Project description:Whole-genome sequencing of carbapenem- and cefiderocol-resistant Enterobacterales in surface water in Kumasi, Ashanti Region, Ghana
Project description:Although several studies have associated Mycobacterium ulcerans (MU) infection, Buruli ulcer (BU), with slow moving water bodies, there is still no definite mode of transmission. Ecological and transmission studies suggest Variable Number Tandem Repeat (VNTR) typing as a useful tool to differentiate MU strains from other Mycolactone Producing Mycobacteria (MPM). Deciphering the genetic relatedness of clinical and environmental isolates is seminal to determining reservoirs, vectors and transmission routes. In this study, we attempted to source-track MU infections to specific water bodies by matching VNTR profiles of MU in human samples to those in the environment. Environmental samples were collected from 10 water bodies in four BU endemic communities in the Ashanti region, Ghana. Four VNTR loci in MU Agy99 genome, were used to genotype environmental MU ecovars, and those from 14 confirmed BU patients within the same study area. Length polymorphism was confirmed with sequencing. MU was present in the 3 different types of water bodies, but significantly higher in biofilm samples. Four MU genotypes, designated W, X, Y and Z, were typed in both human and environmental samples. Other reported genotypes were only found in water bodies. Animal trapping identified 1 mouse with lesion characteristic of BU, which was confirmed as MU infection. Our findings suggest that patients may have been infected from community associated water bodies. Further, we present evidence that small mammals within endemic communities could be susceptible to MU infections. M. ulcerans transmission could involve several routes where humans have contact with risk environments, which may be further compounded by water bodies acting as vehicles for disseminating strains.
Project description:BackgroundCommunity-acquired carbapenem-resistant Enterobacterales (CA-CRE) are an important threat.MethodsIn CRACKLE-2, we defined patients with CA-CRE as admitted from home, without pre-existing conditions, and a positive culture within 48 h of admission. Healthcare-associated CRE (HA-CRE) were those with the lowest likelihood of community acquisition, not admitted from home and cultured >48 h after admission. Specific genetic markers in carbapenemase-producing Klebsiella pneumoniae were evaluated through random forest modelling.ResultsCA-CRE and HA-CRE were detected in 83 (10%) and 208 (26%) of 807 patients. No significant differences were observed in bacterial species or strain type distribution. K. pneumoniae (204/291, 70%) was the most common CRE species, of these 184/204 (90%) were carbapenemase producers (CPKP). The top three genetic markers in random forest models were kpi_SA15, fimE, and kpfC. Of these, kpi_SA15 (which encodes a chaperone/usher system) was positively associated (OR 3.14, 95% CI 1.13-8.87, P = 0.026), and kpfC negatively associated (OR 0.21, 95% CI 0.05-0.72, P = 0.015) with CA-CPKP.ConclusionsTen percent of CDC-defined CRE were CA. The true proportion of CA-CRE in hospitalized patients is likely lower as patients may have had unrecorded prior healthcare exposure. The kpi_SA15 operon was associated with the CA phenotype.
Project description:BackgroundDespite the fact that carbapenem-resistant Enterobacterales (CRE) mostly cause urinary tract infections (UTIs), only few studies have focused on the efficacity of mecillinam against these CRE.ObjectivesTo evaluate the mecillinam susceptibility of a huge collection of CRE, including carbapenemase-producing Enterobacterales (CPE) and non-CPE (ESBL and AmpC producers with decreased permeability of the outer membrane).MethodsA total of 8310 non-duplicate clinical CRE, including 4042 OXA-48-like producers, 1094 NDM producers, 411 VIM producers, 174 KPC producers, 42 IMI producers, 153 multiple-carbapenemase producers and 45 isolates producing other types of carbapenemases (such as IMP-like enzymes or GES-5), were included in the study. WGS was performed on all CPE using Illumina technology. Categorization of susceptibility to mecillinam was performed using disc diffusion (mecillinam discs at 10 μg; I2A, France) according to EUCAST recommendations. The results were interpreted according to EUCAST guidelines (S ≥15 mm).ResultsSignificantly higher susceptibility rates were observed for carbapenem-resistant Proteus spp. (85%) and carbapenem-resistant Escherichia coli (84%), which are the two most common species responsible for UTIs, than for Klebsiella pneumoniae (67%), Enterobacter cloacae complex (75%), Citrobacter spp. (65%), Serratia spp. (34%) and Morganella morganii (12%). Susceptibility rates were 84%, 71% and 91% for OXA-48-like, NDM and IMI producers and 70% for non-CPE CRE. Mecillinam was less active against VIM and KPC producers (14% and 0%, respectively).ConclusionsMecillinam might be an alternative for the treatment of infections due to CRE, particularly UTIs, except for VIM and KPC producers and for M. morganii and Serratia spp species.
