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

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, 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

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.

Trial registration: ClinicalTrials.gov NCT01872702.

Conflict of interest statement

The authors have declared that no competing interests exist. LvS receives a stipend as a Specialty Consulting Editor for PLOS Medicine and serves on the journal's Editorial Board. NJW is a member of the Editorial Board of PLOS Medicine.

Figures

Fig 1. Countries and study sites in…
Fig 1. Countries and study sites in the Greater Mekong Subregion.
Baseline P. falciparum (Pf) prevalence is shown for the 5 study sites (1 in each country except Vietnam, which had 2).
Fig 2. CONSORT flow chart—the first 12…
Fig 2. CONSORT flow chart—the first 12 months.
M[number], month [number]; MDA, mass drug administration; Pf, P. falciparum.
Fig 3. Prevalence and incidence of P…
Fig 3. Prevalence and incidence of P. falciparum (with 95% confidence intervals) detected using ultrasensitive quantitative PCR in 8 intervention (early MDA) and 8 control (deferred MDA) villages over a 12-month follow-up period.
M[number], month [number]; MDA, mass drug administration; Pf, P. falciparum.
Fig 4. Comparison of incidence rate ratios…
Fig 4. Comparison of incidence rate ratios of P. falciparum infections detected by ultrasensitive quantitative PCR between early MDA and deferred MDA villages, by country. MDA, mass drug administration; Pf, P. falciparum.
Fig 5. P . falciparum clearance after…
Fig 5. P. falciparum clearance after MDA: Dihydroartemisinin-piperaquine efficacy against asymptomatic infections estimated from individual-participant-level data from villages randomised to both early and deferred MDA in Myanmar and Vietnam, and from early MDA villages only in Cambodia and Lao PDR. Subscripts in red indicate the number of participants with the P. falciparum PfPailin genotype [8]—a long haplotype containing PfKelch13 C580Y, conferring artemisinin resistance, and multiple copies of the Pfplasmepsin2/3 genotype conferring piperaquine resistance.
F/U, follow-up; Lao PDR, Lao People’s Democratic Republic; MDA, mass drug administration; Pf, P. falciparum.

