The use of antibiotics prior to a hospital visit is a common practice in many resource-limited settings and a potential threat to antibiotics stewardship and resistance globally. The current facility-based study investigated pre-hospital antibiotic use among children presenting with fever at a tertiary health facility in northern Uganda and offers new insights and understanding of inappropriate antibiotic use among children in a resource-limited context.
Prevalence of antibiotics use in children with fever prior to a hospital visit
The prevalence of pre-hospital exposure to antibiotics in this study was 39.5%, over half (54.5%) of which were on a self-treatment basis and 44.5% as empiric prescriptions from clinics or other health units. This finding is similar to the 40.1% antibiotic use by caregivers of children with fever reported in Kenya [
24]. Our prevalence, however, is lower than the 70.5% and 69% previously reported in Uganda [
25] and Vietnam [
26] respectively, but higher than the 13.5% reported in an Iranian study [
15]. The 39.5% rate of antibiotic use in the current study could, however, be an underestimate as evidenced by a recent finding indicating a low validity of caregivers’ reports on prior intake of antibacterials by their children (14.4% reported vs 63.7% antibacterial detection in blood and urine samples) [
27]. It is also possible that the covid-19 pandemic could have had an impact on the level of antibiotic use, drawing from a recent report from Kampala, Uganda’s capital city, showing a general reduction in access to maternal and child health services during the covid-19-related lockdowns and restrictions [
28]. However, it’s difficult to state with certainty in which direction this could have affected antibiotics use.
The high prevalence of antibiotic use in our study may not be surprising as most of the antibiotics in Uganda, just like in many low-income countries, can be bought from private pharmacies without prescription by qualified health providers. This is concerning and could present enormous challenges, including delayed healthcare seeking, exacerbating or masking symptoms, affecting the laboratory diagnostic results, as well as the development of antimicrobial resistance [
29]. While antibacterial resistance will often develop, the risk is likely to be higher with inappropriate use and self-medication [
30].
The antibiotics used prior to a hospital visit in the current study were mainly bought from the drug shops on a non-prescription basis, given from a clinic on empiric prescription, remnants at home, or picked from a neighbour. This finding resonates with that reported in China where one-third of caregivers used leftover antibiotics to treat fever and respiratory problems [
31] and attests to an earlier finding in Uganda that pharmacies, drug shops, and clinics dispense whatever medicines the client requests [
19]. The use of home remnants of antibiotics as found in this study should be concerning given the usually un-ideal storage conditions and risks of expiry, rendering the medicines ineffective due to loss of potency, besides toxic metabolites [
32]. Further analysis in this study indicates that caregivers from rural settings were more likely to use leftovers of drugs in the house or pick drugs from their neighbours and friends, than the urban dwellers. This finding mirrors one previously reported in Nigeria - postulated to be a result of the homogenous nature of the rural residents with regards to culture as opposed to the urban dwellers who tend to be heterogeneous with differing cultural backgrounds [
33]. The rural-urban difference may also be attributed to the fact that urban residents are more exposed to health educative information from the media, as well as the ease of access to primary healthcare facilities. In fact, in this study, the caregivers from the urban areas were more likely to be living within less than 5 km from the nearest health facility compared to their rural counterparts. The fact that the respondents in this study did not significantly, in their first actions, use the primary health centres meant to be the first points of contact might be that they were not easily accessible geographically or a reflection of the level of confidence they have in these lower public health facilities to manage their children’s conditions.
The main reasons advanced by the respondents for, largely inappropriate, pre-hospital use of antibiotics, included: advice from a relative, having always used the drug for febrile illnesses, advice from a health worker, long-distance to a health facility, the drug being previously prescribed by a health worker, and long waiting time in hospitals, among others. This finding seems to agree with that in earlier reports among adults presenting to hospitals in the study setting [
3] and Malawi [
29], where previous experience with the antibiotics informed patient’s choice for self-medication, despite their limited knowledge regarding the therapeutic indications and correct dosage schedule [
29]. The influence of distance to a health facility and lengthy-time at health facilities on inappropriate use of antibiotics as found in this study resonates with findings reported in Tanzania [
34] and Nigeria [
10], and speak to the health system challenges in low-income countries. Importantly, our finding also implies that the inappropriate use of antibiotics can be blamed not on patients alone because the healthcare workers also played a contributory role through inappropriate advice and prescriptions. While the study covered only a short time period, we believe the results would not have vastly varied by time points since antibiotics use in Uganda is not believed to vary a lot with seasonality, being driven by the year-round high burden of infectious causes of morbidity coupled with the weak antibiotic stewardship.
