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Objectives Globally, tuberculosis (TB) incidence and mortality are declining; however, low detection of drug-resistant disease threatens to reverse current progress toward global TB control. Multiple, rapid molecular diagnostic tests have recently been developed to detect genetic mutations in Mycobacterium tuberculosis (Mtb) known to confer anti-TB drug resistance. Their utility, though, depends on the frequency and distribution of the resistance-associated mutations in the pathogen population. Therefore, this review aimed to assess the prevalence of the gene mutations associated with rifampicin (RIF) and isoniazid (INH) resistant Mtb in Ethiopia. Methods Using PRISMA guidelines, we searched the literature on PubMed/MEDLINE, Web of Science, Scopus, and Cochrane library databases. Data analysis was conducted in STATA 11. Results In total, 909 (95.8%) of 949 INH resistant Mtb isolates had detectable gene mutations: 95.8% in katG315 and 5.9% in the inhA-promoter region. The meta-analysis resulting an estimated prevalence of katGMUT1(S315T1) was 89.2% (95%CI:81.94-96.43%), while a pooled prevalence of inhAMUT1 (C15T) was 77.5% (95%CI:57.84-97.13%). Besides, 769 (90.8%) of 847 RIF resistant strains had detectable rpoB gene mutations, and the meta-analysis resulting in a pooled prevalence of rpoBMUT3 (S531L) was 74.2% (95%CI: 66.39-82.00%). Conclusions RIF-resistant Mtb isolates were spread widely, particularly those harboring S531L mutations. Similarly, INH-resistant Mtb strains with S315T1 and C15T mutations were common. Tracking S531L, S315T1, and C15T mutations among RIF and INH resistant isolates, respectively, would be diagnostically and epidemiologically valuable. Rapid diagnosis of RIF and INH-resistant Mtb in TB patients would expedite alteration of treatment regimens, and proper timely infection control interventions could reduce the risk of progression and transmission of multidrug-resistant TB (MDR-TB).

In the following systematic review and meta-analyses, we report several conclusions about resistance to carbapenem and polymyxin last-resort antibiotics for treating multidrug-resistant bacterial infections among pregnant women and infants. Resistance to carbapenems and polymyxins is increasing, even in otherwise vulnerable groups such as pregnant women, toddlers, and infants, for whom therapeutic options are limited. In almost all countries, carbapenem-/polymyxin-resistant Klebsiella pneumoniae, Escherichia coli, and Acinetobacter baumannii infect and/or colonize neonates and pregnant women, causing periodic outbreaks with very high infant mortalities. Downregulation of plasmid-borne blaNDM , blaKPC , blaOXA-48 , blaIMP, blaVIM , blaGES-5 , and ompK35/36 in clonal strains accelerates the horizontal and vertical transmissions of carbapenem resistance among these pathogens. New Delhi metallo-β-lactamase (NDM)-positive isolates in infants/neonates have been mainly detected in China and India, while OXA-48-positive isolates in infants/neonates have been mainly detected in Africa. NDM-positive isolates in pregnant women have been found only in Madagascar. Antibiotic therapy, prolonged hospitalization, invasive procedures, mechanical ventilation, low birth weight, and preterm delivery have been common risk factors associated with carbapenem/polymyxin resistance. The use of polymyxins to treat carbapenem-resistant infections may be selecting for resistance to both agents, restricting therapeutic options for infected infants and pregnant women. Currently, low- and middle-income countries have the highest burden of these pathogens. Antibiotic stewardship, periodic rectal and vaginal screening, and strict infection control practices in neonatal ICUs are necessary to forestall future outbreaks and deaths.

