Monitoring antibacterial use in children under five years in rural communities of Northern Uganda

Abstract

Background: Acute respiratory tract infections (ARIs) and diarrhea are leading causes of childhood morbidity and mortality in low- and middle-income countries (LMICs), the burden is high among children under five years of age, and there is a high frequency of use of antibacterials in children who suffer community acquired infectious diseases. Children with community acquired infections are often inappropriately treated with antibacterials, and this is likely to increase the risk of emergence of antibacterial resistance. Regular and objective monitoring of antibacterial use is a pre-requisite for appropriate treatment, but this is often not done in children under five years. Self-reports of medicine use that are often utilized in such studies have often been reported as having low validity thereby necessitating the use of more objective monitoring tools. Aim: The overall aim of this study was to monitor the use of antibacterials in children under five years in rural communities of northern Uganda. Method: This study was divided into three sub-studies. Sub-study one used a cross-sectional study design to assess the use of antibacterials in children under five years with acute respiratory tract infections (ARIs) and/or diarrhea in households in rural communities. Data were collected through interviews of the care-givers of children under five years that had ARIs and/or diarrhea, using a structured interviewer administered questionnaire. Sub-study two was an experimental study where, a qualitative liquid chromatography with tandem mass spectrometry (LC-MS/MS) method was developed and validated for identification of fifteen (15) antibacterials in dried blood spots (DBS) and dried urine spots (DUS)). In sub-study three, the validity of care-giver reports on prior administration of antibacterials was investigated in a cross-sectional study that was conducted among children under five years seeking care at healthcare facilities in Gulu district, northern Uganda. Using a researcher administered questionnaire, data were obtained from care-givers regarding reported antibacterial intake prior to visiting the healthcare facility. After collecting data on prior antibacterial intake, urine and blood samples were collected from the children on filter paper. These reports were validated by comparing them to the antibacterials detected in blood and urine samples collected from the children using LC-MS/MS methods. Results: In sub-study one, 856 children under five years who had ARIs (52.1% male, mean age 30± 17 (SD) months) and 318 who had diarrhea (55% male, mean age 19 ± 5 (SD) months) were recruited in the study. The prevalence of antibacterial use in children under five who presented with symptoms of ARIs was 60.2% (95% CI: 54.5-65.6), while the prevalence of antibacterial use in under children five years with diarrhea was 52% (95% CI: 46-57). The determinants of antibacterial use in children under five years with ARIs include, getting treatment from a healthcare facility (AOR: 1.85, CI: 1.34-2.56), households located in peri-urban areas (AOR: 2.54, CI: 1.34-4.84) and presence of cough (AOR: 7.02, CI: 4.36-11.31)., while the determinants of antibacterial use in those who had diarrhea include, getting treatment from a healthcare facility (AOR: 1.76, CI: 1.06-2.93), households located in peri-urban areas (AOR: 3.41, CI: 1.65-7.08) and having diarrhea with ARIs (AOR: 3.09, CI: 1.49-6.42). In sub-study two, a qualitative method using liquid chromatography with tandem mass spectrometry, was developed and validated for simultaneous identification of 15 antibacterials in dried blood and dried urine samples. In sub-study three, 355 (53.2% female, median age 29 (IQR: 16-46) months) children under five years were recruited in the study. There was a low validity for self-reported antibacterial intake prior to healthcare facility visit with a sensitivity, specificity, positive predictive value, negative predictive value, agreement and kappa coefficient of; 17.3% (95% CI: 12.6-22.8), 90.7% (95% CI: 84.3-95.1), 76.5% (95% CI: 62.5-87.2), 38.5% (95% CI: 33.0-44.2) 43.9% (95% CI: 38.7-49.3%) and 0.06 (0.01-0.12) respectively. Conclusions and recommendations: The use of antibacterials among children under five years with ARIs and diarrhea is high in communities of Gulu district, northern Uganda. The validity of care-givers’ reports on intake of antibacterials by their children prior to healthcare facility visit is low, however a qualitative LC-MS/MS method can be used to determine the prevalence of prior intake of antibacterials. There is therefore need for targeted education on appropriate antibacterial use in rural communities and hospital settings where over prescription is most likely.