Characterization of NMCR-3, NMCR-4 and NMCR-5, three novel non-mobile colistin resistance determinants: Implications for MCR-3, MCR-7, and MCR-5 progenitors, respectively.

In this study, the progenitors of MCR-3, MCR-7 and MCR-5, namely NMCR-3, NMCR-4 and NMCR-5, were firstly discovered and indicating Aeromonas was a natural reservoir for MCR-3 and MCR-7. Furthermore, different evolutionary models for MCR-3, MCR-7 and MCR-5 were proposed.

Molecular Epidemiology of Underreported Emerging Zoonotic Pathogen Streptococcus suis in Europe.

Streptococcus suis, a zoonotic bacterial pathogen circulated through swine, can cause severe infections in humans. Because human S. suis infections are not notifiable in most countries, incidence is underestimated. We aimed to increase insight into the molecular epidemiology of human S. suis infections in Europe. To procure data, we surveyed 7 reference laboratories and performed a systematic review of the scientific literature. We identified 236 cases of human S. suis infection from those sources and an additional 87 by scanning gray literature. We performed whole-genome sequencing to type 46 zoonotic S. suis isolates and combined them with 28 publicly available genomes in a core-genome phylogeny. Clonal complex (CC) 1 isolates accounted for 87% of typed human infections; CC20, CC25, CC87, and CC94 also caused infections. Emergence of diverse zoonotic clades and notable severity of illness in humans support classifying S. suis infection as a notifiable condition.

Filling the gaps in the global prevalence map of clinical antimicrobial resistance.

Surveillance is critical in containing globally increasing antimicrobial resistance (AMR). Affordable methodologies to prioritize AMR surveillance efforts are urgently needed, especially in low- and middle-income countries (LMICs), where resources are limited. While socioeconomic characteristics correlate with clinical AMR prevalence, this correlation has not yet been used to estimate AMR prevalence in countries lacking surveillance. We captured the statistical relationship between AMR prevalence and socioeconomic characteristics in a suite of beta-binomial principal component regression models for nine pathogens resistant to 19 (classes of) antibiotics. Prevalence data from ResistanceMap were combined with socioeconomic profiles constructed from 5,595 World Bank indicators. Cross-validated models were used to estimate clinical AMR prevalence and temporal trends for countries lacking data. Our approach provides robust estimates of clinical AMR prevalence in LMICs for most priority pathogens (cross-validated q2 > 0.78 for six out of nine pathogens). By supplementing surveillance data, 87% of all countries worldwide, which represent 99% of the global population, are now informed. Depending on priority pathogen, our estimates benefit 2.1 to 4.9 billion people living in countries with currently insufficient diagnostic capacity. By estimating AMR prevalence worldwide, our approach allows for a data-driven prioritization of surveillance efforts. For carbapenem-resistant Acinetobacter baumannii and third-generation cephalosporin-resistant Escherichia coli, specific countries of interest are located in the Middle East, based on the magnitude of estimates; sub-Saharan Africa, based on the relative prevalence increase over 1998 to 2017; and the Pacific Islands, based on improving overall model coverage and performance.

Genome-wide association reveals host-specific genomic traits in Escherichia coli.

BACKGROUND: Escherichia coli is an opportunistic pathogen which colonizes various host species. However, to what extent genetic lineages of E. coli are adapted or restricted to specific hosts and the genomic determinants of such adaptation or restriction is poorly understood. RESULTS: We randomly sampled E. coli isolates from four countries (Germany, UK, Spain, and Vietnam), obtained from five host species (human, pig, cattle, chicken, and wild boar) over 16 years, from both healthy and diseased hosts, to construct a collection of 1198 whole-genome sequenced E. coli isolates. We identified associations between specific E. coli lineages and the host from which they were isolated. A genome-wide association study (GWAS) identified several E. coli genes that were associated with human, cattle, or chicken hosts, whereas no genes associated with the pig host could be found. In silico characterization of nine contiguous genes (collectively designated as nan-9) associated with the human host indicated that these genes are involved in the metabolism of sialic acids (Sia). In contrast, the previously described sialic acid regulon known as sialoregulon (i.e. nanRATEK-yhcH, nanXY, and nanCMS) was not associated with any host species. In vitro growth experiments with a Δnan-9 E. coli mutant strain, using the sialic acids 5-N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc) as sole carbon source, showed impaired growth behaviour compared to the wild-type. CONCLUSIONS: This study provides an extensive analysis of genetic determinants which may contribute to host specificity in E. coli. Our findings should inform risk analysis and epidemiological monitoring of (antimicrobial resistant) E. coli.

