Antibiotic prescribing practices in community and clinical settings during the COVID-19 pandemic in Nairobi, Kenya.

The COVID-19 pandemic has significantly impacted healthcare systems, including antibiotic use practices. We present data on patterns of antibiotic dispensing and use in community and hospital settings respectively in Nairobi, Kenya during the pandemic. We conducted interviews with 243 pharmacies in Nairobi using a standardised questionnaire from November to December 2021. The data collected included demographic characteristics, antibiotic customers, types of antibiotics sold, and antibiotic prescribing practices. Additionally, we retrospectively reviewed health records for 992 and 738 patients admitted in COVID-19 and general wards at two large inpatient hospitals between April 2020 and May 2021, and January 2019 to October 2021, respectively. Demographic, utilisation of laboratory services, treatment, clinical, and outcome data were collected using a modified Global WHO Point Prevalence Surveys (Global-PPS) tool. Almost all pharmacies (91.4%) served customers suspected of having COVID-19 with a mean weekly number of 15.6 customers. All pharmacies dispensed antibiotics, mainly azithromycin and beta lactams to suspected COVID-19 infected customers. 83.4% of hospitalised COVID-19 patients received at least one antibiotic at some point during their hospitalisation, which was significantly higher than the 53.8% in general ward patients (p<0.001). Similarly, the average number of antibiotics administered to COVID-19 patients was higher than that of patients in the general ward (1.74 vs 0.9). Azithromycin and ceftriaxone were the most commonly used antibiotics in COVID-19 patients compared to ceftriaxone and metronidazole in the general wards. Only 2% of antibiotic prescriptions for COVID-19 patients were supported by microbiological investigations, which was consistent with the proportion of 6.8% among the general ward population. Antibiotics were commonly prescribed to customers and patients suspected of having COVID-19 either in community pharmacies or in hospital, without a prescription or laboratory diagnosis. These findings emphasize the crucial role of antibiotic stewardship, particularly in community pharmacies, in the context of COVID-19.

Mapping the flow of veterinary antibiotics in Kenya.

Introduction: To effectively regulate and reduce antibiotic use, in the livestock sector, a thorough understanding of the flow of veterinary antibiotics will help to identify key nodes in the chain for targeted interventions. The aim of this study was to understand the flow of antibiotics from import to end-user, and identify relevant governance mechanisms. Methods: A mixed methods approach was used to collect data in three Kenyan counties (Nairobi, Kiambu, and Kajiado). Focus group discussions (n = 23), individual interviews (n = 148), and key informant interviews (n = 10) were conducted. Results: The key actors identified include primary wholesalers, secondary wholesalers, retailers, animal health service providers (AHSPs), and farmers. Kenya imports 100% of its veterinary antibiotics: primary wholesalers legally import antibiotics as finished pharmaceutical products (90%) or active pharmaceutical ingredients (10%) after approval by the Veterinary Medicines Directorate. Secondary wholesalers play a major role in the distribution of antibiotics (60% of antibiotics) from importers to farmers, AHSPs, and retailers. Some of the illegal sources of antibiotics include unlicenced/unauthorized middlemen and online platforms that sell directly to retailers, AHSPs, and farmers. Discussion: Despite the presence of various laws and regulations governing the antibiotic value chain, implementation has been a challenge due to financial and human resource constraints. This contributes to over-the-counter sale of antibiotics without prescription, unlicensed businesses selling antibiotics, illegal importation, and presence of poor-quality drugs. There is a need to review the applicability of existing policies and address policy gaps (e.g., product containing antibiotic combinations, and use of human critically important antibiotics) to ensure the prudent sale and use of antibiotics, pharmacovigilance, antimicrobial use surveillance, and developing a business model that aligns with antibiotic stewardship. Additional interventions include awareness raising and capacity building of the different stakeholders along the antibiotic distribution chain to reduce antibiotic mis- and overuse.

Antibiotic quality and use practices amongst dairy farmers and drug retailers in central Kenyan highlands.

