Yemen is currently experiencing the largest cholera epidemic in recent history. The first cases were declared in September 2016, and over 1.1 million cases and 2,300 deaths have since been reported1. We investigated the phylogenetic relationships, pathogenesis, and antimicrobial resistance determinants by sequencing the genomes of Vibrio cholerae isolates from the Yemen epidemic and recent isolates from neighbouring regions. These 116 genomic sequences were placed within the phylogenetic context of a global collection of 1087 seventh pandemic V. cholerae serogroup O1 and O139 biotype El Tor isolates [2–4]. We show that the Yemeni isolates collected during the two epidemiological waves of the epidemic [1], —the first between September 28th 2016 and April 23rd 2017 (25,839 suspected cases) and the second beginning on April 24th, 2017 (more than one million suspected cases), — are seventh pandemic V. cholerae O1 El Tor (7PET) serotype Ogawa isolates from a single sublineage. Using genomic approaches, we link the Yemen epidemic to global radiations of pandemic V. cholerae and show that this sublineage originated from South Asia and that it caused outbreaks in East Africa before appearing in Yemen. We also show that the Yemeni isolates are susceptible to several antibiotics commonly used to treat cholera, and to polymyxins, resistance to which is used as a marker of the El Tor biotype.

In Africa, multidrug-resistant non-typhoidal salmonellae (NTS) are one of the leading causes of morbidity and high mortality in children under 5 years of age, second in importance only to pneumococcal disease. The authors studied NTS isolates from paediatric admissions at two hospitals in Nairobi, Kenya, and followed the index cases to their homes, where rectal swabs and stools from parents and siblings, and from animals in close contact, were obtained. The majority of NTS obtained from cases were Salmonella enterica serotype Typhimurium (106 out of 193; 54?9 %) and Salmonella enterica serotype Enteritidis (64; 33?2 %), a significant proportion (34?2 %) of which were multiply resistant to three or more antibiotics, including ampicillin, tetracycline, cotrimoxazole and chloramphenicol. Only 23?4 % of NTS were fully susceptible to all 10 antibiotics tested. Of the 32 NTS obtained from contacts (nine adults and 23 children) at the homes of index cases, 21 (65?6 %) isolates were similar by antibiotic-susceptibility profiles and plasmid content, and their XbaI-and SpeI-digested chromosomal DNA patterns were indistinguishable from those of the corresponding index cases. Only three out of 180 (1?7 %) samples from environmental sources, including animals, soil, sewers and food, contained NTS matching those from corresponding index cases. The carriage of NTS in an asymptomatic population was represented by 6?9 % of human contacts from 27 out of 127 homes sampled. This population of carriers may represent an important reservoir of NTS that would play a significant role in the epidemiology of community-acquired NTS bacteraemia in children.

In sub-Saharan Africa, the burden of typhoid fever, caused by Salmonella enterica serovar Typhi, remains largely unknown, in part because of a lack of blood or bone marrow culture facilities. We characterized a total of 323 S. Typhi isolates from outbreaks in Kenya over the period 1988 to 2008 for antimicrobial susceptibilities and phylogenetic relationships using single-nucleotide polymorphism (SNP) analysis. There was a dramatic increase in the number and percentage of multidrug-resistant (MDR) S. Typhi isolates over the study period. Overall, only 54 (16.7%) S. Typhi isolates were fully sensitive, while the majority, 195 (60.4%), were multiply resistant to most commonly available drugs-ampicillin, chloramphenicol, tetracycline, and cotrimoxazole; 74 (22.9%) isolates were resistant to a single antimicrobial, usually ampicillin, cotrimoxazole, or tetracycline. Resistance to these antibiotics was encoded on self-transferrable IncHI1 plasmids of the ST6 sequence type. Of the 94 representative S. Typhi isolates selected for genome-wide haplotype analysis, sensitive isolates fell into several phylogenetically different groups, whereas MDR isolates all belonged to a single haplotype, H58, associated with MDR and decreased ciprofloxacin susceptibility, which is also dominant in many parts of Southeast Asia. Derivatives of the same S. Typhi lineage, H58, are responsible for multidrug resistance in Kenya and parts of Southeast Asia, suggesting intercontinental spread of a single MDR clone. Given the emergence of this aggressive MDR haplotype, careful selection and monitoring of antibiotic usage will be required in Kenya, and potentially other regions of sub-Saharan Africa.

