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Determinants of the accuracy of rapid diagnostic tests in malaria case management: evidence from low and moderate transmission settings in the East African highlands.

Abeku TA, Kristan M, Jones C, Beard J, Mueller DH, Okia M, Rapuoda B, Greenwood B, Cox J - Malar. J. (2008)

Bottom Line: Specificity was relatively high in older age groups and increased towards the end of the transmission season, indicating the role played by anti-HRP2 antibodies.RDTs may be effective when used in low endemicity situations, but high false positive error rates may occur in areas with moderately high transmission.Reports on specificity of RDTs and cost-effectiveness analyses on their use should be interpreted with caution as there may be wide variations in these measurements depending upon endemicity, season and the age group of patients studied.

View Article: PubMed Central - HTML - PubMed

Affiliation: London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT, UK. tarekegn.abeku@gmail.com

ABSTRACT

Background: The accuracy of malaria diagnosis has received renewed interest in recent years due to changes in treatment policies in favour of relatively high-cost artemisinin-based combination therapies. The use of rapid diagnostic tests (RDTs) based on histidine-rich protein 2 (HRP2) synthesized by Plasmodium falciparum has been widely advocated to save costs and to minimize inappropriate treatment of non-malarial febrile illnesses. HRP2-based RDTs are highly sensitive and stable; however, their specificity is a cause for concern, particularly in areas of intense malaria transmission due to persistence of HRP2 antigens from previous infections.

Methods: In this study, 78,454 clinically diagnosed malaria patients were tested using HRP2-based RDTs over a period of approximately four years in four highland sites in Kenya and Uganda representing hypoendemic to mesoendemic settings. In addition, the utility of the tests was evaluated in comparison with expert microscopy for disease management in 2,241 subjects in two sites with different endemicity levels over four months.

Results: RDT positivity rates varied by season and year, indicating temporal changes in accuracy of clinical diagnosis. Compared to expert microscopy, the sensitivity, specificity, positive predictive value and negative predictive value of the RDTs in a hypoendemic site were 90.0%, 99.9%, 90.0% and 99.9%, respectively. Corresponding measures at a mesoendemic site were 91.0%, 65.0%, 71.6% and 88.1%. Although sensitivities at the two sites were broadly comparable, levels of specificity varied considerably between the sites as well as according to month of test, age of patient, and presence or absence of fever during consultation. Specificity was relatively high in older age groups and increased towards the end of the transmission season, indicating the role played by anti-HRP2 antibodies. Patients with high parasite densities were more likely to test positive with RDTs than those with low density infections.

Conclusion: RDTs may be effective when used in low endemicity situations, but high false positive error rates may occur in areas with moderately high transmission. Reports on specificity of RDTs and cost-effectiveness analyses on their use should be interpreted with caution as there may be wide variations in these measurements depending upon endemicity, season and the age group of patients studied.

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Sensitivity, specificity, PPV and NPV of RDTs compared to microscopy in Kebisoni (mesoendemic area) and Kilibwoni (hypoendemic area). Error bars indicate 95% confidence intervals.
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Figure 3: Sensitivity, specificity, PPV and NPV of RDTs compared to microscopy in Kebisoni (mesoendemic area) and Kilibwoni (hypoendemic area). Error bars indicate 95% confidence intervals.

Mentions: At the hypoendemic site (Kilibwoni), only 10/1,000 (1.0%) of cases examined microscopically were positive for P. falciparum by RDT, whereas at the mesoendemic site (Kebisoni), 609/1,237 (49.2%) were positive. The sensitivity, specificity, PPV and NPV of the RDTs at Kilibwoni were 90.0%, 99.9%, 90.0% and 99.9%, respectively, whereas the corresponding figures at Kebisoni were 91.0%, 65.0%, 71.6% and 88.1%, respectively. A significantly higher specificity was observed at Kilibwoni compared to that of the more endemic Kebisoni (p < 0.0001) (Figure 3). This resulted in a significantly higher NPV for RDTs in the former (p < 0.0001), but there was no significant difference between the two sites in terms of PPV (p = 0.198). At Kebisoni, 220/628 patients (35%) who tested negative by microscopy tested positive by RDT. At Kilibwoni, only one of the 990 patients who tested negative by microscopy tested positive by RDT. Fifty-five of the 609 patients (9%) confirmed to be positive with microscopy at Kebisoni were declared negative with RDTs. Most of these patients had low mean parasite densities (below 1,000/μl in 34/55). However, six of the 55 false negative patients at Kebisoni (11%) had parasite densities exceeding 8,000/μl. At Kilibwoni, one patient was false negative by RDT out of a total of 10 who were confirmed positive by microscopy.


