Impact of a package of diagnostic tools, clinical algorithm, and training and communication on outpatient acute fever case management in low- and middle-income countries: protocol for a randomized controlled trial

Olawale Salami,David Kaawa-Mafigiri,Rita Baiden,Sarabjit Chadha ,Philip Horgan,Vida Kukula,Freddy Eric Kitutu ,James Kapisi,Stefano Ongarello,Adélaïde Compaoré ,Catrin E Moore,Cassandra Kelly-Cirino,Shanta Dutta,Heidi Hopkins,Frank Smithuis,Asadu Sserwanga,Ashish Pathak,Myo Maung Maung Swe,Kāmini Walia ,Rashida Hussein,Abhishek Giri,Anjana Tomar,Halidou Tinto,Buddha Basnyat,Summita Udas Shakya,François Kiemdé ,Neelam Taneja,Gajanan Phutke,Piero Olliaro

doi:10.1186/s13063-020-04897-9

Abstract

BackgroundThe management of acute febrile illnesses places a heavy burden on clinical services in many low- and middle-income countries (LMICs). Bacterial and viral aetiologies of acute fevers are often clinically indistinguishable and, in the absence of diagnostic tests, the ‘just-in-case’ use of antibiotics by many health workers has become common practice, which has an impact on drug-resistant infections.Our study aims to answer the following question: in patients with undifferentiated febrile illness presenting to outpatient clinics/peripheral health centres in LMICs, can we demonstrate an improvement in clinical outcomes and reduce unnecessary antibiotic prescription over current practice by using a combination of simple, accurate diagnostic tests, clinical algorithms, and training and communication (intervention package)?MethodsWe designed a randomized, controlled clinical trial to evaluate the impact of our intervention package on clinical outcomes and antibiotic prescription rates in acute febrile illnesses. Available, point-of-care, pathogen-specific and non-pathogen specific (host markers), rapid diagnostic tests (RDTs) included in the intervention package were selected based on pre-defined criteria. Nine clinical study sites in six countries (Burkina Faso, Ghana, India, Myanmar, Nepal and Uganda), which represent heterogeneous outpatient care settings, were selected. We considered the expected seasonal variations in the incidence of acute febrile illnesses across all the sites by ensuring a recruitment period of 12 months. A master protocol was developed and adapted for country-specific ethical submissions. Diagnostic algorithms and choice of RDTs acknowledged current data on aetiologies of acute febrile illnesses in each country. We included a qualitative evaluation of drivers and/or deterrents of uptake of new diagnostics and antibiotic use for acute febrile illnesses. Sample size estimations were based on historical site data of antibiotic prescription practices for malarial and non-malarial acute fevers. Overall, 9 semi-independent studies will enrol a minimum of 21,876 patients and an aggregate data meta-analysis will be conducted on completion.DiscussionThis study is expected to generate vital evidence needed to inform policy decisions on the role of rapid diagnostic tests in the clinical management of acute febrile illnesses, with a view to controlling the rise of antimicrobial resistance in LMICs.Trial registrationClinicaltrials.gov NCT04081051. Registered on 6 September 2019. Protocol version 1.4 dated 20 December 2019

Highlights

The management of acute febrile illnesses places a heavy burden on clinical services in many lowand middle-income countries (LMICs)
Study objectives This study aims to address the following question that is based on the PICO process [17]: In children and adolescents (+/− adults) who present to outpatient clinics or peripheral health centres in LMICs with acute febrile illness (Population), will introducing a package of available diagnostic tests, diagnostic algorithms, new clinic process flows, and training and communication for healthcare workers and patients or caregivers (Intervention), as compared with current practice (Control), improve case management of acute febrile illnesses and better target the correct use of antibiotics (Outcome)?
The FIND AMR Diagnostics Use Accelerator is a platform to evaluate a package of interventions and provide evidence to inform policy change that can positively impact antimicrobial resistance (AMR) and contribute to universal health coverage (UHC)

Summary

Introduction

The management of acute febrile illnesses places a heavy burden on clinical services in many lowand middle-income countries (LMICs). Bacterial and viral aetiologies of acute fevers are often clinically indistinguishable and, in the absence of diagnostic tests, the ‘just-in-case’ use of antibiotics by many health workers has become common practice, which has an impact on drug-resistant infections. Most health facilities in LMICs lack the diagnostic capacity to correctly identify the cause of an acute febrile illness, undermining a health worker’s ability to determine whether an antibiotic is required or not [6]. To this end, an adaptation in prescription practices needs to occur to improve patient management by healthcare staff and to change patient behaviours as well as treatment-seeking behaviours. Success will mean making significant steps toward achieving the dual goal of tackling AMR and providing universal health coverage (UHC)

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