Understanding antibiotic use in dairy systems is critical to guide antimicrobial stewardship programs. We investigated antibiotic use practices in small-holder dairy farms, antibiotic quality, and antimicrobial resistance (AMR) awareness among veterinary drug retailers in a mixed farming community in the central Kenyan highlands. Data were collected from 248 dairy farms and 72 veterinary drug stores between February 2020 and October 2021. A scale was developed to measure knowledge about AMR and antibiotic use using item response theory, and regression models were used to evaluate factors associated with antibiotic use and AMR knowledge. The active pharmaceutical ingredient (API) content of 27 antibiotic samples was determined using high-performance liquid chromatography (HPLC). The presence and levels of 11 antibiotic residues in 108 milk samples collected from the study farms were also investigated using liquid chromatography tandem mass spectrometry (LC-MS/MS). Almost all farms (98.8%, n = 244) reported using antibiotics at least once in the last year, mostly for therapeutic reasons (35.5%). The most used antibiotics were tetracycline (30.6%), penicillin (16.7%), and sulfonamide (9.4%), either individually or in combination, and predominantly in the injectable form. Larger farm size (OR = 1.02, p < 0.001) and history of vaccination use (OR = 1.17, p < 0.001) were significantly associated with a higher frequency of antibiotic use. Drug retailers who advised on animal treatments had a significantly higher mean knowledge scores than those who only sold drugs. We found that 44.4% (12/27) of the tested antibiotics did not meet the United States Pharmacopeial test specifications (percentage of label claim). We detected nine antibiotics in milk, including oxytetracycline, sulfamethoxazole, and trimethoprim. However, only three samples exceeded the maximum residue limits set by the Codex Alimentarius Commission. Our findings indicate that antibiotics of poor quality are accessible and used in small-holder dairy systems, which can be found in milk. These results will aid future investigations on how to promote sustainable antibiotic use practices in dairy systems.

Evidence review and recommendations for the implementation of genomics for antimicrobial resistance surveillance: reports from an international expert group.

Nearly a century after the beginning of the antibiotic era, which has been associated with unparalleled improvements in human health and reductions in mortality associated with infection, the dwindling pipeline for new antibiotic classes coupled with the inevitable spread of antimicrobial resistance (AMR) poses a major global challenge. Historically, surveillance of bacteria with AMR typically relied on phenotypic analysis of isolates taken from infected individuals, which provides only a low-resolution view of the epidemiology behind an individual infection or wider outbreak. Recent years have seen increasing adoption of powerful new genomic technologies with the potential to revolutionise AMR surveillance by providing a high-resolution picture of the AMR profile of the bacteria causing infections and providing real-time actionable information for treating and preventing infection. However, many barriers remain to be overcome before genomic technologies can be adopted as a standard part of routine AMR surveillance around the world. Accordingly, the Surveillance and Epidemiology of Drug-resistant Infections Consortium convened an expert working group to assess the benefits and challenges of using genomics for AMR surveillance. In this Series, we detail these discussions and provide recommendations from the working group that can help to realise the massive potential benefits for genomics in surveillance of AMR.

Exploiting genomics for antimicrobial resistance surveillance at One Health interfaces.

The intersection of human, animal, and ecosystem health at One Health interfaces is recognised as being of key importance in the evolution and spread of antimicrobial resistance (AMR) and represents an important, and yet rarely realised opportunity to undertake vital AMR surveillance. A working group of international experts in pathogen genomics, AMR, and One Health convened to take part in a workshop series and online consultation focused on the opportunities and challenges facing genomic AMR surveillance in a range of settings. Here we outline the working group's discussion of the potential utility, advantages of, and barriers to, the implementation of genomic AMR surveillance at One Health interfaces and propose a series of recommendations for addressing these challenges. Embedding AMR surveillance at One Health interfaces will require the development of clear beneficial use cases, especially in low-income and middle-income countries. Evidence of directionality, risks to human and animal health, and potential trade implications were also identified by the working group as key issues. Addressing these challenges will be vital to enable genomic surveillance technology to reach its full potential for assessing the risk of transmission of AMR between the environment, animals, and humans at One Health interfaces.

Practices and drivers for antibiotic use in cattle production systems in Kenya.