BackgroundCarbapenems and polymyxins are last-resort antibiotics used to treat multidrug-resistant bacterial infections. However, resistance is increasing, even in vulnerable groups such as pregnant women and infants, for whom therapeutic options are limited.MethodUsing a diversity of databases, the literature was searched for studies investigating carbapenem and polymyxin resistance in pregnant women and infants (< 5 years).ResultA final set of 73 manuscripts were used. In almost all countries, carbapenem/polymyxin-resistant Klebsiella pneumoniae, Escherichia coli, and Acinetobacter baumannii infect and/or colonizes neonates and pregnant women, causing periodic outbreaks with very high infant mortalities. Plasmid-borne blaNDM, blaKPC, blaOXA-48, blaIMP,blaVIM and blaGES-5 and ompK35/36 downregulation in clonal strains accelerate the horizontal and vertical transmission of carbapenem resistance in these pathogens. High prevalence of carbapenem/polymyxin resistance and carbapenemases were present in India, China, Pakistan, Thailand, Taiwan, Turkey, Egypt, Italy, USA, South Africa, Algeria, Ghana, and Madagascar. Factors such as antibiotic therapy, prolonged hospitalization, invasive procedures, mother/infant colonization, mechanical ventilation, low-birth weight and preterm state placed infants at high risk of carbapenem/polymyxin-resistant infections. Infant mortalities ranged from 0.2% to 36.8% in different countries.ConclusionUse of polymyxins to treat carbapenem-resistant infections is selecting for resistance to both agents, restricting therapeutic options for infected infants and pregnant women. However, appropriate infection control and antibiotic therapy can contain outbreaks and clear these infections. Antibiotic stewardship, periodic rectal and vaginal screening, and strict infection control practices in neonatal ICUs are necessary to forestall future outbreaks and deaths.HighlightsCarbapenems & polymyxins are last-resort antibiotics used for multidrug-resistant infectionsResistance to these two agents are reported in infants & pregnant womenK. pneumoniae, E. coli, and A. baumannii are the most common pathogensCarbapenem & polymyxin resistance cause outbreaks with high infant mortalitiesAppropriate treatment & infection control can outbreaks & save lives

Antibiotic resistance (AR) is one of the major public health threats and challenges to effective containment and treatment of infectious bacterial diseases worldwide. Here, we used different methods to map out the geographical hot spots, sources, and evolutionary epidemiology of AR. Escherichia coli, Klebsiella pneumoniae, Salmonella enterica, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp., Neisseria meningitis/gonorrhoeae, Vibrio cholerae, Campylobacter jejuni, etc., were common pathogens shuttling AR genes in Africa. Transmission of the same clones/strains across countries and between animals, humans, plants, and the environment was observed. We recommend Enterobacter spp. or K. pneumoniae as better sentinel species for AR surveillance., Antibiotic resistance (AR) remains a major threat to public and animal health globally. However, AR ramifications in developing countries are worsened by limited molecular diagnostics, expensive therapeutics, inadequate numbers of skilled clinicians and scientists, and unsanitary environments. The epidemiology of Gram-negative bacteria, their AR genes, and geographical distribution in Africa are described here. Data were extracted and analyzed from English-language articles published between 2015 and December 2019. The genomes and AR genes of the various species, obtained from the Pathosystems Resource Integration Center (PATRIC) and NCBI were analyzed phylogenetically using Randomized Axelerated Maximum Likelihood (RAxML) and annotated with Figtree. The geographic location of resistant clones/clades was mapped manually. Thirty species from 31 countries and 24 genera from 41 countries were analyzed from 146 articles and 3,028 genomes, respectively. Genes mediating resistance to β-lactams (including blaTEM-1, blaCTX-M, blaNDM, blaIMP, blaVIM, and blaOXA-48/181), fluoroquinolones (oqxAB, qnrA/B/D/S, gyrA/B, and parCE mutations, etc.), aminoglycosides (including armA and rmtC/F), sulfonamides (sul1/2/3), trimethoprim (dfrA), tetracycline [tet(A/B/C/D/G/O/M/39)], colistin (mcr-1), phenicols (catA/B, cmlA), and fosfomycin (fosA) were mostly found in Enterobacter spp. and Klebsiella pneumoniae, and also in Serratia marcescens, Escherichia coli, Salmonella enterica, Pseudomonas, Acinetobacter baumannii, etc., on mostly IncF-type, IncX3/4, ColRNAI, and IncR plasmids, within IntI1 gene cassettes, insertion sequences, and transposons. Clonal and multiclonal outbreaks and dissemination of resistance genes across species and countries and between humans, animals, plants, and the environment were observed; Escherichia coli ST103, K. pneumoniae ST101, S. enterica ST1/2, and Vibrio cholerae ST69/515 were common strains. Most pathogens were of human origin, and zoonotic transmissions were relatively limited. IMPORTANCE Antibiotic resistance (AR) is one of the major public health threats and challenges to effective containment and treatment of infectious bacterial diseases worldwide. Here, we used different methods to map out the geographical hot spots, sources, and evolutionary epidemiology of AR. Escherichia coli, Klebsiella pneumoniae, Salmonella enterica, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp., Neisseria meningitis/gonorrhoeae, Vibrio cholerae, Campylobacter jejuni, etc., were common pathogens shuttling AR genes in Africa. Transmission of the same clones/strains across countries and between animals, humans, plants, and the environment was observed. We recommend Enterobacter spp. or K. pneumoniae as better sentinel species for AR surveillance.

