False-negative malaria rapid diagnostic test results and their impact on community-based malaria surveys in sub- Saharan Africa
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Surveillance and diagnosis of Plasmodium falciparum malaria relies predominantly on rapid diagnostic tests (RDTs). However, false-negative RDT results are known to occur for a variety of reasons, including operator error, poor storage conditions, pfhrp2/3 gene deletions, poor performance of specific RDT brands and lots, and low-parasite-density infections. We used RDT and microscopy results from 85,000 children enrolled in Demographic Health Surveys and Malaria Indicator Surveys from 2009 to 2015 across 19 countries to explore the distribution of and risk factors for false-negative RDTs in Sub40 Saharan Africa, where malaria’s impact is greatest. We sought to (i) identify spatial and demographic patterns of false-negative RDT (FN-RDT) results, defined as a negative RDT but positive gold-standard microscopy test, and (ii) estimate the percentage of infections missed within community-based malaria surveys due to FN-RDT results. Across all studies, 19.9% [95% CI: 19.0 – 20.9] of microscopy-positive subjects were negative by RDT. The distribution of FN-RDT results was spatially heterogeneous. The variance in FN-RDT results was best explained by the prevalence of malaria, with an increase in FN46 RDT results observed at lower transmission intensities, among younger subjects, and in urban areas. The observed proportion of FN-RDT results was not predicted by differences in RDT brand or lot performance alone. These findings characterise how the probability of detection by RDTs varies in different transmission settings and emphasize the need for careful interpretation of prevalence estimates based on surveys employing RDTs alone. Further studies are needed to characterise the cost-effectiveness of improved malaria diagnostics (e.g. PCR or highly sensitive RDTs) in community52 based surveys, especially in regions of low transmission intensity or high urbanicity.
Date Issued
2019-07-29
Date Acceptance
2019-07-02
Citation
BMJ Global Health, 2019, 4 (4), pp.1-9
ISSN
2059-7908
Publisher
BMJ Publishing Group
Start Page
1
End Page
9
Journal / Book Title
BMJ Global Health
Volume
4
Issue
4
Copyright Statement
© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.
This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/
This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/
Sponsor
Wellcome Trust
Bill and Melinda Gates Foundation
Medical Research Council (MRC)
Identifier
https://gh.bmj.com/content/4/4/e001582
Grant Number
109312/Z/15/Z
MR/R015600/1
Subjects
Science & Technology
Life Sciences & Biomedicine
Public, Environmental & Occupational Health
malaria diagnosis
rapid diagnostic tests
RDTs
pfhrp2
pfhrp2 deletion
Plasmodium falciparum
mathematical modelling
mapping
PLASMODIUM-FALCIPARUM
Plasmodium falciparum
RDTs
malaria diagnosis
mapping
mathematical modelling
pfhrp2
pfhrp2 deletion
rapid diagnostic tests
Publication Status
Published
Date Publish Online
2019-07-29