MULTIDRUG RESISTANT TUBERCULOSIS - BIOMECHANISM, EPIDEMIOLOGY AND MANAGEMENT STRATEGIES.
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ABSTRACT:
SUBMITTER: Tewari SC
PROVIDER: S-EPMC5531036 | biostudies-other | 1997 Jul
REPOSITORIES: biostudies-other
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Project description:The transcontinental spread of multidrug-resistant (MDR) tuberculosis is poorly characterized in molecular epidemiologic studies. We used genomic sequencing to understand the establishment and dispersion of MDR Mycobacterium tuberculosis within a group of immigrants to the United States. We used a genomic epidemiology approach to study a genotypically matched (by spoligotype, IS6110 restriction fragment length polymorphism, and mycobacterial interspersed repetitive units-variable number of tandem repeat signature) lineage 2/Beijing MDR strain implicated in an outbreak of tuberculosis among refugees in Thailand and consecutive cases within California. All 46 MDR M. tuberculosis genomes from both Thailand and California were highly related, with a median difference of 10 single-nucleotide polymorphisms (SNPs). The Wat Tham Krabok (WTK) strain is a new sequence type distinguished from all known Beijing strains by 55 SNPs and a genomic deletion (Rv1267c) associated with increased fitness. Sequence data revealed a highly prevalent MDR strain that included several closely related but distinct allelic variants within Thailand, rather than the occurrence of a single outbreak. In California, sequencing data supported multiple independent introductions of WTK with subsequent transmission and reactivation within the state, as well as a potential super spreader with a prolonged infectious period. Twenty-seven drug resistance-conferring mutations and 4 putative compensatory mutations were found within WTK strains. Genomic sequencing has substantial epidemiologic value in both low- and high-burden settings in understanding transmission chains of highly prevalent MDR strains.
| S-EPMC4490235 | biostudies-literature
Project description:ObjectivesTo estimate the pooled proportion of extensively drug-resistant tuberculosis (XDR-TB) and pre-extensively drug-resistant tuberculosis (pre-XDR-TB) in patients with multidrug-resistant TB (MDR-TB).MethodsWe systematically searched articles from electronic databases: MEDLINE (PubMed), ScienceDirect, and Google Scholar. We also searched gray literature from the different literature sources main outcome of the review was either XDR-TB or pre-XDR-TB in patients with MDR-TB. We used the random-effects model, considering the substantial heterogeneity among studies. Heterogeneity was assessed by subgroup analyses. STATA version 14 was used for analysis.ResultsA total of 64 studies that reported on 12,711 patients with MDR-TB from 22 countries were retrieved. The pooled proportion of pre-XDR-TB was 26% (95% confidence interval [CI]: 22-31%), whereas XDR-TB in MDR-TB cases was 9% (95% CI: 7-11%) in patients treated for MDR-TB. The pooled proportion of resistance to fluoroquinolones was 27% (95% CI: 22-33%) and second-line injectable drugs was 11% (95% CI: 9-13%). Whereas the pooled resistance proportions to bedaquiline, clofazimine, delamanid, and linezolid were 5% (95% CI: 1-8%), 4% (95% CI: 0-10%), 5% (95% CI; 2-8%), and 4% (95% CI: 2-10%), respectively.ConclusionThe burden of pre-XDR-TB and XDR-TB in MDR-TB were considerable. The high burdens of pre-XDR-TB and XDR-TB in patients treated for MDR-TB suggests the need to strengthen TB programs and drug resistance surveillance.
| S-EPMC10302157 | biostudies-literature
Project description:Background:Multidrug-resistant tuberculosis (MDR-TB) is an important global public health threat, but accurate estimates of MDR-TB burden among children are lacking. Methods:We analyzed demographic, clinical, and laboratory data for newly diagnosed pediatric (age <15 years) TB cases reported to the US National TB Surveillance System during 1993-2014. MDR-TB was defined as culture-confirmed TB disease with resistance to at least isoniazid and rifampicin. To ascertain potential underestimation of pediatric MDR-TB, we surveyed high-burden states for clinically diagnosed cases treated for MDR-TB. Results:Of 20789 pediatric TB cases, 5162 (24.8%) had bacteriologically confirmed TB. Among 4826 (93.5%) with drug susceptibility testing, 82 (1.7%) had MDR-TB. Most pediatric MDR-TB cases were female (n = 51 [62%]), median age was 5 years (interquartile range, 1-12 years), one-third were Hispanic (n = 28 [34%]), and two-thirds (n = 55 [67%]) were born in the United States. Most cases had additional resistance to ?1 other first-line drug (n = 66 [81%]) and one-third had resistance to ?1 second-line drug (24/73 tested). Of 77 who started treatment prior to 2013, 66 (86%) completed treatment and 4 (5%) died. Among the 4 high-TB-burden states/jurisdictions surveyed, there was 42%-55% underestimation of pediatric MDR-TB cases when using only culture-confirmed case definitions. Conclusions:Only one-quarter of pediatric TB cases had culture-confirmed TB, likely resulting in underestimation of true pediatric MDR-TB burden in the United States using strictly bacteriologic criteria. Better estimates of pediatric MDR-TB burden in the United States are needed and should include clinical diagnoses based on epidemiologic criteria.