Citrobacter spp., Enterobacter hormaechei subsp., Klebsiella variicola and Proteae tribe members are rarely isolated Enterobacterales increasingly implicated in nosocomial infections. Herein, we show that these species contain multiple genes encoding resistance to important antibiotics and are widely and globally distributed, being isolated from human, animal, plant, and environmental sources in 67 countries. Certain clones and clades of these species were internationally disseminated, serving as reservoirs and mediums for the global dissemination of antibiotic resistance genes. As they can easily transmit these genes to more pathogenic species, additional molecular surveillance studies should be undertaken to identify and contain these antibiotic-resistant species.

BackgroundDrug resistance tuberculosis (DR-TB) continues to be a major public health threat globally. Due to the development of many rapid molecular diagnostic tools to detect gene mutations in M.tuberculosis (Mtb), specific genes conferring resistance to different anti-TB drugs have been identified. The aim of this meta-analysis was to assess the prevalence of the gene mutations associated with rifampicin (RIF) and isoniazid (INH) resistant Mtb in Ethiopia.MethodsUsing PRISMA guideline, we systematically searched a literature on PubMed/MEDLINE, Web of Science, Scopus electronic databases, Cochrane library, and other database sources. The data analysis was done using STATA 11. The pooled prevalence of the gene mutations associated with resistance to RIF and INH were estimated using the random effect model. Heterogeneity was measured by the I2 statistical test, and the publication bias through the funnel plot and the Egger’s regression test.ResultsAmong all antimycobacterial resistance tested TB patients, prevalence of resistance to any anti-TB drug was 31.3%, while multidrug resistance TB (MDR-TB), any RIF and INH resistance were 22.2%, 24.9%, and 27.9%, respectively. In total, 909 (95.8%) of 949 INH resistant Mtb isolates had detectable gene mutation in katG315 and 5.9% in the inhA gene. The meta-analysis derived an estimated pooled prevalence of katGMUT1(S315T1) in INH resistant Mtb was 89.18% (95%CI 81.94-96.43%), while a pooled inhAMUT1 (C15T) resistant Mtb prevalence was 77.48% (95% CI 57.84-97.13%). Besides, 769 (90.8%) of 847 RIF resistant strains had detectable rpoB gene mutation, commonly in rpoBMUT3(S531L) probe (550 cases). The meta-analysis resulting a pooled rpoBMUT3(S531L) resistant Mtb prevalence of 74.20 % (95%CI 66.39-82.00%).ConclusionsRIF resistant Mtb isolates were spread widely, mainly with S531L mutation. Similarly, INH resistant Mtb isolates were spread with S315T1 and C15T mutations. It is significant to detect S531L among RIF resistant and S315T1 and C15T mutations among INH resistant isolates as it may be a determinant for subsequent development of MDR-TB. Rapid diagnosis of RIF and INH resistant Mtb strains in TB patients would expedite modification of treatment regimens, and proper infection control interventions could be taken on time to reduce the risk of further development and transmission of MDR-TB.HighlightsTuberculosis(TB), particularly drug resistance TB (DR-TB) continues to be a major public health threat globally. Herein, we used a systematic literature search on reliable electronic databases, and perform a meta-analysis to assess the prevalence of the gene mutations associated with rifampicin (RIF) and isoniazid (INH) resistant Mtb in Ethiopia. The meta-analysis derived an estimated pooled prevalence of katGMUT1 (S315T1) in INH resistant Mtb was 89.18% (95%CI 81.94-96.43%), while inhAMUT1(C15T) resistant Mtb prevalence was 77.48% (95% CI 57.84-97.13%). Besides, among 90.8% of RIF resistant strains which had detectable rpoB gene mutation, a pooled S531L resistant Mtb prevalence was 74.20% (95%CI 66.39-82.00%). This review revealed that the RIF resistant Mtb strains were spread widely, mainly with S531L mutation, while the INH resistant Mtb isolates were spread widely with S315T1 and C15T mutations. So, it is significant to detect S531L among RIF resistant and S315T1 and C15T mutations among INH resistant isolates as it may be a determinant for subsequent development of MDR-TB. Rapid diagnosis of RIF and INH resistant Mtb strains in TB patients would expedite alteration of treatment regimens, and proper infection control interventions could be taken on time to reduce the risk of further development and transmission of MDR-TB.

