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Title: The impact of targeted malaria elimination with mass drug administrations on falciparum malaria in southeast Asia: A cluster randomised trial
Authors: Lorenz von Seidlein
Thomas J. Peto
Jordi Landier
Thuy Nhien Nguyen
Rupam Tripura
Koukeo Phommasone
Tiengkham Pongvongsa
Khin Maung Lwin
Lilly Keereecharoen
Ladda Kajeechiwa
May Myo Thwin
Daniel M. Parker
Jacher Wiladphaingern
Suphak Nosten
Stephane Proux
Vincent Corbel
Nguyen Tuong-Vy
Truong Le Phuc-Nhi
Do Hung Son
Pham Nguyen Huong-Thu
Nguyen Thi Kim Tuyen
Nguyen Thanh Tien
Le Thanh Dong
Dao Van Hue
Huynh Hong Quang
Chea Nguon
Chan Davoeung
Huy Rekol
Bipin Adhikari
Gisela Henriques
Panom Phongmany
Preyanan Suangkanarat
Atthanee Jeeyapant
Benchawan Vihokhern
Rob W. van der Pluijm
Yoel Lubell
Lisa J. White
Ricardo Aguas
Cholrawee Promnarate
Pasathorn Sirithiranont
Benoit Malleret
Laurent Rénia
Carl Onsjö
Xin Hui Chan
Jeremy Chalk
Olivo Miotto
Krittaya Patumrat
Kesinee Chotivanich
Borimas Hanboonkunupakarn
Podjanee Jittmala
Nils Kaehler
Phaik Yeong Cheah
Christopher Pell
Mehul Dhorda
Mallika Imwong
Georges Snounou
Mavuto Mukaka
Pimnara Peerawaranun
Sue J. Lee
Julie A. Simpson
Sasithon Pukrittayakamee
Pratap Singhasivanon
Martin P. Grobusch
Frank Cobelens
Frank Smithuis
Paul N. Newton
Guy E. Thwaites
Nicholas P.J. Day
Mayfong Mayxay
Tran Tinh Hien
Francois H. Nosten
Arjen M. Dondorp
Nicholas J. White
Melbourne School of Population and Global Health
A-Star, Singapore Immunology Network
Université de Montpellier
Centre de Recherche en Immunologie des Infections Virales et des Maladies Auto-Immunes
London School of Hygiene & Tropical Medicine
IRD Institut de Recherche pour le Developpement
Yong Loo Lin School of Medicine
Mahidol University
Linköpings universitet
Nuffield Department of Clinical Medicine
University of California, Irvine
Wellcome Sanger Institute
Amsterdam UMC - University of Amsterdam
Center for Malariology, Parasitology and Entomology
University of Health Sciences
Amsterdam Institute for Global Health and Development
Mahosot Hospital
Myanmar Oxford Clinical Research Unit
Savannakhet Provincial Health Department
National Center for Parasitology, Entomology and Malaria Control
Royal Society of Thailand
Provincial Health Department
Institute of Malariology, Parasitology and Entomology
Oxford University Clinical Research Unit
Keywords: Medicine
Issue Date: 1-Feb-2019
Citation: PLoS Medicine. Vol.16, No.2 (2019)
Abstract: © 2019 von Seidlein et al. 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 pipera-quine-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.
ISSN: 15491676
Appears in Collections:Scopus 2019

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