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

Gruenberg, M; Moniz, CA; Hofmann, NE; Koepfli, C; Robinson, LJ; Nate, E; Monteiro, WM; de Melo, GC; Kuehn, A; Siqueira, AM; Nguitragool, W; Bassat, Q; Lacerda, M; Sattabongkot, J; Mueller, I; Felger, I

Author(s): Gruenberg, M; Moniz, CA; Hofmann, NE; Koepfli, C; Robinson, LJ; Nate, E; Monteiro, WM; de Melo, GC; Kuehn, A; Siqueira, AM; Nguitragool, W; Bassat, Q; Lacerda, M; Sattabongkot, J; Mueller, I; Felger, I;
Details: Publication Year 2020-09-03,Volume 19,Issue #1,Page 319
Journal Title: Malaria Jourbnal
Publication Type: Journal Article
Abstract: 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.
Publisher: BMC
Research Division(s): Population Health And Immunity
PubMed ID: 32883308
Publisher's Version: https://doi.org/10.1186/s12936-020-03374-7
Open Access at Publisher's Site: https://doi.org/10.1186/s12936-020-03374-7
Terms of Use/Rights Notice: Refer to copyright notice on published article.
Documents: Gruenberg et al_Malaria J 2020.pdf - (1.35MB, application/pdf)

Creation Date: 2020-10-02 09:53:40

Last Modified: 2020-10-02 10:24:38