Understanding antibiotic use in livestock systems is key in combating antimicrobial resistance (AMR) and developing effective interventions. Using a standardised questionnaire, we investigated the patterns and drivers of antibiotic use in 165 cattle farms across the three major cattle production systems in Kenya: intensive, extensive, and semi-intensive systems across in three counties: Machakos, Makueni and Narok in Kenya. We used a causal diagram to inform regression models to explore the drivers of antibiotic use in the study farms. Antibiotic use was reported in 92.7% of farms, primarily for prophylactic purposes. Oxytetracycline, penicillin, and streptomycin were the most used antibiotics to treat and control the most reported diseases including mastitis, diarrhoea and East Coast fever (ECF). Regression analysis indicated a positive association between the frequency of antibiotic use at the farm level and both disease incidence and herd size. Conversely, farms that provided cattle with appropriate housing were less likely to use antibiotics, and there was no difference in antibiotic use between those who consulted with veterinarians or sourced antibiotics directly from animal health providers. Our study highlights the complexities around understanding the interplay between practices and drivers of antibiotic use. It also underscores the necessity to enhance education regarding the appropriate usage of antibiotics among cattle farmers, encourage the adoption of proper herd management practices which may reduce disease burden, and reinforce veterinary services and supportive legislation to promote the prudent use of antimicrobials.

Risk factors for diarrheagenic Escherichia coli infection in children aged 6-24 months in peri-urban community, Nairobi, Kenya.

Escherichia coli commonly inhabits the gut of humans and animals as part of their microbiota. Though mostly innocuous, some strains have virulence markers that make them pathogenic. This paper presents results of a cross-sectional epidemiological study examining prevalence of diarrheagenic E. coli (DEC) pathotypes in stool samples of asymptomatic healthy children (n = 540) in Dagoretti South subcounty, Nairobi, Kenya. E. coli was cultured and pathotyped using PCR to target specific virulence markers associated with Shiga-toxin, enteropathogenic, enterotoxigenic, enteroaggregative, entero-invasive and diffusely adherent E. coli. Overall prevalence of DEC pathotypes was 20.9% (113/540) with enteropathogenic E. coli being the most prevalent (34.1%), followed by enteroaggregative E. coli (23.5%) and Shiga-toxin producing E. coli (22.0%) among positive samples. We found evidence of co-infection with multiple pathotypes in 15% of the positive samples. Our models indicated that at the household level, carriage of DEC pathotypes in children was associated with age group [12-18 months] (OR 1.78; 95%CI 1.03-3.07; p = 0.04), eating matoke (mashed bananas) (OR 2.32; 95%CI 1.44-3.73; p = 0.001) and pulses/legumes (OR 1.74; 95%CI 1.01-2.99; p = 0.046) while livestock ownership or contact showed no significant association with DEC carriage (p>0.05). Our findings revealed significant prevalence of pathogenic DEC circulating among presumptive healthy children in the community. Since there has been no previous evidence of an association between any food type and DEC carriage, unhygienic handling, and preparation of matoke and pulses/legumes could be the reason for significant association with DEC carriage. Children 12-18 months old are more prone to DEC infections due to exploration and hand-to-mouth behavior. A detailed understanding is required on what proportion of positive cases developed severe symptomatology as well as fatal outcomes. The co-infection of pathotypes in the rapidly urbanizing environment needs to be investigated for hybrid or hetero-pathotype circulation that have been implicated in previous infection outbreaks.

Epidemiological connectivity between humans and animals across an urban landscape.

Urbanization is predicted to be a key driver of disease emergence through human exposure to novel, animal-borne pathogens. However, while we suspect that urban landscapes are primed to expose people to novel animal-borne diseases, evidence for the mechanisms by which this occurs is lacking. To address this, we studied how bacterial genes are shared between wild animals, livestock, and humans (n = 1,428) across Nairobi, Kenya-one of the world's most rapidly developing cities. Applying a multilayer network framework, we show that low biodiversity (of both natural habitat and vertebrate wildlife communities), coupled with livestock management practices and more densely populated urban environments, promotes sharing of Escherichia coli-borne bacterial mobile genetic elements between animals and humans. These results provide empirical support for hypotheses linking resource provision, the biological simplification of urban landscapes, and human and livestock demography to urban dynamics of cross-species pathogen transmission at a landscape scale. Urban areas where high densities of people and livestock live in close association with synanthropes (species such as rodents that are more competent reservoirs for zoonotic pathogens) should be prioritized for disease surveillance and control.

