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Review
. 2014 Dec 18;2014(12):CD011431.
doi: 10.1002/14651858.CD011431.

Rapid diagnostic tests for diagnosing uncomplicated non-falciparum or Plasmodium vivax malaria in endemic countries

Affiliations
Review

Rapid diagnostic tests for diagnosing uncomplicated non-falciparum or Plasmodium vivax malaria in endemic countries

Katharine Abba et al. Cochrane Database Syst Rev. .

Abstract

Background: In settings where both Plasmodium vivax and Plasmodium falciparum infection cause malaria, rapid diagnostic tests (RDTs) need to distinguish which species is causing the patients' symptoms, as different treatments are required. Older RDTs incorporated two test lines to distinguish malaria due to P. falciparum, from malaria due to any other Plasmodium species (non-falciparum). These RDTs can be classified according to which antibodies they use: Type 2 RDTs use HRP-2 (for P. falciparum) and aldolase (all species); Type 3 RDTs use HRP-2 (for P. falciparum) and pLDH (all species); Type 4 use pLDH (fromP. falciparum) and pLDH (all species).More recently, RDTs have been developed to distinguish P. vivax parasitaemia by utilizing a pLDH antibody specific to P. vivax.

Objectives: To assess the diagnostic accuracy of RDTs for detecting non-falciparum or P. vivax parasitaemia in people living in malaria-endemic areas who present to ambulatory healthcare facilities with symptoms suggestive of malaria, and to identify which types and brands of commercial test best detect non-falciparum and P. vivax malaria.

Search methods: We undertook a comprehensive search of the following databases up to 31 December 2013: Cochrane Infectious Diseases Group Specialized Register; MEDLINE; EMBASE; MEDION; Science Citation Index; Web of Knowledge; African Index Medicus; LILACS; and IndMED.

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 non-falciparum endemic areas.

Data collection and analysis: For each study, two review authors independently extracted a standard set of data using a tailored data extraction form. We grouped comparisons by type of RDT (defined by the combinations of antibodies used), and combined in meta-analysis where appropriate. Average sensitivities and specificities are presented alongside 95% confidence intervals (95% CI).

Main results: We included 47 studies enrolling 22,862 participants. Patient characteristics, sampling methods and reference standard methods were poorly reported in most studies. RDTs detecting 'non-falciparum' parasitaemiaEleven studies evaluated Type 2 tests compared with microscopy, 25 evaluated Type 3 tests, and 11 evaluated Type 4 tests. In meta-analyses, average sensitivities and specificities were 78% (95% CI 73% to 82%) and 99% (95% CI 97% to 99%) for Type 2 tests, 78% (95% CI 69% to 84%) and 99% (95% CI 98% to 99%) for Type 3 tests, and 89% (95% CI 79% to 95%) and 98% (95% CI 97% to 99%) for Type 4 tests, respectively. Type 4 tests were more sensitive than both Type 2 (P = 0.01) and Type 3 tests (P = 0.03).Five studies compared Type 3 tests with PCR; in meta-analysis, the average sensitivity and specificity were 81% (95% CI 72% to 88%) and 99% (95% CI 97% to 99%) respectively. RDTs detecting P.vivax parasitaemiaEight studies compared pLDH tests to microscopy; the average sensitivity and specificity were 95% (95% CI 86% to 99%) and 99% (95% CI 99% to 100%), respectively.

Authors' conclusions: RDTs designed to detect P. vivax specifically, whether alone or as part of a mixed infection, appear to be more accurate than older tests designed to distinguish P. falciparum malaria from non-falciparum malaria. Compared to microscopy, these tests fail to detect around 5% ofP. vivax cases. This Cochrane Review, in combination with other published information about in vitro test performance and stability in the field, can assist policy-makers to choose between the available RDTs.

PubMed Disclaimer

Conflict of interest statement

PG is Director of Evidence Building and Synthesis Research Consortium that receives money to increase the number of evidence‐informed decisions by intermediary organizations, including WHO and national decision‐makers that benefit the poor in middle‐ and low‐income countries. PG is the coordinator of a WHO Collaborating Centre for Evidence Synthesis for Infectious and Tropical Diseases; one of the Centre's aims is to help WHO in its role as an infomediary in communicating reliable summaries of research evidence to policy makers, clinicians, teachers, and the public in developing countries.

