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Co-infection of the four major Plasmodium species: effects on densities and gametocyte carriage

Holzschuh, A. and Gruenberg, M. and Hofmann, N. E. and Wampfler, R. and Kiniboro, B. and Robinson, L. J. and Mueller, I. and Felger, I. and White, M. T.. (2022) Co-infection of the four major Plasmodium species: effects on densities and gametocyte carriage. PLoS Negl Trop Dis, 16 (9). e0010760.

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Abstract

BACKGROUND: Co-infection of the four major species of human malaria parasite Plasmodium falciparum (Pf), P. vivax (Pv), P. malariae (Pm), and P. ovale sp. (Po) is regularly observed, but there is limited understanding of between-species interactions. In particular, little is known about the effects of multiple Plasmodium species co-infections on gametocyte production. METHODS: We developed molecular assays for detecting asexual and gametocyte stages of Pf, Pv, Pm, and Po. This is the first description of molecular diagnostics for Pm and Po gametocytes. These assays were implemented in a unique epidemiological setting in Papua New Guinea with sympatric transmission of all four Plasmodium species permitting a comprehensive investigation of species interactions. FINDINGS: The observed frequency of Pf-Pv co-infection for asexual parasites (14.7%) was higher than expected from individual prevalence rates (23.8%Pf x 47.4%Pv = 11.3%). The observed frequency of co-infection with Pf and Pv gametocytes (4.6%) was higher than expected from individual prevalence rates (13.1%Pf x 28.2%Pv = 3.7%). The excess risk of co-infection was 1.38 (95% confidence interval (CI): 1.09, 1.67) for all parasites and 1.37 (95% CI: 0.95, 1.79) for gametocytes. This excess co-infection risk was partially attributable to malaria infections clustering in some villages. Pf-Pv-Pm triple infections were four times more frequent than expected by chance alone, which could not be fully explained by infections clustering in highly exposed individuals. The effect of co-infection on parasite density was analyzed by systematic comparison of all pairwise interactions. This revealed a significant 6.57-fold increase of Pm density when co-infected with Pf. Pm gametocytemia also increased with Pf co-infection. CONCLUSIONS: Heterogeneity in exposure to mosquitoes is a key epidemiological driver of Plasmodium co-infection. Among the four co-circulating parasites, Pm benefitted most from co-infection with other species. Beyond this, no general prevailing pattern of suppression or facilitation was identified in pairwise analysis of gametocytemia and parasitemia of the four species. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov, Trial ID: NCT02143934.
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 > Intervention 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:Holzschuh, Aurel and Gr├╝nberg, Maria and Hofmann, Natalie and Wampfler, Rahel and Felger, Ingrid
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:1935-2735 (Electronic)1935-2727 (Linking)
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:27 Dec 2022 10:12
Deposited On:27 Dec 2022 10:12

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