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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 and specificity of RDTs as a function of the true parasite rate (as determined by microscopy) at Kebisoni, Rukungiri District, Uganda, by (a) month and (b) age groups (error bars indicate 95% confidence intervals).
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Figure 4: Sensitivity and specificity of RDTs as a function of the true parasite rate (as determined by microscopy) at Kebisoni, Rukungiri District, Uganda, by (a) month and (b) age groups (error bars indicate 95% confidence intervals).

Mentions: At Kebisoni, true parasite rates (as determined by microscopy) declined during the four months (December 2005 – March 2006) of concurrent collection of blood samples for comparison of RDTs with microscopy. During this period, the specificity of RDTs increased steadily from 56% in December 2005 to 79% in March 2006 (Figure 4a). There was no substantial change in the sensitivity of RDTs. During the same period, the NPV of RDTs increased from 67% to 92% whereas there was little change in PPV (76% in December 2005 and 77% in March 2006).


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 and specificity of RDTs as a function of the true parasite rate (as determined by microscopy) at Kebisoni, Rukungiri District, Uganda, by (a) month and (b) age groups (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 4: Sensitivity and specificity of RDTs as a function of the true parasite rate (as determined by microscopy) at Kebisoni, Rukungiri District, Uganda, by (a) month and (b) age groups (error bars indicate 95% confidence intervals).
Mentions: At Kebisoni, true parasite rates (as determined by microscopy) declined during the four months (December 2005 – March 2006) of concurrent collection of blood samples for comparison of RDTs with microscopy. During this period, the specificity of RDTs increased steadily from 56% in December 2005 to 79% in March 2006 (Figure 4a). There was no substantial change in the sensitivity of RDTs. During the same period, the NPV of RDTs increased from 67% to 92% whereas there was little change in PPV (76% in December 2005 and 77% in March 2006).

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