Genomic epidemiology of Escherichia coli: antimicrobial resistance through a One Health lens in sympatric humans, livestock and peri-domestic wildlife in Nairobi, Kenya.

BACKGROUND: Livestock systems have been proposed as a reservoir for antimicrobial-resistant (AMR) bacteria and AMR genetic determinants that may infect or colonise humans, yet quantitative evidence regarding their epidemiological role remains lacking. Here, we used a combination of genomics, epidemiology and ecology to investigate patterns of AMR gene carriage in Escherichia coli, regarded as a sentinel organism. METHODS: We conducted a structured epidemiological survey of 99 households across Nairobi, Kenya, and whole genome sequenced E. coli isolates from 311 human, 606 livestock and 399 wildlife faecal samples. We used statistical models to investigate the prevalence of AMR carriage and characterise AMR gene diversity and structure of AMR genes in different host populations across the city. We also investigated household-level risk factors for the exchange of AMR genes between sympatric humans and livestock. RESULTS: We detected 56 unique acquired genes along with 13 point mutations present in variable proportions in human and animal isolates, known to confer resistance to nine antibiotic classes. We find that AMR gene community composition is not associated with host species, but AMR genes were frequently co-located, potentially enabling the acquisition and dispersal of multi-drug resistance in a single step. We find that whilst keeping livestock had no influence on human AMR gene carriage, the potential for AMR transmission across human-livestock interfaces is greatest when manure is poorly disposed of and in larger households. CONCLUSIONS: Findings of widespread carriage of AMR bacteria in human and animal populations, including in long-distance wildlife species, in community settings highlight the value of evidence-based surveillance to address antimicrobial resistance on a global scale. Our genomic analysis provided an in-depth understanding of AMR determinants at the interfaces of One Health sectors that will inform AMR prevention and control.

Detection of Antibodies to Ehrlichia spp. in Dromedary Camels and Co-Grazing Sheep in Northern Kenya Using an Ehrlichia ruminantium Polyclonal Competitive ELISA.

A disease with clinical and post-mortem presentation similar to those seen in heartwater, a tick-borne disease of domestic and wild ruminants caused by the intracellular bacterium Ehrlichia ruminantium, was first reported in dromedary camels in Kenya in 2016; investigations carried out at the time to determine the cause were inconclusive. In the present study, we screened sera from Kenyan camels collected before (2015) and after (2020) the 2016 disease outbreak for antibodies to Ehrlichia spp. using an E. ruminantium polyclonal competitive ELISA (PC-ELISA). Median antibody levels were significantly higher (p < 0.0001) amongst camels originating from areas where the heartwater-like disease was reported than from disease-free areas, for animals sampled in both 2015 and 2020. Overall median seropositivity was higher in camels sampled in 2015 than in 2020, which could have been due to higher mean age in the former group. Camels that were PCR-positive for Candidatus Ehrlichia regneryi had significantly lower (p = 0.03) median antibody levels than PCR-negative camels. Our results indicate that Kenyan camels are frequently exposed to E. ruminantium from an early age, E. ruminantium was unlikely to have been the sole cause of the outbreak of heartwater-like disease; and Ca. E. regneryi does not appreciably cross-react with E. ruminantium in the PC-ELISA.

Population genomics of Escherichia coli in livestock-keeping households across a rapidly developing urban landscape.

Quantitative evidence for the risk of zoonoses and the spread of antimicrobial resistance remains lacking. Here, as part of the UrbanZoo project, we sampled Escherichia coli from humans, livestock and peri-domestic wildlife in 99 households across Nairobi, Kenya, to investigate its distribution among host species in this rapidly developing urban landscape. We performed whole-genome sequencing of 1,338 E. coli isolates and found that the diversity and sharing patterns of E. coli were heavily structured by household and strongly shaped by host type. We also found evidence for inter-household and inter-host sharing and, importantly, between humans and animals, although this occurs much less frequently. Resistome similarity was differently distributed across host and household, consistent with being driven by shared exposure to antimicrobials. Our results indicate that a large, epidemiologically structured sampling framework combined with WGS is needed to uncover strain-sharing events among different host populations in complex environments and the major contributing pathways that could ultimately drive the emergence of zoonoses and the spread of antimicrobial resistance.

