Combating antibiotic resistance using guidelines and enhanced stewardship in Kenya: a protocol for an implementation science approach.

INTRODUCTION: Antimicrobial resistance (AMR) is a growing problem globally especially in Sub-Saharan Africa including Kenya. Without any intervention, lower/middle-income countries (LMICs) will be most affected due to already higher AMR levels compared with higher income countries and due to the far higher burden of diseases in the LMICs. Studies have consistently shown that inappropriate use of antimicrobials is the major driver of AMR. To address this challenge, hospitals are now implementing antibiotic stewardship programmes (ASPs), which have been shown to achieve reduced antibiotic usage, to decrease the prevalence of resistance and lead to significant economic benefits. However, the implementation of the guideline is highly dependent on the settings in which they are rolled out. This study, employing an implementation science approach, aims to address the knowledge gap in this area and provide critical data as well as practical experiences when using antibiotic guidelines and stewardship programmes in the public health sector. This will provide evidence of ASP performance and potentially contribute to the county, national and regional policies on antibiotics use. METHODS AND ANALYSIS: The study will be conducted in three geographically diverse regions, each represented by two hospitals. A baseline study on antibiotic usage, resistance and de-escalation, duration of hospital stay, rates of readmission and costs will be carried out in the preimplementation phase. The intervention, that is, the use of antibiotic guidelines and ASPs will be instituted for 18 months using a stepwise implementation strategy that will facilitate learning and continuous improvement of stewardship activities and updating of guidelines to reflect the evolving antibiotic needs. ETHICS AND DISSEMINATION: Approvals to carry out the study have been obtained from the National Commission for Science, Technology and Innovation and the Mount Kenya University Ethics Review Committee. The approvals from the two institutions were used to obtain permission to conduct the study at each of the participating hospitals. Study findings will be presented to policy stakeholders and published in peer-reviewed scientific journals. It is anticipated that the findings will inform the appropriate antibiotic use guidelines within our local context.

Author Correction: Genetic homogeneity of goat malaria parasites in Asia and Africa suggests their expansion with domestic goat host.

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Genetic homogeneity of goat malaria parasites in Asia and Africa suggests their expansion with domestic goat host.

Plasmodium was first identified in a goat in Angola in 1923, and only recently characterized by DNA isolation from a goat blood sample in Zambia. Goats were first domesticated in the Fertile Crescent approximately 10,000 years ago, and are now globally distributed. It is not known if the Plasmodium identified in African goats originated from parasites circulating in the local ungulates, or if it co-evolved in the goat before its domestication. To address this question, we performed PCR-based surveillance using a total of 1,299 goat blood samples collected from Sudan and Kenya in Africa, Iran in west Asia, and Myanmar and Thailand in southeast Asia. Plasmodium DNA was detected from all locations, suggesting that the parasite is not limited to Africa, but widely distributed. Whole mitochondrial DNA sequences revealed that there was only one nucleotide substitution between Zambian/Kenyan samples and others, supporting the existence of a goat-specific Plasmodium species, presumably Plasmodium caprae, rather than infection of goats by local ungulate malaria parasites. We also present the first photographic images of P. caprae, from one Kenyan goat sample.

Cytochrome P450 3A mRNA expression along goat and rat gastrointestinal tracts.

The cytochrome P450 (CYP) 3A family is involved in the elimination processes of almost 50% of commonly used drugs. CYP3A mRNA expressions in goat and rat gastrointestinal tracts in comparison to the liver were investigated using real-time PCR. In goats, the expression of CYP3A-like mRNAs was comparatively higher in the liver than in the gastrointestinal tract. The intestinal expression of CYP3A-like mRNA showed a gradual decrease from the duodenum to the ileum. In rats, the highest CYP3A62 mRNA expression was found in the duodenum followed by the liver. This study provides insights into the contribution of CYP3A enzymes to xenobiotic metabolism, especially in small ruminants such as goats.