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Economic considerations support C-reactive protein testing alongside malaria rapid diagnostic tests to guide antimicrobial therapy for patients with febrile illness in settings with low malaria endemicity.

ABSTRACT: Malaria is no longer a common cause of febrile illness in many regions of the tropics. In part, this success is a result of improved access to accurate diagnosis and effective anti-malarial treatment, including in many hard-to-reach rural areas. However, in these settings, management of other causes of febrile illness remains challenging. Health systems are often weak and other than malaria rapid tests no other diagnostics are available. With millions of deaths occurring annually due to treatable bacterial infections and the ever increasing spread of antimicrobial resistance, improvement in the management of febrile illness is a global public health priority. Whilst numerous promising point-of-care diagnostics are in the pipeline, substantial progress can be made in the interim with existing tools: C-reactive protein (CRP) is a highly sensitive and moderately specific biomarker of bacterial infection and has been in clinical use for these purposes for decades, with dozens of low-cost devices commercially available. This paper takes a health-economics approach to consider the possible advantages of CRP point-of-care tests alongside rapid diagnostic tests for malaria, potentially in a single multiplex device, to guide antimicrobial therapy for patients with febrile illness. Three rudimentary assessments of the costs and benefits of this approach all indicate that this is likely to be cost-effective when considering the incremental costs of the CRP tests as compared with either (i) the improved health outcomes for patients with bacterial illnesses; (ii) the costs of antimicrobial resistance averted; or (iii) the economic benefits of better management of remaining malaria cases and shorter malaria elimination campaigns in areas of low transmission. While CRP-guided antibiotic therapy alone cannot resolve all challenges associated with management of febrile illness in remote tropical settings, in the short-term a multiplexed CRP and malaria RDT could be highly cost-effective and utilize the well-established funding and distribution systems already in place for malaria RDTs. These findings should spark further interest amongst industry, academics and policy-makers in the development and deployment of such diagnostics, and discussion on their geographically appropriate use.

SUBMITTER: Lubell Y

PROVIDER: S-EPMC6933672 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Economic considerations support C-reactive protein testing alongside malaria rapid diagnostic tests to guide antimicrobial therapy for patients with febrile illness in settings with low malaria endemicity.

Lubell Yoel Y Chandna Arjun A Smithuis Frank F White Lisa L Wertheim Heiman F L HFL Redard-Jacot Maël M Katz Zachary Z Dondorp Arjen A Day Nicholas N White Nicholas N Dittrich Sabine S

Malaria journal 20191226 1

Malaria is no longer a common cause of febrile illness in many regions of the tropics. In part, this success is a result of improved access to accurate diagnosis and effective anti-malarial treatment, including in many hard-to-reach rural areas. However, in these settings, management of other causes of febrile illness remains challenging. Health systems are often weak and other than malaria rapid tests no other diagnostics are available. With millions of deaths occurring annually due to treatabl ...[more]

PMID: 31878978

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Project description:BackgroundUganda embraced the World Health Organization guidelines that recommend a universal 'test and treat' strategy for malaria, mainly by use of rapid diagnostic test (RDT) and microscopy. However, little is known how increased parasitological diagnosis for malaria influences antibiotic treatment among patients with febrile illness.MethodsData collection was carried out within a feasibility trial of presumptive diagnosis of malaria (control) and two diagnostic interventions (microscopy or RDT) in a district of low transmission intensity. Five primary level health centres (HCs) were randomized to each diagnostic arm (diagnostic method in a defined group of patients). All 52,116 outpatients (presumptive 16,971; microscopy 17,508; and RDT 17,638) aged 5 months to ninety five years presenting with fever (by statement or measured) were included. Information from outpatients and laboratory registers was extracted weekly from March 2010 to July 2011. The proportion of patients who were prescribed antibiotics was calculated among those not tested for malaria, those who tested positive and in those who tested negative.ResultsSeven thousand and forty (41.5%) patients in the presumptive arm were prescribed antibiotics. Of the patients not tested for malaria, 1,537 (23.9%) in microscopy arm and 810 (56.2%) in RDT arm were prescribed antibiotics. Among patients who tested positive for malaria, 845 (25.8%) were prescribed antibiotics in the RDT and 273(17.6%) in the microscopy arm. Among patients who tested negative for malaria, 7809 (61.4%) were prescribed antibiotics in the RDT and 3749 (39.3%) in the microscopy arm. Overall the prescription of antibiotics was more common for children less than five years of age 5,388 (63%) compared to those five years and above 16798 (38.6%).ConclusionPrescription of antibiotics in patients with febrile illness is high. Testing positive for malaria reduces antibiotic treatment but testing negative for malaria increases use of antibiotics.Trial registrationClinicalTrials.gov: NCT00565071.

