Utility of ultra-sensitive qPCR to detect Plasmodium falciparum and Plasmodium vivax infections under different transmission intensities.

Autor: Gruenberg M; Swiss Tropical and Public Health Institute, Basel, Switzerland.; University of Basel, Basel, Switzerland., Moniz CA; Swiss Tropical and Public Health Institute, Basel, Switzerland.; University of Basel, Basel, Switzerland., Hofmann NE; Swiss Tropical and Public Health Institute, Basel, Switzerland.; University of Basel, Basel, Switzerland., Koepfli C; Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.; Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN, USA., Robinson LJ; Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea.; Burnet Institute, Melbourne, Australia., Nate E; Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea., Monteiro WM; Fundação de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD), Manaus, Brazil., de Melo GC; Fundação de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD), Manaus, Brazil., Kuehn A; Fundação de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD), Manaus, Brazil.; ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, Spain., Siqueira AM; Fundação de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD), Manaus, Brazil.; Instituto Nacional de Infectologia Evandro Chagas, Fiocruz, Rio de Janeiro, Brazil., Nguitragool W; Department of Molecular Tropical Medicine & Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand., Bassat Q; ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, Spain., Lacerda M; Fundação de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD), Manaus, Brazil.; Universidade Do Estado Do Amazonas, Manaus, Brazil., Sattabongkot J; Mahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand., Mueller I; Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.; Department of Medical Biology, University of Melbourne, Melbourne, Australia.; Malaria Parasite & Hosts Unit, Institut Pasteur, Paris, France., Felger I; Swiss Tropical and Public Health Institute, Basel, Switzerland. ingrid.felger@unibas.ch.; University of Basel, Basel, Switzerland. ingrid.felger@unibas.ch.
Jazyk: angličtina
Zdroj: Malaria journal [Malar J] 2020 Sep 03; Vol. 19 (1), pp. 319. Date of Electronic Publication: 2020 Sep 03.
DOI: 10.1186/s12936-020-03374-7
Abstrakt: Background: The use of molecular diagnostics has revealed an unexpectedly large number of asymptomatic low-density malaria infections in many malaria endemic areas. This study compared the gains in parasite prevalence obtained by the use of ultra-sensitive (us)-qPCR as compared to standard qPCR in cross-sectional surveys conducted in Thailand, Brazil and Papua New Guinea (PNG). The compared assays differed in the copy number of qPCR targets in the parasite genome.
Methods: Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) parasites were quantified by qPCR amplifying the low-copy Pf_ and Pv_18S rRNA genes or the multi-copy targets Pf_varATS and Pv_mtCOX1. Cross-sectional surveys at the three study sites included 2252 participants of all ages and represented different transmission intensities.
Results: In the two low-transmission areas, P. falciparum positivity was 1.3% (10/773) (Thailand) and 0.8% (5/651) (Brazil) using standard Pf_18S rRNA qPCR. In these two countries, P. falciparum positivity by Pf_varATS us-qPCR increased to 1.9% (15/773) and 1.7% (11/651). In PNG, an area with moderate transmission intensity, P. falciparum positivity significantly increased from 8.6% (71/828) by standard qPCR to 12.2% (101/828) by us-qPCR. The proportions of P. falciparum infections not detected by standard qPCR were 33%, 55% and 30% in Thailand, Brazil and PNG. Plasmodium vivax was the predominating species in Thailand and Brazil, with 3.9% (30/773) and 4.9% (32/651) positivity by Pv_18S rRNA qPCR. In PNG, P. vivax positivity was similar to P. falciparum, at 8.0% (66/828). Use of Pv_mtCOX1 us-qPCR led to a significant increase in positivity to 5.1% (39/773), 6.4% (42/651) and 11.5% (95/828) in Thailand, Brazil, and PNG. The proportions of P. vivax infections missed by standard qPCR were similar at all three sites, with 23%, 24% and 31% in Thailand, Brazil and PNG.
Conclusion: The proportional gains in the detection of P. falciparum and P. vivax infections by ultra-sensitive diagnostic assays were substantial at all three study sites. Thus, us-qPCR yields more precise prevalence estimates for both P. falciparum and P. vivax at all studied levels of endemicity and represents a significant diagnostic improvement. Improving sensitivity in P. vivax surveillance by us-qPCR is of particular benefit, because the additionally detected P. vivax infections signal the potential presence of hypnozoites and subsequent risk of relapse and further transmission.
Databáze: MEDLINE
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