Limits...
Modelling the Impact and Cost-Effectiveness of Biomarker Tests as Compared with Pathogen-Specific Diagnostics in the Management of Undifferentiated Fever in Remote Tropical Settings.

Lubell Y, Althaus T, Blacksell SD, Paris DH, Mayxay M, Pan-Ngum W, White LJ, Day NP, Newton PN - PLoS ONE (2016)

Bottom Line: All testing strategies are likely to result in higher average costs, but only the scrub typhus and CRP tests are likely to be cost-effective when considering direct health benefits, with median cost per disability adjusted life year averted of approximately $48 USD and $94 USD, respectively.Testing for viral infections is unlikely to be cost-effective when considering only direct health benefits to patients.Testing for biomarkers of host inflammation is likely to be consistently cost-effective despite high heterogeneity, and can also offer substantial reductions in over-use of antimicrobials in viral infections.

View Article: PubMed Central - PubMed

Affiliation: Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

ABSTRACT

Background: Malaria accounts for a small fraction of febrile cases in increasingly large areas of the malaria endemic world. Point-of-care tests to improve the management of non-malarial fevers appropriate for primary care are few, consisting of either diagnostic tests for specific pathogens or testing for biomarkers of host response that indicate whether antibiotics might be required. The impact and cost-effectiveness of these approaches are relatively unexplored and methods to do so are not well-developed.

Methods: We model the ability of dengue and scrub typhus rapid tests to inform antibiotic treatment, as compared with testing for elevated C-Reactive Protein (CRP), a biomarker of host-inflammation. Using data on causes of fever in rural Laos, we estimate the proportion of outpatients that would be correctly classified as requiring an antibiotic and the likely cost-effectiveness of the approaches.

Results: Use of either pathogen-specific test slightly increased the proportion of patients correctly classified as requiring antibiotics. CRP testing was consistently superior to the pathogen-specific tests, despite heterogeneity in causes of fever. All testing strategies are likely to result in higher average costs, but only the scrub typhus and CRP tests are likely to be cost-effective when considering direct health benefits, with median cost per disability adjusted life year averted of approximately $48 USD and $94 USD, respectively.

Conclusions: Testing for viral infections is unlikely to be cost-effective when considering only direct health benefits to patients. Testing for prevalent bacterial pathogens can be cost-effective, having the benefit of informing not only whether treatment is required, but also as to the most appropriate antibiotic; this advantage, however, varies widely in response to heterogeneity in causes of fever. Testing for biomarkers of host inflammation is likely to be consistently cost-effective despite high heterogeneity, and can also offer substantial reductions in over-use of antimicrobials in viral infections.

Show MeSH

Related in: MedlinePlus

Antibiotic targeting using the Laos data (A) and across a range of simulated incidences and test accuracies (B). Figure A illustrates that CRP testing achieved the largest proportion of patients that are correctly prescribed an antibiotic (the bottom dark green segment of the bars show the percentages of patients with viral infections not prescribed an antibiotic; the light green segment shows the percentages of patients with bacterial infections correctly prescribed an antibiotic; the yellow segment shows the percentages of patients with viral infections prescribed an antibiotic; and the red segment shows the percentages of patients with untreated bacterial infections). The panel on the left shows that this advantage of CRP testing is consistent when modelling extensive heterogeneity in causes of fever, while the pathogen specific tests and the scrub typhus one in particular are more affected by such heterogeneity. ST–scrub typhus; CRP–C reactive protein; RDT–rapid diagnostic test.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4814092&req=5

pone.0152420.g003: Antibiotic targeting using the Laos data (A) and across a range of simulated incidences and test accuracies (B). Figure A illustrates that CRP testing achieved the largest proportion of patients that are correctly prescribed an antibiotic (the bottom dark green segment of the bars show the percentages of patients with viral infections not prescribed an antibiotic; the light green segment shows the percentages of patients with bacterial infections correctly prescribed an antibiotic; the yellow segment shows the percentages of patients with viral infections prescribed an antibiotic; and the red segment shows the percentages of patients with untreated bacterial infections). The panel on the left shows that this advantage of CRP testing is consistent when modelling extensive heterogeneity in causes of fever, while the pathogen specific tests and the scrub typhus one in particular are more affected by such heterogeneity. ST–scrub typhus; CRP–C reactive protein; RDT–rapid diagnostic test.

Mentions: When aggregating pathogens into bacterial and viral groups, the model predicted that use of either pathogen-specific tests offers modest improvements over current practice in their ability to classify patients as requiring an antibiotic. Use of dengue RDTs would lead to a reduction in antibiotics prescribed to viral infections, while use of scrub typhus RDTs implied a larger proportion of bacterial infections receiving antibiotics (Fig 3A). The CRP test outperformed the pathogen-specific tests, with reductions in both unnecessary use of antibiotics in viral infections as well as less bacterial infections going untreated. In total, 80% of patients were classified correctly using the CRP test, compared with 52% based on current practice, 46% using a dengue test, and 59% using scrub typhus test.


