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Utility and costs of reactive case detection using molecular detection and genotyping in Thailand, a near-elimination setting with predominantly Plasmodium vivax transmission
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. University of California San Francisco.ORCID iD: 0000-0001-5769-1867
(English)Manuscript (preprint) (Other academic)
Abstract [en]

In Thailand, progress toward malaria elimination has slowed, largely due to the challenge of residual Plasmodium vivax transmission. Screening and testing for malaria in the vicinity of recent passively-identified index cases, also called reactive case detection (RACD), is commonly used in near-elimination settings, but standard diagnostics such as microscopy miss low-level infections. We assessed the utility, costs, and cost-effectiveness of RACD using loop-mediated isothermal amplification (LAMP) versus standard RACD using microscopy to detect infections in RACD. We also assessed the utility of microsatellite genotyping to determine relatedness of index and RACD-identified infections. Each of 27 microscopy-positive index cases reported through passive surveillance (20 Plasmodium vivax, 5 P. falciparum, and 2 mixed P. falciparum/ P. vivax infections) triggered RACD, whereby 1,973 index case household members or surrounding neighbors received malaria testing. Of these, no infections were detected in RACD by microscopy, but 12 (0.6%) confirmed or probable infections were detected in RACD by molecular testing using LAMP, out of which four infections were confirmed by PCR. Among these four, one (25%) was genetically related to the index case suggesting low levels of local transmission. The average cost per individual screened for RACD using microscopy and RACD using LAMP was $15 and $22, respectively, and the incremental cost effectiveness ratio to detect infections was $1,191 per additional infection detected. In this near elimination setting, RACD using molecular detection and genotyping can make RACD a more effective strategy by identifying additional infections and transmission foci to facilitate a better understanding regarding local patterns of transmission.

Keywords [en]
malaria, surveillance, genetic surveillance, reactive case detection, LAMP, Plasmodium vivax, cost, cost-effectiveness
National Category
Public Health, Global Health and Social Medicine
Research subject
Infectious Diseases
Identifiers
URN: urn:nbn:se:uu:diva-499491OAI: oai:DiVA.org:uu-499491DiVA, id: diva2:1747722
Available from: 2023-03-30 Created: 2023-03-30 Last updated: 2025-02-20
In thesis
1. Evaluating and optimizing surveillance and response strategies for malaria elimination in the Asia Pacific region
Open this publication in new window or tab >>Evaluating and optimizing surveillance and response strategies for malaria elimination in the Asia Pacific region
2023 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Malaria case investigation and reactive case detection (RACD) activities are widely implemented in low transmission settings to identify additional malaria infections and gather surveillance information, but with varying degrees of success. Challenges in conducting RACD include poor diagnostic sensitivity (particularly for low density and asymptomatic infections), knowledge gaps among those conducting RACD, financial and resource constraints, and operational and logistical difficulties. To improve infection detection and better target individuals at highest risk for infection, RACD strategies need to be evaluated and optimized to provide quality and nuanced surveillance information.

To support more effective surveillance and response strategies, this PhD project focused on evaluating RACD strategies to improve and optimize malaria surveillance in low transmission settings in the Asia Pacific region. Using a standardized monitoring and evaluation (M&E) tool, case investigation and RACD indicators were assessed, including the knowledge and practices of the staff conducting RACD. This PhD project explored the utility of molecular diagnostics and genotyping and targeted sociobehavorial RACD strategies for increasing infection detection and to understand the relatedness of infections identified during RACD. Also, the acceptability and feasibility of a presumptive treatment-based strategy to reduce malaria (referred to as reactive drug administration (RDA)) was evaluated.

Results revealed gaps in case investigation and RACD reporting completeness and timeliness and that staff were not always equipped with the appropriate documentation or have accurate knowledge on how to conduct RACD. Molecular diagnostics used in RACD in Thailand identified an additional 12 (0.6%) infections compared to no RACD-identified infections detected by microscopy. Of the four confirmed infections, only one (25%) was genetically related to the index case. In Indonesia, a sociobehavorial RACD strategy targeting high risk populations and work venues was able to identify 180 individuals for RACD yielding 8 infections compared to only one infection during household-based RACD. Shared risk factors between sociobehavorial RACD individuals and index patients include being male, 30-45 years of age, and occupation of logging or mining. In Thailand, an RDA strategy targeting within and around the household and forest-going co-workers was found to be acceptable by those that participated and feasible to be implemented by the malaria staff.

The quality of malaria case investigation and RACD activities and the knowledge of those implementing it can be improved using a standardized M&E tool. The molecular and genotyping findings may be useful for malaria programs in low transmission settings to increase infection detection in persistent malaria foci or among high-risk populations and to characterize local transmission patterns. When the highest risk individuals for malaria can be identified, a strategy like RDA may be useful to target and eliminate malaria to accelerate elimination efforts.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2023. p. 103
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1935
Keywords
malaria elimination, surveillance and response, reactive case detection, sociobehavorial, reactive drug administration, molecular diagnostics, microsatellite genotyping, Plasmodium vivax, low transmission
National Category
Public Health, Global Health and Social Medicine
Identifiers
urn:nbn:se:uu:diva-499580 (URN)978-91-513-1781-6 (ISBN)
Public defence
2023-05-24, Sal IX, University Building, Uppsala, 13:15 (English)
Opponent
Supervisors
Available from: 2023-05-02 Created: 2023-04-01 Last updated: 2025-02-20

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