article · American Journal of Tropical Medicine and Hygiene
Rapid diagnostic tests detecting histidine-rich protein 2 are central to diagnosing falciparum malaria across Sub-Saharan Africa. However, their reliability during surveillance in asymptomatic populations requires careful assessment. A study conducted between 2018 and 2021 screened 5,966 asymptomatic individuals aged over five years in Bagamoyo District, Tanzania, comparing rapid diagnostic tests against microscopy and real-time polymerase chain reaction. Among individuals testing positive on rapid diagnostic tests, 12 percent were false positives, showing negative results by both microscopy and reference testing, with children disproportionately affected. Conversely, 22 percent of individuals with negative rapid test results were actually infected, mainly due to very low parasite densities below 100 parasites per microlitre. Gene deletions of histidine-rich protein 2 or 3 were detected in a subset of samples with higher parasite densities, but they accounted for less than one percent of total false-negative results.
Malaria control programmes depend heavily on rapid test kits to track infections. Demonstrating that substantial numbers of asymptomatic infections are missed due to low parasite levels, alongside notable false-positive rates in children, informs public health officials on the limitations of relying solely on standard rapid tests for community-level malaria surveillance and elimination efforts.
The findings are relevant to diagnostic manufacturers and public health agencies developing next-generation malaria surveillance tools. While gene deletions remain rare, the high rate of false negatives highlights a clear demand for more sensitive, low-density field diagnostics. This research represents applied field evaluation rather than a commercial product, indicating that diagnostic developers must focus on lowering the limit of parasite detection for asymptomatic screening use cases.
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Malaria rapid diagnostic tests (mRDTs) that detect histidine-rich protein 2 (HRP2) remain the mainstay of falciparum malaria diagnosis in Sub-Saharan Africa. Understanding their test characteristics when used for surveillance in asymptomatic populations is important. We explored the rate of false-positive and false-negative mRDT results among asymptomatic persons >5 years old screened for malaria at schools and clinics in the rural Bagamoyo District using 18S ribosomal RNA real-time polymerase chain reaction (qPCR) as the reference test. Among 5,966 persons screened using mRDTs, microscopy, and qPCR tests from 2018 to 2021, 14% (832) were mRDT-positive. Twelve percent of these (98/832) were negative by both microscopy and qPCR, with children overrepresented among those with false-positive mRDTs. Among those who were mRDT-negative, 22% (1,136/5,134) tested qPCR-positive, predominantly because of low-density parasitemia (92% had <100 p/µL by qPCR). Among mRDT-negative samples with >100 p/µL, we looked for evidence of hrp2 or histidine-rich protein 3 (hrp3) deletion using two methods, multiplexed qPCR and multiplex bead-based immunoassay. When sufficient parasite material existed for a reliable deletion assessment, 12/34 (35%) had evidence of hrp2/3 deletion by qPCR (nine hrp2-/3+ and three hrp2-/3-), and 20/52 (38%) had evidence of deletion by immunoassay. Only three isolates showed evidence of hrp2 deletion by both assays. In an area of low to moderate transmission in Tanzania, false-positive mRDTs are relatively common (12% of positive tests), and false-negative mRDTs are even more common (22% of negative tests), but hrp2/3 deletion causing false-negative mRDTs remains rare (<1% of negative tests).
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DOI: 10.4269/ajtmh.24-0209
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