Accuracy of commercially available c-reactive protein rapid tests in the context of undifferentiated fevers in rural Laos

Phommasone, Koukeo; Althaus, Thomas; Souvanthong, Phonesavanh; Phakhounthong, Khansoudaphone; Soyvienvong, Laxoy; Malapheth, Phatthaphone; Mayxay, Mayfong; Pavlicek, Rebecca L.; Paris, Daniel; Dance, David A. B.; Newton, Paul N.; Lubell, Yoel

doi:10.1186/s12879-016-1360-2

Cited by 23 publications

(30 citation statements)

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“…The intervention has the potential of being scaled up as several commercially affordable CRP rapid point-of-care tests have been assessed and seen to be reliable. 29 Before widely introducing CRP point-of-care tests as routine care, a cost-effectiveness analysis should be done to assess other additional requirements, including test cost, training, and consultation time, compared with the reduction in antibiotic prescription and subsequent burden of resistance. To achieve maximal impact on antibiotic consumption in settings, such as Vietnam, where antibiotic use is commonly off-prescription, further work investigating the potential for point-of-care CRP testing in pharmacies and drug stores will be needed.…”

Section: Discussionmentioning

confidence: 99%

Point-of-care C-reactive protein testing to reduce inappropriate use of antibiotics for non-severe acute respiratory infections in Vietnamese primary health care: a randomised controlled trial

Tran

et al. 2016

The Lancet Global Health

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SummaryBackgroundInappropriate antibiotic use for acute respiratory tract infections is common in primary health care, but distinguishing serious from self-limiting infections is difficult, particularly in low-resource settings. We assessed whether C-reactive protein point-of-care testing can safely reduce antibiotic use in patients with non-severe acute respiratory tract infections in Vietnam.MethodWe did a multicentre open-label randomised controlled trial in ten primary health-care centres in northern Vietnam. Patients aged 1–65 years with at least one focal and one systemic symptom of acute respiratory tract infection were assigned 1:1 to receive either C-reactive protein point-of-care testing or routine care, following which antibiotic prescribing decisions were made. Patients with severe acute respiratory tract infection were excluded. Enrolled patients were reassessed on day 3, 4, or 5, and on day 14 a structured telephone interview was done blind to the intervention. Randomised assignments were concealed from prescribers and patients but not masked as the test result was used to assist treatment decisions. The primary outcome was antibiotic use within 14 days of follow-up. All analyses were prespecified in the protocol and the statistical analysis plan. All analyses were done on the intention-to-treat population and the analysis of the primary endpoint was repeated in the per-protocol population. This trial is registered under number NCT01918579.FindingsBetween March 17, 2014, and July 3, 2015, 2037 patients (1028 children and 1009 adults) were enrolled and randomised. One adult patient withdrew immediately after randomisation. 1017 patients were assigned to receive C-reactive protein point-of-care testing, and 1019 patients were assigned to receive routine care. 115 patients in the C-reactive protein point-of-care group and 72 patients in the routine care group were excluded in the intention-to-treat analysis due to missing primary endpoint. The number of patients who used antibiotics within 14 days was 581 (64%) of 902 patients in the C-reactive protein group versus 738 (78%) of 947 patients in the control group (odds ratio [OR] 0·49, 95% CI 0·40–0·61; p<0·0001). Highly significant differences were seen in both children and adults, with substantial heterogeneity of the intervention effect across the 10 sites (I2=84%, 95% CI 66–96). 140 patients in the C-reactive protein group and 137 patients in the routine care group missed the urine test on day 3, 4, or 5. Antibiotic activity in urine on day 3, 4, or 5 was found in 267 (30%) of 877 patients in the C-reactive protein group versus 314 (36%) of 882 patients in the routine treatment group (OR 0·78, 95% CI 0·63–0·95; p=0·015). Time to resolution of symptoms was similar in both groups. Adverse events were rare, with no deaths and a total of 14 hospital admissions (six in the C-reactive protein group and eight in the control group).InterpretationC-reactive protein point-of-care testing reduced antibiotic use for non-severe acute respiratory tract infection w...

