Background Multidrug-resistant (MDR) Mycobacterium tuberculosis complex (MTBC) strains are a serious health problem in India, also contributing to one-fourth of the global MDR tuberculosis (TB) ...burden. About 36% of the MDR MTBC strains are reported fluoroquinolone (FQ) resistant leading to high pre-extensively drug-resistant (pre-XDR) and XDR-TB (further resistance against bedaquiline and/or linezolid) rates. Still, factors driving the MDR/pre-XDR epidemic in India are not well defined. Methods In a retrospective study, we analyzed 1852 consecutive MTBC strains obtained from patients from a tertiary care hospital laboratory in Mumbai by whole genome sequencing (WGS). Univariate and multivariate statistics was used to investigate factors associated with pre-XDR. Core genome multi locus sequence typing, time scaled haplotypic density (THD) method and homoplasy analysis were used to analyze epidemiological success, and positive selection in different strain groups, respectively. Results In total, 1016 MTBC strains were MDR, out of which 703 (69.2%) were pre-XDR and 45 (4.4%) were XDR. Cluster rates were high among MDR (57.8%) and pre-XDR/XDR (79%) strains with three dominant L2 (Beijing) strain clusters (Cl 1-3) representing half of the pre-XDR and 40% of the XDR-TB cases. L2 strains were associated with pre-XDR/XDR-TB (P < 0.001) and, particularly Cl 1-3 strains, had high first-line and FQ resistance rates (81.6-90.6%). Epidemic success analysis using THD showed that L2 strains outperformed L1, L3, and L4 strains in short- and long-term time scales. More importantly, L2 MDR and MDR + strains had higher THD success indices than their not-MDR counterparts. Overall, compensatory mutation rates were highest in L2 strains and positive selection was detected in genes of L2 strains associated with drug tolerance (prpB and ppsA) and virulence (Rv2828c). Compensatory mutations in L2 strains were associated with a threefold increase of THD indices, suggesting improved transmissibility. Conclusions Our data indicate a drastic increase of FQ resistance, as well as emerging bedaquiline resistance which endangers the success of newly endorsed MDR-TB treatment regimens. Rapid changes in treatment and control strategies are required to contain transmission of highly successful pre-XDR L2 strains in the Mumbai Metropolitan region but presumably also India-wide. Keywords: Tuberculosis, Resistant TB, Multidrug-resistant TB, Fluoroquinolone resistance, India; Pre-XDR/XDR-TB, Pre-XDR/XDR-TB transmission, Transmission success
Anesthesiology Merin, Robert G; Brown, Jerry L; Watson, David ...
The New England journal of medicine,
03/1998, Letnik:
338, Številka:
10
Journal Article
Recenzirano
To the Editor:
In an otherwise excellent and long-overdue review of anesthesiology, Wiklund and Rosenbaum (Oct. 16 and 23 issues)
1
have included several errors. Their discussion of halothane, in the ...section on inhalational anesthetics in part 1, states, “Hepatotoxicity has not been reported in children.” In fact, halothane hepatitis has been reported in children, although it is generally agreed that the incidence in children is lower than that in adults.
2
The authors also state, “Desflurane is highly fluorinated, nearly as insoluble as nitrous oxide, and as potent as isoflurane.” One of the minor disadvantages of desflurane is that it is . . .
This thesis examines C. neoformans and the meningitis it causes, based largely in Papua New Guinea (PNG). Investigation of possible environmental associations in PNG revealed that few E. ...camaldulensis survive experimental planting, while E. tereticornis is endemic. In Port Moresby E. confertiflora, E. papuana and E. alba are common. Examination of 1130 specimens from plant, bird and animal sources, failed to identify the ecological niche of C. neoformans in PNG. Epidemiological study of 96 patients presenting to Port Moresby General Hospital with cryptococcal meningitis from 1972-1993 showed an annual incidence of 33 cases per million population of Central Province and the National Capital District. 21 of these were infected with var. gattii and 12 with var. neoformans. On average 11 cases of cryptococcal meningitis present here annually. In this study geographical clustering, male predominance and possible seasonal variation were found. Eleven patients with cryptococcal meningitis were prospectively diagnosed and isolates biotyped. Seven isolates were var. gattii (one patient with diabetes mellitus) and four were var. neoformans. The latter came from adult patient with HVI infection, tuberculosis or Plasmodium vivax malaria. Five patients (45.5%) died; the 2 var. neoformans HIVI infected men and 3 adult var. gattii patients. In PNG, where var. gattii has been predominant in the immunocompetent, var. neoformans is emerging amongst immunosuppressed patients, notably those with HIVI infection. These studies confirm the high prevalence in PNG of meningitis caused by C. neoformans var. gattii in immunocompetent individuals. Potential mammal and plant sources are similar to those found in Australia.
This thesis examines C. neoformans and the meningitis it causes, based largely in Papua New Guinea (PNG). Investigation of possible environmental associations in PNG revealed that few E. ...camaldulensis survive experimental planting, while E. tereticornis is endemic. In Port Moresby E. confertiflora, E. papuana and E. alba are common. Examination of 1130 specimens from plant, bird and animal sources, failed to identify the ecological niche of C. neoformans in PNG. Epidemiological study of 96 patients presenting to Port Moresby General Hospital with cryptococcal meningitis from 1972-1993 showed an annual incidence of 33 cases per million population of Central Province and the National Capital District. 21 of these were infected with var. gattii and 12 with var. neoformans. On average 11 cases of cryptococcal meningitis present here annually. In this study geographical clustering, male predominance and possible seasonal variation were found. Eleven patients with cryptococcal meningitis were prospectively diagnosed and isolates biotyped. Seven isolates were var. gattii (one patient with diabetes mellitus) and four were var. neoformans. The latter came from adult patient with HVI infection, tuberculosis or Plasmodium vivax malaria. Five patients (45.5%) died; the 2 var. neoformans HIVI infected men and 3 adult var. gattii patients. In PNG, where var. gattii has been predominant in the immunocompetent, var. neoformans is emerging amongst immunosuppressed patients, notably those with HIVI infection. These studies confirm the high prevalence in PNG of meningitis caused by C. neoformans var. gattii in immunocompetent individuals. Potential mammal and plant sources are similar to those found in Australia.
Lung infections with
Mycobacterium abscessus,
a species of multidrug resistant nontuberculous mycobacteria, are emerging as an important global threat to individuals with cystic fibrosis (CF) where ...they accelerate inflammatory lung damage leading to increased morbidity and mortality. Previously,
M. abscessus
was thought to be independently acquired by susceptible individuals from the environment. However, using whole genome analysis of a global collection of clinical isolates, we show that the majority of
M. abscessus
infections are acquired through transmission, potentially
via
fomites and aerosols, of recently emerged dominant circulating clones that have spread globally. We demonstrate that these clones are associated with worse clinical outcomes, show increased virulence in cell-based and mouse infection models, and thus represent an urgent international infection challenge.
PDF