Background.The global epidemiology and resistomes dynamics of multidrug-resistant Citrobacter spp., Enterobacter hormaechei, Klebsiella variicola, morganella morganii, Proteus mirabilis and Providencia spp. have not been described, despite their importance as emerging opportunistic clinical pathogens.Methods.The genomes of the above-mentioned organisms were curated from PATRIC and NCBI and used for evolutionary epidemiology, phylogeography and resistome analyses. The phylogeny trees were drawn using RAXmL and edited with Figtree. The resistomes were curated from GenBank and the phylogeography was manually mapped.Results and conclusion.Mcr-9 and other mcr variants were highly prevalent in E. hormaechei subsp. and substantial in C. freundii whilst KPC, OXA-48, NDM, IMP, VIM, TEM, OXA and SHV were abundant in global E. hormaechei subsp., Citrobacter freundii, P. mirabilis, P. stuartii and P. rettgeri clones/clades. Species-specific ampCs were highly conserved in respective species whilst fluoroquinolones, aminoglycosides, macrolides, fosfomycin, chloramphenicol, tetracycline, sulphamethoxazole and trimethoprim resistance mechanisms were abundantly enriched in almost all clades of most of the species, making them extensively and pandrug resistant; K. variicola, C. amalonaticus and C, koseri had relatively few resistance genes. Vertical and horizontal resistome transmissions as well as local and international dissemination of strains evolving from common ancestors were observed, suggesting the anthroponotic, zoonotic, and food-/water-borne infectiousness of these pathogens. There is a global risk of pandrug resistant strains escalating local and international outbreaks of antibiotic-insensitive infections, initiating the dawn of a post-antibiotic era.

Recent evidence suggests that, in some foci, elimination of onchocerciasis from Africa may be feasible with mass drug administration (MDA) of ivermectin. To achieve continental elimination of transmission, mapping surveys will need to be conducted across all implementation units (IUs) for which endemicity status is currently unknown. Using boosted regression tree models with optimised hyperparameter selection, we estimated environmental suitability for onchocerciasis at the 5 × 5-km resolution across Africa. In order to classify IUs that include locations that are environmentally suitable, we used receiver operating characteristic (ROC) analysis to identify an optimal threshold for suitability concordant with locations where onchocerciasis has been previously detected. This threshold value was then used to classify IUs (more suitable or less suitable) based on the location within the IU with the largest mean prediction. Mean estimates of environmental suitability suggest large areas across West and Central Africa, as well as focal areas of East Africa, are suitable for onchocerciasis transmission, consistent with the presence of current control and elimination of transmission efforts. The ROC analysis identified a mean environmental suitability index of 0·71 as a threshold to classify based on the location with the largest mean prediction within the IU. Of the IUs considered for mapping surveys, 50·2% exceed this threshold for suitability in at least one 5 × 5-km location. The formidable scale of data collection required to map onchocerciasis endemicity across the African continent presents an opportunity to use spatial data to identify areas likely to be suitable for onchocerciasis transmission. National onchocerciasis elimination programmes may wish to consider prioritising these IUs for mapping surveys as human resources, laboratory capacity, and programmatic schedules may constrain survey implementation, and possibly delaying MDA initiation in areas that would ultimately qualify., Author summary As of 2018, it was unknown if onchocerciasis transmission occurred among approximately 2 400 implementation units (IUs; typically, second administrative-level units, such as districts) considered potentially endemic. These IUs have either never been surveyed for onchocerciasis or historical data are not sufficient to define contemporary endemicity status. Given the large number of IUs for which baseline data collection is likely required to achieve continental elimination, there is a need to prioritise areas for surveys to ensure that those suitable for endemic transmission, and therefore potentially eligible for mass drug administration, are able to initiate interventions as soon as possible. We used boosted regression trees to predict environmental suitability for onchocerciasis, with corresponding measures of uncertainty. We summarized the fine scale spatial predictions at the IU level by using receiver operating characteristic (ROC) curve analysis to identify a threshold that maximized agreement with the occurrence locations to identify IUs that may warrant prioritisation for mapping surveys. This analysis suggests that approximately half of the IUs considered for surveys could be classified as environmentally suitable for onchocerciasis. In order to develop an elimination strategy, many national onchocerciasis elimination programmes (NOEPs) need a mechanism to synthesise historical data to define priority areas for surveys.

