A one health approach to strengthening antimicrobial stewardship in Wakiso District, Uganda

Antimicrobial stewardship (AMS), as one of the global strategies to promote responsible use of antimicrobials to prevent antimicrobial resistance (AMR), remains poor in many low-and middle-income countries (LMICs). We implemented a project aimed at strengthening AMS in Wakiso district, Uganda using a One Health approach. A total of 86 health practitioners (HPs), including animal health workers, and 227 community health workers (CHWs) participated in training workshops, and over 300 pupils from primary schools were sensitized on AMR, AMS, and infection prevention and control (IPC). We further established two multidisciplinary online communities of practice (CoPs) for health professionals and students, with a current membership of 321 and 162, respectively. In addition, a Medicine and Therapeutics Committee (MTC) was set up at Entebbe Regional Referral Hospital. The project evaluation, conducted three months after training, revealed that the majority of the HPs (92.2%) and CHWs (90.3%) reported enhanced practices, including improved hand washing (57.3% and 81.0%, respectively). In addition, 51.5% of the HPs reported a reduction in the quantity of unnecessary antibiotics given per patient. This project demonstrates that AMS interventions using a One Health approach can promote understanding of the prudent use of antimicrobials and improve practices at health facilities and in communities

Absence of O antigen suppresses Shigella flexneri IcsA autochaperone region mutations

The Shigella flexneri IcsA (VirG) protein is a polarly distributed autotransporter protein. IcsA functions as a virulence factor by interacting with the host actin regulatory protein N-WASP, which in turn activates the Arp2/3 complex, initiating actin polymerization. Formation of F-actin comet tails allows bacterial cell-to-cell spreading. Although various accessory proteins such as periplasmic chaperones and the β-barrel assembly machine (BAM) complex have been shown to be involved in the export of IcsA, the IcsA translocation mechanism remains to be fully elucidated. A putative autochaperone (AC) region (amino acids 634–735) located at the C-terminal end of the IcsA passenger domain, which forms part of the self-associating autotransporter (SAAT) domain, has been suggested to be required for IcsA biogenesis, as well as for N-WASP recruitment, based on mutagenesis studies. IcsAi proteins with linker insertion mutations within the AC region have a significant reduction in production and are defective in N-WASP recruitment when expressed in smooth LPS (S-LPS) S. flexneri. In this study, we have found that the LPS O antigen plays a role in IcsAi production based on the use of an rmlD (rfbD) mutant having rough LPS (R-LPS) and a novel assay in which O antigen is depleted using tunicamycin treatment and then regenerated. In addition, we have identified a new N-WASP binding/interaction site within the IcsA AC region.Min Yan Teh, Elizabeth Ngoc Hoa Tran and Renato Moron

Scaling-up interventions for strengthening antimicrobial stewardship using a one health approach in Wakiso District, Uganda

We implemented a multidisciplinary project between Uganda and the UK aimed at strengthening antimicrobial stewardship (AMS) in Wakiso district, with a focus on capacity building, stakeholder engagement, and knowledge exchange using a One Health approach. Project activities included: trainings and workshops on antimicrobial resistance (AMR), AMS, infection prevention and control (IPC); Global Point Prevalence Survey (GPPS) data collection and analysis; and the mentorship of lower level health facilities. Our project demonstrated that AMS interventions using a One Health approach can enhance understanding of the prudent use of antimicrobials and improve practices at health facilities and within communities

Antimicrobial stewardship in private pharmacies in Wakiso district, Uganda: a qualitative study

