Development, roll-out and implementation of an antimicrobial resistance training curriculum harmonizes delivery of in-service training to healthcare workers in Kenya.

Background: Antimicrobial resistance (AMR) is an increasingly severe threat to global public health that requires action across different sectors. Selection of appropriate antimicrobials is an urgent challenge due to the emergence of drug resistance. In 2017, Kenya developed an AMR policy and National Action Plan to drive prevention and containment of AMR. A priority activity under AMR surveillance strategic objective was to develop a national AMR training curriculum for in-service healthcare workers. In this paper we discuss the development process, gains achieved through implementation across the country and lessons learned. Methods: An initial stakeholders' forum was convened to brainstorm on the process for developing the curriculum and some issues deliberated upon include the design approach, development roadmap, curriculum outline and scope, delivery, and evaluation methodologies. A dedicated team of subject matter experts (SMEs), drawn from the project and government ministries, compiled the initial draft of the curriculum and later the training materials. A series of other stakeholders' meetings were convened to review these materials. The National Antimicrobial Stewardship Interagency Committee (NASIC) of the MOH in Kenya identified a team of experts from academia, research, and government to work with the SMEs in reviewing and providing valuable inputs to the curriculum. Additionally, principles of adult learning and a One Health approach for development were considered as AMR has drivers and impacts across sectors. A validation workshop was held to finalize the documents with a formal launch conducted during the World Antibiotics Awareness Week of 2020. Results: A multisectoral AMR surveillance training curriculum and facilitator and trainee manuals were developed and endorsed by MOH and Ministry of Agriculture, Livestock, Fisheries and Cooperatives within one year. Over 500 healthcare workers in 19 counties were trained, with overwhelming adoption by other stakeholders in Kenya and beyond. Conclusion: This curriculum was developed to standardize training for AMR detection and surveillance. The central role played by the MOH ensured expeditious development and roll-out of this curriculum. The in-service curriculum, now available on an e-learning platform, provides a ready opportunity to build capacity of healthcare professionals. Additional resources are needed to standardize and scale these efforts to reach all healthcare workers.

Molecular survey of Coxiella burnetii in wildlife and ticks at wildlife-livestock interfaces in Kenya.

Coxiella burnetii is the causative agent of Q fever, a zoonotic disease of public health importance. The role of wildlife and their ticks in the epidemiology of C. burnetii in Kenya is unknown. This study analysed the occurrence and prevalence of the pathogen in wildlife and their ticks at two unique wildlife-livestock interfaces of Laikipia and Maasai Mara National Reserve (MMNR) with the aim to determine the potential risk of transmission to livestock and humans. Blood from 79 and 73 animals in Laikipia and MMNR, respectively, and 756 and 95 ixodid ticks in each of the areas, respectively, was analysed. Ticks were pooled before analyses into 137 and 29 samples in Laikipia and MMNR, respectively, of one to eight non-engorged ticks according to species and animal host. Real-time PCR amplifying the repetitive insertion element IS1111a of the transposase gene was used to detect C. burnetii DNA. Although none of the animals and ticks from MMNR tested positive, ticks from Laikipia had an overall pooled prevalence of 2.92% resulting in a maximum-likelihood estimate of prevalence of 0.54%, 95% CI 0.17-1.24. Ticks positive for C. burnetii DNA belonged to the genus Rhipicephalus at a pooled prevalence of 2.96% (maximum-likelihood estimate of prevalence of 0.54%, 95% CI 0.17-1.26). These ticks were Rhipicephalus appendiculatus, R. pulchellus and R. evertsi at pooled prevalence of 3.77, 3.03 and 2.04%, respectively. The presence of C. burnetii in ticks suggests circulation of the pathogen in Laikipia and demonstrates they may play a potential role in the epidemiology of Q fever in this ecosystem. The findings warrant further studies to understand the presence of C. burnetii in domestic animals and their ticks within both study areas.

Molecular surveillance of spotted fever group rickettsioses in wildlife and detection of Rickettsia sibirica in a Topi (Damaliscus lunatus ssp. jimela) in Kenya.

Spotted fever group rickettsioses are a group of tick-borne zoonotic diseases caused by intracellular bacteria of the genus Rickettsia. The diseases are widely reported amongst international travellers returning from most sub-Saharan Africa with fever, yet their importance in local populations largely remains unknown. Although this has started to change and recently there have been increasing reports of the diseases in livestock, ticks and humans in Kenya, they have not been investigated in wildlife. We examined the presence, prevalence and species of Rickettsia present in wildlife in two regions of Kenya with a unique human-wildlife-livestock interface. For this purpose, 79 wild animals in Laikipia County and 73 in Maasai Mara National Reserve were sampled. DNA extracted from blood was tested using the polymerase chain reaction (PCR) to amplify the intergenic spacer rpmE-tRNAfMet and the citrate synthase-encoding gene gltA. Rickettsial DNA was detected in 2 of the 79 (2.5%) animals in Laikipia and 4 of the 73 (5.5%) in Maasai Mara. The PCR-positive amplicons of the gltA gene were sequenced to determine the detected Rickettsia species. This revealed Rickettsia sibirica in a Topi (Damaliscus lunatus ssp. jimela). This is the first report of spotted fever group rickettsioses in wildlife and the first to report R. sibirica in Kenya. The finding demonstrates the potential role of wild animals in the circulation of the diseases.

