Heidi Hopkins, associate professor in malaria and diagnostics1, Katia J Bruxvoort, assistant professor in epidemiology1, Matthew E Cairns, associate professor in epidemiology1, Clare I R Chandler, associate professor in medical anthropology1, Baptiste Leurent, assistant professor in medical statistics and epidemiology1, Evelyn K Ansah, deputy director2, Frank Baiden, lecturer in epidemiology3, Kimberly A Baltzell, associate professor4, Anders Björkman, professor5, Helen E D Burchett, assistant professor1, Siân E Clarke, associate professor in malaria research and control1, Deborah D DiLiberto, PhD candidate1, Kristina Elfving, paediatrician6, Catherine Goodman, reader in health economics and policy1, Kristian S Hansen, lecturer in health economics, associate professor1 7, S Patrick Kachur, malaria branch chief8, Sham Lal, research fellow1, David G Lalloo, professor of tropical medicine9, Toby Leslie, department visitor,, clinical trial manager1 10, Pascal Magnussen, senior researcher11, Lindsay Mangham Jefferies, assistant professor in health economics1, Andreas Mårtensson, professor of international child health12, Ismail Mayan, clinical trial manager10, Anthony K Mbonye, director health services, associate professor13 14, Mwinyi I Msellem, medical laboratory scientist15, Obinna E Onwujekwe, professor16, Seth Owusu-Agyei, director1 17, Hugh Reyburn, senior lecturer in clinical epidemiology1, Mark W Rowland, professor of medical entomology and vector control1, Delér Shakely, physician and researcher18, Lasse S Vestergaard, senior research associate19, Jayne Webster, associate professor1, Virginia L Wiseman, associate professor in health economics, associate professor1 20, Shunmay Yeung, associate professor in tropical medicine1, David Schellenberg, professor of malaria and international health1, Sarah G Staedke, professor of malaria and global health1, Christopher J M Whitty, professor of public and international health

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.

BMJ