Background: Private pharmacies are the first point of contact for the public regarding acquisition of medicines and other pharmaceuticals in many low- and middle-income countries including Uganda. Most antimicrobial stewardship (AMS) programmes in Uganda have targeted pharmacies in public health facilities, with little known about private pharmacies. This study explored knowledge and practices related to AMS in private pharmacies in Wakiso district, central Uganda. Methods: This was a qualitative study that involved 31 in-depth interviews to explore AMS among retail private pharmacy staff including pharmacists, pharmacy technicians/dispensers, and nurses. Participants were asked about antimicrobial resistance (AMR) and AMS practices at their pharmacy. The audio-recorded interviews were transcribed verbatim and imported to NVivo 2020 (QSR International) for thematic analysis. Results: Five major themes emerged from the study: commonly sold antimicrobials; knowledge on AMR and AMS; potential contributors to AMR; practices related to AMS; and challenges to AMS. The commonly sold antimicrobials in the pharmacies with or without prescriptions were oral azithromycin, Ampiclox® (ampicillin and cloxacillin), amoxicillin, ciprofloxacin, Septrin® (co-trimoxazole), metronidazole, Flucamox® (amoxicillin and flucloxacillin), Augmentin® (amoxicillin and clavulanic acid), cephalexin, doxycycline, and chloramphenicol. Participants had heard about AMR but not AMS, although only a few correctly defined AMR. Lack of knowledge among health workers and local communities; the overuse, misuse, and abuse of antimicrobials such as non-adherence to dosage; self-medication; and purchase of drugs without prescription were identified as potential accelerators to the emergence of AMR. Current practices related to AMS in private pharmacies were limited to meetings, antimicrobial dispensing, providing client advice, record keeping, and monitoring of drugs. Cost of healthcare, client satisfaction and retention, outdated guidelines, and the business orientation of pharmacies were the main challenges related to AMS. Conclusion: There was poor knowledge of AMR and AMS, and limited AMS practices in private pharmacies. Private pharmacies have the potential to contribute to Uganda’s fight against AMR if motivated and equipped with adequate knowledge to enhance their practices related to AMS

Knowledge, perceptions and practices on antimicrobial resistance in humans and animals in Wakiso district, Uganda: a cross sectional study

Despite increasing evidence on antimicrobial resistance (AMR), there is limited literature on antimicrobial access and use in humans and animals in community settings globally. This study assessed knowledge and perceptions of AMR, as well as practices relating to the use of antimicrobials in humans and animals in Wakiso district, Uganda. This was a cross-sectional study among 418 participants that employed quantitative data collection methods. A structured questionnaire that included questions on knowledge, perceptions, practices related to AMR, and perceptions on access to antimicrobials in humans and animals was used. Data was analysed in STATA version 10. The majority of participants 63.6% (266/418) had heard about AMR mainly from family and friends 57.5% (153/266), and most 70.8% (296/418) were aware that resistant microorganisms cause infections that are difficult to treat. Most participants 62.7% (262/418) thought that they should complete the full dose of antimicrobials when on treatment. However, on the last occasion of antimicrobial use, 13.0% (44/338) revealed that they did not complete the full course of treatment. Participants who were single (APR = 1.12, C.I = 1.03–1.12, p-value = 0.01) and earning between 91 and 290 USD on average per month (APR = 1.12, C.I = 1.02–1.23, p-value = 0.02) were more likely to have completed a given antimicrobial course as compared to those who were married/cohabiting and earned less than 15 USD respectively. The majority of participants 60% (251/418) owned animals, and 81.3% (204/251) reported using antimicrobials mainly for prevention 61.3% (125/204) or treatment of sick animals 70.6% (144/204). Among the participants, 57.4% (117/204) reported not having sold or consumed animal products within a week after exposure to antimicrobials. Interventions to prevent AMR should adopt a One Health approach to address the gap in knowledge and practices relating to the use of antimicrobials in humans and animals

Antibiotic Prescribing Patterns in Ghana, Uganda, Zambia and Tanzania Hospitals: Results from the Global Point Prevalence Survey (G-PPS) on Antimicrobial Use and Stewardship Interventions Implemented

