Field performance of ultrasensitive and conventional malaria rapid diagnostic tests in southern Mozambique

Beatriz Galatas,Quique Bassat,Wilson Simone,Lidia Nhamussua,Ihn Kyung Jang,Himanshu Gupta,Pau Cisteró,Humberto Munguambe,Arlindo Chidimatembue,Alfredo Mayor,Núria Balanza,Francisco Saúte,Pedro Aide

doi:10.1186/s12936-020-03526-9

Abstract

BackgroundAn ultrasensitive malaria rapid diagnostic test (RDT) was recently developed for the improved detection of low-density Plasmodium falciparum infections. This study aimed to compare the diagnostic performance of the PfHRP2-based Abbott Malaria Ag P. falciparum ultrasensitive RDT (uRDT) to that of the conventional SD-Bioline Malaria Ag P. falciparum RDT (cRDT) when performed under field conditions.MethodsFinger-prick blood samples were collected from adults and children in two cross-sectional surveys in May of 2017 in southern Mozambique. Using real-time quantitative PCR (RT-qPCR) as the reference method, the age-specific diagnostic performance indicators of the cRDT and uRDT were compared. The presence of histidine-rich protein 2 (HRP2) and Plasmodium lactate dehydrogenase (pLDH) antigens was evaluated in a subset from dried blood spots by a quantitative antigen assay. pfhrp2 and pfhrp3 gene deletions were assessed in samples positive by RT-qPCR and negative by both RDTs.ResultsAmong the 4,396 participants with complete test results, the sensitivity of uRDTs (68.2; 95% CI 60.8 to 74.9) was marginally better than that of cRDTs (61.5; 95% CI 53.9 to 68.6) (p-value = 0.004), while the specificities were similar (uRDT: 99.0 [95% CI 98.6 to 99.2], cRDT: 99.2 [95% CI 98.9 to 99.4], p-value = 0.02). While the performance of both RDTs was lowest in ≥ 15-year-olds, driven by the higher prevalence of low parasite density infections in this group, the sensitivity of uRDTs was significantly higher in this age group (54.9, 95% CI 40.3 to 68.9) compared to the sensitivity of cRDTs (39.2, 95% CI 25.8 to 53.9) (p-value = 0.008). Both RDTs detected P. falciparum infections at similar geometric mean parasite densities (112.9 parasites/μL for uRDTs and 145.5 parasites/μL for cRDTs). The presence of HRP2 antigen was similar among false positive (FP) samples of both tests (80.5% among uRDT-FPs and 84.4% among cRDT-FPs). Only one false negative sample was detected with a partial pfhrp2 deletion.ConclusionThis study showed that the uRDTs developed by Abbott do not substantially outperform SD-Bioline Pf malaria RDTs in the community and are still not comparable to molecular methods to detect P. falciparum infections in this study setting.

Highlights

An ultrasensitive malaria rapid diagnostic test (RDT) was recently developed for the improved detection of low-density Plasmodium falciparum infections
Microscopic visualization of peripheral blood smears has traditionally been the most commonly used method to confirm the presence of Plasmodium parasites, but this changed with the appearance of malaria rapid diagnostic tests (RDTs) in the early 2000s [1]
The study showed that the sensitivity of the Abbott Plasmodium falciparum (Pf) malaria ultrasensitive RDT (uRDT) (68.2) was marginally higher compared to the SD-Bioline Pf malaria conventional RDTs (cRDTs) (61.5), while specificities were very similar (99.0 for uRDT vs. 99.2 for cRDT)

Summary

Introduction

An ultrasensitive malaria rapid diagnostic test (RDT) was recently developed for the improved detection of low-density Plasmodium falciparum infections. Despite control and elimination efforts worldwide, malaria remains a major global health problem This mosquito-borne disease caused by Plasmodium parasites. Malaria RDTs are a simple, rapid, cheap and field-deployable way to accurately identify a malaria infection at the point of care, being especially useful in low-resource and rural settings without access to laboratory facilities. Their use has sharply increased in the last years and an estimated 412 million tests were sold globally in 2018 [1]. There are various commercially available tests that detect different parasite molecules produced during the erythrocytic cycle, namely the Plasmodium falciparum (Pf) histidine-rich protein 2 (HRP2), the Plasmodium genus or species-specific lactate dehydrogenase (pLDH) and the Plasmodium genus or species-specific aldolase [3]

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