Treatment seeking behaviours, antibiotic use and relationships to multi-drug resistance: A study of urinary tract infection patients in Kenya, Tanzania and Uganda.

Antibacterial resistance (ABR) is a major public health threat. An important accelerating factor is treatment-seeking behaviour, including inappropriate antibiotic (AB) use. In many low- and middle-income countries (LMICs) this includes taking ABs with and without prescription sourced from various providers, including health facilities and community drug sellers. However, investigations of complex treatment-seeking, AB use and drug resistance in LMICs are scarce. The Holistic Approach to Unravel Antibacterial Resistance in East Africa (HATUA) Consortium collected questionnaire and microbiological data from adult outpatients with urinary tract infection (UTI)-like symptoms presenting at healthcare facilities in Kenya, Tanzania and Uganda. Using data from 6,388 patients, we analysed patterns of self-reported treatment seeking behaviours ('patient pathways') using process mining and single-channel sequence analysis. Among those with microbiologically confirmed UTI (n = 1,946), we used logistic regression to assess the relationship between treatment seeking behaviour, AB use, and the likelihood of having a multi-drug resistant (MDR) UTI. The most common treatment pathway for UTI-like symptoms in this sample involved attending health facilities, rather than other providers like drug sellers. Patients from sites in Tanzania and Uganda, where over 50% of patients had an MDR UTI, were more likely to report treatment failures, and have repeat visits to providers than those from Kenyan sites, where MDR UTI proportions were lower (33%). There was no strong or consistent relationship between individual AB use and likelihood of MDR UTI, after accounting for country context. The results highlight the hurdles East African patients face in accessing effective UTI care. These challenges are exacerbated by high rates of MDR UTI, suggesting a vicious cycle of failed treatment attempts and sustained selection for drug resistance. Whilst individual AB use may contribute to the risk of MDR UTI, our data show that factors related to context are stronger drivers of variations in ABR.

Unravelling patient pathways in the context of antibacterial resistance in East Africa.

BACKGROUND: A key factor driving the development and maintenance of antibacterial resistance (ABR) is individuals' use of antibiotics (ABs) to treat illness. To better understand motivations and context for antibiotic use we use the concept of a patient treatment-seeking pathway: a treatment journey encompassing where patients go when they are unwell, what motivates their choices, and how they obtain antibiotics. This paper investigates patterns and determinants of patient treatment-seeking pathways, and how they intersect with AB use in East Africa, a region where ABR-attributable deaths are exceptionally high. METHODS: The Holistic Approach to Unravelling Antibacterial Resistance (HATUA) Consortium collected quantitative data from 6,827 adult outpatients presenting with urinary tract infection (UTI) symptoms in Kenya, Tanzania, and Uganda between February 2019- September 2020, and conducted qualitative in-depth patient interviews with a subset (n = 116). We described patterns of treatment-seeking visually using Sankey plots and explored explanations and motivations using mixed-methods. Using Bayesian hierarchical regression modelling, we investigated the associations between socio-demographic, economic, healthcare, and attitudinal factors and three factors related to ABR: self-treatment as a first step, having a multi-step treatment pathway, and consuming ABs. RESULTS: Although most patients (86%) sought help from medical facilities in the first instance, many (56%) described multi-step, repetitive treatment-seeking pathways, which further increased the likelihood of consuming ABs. Higher socio-economic status patients were more likely to consume ABs and have multi-step pathways. Reasons for choosing providers (e.g., cost, location, time) were conditioned by wider structural factors such as hybrid healthcare systems and AB availability. CONCLUSION: There is likely to be a reinforcing cycle between complex, repetitive treatment pathways, AB consumption and ABR. A focus on individual antibiotic use as the key intervention point in this cycle ignores the contextual challenges patients face when treatment seeking, which include inadequate access to diagnostics, perceived inefficient public healthcare and ease of purchasing antibiotics without prescription. Pluralistic healthcare landscapes may promote more complex treatment seeking and therefore inappropriate AB use. We recommend further attention to healthcare system factors, focussing on medical facilities (e.g., accessible diagnostics, patient-doctor interactions, information flows), and community AB access points (e.g., drug sellers).

