Impact of introduction of rapid diagnostic tests for malaria on antibiotic prescribing: analysis of observational and randomised studies in public and private healthcare settings

Heidi Hopkins, Katia J Bruxvoort, Matthew E Cairns, Clare I R Chandler, Baptiste Leurent, Evelyn K Ansah, Frank Baiden, Kimberly A Baltzell, Anders Björkman, Helen E D Burchett, Siân E Clarke, Deborah D DiLiberto, Kristina Elfving, Catherine Goodman, Kristian S Hansen, S Patrick Kachur, Sham Lal, David G Lalloo, Toby Leslie, Pascal Magnussen, Lindsay Mangham Jefferies, Andreas Mårtensson, Ismail Mayan, Anthony K Mbonye, Mwinyi I Msellem, Obinna E Onwujekwe, Seth Owusu-Agyei, Hugh Reyburn, Mark W Rowland, Delér Shakely, Lasse S Vestergaard, Jayne Webster, Virginia L Wiseman, Shunmay Yeung, David Schellenberg, Sarah G Staedke, Christopher J M Whitty, Heidi Hopkins, Katia J Bruxvoort, Matthew E Cairns, Clare I R Chandler, Baptiste Leurent, Evelyn K Ansah, Frank Baiden, Kimberly A Baltzell, Anders Björkman, Helen E D Burchett, Siân E Clarke, Deborah D DiLiberto, Kristina Elfving, Catherine Goodman, Kristian S Hansen, S Patrick Kachur, Sham Lal, David G Lalloo, Toby Leslie, Pascal Magnussen, Lindsay Mangham Jefferies, Andreas Mårtensson, Ismail Mayan, Anthony K Mbonye, Mwinyi I Msellem, Obinna E Onwujekwe, Seth Owusu-Agyei, Hugh Reyburn, Mark W Rowland, Delér Shakely, Lasse S Vestergaard, Jayne Webster, Virginia L Wiseman, Shunmay Yeung, David Schellenberg, Sarah G Staedke, Christopher J M Whitty

Abstract

Objectives To examine the impact of use of rapid diagnostic tests for malaria on prescribing of antimicrobials, specifically antibiotics, for acute febrile illness in Africa and Asia.Design Analysisof nine preselected linked and codesigned observational and randomised studies (eight cluster or individually randomised trials and one observational study).Setting Public and private healthcare settings, 2007-13, in Afghanistan, Cameroon, Ghana, Nigeria, Tanzania, and Uganda.Participants 522 480 children and adults with acute febrile illness.Interventions Rapid diagnostic tests for malaria.Main outcome measures Proportions of patients for whom an antibiotic was prescribed in trial groups who had undergone rapid diagnostic testing compared with controls and in patients with negative test results compared with patients with positive results. A secondary aim compared classes of antibiotics prescribed in different settings.Results Antibiotics were prescribed to 127 052/238 797 (53%) patients in control groups and 167 714/283 683 (59%) patients in intervention groups. Antibiotics were prescribed to 40% (35 505/89 719) of patients with a positive test result for malaria and to 69% (39 400/57 080) of those with a negative result. All but one study showed a trend toward more antibiotic prescribing in groups who underwent rapid diagnostic tests. Random effects meta-analysis of the trials showed that the overall risk of antibiotic prescription was 21% higher (95% confidence interval 7% to 36%) in intervention settings. In most intervention settings, patients with negative test results received more antibiotic prescriptions than patients with positive results for all the most commonly used classes: penicillins, trimethoprim-sulfamethoxazole (one exception), tetracyclines, and metronidazole.Conclusions Introduction of rapid diagnostic tests for malaria to reduce unnecessary use of antimalarials-a beneficial public health outcome-could drive up untargeted use of antibiotics. That 69% of patients were prescribed antibiotics when test results were negative probably represents overprescription.This included antibiotics from several classes, including those like metronidazole that are seldom appropriate for febrile illness, across varied clinical, health system, and epidemiological settings. It is often assumed that better disease specific diagnostics will reduce antimicrobial overuse, but they might simply shift it from one antimicrobial class to another. Current global implementation of malaria testing might increase untargeted antibiotic use and must be examined.

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Figures

https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5370398/bin/hoph035417.f1_default.jpg
Fig 1 Risk ratios for antibiotic prescription in randomised studies comparing patients in control settings with patients in settings where malaria rapid diagnostic test intervention was implemented. Weights are from random effects analysis
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5370398/bin/hoph035417.f2_default.jpg
Fig 2 Risk ratios for antibiotic prescription in settings with malaria rapid diagnostic test intervention, comparing patients with positive versus negative malaria test results. Afgh-com/b is not included because risk ratio could not be calculated; comparison is not possible when no patients with positive test results received antibiotic
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5370398/bin/hoph035417.f3_default.jpg
Fig 3 Antibiotic class as proportion of all antibiotics prescribed in each study (control and intervention settings combined). Afghanistan data are from Afgh-pub only; Afgh-com health workers had access only to trimethoprim-sulfamethoxazole. White areas for Cameroon, Nigeria, Afghanistan, and Tanzania-1 indicate that systemic (oral or injectable) antibiotic was prescribed but that name was not specified in study records. Labels indicate classes that accounted for ≥5% of all antibiotics prescribed for each study

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