Antibiotic use and resistance in under five children in rural central India : implications of caregivers’ healthcare-seeking behaviour and informal healthcare providers’ practices

Sammanfattning: Background: Antibiotic-resistant bacteria are becoming increasingly prevalent around the world, and this is true for both pathogenic and commensal bacteria. The findings of prior investigations have revealed a statistically significant relationship between antibiotic usage and the development of antibiotic resistance. More than 60% of India's population resides in rural areas; however, the country's access to healthcare facilities is unevenly concentrated in urban areas. In rural communities, seeking healthcare often involves exploring all available options, from home care and traditional healers to formal and informal healthcare providers. The healthcare-seeking behaviour of an individual is complex and is influenced by factors such as existing healthcare providers' practices, geographical location, and sociodemographic factors. These factors influence antibiotic prescribing and, consequently contribute to antibiotic resistance. Informal healthcare providers (IHCPs) are the most common type of healthcare professional in rural India, and they are those who prescribe without having had formal training. Antibiotic prescribing by IHCPs has the potential to give critical information for the control of antibiotic resistance in the future. Prescription decisions, on the other hand, are complicated and influenced by a wide range of interlinked factors. As a result, in order to change prescribing behaviour, it is necessary to first gain a thorough understanding of antibiotic prescribing as well as the factors that influence this behaviour. As of now, there is little information available about the factors that influence HSB and prescribing by IHCPs with regards to antibiotic use resistance from rural parts of India. Aim: The aim of this thesis was to investigate the HSB of caregivers of under 5 (U-5) children; to investigate the prescribing practices of IHCPs in rural areas and to analyse the internal and external drivers that influence IHCPs‘ prescribing behaviour; and to determine the relationship between individual-level antibiotic consumption and antibiotic resistance in commensal E. coli in a cohort of children in rural India Methods: All the studies from I to IV were conducted in rural areas of the Ujjain district of Madhya Pradesh in central India. Specifically, the studies were carried out at the rural Demographic Surveillance Site, Palwa of Ruxmaniben Deepchand Gardi Medical College, Ujjain. Two methods were used: quantitative studies (Papers I, II and IV) and qualitative study (Paper III). The quantitative Paper I was a prospective cohort study where the healthcare-seeking behaviour of a cohort of caregivers of 125 U-5 children was collected over a period of 2 years (August 2014 – October 2016) and the sociodemographic factors associated with the healthcare-seeking behaviour of the caregivers were determined using mixed-effects multinomial logistic regression. Paper II was a repeated cross-sectional study in which the prescriptions from 12 informal healthcare providers were collected monthly for over a period of 18 months. Descriptive statistics were used to examine the informal healthcare providers‘ characteristics and the prescriptions. Paper IV was a correlation study where the association between the individual child-level antibiotic consumption from Paper I and resistance to selected antibiotic classes among E.coli isolates from stool samples of a cohort of 125 U-5 children was explored using Spearman correlation coefficient and mixed-effects logistic regression models. In the qualitative study Paper III, focus group discussions were conducted with 48 IHCPs, and thematic framework analysis with an inductive approach was used, and findings were collated in the theoretical framework based on knowledge, attitude, and practice model. Results: The most common illnesses found in Paper I were respiratory tract infections (69%) and gastrointestinal tract infections (8%). No healthcare was sought in 33% of illness episodes, mostly for RTIs. The most common healthcare-seeking pathway was to visit IHCPs (in 49% of illness episodes). The adjusted relative risk for obtaining no treatment, home treatment, and treatment by IHCPs was higher for RTIs (adjusted risk ratio (aRR) = 11.54, 1.82 and 1.29, respectively), illiterate mothers (aRR = 2.86, 2.38 and 1.93, respectively), and mothers who were homemakers (aRR = 2.90, 4.17 and 2.10, respectively). During the HSB follow-up antibiotic prescriptions were found in 46% of the illness episodes. IHCPs‘ prescribed antibiotics in 74% of the total prescriptions analysed in Paper II, the majority (95%) of the antibiotics prescribed were broad-spectrum. Antibiotics were prescribed more frequently in oral and dental problems (1126, 88%), fever (3569, 87%), and upper respiratory tract infections (3273, 81%). According to the findings of Paper III, the decisions made by IHCPs while prescribing antibiotics are complex and impacted by a range of external and internal drivers. Antibiotics are believed to boost the effectiveness of other medications, cure patients faster, and hence help to retain patients. Formal healthcare providers are the source of information of IHCPs, which influences IHCPs‘ antibiotic prescribing. Results of Paper IV showed that the cephalosporins consumption during the study period was positively correlated with the resistance to cefotaxime (Coefficient ± SE = 0.13 ± 0.09, p<0.001) among the commensal E.coli in a cohort of 125 children. Conclusions: In the rural study cohort, the most common healthcare-seeking pathway is to visit IHCPs, which indicates that they are the major healthcare providers in rural areas. IHCPs‘ antibiotic prescribing for common illnesses in children U-5 in rural Ujjain is high. The overuse of broad-spectrum antibiotics for common illnesses is concerning and shows inappropriate antibiotic use. Our findings also showed a positive correlation between individual child-level antibiotic consumption and resistance development in commensal E.coli. IHCPs' antibiotic prescribing behaviour was found to be influenced by a variety of factors. In order to modify caregivers‘ HSB, IHCPs' antibiotic prescribing practices and modify antibiotic false beliefs among IHCPs and caregivers, targeted and coordinated actions involving all stakeholders will be required.