qRT-PCR versus IFA-based Quantification of Male and Female Gametocytes in Low-Density Plasmodium falciparum Infections and Their Relevance for Transmission.

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  • Additional Information
    • Source:
      Publisher: Oxford University Press Country of Publication: United States NLM ID: 0413675 Publication Model: Print Cited Medium: Internet ISSN: 1537-6613 (Electronic) Linking ISSN: 00221899 NLM ISO Abbreviation: J Infect Dis Subsets: MEDLINE
    • Publication Information:
      Publication: Jan. 2011- : Oxford : Oxford University Press
      Original Publication: 1904-2010 : Chicago, IL : University of Chicago Press
    • Subject Terms:
      Fluorescent Antibody Technique, Indirect/*methods ; Malaria, Falciparum/*epidemiology ; Malaria, Falciparum/*transmission ; Oocytes/*chemistry ; Plasmodium falciparum/*chemistry ; Protozoan Proteins/*genetics ; Reverse Transcriptase Polymerase Chain Reaction/*methods ; Spermatocytes/*chemistry; Biomarkers/chemistry ; Cross-Sectional Studies ; Female ; Humans ; Malaria, Falciparum/parasitology ; Male ; Papua New Guinea/epidemiology ; RNA, Protozoan/blood ; RNA, Protozoan/genetics ; Sensitivity and Specificity
    • Abstract:
      Background: 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.
      Methods: 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).
      Results: 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.
      Conclusions: 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.
      (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)
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    • Grant Information:
      U19 AI129392 United States AI NIAID NIH HHS
    • Contributed Indexing:
      Keywords: Plasmodium falciparum; low density; male gametocytes; sex ratio; transmission reservoir; ultrasensitive diagnostics
    • Accession Number:
      0 (Biomarkers)
      0 (Pfs25 protein, Plasmodium falciparum)
      0 (Protozoan Proteins)
      0 (RNA, Protozoan)
    • Publication Date:
      Date Created: 20190823 Date Completed: 20200921 Latest Revision: 20200921
    • Publication Date:
      20221213
    • Accession Number:
      PMC7325619
    • Accession Number:
      10.1093/infdis/jiz420
    • Accession Number:
      31437280