JMIR Publications

ABSTRACT

Background:

A challenge in achieving the malaria-elimination target in the Greater Mekong Subregion, including Thailand, is the predominance of Plasmodium vivax malaria, which has shown extreme resilience to control measures.

Objective:

This proof-of-concept study aimed to provide evidence for implementing primaquine mass drug administration (pMDA) as a strategy for P.vivax elimination in low-endemicity settings.

Methods:

The study employed a mixed-methods trial to thoroughly evaluate the effectiveness, safety, acceptability and community-engagement of pMDA. The quantitative part was designed as a two-period cluster-crossover randomized control trial. The intervention was pMDA augmented to the national prevention and control standards with directly observed treatment (DOT) by village health volunteers. The qualitative part employed indepth interviews and brainstorming discussion. The study was conducted in seven clusters in two districts of two southern provinces in Thailand with persistently low P.vivax transmission. In the quantitative part, five cross-sectional blood surveys were conducted for both pMDA and control groups before and 3-months after pMDA. The effectiveness of pMDA was determined by comparing proportions of P.vivax per 1000 population between the two groups with a multilevel zero-inflated negative-binomial model adjusted for cluster and time as covariate and interaction. The safety data comprised adverse events after drug administration. Thematic content analysis was used to assess the acceptability and engagement of stakeholders.

Results:

At the pre-pMDA period, the proportions of P.vivax in the pMDA (n=1536) and control (n=1577) groups were 13.0 (95%CI: 8.2-20.4) and 12.0 (95%CI: 7.5-19.1), respectively. At month-3 post-pMDA, the proportions of P.vivax of the pMDA (n=1430) and the control (n=1420) groups were 8.4 (95%CI: 4.6-15.1) and 5.6 (95%CI: 2.6-11.5), respectively. No statistically significant differences were found between the two groups. The number of malaria cases was reduced in all clusters, regardless of their being in the pMDA group or control group, and thus the impact of the pMDA was inconclusive. There were no major safety concerns. Acceptance among the study participants and public healthcare providers at local and national levels was high, and they believed that pMDA had boosted awareness in the community.

Conclusions:

pMDA showed high adherence, safety and tolerability, but may not significantly impact P.vivax transmission. As a proof-of-concept, we decided not to go with the scaleup with larger sizes of clusters and samples. An alternative approach is currently being implemented, a targeted primaquine treatment strategy, providing primaquine with DOT only to the targeted population in the households around each index case in the intervention clusters. However, we have a success story of effective healthcare workforces at the point-of-care, collaborations with community, and commitment from authorities at local and national levels. Our efforts boosted the acceptability of the malaria-elimination initiative. In striving to achieve elimination targets, community-engagement with any elimination measures is recommended. Clinical Trial: Thai Clinical Trials Registry. TCTR ID :TCTR20190806004 :