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Molecular methods for tracking residual Plasmodium falciparum transmission in a close-to-elimination setting in Zanzibar

Grossenbacher, Benjamin and Holzschuh, Aurel and Hofmann, Natalie E. and Omar, Kali Abdullah and Stuck, Logan and Fakih, Bakar Shariff and Ali, Abdullah and Yukich, Joshua and Hetzel, Manuel W. and Felger, Ingrid. (2020) Molecular methods for tracking residual Plasmodium falciparum transmission in a close-to-elimination setting in Zanzibar. Malaria journal, 19. p. 50.

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Abstract

Molecular detection of low-density Plasmodium falciparum infections is essential for surveillance studies conducted to inform malaria control strategies in close-to-elimination settings. Molecular monitoring of residual malaria infections usually requires a large study size, therefore sampling and diagnostic processes need to be economical and optimized for high-throughput. A method comparison was undertaken to identify the most efficient diagnostic procedure for processing large collections of community samples with optimal test sensitivity, simplicity, and minimal costs.; In a reactive case detection study conducted on Zanzibar, parasitaemia of 4590 individuals of all ages was investigated by a highly sensitive quantitative (q) PCR that targets multiple var gene copies per parasite genome. To reduce cost, a first round of positivity screening was performed on pools of dried blood spots from five individuals. Ten cycles of a pre-PCR were performed directly on the filter paper punches, followed by qPCR. In a second round, samples of positive pools were individually analysed by pre-PCR and qPCR.; Prevalence in household members and neighbors of index cases was 1.7% (78/4590) with a geometric mean parasite density of 58 parasites/µl blood. Using qPCR as gold standard, diagnostic sensitivity of rapid diagnostic tests (RDTs) was 37% (29/78). Infections positive by qPCR but negative by RDT had mean densities of 15 parasites/µl blood.; The approach of pre-screening reactive case detection samples in pools of five was ideal for a low prevalence setting such as in Zanzibar. Performing direct PCR on filter paper punches saves substantial time and justifies the higher cost for a polymerase suitable for amplifying DNA directly from whole blood. Molecular monitoring in community samples provided a more accurate picture of infection prevalence, as it identified a potential reservoir of infection that was largely missed by RDT. The developed qPCR-based methodology for screening large sample sets represents primarily a research tool that should inform the design of malaria elimination strategies. It may also prove beneficial for diagnostic tasks in surveillance-response activities.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Health Interventions > Effectiveness and Impact (Hetzel)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Former Units within Swiss TPH > Molecular Diagnostics (Felger)
UniBasel Contributors:Grossenbacher, Benjamin and Holzschuh, Aurel and Hofmann, Natalie and Hetzel, Manuel W. and Felger, Ingrid
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:BioMed Central
ISSN:1475-2875
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:14 May 2020 08:56
Deposited On:14 May 2020 08:56

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