Antimicrobial resistance (AMR) remains an important global public health issue with antimicrobial misuse and overuse being one of the main drivers. The Global Point Prevalence Survey (G-PPS) of Antimicrobial Consumption and Resistance assesses the prevalence and the quality of antimicrobial prescriptions across hospitals globally. G-PPS was carried out at 17 hospitals across Ghana, Uganda, Zambia and Tanzania. The overall prevalence of antimicrobial use was 50% (30–57%), with most antibiotics prescribed belonging to the WHO ‘Access’ and ‘Watch’ categories. No ‘Reserve’ category of antibiotics was prescribed across the study sites while antimicrobials belonging to the ‘Not Recommended’ group were prescribed infrequently. Antimicrobials were most often prescribed for prophylaxis for obstetric or gynaecological surgery, making up between 12 and 18% of total prescriptions across all countries. The most prescribed therapeutic subgroup of antimicrobials was ‘Antibacterials for systemic use’. As a result of the programme, PPS data are now readily available for the first time in the hospitals, strengthening the global commitment to improved antimicrobial surveillance. Antimicrobial stewardship interventions developed included the formation of AMS committees, the provision of training and the preparation of new AMS guidelines. Other common interventions included the presentation of findings to clinicians for increased awareness, and the promotion of a multi-disciplinary approach to successful AMS programmes. Repeat PPS would be necessary to continually monitor the impact of interventions implemented. Broader participation is also encouraged to strengthen the evidence base

Access, use and disposal of antimicrobials among humans and animals in Wakiso district, Uganda: a qualitative study

Background: Inappropriate use of antimicrobials in both humans and animals is a key driver of antimicrobial resistance (AMR). In addition, human behaviours such as poor disposal of antimicrobials in the environment can increase their exposure to microbes which can impact on humans and animals. However, evidence on access, use and disposal of antimicrobials for humans and animals at community level in Uganda is limited. This study therefore explored access, use and disposal of antimicrobials among humans and animals in Wakiso district, Uganda. Methods: A qualitative study was conducted that involved focus group discussions (FGDs) and key informant interviews (KIIs). Participants of the FGDs were community health workers (CHWs) and farmers involved in animal husbandry, while key informants included: officials from the Ministry of Health; Ministry of Agriculture, Animal Industry and Fisheries; human and animal health professionals; district health officials; and members of the national AMR surveillance committee. Twelve FGDs were held (8 for CHWs and 4 for farmers) while 15 KIIs were conducted. Thematic analysis in NVivo (version 12) was performed. Results: Five main themes emerged from the study: access to antimicrobials in humans; access to antimicrobials in animals; use of antimicrobials in humans; use of antimicrobials in animals; and disposal of antimicrobials. Community members mainly accessed antimicrobials for humans from public health facilities such as government health centres, as well as private facilities, including drug shops and clinics. Antimicrobials for animals were obtained from veterinary practitioners and drug shops (both for humans and veterinary). Examples of inappropriate use of antimicrobials in both humans and animals was evident, such as sharing antibiotics among household members, and giving human-prescribed antimicrobials to food-producing animals as growth promoters. While some CHWs returned unused antimicrobials to public health facilities for proper disposal, community members mainly disposed of antimicrobials with general household waste including dumping in rubbish pits. Conclusions: There is a need to increase awareness among the population on proper access, use and disposal of antimicrobials for both humans and animals. Development of a drug disposal system at community level would facilitate improved waste management of antimicrobials. Together, these measures would help prevent the rate of progression of AMR in communities

Adaptation of High-Throughput Screening in Drug Discovery—Toxicological Screening Tests

High-throughput screening (HTS) is one of the newest techniques used in drug design and may be applied in biological and chemical sciences. This method, due to utilization of robots, detectors and software that regulate the whole process, enables a series of analyses of chemical compounds to be conducted in a short time and the affinity of biological structures which is often related to toxicity to be defined. Since 2008 we have implemented the automation of this technique and as a consequence, the possibility to examine 100,000 compounds per day. The HTS method is more frequently utilized in conjunction with analytical techniques such as NMR or coupled methods e.g., LC-MS/MS. Series of studies enable the establishment of the rate of affinity for targets or the level of toxicity. Moreover, researches are conducted concerning conjugation of nanoparticles with drugs and the determination of the toxicity of such structures. For these purposes there are frequently used cell lines. Due to the miniaturization of all systems, it is possible to examine the compound’s toxicity having only 1–3 mg of this compound. Determination of cytotoxicity in this way leads to a significant decrease in the expenditure and to a reduction in the length of the study