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qRT-PCR versus IFA-based quantification of male and female gametocytes in low-density Plasmodium falciparum infections and their relevance for transmission

Gruenberg, Maria and Hofmann, Natalie E. and Nate, Elma and Karl, Stephan and Robinson, Leanne J. and Lanke, Kjerstin and Smith, Thomas A. and Bousema, Teun and Felger, Ingrid. (2020) qRT-PCR versus IFA-based quantification of male and female gametocytes in low-density Plasmodium falciparum infections and their relevance for transmission. Journal of infectious diseases, 221 (4). pp. 598-607.

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Abstract

Accurate quantification of female and male gametocytes and sex ratios in asymptomatic low-density malaria infections are important for assessing their transmission potential. Gametocytes often escape detection even by molecular methods, therefore ultralow gametocyte densities were quantified in large blood volumes.; Female and male gametocytes were quantified in 161 PCR-positive Plasmodium falciparum infections from a cross-sectional survey in Papua New Guinea. Ten-fold concentrated RNA from 800 µL blood was analyzed using female-specific pfs25 and male-specific pfmget or mssp qRT-PCR. Gametocyte sex ratios from qRT-PCR were compared with those from immunofluorescence assays (IFA).; Gametocytes were identified in 58% (93/161) P. falciparum-positive individuals. Mean gametocyte densities were frequently below 1 female and 1 male gametocyte/µL by qRT-PCR. The mean proportion of males was 0.39 (95% confidence interval, 0.33-0.44) by pfs25/pfmget qRT-PCR; this correlated well with IFA results (Pearsons r2 = 0.91; P < .001). A Poisson model fitted to our data predicted 16% P. falciparum-positive individuals that are likely to transmit, assuming at least 1 female and 1 male gametocyte per 2.5 µL mosquito bloodmeal.; Based on model estimates of female and male gametocytes per 2.5 µL blood, P. falciparum-positive individuals detected exclusively by ultrasensitive diagnostics are negligible for human-to-mosquito transmission.Estimating the transmission potential of ultralow-density malaria infections informs interventions. Almost all infections with ≥1 female and male gametocyte per 2.5 µL mosquito bloodmeal, and thus with highest likelihood of contributing to human-to-mosquito transmission, were detectable by standard molecular diagnostics.
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) > Infectious Disease Modelling > Epidemiology and Transmission Dynamics (Smith)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Former Units within Swiss TPH > Molecular Diagnostics (Felger)
UniBasel Contributors:Grünberg, Maria and Hofmann, Natalie and Smith, Thomas A. and Felger, Ingrid
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Oxford University Press
ISSN:0022-1899
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:05 Mar 2020 11:56
Deposited On:05 Mar 2020 11:56

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