Malaria burden and artemisinin resistance in the mobile and migrant population on the Thai-Myanmar border, 1999-2011: an observational study

Abstract

Background: The Shoklo Malaria Research Unit has been working on the Thai-Myanmar border for 25 y providing early diagnosis and treatment (EDT) of malaria. Transmission of Plasmodium falciparum has declined, but resistance to artesunate has emerged. We expanded malaria activities through EDT and evaluated the impact over a 12-y period.

Methods and findings: Between 1 October 1999 and 30 September 2011, the Shoklo Malaria Research Unit increased the number of cross-border (Myanmar side) health facilities from two to 11 and recorded the number of malaria consultations. Changes in malaria incidence were estimated from a cohort of pregnant women, and prevalence from cross-sectional surveys. In vivo and in vitro antimalarial drug efficacy were monitored. Over this period, the number of malaria cases detected increased initially, but then declined rapidly. In children under 5 y, the percentage of consultations due to malaria declined from 78% (95% CI 76-80) (1,048/1,344 consultations) to 7% (95% CI 6.2-7.1) (767/11,542 consultations), p<0.001. The ratio of P. falciparum/P. vivax declined from 1.4 (95% CI 1.3-1.4) to 0.7 (95% CI 0.7-0.8). The case fatality rate was low (39/75,126; 0.05% [95% CI 0.04-0.07]). The incidence of malaria declined from 1.1 to 0.1 episodes per pregnant women-year. The cumulative proportion of P. falciparum decreased significantly from 24.3% (95% CI 21.0-28.0) (143/588 pregnant women) to 3.4% (95% CI 2.8-4.3) (76/2,207 pregnant women), p<0.001. The in vivo efficacy of mefloquine-artesunate declined steadily, with a sharp drop in 2011 (day-42 PCR-adjusted cure rate 42% [95% CI 20-62]). The proportion of patients still slide positive for malaria at day 3 rose from 0% in 2000 to reach 28% (95% CI 13-45) (8/29 patients) in 2011.

Conclusions: Despite the emergence of resistance to artesunate in P. falciparum, the strategy of EDT with artemisinin-based combination treatments has been associated with a reduction in malaria in the migrant population living on the Thai-Myanmar border. Although limited by its observational nature, this study provides useful data on malaria burden in a strategically crucial geographical area. Alternative fixed combination treatments are needed urgently to replace the failing first-line regimen of mefloquine and artesunate. Please see later in the article for the Editors' Summary.

Figure 1. Location of SMRU clinics and cross-border health posts run by village health workers.

Blue crosses indicate SMRU clinics; inverted red triangles indicate SMRU health posts. The Thai–Myanmar border is represented by a black line, and the main roads by grey lines.

Figure 2. Proportion of malaria smears with P. falciparum or P. vivax gametocytes.

Annual proportion of all patients whose smears were positive for P. falciparum malaria who had P. falciparum gametocytes present on their malaria smear (red), and those whose smears were positive for P. vivax malaria who had P. vivax gametocytes present on their malaria smear (blue). Bars indicate 95% CIs.

Figure 3. P. falciparum and P. vivax malaria incidence among pregnant women.

Red line indicates P. falciparum; blue line indicates P. vivax. Bars indicate 95% CIs.

Figure 4. Annual proportion of P. falciparum and P. vivax infections among pregnant women.

Red line indicates P. falciparum; blue line indicates P. vivax. Bars indicate 95% CIs.

Figure 5. Proportion of pregnant women with anaemia during their pregnancy.

Anaemia was considered present if there was at least one haematocrit value<30% during the course of the pregnancy. Bars indicate 95% CIs.

Figure 6. P. falciparum infection/P. vivax infection ratio from village surveys in Myanmar within SMRU clinic/health post catchment area.

Red squares indicate the P. falciparum infection/P. vivax infection (PF/PV) ratio; bars indicate 95% CIs. A ratio above 1 indicates the predominance of P. falciparum over P. vivax; a ratio below 1 indicates the predominance of P. vivax.

Figure 7. Day-42 PCR-adjusted MAS₃ parasitological efficacy and proportion of patients still parasitaemic at day 3.

This graph shows the changes in day-42 PCR-adjusted MAS₃ parasitological efficacy (black dashed line) and proportion of patients still parasitaemic at day 3 (red line) from 2000 to 2011. Bars indicate 95% CIs.

Figure 8. P. falciparum isolate in vitro sensitivity to mefloquine, artesunate, and di-hydroartemisinin from 2000 to 2010.

Red lines indicate in vitro sensitivity of P. falciparum isolates to (A) mefloquine, (B) artesunate, and (C) dihydroartemisinin. Bars indicate 95% CIs. No data were available for 2011.

Figure 9. Annual rainfall and mean annual temperature between 2000 and 2011.

Black line indicates mean annual temperature in degrees Celsius, and grey bars indicate annual rainfall in millimetres.