BackgroundTuberculosis (TB) remains a main global public health problem. However, a systematic review of TB resistance epidemiology in Africa is wanting.MethodsA comprehensive systematic search of PubMed, Web of Science and ScienceDirect for English research articles reporting on the molecular epidemiology of Mycobacterium tuberculosis complex resistance in Africa from January 2007 to December 2018 was undertaken.Results and conclusionQualitative and quantitative synthesis were respectively undertaken with 232 and 186 included articles, representing 32 countries. TB monoresistance rate was highest for isoniazid (59%) and rifampicin (27%), particularly in Zimbabwe (100%), Swaziland (100%), and Sudan (67.9%) whilst multidrug resistance (MDR) rate was substantial in Zimbabwe (100%), Sudan (34.6%), Ivory Coast (24.5%) and Ethiopia (23.9%). Resistance-conferring mutations were commonly found in katG (n=3694), rpoB (n=3591), rrs (n=1272), inhA (n=1065), pncA (n=1063) and embB (n=705) in almost all included countries: S315G/I/N/R/T, V473D/F/G/I, Q471H/Q/R/Y, S303C/L etc. in katG; S531A/F/S/G, H526A/C/D/G, D516A/E/G etc. in rpoB; A1401G, A513C etc. in rrs; C15T, G17A/T, -A16G etc. in inhA; Ins456C, Ins 172G, L172P, C14R, Ins515G etc in pncA. Commonest lineages and families such as T (n=8139), LAM (n=5243), Beijing (n=5471), Cameroon (n=3315), CAS (n=2021), H (n=1773) etc., with the exception of T, were not fairly distributed; Beijing, Cameroon and CAS were prevalent in South Africa (n=4964), Ghana (n=2306), and Ethiopia/Tanzania (n=799/635) respectively. Resistance mutations were not lineage-specific and sputum (96.2%) were mainly used for diagnosing TB resistance using the LPA (38.5%), GeneXpert (17.2%), whole-genome sequencing (12.3%) and PCR/amplicon sequencing (9%/23%). Intercountry spread of strains were limited while intra-country dissemination was common. TB resistance and its diagnosis remain a major threat in Africa, necessitating urgent action to contain this global menace.

Background Bacterial meningitis is still a major public health threat in developing countries. It is an overwhelming infection with a high morbidity and mortality rate, especially in neonates. The aim of this study was to determine the prevalence and etiological agents that cause bacterial neonatal meningitis at Tikur Anbessa Specialized Hospital (TASH). Methods This is a retrospective analysis of 1189 cerebrospinal fluid (CSF) specimens submitted to the bacteriology laboratory of TASH for culture from 2001 to 2010. All newborns younger than 29 days old that were suspected for bacterial meningitis cases were included in the study. Results Based on CSF culture, 56 newborns were identified as having bacterial meningitis from a total of 1189 suspected cases. The overall prevalence of neonatal bacterial meningitis from the total suspected cases was 4.7%. The organisms identified and their prevalence rates were Streptococcus pneumoniae 13 (23%), Escherichia coli 9 (16%), Acinetobacter 7 (13%), Neisseria meningitides 5 (9%), Klebsiella spp. 5 (9%), Staphylococcus aureus 3 (5%) and Streptococcus pyogen 3 (5%). There were two (4%) cases each that was caused by Coagulase-Negative-Staphylococcus and Non-Group-A-Streptococcus, while 1 (2%) caused by Haemophilus influenzae. S. pneumoniae was the main etiological agent identified from CSF culture. The male to female ratio was 1:0.88 (53% were male). The birth weights of 34 (61%) patients were under 2500 g, and 22 (39%) patients had normal birth weights. Twenty-seven (48%) were early onset cases, and 29 (52%) were late-onset. Conclusion Streptococcus pneumoniae and Escherichia coli were the two main etiological agents for neonatal bacterial meningitis infection in the study area.