Bionomics of malaria vectors in Lao PDR, 2018-2020: entomological surveillance as a key tool for malaria elimination.

BACKGROUND: The Lao PDR National Strategic Plan for malaria control and elimination for year 2021-2025 emphasizes the importance of routine entomological surveillance being conducted in areas with high transmission and in active malaria foci in elimination targeted areas. The collection of entomological surveillance data that is closely linked to recent epidemiological data is crucial for improving impact, as it contributes to the evidence package that supports operational and strategic decision-making of national malaria programmes, as they accelerate their last mile of elimination. METHODS: The Center for Malariology Parasitology and Epidemiology (CMPE) entomology team conducted entomological surveillance activities at 13 sentinel sites in 8 provinces and at active transmission foci sites from 2018 to 2020. The techniques used for the mosquito collection were indoor and outdoor human landing collections (from houses and from cultivation areas) and cattle baited net trap collections. RESULTS: There were 5601 Anopheles mosquito females captured and identified throughout the study, on both human and cow bait. They represented 15 different species or species complexes. The primary malaria vectors as well as the secondary vectors were present in all collection sites in the south, indicating that people living in these rural areas with high malaria incidence are exposed to the vectors. The vectors were highly zoophilic, but they still bite humans throughout the night with a high peak of activity before midnight, both indoors and outdoors. Overall, 17% of the malaria vectors were collected indoors when the people are sleeping. This confirms the importance of bed net use during the night. Thirty-two percent of primary and secondary vectors were collected outdoors at times when people are usually awake and outdoors, which shows that people are exposed to potentially infectious mosquitoes and the importance of personal protection at these times. The findings showed that residual transmission may occur outdoors in the villages, and outside the villages in cultivation fields and forested areas. Epidemiological data showed that transmission was higher in surveillance sites which were targeted as part of a malaria response rather than sentinel sites. CONCLUSIONS: Understanding where and how transmission is persisting, monitoring and mapping vector species distribution in areas with active transmission, monitoring biting trends, and designing evidence based and effective vector control interventions are critical to accelerating progress toward malaria elimination. In this context, the role of entomological surveillance combined with epidemiological data should be considered as a cornerstone in achieving malaria elimination.

Malaria outbreak in Laos driven by a selective sweep for Plasmodium falciparum kelch13 R539T mutants: a genetic epidemiology analysis.

BACKGROUND: Malaria outbreaks are important public health concerns that can cause resurgence in endemic regions approaching elimination. We investigated a Plasmodium falciparum outbreak in Attapeu Province, Laos, during the 2020-21 malaria season, using genomic epidemiology methods to elucidate parasite population dynamics and identify its causes. METHODS: In this genetic analysis, 2164 P falciparum dried blood spot samples were collected from southern Laos between Jan 1, 2017, and April 1, 2021, which included 249 collected during the Attapeu outbreak between April 1, 2020, and April 1, 2021, by routine surveillance. Genetic barcodes obtained from these samples were used to investigate epidemiological changes underpinning the outbreak, estimate population diversity, and analyse population structure. Whole-genome sequencing data from additional historical samples were used to reconstruct the ancestry of outbreak strains using identity-by-descent analyses. FINDINGS: The outbreak parasite populations were characterised by unprecedented loss of genetic diversity, primarily caused by rapid clonal expansion of a multidrug-resistant strain (LAA1) carrying the kelch13 Arg539Thr (R539T) mutation. LAA1 replaced kelch13 Cys580Tyr (C580Y) mutants resistant to dihydroartemisinin-piperaquine (KEL1/PLA1) as the dominant strain. LAA1 inherited 58·8% of its genome from a strain circulating in Cambodia in 2008. A secondary outbreak strain (LAA2) carried the kelch13 C580Y allele, and a genome that is essentially identical to a Cambodian parasite from 2009. A third, low-frequency strain (LAA7) was a recombinant of KEL1/PLA1 with a kelch13 R539T mutant. INTERPRETATION: These results strongly suggest that the outbreak was driven by a selective sweep, possibly associated with multidrug-resistant phenotypes of the outbreak strains. Established resistant populations can circulate at low frequencies for years before suddenly overwhelming dominant strains when the conditions for selection become favourable-eg, when front-line therapies change. Genetic surveillance can support elimination by characterising key properties of outbreaks such as population diversity, drug resistance marker prevalence, and the origins of outbreak strains. FUNDING: Bill & Melinda Gates Foundation; The Global Fund to Fight AIDS, Tuberculosis and Malaria; Wellcome Trust. TRANSLATION: For the Lao translation of the abstract see Supplementary Materials section.

Evaluating Vertical Malaria Community Health Worker Programs as Malaria Declines: Learning From Program Evaluations in Honduras and Lao PDR.

BACKGROUND: Across the Greater Mekong Subregion (GMS) and Central America, governments commonly employ community health workers (CHWs) to improve access to and uptake of malaria services. Many of these networks are vertical in design, organized to extend malaria-only services to those remaining communities in which malaria persists. METHODS: Between 2019 and 2020, national ministries of health (MOH) and Clinton Health Access Initiative conducted mixed-methods CHW program evaluations across the GMS and Central America. Routine surveillance and programmatic data were analyzed to quantify CHW contributions to malaria elimination objectives and identify gaps and challenges. Semistructured interviews were conducted with governmental and nongovernmental stakeholders from central to community level. This article draws comparisons between the Lao People's Democratic Republic (PDR) and Honduras CHW program evaluation results to distill broader hypotheses about how vertical CHW programs might evolve as their primary mission nears its end. RESULTS: CHWs contribute substantially to malaria case detection and surveillance, diagnosing and treating 27% of malaria cases in Lao PDR and 55% in the department of Gracias a Dios, Honduras in 2019. In the same year, malaria test positivity neared less than 1% in both countries. In 2019, 80% of CHWs in Lao PDR and 74% in Gracias a Dios, Honduras did not report a single malaria case. From inception, both programs were organized as vertical (malaria-only) CHW programs reliant upon Global Fund financing for malaria commodities, training, supervision and, where applicable, remuneration. CONCLUSIONS: Although community case management by CHWs has been highly impactful in reducing malaria cases to near zero, new challenges of acceptability and effectiveness of malaria-only service delivery, feasibility of continued vertical program management, and sustainable financing have emerged. To achieve and sustain reductions in malaria, surveillance and delivery platforms must be redesigned to encourage (and reward) care seeking based on experience of symptoms and not on a patient or caregiver's presumptive diagnosis of disease. By expanding the roles and responsibilities of currently vertical malaria CHWs, malarial interventions can be optimized and sustained. Such a shift will also position existing community-based platforms to be resilient and responsive as epidemiology of disease and community need shift.