Strengthening global health security by improving disease surveillance in remote rural areas of low-income and middle-income countries.

The COVID-19 pandemic has underscored the need to strengthen national surveillance systems to protect a globally connected world. In low-income and middle-income countries, zoonotic disease surveillance has advanced considerably in the past two decades. However, surveillance efforts often prioritise urban and adjacent rural communities. Communities in remote rural areas have had far less support despite having routine exposure to zoonotic diseases due to frequent contact with domestic and wild animals, and restricted access to health care. Limited disease surveillance in remote rural areas is a crucial gap in global health security. Although this point has been made in the past, practical solutions on how to implement surveillance efficiently in these resource-limited and logistically challenging settings have yet to be discussed. We highlight why investing in disease surveillance in remote rural areas of low-income and middle-income countries will benefit the global community and review current approaches. Using semi-arid regions in Kenya as a case study, we provide a practical approach by which surveillance in remote rural areas can be strengthened and integrated into existing systems. This Viewpoint represents a transition from simply highlighting the need for a more holistic approach to disease surveillance to a solid plan for how this outcome might be achieved.

Co-infection of pigs with Taenia solium cysticercosis and gastrointestinal parasites in Eastern and Western Uganda.

A study was carried out in Kamuli and Hoima districts in Eastern and Western regions of Uganda to determine the Taenia solium porcine cysticercosis (PCC) and gastrointestinal (GI) parasites co-infection status in pigs. One hundred sixty-one households were selected randomly and visited between November and December 2019. A household questionnaire was administered, and faecal and blood samples were collected from at least one pig older than 3 months per household. A blood sample was obtained from a jugular venipuncture, and a rectal faecal sample was obtained. Taenia spp. circulating antigen levels in the sample sera were tested using a commercial enzyme-linked immunosorbent assay kit, apDia™ cysticercosis Ag ELISA. The modified McMaster technique was used to identify and quantify the GI parasites. The apparent animal-level seroprevalence for PCC was 4.8% (95% CI 2.7-7.1) and differed across the two districts (p = 0.018). At the pig herd level, the prevalence was 9.7% (95% CI 5.5-14.4). The prevalence of the different nematode eggs and coccidian oocysts in the two districts was as follows: strongyles 79.0% (95% CI 74.3-83.6), coccidia 73.3% (95% CI 68.3-78.6), Trichuris spp. 7.4% (95% CI 4.9-10.6), Strongyloides ransomi 2.1 (95% CI 0.7-3.5) and Ascaris spp. 4.9 (95% CI 2.8-7.4). Overall, across the two districts, the arithmetic mean for the oocysts per gram (OPG) for coccidia was 2042.2 ± 5776.1, and eggs per gram (EPG) were the highest in strongyles 616.1 ± 991. Overall, 57.4% of the porcine cysticercosis seropositive pigs were also positive for at least one of the gastrointestinal helminths which included strongyles, Strongyloides ransomi, Trichuris spp. and Ascaris spp. The co-infection status of pigs with both PCC and GI parasites demonstrated by this study can provide an incentive for integrating the control and management of both parasites with oxfendazole. Further studies are required to understand the feasibility of using oxfendazole including cost-benefit analysis and the acceptability by local stakeholders for the control of T. solium cysticercosis and gastrointestinal parasites in pigs.

The Nairobi Pork Value Chain: Mapping and Assessment of Governance, Challenges, and Food Safety Issues.