References

    1. Bulchis A, Larson E. Sri Lanka celebrates malaria-free certification after long history of malaria control. San Francisco: Malaria Elimination Initiative; 2016 Sep 6 [cited 2019 Jan 18]. Available: .
    1. Hemingway J, Ranson H, Magill A, Kolaczinski J, Fornadel C, Gimnig J, et al. Averting a malaria disaster: will insecticide resistance derail malaria control? Lancet. 2016;387(10029):1785–8. 10.1016/S0140-6736(15)00417-1
    1. Ashley EA, Dhorda M, Fairhurst RM, Amaratunga C, Lim P, Suon S, et al. Spread of artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med. 2014;371(5):411–23. 10.1056/NEJMoa1314981
    1. Amaratunga C, Lim P, Suon S, Sreng S, Mao S, Sopha C, et al. Dihydroartemisinin-piperaquine resistance in Plasmodium falciparum malaria in Cambodia: a multisite prospective cohort study. Lancet Infect Dis. 2016;16(3):357–65. 10.1016/S1473-3099(15)00487-9
    1. Duru V, Khim N, Leang R, Kim S, Domergue A, Kloeung N, et al. Plasmodium falciparum dihydroartemisinin-piperaquine failures in Cambodia are associated with mutant K13 parasites presenting high survival rates in novel piperaquine in vitro assays: retrospective and prospective investigations. BMC Med. 2015;13:305 10.1186/s12916-015-0539-5
    1. Spring MD, Lin JT, Manning JE, Vanachayangkul P, Somethy S, Bun R, et al. Dihydroartemisinin-piperaquine failure associated with a triple mutant including kelch13 C580Y in Cambodia: an observational cohort study. Lancet Infect Dis. 2015;15(6):683–91. 10.1016/S1473-3099(15)70049-6
    1. Mita T, Tanabe K. Evolution of Plasmodium falciparum drug resistance: implications for the development and containment of artemisinin resistance. Jpn J Infect Dis. 2012;65(6):465–75.
    1. Imwong M, Hien TT, Thuy-Nhien NT, Dondorp AM, White NJ. Spread of a single multidrug resistant malaria parasite lineage (PfPailin) to Vietnam. Lancet Infect Dis. 2017;17(10):1022–3. 10.1016/S1473-3099(17)30524-8
    1. Imwong M, Suwannasin K, Kunasol C, Sutawong K, Mayxay M, Rekol H, et al. The spread of artemisinin-resistant Plasmodium falciparum in the Greater Mekong subregion: a molecular epidemiology observational study. Lancet Infect Dis. 2017;17(5):491–7. 10.1016/S1473-3099(17)30048-8
    1. Newby G, Hwang J, Koita K, Chen I, Greenwood B, von Seidlein L, et al. Review of mass drug administration for malaria and its operational challenges. Am J Trop Med Hyg. 2015;93(1):125–34. 10.4269/ajtmh.14-0254
    1. von Seidlein L, Greenwood BM. Mass administrations of antimalarial drugs. Trends Parasitol. 2003;19(10):452–60.
    1. Poirot E, Skarbinski J, Sinclair D, Kachur SP, Slutsker L, Hwang J. Mass drug administration for malaria. Cochrane Database Syst Rev. 2013;12:CD008846. 10.1002/14651858.CD008846.pub2
    1. Kaneko A, Taleo G, Kalkoa M, Yamar S, Kobayakawa T, Bjorkman A. Malaria eradication on islands. Lancet. 2000;356(9241):1560–4. 10.1016/S0140-6736(00)03127-5
    1. Eisele TP, Bennett A, Silumbe K, Finn TP, Chalwe V, Kamuliwo M, et al. Short-term impact of mass drug administration with dihydroartemisinin plus piperaquine on malaria in Southern Province Zambia: a cluster-randomized controlled trial. J Infect Dis. 2016;214(12):1831–9. 10.1093/infdis/jiw416
    1. Deng C, Huang B, Wang Q, Wu W, Zheng S, Zhang H, et al. Large-scale artemisinin-piperaquine mass drug administration with or without primaquine dramatically reduces malaria in a highly endemic region of Africa. Clin Infect Dis. 2018;67(11):1670–6. 10.1093/cid/ciy364
    1. Chakir I, Said AI, Affane B, Jambou R. Control of malaria in the Comoro Islands over the past century. Malar J. 2017;16(1):387 10.1186/s12936-017-2027-1
    1. Luxemburger C, Thwai KL, White NJ, Webster HK, Kyle DE, Maelankirri L, et al. The epidemiology of malaria in a Karen population on the western border of Thailand. Trans R Soc Trop Med Hyg. 1996;90(2):105–11.
    1. Paul RE, Hackford I, Brockman A, Muller-Graf C, Price R, Luxemburger C, et al. Transmission intensity and Plasmodium falciparum diversity on the northwestern border of Thailand. Am J Trop Med Hyg. 1998;58(2):195–203.
    1. Carrara VI, Lwin KM, Phyo AP, Ashley E, Wiladphaingern J, Sriprawat K, et al. Malaria burden and artemisinin resistance in the mobile and migrant population on the Thai-Myanmar border, 1999–2011: an observational study. PLoS Med. 2013;10(3):e1001398 10.1371/journal.pmed.1001398
