Rapid diagnostic tests for diagnosing uncomplicated P. falciparum malaria in endemic countries
- PMID: 21735422
- PMCID: PMC6532563
- DOI: 10.1002/14651858.CD008122.pub2
Rapid diagnostic tests for diagnosing uncomplicated P. falciparum malaria in endemic countries
Abstract
Background: Rapid diagnostic tests (RDTs) for Plasmodium falciparum malaria use antibodies to detect either HRP-2 antigen or pLDH antigen, and can improve access to diagnostics in developing countries.
Objectives: To assess the diagnostic accuracy of RDTs for detecting P. falciparum parasitaemia in persons living in endemic areas who present to ambulatory healthcare facilities with symptoms suggestive of malaria by type and brand.
Search strategy: We undertook a comprehensive search of the following databases: Cochrane Infectious Diseases Group Specialized Register; MEDLINE; EMBASE; MEDION; Science Citation Index; Web of Knowledge; African Index Medicus; LILACS; IndMED; to January 14, 2010.
Selection criteria: Studies comparing RDTs with a reference standard (microscopy or polymerase chain reaction) in blood samples from a random or consecutive series of patients attending ambulatory health facilities with symptoms suggestive of malaria in P. falciparum endemic areas.
Data collection and analysis: For each study, a standard set of data was extracted independently by two authors, using a tailored data extraction form. Comparisons were grouped hierarchically by target antigen, and type and brand of RDT, and combined in meta-analysis where appropriate.
Main results: We identified 74 unique studies as eligible for this review and categorized them according to the antigens they detected. Types 1 to 3 include HRP-2 (from P. falciparum) either by itself or with other antigens. Types 4 and 5 included pLDH (from P. falciparum) either by itself or with other antigens. In comparisons with microscopy, we identified 71 evaluations of Type 1 tests, eight evaluations of Type 2 tests and five evaluations of Type 3 tests. In meta-analyses, average sensitivities and specificities (95% CI) were 94.8% (93.1% to 96.1%) and 95.2% (93.2% to 96.7%) for Type 1 tests, 96.0% (94.0% to 97.3%) and 95.3% (87.3% to 98.3%) for Type 2 tests, and 99.5% (71.0% to 100.0%) and 90.6% (80.5% to 95.7%) for Type 3 tests, respectively. Overall for HRP-2, the meta-analytical average sensitivity and specificity (95% CI) were 95.0% (93.5% to 96.2%) and 95.2% (93.4% to 99.4%), respectively. For pLDH antibody-based RDTs verified with microscopy, we identified 17 evaluations of Type 4 RDTs and three evaluations of Type 5 RDTs. In meta-analyses, average sensitivity for Type 4 tests was 91.5% (84.7% to 95.3%) and average specificity was 98.7% (96.9% to 99.5%). For Type 5 tests, average sensitivity was 98.4% (95.1% to 99.5%) and average specificity was 97.5% (93.5% to 99.1%). Overall for pLDH, the meta-analytical average sensitivity and specificity (95% CI) were 93.2% (88.0% to 96.2%) and 98.5% (96.7% to 99.4%), respectively. For both categories of test, there was substantial heterogeneity in study results. Quality of the microscopy reference standard could only be assessed in 40% of studies due to inadequate reporting, but results did not seem to be influenced by the reporting quality.Overall, HRP-2 antibody-based tests (such as the Type 1 tests) tended to be more sensitive and were significantly less specific than pLDH-based tests (such as the Type 4 tests). If the point estimates for Type 1 and Type 4 tests are applied to a hypothetical cohort of 1000 patients where 30% of those presenting with symptoms have P. falciparum, Type 1 tests will miss 16 cases, and Type 4 tests will miss 26 cases. The number of people wrongly diagnosed with P. falciparum would be 34 with Type 1 tests, and nine with Type 4 tests.
Authors' conclusions: The sensitivity and specificity of all RDTs is such that they can replace or extend the access of diagnostic services for uncomplicated P. falciparum malaria. HRP-2 antibody types may be more sensitive but are less specific than pLDH antibody-based tests, but the differences are small. The HRP-2 antigen persists even after effective treatment and so is not useful for detecting treatment failures.