Modelling the Impact and Cost-Effectiveness of Biomarker Tests as Compared with Pathogen-Specific Diagnostics in the Management of Undifferentiated Fever in Remote Tropical Settings.

Lubell Y, Althaus T, Blacksell SD, Paris DH, Mayxay M, Pan-Ngum W, White LJ, Day NP, Newton PN - PLoS ONE (2016)

Antibiotic targeting using the Laos data (A) and across a range of simulated incidences and test accuracies (B). Figure A illustrates that CRP testing achieved the largest proportion of patients that are correctly prescribed an antibiotic (the bottom dark green segment of the bars show the percentages of patients with viral infections not prescribed an antibiotic; the light green segment shows the percentages of patients with bacterial infections correctly prescribed an antibiotic; the yellow segment shows the percentages of patients with viral infections prescribed an antibiotic; and the red segment shows the percentages of patients with untreated bacterial infections). The panel on the left shows that this advantage of CRP testing is consistent when modelling extensive heterogeneity in causes of fever, while the pathogen specific tests and the scrub typhus one in particular are more affected by such heterogeneity. ST–scrub typhus; CRP–C reactive protein; RDT–rapid diagnostic test.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4814092&req=5

pone.0152420.g003: Antibiotic targeting using the Laos data (A) and across a range of simulated incidences and test accuracies (B). Figure A illustrates that CRP testing achieved the largest proportion of patients that are correctly prescribed an antibiotic (the bottom dark green segment of the bars show the percentages of patients with viral infections not prescribed an antibiotic; the light green segment shows the percentages of patients with bacterial infections correctly prescribed an antibiotic; the yellow segment shows the percentages of patients with viral infections prescribed an antibiotic; and the red segment shows the percentages of patients with untreated bacterial infections). The panel on the left shows that this advantage of CRP testing is consistent when modelling extensive heterogeneity in causes of fever, while the pathogen specific tests and the scrub typhus one in particular are more affected by such heterogeneity. ST–scrub typhus; CRP–C reactive protein; RDT–rapid diagnostic test.
Mentions: When aggregating pathogens into bacterial and viral groups, the model predicted that use of either pathogen-specific tests offers modest improvements over current practice in their ability to classify patients as requiring an antibiotic. Use of dengue RDTs would lead to a reduction in antibiotics prescribed to viral infections, while use of scrub typhus RDTs implied a larger proportion of bacterial infections receiving antibiotics (Fig 3A). The CRP test outperformed the pathogen-specific tests, with reductions in both unnecessary use of antibiotics in viral infections as well as less bacterial infections going untreated. In total, 80% of patients were classified correctly using the CRP test, compared with 52% based on current practice, 46% using a dengue test, and 59% using scrub typhus test.

Bottom Line: All testing strategies are likely to result in higher average costs, but only the scrub typhus and CRP tests are likely to be cost-effective when considering direct health benefits, with median cost per disability adjusted life year averted of approximately $48 USD and $94 USD, respectively.Testing for viral infections is unlikely to be cost-effective when considering only direct health benefits to patients.Testing for biomarkers of host inflammation is likely to be consistently cost-effective despite high heterogeneity, and can also offer substantial reductions in over-use of antimicrobials in viral infections.

View Article: PubMed Central - PubMed

Affiliation: Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

ABSTRACT

Background: Malaria accounts for a small fraction of febrile cases in increasingly large areas of the malaria endemic world. Point-of-care tests to improve the management of non-malarial fevers appropriate for primary care are few, consisting of either diagnostic tests for specific pathogens or testing for biomarkers of host response that indicate whether antibiotics might be required. The impact and cost-effectiveness of these approaches are relatively unexplored and methods to do so are not well-developed.

Methods: We model the ability of dengue and scrub typhus rapid tests to inform antibiotic treatment, as compared with testing for elevated C-Reactive Protein (CRP), a biomarker of host-inflammation. Using data on causes of fever in rural Laos, we estimate the proportion of outpatients that would be correctly classified as requiring an antibiotic and the likely cost-effectiveness of the approaches.

Results: Use of either pathogen-specific test slightly increased the proportion of patients correctly classified as requiring antibiotics. CRP testing was consistently superior to the pathogen-specific tests, despite heterogeneity in causes of fever. All testing strategies are likely to result in higher average costs, but only the scrub typhus and CRP tests are likely to be cost-effective when considering direct health benefits, with median cost per disability adjusted life year averted of approximately $48 USD and $94 USD, respectively.

Conclusions: Testing for viral infections is unlikely to be cost-effective when considering only direct health benefits to patients. Testing for prevalent bacterial pathogens can be cost-effective, having the benefit of informing not only whether treatment is required, but also as to the most appropriate antibiotic; this advantage, however, varies widely in response to heterogeneity in causes of fever. Testing for biomarkers of host inflammation is likely to be consistently cost-effective despite high heterogeneity, and can also offer substantial reductions in over-use of antimicrobials in viral infections.

Show MeSH
Related in: MedlinePlus