Determinants of the accuracy of rapid diagnostic tests in malaria case management: evidence from low and moderate transmission settings in the East African highlands.

Abeku TA, Kristan M, Jones C, Beard J, Mueller DH, Okia M, Rapuoda B, Greenwood B, Cox J - Malar. J. (2008)

Sensitivity, specificity, PPV and NPV of RDTs compared to microscopy in Kebisoni (mesoendemic area) and Kilibwoni (hypoendemic area). Error bars indicate 95% confidence intervals.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2571107&req=5

Figure 3: Sensitivity, specificity, PPV and NPV of RDTs compared to microscopy in Kebisoni (mesoendemic area) and Kilibwoni (hypoendemic area). Error bars indicate 95% confidence intervals.
Mentions: At the hypoendemic site (Kilibwoni), only 10/1,000 (1.0%) of cases examined microscopically were positive for P. falciparum by RDT, whereas at the mesoendemic site (Kebisoni), 609/1,237 (49.2%) were positive. The sensitivity, specificity, PPV and NPV of the RDTs at Kilibwoni were 90.0%, 99.9%, 90.0% and 99.9%, respectively, whereas the corresponding figures at Kebisoni were 91.0%, 65.0%, 71.6% and 88.1%, respectively. A significantly higher specificity was observed at Kilibwoni compared to that of the more endemic Kebisoni (p < 0.0001) (Figure 3). This resulted in a significantly higher NPV for RDTs in the former (p < 0.0001), but there was no significant difference between the two sites in terms of PPV (p = 0.198). At Kebisoni, 220/628 patients (35%) who tested negative by microscopy tested positive by RDT. At Kilibwoni, only one of the 990 patients who tested negative by microscopy tested positive by RDT. Fifty-five of the 609 patients (9%) confirmed to be positive with microscopy at Kebisoni were declared negative with RDTs. Most of these patients had low mean parasite densities (below 1,000/μl in 34/55). However, six of the 55 false negative patients at Kebisoni (11%) had parasite densities exceeding 8,000/μl. At Kilibwoni, one patient was false negative by RDT out of a total of 10 who were confirmed positive by microscopy.

Bottom Line: Specificity was relatively high in older age groups and increased towards the end of the transmission season, indicating the role played by anti-HRP2 antibodies.RDTs may be effective when used in low endemicity situations, but high false positive error rates may occur in areas with moderately high transmission.Reports on specificity of RDTs and cost-effectiveness analyses on their use should be interpreted with caution as there may be wide variations in these measurements depending upon endemicity, season and the age group of patients studied.

View Article: PubMed Central - HTML - PubMed

Affiliation: London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT, UK. tarekegn.abeku@gmail.com

ABSTRACT

Background: The accuracy of malaria diagnosis has received renewed interest in recent years due to changes in treatment policies in favour of relatively high-cost artemisinin-based combination therapies. The use of rapid diagnostic tests (RDTs) based on histidine-rich protein 2 (HRP2) synthesized by Plasmodium falciparum has been widely advocated to save costs and to minimize inappropriate treatment of non-malarial febrile illnesses. HRP2-based RDTs are highly sensitive and stable; however, their specificity is a cause for concern, particularly in areas of intense malaria transmission due to persistence of HRP2 antigens from previous infections.

Methods: In this study, 78,454 clinically diagnosed malaria patients were tested using HRP2-based RDTs over a period of approximately four years in four highland sites in Kenya and Uganda representing hypoendemic to mesoendemic settings. In addition, the utility of the tests was evaluated in comparison with expert microscopy for disease management in 2,241 subjects in two sites with different endemicity levels over four months.

Results: RDT positivity rates varied by season and year, indicating temporal changes in accuracy of clinical diagnosis. Compared to expert microscopy, the sensitivity, specificity, positive predictive value and negative predictive value of the RDTs in a hypoendemic site were 90.0%, 99.9%, 90.0% and 99.9%, respectively. Corresponding measures at a mesoendemic site were 91.0%, 65.0%, 71.6% and 88.1%. Although sensitivities at the two sites were broadly comparable, levels of specificity varied considerably between the sites as well as according to month of test, age of patient, and presence or absence of fever during consultation. Specificity was relatively high in older age groups and increased towards the end of the transmission season, indicating the role played by anti-HRP2 antibodies. Patients with high parasite densities were more likely to test positive with RDTs than those with low density infections.

Conclusion: RDTs may be effective when used in low endemicity situations, but high false positive error rates may occur in areas with moderately high transmission. Reports on specificity of RDTs and cost-effectiveness analyses on their use should be interpreted with caution as there may be wide variations in these measurements depending upon endemicity, season and the age group of patients studied.

Show MeSH
Related in: MedlinePlus