Antimicrobial resistance (AMR) was a leading cause of death globally in 2019. Sadly, COVID-19 has exacerbated AMR, nonetheless, the process of developing new antibiotics remains very challenging. ...This urgently requires the adoption of alternative approaches to treat multi-drug-resistant bacterial infections. This editorial introduces the 'Bacteriophages against multi-drug resistant bacteria' collection launched at BMC Infectious Diseases which highlights progress towards using bacteriophages to tackle AMR.
Antimicrobial resistance (AMR) remains a significant global health threat particularly impacting low- and middle-income countries (LMICs). These regions often grapple with limited healthcare ...resources and access to advanced diagnostic tools. Consequently, there is a pressing need for innovative approaches that can enhance AMR surveillance and management. Machine learning (ML) though underutilized in these settings, presents a promising avenue. This study leverages ML models trained on whole-genome sequencing data from England, where such data is more readily available, to predict AMR in E. coli, targeting key antibiotics such as ciprofloxacin, ampicillin, and cefotaxime. A crucial part of our work involved the validation of these models using an independent dataset from Africa, specifically from Uganda, Nigeria, and Tanzania, to ascertain their applicability and effectiveness in LMICs.
Model performance varied across antibiotics. The Support Vector Machine excelled in predicting ciprofloxacin resistance (87% accuracy, F1 Score: 0.57), Light Gradient Boosting Machine for cefotaxime (92% accuracy, F1 Score: 0.42), and Gradient Boosting for ampicillin (58% accuracy, F1 Score: 0.66). In validation with data from Africa, Logistic Regression showed high accuracy for ampicillin (94%, F1 Score: 0.97), while Random Forest and Light Gradient Boosting Machine were effective for ciprofloxacin (50% accuracy, F1 Score: 0.56) and cefotaxime (45% accuracy, F1 Score:0.54), respectively. Key mutations associated with AMR were identified for these antibiotics.
As the threat of AMR continues to rise, the successful application of these models, particularly on genomic datasets from LMICs, signals a promising avenue for improving AMR prediction to support large AMR surveillance programs. This work thus not only expands our current understanding of the genetic underpinnings of AMR but also provides a robust methodological framework that can guide future research and applications in the fight against AMR.
We propose a novel, non-discriminatory classification of monkeypox virus diversity. Together with the World Health Organization, we named three clades (I, IIa and IIb) in order of detection. Within ...IIb, the cause of the current global outbreak, we identified multiple lineages (A.1, A.2, A.1.1 and B.1) to support real-time genomic surveillance.
Susceptibility testing for pyrazinamide (PZA), a cornerstone anti-TB drug is not commonly done in Uganda because it is expensive and characterized with technical difficulties thus resistance to this ...drug is less studied. Resistance is commonly associated with mutations in the pncA gene and its promoter region. However, these mutations vary geographically and those conferring phenotypic resistance are unknown in Uganda. This study determined the prevalence of PZA resistance and its association with pncA mutations.
Using a cross-sectional design, archived isolates collected during the Uganda national drug resistance survey between 2008-2011 were sub-cultured. PZA resistance was tested by BACTEC Mycobacterial Growth Indicator Tube (MGIT) 960 system. Sequence reads were downloaded from the NCBI Library and bioinformatics pipelines were used to screen for PZA resistance-conferring mutations.
The prevalence of phenotypic PZA resistance was found to be 21%. The sensitivity and specificity of pncA sequencing were 24% (95% CI, 9.36-45.13%) and 100% (73.54% - 100.0%) respectively. We identified four mutations associated with PZA phenotypic resistance in Uganda; K96R, T142R, R154G and V180F.
There is a high prevalence of phenotypic PZA resistance among TB patients in Uganda. The low sensitivity of pncA gene sequencing confirms the already documented discordances suggesting other mechanisms of PZA resistance in Mycobacterium tuberculosis.
Childhood HBV immunization remains globally fundamental to the elimination of hepatitis B virus (HBV). However, monitoring proportions of HBV vaccine seroprotection and their determinants among ...African Pediatric recipients is crucial. This study sought to verify extent of immune protection accorded by the HBV vaccine in African children of up to 17 years of age by pooling the prevalence of seroprotection reported by primary studies conducted in the Northern, Western, and Southern African regions. We included 19 eligible articles out of the 197 initially downloaded, published from 1999 to 2021 from African Journals Online (AJOL), EMBASE, Scopus, and PubMed. The study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO), University of York Centre for Reviews and Dissemination, under the registration number CRD42022361277. Significantly higher (p < 0.0001) proportion of HBV vaccine seroprotection (69.07%) was found among children under 15 years of age than children 15-17 years (32.368%), 95% CI 34.2454-39.0847%. Whereas successful integration of the HBV vaccine on the extended programs on immunizations (EPI) has been a major achievement in the reduction of HBV infection in Africa, markedly reduced HBV vaccine seroprotection is persistently demonstrated among adolescent children 15-17 years of age. Future studies are required to clarify the need for booster dose vaccination in most at risk populations and age groups.
