Effectiveness, Safety, and Acceptability of Primaquine Mass Drug Administration in Low-Endemicity Areas in Southern Thailand: Proof-of-Concept Study.

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 2-period cluster-crossover randomized controlled 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 in-depth interviews and brainstorming discussions. The study involved 7 clusters in 2 districts of 2 southern provinces in Thailand with persistently low P. vivax transmission. In the quantitative part, 5 cross-sectional blood surveys were conducted in both the pMDA and control groups before and 3 months after pMDA. The effectiveness of pMDA was determined by comparing the proportions of P. vivax infections per 1000 population between the 2 groups, with a multilevel zero-inflated negative binomial model adjusted for cluster and time as covariates and the interaction. The safety data comprised adverse events after drug administration. Thematic content analysis was used to assess the acceptability and engagement of stakeholders. RESULTS: In the pre-pMDA period, the proportions of P. vivax infections 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, these proportions in the pMDA (n=1430) and 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 groups. The number of malaria cases reduced in all clusters in both groups, and thus, the impact of pMDA was inconclusive. There were no major safety concerns. Acceptance among the study participants and public health care providers at local and national levels was high, and they believed that pMDA had boosted awareness in the community. CONCLUSIONS: pMDA was associated with high adherence, safety, and tolerability, but it may not significantly impact P. vivax transmission. As this was a proof-of-concept study, we decided not to scale up the intervention with larger clusters and samples. An alternative approach involving a targeted primaquine treatment strategy with primaquine and DOT is currently being implemented. We experienced success regarding effective health care workforces at point-of-care centers, effective collaborations in the community, and commitment from authorities at local and national levels. Our efforts boosted the acceptability of the malaria-elimination initiative. Community engagement is recommended to achieve elimination targets. TRIAL REGISTRATION: Thai Clinical Trials Registry TCTR20190806004; https://www.thaiclinicaltrials.org/show/TCTR20190806004.

Malaria Research for Tailored Control and Elimination Strategies in the Greater Mekong Subregion.

The malaria landscape in the Greater Mekong Subregion has experienced drastic changes with the ramp-up of the control efforts, revealing formidable challenges that slowed down the progress toward malaria elimination. Problems such as border malaria and cross-border malaria introduction, multidrug resistance in Plasmodium falciparum, the persistence of Plasmodium vivax, the asymptomatic parasite reservoirs, and insecticide resistance in primary vectors require integrated strategies tailored for individual nations in the region. In recognition of these challenges and the need for research, the Southeast Asian International Center of Excellence for Malaria Research has established a network of researchers and stakeholders and conducted basic and translational research to identify existing and emerging problems and develop new countermeasures. The installation of a comprehensive disease and vector surveillance system at sentinel sites in border areas with the implementation of passive/active case detection and cross-sectional surveys allowed timely detection and management of malaria cases, provided updated knowledge for effective vector control measures, and facilitated the efficacy studies of antimalarials. Incorporating sensitive molecular diagnosis to expose the significance of asymptomatic parasite reservoirs for sustaining transmission helped establish the necessary evidence to guide targeted control to eliminate residual transmission. In addition, this program has developed point-of-care diagnostics to monitor the quality of artemisinin combination therapies, delivering the needed information to the drug regulatory authorities to take measures against falsified and substandard antimalarials. To accelerate malaria elimination, this program has actively engaged with stakeholders of all levels, fostered vertical and horizontal collaborations, and enabled the effective dissemination of research findings.

The Potential Container Habitats of Chikungunya Vector in Outbreak Area of Southern Thailand.

Chikungunya virus (CHIKV) is primarily transmitted by Aedes mosquitoes and is responsible for reemerging disease internationally. Container habitats of immature Aedes mosquitoes are often found around residential areas, thus water-holding container investigation is an important vector control strategy. This study aimed to survey mosquito species in container inhabiting stages and water-holding containers associated with the CHIKV outbreak in urban areas within the 4 villages of Hat Yai district in Songkhla province during 2019. The results indicated that of the 75 houses surveyed, 34 had water-holding containers; 78 out of 438 containers were positive for mosquitoes; and 34 were positive for mosquito stages. The house index (HI), Breteau index (BI), container index (CI), and pupal index (PI) were 46.87, 93.75, 14.92, and 271.88 for case houses, respectively. Specific container index (SCI) showed discarded containers such as bottles, cans, and tires. The findings suggest that Aedes aegypti was predominant in the surveyed urban area and might be the vector responsible for CHIKV transmission in Songkhla province.

Chikungunya Fever in Southern Thailand, 2018.

Infection by the mosquito-borne chikungunya virus (CHIKV) causes acute febrile illness and debilitating arthralgia. Outbreaks are sometimes not recognized because of its clinical resemblance to the more common dengue fever ubiquitous in tropical countries. An upsurge of dengue-like illness was reported in Satun province located in southern Thailand during the rainy season in 2018. We investigated probable outbreak of CHIKV disease. We collected serum samples from 127 patients and tested for CHIKV infection based on nucleic acid and serological tests. CHIKV RNA amplified by real-time reverse-transcription polymerase chain reaction (RT-PCR) and IgM antibody against CHIKV were determined by immunochromatographic rapid test. Mosquitoes in the community were also trapped and tested for CHIKV. Conventional RT-PCR on initially positive samples was performed to obtain nucleotide sequences for subsequent phylogenetic analysis. In all, 39% (50/127) of the samples tested positive for CHIKV RNA, IgM, or both. Of these, CHIKV RNA was identified in 17% (21/127) of the samples. Fourteen percent (18/127) of the samples were simultaneously positive for both IgM and IgG, which suggest recent infection. One sample tested positive for both CHIKV IgM and RNA. Several samples from Aedes aegypti and Aedes albopictus mosquitoes were also CHIKV RNA-positive. Sequence analysis revealed that the Satun CHIKV belonged to the Indian Ocean lineage within the East/Central/South African (ECSA) clade with residues K211E and A226 in the E1 gene, and G205S and V264A in the E2 gene. The ECSA strain of CHIKV continues to evolve and possesses virulent potential despite causing prior outbreaks in the region.

Case Report: Case Series of Human Plasmodium knowlesi Infection on the Southern Border of Thailand.

Although human infections of Plasmodium knowlesi have been found throughout Southeast Asia, most cases originated from Malaysian Borneo. In Thailand, P. knowlesi malaria was considered extremely rare. However, during October 2017-September 2018, there was a surge in the number of reported P. knowlesi cases. Here, a series of six cases of P. knowlesi malaria found during this period in Songkhla and Narathiwat provinces of southern Thailand are presented. All cases were confirmed by polymerase chain reaction. The unprecedented case number in the affected area is a warning sign of an increasing P. knowlesi burden in the south of Thailand.