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.

Comparative Analysis of Commercially Available Typhoid Point-of-Care Tests: Results of a Prospective and Hybrid Retrospective Multicenter Diagnostic Accuracy Study in Kenya and Pakistan.

Blood and bone marrow cultures are considered the gold standard for the diagnosis of typhoid, but these methods require infrastructure and skilled staff that are not always available in low- and middle-income countries where typhoid is endemic. The objective of the study is to evaluate the sensitivity and specificity of nine commercially available Salmonella Typhi rapid diagnostic tests (RDTs) using blood culture as a reference standard in a multicenter study. This was a prospective and retrospective multicenter diagnostic accuracy study conducted in two geographically distant areas where typhoid is endemic (Pakistan and Kenya; NCT04801602). Nine RDTs were evaluated, including the Widal test. Point estimates for sensitivity and specificity were calculated using the Wilson method. Latent class analyses were performed using R to address the imperfect gold standard. A total of 531 serum samples were evaluated (264 blood culture positive; 267 blood culture negative). The sensitivity of RDTs varied widely (range, 0 to 78.8%), with the best overall performance shown by Enterocheck WB (72.7% sensitivity, 86.5% specificity). In latent class modeling, CTK IgG was found to have the highest sensitivity (79.1%), while the highest overall accuracy was observed with Enterocheck (73.8% sensitivity, 94.5% specificity). All commercially available Salmonella Typhi RDTs evaluated in the study had sensitivity and specificity values that fell below the required levels to be recommended for an accurate diagnosis. There were minimal differences in RDT performances between regions of endemicity. These findings highlight the clear need for new and more-accurate Salmonella Typhi tests.

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.

Azithromycin to prevent post-discharge morbidity and mortality in Kenyan children: a protocol for a randomised, double-blind, placebo-controlled trial (the Toto Bora trial).

INTRODUCTION: Child mortality due to infectious diseases remains unacceptably high in much of sub-Saharan Africa. Children who are hospitalised represent an accessible population at particularly high risk of death, both during and following hospitalisation. Hospital discharge may be a critical time point at which targeted use of antibiotics could reduce morbidity and mortality in high-risk children. METHODS AND ANALYSIS: In this randomised, double-blind, placebo-controlled trial (Toto Bora Trial), 1400 children aged 1-59 months discharged from hospitals in Western Kenya, in Kisii and Homa Bay, will be randomised to either a 5-day course of azithromycin or placebo to determine whether a short course of azithromycin reduces rates of rehospitalisation and/or death in the subsequent 6-month period. The primary analysis will be modified intention-to-treat and will compare the rates of rehospitalisation or death in children treated with azithromycin or placebo using Cox proportional hazard regression. The trial will also evaluate the effect of a short course of azithromycin on enteric and nasopharyngeal infections and cause-specific morbidities. We will also identify risk factors for postdischarge morbidity and mortality and subpopulations most likely to benefit from postdischarge antibiotic use. Antibiotic resistance in Escherichia coli and Streptococcus pneumoniae among enrolled children and their primary caregivers will also be assessed, and cost-effectiveness analyses will be performed to inform policy decisions. ETHICS AND DISSEMINATION: Study procedures were reviewed and approved by the institutional review boards of the Kenya Medical Research Institute, the University of Washington and the Kenyan Pharmacy and Poisons Board. The study is being externally monitored, and a data safety and monitoring committee has been assembled to monitor patient safety and to evaluate the efficacy of the intervention. The results of this trial will be published in peer-reviewed scientific journals and presented at relevant academic conferences and to key stakeholders. TRIAL REGISTRATION NUMBER: NCT02414399.

Antibiotic resistance-the need for global solutions.

The causes of antibiotic resistance are complex and include human behaviour at many levels of society; the consequences affect everybody in the world. Similarities with climate change are evident. Many efforts have been made to describe the many different facets of antibiotic resistance and the interventions needed to meet the challenge. However, coordinated action is largely absent, especially at the political level, both nationally and internationally. Antibiotics paved the way for unprecedented medical and societal developments, and are today indispensible in all health systems. Achievements in modern medicine, such as major surgery, organ transplantation, treatment of preterm babies, and cancer chemotherapy, which we today take for granted, would not be possible without access to effective treatment for bacterial infections. Within just a few years, we might be faced with dire setbacks, medically, socially, and economically, unless real and unprecedented global coordinated actions are immediately taken. Here, we describe the global situation of antibiotic resistance, its major causes and consequences, and identify key areas in which action is urgently needed.