Project description:BackgroundDuring prolonged FDC therapy, the emergence of FDC non-susceptibility in CRAB has been reported. Here, we report a transmission cluster of FDC-non-susceptible CRAB in four patients, all naïve to FDC treatment, characterized by a premature stop codon and amino acid deletion in the PirA protein.MethodsCRAB strains obtained from patients admitted in a single medicine ward of the IRCCS Fondazione Ospedale Maggiore Policlinico between March and July 2024 were analyzed by WGS and antimicrobial susceptibility testing. Phylogenetic analysis was used to assess their genetic relatedness.ResultsBetween March and July 2024, an outbreak of 33 CRAB was observed among hospitalized patients in a single ward at IRCCS. Genomic analysis, available in 29 cases, revealed that 24 isolates belonged to ST208/1806, 4 to ST369, and one to ST195/1816 (according to the Oxford scheme). FDC susceptibility was affected only in the four ST369 isolates (Kirby-Bauer disk diffusion diameter: 13 mm; UMIC® method MIC: 4 mg/L), all characterized by a premature stop codon followed by a 52 amino acid deletion located between the amino acids 377 and 428 of the siderophore-drug receptor PirA. No other relevant mutations were detected in the iron-uptake genes. Core-genome ML tree including ST369 reference strains revealed that the four ST369 isolates were highly related and formed a distinct cluster (SNP distance: 3 [IQR: 1-6]). Of note, the four isolates were collected from four FDC-naïve individuals, two experiencing a CRAB-mediated infection.ConclusionsOur findings alert about the circulation of clones carrying modified siderophore-drug receptors without evidence of previous FDC treatment and support the importance of testing FDC susceptibility appropriately before its administration.
Project description:Mathematical models can aid in elucidating the spread of infectious disease dynamics within a given population over time. In an attempt to model tuberculosis (TB) dynamics among high-burden districts in the Ashanti Region of Ghana, the SEIR epidemic model with demography was employed within both deterministic and stochastic settings for comparison purposes. The deterministic model showed success in modelling TB infection in the region to the transmission dynamics of the stochastic SEIR model over time. It predicted tuberculosis dying out in ten of twelve high-burden districts in the Ashanti Region, but an outbreak in Obuasi municipal and Amansie West district. The effect of introducing treatment at the incubation stage of TB transmission was also investigated, and it was discovered that treatment introduced at the exposed stage decreased the spread of TB. Branching process approximation was used to derive explicit forms of relevant epidemiological quantities of the deterministic SEIR model for stability analysis of equilibrium points. Numerical simulations were performed to validate the overall infection rate, basic reproductive number, herd immunity threshold, and Malthusian parameter based on bootstrapping, jackknife, and Latin Hypercube sampling schemes. It was recommended that the Ghana Health Service should find a good mechanism to detect TB in the early stages of infection in the region. Public health attention must also be given to districts with a potentially higher risk of experiencing endemic TB even though the estimates of the overall epidemic thresholds from our SEIR model suggested that the Ashanti Region as a whole had herd immunity against TB infection.
