Progress and challenges of integrated drug efficacy surveillance for uncomplicated malaria in Thailand

Abstract

Background: Integrated drug efficacy surveillance (iDES) was formally introduced nationally across Thailand in fiscal year 2018 (FY2018), building on a history of drug efficacy monitoring and interventions. According to the National Malaria Elimination Strategy for Thailand 2017-2026, diagnosis is microscopically confirmed, treatment is prescribed, and patients are followed up four times to ensure cure.

Methods: Routine patient data were extracted from the malaria information system for FY2018-FY2020. Treatment failure of first-line therapy was defined as confirmed parasite reappearance within 42 days for Plasmodium falciparum and 28 days for Plasmodium vivax. The primary outcome was the crude drug efficacy rate, estimated using Kaplan-Meier methods, at day 42 for P. falciparum treated with dihydroartemisinin-piperaquine plus primaquine, and day 28 for P. vivax treated with chloroquine plus primaquine; day 60 and day 90 efficacy were secondary outcomes for P. vivax.

Results: The proportion of patients with outcomes recorded at day 42 for P. falciparum malaria and at day 28 for P. vivax malaria has been increasing, with FY2020 follow-up rates of 61.5% and 57.2%, respectively. For P. falciparum malaria, day 42 efficacy in FY2018 was 92.4% (n = 249), in FY2019 93.3% (n = 379), and in FY2020 98.0% (n = 167). Plasmodium falciparum recurrences occurred disproportionally in Sisaket Province, with day 42 efficacy rates of 75.9% in FY2018 (n = 59) and 49.4% in FY2019 (n = 49), leading to an update in first-line therapy to pyronaridine-artesunate at the provincial level, rolled out in FY2020. For P. vivax malaria, day 28 efficacy (chloroquine efficacy) was 98.5% in FY2018 (n = 2048), 99.1% in FY2019 (n = 2206), and 99.9% in FY2020 (n = 2448), and day 90 efficacy (primaquine efficacy) was 94.8%, 96.3%, and 97.1%, respectively.

Conclusions: In Thailand, iDES provided operationally relevant data on drug efficacy, enabling the rapid amendment of treatment guidelines to improve patient outcomes and reduce the potential for the spread of drug-resistant parasites. A strong case-based surveillance system, integration with other health system processes, supporting biomarker collection and molecular analyses, and cross-border collaboration may maximize the potential of iDES in countries moving towards elimination.

Keywords: Antimalarial; Drug efficacy; Drug resistance; Malaria elimination; Surveillance.

Fig. 1

Malaria case follow-up form

Fig. 2

Malaria trends in Thailand FY2013–FY2020. Malaria mortality figures for FY2020 are provisional until officially approved by the Division of Planning and Strategy, Ministry of Public Health, Thailand

Fig. 3

Temporal and geographical distribution of malaria cases in Thailand FY2020

Fig. 4

Characteristics of malaria cases in Thailand FY2020. Each square represents 100% and each dot 1% of the population. Residency background was categorized as resident Thai, long-term migrant (≥ 6 months residency), or short-term migrant (< 6 months residency)

Fig. 5

Malaria case follow-up rates in Thailand. A All patients FY2018–FY2020, and B By patient origin in FY2020

Fig. 6

Efficacy of dihydroartemisinin–piperaquine plus primaquine against P. falciparum malaria in Thailand FY2018–FY2020. Data are Kaplan–Meier estimates for patients who had P. falciparum monoinfection, received at least one dose of both dihydroartemisinin–piperaquine and primaquine, and attended at least one follow-up visit. In Sisaket Province, pyronaridine–artesunate was rolled out as a new first-line treatment in FY2020, so data for this province are not shown for that year (see text)

Fig. 7

Efficacy of chloroquine plus primaquine for P. vivax malaria in Thailand FY2018–FY2020. Data are Kaplan–Meier estimates for patients who had P. vivax monoinfection, received at least one dose of both chloroquine and primaquine, and attended at least one follow-up visit. Recurrences occurring on or before day 28 were considered chloroquine treatment failures. Recurrences occurring after day 28 until day 90 were assumed to be primaquine treatment failures as a conservative analysis but could be caused by re-infection