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Section: Discussionmentioning

confidence: 99%

Point-of-care C-reactive protein testing to reduce inappropriate use of antibiotics for non-severe acute respiratory infections in Vietnamese primary health care: a randomised controlled trial

Tran

et al. 2016

The Lancet Global Health

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129

173

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“…Testing for biomarkers of inflammation could offer a robust approach to targeting antibiotics in rural settings for heterogeneous causes of fever. In this analysis we focus on CRP testing given the large body of evidence supporting its use to guide antibiotics in acute respiratory infections and fevers [ 10 , 14 ], and the commercial availability of accurate rapid tests [ 20 ]. CRP testing was consistently predicted to be the best performer in identifying whether or not antibiotics were at all required, despite heterogeneity in causes of fever, with the disadvantage of lacking indication as to the specific pathogen and therefore the optimal antibiotic.…”

Section: Discussionmentioning

confidence: 99%

“…For the biomarker approach, we modelled use of a CRP rapid test, based on evidence supporting its ability to distinguish bacterial from viral infections prevalent in Southeast Asia [ 14 ]. Rapid qualitative and semi-quantitative lateral flow tests are commercially available and some have been shown to accurately detect elevated CRP levels as compared with quantitative readers [ 20 ].…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2016

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BackgroundMalaria 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.MethodsWe 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.ResultsUse 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.ConclusionsTesting 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.

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“…If implemented at scale, CRP testing could be carried out using simple lateral flow devices that can be used by relatively untrained personnel. Such tests have been shown to be accurate and available at under $0.5 [ 15 , 23 ]. By way of comparison World Health Organisation (WHO) pre-qualified lateral flow malaria rapid diagnostic tests (RDTs) are available at under $0.3.…”

Section: Methodsmentioning

confidence: 99%

“…Point-of-care (PoC) CRP tests are commercially available and can be performed in primary care using capillary blood samples, with results available within minutes [ 14 , 15 ]. This approach is already taken in a number of high income countries such as Norway and Sweden [ 16 ] and is recommended by Public Health England and the National Institute for Health and Clinical Excellence (NICE) [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

C-reactive protein point of care testing in the management of acute respiratory infections in the Vietnamese primary healthcare setting – a cost benefit analysis

Lubell

Nguyen

et al. 2018

Antimicrob Resist Infect Control

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AimWe assess the cost-benefit implications of C-reactive protein (CRP) testing in reducing antibiotic prescription for acute respiratory infection in Viet Nam by comparing the incremental costs of CRP testing with the economic costs of antimicrobial resistance averted due to lower antibiotic prescribing.FindingsPatients in the CRP group and the controls incurred similar costs in managing their illness, excluding the costs of the quantitative CRP tests, provided free of charge in the trial context. Assuming a unit cost of $1 per test, the incremental cost of CRP testing was $0.93 per patient. Based on a previous modelling analysis, the 20 percentage point reduction in prescribing observed in the trial implies a societal benefit of $0.82 per patient. With the low levels of adherence to the test results observed in the trial, CRP testing would not be cost-beneficial. The sensitivity analyses showed, however, that with higher adherence to test results their use would be cost-beneficial.Electronic supplementary materialThe online version of this article (10.1186/s13756-018-0414-1) contains supplementary material, which is available to authorized users.

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Accuracy of commercially available c-reactive protein rapid tests in the context of undifferentiated fevers in rural Laos

Cited by 23 publications

References 17 publications

Point-of-care C-reactive protein testing to reduce inappropriate use of antibiotics for non-severe acute respiratory infections in Vietnamese primary health care: a randomised controlled trial

Point-of-care C-reactive protein testing to reduce inappropriate use of antibiotics for non-severe acute respiratory infections in Vietnamese primary health care: a randomised controlled trial

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

C-reactive protein point of care testing in the management of acute respiratory infections in the Vietnamese primary healthcare setting – a cost benefit analysis

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