Antibiotics commonly used among children with fever
The antibiotics most commonly used by children under five years with fever, largely inappropriately, included amoxicillin, followed by erythromycin, metronidazole, ciprofloxacin and ampicillin. This finding mirrors that reported in a study in Lagos State University Teaching Hospital, Nigeria, where amoxicillin, ampicillin/cloxacillin, cotrimoxazole and Amoxil-clavulanic acid were the common antibiotics used for the treatment of children with fever [
15]. Similarly, in Vietnam, ampicillin, amoxicillin, cephalosporins, sulphonamides, trimethoprim and macrolides were the most commonly used drugs for treating children with fever [
13]. This finding has important implications on antibacterials in low-income countries and the heightened risk of antibacterial resistance. This study, however, was unable to ascertain the dosing of the antibiotics given to the children before the hospital visit. The ascertainment of dosing would be important given that in addition to predisposing to the development of resistance, inappropriate dosing of antibiotics could also lead to adverse outcomes - as pediatric doses are weight-based and differ significantly between age groups.
Predictors of pre-hospital use of antibiotics among children with fever
This study brings to light significant differences in pre-hospital exposure to antibiotics with regard to several respondents’ characteristics. We observed a strong association between the respondents’ place of residence and pre-hospital exposure to antibiotics. Individuals residing in rural settings had a significantly higher likelihood of using antibiotics to treat children prior to a hospital visit than those from urban settings. This finding contrasts with that from an earlier report by Kibuule et al in Kampala, Uganda’s capital city, where households living in urban settings more likely used antibiotics than their rural counterparts [
25]. We believe this difference could partly be contextual given the big contrast between the two settings.
Residing within less than 5km distance from the nearest health facility was significantly associated with less use of antibiotics prior to a hospital visit. This finding may not be unexpected since the distance from a health facility is an important determinant of access to healthcare – a reason advanced by the respondents for choosing to give treatment from home and speaks to the importance of improving access to healthcare services in low-income countries. Our study did not find a statistically significant association between the child’s age and antibiotics use, contrary to a report by Nguyen et al in Vietnam [
26]. This might be that caregivers do not consider that the child’s age could have a bearing on the adverse effects of antibiotics.
Female caregivers of children with fever were significantly less likely to use antibiotics compared to their male counterparts, a finding which accords with that reported in the Kingdom of Saudi Arabia where men were more likely to self-prescribe antibiotics than females [
35]. This could be attributed to the fact that females generally have better healthcare-seeking behaviour [
36], a phenomenon supported by the high proportion of female caregivers found in this study. We did not find an independent association between caregivers’ age and use of antibiotics among children with fever, though caregivers aged 30 years and below had a 51% reduced chance of exposing their children to antibiotics prior to a hospital visit at bivariate analysis compared to those aged above 30 years. This finding reflects that reported in the Kingdom Republic of Saudi Arabia where the probability of self-prescription was higher among respondents older than 30 years compared to those aged 18-30 years [
35], probably attributed to previous experiences that develop over time.
Symptom-wise, pre-hospital use of antibiotics was significantly dependent on the child’s symptoms and caregivers’ perceived indications for use of antibiotics. Children presenting to the hospital with a long duration of illness - denoted by fever lasting 7 days or more, were significantly more likely to be given antibiotics prior to a hospital visit. We believe, as postulated by Nguyen et al, this might be due to the perception that febrile illness of longer duration is more severe and requires antibiotics [
26]. On the other hand, pre-hospital medication may, in itself be a cause for delay in health-seeking, consequently leading to more severe illness, delayed diagnosis, serious complications, and even death.
Our study also showed that children who had cough and diarrhoea during their febrile illnesses were significantly more likely to be given antibiotics compared to those who did not have these symptoms. This finding could relate to the respondents’ perception regarding the indications for antibiotics, given that in this study, caregivers who believed that fever, cough, diarrhoea and any form of infection are indications for antibiotics were significantly more likely to use the same. This relationship could explain the 39.5% observed rate of antibiotic use found in this study given that the majority of the children presenting with fever also had a cough (87.7%), common cold (90.5%) and diarrhoea (45.2%). In fact, 96.4% of the children who received antibiotics during their febrile illnesses in this study also had a cough. This finding correlates with reports from Nigeria [
14], Uganda [
25] and Vietnam [
26] where upper respiratory tract infections (common cold) were a cause of up to 83.7, 70.5 and 63% antibiotics exposure among children respectively, and corroborates that reported among adult patients in the Kingdom of Saudi Arabia [
35]. Similarly, in surveys conducted in rural China [
31] and Indonesia [
37], antibiotics were 42% more likely to be used if the child had a cough and/or common cold. Symptoms-driven use of antibiotics in the current study could reflect limited knowledge among the population regarding the therapeutic indications for antibiotics, just as reported in Malawi [
29].