Prevalence and clinical impact of malaria infections detected with a highly sensitive HRP2 rapid diagnostic test in Beninese pregnant women

Valérie Briand, Gilles Cottrell, Nicaise Tuike Ndam, Xavier Martiáñez-Vendrell, Bertin Vianou, Atika Mama, Bienvenue Kouwaye, Sandrine Houzé, Justine Bailly, Erasme Gbaguidi, Darius Sossou, Achille Massougbodji, Manfred Accrombessi, Alfredo Mayor, Xavier C Ding, Nadine Fievet, Valérie Briand, Gilles Cottrell, Nicaise Tuike Ndam, Xavier Martiáñez-Vendrell, Bertin Vianou, Atika Mama, Bienvenue Kouwaye, Sandrine Houzé, Justine Bailly, Erasme Gbaguidi, Darius Sossou, Achille Massougbodji, Manfred Accrombessi, Alfredo Mayor, Xavier C Ding, Nadine Fievet

Abstract

Background: While sub-microscopic malarial infections are frequent and potentially deleterious during pregnancy, routine molecular detection is still not feasible. This study aimed to assess the performance of a Histidine Rich Protein 2 (HRP2)-based ultrasensitive rapid diagnostic test (uRDT, Alere Malaria Ag Pf) for the detection of infections of low parasite density in pregnant women.

Methods: This was a retrospective study based on samples collected in Benin from 2014 to 2017. A total of 942 whole blood samples collected in 327 women in the 1st and 3rd trimesters and at delivery were tested by uRDT, conventional RDT (cRDT, SD BIOLINE Malaria Ag Pf), microscopy, quantitative polymerase chain-reaction (qPCR) and Luminex-based suspension array technology targeting P. falciparum HRP2. The performance of each RDT was evaluated using qPCR as reference standard. The association between infections detected by uRDT, but not by cRDT, with poor maternal and birth outcomes was assessed using multivariate regression models.

Results: The overall positivity rate detected by cRDT, uRDT, and qPCR was 11.6% (109/942), 16.2% (153/942) and 18.3% (172/942), respectively. Out of 172 qPCR-positive samples, 68 were uRDT-negative. uRDT had a significantly better sensitivity (60.5% [52.7-67.8]) than cRDT (44.2% [36.6-51.9]) and a marginally decreased specificity (93.6% [91.7-95.3] versus 95.7% [94.0-97.0]). The gain in sensitivity was particularly high (33%) and statistically significant in the 1st trimester. Only 28 (41%) out of the 68 samples which were qPCR-positive, but uRDT-negative had detectable but very low levels of HRP2 (191 ng/mL). Infections that were detected by uRDT but not by cRDT were associated with a 3.4-times (95%CI 1.29-9.19) increased risk of anaemia during pregnancy.

Conclusions: This study demonstrates the higher performance of uRDT, as compared to cRDTs, to detect low parasite density P. falciparum infections during pregnancy, particularly in the 1st trimester. uRDT allowed the detection of infections associated with maternal anaemia.

Keywords: Africa; Diagnostic tests; HRP-2 antigen; Malaria; Pregnancy.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flow diagram of included women and available specimens tested by uRDT, cRDT, qPCR and qSA for HRP2 concentration. RECIPAL study (Benin, 2014–2017)
Fig. 2
Fig. 2
Venn diagram of Plasmodium falciparum positivity by uRDT, cRDT and qPCR. RECIPAL study (Benin, 2014–2017)
Fig. 3
Fig. 3
Distribution of specimens by parasite density (a) and HRP2 concentration (b), according to Das et al. [19]. a The outer clear bars represent the specimens that were positive by qPCR only; the gray bars are the number of specimens positive by uRDT and the black bars are the number of specimens positive by cRDT. b The outer clear bars represent the specimens that were positive by quantitative HRP2 assay, but not by RDTs; the gray bars are the number of specimens positive by uRDT and the black bars are the number of specimens positive by cRDT

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