Point-of-care C-reactive protein measurement by community health workers safely reduces antimicrobial use among children with respiratory illness: results from a stepped wedge cluster-randomized trial in rural Uganda
Authors: Ciccone Emily J. , Hu Di , Preisser John S. , Cassidy Caitlin A. , Kabugho Lydia , Emmanuel Baguma , Kibaba Georget , Mwebembezi Fred , Juliano Jonathan J. , Mulogo Edgar M. , Boyce Ross M. 
Published: May 2024

Background

Acute respiratory illness (ARI) is one of the most common reasons children receive antibiotic treatment. Measurement of C-reaction protein (CRP) to identify children at high risk for bacterial infection has been shown to reduce unnecessary antibiotic use among children with ARI in a range of clinical settings. Yet in many resource-constrained contexts, patients seek care outside the formal health sector, often from lay community health workers (CHW). The objective of this study was to determine the impact of CRP measurement on antibiotic use among children under 5 years of age presenting with febrile ARI to CHW in rural western Uganda.

Methods and Findings

We conducted a stepped wedge cluster randomized trial comparing a clinical algorithm that included CRP measurement by CHW to guide antibiotic treatment decisions (STAR Sick Child Job Aid [SCJA]) with the Integrated Community Care Management (iCCM) SCJA currently in use by CHW in the region. Children under 5 years presenting to CHW in 15 villages in Bugoye sub-county with fever and cough were eligible. The CHW conducted follow-up assessments 7 days after the initial visit. Our primary outcome was the proportion of children who were given or prescribed an antibiotic at the initial visit. Our secondary outcomes were (1) persistent fever on Day 7, (2) development of pre-specified danger signs, (3) unexpected visits to the CHW, (4) hospitalizations, (5) deaths, (6) lack of perceived improvement per the child’s caregiver on Day 7, and (7) clinical failure, which was a composite outcome of persistence of fever on Day 7, development of danger signs, hospitalization, or death.

The 65 participating CHW enrolled 1,280 children, 1,220 (95.3%) of whom had sufficient data to be included in this analysis; 48% (587/1,220) and 52% (633/1,220) were enrolled during control (iCCM SCJA) and intervention periods (STAR SCJA), respectively. The observed percentage of children who were given or prescribed antibiotics at the initial visit was 91.8% (539/587) in the control periods as compared to 70.8% (448/633) during the intervention periods (prevalence difference -21.0%; 95% CI: (-30.4%, - 11.7%). The odds of antibiotic prescription by the CHW were over 80% lower in the intervention as compared to the control periods (OR 0.18, 95% CI (0.07-0.45)). There was no difference in frequency of clinical failure or lack of perceived improvement by the caregiver between groups. There were no unexpected visits to the CHW or deaths in either group.

Conclusions

Incorporating CRP measurement into iCCM algorithms for evaluation of children with febrile ARI by CHW in rural Uganda decreased antibiotic use without negatively affecting clinical outcomes. These findings support expanded access to simple, point-of-care diagnostics to improve antibiotic stewardship in rural, resource-constrained settings where individuals with limited medical training provide a substantial proportion of care.