Impact of antibiotics on gut microbiome composition and resistome in the first years of life in low- to middle-income countries: A systematic review.

BACKGROUND: Inappropriate antimicrobial usage is a key driver of antimicrobial resistance (AMR). Low- and middle-income countries (LMICs) are disproportionately burdened by AMR and young children are especially vulnerable to infections with AMR-bearing pathogens. The impact of antibiotics on the microbiome, selection, persistence, and horizontal spread of AMR genes is insufficiently characterized and understood in children in LMICs. This systematic review aims to collate and evaluate the available literature describing the impact of antibiotics on the infant gut microbiome and resistome in LMICs. METHODS AND FINDINGS: In this systematic review, we searched the online databases MEDLINE (1946 to 28 January 2023), EMBASE (1947 to 28 January 2023), SCOPUS (1945 to 29 January 2023), WHO Global Index Medicus (searched up to 29 January 2023), and SciELO (searched up to 29 January 2023). A total of 4,369 articles were retrieved across the databases. Duplicates were removed resulting in 2,748 unique articles. Screening by title and abstract excluded 2,666 articles, 92 articles were assessed based on the full text, and 10 studies met the eligibility criteria that included human studies conducted in LMICs among children below the age of 2 that reported gut microbiome composition and/or resistome composition (AMR genes) following antibiotic usage. The included studies were all randomized control trials (RCTs) and were assessed for risk of bias using the Cochrane risk-of-bias for randomized studies tool. Overall, antibiotics reduced gut microbiome diversity and increased antibiotic-specific resistance gene abundance in antibiotic treatment groups as compared to the placebo. The most widely tested antibiotic was azithromycin that decreased the diversity of the gut microbiome and significantly increased macrolide resistance as early as 5 days posttreatment. A major limitation of this study was paucity of available studies that cover this subject area. Specifically, the range of antibiotics assessed did not include the most commonly used antibiotics in LMIC populations. CONCLUSION: In this study, we observed that antibiotics significantly reduce the diversity and alter the composition of the infant gut microbiome in LMICs, while concomitantly selecting for resistance genes whose persistence can last for months following treatment. Considerable heterogeneity in study methodology, timing and duration of sampling, and sequencing methodology in currently available research limit insights into antibiotic impacts on the microbiome and resistome in children in LMICs. More research is urgently needed to fill this gap in order to better understand whether antibiotic-driven reductions in microbiome diversity and selection of AMR genes place LMIC children at risk for adverse health outcomes, including infections with AMR-bearing pathogens.

Readiness of health facilities to deliver non-communicable diseases services in Kenya: a national cross-sectional survey.

