DISCUSSION
illness, acute febrile illnesses, malaria, presenting syndrome, nonbacterial, typhoid, bacterial infections, febrile, acute febrile illness
MALARIA, BACTERIAL INFECTIONS, SYNDROMES, TYPHOID
This trial evaluated the impact on antibiotic prescribing and clinical outcomes, for child and adult outpatients with acute febrile illness who presented to public health centers in Uganda, of an intervention that provided diagnostic POCTs along with a case-management algorithm and behavior change materials.A primary goal of diagnostic interventions like the one in this study is to improve antibiotic stewardship—that is, to improve targeting of antibiotics by providing them to patients with bacterial infections while reducing unnecessary use in those with nonbacterial illnesses. In this study, the overall impact on antibiotic prescribing was not consistent across sites and patient subgroups. The use of a clinical algorithm and diagnostic POCTs did not demonstrate a substantial reduction in antibiotic prescribing in the intervention arm, except in patients with a negative malaria test who were consistently prescribed fewer antibiotics. There are a few potential reasons for this.First, our intervention introduced commercially available POCTs for specific bacterial infections (typhoid, group A In addition, the intervention-arm diagnostic and treatment algorithm allowed for clinical judgment on the part of the treating clinician rather than strict adherence to the results of diagnostic tests. This is important as the nuances of individual cases cannot adequately be addressed in a simple algorithm, but again, experience implementing malaria RDTs in similar settings has shown a range of adherence to test results in prescribing practices [Finally, the impact of the intervention on antibiotic prescribing in our study may have been limited by the study design. While many patients were enrolled, just a few clinicians were responsible for diagnosis and prescribing decisions—1 clinician per site for the intervention arm and 2 or 3 clinicians per site for the control arm. These staffing levels were appropriate for the typical patient flow at each health center but mean that individual clinician preferences could have had an outsized influence on diagnoses made and prescribing practices observed. Furthermore, the intervention- and control-arm activities at each site were conducted in the same building; however, the clinical and laboratory staff for each arm were different personnel who worked in separate rooms, reducing the risk of cross-contamination. In addition, our results may not be directly extrapolatable to the potential uptake of the POCT panel and strategy by clinicians working under routine conditions at Ugandan health centers, because intervention-arm clinicians were hired specifically for the study. This was necessary to avoid overloading the government-employed staff who provide routine care at participating health centers, but the issue of how to sustainably incorporate diagnostics into routine care in these settings needs to be addressed in any future implementation work.The second main objective of this study was to evaluate the impact of the intervention on patients' clinical outcomes. The study was conducted only among outpatients who presented without signs of severe illness, a group for whom, in general, poor outcomes are rare, and fortunately, the large majority of patients at all sites and study arms had favorable outcomes. The fact that statistically significant differences were not seen between study arms, even within subgroup analyses stratified by age, presenting syndrome, and other features, may be explained by the fact that many outpatient febrile illnesses are likely due to self-limiting causes—viral, bacterial, or other—that eventually would resolve satisfactorily without specific treatment [A strength of this study is its inclusion of both adult and child patients older than 1 year, allowing the assessment of potential prescribing and outcome differences across age groups. In keeping with observations elsewhere [More amoxicillin was prescribed for intervention-arm patients, presumably due to algorithm guidance for respiratory syndromes. Antibiotic choice for empiric prescribing varied across sites, likely due to local availability, individual health facility and clinician preferences, as was seen in control arms in this study and in other studies in similar settings [In conclusion, this study found that a diagnostic intervention for the management of febrile outpatients did not achieve the desired impact on antibiotic prescribing at 3 diverse and representative sites in Uganda. Further work is needed to design and evaluate effective strategies to safely reduce inappropriate antibiotic use and improve antibiotic targeting for patients with acute febrile illnesses in similar settings.