The Nairobi pork food system is a growing livestock sub-sector which serves as a source of food and livelihood to its inhabitants. The study aimed to map Nairobi's pork value chains, assess their governance, operational challenges and their impacts on food safety risks and management practices. Qualitative data were collected in seven focus group discussions and 10 key informants' interviews on animal movements and product flows, stakeholders' interactions, perceptions on system governance and challenges, and on their potential impact on food safety management. Quantitative data were obtained to show the importance of flows, business operations and market share. Thematic analysis was conducted to identify themes that provide understanding on the governance, challenges and food safety practices in each profile. The predominant chains identified were [1] The "large integrated company" profile which accounted for 83.6% of pork marketed through abattoirs, and was based on a well-structured supply system, with owned farms (representing 50% of their supply), contract farms and semi-contract farms and [2] Local independent abattoirs, accounting for 16.4%, are privately owned small-scale production, supplied mainly (70%) by small farmers from the immediate neighboring areas. The main challenges associated with governance themes included; (i) Inadequate/lack of enforcement of existing regulation (ii) Negative effect of devolution system of governance (iii) Pig traders' dominance (iii) Lack of association at all system nodes, and (iv) Male dominance across the pig system. The main challenges reported included; (i) Lack of capital to upscale (ii) Poor infrastructure (iii) Pig shortage (iv) Excessive regulation (v) Lack of training (vi) Diseases (v) Lack of knowledge (vi) Unfair competition. Food safety themes were associated with (i) Inadequate slaughter facilities forcing traders/farmers to undertake home slaughter (ii) Lack of knowledge on disease management (iii) Lack of training on hygienic practices in the slaughterhouse and (iv) Lack/insufficient capital to purchase equipment's to ensure proper hygiene e.g., boilers. The study provides insights into the structure of the pork system supplying Nairobi, the governance issues important to the stakeholders, challenges and food safety issues. The framework obtained can be used by policy makers and researchers to investigate and develop pork industry and for food safety and disease control programmes.

Socio-ecological drivers of vertebrate biodiversity and human-animal interfaces across an urban landscape.

Urbanization can have profound impacts on the distributional ecology of wildlife and livestock, with implications for biodiversity conservation, ecosystem services and human health. A wealth of studies have assessed biotic responses to urbanization in North America and Europe, but there is little empirical evidence that directly links human activities to urban biodiversity in the tropics. Results from a large-scale field study conducted in Nairobi, Kenya, are used to explore the impact of human activities on the biodiversity of wildlife and livestock with which humans co-exist across the city. The structure of sympatric wildlife, livestock and human populations are characterized using unsupervised machine learning, and statistical modelling is used to relate compositional variation in these communities to socio-ecological drivers occurring across the city. By characterizing landscape-scale drivers acting on these interfaces, we demonstrate that socioeconomics, elevation and subsequent changes in habitat have measurable impacts upon the diversity, density and species assemblage of wildlife, livestock and humans. Restructuring of wildlife and livestock assemblages (both in terms of species diversity and composition) has important implications for the emergence of novel diseases at urban interfaces, and we therefore use our results to generate a set of testable hypotheses that explore the influence of urban change on microbial communities. These results provide novel insight into the impact of urbanization on biodiversity in the tropics. An understanding of associations between urban processes and the structure of human and animal populations is required to link urban development to conservation efforts and risks posed by disease emergence to human health, ultimately informing sustainable urban development policy.

Quantifying the transmission of antimicrobial resistance at the human and livestock interface with genomics.

BACKGROUND: Livestock have been implicated as a reservoir for antimicrobial resistance (AMR) that can spread to humans. Close proximity and ecological interfaces involving livestock have been posited as risk factors for the transmission of AMR. In spite of this, there are sparse data and limited agreement on the transmission dynamics that occur. OBJECTIVES: To identify how genome sequencing approaches can be used to quantify the dynamics of AMR transmission at the human-livestock interface, and where current knowledge can be improved to better understand the impact of transmission on the spread of AMR. SOURCES: Key articles investigating various aspects of AMR transmission at the human-livestock interface are discussed, with a focus on Escherichia coli. CONTENT: We recapitulate the current understanding of the transmission of AMR between humans and livestock based on current genomic and epidemiological approaches. We discuss how the use of well-designed, high-resolution genome sequencing studies can improve our understanding of the human-livestock interface. IMPLICATIONS: A better understanding of the human-livestock interface will aid in the development of evidence-based and effective One Health interventions that can ultimately reduce the burden of AMR in humans.