Project description:BackgroundInterprofessional collaboration ensures that high-quality health care is provided leading to improved health outcomes and provider satisfaction. Assessing the attitudes of health care professionals towards teamwork in Ghana is novel.ObjectiveTo examine the attitudes of health care professionals towards interprofessional teamwork and assess specific attributes influencing these attitudes in the Ashanti region, prior to implementing an in-service interprofessional HIV training programme.MethodsA cross-sectional pre-training online survey using a modified Attitudes Toward Health Care Teams Scale was conducted among health care practitioners undergoing a two-day interactive interprofessional HIV training in Kumasi and Agogo from November 2019 to January 2020. Trainees were diverse health professional cadres selected from five hospitals in the Ashanti region of Ghana. Data was summarised using the mean and standard deviation for continuous variables, and frequencies and percentages for categorical variables. An exploratory factor analysis was conducted to categorise the 14 items of the modified attitudes scale. The Wilcoxon rank-sum (Mann-Whitney) and Kruskal-Wallis tests were used to test the mean attitude difference among the demographic characteristics. Statistical significance was set at p < 0.05.ResultsAltogether, 302 health professionals completed the survey. The ages ranged from 20-58 years, mean age 27.96 years (standard deviation 5.90 years). Up to 95% of the trainees agreed with the 14 statements on the modified attitudes scale. Three factors were identified; "quality of care", "team efficiency", and "time constraint" with Cronbach's alpha measures of 0.73, 0.50, and 0.45 respectively. The overall mean attitude score was 58.15 ± 6.28 (95% CI, 57.42-58.88). Attitude of health care professionals towards interdisciplinary teams for patient care varied significantly by age (p = 0.014), health profession cadre (p = 0.005), facility (p = 0.037), and professional experience (p = 0.034).ConclusionStrengthening in-service interprofessional training for health practitioners especially early career professionals in the Ashanti region would be valuable.
Project description:ObjectiveAlthough several studies have assessed treatment outcomes of drug-susceptible tuberculosis (TB) in Ghana, very little has been done in the area of multidrug-resistant TB (MDR-TB). The aim of this study was to determine treatment outcomes and associated factors among patients treated for MDR-TB in the Ashanti Region, Ghana.DesignA retrospective, cross-sectional analysis.SettingThe study was conducted in the Ashanti Region, the second most populous region in Ghana. The regional MDR-TB register, which contains information on all patients with MDR-TB being treated at the various TB centres in the region, was analysed between February and May 2021.ParticipantsThe participants consisted of all registered patients with MDR-TB who were placed on treatment between 1 January 2015 and 31 December 2020. Patients were included in the analysis if their treatment outcome had been assigned. Patients with no record of treatment outcome were excluded from the study.Outcome measuresThe main outcome variable for the study was MDR-TB treatment outcome, standardised as 'cured', 'treatment completed', 'treatment failure', 'died' and 'lost to follow-up'. A logistic regression model was fitted for factors associated with the outcome measure.ResultsOut of 159 patients included in the analysis, 86 (54.1%) were declared cured, 28 (17.6%) completed their treatment successfully, 6 (3.8%) were declared treatment failure, 12 (7.5%) were lost to follow-up and 27 (17.0%) died. The overall treatment success rate was 71.7%. Patients who were female (adjusted OR (AOR)=1.27, 95% CI: 1.18 to 1.39, p=0.023), younger (AOR=0.53, 95% CI: 0.19 to 2.11, p=0.012), had a higher level of education (AOR=1.12, 95% CI: 0.65 to 1.90, p=0.034), had a baseline body mass index of 18.5 kg/m2 or above (AOR=1.57, 95% CI: 1.23 to 2.47, p=0.011) and those who did not have a history of TB (AOR=0.47, 95% CI: 0.10 to 0.75, p=0.028) were more likely to have successful MDR-TB treatment outcomes.ConclusionsFavourable treatment outcomes for patients with MDR-TB can be achieved in a resource-limited country. Although the recommended WHO target of ≥75% was not met, the current result (71.7% treatment success rate) is still commendable considering all the challenges associated with TB treatment in Ghana.