| S-EPMC5801661 | biostudies-literature
Project description:Infants admitted to the neonatal intensive care unit, particularly those born preterm, are at high risk for infection due to the combination of an immature immune system, prolonged hospitalization, and frequent use of invasive devices. Emerging evidence suggests that multidrug-resistant gram-negative (MDR-GN) infections are increasing in neonatal settings, which directly threatens recent and ongoing advances in contemporary neonatal care. A rising prevalence of antibiotic resistance among common neonatal pathogens compounds the challenge of optimal management of suspected and confirmed neonatal infection. We review the epidemiology of MDR-GN infections in neonates in the United States and internationally, with a focus on extended-spectrum β-lactamase (ESBL)-producing Enterobacterales and carbapenem-resistant Enterobacterales (CRE). We include published single-center studies, neonatal collaborative reports, and national surveillance data. Risk factors for and mechanisms of resistance are discussed. In addition, we discuss current recommendations for empiric antibiotic therapy for suspected infections, as well as definitive treatment options for key MDR organisms. Finally, we review best practices for prevention and identify current knowledge gaps and areas for future research. IMPACT: Surveillance and prevention of MDR-GN infections is a pediatric research priority. A rising prevalence of MDR-GN neonatal infections, specifically ESBL-producing Enterobacterales and CRE, compounds the challenge of optimal management of suspected and confirmed neonatal infection. Future studies are needed to understand the impacts of MDR-GN infection on neonatal morbidity and mortality, and studies of current and novel antibiotic therapies should include a focus on the pharmacokinetics of such agents among neonates.
| S-EPMC8819496 | biostudies-literature
Project description:The epidemiology and genotypes of multidrug-resistant tuberculosis (MDR-TB), a global public health threat, remain limited. The genotypic distribution and factors associated with MDR-TB in upper northern Thailand between 2015 and 2019 were investigated. The DNA sequencing of rpoB, katG, and inhA promoter of 51 multidrug-resistant Mycobacterium tuberculosis isolates revealed nine patterns of the rpoB gene mutation distributed in seven provinces. The S531L mutation was the most common mutation in all provinces. The rpoB mutation in Chiang Rai, Chiang Mai, and Lampang was highly diverse compared to other areas. Here, the mutation profiles that have yet to be reported in northern Thailand (H526P, Q513P, and H526C) were detected in Chiang Rai province. The S315T katG mutation was the most common genotype associated with INH resistance, especially in Chiang Mai and Lampang. Further analysis of data from 110 TB patients (42 MDR-TB and 68 drug-susceptible TB) revealed that <60 years of age was a significant factor associated with MDR-TB (OR = 0.316, 95% CI 0.128−0.784, p = 0.011) and ≥60 years of age was a significant factor associated with the S315T katG-mutation (OR = 8.867, 95% CI 0.981−80.177, p = 0.047). This study highlighted the necessity for continuous surveillance and risk factor monitoring for effective control of MDR-TB.
| S-EPMC9774302 | biostudies-literature
Project description:The spread of multidrug-resistant tuberculosis (MDR-TB) is a serious public health issue, particularly in developing nations. The current methods of monitoring drug-resistant TB (DR-TB) using clinical diagnoses and hospital records are insufficient due to limited healthcare access and underreporting. This study proposes using Wastewater-Based Epidemiology (WBE) to monitor DR-TB in six African countries (Ghana, Nigeria, Kenya, Uganda, Cameroon, and South Africa) and examines the impact of treated wastewater on the spread of TB drug-resistant genes in the environment. Using droplet-digital polymerase chain reaction (ddPCR), the study evaluated untreated and treated wastewater samples in selected African countries for TB surveillance. There was a statistically significant difference in concentrations of genes conferring resistance to TB drugs in wastewater samples from the selected countries (p-value<0.05); South African samples exhibited the highest concentrations of 4.3(±2,77), 4.8(±2.96), 4.4(±3,10) and 4.7(±3,39) log copies/ml for genes conferring resistance to first-line TB drugs (katG, rpoB, embB and pncA respectively) in untreated wastewater. This may be attributed to the higher prevalence of TB/MDR-TB in SA compared to other African countries. Interestingly, genes conferring resistance to second-line TB drugs such as delamanid (ddn gene) and bedaquiline (atpE gene) were detected in relatively high concentrations (4.8(±3,67 and 3.2(±2,31 log copies/ml for ddn and atpE respectively) in countries, such as Cameroon, where these drugs are not part of the MDR-TB treatment regimens, perhaps due to migration or the unapproved use of these drugs in the country. The gene encoding resistance to streptomycin (rrs gene) was abundant in all countries, perhaps due to the common use of this antibiotic for infections other than TB. These results highlight the need for additional surveillance and monitoring, such as WBE, to gather data at a community level. Combining WBE with the One Health strategy and current TB surveillance systems can help prevent the spread of DR-TB in populations.
