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

Issued Date

2019-02-01

Resource Type

Article

ISSN

15491676
15491277

DOI

10.1371/journal.pmed.1002745

Other identifier(s)

2-s2.0-85061580866

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Mahidol University

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SCOPUS

Bibliographic Citation

PLoS Medicine. Vol.16, No.2 (2019)

Suggested Citation

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 The impact of targeted malaria elimination with mass drug administrations on falciparum malaria in southeast Asia: A cluster randomised trial. PLoS Medicine. Vol.16, No.2 (2019). doi:10.1371/journal.pmed.1002745 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/51943

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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

Author(s)

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

Other Contributor(s)

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

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.

Keyword(s)

Medicine

Availability

URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/51943

Collections

Scopus 2019