Conflict of interest statement
There are no known conflicts of interest.
Figures
Comment in
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Assessing rapid diagnostic tests for malaria.Cochrane Database Syst Rev. 2011 Jul 26;(9):ED000031. doi: 10.1002/1305223.ed000031. Cochrane Database Syst Rev. 2011. PMID: 21901735 No abstract available.
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Cochrane Column * Rapid diagnostic tests can extend access of diagnostic services for uncomplicated Plasmodium falciparum malaria * Commentary: Rapid diagnostic tests for diagnosing uncomplicated Plasmodium falciparum malaria in endemic countries (Review) * Approach to conducting Cochrane Diagnostic Test Accuracy Reviews.Int J Epidemiol. 2012 Jun;41(3):607-10. doi: 10.1093/ije/dys083. Int J Epidemiol. 2012. PMID: 22798691 No abstract available.
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- Singh N, Valecha N, Nagpal AC, Mishra SS, Varma HS, Subbaro SK. The hospital and field‐based performances of the OptiMAL tests, for malaria diagnosis and treatment monitoring in central India. Annals of Tropical Medicine and Parasitology 2003;97(1):5‐13. - PubMed
Singh 2003b {published data only}
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- Singh N, Valecha N, Nagpal AC, Mishra SS, Varma HS, Subbaro SK. The hospital and field‐based performances of the OptiMAL tests, for malaria diagnosis and treatment monitoring in central India. Annals of Tropical Medicine and Parasitology 2003;97(1):5‐13. - PubMed
Stephens 1999 {published data only}
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Stow 1999 {published data only}
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- Stow NW, Torrens JK, Walker J. An assessment of the accuracy of clinical diagnosis, local microscopy and a rapid immunochromatographic card test in comparison with expert microscopy in the diagnosis of malaria in rural Kenya. Transactions of the Royal Society of Tropical Medicine and Hygiene 1999;93:519‐20. - PubMed
Tagbo 2007 {published data only}
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Tjitra 1999 {published data only}
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- Tjitra E, Suprianto S, Dyer M, Currie BJ, Anstey NM. Field evaluation of the ICT malaria Pf/Pv immunochromatographic test in detection of Plasmodium falciparum and Plasmodium vivax in patients with a presumptive clinical diagnosis of malaria in Eastern Indonesia . Journal of Clinical Microbiology 1999;37(8):2412‐7. - PMC - PubMed
Valecha 2003 {published data only}
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- Valecha N, Singh N, Yadav RS, Dev V, Aggarwal A, Subbarao SK. Field evaluation of OptiMAL48 rapid malaria diagnostic test in India. Acta Parasitologica 2003;48(3):229‐32.
Van den Broek 2006 {published data only}
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Willcox 2009a {published data only}
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Willcox 2009b {published data only}
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Wongsrichanalai 1999 {published data only}
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Bartoloni 1998 {published data only}
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Bhandari 2008 {published data only}
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Buchachart 2004 {published data only}
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Cabezas 2004 {published data only}
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Cavallo 1997 {published data only}
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Chilton 2006 {published data only}
Chiodini 1998 {published data only}
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Coleman 2002a {published data only}
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Coleman 2002b {published data only}
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Cong Le 2002 {published data only}
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Craig 2002 {published data only}
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Cropley 2000 {published data only}
Cuadros 2007 {published data only}
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De Carsalade 2009 {published data only}
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Drakeley 2009 {published data only}
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Durand 2005a {published data only}
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Dyer 2000 {published data only}
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Eisen 2000 {published data only}
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El‐Moamly 2007 {published data only}
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Elmardi 2009 {published data only}
Endeshaw 2008 {published data only}
Fan 2000 {published data only}
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Farcas 2003 {published data only}
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Farcas 2004 {published data only}
Ferro 2002 {published data only}
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Figueiredo 2003 {published data only}
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Ghanchi 2009 {published data only}
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Gillet 2009 (b) {published data only}
Gillet 2009 (c) {published data only}
Gogtay 1999 {published data only}
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