Abstract
BackgroundRapid diagnostic tests (RDT) for malaria are common, but their performance varies. Tests using histidine-rich protein 2 (HRP2) antigen are most common, and many have high sensitivity. HRP2 tests can remain positive for weeks after treatment, limiting their specificity and usefulness in high-transmission settings. Tests using Plasmodium lactate dehydrogenase (pLDH) have been less widely used but have higher specificity, mostly due to a much shorter time to become negative.MethodsA prospective, health centre-based, diagnostic evaluation of two malaria RDTs was performed in rural Niger during the high malaria transmission season (3–28 October, 2017) and during the low transmission season (28 January–31 March, 2018). All children under 5 years of age presenting with fever (axillary temperature > 37.5 °C) or history of fever in the previous 24 h were eligible. Capillary blood was collected by finger prick. The SD Bioline HRP2 (catalog: 05FK50) and the CareStart pLDH(pan) (catalog: RMNM-02571) were performed in parallel, and thick and thin smears were prepared. Microscopy was performed at Epicentre, Maradi, Niger, with external quality control. The target sample size was 279 children with microscopy-confirmed malaria during each transmission season.ResultsIn the high season, the sensitivity of both tests was estimated at > 99%, but the specificity of both tests was lower: 58.0% (95% CI 52.1–63.8) for the pLDH test and 57.4% (95% CI 51.5–63.1) for the HRP2 test. The positive predictive value was 66.3% (95% CI 61.1–71.2) for both tests. In the low season, the sensitivity of both tests dropped: 91.0% (95% CI 85.3–95.0) for the pLDH test and 85.8% (95% CI 79.3–90.9) for the HRP2 test. The positive predictive value remained low for both tests in the low season: 60.5% (95% CI 53.9–66.8) for the pLDH test and 61.9% (55.0–68.4) for the HRP2 test. Performance was similar across different production lots, gender, age of the children, and, during the high season, time since the most recent distribution of seasonal malaria chemoprevention.ConclusionsThe low specificity of the pLDH RDT in this setting was unexpected and is not easily explained. As the pLDH test continues to be introduced into new settings, the questions raised by this study will need to be addressed.
Highlights
Rapid diagnostic tests (RDT) for malaria are common, but their performance varies
The two most commonly targeted antigens are histidine-rich protein 2 (HRP2), which is specific to Plasmodium falciparum, and Plasmodium lactate dehydrogenase, which is present in all Plasmodium species; currently available tests detect one or both antigens
The two antigens are cleared with different speeds, which appears to affect their specificities depending on the context. An evaluation in both high- and lowtransmission areas in Uganda showed that median time for an HRP2 test to become negative after an effective treatment was 35–42 days, but that the median time to become negative for a Plasmodium lactate dehydrogenase (pLDH) test was only 2 days [3]
Summary
Rapid diagnostic tests (RDT) for malaria are common, but their performance varies. Tests using histidine-rich protein 2 (HRP2) antigen are most common, and many have high sensitivity. The two antigens are cleared with different speeds, which appears to affect their specificities (notably, their ability to detect current infection) depending on the context An evaluation in both high- and lowtransmission areas in Uganda showed that median time for an HRP2 test to become negative after an effective treatment was 35–42 days, but that the median time to become negative for a pLDH test was only 2 days [3]. The higher specificity of pLDH tests was seen in hospitalized children in Burkina Faso [4] These findings have important implications in high-transmission environments, where interpretation of HRP2 tests can be difficult in the peak malaria season, leading to false positive results and unnecessary treatments. In all other health centres of the District, and throughout the rest of Niger, HRP2-based tests are used by the Ministry of Public Health and its partners
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