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Analysis of false-negative rapid diagnostic tests for symptomatic malaria in the Democratic Republic of the Congo.

ABSTRACT: The majority of Plasmodium falciparum malaria diagnoses in Africa are made using rapid diagnostic tests (RDTs) that detect histidine-rich protein 2. Increasing reports of false-negative RDT results due to parasites with deletions of the pfhrp2 and/or pfhrp3 genes (pfhrp2/3) raise concern about existing malaria diagnostic strategies. We previously identified pfhrp2-negative parasites among asymptomatic children in the Democratic Republic of the Congo (DRC), but their impact on diagnosis of symptomatic malaria is unknown. We performed a cross-sectional study of false-negative RDTs in symptomatic subjects in 2017. Parasites were characterized by microscopy; RDT; pfhrp2/3 genotyping and species-specific PCR assays; a bead-based immunoassay for Plasmodium antigens; and/or whole-genome sequencing. Among 3627 symptomatic subjects, 427 (11.8%) had RDT-/microscopy + results. Parasites from eight (0.2%) samples were initially classified as putative pfhrp2/3 deletions by PCR, but antigen testing and whole-genome sequencing confirmed the presence of intact genes. 56.8% of subjects had PCR-confirmed malaria. Non-falciparum co-infection with P. falciparum was common (13.2%). Agreement between PCR and HRP2-based RDTs was satisfactory (Cohen's kappa = 0.66) and superior to microscopy (0.33). Symptomatic malaria due to pfhrp2/3-deleted P. falciparum was not observed. Ongoing HRP2-based RDT use is appropriate for the detection of falciparum malaria in the DRC.

SUBMITTER: Parr JB

PROVIDER: S-EPMC7985209 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Analysis of false-negative rapid diagnostic tests for symptomatic malaria in the Democratic Republic of the Congo.

Parr Jonathan B JB Kieto Eddy E Phanzu Fernandine F Mansiangi Paul P Mwandagalirwa Kashamuka K Mvuama Nono N Landela Ange A Atibu Joseph J Efundu Solange Umesumbu SU Olenga Jean W JW Thwai Kyaw Lay KL Morgan Camille E CE Denton Madeline M Poffley Alison A Juliano Jonathan J JJ Mungala Pomie P Likwela Joris L JL Sompwe Eric M EM Rogier Eric E Tshefu Antoinette K AK N'Siala Adrien A Kalonji Albert A

Scientific reports 20210322 1

The majority of Plasmodium falciparum malaria diagnoses in Africa are made using rapid diagnostic tests (RDTs) that detect histidine-rich protein 2. Increasing reports of false-negative RDT results due to parasites with deletions of the pfhrp2 and/or pfhrp3 genes (pfhrp2/3) raise concern about existing malaria diagnostic strategies. We previously identified pfhrp2-negative parasites among asymptomatic children in the Democratic Republic of the Congo (DRC), but their impact on diagnosis of sympto ...[more]

PMID: 33753817

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Project description:BackgroundLow peripheral parasitaemia caused by sequestration of Plasmodium falciparum in the placenta hampers the diagnosis of malaria in pregnant women, leading to microscopy or conventional rapid diagnostic tests (RDTs) false-negative results. Although mainly asymptomatic, maternal malaria remains harmful to pregnant women and their offspring in endemic settings and must be adequately diagnosed. Ultra-sensitive RDTs (uRDTs) are thought to be more sensitive than RDTs, and their diagnostic performance was assessed in the current study in pregnant women living in Kinshasa, a stable malaria transmission area in the Democratic Republic of the Congo.MethodsTo assess and compare the diagnostic performances of both RDTs and uRDTs, 497 peripheral blood samples were tested using microscopy and quantitative polymerase chain reaction (qPCR) as the index and the reference tests, respectively. The agreement between the different diagnostic tests assessed was estimated by Cohen's Kappa test.ResultsThe median parasite density by qPCR was 292 p/μL of blood [IQR (49.7-1137)]. Using qPCR as the reference diagnostic test, the sensitivities of microscopy, RDT and uRDT were respectively [55.7% (95% CI 47.6-63.6)], [81.7% (95%CI 74.7-87.3)] and [88% (95% CI 81.9-92.6)]. The specificities of the tests were calculated at 98.5% (95% CI 96.6-99.5), 95.2% (95% CI 92.5-97.2) and 94.4% (95% CI 91.4-96.6) for microscopy, RDT and uRDT, respectively. The agreement between qPCR and uRDT was almost perfect (Kappa = 0.82). For parasite density (qPCR) below 100 p/µL, the sensitivity of RDT was 62% (95% CI 47.1-75.3) compared to 68% (95% CI 53.3-80.4) for uRDT. Between 100 and 200 p/µL, the sensitivity of RDT was higher, but still lower compared to uRDT: 89.4% (95% CI 66.8-98.7) for RDT versus 100% (95% CI 82.3-100) for uRDT. In both cases, microscopy was lower, with 20% (95% CI 10-33.7) and 47.3% (95% CI 24.4-71.1) respectively.ConclusionsuRDT has the potential to improve malaria management in pregnant women as it has been found to be slightly more sensitive than RDT in the detection of malaria in pregnant women but the difference was not significant. Microscopy has a more limited value for the diagnosis of malaria during the pregnancy, because of its lower sensitivity.