Antimicrobial resistance is a growing public health challenge that is expected to disproportionately burden lower-and middle-income countries (LMICs) in the coming decades. Although the contributions of human and veterinary antibiotic misuse to this crisis are well-recognized, environmental transmission (via water, soil, or food contaminated with human and animal feces) has been given less attention as a global driver of antimicrobial resistance (AMR), especially in urban informal settlements in LMICs, commonly known as "shantytowns" or "slums." These settlements may be unique hotspots for environmental AMR transmission given: 1) the high density of humans, livestock, and vermin living in close proximity; 2) frequent antibiotic misuse; and 3) insufficient drinking water, drainage, and sanitation infrastructure. Here, we highlight the need for strategies to disrupt environmental AMR transmission in urban informal settlements. We propose that water and waste infrastructure improvements tailored to these settings should be evaluated for their effectiveness in limiting environmental AMR dissemination, lowering the community-level burden of antimicrobial-resistant infections, and preventing antibiotic misuse. We also suggest that additional research is directed towards developing economic and legal incentives for evaluating and implementing water and waste infrastructure in these settings. Given that almost 90% of urban population growth will occur in regions predicted to be most burdened by the AMR crisis, there is an urgent need to build effective, evidence-based policies that could influence massive investments in the built urban environment in LMICs over the next few decades. Urban informal settlements are densely populated residential areas characterized by insufficient access to improved water and sanitation services, households constructed of non-durable material, insufficient living area, insecure residential status, and high participation in the informal economy 1-3. Four of the five largest slums in the world are in Asian and African LMICs, and in some countries, over 50% of the urban population resides in these types of settlements (e.g., Bangladesh, Kenya, Ethiopia) 1. Population densities are difficult to measure in urban informal settlements but they are estimated to exceed 125,000 persons/square km in multiple major LMIC cities, including Hyderabad

BackgroundAlthough β-lactam antibiotics are heavily used in many developing countries, the diversity of β-lactamase genes (bla) is poorly understood. We screened for major β-lactamase phenotypes and diversity of bla genes among 912 E. coli strains isolated from clinical samples obtained between 1992 and 2010 from hospitalized and non-hospitalized patients.ResultsNone of the isolates was resistant to carbapenems but 30% of all isolates were susceptible to cefepime, cephamycins and piperacillin-tazobactam. Narrow spectrum β-lactamase (NSBL) phenotype was observed in 278 (30%) isolates that contained blaTEM-1 (54%) or blaSHV-1 (35%) or both (11%). Extended Spectrum β-lactamase (ESBL) phenotype was detected in 247 (27%) isolates which carried blaCTX-M-14 (29%), blaCTX-M-15 (24%), blaCTX-M-9 (2%), blaCTX-M-8 (4%), blaCTX-M-3 (11%), blaCTX-M-1 (6%), blaSHV-5 (3%), blaSHV-12 (5%), and blaTEM-52 (16%). Complex Mutant TEM-like (CMT) phenotype was detected in 220 (24%) isolates which carried blaTEM-125 (29%), while blaTEM-50, blaTEM-78, blaTEM-109, blaTEM −152 and blaTEM-158 were detected in lower frequencies of between 7% and 11%. Majority of isolates producing a combination of CTX-M-15 + OXA-1 + TEM-1 exhibited resistance phenotypes barely indistinguishable from those of CMT-producers. Although 73 (8%) isolates exhibited Inhibitor Resistant TEM-like (IRT) phenotype, blaTEM-103 was the only true IRT-encoding gene identified in 18 (25%) of strains with this phenotype while the rest produced a combination of TEM-1 + OXA-1. The pAmpCs-like phenotype was observed in 94 (10%) isolates of which 77 (82%) carried blaCMY-2 while 18% contained blaCMY-1.Isolates from urine accounted for 53%, 53%, 74% and 72% of strains exhibiting complex phenotypes such as IRT, ESBL, CMT or pAmpC respectively. On the contrary, 55% isolates from stool exhibited the relatively more susceptible NSBL-like phenotype. All the phenotypes, and majority of the bla genes, were detected both in isolates from hospitalized and non-hospitalized patients but complex phenotypes were particularly common among strains obtained between 2000 and 2010 from urine of hospitalized patients.ConclusionsThe phenotypes and diversity of bla genes in E. coli strains implicated in clinical infections in non-hospitalized and hospitalized patients in Kenya is worryingly high. In order to preserve the efficacy of β-lactam antibiotics, culture and susceptibility data should guide therapy and surveillance studies for β-lactamase-producers in developing countries should be launched.

Multidrug-resistant bacteria pose a major challenge to the clinical management of infections in resource-poor settings. Although nontyphoidal Salmonella (NTS) bacteria cause predominantly enteric self-limiting illness in developed countries, NTS is responsible for a huge burden of life-threatening bloodstream infections in sub-Saharan Africa. Here, we characterized nine S. Typhimurium isolates from an outbreak involving patients who initially failed to respond to ceftriaxone treatment at a referral hospital in Kenya. These Salmonella enterica serotype Typhimurium isolates were resistant to ampicillin, chloramphenicol, cefuroxime, ceftriaxone, aztreonam, cefepime, sulfamethoxazole-trimethoprim, and cefpodoxime. Resistance to β-lactams, including to ceftriaxone, was associated with carriage of a combination of blaCTX-M-15, blaOXA-1, and blaTEM-1 genes. The genes encoding resistance to heavy-metal ions were borne on the novel IncHI2 plasmid pKST313, which also carried a pair of class 1 integrons. All nine isolates formed a single clade within S. Typhimurium ST313, the major clone of an ongoing invasive NTS epidemic in the region. This emerging ceftriaxone-resistant clone may pose a major challenge in the management of invasive NTS in sub-Saharan Africa.

Background: In sub-Saharan Africa community-acquired non-typhoidal Salmonella (NTS) is a major cause of high morbidity and death among children under 5 years of age especially from resource poor settings. The emergence of multidrug resistance is a major challenge in treatment of life threatening invasive NTS infections in these settings.

Summary 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 ...