Volunteer based approach to dog vaccination campaigns to eliminate human rabies: Lessons from Laikipia County, Kenya.

BACKGROUND: An estimated 59,000 people die from rabies annually, with 99% of those deaths attributable to bites from domestic dogs (Canis lupus familiaris). This preventable Neglected Tropical Disease has a large impact across continental Africa, especially for rural populations living in close contact with livestock and wildlife. Mass vaccinations of domestic dogs are effective at eliminating rabies but require large amounts of resources, planning, and political will to implement. Grassroots campaigns provide an alternative method to successful implementation of rabies control but remain understudied in their effectiveness to eliminate the disease from larger regions. METHODOLOGY/PRINCIPAL FINDINGS: We report on the development, implementation, and effectiveness of a grassroots mass dog rabies vaccination campaign in Kenya, the Laikipia Rabies Vaccination Campaign. During 2015-2017, a total of 13,155 domestic dogs were vaccinated against rabies in 17 communities covering approximately 1500 km2. Based on an estimated population size of 34,275 domestic dogs, percent coverages increased across years, from 2% in 2015 to 24% in 2017, with only 3 of 38 community-years of vaccination exceeding the 70% target. The average cost of vaccinating an animal was $3.44 USD with in-kind contributions and $7.44 USD without in-kind contributions. CONCLUSIONS/SIGNIFICANCE: The evolution of the Laikipia Rabies Vaccination Campaign from a localized volunteer-effort to a large-scale program attempting to eliminate rabies at the landscape scale provides a unique opportunity to examine successes, failures, and challenges facing grassroots campaigns. Success, in the form of vaccinating more dogs across the study area, was relatively straightforward to achieve. However, lack of effective post-vaccination monitoring and education programs, limited funding, and working in diverse community types appeared to hinder achievement of 70% coverage levels. These results indicate that grassroots campaigns will inevitably be faced with a philosophical question regarding the value of local impacts versus their contributions to a larger effort to eliminate rabies at the regional, country, or global scale.

A cross-sectional survey of practices and knowledge among antibiotic retailers in Nairobi, Kenya.

BACKGROUND: Antimicrobial resistance (AMR) driven by antibiotic consumption is a growing global health threat. However, data on antimicrobial consumption patterns in low- and middle-income countries (LMICs) is sparse. Here, we investigate the patterns of antibiotic sales in humans and livestock in urban Nairobi, Kenya, and evaluate the level of awareness and common behaviours related to antibiotic use and AMR amongst human and veterinary pharmacists. METHODS: A total of 40 human and 19 veterinary drug store pharmacists were interviewed in Nairobi in 2018 using a standard questionnaire. Data recorded included demographic variables, types of antibiotics sold, antibiotic customers, antibiotic prescribing practices and knowledge of antibiotic use and AMR. RESULTS: Our study shows that at the retail level, there is a considerable overlap between antibiotic classes (10/15) sold for use in both human and veterinary medicine. Whilst in our study, clinical training significantly influenced knowledge on issues related to antibiotic use and AMR and respondents had a relatively adequate level of knowledge about AMR, several inappropriate prescribing practices were identified. For example, we found that most veterinary and human drug stores (100% and 52% respectively) sold antibiotics without a prescription and noted that customer preference was an important factor when prescribing antibiotics in half of the drug stores. CONCLUSION: Although more research is needed to understand the drivers of antibiotic consumption in both human and animal populations, these findings highlight the need for immediate strategies to improve prescribing practices across the pharmacists in Nairobi and by extension other low- and middle-income country settings.

Epidemiology of antimicrobial-resistant Escherichia coli carriage in sympatric humans and livestock in a rapidly urbanizing city.

