Sasithon Pukrittayakamee 1, 10, 28 Pratap Singhasivanon 25 Martin Grobusch 6 Frank Cobelens 8 Frank Smithuis 29 Paul Newton 2, 7 Guy Thwaites 2, 5 Nicholas Day 1, 2 Mayfong Mayxay 30, 7 Tran Hien 2, 3 Francois Nosten 2, 4 Arjen Dondorp 1, 2 Nicholas White 1, 2
* Corresponding author
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 incidence and prevalence of falciparum malaria over a 1-year period in areas affected by artemisinin resistance. P. falciparum infections returned during the follow-up period as the remaining infections spread and malaria was reintroduced from surrounding areas. Limitations of this study include a relatively small sample of villages, heterogeneity between villages, and mobility of villagers that may have limited the impact of the intervention. These results suggest that, if used as part of a comprehensive, well-organised, and well-resourced elimination programme, DP MDA can be a useful additional tool to accelerate malaria elimination.
Complete list of metadatas

Cited literature [55 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-02143366
Contributor : Christine Dupuis <>
Submitted on : Wednesday, May 29, 2019 - 12:31:34 PM
Last modification on : Tuesday, November 5, 2019 - 10:00:18 AM

File

journal.pmed.1002745.pdf
Publisher files allowed on an open archive

Identifiers

Citation

Lorenz von Seidlein, Thomas Peto, Jordi Landier, Thuy-Nhien Nguyen, Rupam Tripura, et al.. The impact of targeted malaria elimination with mass drug administrations on falciparum malaria in Southeast Asia: A cluster randomised trial. PLoS Medicine, Public Library of Science, 2019, 16 (2), pp.e1002745. ⟨10.1371/journal.pmed.1002745⟩. ⟨inserm-02143366⟩

Share

Metrics

Record views

158

Files downloads

81