PhD defence Daniel Valia

Supervisors

• Em. prof. dr. Marianne van der Sande (ITM)

• Prof. dr. Annie Robert (UCL)

• Prof. dr. Hector Rodriguez Villalobos (UCL)

• Prof. dr. Halidou Tinto (CRUN, Burkina Faso)  

Summary

In Burkina Faso, from 2012 to 2018, extended-spectrum β-lactamase-Producing Escherichia coli (ESBL-EC) and Klebsiella pneumoniae (ESBL-KP) have been increasingly isolated from community-acquired invasive infections. This increase could be reflecting a high and increasing prevalence of faecal colonisation with these resistant bacteria in the community, as far as gut colonisation was identified as precursor to bloodstream infections. The overall objective of this thesis was therefore to assess the extent of these resistant bacteria in the community in rural Burkina Faso and to understand associated factors, in order to inform tailored infection prevention and control (IPC) interventions.

Our data showed an estimated prevalence of faecal colonisation with ESBL-EC and ESBL-KP at 61.3% in rural Burkina Faso. This prevalence was higher during the rainy season compared to the dry season (70.2% vs 53.6%, p<0.001) and higher among study participants reporting not washing hands with soap before meals compared to those who did (62.5 vs 49.0%, p<0.001). In both bacteria, blaCTX-M-15 was the most prevalent (47.3% in E. coli and 19.9%; in K. pneumoniae) β-Lactamase genes. Plasmid-mediated quinolone resistance (PMQR) genes as qnr (48.1% in E. coli and 81.1% in K. pneumoniae), aac(6’)-ib-cr (21.2% in E. coli and 18.9% in K. pneumoniae) as well as OqxAB (5.8% in E. coli, and 78.4% in K. pneumoniae) were found along with β-Lactamase genes.

In patients with severe acute febrile illness attending the Nanoro district hospital, 39.5% reported pre-hospital antibiotic use. This pre-hospital antibiotic use was significantly higher among patients referred from primary healthcare centers than among those who self-referred (54.0% vs 26.7%, p<0.001). Among all pre-hospital antibiotic use reported (424), Watch antibiotics were more frequently reported by referrals compared to self-referred patients (42.2% vs 28.1%, p=0.004).

The investigations to understand the role of different healthcare providers and knowledge of antibiotics, showed that 33.5% healthcare were seeking outside healthcare facilities, including informal medicine vendors (47.7%), self-medication with left-over medicines kept at home (26.5%), medicine vendors in formal pharmacies (16.4%), traditional healers (9.4%) and only the latters (traditional healers) were not antibiotic dispensers. Reported reasons for seeking healthcare outside healthcare facilities included financial limitation, proximity to informal drug vendors, long waiting times at healthcare facilities and health professionals’ non-empathetic attitudes towards their patients. Antibiotics knowledge (only for illnesses of bacterial origin) was limited among healthcare professionals, very limited among medicines vendors in formal pharmacies, and non-existent among informal medicine vendors and the general community.

While investigating antibiotic use by clinical presentation across all healthcare providers, we found that outpatient antibiotic use was more frequent after health center visits (54.8%, of which 16.5% Watch, n = 1249) than after visits to pharmacies (26.2%, 16.3% Watch, n = 328) and informal medicine vendors (26.9%, 50.0% Watch, n = 349). Across all healthcare providers, patients presenting with clinical presentations for which antibiotics were not recommended such as malaria, rhinopharyngitis, bronchitis, gastroenteritis, pain and wound were dispensed (Watch) antibiotics. Compliance with WHO’s AWaRe Antibiotic Book could have averted at least 68.4% of all Watch antibiotic use in outpatients at health centers. Community-wide, 2.9 DDD (95% CI 1.9–3.9) were used per 1000 adult inhabitants per day, health centers representing 89.7% of it.

We concluded that the challenge of controlling antimicrobial resistance in such a setting should be multifaceted and combine both tailored antimicrobial stewardship (AMS) across all healthcare providers and the community to reduce antibiotic selective pressure and community-based hygiene interventions to break the cycle of transmission in order to mitigate and/or prevent spread. Antimicrobial stewardship program should be particularly intensified in health centers and should include dedicated education and awareness on AMR for healthcare workers, improved diagnostic tools to differentiate bacterial from non-bacterial infections, patient management algorithms based on the latest WHO recommendations for antibiotic prescription. At formal pharmacies, regulation on antibiotic sales should be strengthened, in combination with regular AMR awareness activities and monitoring to mitigate over-the-counter dispensing. At informal medicine vendors, AMR awareness programs should help self- restriction of Watch antibiotic sales. At community level, awareness activities should include risk behaviours leading to emergence and spread of resistant microorganisms in the community. Regarding community-based hygiene interventions, improving hand hygiene practices and enhancing sanitation can be effective steps toward mitigating the burden of antimicrobial resistance.