BACKGROUND: Non-communicable diseases (NCDs) account for an estimated 71% of all global deaths annually and nearly 80% of these deaths occur in low- and middle-income countries. This study aimed to assess the readiness of existing healthcare systems at different levels of health care in delivering NCDs management and prevention services in Kenya. METHODS: A cross-sectional survey of 258 facilities was conducted between June 2019 and December 2020 using multistage sampling, examining facility readiness based on the availability of indicators such as equipment, diagnostic capacity, medicines and commodities, trained staff and guidelines for NCDs management. Readiness scores were calculated as the mean availability of tracer items expressed as a percentage and a cut-off threshold of ≥ 70% was used to classify facilities as "ready" to manage NCDs. Descriptive and bivariate analyses were performed to assess the readiness of facilities by type, level, and location settings. Logistic regressions were used to identify factors associated with the readiness of facilities to provide disease-specific services. RESULTS: Of the surveyed facilities, 93.8% offered chronic respiratory disease (CRD) diagnosis and/or management services, 82.2% diabetes mellitus, 65.1% cardiovascular disease (CVD), and only 24.4% cervical cancer screening services. The mean readiness scores for diabetes mellitus (71%; 95% CI: 67-74) and CVD (69%; 95% CI: 66-72) were relatively high. Although CRD services were reportedly the most widely available, its mean readiness score was low (48%; 95% CI: 45-50). The majority of facilities offering cervical cancer services had all the necessary tracer items available to provide these services. Modeling results revealed that private facilities were more likely to be "ready" to offer NCDs services than public facilities. Similarly, hospitals were more likely "ready" to provide NCDs services than primary health facilities. These disparities in service readiness extended to the regional and urban/rural divide. CONCLUSIONS: Important gaps in the current readiness of facilities to manage NCDs in Kenya at different levels of health care were revealed, showing variations by disease and healthcare facility type. A collective approach is therefore needed to bridge the gap between resource availability and population healthcare needs.

Rethinking Antimicrobial Resistance Surveillance: A Role for Lot Quality Assurance Sampling.

Global surveillance of antimicrobial resistance (AMR) is a key component of the 68th World Health Assembly Global Action Plan on AMR. Laboratory-based surveillance is inherently biased and lacks local relevance due to aggregation of data. We assessed the feasibility, sensitivity, and affordability of a population-based AMR survey using lot quality assurance sampling (LQAS), which classifies a population as having a high or low prevalence of AMR based on a priori defined criteria. Three studies were carried out in Medan and Bandung, Indonesia, between April 2014 and June 2017. LQAS classifications for 15 antibiotics were compared with AMR estimates from a conventional population-based survey, with an assessment of the cost of a single LQAS classification using microcosting methodology, among patients suspected of urinary tract infection at 11 sites in Indonesia. The sensitivity of LQAS was above 98%. The approach detected local variation in the prevalence of AMR across sites. Time to reach LQAS results ranged from 47 to 138 days. The average cost of an LQAS classification in a single facility was US$466. The findings indicate that LQAS-based AMR survey is a feasible, sensitive, and affordable strategy for population-based AMR surveys, providing essential data to inform local empirical treatment guidelines and antimicrobial stewardship efforts.

Quantifying the contribution of four resistance mechanisms to ciprofloxacin MIC in Escherichia coli: a systematic review.

Background: Reviews assessing the genetic basis of ciprofloxacin resistance in Escherichia coli have mostly been qualitative. However, to predict resistance phenotypes based on genotypic characteristics, it is essential to quantify the contribution of genotypic determinants to resistance. Objectives: We performed a systematic review to assess the relative contribution of known genomic resistance determinants to the MIC of ciprofloxacin in E. coli. Methods: PubMed and Web of Science were searched for English language studies that assessed ciprofloxacin MIC and presence or introduction of genetic determinants of ciprofloxacin resistance in E. coli. We included experimental and observational studies without time restrictions. Medians and ranges of MIC fold changes were calculated for individual resistance determinants and combinations thereof. Results: We included 66 studies, describing 604 E. coli isolates that carried at least one genetic ciprofloxacin resistance determinant. Mutations in gyrA and parC, genes encoding targets of ciprofloxacin, contribute to the largest fold changes in ciprofloxacin resistance in E. coli compared with the WT. Efflux and physical blocking or enzymatic modifications confer smaller increases in ciprofloxacin MIC than mutations in gyrA and parC. However, the presence of these other resistance mechanisms in addition to target alteration mutations further increases ciprofloxacin MIC, thus resulting in ciprofloxacin MIC increases ranging from 250- to 4000-fold. Conclusions: This quantitative review of genomic determinants of ciprofloxacin resistance in E. coli demonstrates the complexity of resistance phenotype prediction from genomic data and serves as a reference point for studies aiming to predict ciprofloxacin MIC from E. coli genomes.

