Advancing Access to Diagnostic Innovation Essential for UHC and AMR Prevention

Background and rationale. 'Just-in-case' antibiotic prescribing practices is one of the causes of inadequate management of 'acute febrile illnesses' and AMR in Low- and Middle-income Countries (LMICs). At the same time, some people who would require antibiotic treatment do not get it. An improvement in case management and prescription practice might lead to a decrease in morbidity and mortality. Success will mean making significant steps toward achieving the dual goal of improving UHC and tackling AMR.

The PICO question addressed is: in children/ adolescents and adults (Population) presenting to outpatient clinics / peripheral health centres in LMICs with acute febrile illness/Respiratory Tract Infection can a combination of available PoC rapid diagnostic tests, diagnostic aids/algorithms, clinic process flow and, training and communication (Intervention) improve management of acute febrile illnesses and better target the use of antibiotics / reduce unnecessary antibiotic prescriptions (Outcomes) compared to current practice (Control)?

Primary objective(s).

To evaluate the impact of a package of interventions (point of care [PoC] tests, clinical algorithm, clinic process flow, training and communication tools) on clinical outcomes and antibiotic prescriptions, with standard-of-care practices, in children and adolescents presenting with acute febrile illnesses (defined as fever with no focus or Respiratory Tract Infection lasting for no more than 7 days), at outpatient clinics.

Secondary objective(s)

• To improve the management of acute febrile illness
• To promote rational and targeted use of antibiotics for acute febrile illness
• To determine the aetiology of fever in patients presenting to outpatient facilities using available PoC diagnostic tests
• To study the safety and feasibility of a package of interventions compared to current practice of care
• To assess the effectiveness of training and communication tools to adherence to the prescribed treatment

Primary endpoints

• Proportion of outpatient cases of acute febrile illness with favourable outcome (defined as being alive and asymptomatic).
• antibiotic prescriptions rates for acute febrile illness in the clinic Secondary endpoints (outcomes) 1. Duration of time spent in the clinic

• Proportion of patients treated for specific bacterial infection 3. Proportion of patients with disease specific diagnosis identified by PoC tests 4. Frequency of serious adverse event (SAE) within 7 days of recruitment 5. Frequency of unscheduled (unplanned) visit within 7 days of recruitment 6. Training and communication package uptake 7. Proportion of patients prescribed antibiotic at clinic who reported adherence to prescription on day 7 8. Proportion of patients who were not prescribed antibiotics at clinic who received antibiotics elsewhere between day 0 and day 7 9. Behaviour Change Intervention Recommendations

Trial design: A multi-centre, open label, two arm, randomized-controlled trial

Trial sites: This study will be conducted in outpatient departments and primary care clinics in Burkina Faso, Ghana, India, Nepal and Uganda.

Trial population: The study population will consist of children, adolescents and adults presenting to the health care facility, or provider, with acute fever or history of fever

Sample Size: 19,922

Inclusion criteria

• Patients presenting with fever with no focus/RTI:

• Children (6 months to <12 years) and adolescents (12 years to less than 18 years old) of both sexes .
• Presenting with an acute febrile illness defined as temperature of >37.5°C or history of fever within the last 7 days with no focus or suspected RTI.
• Parent/guardian providing written informed consent for their children if less than 18 years of age.
• Obtain assent for adolescent between 12 and less than 18 years old
• Willing to provide blood and other samples and adhere to study procedures explained in the consent forms following the protocol.
• Available and willing to return for follow-up visit at the health facility on day 7 (+/- 2 days).

Exclusion criteria

• o Children and adolescents from 6 months to less than 18 years old presenting with chronic febrile illness (fever lasting more than 7 days).

• Patients with acute febrile illness outside the allowed age range for the site.
• Severely ill patients requiring hospital admission or referral as assessed by the study clinicians.
• Anyone refusing consent to the study or not able to attend the health centre for follow-up (adults, the children of parents/guardians, or adolescents who refuse or are missed when asking for consent).