Project description:BackgroundEbola virus disease (EVD) outbreaks have emerged in Central and West Africa. EVD diagnosis relies principally on RT-PCR testing with GeneXpert®, which has logistical and cost restrictions at the peripheral level of the health system. Rapid diagnostic tests (RDTs) would offer a valuable alternative at the point-of-care to reduce the turn-around time, if they show good performance characteristics. We evaluated the performance of four EVD RDTs against the reference standard GeneXpert® on stored EVD positive and negative blood samples collected between 2018 and 2021 from outbreaks in eastern Democratic Republic of the Congo (DRC).MethodsWe conducted a prospective and observational study in the laboratory on QuickNavi-Ebola™, OraQuick® Ebola Rapid Antigen, Coris® EBOLA Ag K-SeT, and Standard® Q Ebola Zaïre Ag RDTs using left-over archived frozen EDTA whole blood samples. We randomly selected 450 positive and 450 negative samples from the EVD biorepositories in DRC, across a range of GeneXpert® cycle threshold values (Ct-values). RDT results were read by three persons and we considered an RDT result as "positive", when it was flagged as positive by at least two out of the three readers. We estimated the sensitivity and specificity through two independent generalized (logistic) linear mixed models (GLMM).Findings476 (53%) of 900 samples had a positive GeneXpert Ebola result when retested. The QuickNavi-Ebola™ showed a sensitivity of 56.8% (95% CI 53.6-60.0) and a specificity of 97.5% (95% CI 96.2-98.4), the OraQuick® Ebola Rapid Antigen test displayed 61.6% (95% CI 57.0-65.9) sensitivity and 98.1% (95% CI 96.2-99.1) specificity, the Coris® EBOLA Ag K-SeT showed 25.0% (95% CI 22.3-27.9) sensitivity and 95.9% (95% CI 94.2-97.1) specificity, and the Standard® Q Ebola Zaïre Ag displayed 21.6% (95% CI 18.1-25.7) sensitivity and 99.1% (95% CI 97.4-99.7) specificity.InterpretationNone of the RDTs evaluated approached the "desired or acceptable levels" for sensitivity set out in the WHO target product profile, while all of the tests met the "desired level" for specificity. Nevertheless, the QuickNavi-Ebola™ and OraQuick® Ebola Rapid Antigen Test demonstrated the most favorable profiles, and may be used as frontline tests for triage of suspected-cases while waiting for RT-qPCR confirmatory testing.FundingInstitute of Tropical Medicine Antwerp/EDCTP PEAU-EBOV-RDC project.

Project description:IntroductionIn 2018, Malaria accounted for 38% of the overall morbidity and 36% of the overall mortality in the Democratic Republic of Congo (DRC). This study aimed to identify malaria socioeconomic predictors among children aged 6-59 months in DRC and to describe a socioeconomic profile of the most-at-risk children aged 6-59 months for malaria infection.Materials and methodsThis study used data from the 2013 DRC Demographic and Health Survey. The sample included 8,547 children aged 6-59 months who were tested for malaria by microscopy. Malaria infection status, the dependent variable, is a dummy variable characterized as a positive or negative test. The independent variables were child's sex, age, and living arrangement; mother's education; household's socioeconomic variables; province of residence; and type of place of residence. Statistical analyses used the chi-square automatic interaction detector (CHAID) model and logistic regression.ResultsOf the 8,547 children included in the sample, 25% had malaria infection. Four variables-child's age, mother's education, province, and wealth index-were statistically associated with the prevalence of malaria infection in bivariate analysis and multivariate analysis (CHAID and logistic regression). The prevalence of malaria infection increases with child's age and decreases significantly with mother's education and the household wealth index. These findings suggest that the prevalence of malaria infection is driven by interactions among environmental factors, socioeconomic characteristics, and probably differences in the implementation of malaria programs across the country. The effect of mother's education on malaria infection was only significant among under-five children living in Ituri, Kasaï-Central, Haut-Uele, Lomami, Nord-Ubangi, and Maniema provinces, and the effect of wealth index was significant in Mai-Ndombe, Tshopo, and Haut-Katanga provinces.ConclusionFindings from this study could be used for targeting malaria interventions in DRC. Although malaria infection is common across the country, the prevalence of children at high risk for malaria infection varies by province and other background characteristics, including age, mother's education, wealth index, and place of residence. In light of these findings, designing provincial and multisectoral interventions could be an effective strategy to achieve zero malaria infection in DRC.

Dataset Information

Analysis of false-negative rapid diagnostic tests for symptomatic malaria in the Democratic Republic of the Congo.

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Analysis of false-negative rapid diagnostic tests for symptomatic malaria in the Democratic Republic of the Congo.

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