Limited contribution of non-intensive chicken farming to ESBL-producing Escherichia coli colonization in humans in Vietnam: an epidemiological and genomic analysis.

OBJECTIVES: To investigate the risk of colonization with ESBL-producing Escherichia coli (ESBL-Ec) in humans in Vietnam associated with non-intensive chicken farming. METHODS: Faecal samples from 204 randomly selected farmers and their chickens, and from 306 age- and sex-matched community-based individuals who did not raise poultry were collected. Antimicrobial usage in chickens and humans was assessed by medicine cabinet surveys. WGS was employed to obtain a high-resolution genomic comparison between ESBL-Ec isolated from humans and chickens. RESULTS: The adjusted prevalence of ESBL-Ec colonization was 20.0% (95% CI 10.8%-29.1%) and 35.2% (95% CI 30.4%-40.1%) in chicken farms and humans in Vietnam, respectively. Colonization with ESBL-Ec in humans was associated with antimicrobial usage (OR = 2.52, 95% CI = 1.08-5.87) but not with involvement in chicken farming. blaCTX-M-55 was the most common ESBL-encoding gene in strains isolated from chickens (74.4%) compared with blaCTX-M-27 in human strains (47.0%). In 3 of 204 (1.5%) of the farms, identical ESBL genes were detected in ESBL-Ec isolated from farmers and their chickens. Genomic similarity indicating recent sharing of ESBL-Ec between chickens and farmers was found in only one of these farms. CONCLUSIONS: The integration of epidemiological and genomic data in this study has demonstrated a limited contribution of non-intensive chicken farming to ESBL-Ec colonization in humans in Vietnam and further emphasizes the importance of reducing antimicrobial usage in both human and animal host reservoirs.

Pharmacy-based hypertension care employing mHealth in Lagos, Nigeria - a mixed methods feasibility study.

BACKGROUND: Access to quality hypertension care is often poor in sub-Saharan Africa. Some community pharmacies offer hypertension monitoring services, with and without involvement of medical doctors. To directly connect pharmacy staff and cardiologists a care model including a mobile application (mHealth) for remote patient monitoring was implemented and pilot tested in Lagos, Nigeria. Pharmacists provided blood pressure measurements and counselling. Cardiologists enrolled patients in the pilot program and remotely monitored them, for which patients paid a monthly fee. We evaluated the feasibility of this care model at five private community pharmacies. Outcome measures were retention in care, blood pressure change, quality of care, and patients' and healthcare providers' satisfaction with the care model. METHODS: Patients participated in the care model's pilot at one of the five pharmacies for approximately 6-8 months from February 2016. We conducted structured patient interviews and blood pressure measurements at pilot entry and exit, and used exports of the mHealth-application, in-depth interviews and focus group discussions with patients, pharmacists and cardiologists. RESULTS: Of 336 enrolled patients, 236 (72%) were interviewed at pilot entry and exit. According to the mHealth data 71% returned to the pharmacy after enrollment, with 3.3 months (IQR: 2.2-5.4) median duration of activity in the mHealth-application. Patients self-reported more visits than recorded in the mHealth data. Pharmacists mentioned use of paper records, understaffing, the application not being user-friendly, and patients' unwillingness to pay as reasons for underreporting. Mean systolic blood pressure decreased 9.9 mmHg (SD: 18). Blood pressure on target increased from 24 to 56% and an additional 10% had an improved blood pressure at endline, however this was not associated with duration of mHealth activity. Patients were satisfied because of accessibility, attention, adherence and information provision. CONCLUSION: Patients, pharmacists and cardiologists adopted the care model, albeit with gaps in mHealth data. Most patients were satisfied, and their mean blood pressure significantly reduced. Usage of the mHealth application, pharmacy incentives, and a modified financing model are opportunities for improvement. In addition, costs of implementation and availability of involved healthcare providers need to be investigated before such a care model can be further implemented.

