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

Abstract

Background: Potentially untreatable Plasmodium falciparum malaria threatens the Greater Mekong subregion. A previous series of pilot projects in Myanmar, Laos, Cambodia, and Vietnam suggested that mass drug administration was safe, and when added to provision of early diagnosis and treatment, could reduce the reservoir of P falciparum and interrupts transmission. We examined the effects of a scaled-up programme of this strategy in four townships of eastern Myanmar on the incidence of P falciparum malaria.

Methods: The programme was implemented in the four townships of Myawaddy, Kawkareik, Hlaingbwe, and Hpapun in Kayin state, Myanmar. Increased access to early diagnosis and treatment of malaria was provided to all villages through community-based malaria posts equipped with rapid diagnostic tests, and treatment with artemether-lumefantrine plus single low-dose primaquine. Villages were identified as malarial hotspots (operationally defined as >40% malaria, of which 20% was P falciparum) with surveys using ultrasensitive quantitative PCR either randomly or targeted at villages where the incidence of clinical cases of P falciparum malaria remained high (ie, >100 cases per 1000 individuals per year) despite a functioning malaria post. During each survey, a 2 mL sample of venous blood was obtained from randomly selected adults. Hotspots received targeted mass drug administration with dihydroartemisinin-piperaquine plus single-dose primaquine once per month for 3 consecutive months in addition to the malaria posts. The main outcome was the change in village incidence of clinical P falciparum malaria, quantified using a multivariate, generalised, additive multilevel model. Malaria prevalence was measured in the hotspots 12 months after mass drug administration.

Findings: Between May 1, 2014, and April 30, 2017, 1222 malarial posts were opened, providing early diagnosis and treatment to an estimated 365 000 individuals. Incidence of P falciparum malaria decreased by 60 to 98% in the four townships. 272 prevalence surveys were undertaken and 69 hotspot villages were identified. By April 2017, 50 hotspots were treated with mass drug administration. Hotspot villages had a three times higher incidence of P falciparum at malarial posts than neighbouring villages (adjusted incidence rate ratio [IRR] 2·7, 95% CI 1·8-4·4). Early diagnosis and treatment was associated with a significant decrease in P falciparum incidence in hotspots (IRR 0·82, 95% CI 0·76-0·88 per quarter) and in other villages (0·75, 0·73-0·78 per quarter). Mass drug administration was associated with a five-times decrease in P falciparum incidence within hotspot villages (IRR 0·19, 95% CI 0·13-0·26). By April, 2017, 965 villages (79%) of 1222 corresponding to 104 village tracts were free from P falciparum malaria for at least 6 months. The prevalence of wild-type genotype for K13 molecular markers of artemisinin resistance was stable over the three years (39%; 249/631).

Interpretation: Providing early diagnosis and effective treatment substantially decreased village-level incidence of artemisinin-resistant P falciparum malaria in hard-to-reach, politically sensitive regions of eastern Myanmar. Targeted mass drug administration significantly reduced malaria incidence in hotspots. If these activities could proceed in all contiguous endemic areas in addition to standard control programmes already implemented, there is a possibility of subnational elimination of P falciparum.

Funding: The Bill & Melinda Gates Foundation, the Regional Artemisinin Initiative (Global Fund against AIDS, Tuberculosis and Malaria), and the Wellcome Trust.

Figure 1

Incidence of (A) Plasmodium falciparum and (B) Plasmodium vivax over 3 years of the programme Data are the number of cases per 1000 individuals per year by village tract (lowest administrative division).

Figure 2

Malaria incidence since malaria post opening in the townships of Hpapun (468 malaria posts) and Myawaddy (100 malaria posts) where hotspots were identified (52 of 69 located in Hpapun Township. 7 of 69 in Myawaddy). Different y-scales are used in each graph. Falciparum in red and vivax in blue. Graphs show (A) non-hotspot villages. The widening CI after 24 months indicated that fewer malaria posts had been active for 2 years or more. The oscillations in Plasmodium vivax incidence are related to seasonal peaks occurring in the same locations in Myawaddy township (appendix). (B) hotspot villages before mass drug administration. Only 16 hotspots contributed to follow-up for durations of malaria post activity above 18 months. These high-incidence locations were only identified during the final campaign of baseline surveys (November, 2016, to January, 2017) and had not been addressed by April, 2017. The median follow-up before mass drug administration was 15 months (IQR 8–22), including addressed hotspots (median 12 months, IQR 5–16, n=50) and hotspots remaining unaddressed (median 32 months, 25–33, n=18). Data missing for one hotspot, which could not be equipped with a malaria post (appendix).

Figure 3

Mean Plasmodium falciparum and Plasmodium vivax incidence in hotspots before and after mass drug administration Data are (A) centred on the date of mass drug administration. Each hotspot contributes different lengths of follow-up before and after mass drug administration. The median follow-up before mass drug administration was 15 months (IQR 8–22), including addressed hotspots (median 12 months, 5–16, n=50) and hotspots remaining unaddressed (median 32 months, 25–33, n=18). The median follow-up after mass drug administration was 20 months (IQR 14–24, n=50). A marked decrease in P falciparum incidence after mass drug administration is observable, despite an increase in incidence around 15 months after mass drug administration. This increase is related to five hotspots (of 52 followed up to month 18) showing an incidence above 50 cases per 1000 individuals for 1 month during the second year after mass drug administration. This increase did not persist. Other graphs show incidence by duration since malaria post opening, according to before, or after, mass drug administration status for (B) P falciparum and (C) P vivax. Non-hotspot incidence trend (dashed line) is presented for reference. Different numbers of villages contributed to each estimate according to the timing of their mass drug administration.