Pattern of pathogens and their sensitivity isolated from surgical site infections at the Aga Khan University Hospital, Nairobi, Kenya.

BACKGROUND: In low income countries, surgical site infections (SSIs) are costly and impose a heavy and potentially preventable burden on both patients and healthcare providers. This study aimed to determine the occurrence of SSI, pathogens associated with SSI, the antibiogram of the causative pathogens and specific risk factors associated with SSI at the hospital. METHODS: Two hundred and sixty-eight respondents admitted for general surgical procedures (other than neurological and cardiothoracic surgeries) at the Aga Khan University Hospital were eligible to take part in the study. Post-surgery patients were observed for symptoms of infection. Follow ups were done through the consulting clinics, breast clinic and casualty dressing clinic by a team of surgeons. In cases of infection, pus swabs were collected for culture. RESULTS: SSI incidence rate was 7.0%, pathogens isolated from SSI included gram negative enteric bacilli and S. aureus which was the most prevalent bacterial isolate. Only one isolate of MRSA was found and all staphylococci were susceptible to Vancomycin. Preoperative stay ≥ 2 days and wound class were the risk factors associated with SSI. CONCLUSION: The SSI incidence rates (7.0%) observed in this study were relatively lower than the ones documented in other studies in Kenya. S. aureus is the most prevalent pathogen associated with SSI. Similar to findings from other studies done in the region; prolonged hospital stay and dirty wounds were the risks associated with postsurgical sepsis at the hospital.

Prevalence and genetic characteristics of Shigatoxigenic Escherichia coli from patients with diarrhoea in Maasailand, Kenya.

INTRODUCTION: Shigatoxigenic Escherichia coli strains are food-borne bacterial pathogens that may cause haemorrhagic colitis (HC) in humans which can lead to life-threatening systemic complication, including haemolytic uremic syndrome (HUS). This study aimed to characterize and analyze virulence properties of pathogenic E. coli isolates among patients with diarrhoea from a Maasai community in Kenya. METHODOLOGY: Stool samples from 380 patients of all ages from the Kajiado and Narok districts of Kenya were investigated for the presence of enteric bacterial pathogens by conventional and molecular methods. RESULTS: Bacterial diarrhoea was diagnosed in 141/380 (37.1%) cases, of which enterotoxigenic E. coli (ETEC) compromised 29.8%, shigatoxigenic E. coli (STEC) 24.1%, enteroaggregative E. coli (EAEC) 14.2%, enteroinvasive E. coli (EIEC) 12.8% and enteropathogenic E. coli (EPEC) 3.5%. Gene analysis for STEC virulence factors showed that 52.9% isolates carried stx1, 29.4% possessed stx2, 14.7% carried both stx1 and stx2, and 2.9% had stx2e. 23.5% isolates carried enterohaemolysin and 20.5% isolates possessed the Intimin gene. From 9 strains that exhibited adherence, 7 contained both Intimin and Haemolysin genes. Infections with Intimin-positive STEC strains (46%) were more frequent in patients with bloody diarrhoea, especially in children under 5 years of age, whereas Intimin-negative STEC infections dominated in adults. CONCLUSION: Although STEC infection as a cause of bloody diarrhoea has not attracted much attention as a medical problem in Kenya, our findings indicate that this is a problem that must be investigated. The 24.1% isolation rate of STEC among the Maasai is one of the highest reported rates worldwide.

Emergence of a globally dominant IncHI1 plasmid type associated with multiple drug resistant typhoid.