Genomic analysis of diversity, population structure, virulence, and antimicrobial resistance in Klebsiella pneumoniae, an urgent threat to public health.

Klebsiella pneumoniae is now recognized as an urgent threat to human health because of the emergence of multidrug-resistant strains associated with hospital outbreaks and hypervirulent strains associated with severe community-acquired infections. K. pneumoniae is ubiquitous in the environment and can colonize and infect both plants and animals. However, little is known about the population structure of K. pneumoniae, so it is difficult to recognize or understand the emergence of clinically important clones within this highly genetically diverse species. Here we present a detailed genomic framework for K. pneumoniae based on whole-genome sequencing of more than 300 human and animal isolates spanning four continents. Our data provide genome-wide support for the splitting of K. pneumoniae into three distinct species, KpI (K. pneumoniae), KpII (K. quasipneumoniae), and KpIII (K. variicola). Further, for K. pneumoniae (KpI), the entity most frequently associated with human infection, we show the existence of >150 deeply branching lineages including numerous multidrug-resistant or hypervirulent clones. We show K. pneumoniae has a large accessory genome approaching 30,000 protein-coding genes, including a number of virulence functions that are significantly associated with invasive community-acquired disease in humans. In our dataset, antimicrobial resistance genes were common among human carriage isolates and hospital-acquired infections, which generally lacked the genes associated with invasive disease. The convergence of virulence and resistance genes potentially could lead to the emergence of untreatable invasive K. pneumoniae infections; our data provide the whole-genome framework against which to track the emergence of such threats.

Zoonotic Transmission of mcr-1 Colistin Resistance Gene from Small-Scale Poultry Farms, Vietnam.

We investigated the consequences of colistin use in backyard chicken farms in Vietnam by examining the prevalence of mcr-1 in fecal samples from chickens and humans. Detection of mcr-1-carrying bacteria in chicken samples was associated with colistin use and detection in human samples with exposure to mcr-1-positive chickens.

Antimicrobial resistance in uropathogens and appropriateness of empirical treatment: a population-based surveillance study in Indonesia.

Objectives: Urinary tract infections (UTIs) are a common reason for empirical treatment with broad-spectrum antibiotics worldwide. However, population-based antimicrobial resistance (AMR) prevalence data to inform empirical treatment choice are lacking in many regions, because of limited surveillance capacity. We aimed to assess the prevalence of AMR to commonly used antimicrobial drugs in Escherichia coli and Klebsiella pneumoniae isolated from patients with community- or healthcare-associated UTIs on two islands of Indonesia. Methods: We performed a cross-sectional patient-based study in public and private hospitals and clinics between April 2014 and May 2015. We screened patients for symptoms of UTIs and through urine dipstick analysis. Urine culture and susceptibility testing were supported by telemicrobiology and interactive virtual laboratory rounds. Surveillance data were entered in forms on mobile phones. Results: Of 3424 eligible patients, 3380 (98.7%) were included in the final analysis, and yielded 840 positive cultures and antimicrobial susceptibility data for 657 E. coli and K. pneumoniae isolates. Fosfomycin was the single oral treatment option with resistance prevalence <20% in both E. coli and K. pneumoniae in community settings. Tigecycline and fosfomycin were the only options for treatment of catheter-associated UTIs with resistance prevalence <20%, whilst the prevalence of resistance to meropenem was 21.3% in K. pneumoniae . Conclusions: Patient-based surveillance of AMR in E. coli and K. pneumoniae causing UTIs indicates that resistance to the commonly available empirical treatment options is high in Indonesia. Smart AMR surveillance strategies are needed to inform policy makers and to guide interventions.