Project description:Background: Across Southeast Asia, declining malaria incidence poses a challenge for healthcare providers, in how best to manage the vast majority of patients with febrile illnesses who have a negative malaria test. In rural regions, where the majority of the population reside, empirical treatment guidelines derived from central urban hospitals are often of limited relevance. In these settings, health workers with limited training deliver care, often without any laboratory diagnostic support. In this paper, we model the impact of point-of-care C-reactive protein testing to inform the decision to prescribe antibiotics and regional surveillance data to inform antibiotic selection, and then simulate the subsequent impact on mortality from febrile illnesses, rooted in the real-world context of rural Savannakhet province, southern Laos. Methods: Our model simulates 100 scenarios with varying quarterly incidence of six key pathogens known to be prevalent in rural Laos. In the simulations, community health workers either prescribe antibiotics in-line with current practice as documented in health facilities in rural Laos, or with the aid of the two interventions. We provide cost-effectiveness estimates for each strategy alone and then for an integrated approach using both interventions. Results: We find that each strategy is predicted to be highly cost-effective, and that the combined approach is predicted to result in the biggest reduction in mortality (averting a predicted 510 deaths per year in rural Savannakhet, a 28% reduction compared to standard practice) and is highly cost-effective, with an incremental cost-effectiveness ratio of just $66 per disability-adjusted life year averted. Conclusions: Substantial seasonal variation in the predicted optimal empirical antibiotic treatment for febrile illness highlights the benefits of up-to-date information on regional causes of fever. In this modelling analysis, an integrated system incorporating point-of-care host biomarker testing and regional surveillance data appears highly cost-effective, and may warrant piloting in a real-life setting.

Project description:ObjectiveTo compare rapid diagnostic tests (RDTs) for malaria with routine microscopy in guiding treatment decisions for febrile patients.DesignRandomised trial.SettingOutpatient departments in northeast Tanzania at varying levels of malaria transmission.Participants2416 patients for whom a malaria test was requested.InterventionStaff received training on rapid diagnostic tests; patients sent for malaria tests were randomised to rapid diagnostic test or routine microscopyMain outcome measureProportion of patients with a negative test prescribed an antimalarial drug.ResultsOf 7589 outpatient consultations, 2425 (32%) had a malaria test requested. Of 1204 patients randomised to microscopy, 1030 (86%) tested negative for malaria; 523 (51%) of these were treated with an antimalarial drug. Of 1193 patients randomised to rapid diagnostic test, 1005 (84%) tested negative; 540 (54%) of these were treated for malaria (odds ratio 1.13, 95% confidence interval 0.95 to 1.34; P=0.18). Children aged under 5 with negative rapid diagnostic tests were more likely to be prescribed an antimalarial drug than were those with negative slides (P=0.003). Patients with a negative test by any method were more likely to be prescribed an antibiotic (odds ratio 6.42, 4.72 to 8.75; P<0.001). More than 90% of prescriptions for antimalarial drugs in low-moderate transmission settings were for patients for whom a test requested by a clinician was negative for malaria.ConclusionsAlthough many cases of malaria are missed outside the formal sector, within it malaria is massively over-diagnosed. This threatens the sustainability of deployment of artemisinin combination treatment, and treatable bacterial diseases are likely to be missed. Use of rapid diagnostic tests, with basic training for clinical staff, did not in itself lead to any reduction in over-treatment for malaria. Interventions to improve clinicians' management of febrile illness are essential but will not be easy.Trial registrationClinical trials NCT00146796 [ClinicalTrials.gov].

Dataset Information

Economic considerations support C-reactive protein testing alongside malaria rapid diagnostic tests to guide antimicrobial therapy for patients with febrile illness in settings with low malaria endemicity.

Publications

Economic considerations support C-reactive protein testing alongside malaria rapid diagnostic tests to guide antimicrobial therapy for patients with febrile illness in settings with low malaria endemicity.

Similar Datasets

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