Nosocomial infections are a major setback in the healthcare delivery system especially in developing countries due to the limited resources. The roles played by medical care equipment and work ...surfaces in the transmission of such organisms have inevitably contributed to the elevated mortality, morbidity and antibiotic resistances.
A total 138 samples were collected during the study from Kawolo general hospital. Swab samples were collected from various work surfaces and fomites which consisted of; beds, sink taps, infusion stands, switches, work tables and scissors. Cultures were done and the susceptibility patterns of the isolates were determined using Kirby Bauer disc diffusion method. Data was analyzed using Stata 13 and Microsoft Excel 2013 packages.
A total of 44.2% (61/138) of the collected swab specimens represented the overall bacterial contamination of the sampled articles. Staphylococcus aureus and Klebsiella pneumoniae accounted for the highest bacterial contaminants constituting of 75.4% (46/61) and 11.5% (7/61) respectively. Infusion stands and patient beds were found to have the highest bacterial contamination levels both constituting 19.67% (12/61). The highest degree of transmission of organisms to patients was found to be statistically significant for patient beds with OR: 20.1 and P-value 8X10
. Vancomycin, ceftriaxone and ciprofloxacin were the most effective antibiotics with 100%, 80% and 80% sensitivity patterns among the isolates respectively. Multi-drug resistant (MDR) Staphylococcus aureus accounted for 52% (24/46) with 4% (1/24) classified as a possible extensively drug resistant (XDR) whereas Gram negative isolates had 27% (4/15) MDR strains out of which 50%(2/4) were classified as possible pan-drug resistant (PDR).
The high prevalence of bacterial contaminants in the hospital work environment is an indicator of poor or ineffective decontamination. The study findings reiterate the necessity to formulate drug usage policies and re-examine effectiveness of decontamination and sterilization practices within Kawolo general hospital. We also recommend installation of a sound Microbiology unit at the hospital to take on susceptibility testing to check on the empirical use of antibiotics as a way of reducing the rampant elevations in drug resistances.
Background
In Africa, health practitioners and the current knowledge of the public on genetics and genomics is still very low and yet this has potential to reduce the burden of common genetic ...diseases. Many initiatives have promoted genomic research, infrastructure, and capacity building in Africa. What remains to be done is to improve genomics literacy among populations and communities while utilizing an array of strategies. Genomic literacy and awareness are key in the management of genetic diseases which includes diagnosis, prevention of complications and therapy. Africa is characterized by great cultural and language diversity thereby requiring a multidisciplinary approach to improving public and community genomics literacy and engagement. However, this is further complicated by having the fact that sub‐Saharan Africa is comprised of countries with the lowest literacy rates in the world.
Methods
We applied the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines to review genomic literacy in Africa using PubMed database.
Results
We found very limited evidence of genomics literacy for genetic diseases in Africa.
Conclusion
We propose a number of approaches that if adopted will significantly increase the genomic literacy and reduce the burden of genetic diseases in Africa.
In Africa, health practitioners and the current knowledge of genetics and genomics of the public is still very low and yet this has potential to reduce the burden of common genetic diseases. What remains to be done is to improve genomic literacy among populations and communities while utilizing an array of strategies.
Bacterial infections involving antibiotic-resistant gram-negative bacteria continue to increase and represent a major global public health concern. Resistance to antibiotics in these bacteria is ...mediated by chromosomal and/or acquired resistance mechanisms, these give rise to multi-drug resistant (MDR), extensive-drug resistant (XDR) or pan-drug resistant (PDR) bacterial strains. Most recently, plasmid-mediated resistance to colistin, an antibiotic that had been set apart as the last resort antibiotic in the treatment of infections involving MDR, XDR and PDR gram-negative bacteria has been reported. Plasmid-mediated colistin resistant gram-negative bacteria have been described to be PDR, implying a state devoid of alternative antibiotic therapeutic options. This review concisely describes the evolution of antibiotic resistance to plasmid-mediated colistin resistance and discusses the potential role of high-throughput sequencing technologies, genomics, and bioinformatics towards improving antibiotic resistance surveillance, the search for novel drug targets and precision antibiotic therapy focused at combating colistin resistance, and antibiotic resistance as a whole.