    1. Kwansomboon N, Chaumeau V, Kittiphanakun P, Cerqueira D, Corbel V, Chareonviriyaphap T. Vector bionomics and malaria transmission along the Thailand-Myanmar border: a baseline entomological survey. J Vector Ecol. 2017;42(1):84–93. 10.1111/jvec.12242
    1. Landier J, Parker DM, Thu AM, Lwin KM, Delmas G, Nosten FH, et al. Effect of generalised access to early diagnosis and treatment and targeted mass drug administration on Plasmodium falciparum malaria in Eastern Myanmar: an observational study of a regional elimination programme. Lancet. 2018;391(10133):1916–26. 10.1016/S0140-6736(18)30792-X
    1. Imwong M, Nguyen TN, Tripura R, Peto TJ, Lee SJ, Lwin KM, et al. The epidemiology of subclinical malaria infections in South-East Asia: findings from cross-sectional surveys in Thailand-Myanmar border areas, Cambodia, and Vietnam. Malar J. 2015;14:381 10.1186/s12936-015-0906-x
    1. Landier J, Kajeechiwa L, Thwin MM, Parker DM, Chaumeau V, Wiladphaingern J, et al. Safety and effectiveness of mass drug administration to accelerate elimination of artemisinin-resistant falciparum malaria: a pilot trial in four villages of Eastern Myanmar. Wellcome Open Res. 2017;2:81 10.12688/wellcomeopenres.12240.1
    1. Goldlust SM, Thuan PD, Giang DDH, Thang ND, Thwaites GE, Farrar J, et al. The decline of malaria in Vietnam, 1991–2014. Malar J. 2018;17(1):226 10.1186/s12936-018-2372-8
    1. Hien TT, Thuy-Nhien NT, Phu NH, Boni MF, Thanh NV, Nha-Ca NT, et al. In vivo susceptibility of Plasmodium falciparum to artesunate in Binh Phuoc Province, Vietnam. Malar J. 2012;11:355 10.1186/1475-2875-11-355
    1. Thanh NV, Thuy-Nhien N, Tuyen NT, Tong NT, Nha-Ca NT, Dong LT, et al. Rapid decline in the susceptibility of Plasmodium falciparum to dihydroartemisinin-piperaquine in the south of Vietnam. Malar J. 2017;16(1):27 10.1186/s12936-017-1680-8
    1. Noedl H, Se Y, Schaecher K, Smith BL, Socheat D, Fukuda MM. Evidence of artemisinin-resistant malaria in western Cambodia. N Engl J Med. 2008;359(24):2619–20. 10.1056/NEJMc0805011
    1. Dondorp AM, Nosten F, Yi P, Das D, Phyo AP, Tarning J, et al. Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med. 2009;361(5):455–67. 10.1056/NEJMoa0808859
    1. World Health Organization. World malaria report 2012 Geneva: World Health Organization; 2012.
    1. World Health Organization. Global plan for artemisinin resistance containment Geneva: World Health Organization; 2012.
    1. World Health Organization. Emergency response plan to artemisinin resistance in the Greater Mekong Subregion Geneva: World Health Organization; 2013.
    1. Hoyer S, Nguon S, Kim S, Habib N, Khim N, Sum S, et al. Focused Screening and Treatment (FSAT): a PCR-based strategy to detect malaria parasite carriers and contain drug resistant P. falciparum, Pailin, Cambodia. PLoS ONE. 2012;7(10):e45797 10.1371/journal.pone.0045797
    1. Cook J, Speybroeck N, Sochanta T, Somony H, Sokny M, Claes F, et al. Sero-epidemiological evaluation of changes in Plasmodium falciparum and Plasmodium vivax transmission patterns over the rainy season in Cambodia. Malar J. 2012;11:86 10.1186/1475-2875-11-86
    1. Tripura R, Peto TJ, Veugen CC, Nguon C, Davoeung C, James N, et al. Submicroscopic Plasmodium prevalence in relation to malaria incidence in 20 villages in western Cambodia. Malar J. 2017;16(1):56 10.1186/s12936-017-1703-5
    1. Tripura R, Peto TJ, Nguon C, Davoeung C, Mukaka M, Sirithiranont P, et al. A controlled trial of mass drug administration to interrupt transmission of multi drug resistant falciparum malaria in Cambodian villages. Clin Infect Dis. 2018;67(6):817–26. 10.1093/cid/ciy196
    1. Lao People’s Democratic Republic Ministry of Health. National strategic plan for malaria control and elimination 2016–2020. Lao People’s Democratic Republic Ministry of Health; 2016 [cited 2019 Jan 18]. Available: .
    1. Phommasone K, Adhikari B, Henriques G, Pongvongsa T, Phongmany P, von Seidlein L, et al. Asymptomatic Plasmodium infections in 18 villages of southern Savannakhet Province, Lao PDR (Laos). Malar J. 2016;15(1):296 10.1186/s12936-016-1336-0
    1. Kajeechiwa L, Thwin MM, Nosten S, Tun SW, Parker D, von Seidlein L, et al. Community engagement for the rapid elimination of malaria: the case of Kayin State, Myanmar. Wellcome Open Res. 2017;2:59 10.12688/wellcomeopenres.12051.1