Colonization of Enteroaggregative Escherichia coli and Shiga toxin-producing Escherichia coli in chickens and humans in southern Vietnam.

BACKGROUND: Enteroaggregative (EAEC) and Shiga-toxin producing Escherichia coli (STEC) are a major cause of diarrhea worldwide. E. coli carrying both virulence factors characteristic for EAEC and STEC and producing extended-spectrum beta-lactamase caused severe and protracted disease during an outbreak of E. coli O104:H4 in Europe in 2011. We assessed the opportunities for E. coli carrying the aggR and stx genes to emerge in 'backyard' farms in south-east Asia. RESULTS: Faecal samples collected from 204 chicken farms; 204 farmers and 306 age- and gender-matched individuals not exposed to poultry farming were plated on MacConkey agar plates with and without antimicrobials being supplemented. Sweep samples obtained from MacConkey agar plates without supplemented antimicrobials were screened by multiplex PCR for the detection of the stx1, stx2 and aggR genes. One chicken farm sample each (0.5 %) contained the stx1 and the aggR gene. Eleven (2.4 %) human faecal samples contained the stx1 gene, 2 samples (0.4 %) contained stx2 gene, and 31 (6.8 %) contained the aggR gene. From 46 PCR-positive samples, 205 E. coli isolates were tested for the presence of stx1, stx2, aggR, wzx O104 and fliC H4 genes. None of the isolates simultaneously contained the four genetic markers associated with E. coli O104:H4 epidemic strain (aggR, stx2, wzx O104 and fliC H4 ). Of 34 EAEC, 64.7 % were resistant to 3(rd)-generation cephalosporins. CONCLUSION: These results indicate that in southern Vietnam, the human population is a more likely reservoir of aggR and stx gene carrying E. coli than the chicken population. However, conditions for transmission of isolates and/or genes between human and animal reservoirs resulting in the emergence of highly virulent E. coli strains are still favorable, given the nature of'backyard' farms in Vietnam.

Host-pathogen Interaction at the Intestinal Mucosa Correlates With Zoonotic Potential of Streptococcus suis.

BACKGROUND: Streptococcus suis has emerged as an important cause of bacterial meningitis in adults. The ingestion of undercooked pork is a risk factor for human S. suis serotype 2 (SS2) infection. Here we provide experimental evidence indicating that the gastrointestinal tract is an entry site of SS2 infection. METHODS: We developed a noninvasive in vivo model to study oral SS2 infection in piglets. We compared in vitro interaction of S. suis with human and porcine intestinal epithelial cells (IEC). RESULTS: Two out of 15 piglets showed clinical symptoms compatible with S. suis infection 24-48 hours after ingestion of SS2. SS2 was detected in mesenteric lymph nodes of 40% of challenged piglets. SS2 strains isolated from patients showed significantly higher adhesion to human IEC compared to invasive strains isolated from pigs. In contrast, invasive SS9 strains showed significantly higher adhesion to porcine IEC. Translocation across human IEC, which occurred predominately via a paracellular route, was significantly associated with clonal complex 1, the predominant zoonotic genotype. Adhesion and translocation were dependent on capsular polysaccharide production. CONCLUSIONS: SS2 should be considered a food-borne pathogen. S. suis interaction with human and pig IEC correlates with S. suis serotype and genotype, which can explain the zoonotic potential of SS2.

Prevalence and risk factors for carriage of antimicrobial-resistant Escherichia coli on household and small-scale chicken farms in the Mekong Delta of Vietnam.

