Rapid Diagnostic Tests to Guide Case Management of and Improve Antibiotic Stewardship for Pediatric Acute Respiratory Illnesses in Resource-Constrained Settings: a Prospective Cohort Study in Southwestern Uganda

Abstract

Pediatric acute respiratory illness (ARI) is one of the most common reasons for evaluation at peripheral health centers in sub-Saharan Africa and is frequently managed based on clinical syndrome alone. Although most ARI episodes are likely caused by self-limited viral infections, the majority are treated with antibiotics. This overuse contributes to the development of antimicrobial resistance. To evaluate the preliminary feasibility and potential impact of adding pathogen-specific and clinical biomarker diagnostic testing to existing clinical management algorithms, we conducted a prospective, observational cohort study of 225 children presenting with malaria-negative, febrile ARI to the outpatient department of a semi-urban peripheral health facility in southwestern Uganda from October 2019 to January 2020. In addition to routine clinical evaluation, we performed influenza and Streptococcus pneumoniae antigen testing and measured levels of C-reactive protein, procalcitonin, and lactate in the clinic's laboratory, and conducted a follow-up assessment by phone 7 days later. Almost one-fifth of participants (40/225) tested positive for influenza. Clinical biomarker measurements were low with C-reactive protein of >40 mg/L in only 11% (13/222) of participants and procalcitonin >0.25 ng/mL in only 13% (16/125). All but two children received antibiotic treatment; only 3% (7/225) were admitted. At follow-up, 59% (118/201) of caregivers reported at least one persistent symptom, but fever had resolved for all children. Positive influenza testing was associated with persistent symptoms. In summary, we demonstrate that simple, rapid pathogen-specific testing and biomarker measurement are possible in resource-limited settings and could improve syndromic management and, in turn, antibiotic stewardship. IMPORTANCE Globally, respiratory illness is one of the most common reasons that children seek care. It is often treated inappropriately with antibiotics, which can drive the development of antibiotic resistance. In resource-rich settings, testing for specific pathogens or measurement of clinical biomarkers, such as procalcitonin and C-reactive protein, is often employed to help determine which children should receive antibiotics. However, there are limited data on the use of these tests in resource-constrained, outpatient contexts in sub-Saharan Africa. We enrolled children with respiratory illness presenting to a clinic in southwestern Uganda and performed testing for influenza, Streptococcus pneumoniae, C-reactive protein, and procalcitonin on-site. Almost all children received antibiotics. We demonstrate that employing clinical algorithms that include influenza and clinical biomarker testing could significantly decrease antibiotic prescriptions. Our study therefore provides preliminary data to support the feasibility and potential utility of diagnostics to improve management of respiratory illness in resource-constrained settings.

Keywords: Uganda; antimicrobial stewardship; biomarkers; diagnostics; influenza; pediatric infectious disease; respiratory infections.

FIG 1

Flow diagram of screening and enrollment process for the prospective, observational cohort study of children presenting with febrile acute respiratory illness to Kasese Health Center from October 2019 to January 2020.

FIG 2

The number of participating children with malaria-negative febrile ARI presenting to the outpatient department at Kasese Health Center from October 2019 to January 2020 who had each of the possible influenza test results by study month.

FIG 3

Visual representation of the potential impact of point-of-care testing on antibiotic use. Dark gray figures represent the proportion of children who did not receive antibiotics in our study. The light gray figures represent the proportion of children who received antibiotics in our study but could have potentially avoided treatment if antibiotics were only given to those with (A) hypoxia (SpO2 < 90%) or CRP of >40 mg/L, (B) hypoxia or PCT of <0.5 ng/mL, or (C) negative influenza testing or positive influenza testing with hypoxia. Black figures represent children who received antibiotics in our study and would still receive them employing the additional criteria. The boxed percentages indicate the total proportion of children who would receive antibiotics if each set of criteria were employed to inform treatment decisions.