| S-EPMC10412881 | biostudies-literature
Project description:Background Multidrug-resistant tuberculosis (MDR-TB) has become a major public health problem in China, with mounting evidence suggesting that recent transmission accounts for the majority of MDR-TB. Here we aimed to reveal the transmission pattern of an MDR-TB outbreak in the Jing'an District of Shanghai between 2010 and 2015. Methods We used whole-genome sequencing (WGS) to conduct genomic clustering analysis along with field epidemiological investigation to determine the transmission pattern and drug resistance profile of a cluster with ten MDR-TB patients in combining field epidemiological investigation. Results The ten MDR-TB patients with genotypically clustered Beijing lineage strains lived in a densely populated, old alley with direct or indirect contact history. The analysis of genomic data showed that the genetic distances of the ten strains (excluding drug-resistant mutations) were 0–20 single nucleotide polymorphisms (SNPs), with an average distance of 9 SNPs, suggesting that the ten MDR-TB patients were infected and developed the onset of illness by the recent transmission of M. tuberculosis. The genetic analysis confirmed definite epidemiological links between the clustered cases. Conclusions The integration of the genotyping tool in routine tuberculosis surveillance can play a substantial role in the detection of MDR-TB transmission events. The leverage of genomic analysis in combination with the epidemiological investigation could further elucidate transmission patterns. Whole-genome sequencing could be integrated into intensive case-finding strategies to identify missed cases of MDR-TB and strengthen efforts to interrupt transmission. Supplementary Information The online version contains supplementary material available at 10.1186/s12879-021-06725-0.
| S-EPMC8557015 | biostudies-literature
Project description:BACKGROUND:Multidrug-resistant tuberculosis (MDR-TB) is burgeoning globally, and has been a serious challenge in TB management. Clinically, the ability to identify MDR-TB is still limited, especially in smear-negative TB. The aim of this study was to develop a nomogram for predicting MDR-TB. METHODS:Demographics and clinical characteristics of both MDR-TB and drug-susceptible TB patients were utilized to develop a nomogram for predicting MDR-TB. The LASSO regression method was applied to filter variables and select predictors, and multivariate logistic regression was used to construct a nomogram. The discriminatory ability of the model was determined by calculating the area under the curve (AUC). Moreover, calibration analysis and decision curve analysis (DCA) of the model were performed. This study involved a second analysis of a completed prospective cohort study conducted in a country with a high TB burden. RESULTS:Five variables of TB patients were selected through the LASSO regression method, and a nomogram was built based on these variables. The predictive model yielded an AUC of 0.759 (95% CI, 0.719-0.799), and in the internal validation, the AUC was 0.757 (95% CI, 0.715-0.793). The predictive model was well-calibrated, and DCA showed that if the threshold probability of MDR-TB was between 70 and 90%, using the proposed nomogram to predict MDR-TB would obtain a net benefit. CONCLUSIONS:In this study, a nomogram was constructed that incorporated five demographic and clinical characteristics of TB patients. The nomogram may be of great value for the prediction of MDR-TB in patients with sputum-free or smear-negative TB.
| S-EPMC7276074 | biostudies-literature
Project description:In a nationwide survey in 2011, multidrug-resistant tuberculosis (MDR TB) was found in 5.2% and 40.8% of patients with new and previously treated TB, respectively. These levels of drug resistance are among the highest ever documented in Africa and the Middle East. This finding presents a serious challenge for TB control in Somalia.
| S-EPMC3647667 | biostudies-literature
Project description:BACKGROUND:The treatment outcomes of multidrug-resistant tuberculosis (MDR-TB) patients in the 1990s in Taiwan was not satisfactory. To strengthen programmatic management of drug-resistant tuberculosis (PMDT), Taiwan MDR-TB Consortium (TMTC) was established in 2007. We assess the performance and epidemiologic impact of TMTC. METHODOLOGY/PRINCIPLE FINDINGS:We analyzed the trends of proportion of TB cases with drug susceptibility testing, enrollment of MDR-TB patients into TMTC and outcomes of treatment of all MDR-TB patients in Taiwan from 2007-2016. We computed the trends of both incidence and prevalence of MDR-TB from 2007-2016. We assessed the trends of MDR-TB among both new and recurrent TB cases. The proportion of TB cases with drug susceptibility testing results increased from 24.2% in 2007 to 97.9% in 2016. Of the 1,452 MDR-TB patients who were eligible for TMTC care, 1,197 (82.4%) were enrolled in TMTC, in whom 82.9% had treatment success. MDR-TB incidence was 9.0 cases per million in 2007, which declined to 4.6 cases per million in 2016 (p<0.0001). MDR-TB prevalence decreased from 19.4 cases per million in 2007 to 8.4 cases per million in 2016 (p<0.0001). The proportion of MDR-TB among new TB cases decreased from 1.4% in 2010 to 1.0% in 2016 (p = 0.039); and that among recurrent TB cases from 9.0% in 2010 to 1.8% in 2016 (p<0.0001). CONCLUSIONS:We concluded that effective PMDT have had a significant impact on the epidemic of drug-resistant TB in Taiwan.
| S-EPMC6445419 | biostudies-literature