Typhoid fever, caused by Salmonella enterica serovar Typhi (S. Typhi), remains a serious global health concern. Since their emergence in the mid-1970s multi-drug resistant (MDR) S. Typhi now dominate drug sensitive equivalents in many regions. MDR in S. Typhi is almost exclusively conferred by self-transmissible IncHI1 plasmids carrying a suite of antimicrobial resistance genes. We identified over 300 single nucleotide polymorphisms (SNPs) within conserved regions of the IncHI1 plasmid, and genotyped both plasmid and chromosomal SNPs in over 450 S. Typhi dating back to 1958. Prior to 1995, a variety of IncHI1 plasmid types were detected in distinct S. Typhi haplotypes. Highly similar plasmids were detected in co-circulating S. Typhi haplotypes, indicative of plasmid transfer. In contrast, from 1995 onwards, 98% of MDR S. Typhi were plasmid sequence type 6 (PST6) and S. Typhi haplotype H58, indicating recent global spread of a dominant MDR clone. To investigate whether PST6 conferred a selective advantage compared to other IncHI1 plasmids, we used a phenotyping array to compare the impact of IncHI1 PST6 and PST1 plasmids in a common S. Typhi host. The PST6 plasmid conferred the ability to grow in high salt medium (4.7% NaCl), which we demonstrate is due to the presence in PST6 of the Tn6062 transposon encoding BetU.

Cholera-like diarrhoea due to Salmonella infection.

An unusually high number of sporadic cholera outbreaks have occurred in various parts of Kenya since January 2009. Clinical symptoms of cholera play an important role in the diagnosis and management of the disease, especially in resource-poor settings in most developing countries. We describe a case report of a patient who was treated for cholera according to symptoms at presentation to hospital. Non-typhoid Salmonella was later isolated and the patient's condition improved after administration of ciprofloxacin.

Trends in Salmonella enteric serovar Typhi in Nairobi, Kenya from 2004 to 2006.

BACKGROUND: Typhoid fever is a global health problem. The World Health Organization (WHO) estimates that the current annual global burden of typhoid is approximately 22 million new cases, 5% of which are fatal. METHODOLOGY: To assess the trends in antibiotic resistance in 100 Salmonella enterica serovar Typhi strains were isolated from the blood of patients in Nairobi, Kenya, from 2004 to 2006. All isolates were tested against ampicilin, chloramphenic, nalidixic acid, ciprofloxacin, cotrimoxazole, cefuroxime, cefriaxone, amoxycillin/clavulanic acid, tetracycline and gentamycin. Susceptibility and resistance were determined using MIC and disk diffusion tests. RESULTS: From 2004 to 2006 a total of 100 strains were studied; 70% of the isolates were multidrug resistant (MDR) while 15% of the isolates were sensitive to all drugs tested. Of 13 isolates that were resistant to ciprofloxacin and nalidixic acid by disk diffusion, 11 had an MIC of 0. 25 microg/ml while two isolates had an MIC of 1.00 microg,/ml. Resistance in ampicillin decreased from 88% in 2004 to 64% in 2005; this increased to 76% in 2006. Similar trends were observed for four other antibiotics tested. CONCLUSION: The prescription of first-line antibiotics used in the treatment of S. Typhi should be stopped temporarily. Drugs such as cipfloxacin would be useful in the treatment of typhoid caused by MDR S. Typhi. There is need to monitor the resistance in flouroquinolones as resistance to these drugs has been observed and they are the current drugs used to treat typhoid.

Costs of hospital care for HIV-positive and HIV-negative patients at Kenyatta National Hospital, Nairobi, Kenya.

OBJECTIVE: To record the costs of hospital care for HIV-positive and -negative patients in Nairobi, and identify costs paid by patients per admission. DESIGN: Cost data were collected on inpatients enrolled in a linked clinical study using standardized costing methods. SETTING: Kenyatta National Hospital, Nairobi's main district hospital. PATIENTS: Consecutive adult medical admissions to one ward over 14 weeks who consented to enrollment; tertiary referrals were excluded. MAIN OUTCOME MEASURE: Average length of stay and cost per patient admission. RESULTS: The hospital costs of 398 patients (163 HIV positive; 33 with clinical AIDS) were analysed. The mean length of stay was 9.3 days and the mean cost per patient admission was US$163. There was no significant difference in costs or mean lengths of stay between HIV-positive and -negative groups, nor were the costs and lengths of stay for clinical AIDS patients significantly different to those for HIV-positive patients without AIDS. The patient charges paid to the hospital per admission, recorded for 344 patients, were on average US$61; and did not differ by HIV status. CONCLUSION: The similar cost patterns for inpatient care irrespective of HIV status or clinical AIDS probably reflects the limited provision of care beyond basic clinical services. Length of stay rather than differing treatment regimes thus appears to be the main cost driver. Private costs of medical care were high and were likely to pressurize households. When resources are limited, the introduction of new, more costly therapies needs careful planning. The study provides cost information for planning care services in resource-poor settings.