    1. Nguyen TN, Thu PN, Hung NT, Son DH, Tien NT, Van Dung N, et al. Community perceptions of targeted anti-malarial mass drug administrations in two provinces in Vietnam: a quantitative survey. Malar J. 2017;16(1):17 10.1186/s12936-016-1662-2
    1. Adhikari B, Phommasone K, Pongvongsa T, Kommarasy P, Soundala X, Henriques G, et al. Factors associated with population coverage of targeted malaria elimination (TME) in southern Savannakhet Province, Lao PDR. Malar J. 2017;16(1):424 10.1186/s12936-017-2070-y
    1. Pell C, Tripura R, Nguon C, Cheah P, Davoeung C, Heng C, et al. Mass anti-malarial administration in western Cambodia: a qualitative study of factors affecting coverage. Malar J. 2017;16(1):206 10.1186/s12936-017-1854-4
    1. Sahan K, Pell C, Smithuis F, Phyo AK, Maung SM, Indrasuta C, et al. Community engagement and the social context of targeted malaria treatment: a qualitative study in Kayin (Karen) State, Myanmar. Malar J. 2017;16(1):75 10.1186/s12936-017-1718-y
    1. Adhikari B, James N, Newby G, von Seidlein L, White NJ, Day NP, et al. Community engagement and population coverage in mass anti-malarial administrations: a systematic literature review. Malar J. 2016;15(1):523 10.1186/s12936-016-1593-y
    1. Peto TJ, Tripura R, Davoeung C, Nguon C, Nou S, Heng C, et al. Reflections on a community engagement strategy for mass antimalarial drug administration in Cambodia. Am J Trop Med Hyg. 2018;98(1):100–4. 10.4269/ajtmh.17-0428
    1. Adhikari B, Pell C, Phommasone K, Soundala X, Kommarasy P, Pongvongsa T, et al. Elements of effective community engagement: lessons from a targeted malaria elimination study in Lao PDR (Laos). Glob Health Action. 2017;10(1):1366136 10.1080/16549716.2017.1366136
    1. Grundy PM, Healy MJR. Restricted randomization and quasi-Latin squares. J R Stat Soc Series B Stat Methodol. 1950;12:215–7.
    1. von Seidlein L, Dondorp A. Fighting fire with fire: mass antimalarial drug administrations in an era of antimalarial resistance. Expert Rev Anti Infect Ther. 2015;13(6):715–30. 10.1586/14787210.2015.1031744
    1. Ashley EA, Recht J, White NJ. Primaquine: the risks and the benefits. Malar J. 2014;13:418 10.1186/1475-2875-13-418
    1. Hanboonkunupakarn B, Ashley EA, Jittamala P, Tarning J, Pukrittayakamee S, Hanpithakpong W, et al. Open-label crossover study of primaquine and dihydroartemisinin-piperaquine pharmacokinetics in healthy adult Thai subjects. Antimicrob Agents Chemother. 2014;58(12):7340–6. 10.1128/AAC.03704-14
    1. White NJ, Qiao LG, Qi G, Luzzatto L. Rationale for recommending a lower dose of primaquine as a Plasmodium falciparum gametocytocide in populations where G6PD deficiency is common. Malar J. 2012;11:418 10.1186/1475-2875-11-418
    1. Sutanto I, Suprijanto S, Kosasih A, Dahlan MS, Syafruddin D, Kusriastuti R, et al. The effect of primaquine on gametocyte development and clearance in the treatment of uncomplicated falciparum malaria with dihydroartemisinin-piperaquine in South Sumatra, Western Indonesia: an open-label, randomized, controlled trial. Clin Infect Dis. 2013;56(5):685–93. 10.1093/cid/cis959
    1. Imwong M, Hanchana S, Malleret B, Renia L, Day NP, Dondorp A, et al. High throughput ultra-sensitive molecular techniques to quantify low density malaria parasitaemias. J Clin Microbiol. 2014;9(52):3003–9. 10.1128/JCM.01057-14
    1. Kamau E, Tolbert LS, Kortepeter L, Pratt M, Nyakoe N, Muringo L, et al. Development of a highly sensitive genus-specific quantitative reverse transcriptase real-time PCR assay for detection and quantitation of plasmodium by amplifying RNA and DNA of the 18S rRNA genes. J Clin Microbiol. 2011;49(8):2946–53. 10.1128/JCM.00276-11
    1. Imwong M, Snounou G, Pukrittayakamee S, Tanomsing N, Kim JR, Nandy A, et al. Relapses of Plasmodium vivax infection usually result from activation of heterologous hypnozoites. J Infect Dis. 2007;195(7):927–33. 10.1086/512241
    1. Snounou G. Detection and identification of the four malaria parasite species infecting humans by PCR amplification. Methods Mol Biol. 1996;50:263–91.