A 56-Day Oral Toxicity Study of the Aqueous Extract of Rapanea melanophloeos (L.) Mez in Rats.

Rapanea melanophloeos is a tropical tree that is extensively utilized in African traditional medicine to treat helminthiases, tuberculosis, and heart-water. As with many other medicinal plants, there is insufficient information regarding the safety of therapeutic R. melanophloeos extracts. An aqueous extract of R. melanophloeos stem bark was administered to Sprague Dawley rats at doses of 100 mg/kg, 300 mg/kg, and 1000 mg/kg for 56 days to characterize its potential toxicity after prolonged dosing. Blood samples were obtained fortnightly for serum chemistry and hematology, while organs were collected at the end of the study. The extract caused an increase in organ weight indices of the kidneys and testis at 300 mg/kg and 1000 mg/kg. Hematological and biochemical examination revealed a drop in leukocyte counts and the hematocrit at 1000 mg/kg dose level, while there was a general but nondose-related elevation in alkaline phosphatase activity. There were time-associated variations in the hematological and clinical chemistry parameters at days 28, 42, and 56 in all dose levels, but most values remained within physiological limits. No pathological lesions were evident at histopathology after treatment with the extract. Our data shows that the aqueous extract of R. melanophloeos is not likely to be toxic at the doses tested and provides support to its medicinal use.

Knowledge, Attitudes and Practices Towards Spotted Fever Group Rickettsioses and Q Fever in Laikipia and Maasai Mara, Kenya.

Many factors contribute to misdiagnosis and underreporting of infectious zoonotic diseases in most sub-Saharan Africa including limited diagnostic capacity and poor knowledge. We assessed the knowledge, practices and attitudes towards spotted fever group rickettsioses (SFGR) and Q fever amongst local residents in Laikipia and Maasai Mara in Kenya. A semi-structured questionnaire was administered to a total of 101 respondents including 51 pastoralists, 17 human health providers, 28 wildlife sector personnel and 5 veterinarians. The pastoralists expressed no knowledge about SFGR and Q fever. About 26.7% of the wildlife sector personnel in Laikipia expressed some knowledge about SFGR and none in Maasai Mara. None of these respondents had knowledge about Q fever. About 45.5 and 33.3% of the health providers in Laikipia and Maasai Mara respectively expressed knowledge about SFGR and 9.1% in Laikipia expressed good knowledge on Q fever and none in Maasai Mara. The diseases are not considered amongst potential causes of febrile illnesses in most medical facilities except in one facility in Laikipia. Majority of pastoralists practiced at least one predisposing activity for transmission of the diseases including consumption of raw milk, attending to parturition and sharing living accommodations with livestock. Education efforts to update knowledge on medical personnel and One-Health collaborations should be undertaken for more effective mitigation of zoonotic disease threats. The local communities should be sensitized through a multidisciplinary approach to avoid practices that can predispose them to the diseases.

Sub-acute toxicity of the chloroformic extract of Rapanea melanophloeos (L.) Mez in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Cape beech (Rapanea melanophloeos) is an important medicinal plant that is widely used in most of Africa. Currently, little toxicological information is available on its safety following prolonged use. AIM OF THE STUDY: In this study, we sought to evaluate the oral sub-acute toxicity of Rapanea melanophloeos stem bark chloroformic extract using Sprague Dawley rats. MATERIALS AND METHODS: Six-week old rats were orally administered with the extract at dosage levels of 100 mg/kg, 300 mg/kg and 1000 mg/kg for 28 days. Clinical signs, hematological and clinical chemistry parameters were monitored, while organ weights and organ pathology were evaluated at the end of the study. RESULTS: The extract caused a significant reduction in bodyweight at 1000 mg/kg. The hematological profiles of animals at this dose showed an increase in the erythrocyte count and the hematocrit that were accompanied by decrease in the mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration. Biochemical parameters were not altered in a dose-related manner when compared to the controls. There were time associated alterations on both hematological and biochemical parameters, but pathological examination did not reveal any treatment related changes in any of the organs. CONCLUSION: Our results demonstrate that the chloroformic stem bark extract of Rapanea melanophloeos may be of no toxicological concern at dosage levels up to 1000mg/kg. Rapanea melanophloeos can therefore be used confidently in African traditional medicine at these or lower dosage levels.