Abstract Background Between January 2015 and July 2017, we investigated the frequency of carbapenem resistant Acinetobacter baumannii (CRAB) and carbapenem resistant Pseudomonas aeruginosa (CRPA) at ...the Mulago Hospital intensive care unit (ICU) in Kampala, Uganda. Carbapenemase production and carbapenemase gene carriage among CRAB and CRPA were determined; mobility potential of carbapenemase genes via horizontal gene transfer processes was also studied. Methods Clinical specimens from 9269 patients were processed for isolation of CRAB and CRPA. Drug susceptibility testing was performed with the disk diffusion method. Carriage of carbapenemase genes and class 1 integrons was determined by PCR. Conjugation experiments that involved bla VIM positive CRAB/CRPA (donors) and sodium azide resistant Escherichia coli J53 (recipient) were performed. Results The 9269 specimens processed yielded 1077 and 488 isolates of Acinetobacter baumannii and Pseudomonas aeruginosa, respectively. Of these, 2.7% (29/1077) and 7.4% (36/488) were confirmed to be CRAB and CRPA respectively, but 46 were available for analysis (21 CRAB and 25 CRPA). Majority of specimens yielding CRAB and CRPA were from the ICU (78%) while 20 and 2% were from the ENT (Ear Nose & Throat) Department and the Burns Unit, respectively. Carbapenemase assays performed with the MHT assay showed that 40 and 33% of CRPA and CRAB isolates respectively, were carbapenemase producers. Also, 72 and 48% of CRPA and CRAB isolates respectively, were metallo-beta-lactamase producers. All the carbapenemase producing isolates were multidrug resistant but susceptible to colistin. bla VIM was the most prevalent carbapenemase gene, and it was detected in all CRAB and CRPA isolates while bla OXA-23 and bla OXA-24 were detected in 29 and 24% of CRAB isolates, respectively. Co-carriage of bla OXA-23 and bla OXA-24 occurred in 14% of CRAB isolates. Moreover, 63% of the study isolates carried class 1 integrons; of these 31% successfully transferred bla VIM to E. coli J53. Conclusions CRAB and CRPA prevalence at the Mulago Hospital ICU is relatively low but carbapenemase genes especially bla VIM and bla OXA-23 are prevalent among them. This requires strengthening of infection control practices to curb selection and transmission of these strains in the hospital.
is a leading cause of nosocomial infections worldwide. It can produce a range of debilitating infections, have a propensity for developing antimicrobial resistance, and present with a variety of ...potent virulence factors. This study investigated the sequence types (ST), phenotypic antimicrobial susceptibility profiles, and resistance and virulence genes among clinical isolates from urinary tract and skin and soft tissue infections. Fifty-six
clinical isolates were obtained from six medical centers across five counties in Kenya between 2015 and 2020. Whole-genome sequencing (WGS) was performed to conduct genomic characterization, sequence typing, and phylogenetic analysis of the isolates. Results showed the presence of globally distributed high-risk clones (ST244 and ST357), local high-risk clones (ST2025, ST455, and ST233), and a novel multidrug-resistant (MDR) clone carrying virulence genes (ST3674). Furthermore, 31% of the study isolates were found to be MDR with phenotypic resistance to a variety of antibiotics, including piperacillin (79%), ticarcillin-clavulanic acid (57%), meropenem (34%), levofloxacin (70%), and cefepime (32%). Several resistance genes were identified, including carbapenemases
(ST1203) and
(ST357), fluoroquinolone genes,
, and
, while 14 and 22 different chromosomal mutations were detected in the
and
genes, respectively. All isolates contained at least three virulence genes. Among the virulence genes identified,
was the most abundant (50/56, 89%). About 21% (12/56) of the isolates had the
- genotype, while 73% (41/56) of the isolates had the
- genotype. This study also discovered 12 novel lineages of
, of which one (ST3674) demonstrated both extensive antimicrobial resistance and the highest number of virulence genes (236/242, 98%). Although most high-risk clones were detected in Nairobi County, high-risk and clones of interest were found throughout the country, indicating the local spread of global epidemic clones and the emergence of new strains. Thus, this study illustrates the urgent need for coordinated local, regional, and international antimicrobial resistance surveillance efforts.