Treatment seeking behaviours, antibiotic use and relationships to multi-drug resistance: A study of urinary tract infection patients in Kenya, Tanzania and Uganda.

Antibacterial resistance (ABR) is a major public health threat. An important accelerating factor is treatment-seeking behaviours, including inappropriate antibiotic (AB) use. In many low- and middle-income countries (LMICs) this includes taking ABs with and without prescription sourced from various providers, including health facilities and community drug sellers. However, investigations of complex treatment-seeking, AB use and drug resistance in LMICs are scarce. The Holistic Approach to Unravel Antibacterial Resistance in East Africa (HATUA) Consortium collected questionnaire and microbiological data from 6,827 adult outpatients with urinary tract infection (UTI)-like symptoms presenting at healthcare facilities in Kenya, Tanzania and Uganda. Among 6,388 patients we analysed patterns of self-reported treatment seeking behaviours ('patient pathways') using process mining and single-channel sequence analysis. Of those with microbiologically confirmed UTI (n=1,946), we used logistic regression to assessed the relationship between treatment seeking behaviour, AB use, and likelihood of having a multi-drug resistant (MDR) UTI. The most common treatment pathways for UTI-like symptoms included attending health facilities, rather than other providers (e.g. drug sellers). Patients from the sites sampled in Tanzania and Uganda, where prevalence of MDR UTI was over 50%, were more likely to report treatment failures, and have repeated visits to clinics/other providers, than those from Kenyan sites, where MDR UTI rates were lower (33%). There was no strong or consistent relationship between individual AB use and risk of MDR UTI, after accounting for country context. The results highlight challenges East African patients face in accessing effective UTI treatment. These challenges increase where rates of MDR UTI are higher, suggesting a reinforcing circle of failed treatment attempts and sustained selection for drug resistance. Whilst individual behaviours may contribute to the risk of MDR UTI, our data show that factors related to context are stronger drivers of ABR.

The role of multidimensional poverty in antibiotic misuse: a mixed-methods study of self-medication and non-adherence in Kenya, Tanzania, and Uganda.

BACKGROUND: Poverty is a proposed driver of antimicrobial resistance, influencing inappropriate antibiotic use in low-income and middle-income countries (LMICs). However, at subnational levels, studies investigating multidimensional poverty and antibiotic misuse are sparse, and the results are inconsistent. We aimed to investigate the relationship between multidimensional poverty and antibiotic use in patient populations in Kenya, Tanzania, and Uganda. METHODS: In this mixed-methods study, the Holistic Approach to Unravelling Antimicrobial Resistance (HATUA) Consortium collected data from 6827 outpatients (aged 18 years and older, or aged 14-18 years and pregnant) with urinary tract infection (UTI) symptoms in health-care facilities in Kenya, Tanzania, and Uganda. We used Bayesian hierarchical modelling to investigate the association between multidimensional poverty and self-reported antibiotic self-medication and non-adherence (ie, skipping a dose and not completing the course). We analysed linked qualitative in-depth patient interviews and unlinked focus-group discussions with community members. FINDINGS: Between Feb 10, 2019, and Sept 10, 2020, we collected data on 6827 outpatients, of whom 6345 patients had complete data; most individuals were female (5034 [79·2%]), younger than 35 years (3840 [60·5%]), worked in informal employment (2621 [41·3%]), and had primary-level education (2488 [39·2%]). Antibiotic misuse was more common among those least deprived, and lowest among those living in severe multidimensional poverty. Regardless of poverty status, difficulties in affording health care, and more familiarity with antibiotics, were related to more antibiotic misuse. Qualitative data from linked qualitative in-depth patient interviews (n=82) and unlinked focus-group discussions with community members (n=44 groups) suggested that self-medication and treatment non-adherence were driven by perceived inconvenience of the health-care system, financial barriers, and ease of unregulated antibiotic access. INTERPRETATION: We should not assume that higher deprivation drives antibiotic misuse. Structural barriers such as inefficiencies in public health care, combined with time and financial constraints, fuel alternative antibiotic access points and treatment non-adherence across all levels of deprivation. In designing interventions to reduce antibiotic misuse and address antimicrobial resistance, greater attention is required to these structural barriers that discourage optimal antibiotic use at all levels of the socioeconomic hierarchy in LMICs. FUNDING: UK National Institute for Health Research, UK Medical Research Council, and the Department of Health and Social Care.

