Abstract

The global burden of malaria has been substantially reduced over the past two decades. Future efforts to reduce malaria further will require moving beyond the treatment of clinical infections to targeting malaria transmission more broadly in the community. As such, the accurate identification of asymptomatic human infections, which can sustain a large proportion of transmission, is becoming a vital component of control and elimination programmes. We determined the relationship across common diagnostics used to measure malaria prevalence - polymerase chain reaction (PCR), rapid diagnostic test and microscopy - for the detection of Plasmodium falciparum infections in endemic populations based on a pooled analysis of cross-sectional data. We included data from more than 170,000 individuals comparing the detection by rapid diagnostic test and microscopy, and 30,000 for detection by rapid diagnostic test and PCR. The analysis showed that, on average, rapid diagnostic tests detected 41% (95% confidence interval = 26-66%) of PCR-positive infections. Data for the comparison of rapid diagnostic test to PCR detection at high transmission intensity and in adults were sparse. Prevalence measured by rapid diagnostic test and microscopy was comparable, although rapid diagnostic test detected slightly more infections than microscopy. On average, microscopy captured 87% (95% confidence interval = 74-102%) of rapid diagnostic test-positive infections. The extent to which higher rapid diagnostic test detection reflects increased sensitivity, lack of specificity or both, is unclear. Once the contribution of asymptomatic individuals to the infectious reservoir is better defined, future analyses should ideally establish optimal detection limits of new diagnostics for use in control and elimination strategies.

Highlights

  • The global burden of malaria has been substantially reduced over the past two decades

  • Only studies that were cross-sectional, that were of populations from a malaria endemic region, that used rapid diagnostic tests (RDTs) targeting P. falciparum only or mixed infections (HRP2 and/or pLDH) and that used polymerase chain reaction (PCR) or loop-mediated isothermal amplification (LAMP) methods were included

  • Combined with additional data sets from Demographic and Health Surveys (DHS) and unpublished studies, the pooled data available for evaluation yielded 323 pairs of prevalence estimates for RDT and microscopy[5,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,44,45,46,47,48,49] and 162 pairs for RDT and PCR . 25,27,34,39,40,42,45–55 The extracted proportions together with the main characteristics of the studies from our literature search are provided in the Supplementary Information

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Summary

Introduction

The global burden of malaria has been substantially reduced over the past two decades. Community chemotherapy (for example, mass screen and treat (MSAT) or mass drug administration (MDA) programmes) in conjunction with ongoing vector control is an approach under consideration for the interruption of transmission This is achieved through the direct treatment of potentially infectious individuals. Over the past three decades, the development of nucleic acid amplification tests has improved the detection limit for malaria infection to less than 1 parasite per microlitre by ultrasensitive quantitative polymerase chain reaction (qPCR)[11,12]. These detection thresholds are more appropriate for

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