OBJECTIVES: To describe the prevalence of antimicrobial resistance among commensal Escherichia coli isolates on household and small-scale chicken farms, common in southern Vietnam, and to investigate the association of antimicrobial resistance with farming practices and antimicrobial usage. METHODS: We collected data on farming and antimicrobial usage from 208 chicken farms. E. coli was isolated from boot swab samples using MacConkey agar (MA) and MA with ceftazidime, nalidixic acid or gentamicin. Isolates were tested for their susceptibility to 11 antimicrobials and for ESBL production. Risk factor analyses were carried out, using logistic regression, at both the bacterial population and farm levels. RESULTS: E. coli resistant to gentamicin, ciprofloxacin and third-generation cephalosporins was detected on 201 (96.6%), 191 (91.8%) and 77 (37.0%) of the farms, respectively. Of the 895 E. coli isolates, resistance to gentamicin, ciprofloxacin and third-generation cephalosporins was detected in 178 (19.9%), 291 (32.5%) and 29 (3.2%) of the isolates, respectively. Ciprofloxacin resistance was significantly associated with quinolone usage (OR = 2.26) and tetracycline usage (OR = 1.70). ESBL-producing E. coli were associated with farms containing fish ponds (OR = 4.82). CONCLUSIONS: Household and small farms showed frequent antimicrobial usage associated with a high prevalence of resistance to the most commonly used antimicrobials. Given the weak biocontainment, the high prevalence of resistant E. coli could represent a risk to the environment and to humans.

Epidemiology, clinical manifestations, and outcomes of Streptococcus suis infection in humans.

Streptococcus suis, a bacterium that affects pigs, is a neglected pathogen that causes systemic disease in humans. We conducted a systematic review and meta-analysis to summarize global estimates of the epidemiology, clinical characteristics, and outcomes of this zoonosis. We searched main literature databases for all studies through December 2012 using the search term "streptococcus suis." The prevalence of S. suis infection is highest in Asia; the primary risk factors are occupational exposure and eating of contaminated food. The pooled proportions of case-patients with pig-related occupations and history of eating high-risk food were 38.1% and 37.3%, respectively. The main clinical syndrome was meningitis (pooled rate 68.0%), followed by sepsis, arthritis, endocarditis, and endophthalmitis. The pooled case-fatality rate was 12.8%. Sequelae included hearing loss (39.1%) and vestibular dysfunction (22.7%). Our analysis identified gaps in the literature, particularly in assessing risk factors and sequelae of this infection.

Antimicrobial drug resistance among clinically relevant bacterial isolates in sub-Saharan Africa: a systematic review.

BACKGROUND: Little is known about the prevalence of antimicrobial resistance (AMR) amongst bacterial pathogens in sub-Saharan Africa (sSA), despite calls for continent-wide surveillance to inform empirical treatment guidelines. METHODS: We searched PubMed and additional databases for susceptibility data of key pathogens for surveillance, published between 1990 and 2013. Extracted data were standardized to a prevalence of resistance in populations of isolates and reported by clinical syndrome, microorganism, relevant antimicrobial drugs and region. RESULTS: We identified 2005 publications, of which 190 were analysed. Studies predominantly originated from east sSA (61%), were hospital based (60%), were from an urban setting (73%) and reported on isolates from patients with a febrile illness (42%). Quality procedures for susceptibility testing were described in <50% of studies. Median prevalence (MP) of resistance to chloramphenicol in Enterobacteriaceae, isolated from patients with a febrile illness, ranged between 31.0% and 94.2%, whilst MP of resistance to third-generation cephalosporins ranged between 0.0% and 46.5%. MP of resistance to nalidixic acid in Salmonella enterica Typhi ranged between 15.4% and 43.2%. The limited number of studies providing prevalence data on AMR in Gram-positive pathogens or in pathogens isolated from patients with a respiratory tract infection, meningitis, urinary tract infection or hospital-acquired infection suggested high prevalence of resistance to chloramphenicol, trimethoprim/sulfamethoxazole and tetracycline and low prevalence to third-generation cephalosporins and fluoroquinolones. CONCLUSIONS: Our results indicate high prevalence of AMR in clinical bacterial isolates to antimicrobial drugs commonly used in sSA. Enhanced approaches for AMR surveillance are needed to support empirical therapy in sSA.