Figures

1
1
Study flow diagram.
2
2
Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
3
3
Forest plot of commercial brands of Type 2 tests for detection of nonfalciparum species (verified with microscopy). We ordered studies by continent, age group and study identifier.
4
4
Summary ROC plot of Type 2 tests for detection of nonfalciparum species (verified with microscopy). The black solid circle corresponds to the summary estimate of sensitivity and specificity, and is shown with a 95% confidence region.
5
5
Forest plot of commercial brands of Type 3 tests for detection of nonfalciparum species (verified with microscopy). We ordered studies by continent, age group and study identifier.
6
6
Summary ROC plot of Type 3 tests for detection of nonfalciparum species (verified with microscopy). The black solid circle corresponds to the summary estimate of sensitivity and specificity, and is shown with a 95% confidence region.
7
7
Forest plot of commercial brands of Type 4 tests for detection of nonfalciparum species (verified with microscopy). We ordered studies by continent, age group and study identifier.
8
8
Summary ROC plot of Type 4 tests for detection of nonfalciparum species (verified with microscopy). The black circle corresponds to the summary estimate of sensitivity and specificity, and is shown with a 95% confidence region.
9
9
Forest plot of Type 2, Type 3 and Type 4 tests for detection of nonfalciparum species (verified with microscopy). We ordered studies by continent, age group and study identifier.
10
10
Summary ROC plot comparing Type 2, Type 3 and Type 4 tests for detection of nonfalciparum species (verified with microscopy). The solid circles correspond to the summary estimates of sensitivity and specificity for each test type, and are shown with 95% confidence regions (dotted lines) and 95% prediction regions (dashed lines). The summary points for Type 2 and Type 3 and their 95% confidence regions are identical but the 95% prediction regions differ. The 95% prediction regions illustrate the extent of between study heterogeneity.
11
11
Summary ROC plot of Type 3 tests for detection of nonfalciparum species (verified with PCR). The solid circles correspond to the summary estimate of sensitivity and specificity, and is shown with a 95% confidence region.
12
12
Forest plot of Pf HRP‐2 and Pv pLDH for detection of P. vivax (verified with microscopy). Studies are ordered by continent, age group and study identifier.
13
13
Summary ROC plot Pf HRP‐2 and Pv pLDH for detection of P. vivax (verified with microscopy). The black circle corresponds to the summary estimate of sensitivity and specificity, and is shown with a 95% confidence region.
1
1. Test
Nonfalciparum species only, microscopy, Type 2, ICT Combo Cassette.
2
2. Test
Nonfalciparum species only, microscopy, Type 2, ICT Malaria Pf/Pv.
3
3. Test
Nonfalciparum species only, microscopy, Type 2, NOW Malaria ICT.
4
4. Test
Non‐falciparum species only, microscopy, Type 2, Malascan.
5
5. Test
Non‐falciparum species only, microscopy, Type 2, VIKIA Ag Pf/Pan.
6
6. Test
Nonfalciparum species only, microscopy, Type 2 (All).
7
7. Test
Non‐falciparum species only, microscopy, Type 3, Parascreen.
8
8. Test
Non‐falciparum species only, microscopy, Type 3, CareStart Pf/Pan.
9
9. Test
Non‐falciparum species only, microscopy, Type 3, SD Malaria Antigen Bioline.
10
10. Test
Non‐falciparum species only, microscopy, Type 3, First Response Malaria Combo.
11
11. Test
Non‐falciparum species only, microscopy, Type 3, One Step Malaria Pf/Pan.
12
12. Test
Non‐falciparum species only, microscopy, Type 3 (All).
13
13. Test
Nonfalciparum species only, microscopy, Type 4, OptiMAL.
14
14. Test
Non‐falciparum species only, microscopy, Type 4, OptiMAL‐IT.
15
15. Test
Non‐falciparum species only, microscopy, Type 4, Carestart.
16
16. Test
Non‐falciparum species only, microscopy, Type 4 (All).
17
17. Test
Nonfalciparum species only, microscopy, Other Type, Malariagen Malaria.
18
18. Test
Non‐falciparum species only, PCR, Type 3, CareStart Pf/Pan.
19
19. Test
Non‐falciparum species only, PCR, Type 3, Parascreen.
20
20. Test
Non‐falciparum species only, PCR, Type 3, One Step Malaria Pf/Pan.
21
21. Test
Non‐falciparum species only, PCR, Type 3, SD Malaria Antigen Bioline.
22
22. Test
Non‐falciparum species only, PCR, Type 3 (All).
23
23. Test
Non‐falciparum species only, PCR, Type 4, OptiMAL (All).
24
24. Test
P. vivax, microscopy, Pf HRP‐2 and Pv pLDH, Carestart Pf/Pv (All).
25
25. Test
P. vivax, microscopy, Pf HRP‐2 and Pv pLDH, Biotech Malaria Pf/Pv.
26
26. Test
P. vivax, microscopy, Pf HRP‐2 and Pv pLDH, Falcivax.
27
27. Test
P. vivax, microscopy, Pf HRp‐2 and Pv pLDH, Onsite Pf/Pv.
28
28. Test
P. vivax, microscopy, Pf HRP‐2 and Pv pLDH, Pf/Pv Malaria Device.
29
29. Test
P. vivax, microscopy, Pf HRP‐2 and Pv pLDH (All).
30
30. Test
P. vivax, PCR, Pf HRP‐2 and Pv pLDH, Falcivax.
31
31. Test
P. vivax, PCR, Pf HRP‐2 and Pv pLDH, OnSite Pf/Pv.
32
32. Test
P. vivax, PCR, Pf HRP‐2 and Pv pLDH, Pf/Pv Malaria Device.
33
33. Test
P. vivax, PCR, Pf HRP‐2 and Pv pLDH (All).
34
34. Test
P. vivax, PCR, Type 6, PALUTOP (All).

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References

References to studies included in this review

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References to studies excluded from this review

Abeku 2008 {published data only}
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Kumar 2000 {published data only}
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Kumar 2004 {published data only}
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Kumar 2012 {published data only}
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Mahajan 2000 {published data only}
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Mikhail 2011 {published data only}
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