There are substantial limitations in understanding of the distribution of antimicrobial resistance (AMR) in humans and livestock in developing countries. This papers present the results of an epidemiological study examining patterns of AMR in Escherichia coli isolates circulating in sympatric human (n = 321) and livestock (n = 633) samples from 99 households across Nairobi, Kenya. E. coli isolates were tested for susceptibility to 13 antimicrobial drugs representing nine antibiotic classes. High rates of AMR were detected, with 47.6% and 21.1% of isolates displaying resistance to three or more and five or more antibiotic classes, respectively. Human isolates showed higher levels of resistance to sulfonamides, trimethoprim, aminoglycosides and penicillins compared with livestock (P<0.01), while poultry isolates were more resistant to tetracyclines (P = 0.01) compared with humans. The most common co-resistant phenotype observed was to tetracyclines, streptomycin and trimethoprim (30.5%). At the household level, AMR carriage in humans was associated with human density (P<0.01) and the presence of livestock manure (P = 0.03), but keeping livestock had no influence on human AMR carriage (P>0.05). These findings revealed a high prevalence of AMR E. coli circulating in healthy humans and livestock in Nairobi, with no evidence to suggest that keeping livestock, when treated as a single risk factor, contributed significantly to the burden of AMR in humans, although the presence of livestock waste was significant. These results provide an understanding of the broader epidemiology of AMR in complex and interconnected urban environments.

Clinically relevant antimicrobial resistance at the wildlife-livestock-human interface in Nairobi: an epidemiological study.

BACKGROUND: Antimicrobial resistance is one of the great challenges facing global health security in the modern era. Wildlife, particularly those that use urban environments, are an important but understudied component of epidemiology of antimicrobial resistance. We investigated antimicrobial resistance overlap between sympatric wildlife, humans, livestock, and their shared environment across the developing city of Nairobi, Kenya. We use these data to examine the role of urban wildlife in the spread of clinically relevant antimicrobial resistance. METHODS: 99 households across Nairobi were randomly selected on the basis of socioeconomic stratification. A detailed survey was administered to household occupants, and samples (n=2102) were collected from the faeces of 75 wildlife species inhabiting household compounds (ie, the household and its perimeter; n=849), 13 livestock species (n=656), and humans (n=333), and from the external environment (n=288). Escherichia coli, our sentinel organism, was cultured and a single isolate from each sample tested for sensitivity to 13 antibiotics. Diversity of antimicrobial resistant phenotypes was compared between urban wildlife, humans, livestock, and the environment, to investigate whether wildlife are a net source for antimicrobial resistance in Nairobi. Generalised linear mixed models were used to determine whether the prevalence of antimicrobial resistant phenotypes and multidrug-resistant E coli carriage in urban wildlife is linked to variation in ecological traits, such as foraging behaviour, and to determine household-level risk factors for sharing of antimicrobial resistance between humans, wildlife, and livestock. FINDINGS: E coli were isolated from 485 samples collected from wildlife between Sept 6,2015, and Sept 28, 2016. Wildlife carried a low prevalence of E coli isolates susceptible to all antibiotics tested (45 [9%] of 485 samples) and a high prevalence of clinically relevant multidrug resistance (252 [52%] of 485 samples), which varied between taxa and by foraging traits. Multiple isolates were resistant to one agent from at least seven antimicrobial classes tested for, and a single isolate was resistant to all antibiotics tested for in the study. The phenotypic diversity of antimicrobial-resistant E coli in wildlife was lower than in livestock, humans, and the environment. Within household compounds, statistical models identified two interfaces for exchange of antimicrobial resistance: between both rodents, humans and their rubbish, and seed-eating birds, humans and their rubbish; and between seed-eating birds, cattle, and bovine manure. INTERPRETATION: Urban wildlife carry a high burden of clinically relevant antimicrobial-resistant E coli in Nairobi, exhibiting resistance to drugs considered crucial for human medicine by WHO. Identifiable traits of the wildlife contribute to this exposure; however, compared with humans, livestock, and the environment, low phenotypic diversity in wildlife is consistent with the hypothesis that wildlife are a net sink rather than source of clinically relevant resistance. Wildlife that interact closely with humans, livestock, and both human and livestock waste within households, are exposed to more antimicrobial resistant phenotypes, and could therefore act as conduits for the dissemination of clinically relevant antimicrobial resistance to the wider environment. These results provide novel insight into the broader epidemiology of antimicrobial resistance in complex urban environments, characteristic of lower-middle-income countries. FUNDING: UK Medical Research Council and CGIAR Research Program on Agriculture for Nutrition and Health.