The Carriage Of Multiresistant Bacteria After Travel (COMBAT) prospective cohort study: methodology and design.

BACKGROUND: Antimicrobial resistance (AMR) is one of the major threats to public health around the world. Besides the intense use and misuse of antimicrobial agents as the major force behind the increase in antimicrobial resistance, the exponential increase of international travel may also substantially contribute to the emergence and spread of AMR. However, knowledge on the extent to which international travel contributes to this is still limited. The Carriage Of Multiresistant Bacteria After Travel (COMBAT) study aims to 1. determine the acquisition rate of multiresistant Enterobacteriaceae during foreign travel 2. ascertain the duration of carriage of these micro-organisms 3. determine the transmission rate within households 4. identify risk factors for acquisition, persistence of carriage and transmission of multiresistant Enterobacteriaceae. METHODS/DESIGN: The COMBAT-study is a large-scale multicenter longitudinal cohort study among travellers (n = 2001) and their non-travelling household members (n = 215). Faecal samples are collected before and immediately after travel and 1 month after return from all participants. Follow-up faecal samples are collected 3, 6 and 12 months after return from travellers (and their non-travelling household members) who acquired multiresistant Enterobacteriaceae. Questionnaires are collected from all participants at each time-point. Faecal samples are screened phenotypically for the presence of extended-spectrum beta-lactamase (ESBL) or carbapenemase-producing Enterobacteriaceae. Positive post-travel isolates from travellers with negative pre-travel samples are genotypically analysed for ESBL and carbapenemase genes with microarray and gene sequencing. DISCUSSION: The design and scale of the COMBAT-study will enable us to provide much needed detailed insights into the risks and dynamics of introduction and spread of ESBL- and carbapenemase-producing Enterobacteriaceae by healthy travellers and the potential need and measures to monitor or manage these risks. TRIAL REGISTRATION: The study is registered at clinicaltrials.gov under accession number NCT01676974.

Perceptions of inhibitors and facilitators for adhering to hypertension treatment among insured patients in rural Nigeria: a qualitative study.

BACKGROUND: Universal health care coverage has been identified as a promising strategy for improving hypertension treatment and control rates in sub Saharan Africa (SSA). Yet, even when quality care is accessible, poor adherence can compromise treatment outcomes. To provide information for adherence support interventions, this study explored what low income patients who received hypertension care in the context of a community based health insurance program in Nigeria perceive as inhibitors and facilitators for adhering to pharmacotherapy and healthy behaviors. METHODS: We conducted a qualitative interview study with 40 insured hypertensive patients who had received hypertension care for > 1 year in a rural primary care hospital in Kwara state, Nigeria. Supported by MAXQDA software, interview transcripts were inductively coded. Codes were then grouped into concepts and thematic categories, leading to matrices for inhibitors and facilitators of treatment adherence. RESULTS: Important patient-identified facilitators of medication adherence included: affordability of care (through health insurance); trust in orthodox "western" medicines; trust in Doctor; dreaded dangers of hypertension; and use of prayer to support efficacy of pills. Inhibitors of medication adherence included: inconvenient clinic operating hours; long waiting times; under-dispensing of prescriptions; side-effects of pills; faith motivated changes of medication regimen; herbal supplementation/substitution of pills; and ignorance that regular use is needed. Local practices and norms were identified as important inhibitors to the uptake of healthier behaviors (e.g. use of salt for food preservation; negative cultural images associated with decreased body size and physical activity). Important factors facilitating such behaviors were the awareness that salt substitutes and products for composing healthier meals were cheaply available at local markets and that exercise could be integrated in people's daily activities (e.g. farming, yam pounding, and household chores). CONCLUSIONS: With a better understanding of patient perceived inhibitors and facilitators of adherence to hypertension treatment, this study provides information for patient education and health system level interventions that can be designed to improve compliance. TRIAL REGISTRATION: ISRCTN47894401 .