DISCUSSION
pneumonia, bacterial infection, fever, malaria, otitis, malaria infection, febrile diseases
PNEUMONIA, BACTERIAL INFECTION, OTITIS, MALARIA, INFECTION
This study shows the potential of interventions to improve the diagnosis and management of febrile diseases and reduce inappropriate prescriptions of antibiotics in children and young people under 18 years attending primary outpatient facilities without compromising clinical outcomes in Burkina Faso. The intervention resulted in significant reductions in antibiotic prescriptions overall, both in relative (29%) and absolute terms (17%), which would save 1 inappropriate antibiotic prescription for every 6 children and adolescents consulting for fever at our peripheral healthcare facilities. The effect was seen in children under 5 years and in those between 10 and 18 years of age.This approach also lends itself to further targeting the intervention, as the largest gains were obtained in patients who tested negative for malaria (1 fewer prescription for every 5 tested) and those with a respiratory presentation (1 fewer prescription for every 6 tested).These effects in malaria-negative cases are particularly important, since an unfortunate side-effect of the WHO's recommendation to confirm malaria infection through rapid diagnostic testing prior to the administration of antimalarial treatment [In the control arm, the antibiotic-prescribing rate with routine practice was approximately 57.5% which is 20% lower than expected based on previous years in these facilities [A more substantial reduction in antibiotic prescription was observed in the dry season (28%) compared with the rainy season (14.4%). Several factors may explain these findings: (1) the limits of histidine-rich protein 2 (HRP2)-based RDTs could hide a potential bacterial infection in the intervention arm [15,24]; (2) the fear of overlooking a potential and treatable bacterial infection in the control arm could lead to antibiotic misuse; and (3) CRP levels can be elevated with a malaria infection, which could also lead to antibiotic misuse [The diagnostic algorithm used in this study recommended that CRP and WBC be tested systematically on all patients in the intervention arm, while the use and choice of pathogen-specific POCTs should be based on clinical presentation according to age. Exceptions to this were children under 5 years who met the criteria for pneumonia (as defined by the WHO) or otitis. In this study, approximately 10.4% (otitis: 2.7%; pneumonia: 7.5%) of children aged 6–59 months in the intervention arm met the clinical criteria for antibiotic prescription based on clinical outcomes alone versus 9.6% in standard practice. Such a small rate of antibiotic prescriptions reported in both arms was based on clinical examination only. This low level of antibiotic prescriptions has also been reported in previous studies of IeDA [23,28,29].Last, the results of this study provide evidence that the intervention in patients aged 5–10 years may be associated with increased antibiotic prescriptions compared with standard of care. However, all cases of hospitalization and treatment failures in this age group were reported in standard practice. This may be because patients in this age group attending outpatient facilities were nonsevere cases, most of whom who did not need antibiotics to improve their clinical outcome. As mentioned previously, the limitations of HRP2-based RDTs and CRP tests to correctly identify patients who require antibiotics could also explain these findings.The improved adherence to prescriptions reported in this study as a result of the implementation of biological POCTs is in line with other studies conducted in LMICs [21,30,31]. Indeed, participants in the intervention arm were more likely to follow healthcare prescriptions, suggesting that, in outpatient facilities, the lack of a T&C package may have contributed to lower adherence to antibiotic prescriptions. The reasonable waiting time of participants in intervention arm can also be a factor that also influenced the adherence to healthcare prescriptions.The study has some limitations. First, this was an individual randomized controlled trial where the intervention package, including the T&C package, was designed for participants in the intervention arm only. The impact of the intervention might have been underestimated as a consequence of potential contamination of arms—that is, that the impact of the T&C package could be diluted due to participants and/or caregivers in both the intervention and control arms living in the same areas. Second, as this was a diagnostic trial conducted at an outpatient clinic and health facility, there is the possibility that nurses' adherence to clinical criteria may have led to deviations from the predefined protocol.In conclusion, the proposed intervention package has the potential to reduce unnecessary prescription of antibiotics compared with standard practice without affecting clinical outcomes. The size of the effect varied with age and season, and was particularly marked in patients who tested negative for malaria and those with a respiratory diagnosis.