Sustaining progress towards malaria elimination by 2025: Lessons from Bhutan & Timor-Leste.

In Asia Pacific, several nations that were part of the World Health Organization's initiative to eliminate malaria by 2020 or the E2020 Initiative reported being off-track. The COVID-19 pandemic further strained health systems and has the potential to stall the efforts and reverse earlier progress made towards the fight against malaria. These nations have since recommitted to eliminating malaria by 2025, in a renewed E2025 Initiative. This viewpoint presents efforts of the national malaria programs in Bhutan and Timor-Leste as they prepare for this new commitment. It includes insights on the approaches adapted by both countries that have helped them keep the spotlight on malaria whilst preventing large COVID-19 outbreaks. This viewpoint proposes key strategies that near-elimination countries can consider to sustain malaria interventions and realize their elimination goal. Of note, it calls for national strategic plans to consider a whole-of-government approach to ensure progress - which includes sustaining political commitment, systematically collaborating across borders, empowering communities and strengthening health systems particularly through surveillance and data management - that will benefit all existing and future infectious threats and pave the way for integrated response mechanisms across diseases.

A checklist of the Anopheles mosquito species (Diptera: Culicidae) in Bhutan.

The present paper records, for the first time, the Anopheles fauna of Bhutan, determined from surveys conducted from 2007 to early 2018. Adult mosquitoes were collected mainly on cattle bait and occasionally in human landing catches. Collections of immature stages were performed in various aquatic habitats. Larvae were preserved or reared to adults. Identification was based on morphological characters using available keys. A total of 30 species were identified, including nine species of subgenus Anopheles and 21 species of subgenus Cellia. Distribution and collection data are provided with notes on the locations and habitats of the species. Anopheles pseudowillmori is suspected to be a vector of malarial parasites in the plains and hilly forested areas of the country because it is widely distributed and the most common species collected in human landing catches. Notes also include observed morphological variation observed in An. baileyi and An. lindesayi, which differ from the type forms. Corrections are made for previous reports of Anopheles in Bhutan. The need for further surveys and molecular identification of members of species complexes and morphological variants is emphasized.

Challenges for achieving safe and effective radical cure of Plasmodium vivax: a round table discussion of the APMEN Vivax Working Group.

The delivery of safe and effective radical cure for Plasmodium vivax is one of the greatest challenges for achieving malaria elimination from the Asia-Pacific by 2030. During the annual meeting of the Asia Pacific Malaria Elimination Network Vivax Working Group in October 2016, a round table discussion was held to discuss the programmatic issues hindering the widespread use of primaquine (PQ) radical cure. Participants included 73 representatives from 16 partner countries and 33 institutional partners and other research institutes. In this meeting report, the key discussion points are presented and grouped into five themes: (i) current barriers for glucose-6-phosphate deficiency (G6PD) testing prior to PQ radical cure, (ii) necessary properties of G6PD tests for wide scale deployment, (iii) the promotion of G6PD testing, (iv) improving adherence to PQ regimens and (v) the challenges for future tafenoquine (TQ) roll out. Robust point of care (PoC) G6PD tests are needed, which are suitable and cost-effective for clinical settings with limited infrastructure. An affordable and competitive test price is needed, accompanied by sustainable funding for the product with appropriate training of healthcare staff, and robust quality control and assurance processes. In the absence of quantitative PoC G6PD tests, G6PD status can be gauged with qualitative diagnostics, however none of the available tests is currently sensitive enough to guide TQ treatment. TQ introduction will require overcoming additional challenges including the management of severely and intermediately G6PD deficient individuals. Robust strategies are needed to ensure that effective treatment practices can be deployed widely, and these should ensure that the caveats are outweighed by  the benefits of radical cure for both the patients and the community. Widespread access to quality controlled G6PD testing will be critical.

Culex (Culiciomyia) sasai (Diptera: Culicidae), senior synonym of Cx. spiculothorax and a new country record for Bhutan.

Culex (Culiciomyia) spiculothorax was described from Thailand based on the presence of spiculation on the thorax of larvae. Adult females are characterized but are indistinguishable from those of related species, such as Cx. pallidothorax. Phylogenetic analysis of mitochondrial oxidase subunit I (COI) sequences revealed that specimens identified as Cx. spiculothorax from Thailand, Japan and Bhutan form a single clade with Cx. sasai from Japan (Kimura 2-parameter genetic distances 0-0.9%) that is clearly distinct from clades comprised of other species of subgenus Culiciomyia. Attempts to collect Cx. sasai from several locations in Japan were unsuccessful - only larvae with thoracic vesicular-like spicules identified as Cx. spiculothorax were collected. Careful examination of specimens collected near the type locality of Cx. sasai revealed the presence of spicules on the thorax. Based on these findings, Cx. spiculothorax is formally synonymized with Cx. sasai, which replaces the former as the species present in Thailand and is a new country record for Bhutan.

Where chloroquine still works: the genetic make-up and susceptibility of Plasmodium vivax to chloroquine plus primaquine in Bhutan.

BACKGROUND: Bhutan has made substantial progress in reducing malaria incidence. The national guidelines recommend chloroquine (CQ) and primaquine (PQ) for radical cure of uncomplicated Plasmodium vivax, but the local efficacy has not been assessed. The impact of cases imported from India on the genetic make-up of the local vivax populations is currently unknown. METHODS: Patients over 4 years of age with uncomplicated P. vivax mono-infection were enrolled into a clinical efficacy study and molecular survey. Study participants received a standard dose of CQ (25 mg/kg over 3 days) followed by weekly review until day 28. On day 28 a 14-day regimen of PQ (0.25 mg/kg/day) was commenced under direct observation. After day 42, patients were followed up monthly for a year. The primary and secondary endpoints were risk of treatment failure at day 28 and at 1 year. Parasite genotyping was undertaken at nine tandem repeat markers, and standard population genetic metrics were applied to examine population diversity and structure in infections thought to be acquired inside or outside of Bhutan. RESULTS: A total of 24 patients were enrolled in the clinical study between April 2013 and October 2015. Eight patients (33.3 %) were lost to follow-up in the first 6 months and another eight patients lost between 6 and 12 months. No (0/24) treatment failures occurred by day 28 and no (0/8) parasitaemia was detected following PQ treatment. Some 95.8 % (23/24) of patients were aparasitaemic by day 2. There were no haemolytic or serious events. Genotyping was undertaken on parasites from 12 autochthonous cases and 16 suspected imported cases. Diversity was high (H E 0.87 and 0.90) in both populations. There was no notable differentiation between the autochthonous and imported populations. CONCLUSIONS: CQ and PQ remains effective for radical cure of P. vivax in Bhutan. The genetic analyses indicate that imported infections are sustaining the local vivax population, with concomitant risk of introducing drug-resistant strains.