C - reactive protein and urinary tract infection due to Gram-negative bacteria in a pediatric population at a tertiary hospital, Mwanza, Tanzania.

INTRODUCTION: Gram-negative bacteria are the major cause of urinary tract infections (UTI) in children. There is limited data on UTI systemic response as measured using C-reactive protein (CRP). Here, we report the association of CRP and UTI among children attending the Bugando Medical Centre, Mwanza, Tanzania. METHODS: A cross-sectional study was conducted between May and July 2017. Urine and blood were collected and processed within an hour of collection. Data were analyzed using STATA version 13. RESULTS: Of 250 enrolled children, 76(30.4%) had significant bacteriuria with 56(22.4%, 95%CI; 11.5-33.3) having gram-negative bacteria infection. There was dual growth of gram-negative bacteria in 3 patients. Escherichia coli (32.2%, 19/59) was the most frequently pathogen detected. A total of 88/250(35.2%) children had positive CRP on qualitative assay. By multinomial logistic regression, positive CRP (RRR=4.02, 95%CI: 2.1-7.7, P<0.001) and age ≤ 2years (RRR=2.4, 95%CI: 1.23-4.73, P<0.01) significantly predicted the presence of significant bacteriuria due to gram-negative enteric bacteria. CONCLUSION: C-reactive protein was significantly positive among children with UTI due to gram-negative bacteria and those with fever. In children with age ≤ 2 years, positive CRP indicates UTI due to gram-negative enteric bacteria.

Multi-resistant gram negative enteric bacteria causing urinary tract infection among malnourished underfives admitted at a tertiary hospital, northwestern, Tanzania.

BACKGROUND: Infections are common complications occurring in malnourished childrenas a result of impaired immunity. Urinary tract infections (UTI) have been found to be the commonest cause of fever in normal children in developing countries. However, data regarding UTI among malnourished children is limited because in most of time severe and moderately malnourished children are afebrile despite significant bacteriuria. METHODS: A total of 402 malnourished underfives were enrolled. Demographic and other clinical characteristics were collected using standardized data collection tool. Urine specimens were cultured and interpreted according to standard operating procedures. Data were analyzed using STATA version 11. RESULTS: Out of 402 malnourished underfives, 229 (56.9 %) were male. The median age in months was 17 (IQR; 12-31). Of 402 malnourished underfives, 83 (20.3 %) had significant bacteriuria of gram negative enteric bacteria. Escherichia coli 35/84 and Klebsiella pneumonia 20/84 were predominant bacteria isolated. More than 37 % of isolates were resistant to third generation cephalosporins with all of them exhibiting extended spectrum beta lactamase (ESBL) phenotype. Rates of resistance to ampicillin, amoxillin/clavulanic acid, gentamicin and ciprofloxacin were 82/84 (98.7 %), 47/55 (85.4 %), 45/84 (57.8 %) and 9/84 (10.8 %) respectively. Decrease in age and increase in lymphocytes count were independent factors on multivariate logistic regression analysis found to predict UTI (p<0.05). CONCLUSIONS: Multi-resistant gram negative enteric bacteria are common cause of UTI among underfives. A significant number of severe and moderate malnourished children with bacteriuria had no fever. Therefore, routine testing for UTI is emphasized in all malnourished underfives so that appropriate treatment can be initiated.