    1. Amato R, Lim P, Miotto O. Genetic markers associated with dihydroartemisinin–piperaquine failure in Plasmodium falciparum malaria in Cambodia: a genotype–phenotype association study. Lancet Infect Dis. 2017;17:164–73. 10.1016/S1473-3099(16)30409-1
    1. Austin PC, Stryhn H, Leckie G, Merlo J. Measures of clustering and heterogeneity in multilevel Poisson regression analyses of rates/count data. Stat Med. 2018;37(4):572–89. 10.1002/sim.7532
    1. Phuc BQ, Rasmussen C, Duong TT, Dong LT, Loi MA, Menard D, et al. Treatment failure of dihydroartemisinin/piperaquine for Plasmodium falciparum malaria, Vietnam. Emerg Infect Dis. 2017;23(4):715–7. 10.3201/eid2304.161872
    1. Chaumeau V, Kajeechiwa L, Fustec B, Landier J, Nyo SN, Hsel SN, et al. The contribution of asymptomatic Plasmodium infections to the transmission of malaria in Kayin state, Myanmar. J Infect Dis. 2018. November 29 10.1093/infdis/jiy686
    1. Smithuis FM, Kyaw MK, Phe UO, van der Broek I, Katterman N, Rogers C, et al. The effect of insecticide-treated bed nets on the incidence and prevalence of malaria in children in an area of unstable seasonal transmission in western Myanmar. Malar J. 2013;12:363 10.1186/1475-2875-12-363
    1. Ya-Umphan P, Cerqueira D, Cottrell G, Parker DM, Fowkes FJI, Nosten F, et al. Anopheles salivary biomarker as a proxy for estimating plasmodium falciparum malaria exposure on the Thailand-Myanmar border. Am J Trop Med Hyg. 2018;99(2):350–6. 10.4269/ajtmh.18-0081
    1. Ya-Umphan P, Cerqueira D, Parker DM, Cottrell G, Poinsignon A, Remoue F, et al. Use of an Anopheles salivary biomarker to assess malaria transmission risk along the Thailand-Myanmar border. J Infect Dis. 2017;215(3):396–404. 10.1093/infdis/jiw543
    1. Durnez L, Mao S, Denis L, Roelants P, Sochantha T, Coosemans M. Outdoor malaria transmission in forested villages of Cambodia. Malar J. 2013;12:329 10.1186/1475-2875-12-329
    1. Gryseels C, Durnez L, Gerrets R, Uk S, Suon S, Set S, et al. Re-imagining malaria: heterogeneity of human and mosquito behaviour in relation to residual malaria transmission in Cambodia. Malar J. 2015;14:165 10.1186/s12936-015-0689-0
    1. Thanh PV, Van Hong N, Van Van N, Van Malderen C, Obsomer V, Rosanas-Urgell A, et al. Epidemiology of forest malaria in Central Vietnam: the hidden parasite reservoir. Malar J. 2015;14:86 10.1186/s12936-015-0601-y
    1. Simpson SH, Eurich DT, Majumdar SR, Padwal RS, Tsuyuki RT, Varney J, et al. A meta-analysis of the association between adherence to drug therapy and mortality. BMJ. 2006;333(7557):15 10.1136/bmj.38875.675486.55
    1. Chewning B. The healthy adherer and the placebo effect. BMJ. 2006;333(7557):18–9. 10.1136/bmj.333.7557.18
    1. Aguas R, Maude RJ, Gomes MGM, White LJ, White NJ, Dondorp AM. Infectivity of chronic malaria infections and its consequences for control and elimination. Clin Infect Dis. 2018;67(2):295–302. 10.1093/cid/ciy055
    1. McLean ARD, Wai HP, Thu AM, Khant ZS, Indrasuta C, Ashley EA, et al. Malaria elimination in remote communities requires integration of malaria control activities into general health care: an observational study and interrupted time series analysis in Myanmar. BMC Med. 2018;16(1):183 10.1186/s12916-018-1172-x
    1. Taylor AR, Schaffner SF, Cerqueira GC, Nkhoma SC, Anderson TJC, Sriprawat K, et al. Quantifying connectivity between local Plasmodium falciparum malaria parasite populations using identity by descent. PLoS Genet. 2017;13(10):e1007065 10.1371/journal.pgen.1007065
    1. Omedo I, Mogeni P, Bousema T, Rockett K, Amambua-Ngwa A, Oyier I, et al. Micro-epidemiological structuring of Plasmodium falciparum parasite populations in regions with varying transmission intensities in Africa. Wellcome Open Res. 2017;2:10 10.12688/wellcomeopenres.10784.2
    1. Pinilla YT, Lopes SCP, Sampaio VS, Andrade FS, Melo GC, Orfano AS, et al. Promising approach to reducing Malaria transmission by ivermectin: sporontocidal effect against Plasmodium vivax in the South American vectors Anopheles aquasalis and Anopheles darlingi. PLoS Negl Trop Dis. 2018;12(2):e0006221 10.1371/journal.pntd.0006221
    1. Tun STT, von Seidlein L, Pongvongsa T, Mayxay M, Saralamba S, Kyaw SS, et al. Towards malaria elimination in Savannakhet, Lao PDR: mathematical modelling driven strategy design. Malar J. 2017;16(1):483 10.1186/s12936-017-2130-3

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