Tuberculosis continues to be a major killer disease, despite an all-out effort launched against it in the postgenomic era. We describe here the population structure of Mycobacterium tuberculosis strains, as revealed by a chromosome-wide scan of fluorescent amplified fragment length polymorphisms (FAFLPs), for more than 1,100 independent isolates from 11 different countries. The bacterial strains were genotyped based on a total of 136 ؎ 1 different FAFLP markers at the genome sequence interface, with details on IS6110 profiles, drug resistance status, clinicopathological observations, and host status integrated into the analysis process. The strains were found to cluster with possible geographic affinities, including the parameters of host species type, IS6110 profile, and drug susceptibility status. Of the five most commonly amplified fragment sets (or amplitypes), type A predominated in strains of mixed origin, deposited in The Netherlands; type B was exclusively observed for Indian isolates; type C was found mainly in strains from Peru and Australia; and types D and E predominated in European strains from France and Italy. The amplitypes were independent of certain large sequence polymorphisms representing two important deletions, TbD1 and Rd9. It appears that M. tuberculosis has a high genomic diversity with a possible geographic evolution. This may have occurred due to specific genomic deletions and synonymous substitutions selected rigorously against host defenses and environmental stresses on an evolutionary timescale. The genotypic data reported here are additionally significant for genotype-phenotype correlations and for determining whether pathogen diversity is a reflection f the host population diversity.Mycobacterium tuberculosis, the underlying cause of tuberculosis, infects almost every third person in the world and has been regarded as the most successful pathogen in the history of the diseases of mankind. The accumulation of changes in the genomic content, occurring through gene acquisition and loss, is the major underlying (historical) event in the emergence of fit and successful strain variants in the M. tuberculosis complex (13,14). A few predominant genotypes circulating throughout the world are responsible for the major outbreaks of the recent past, and these belong to the so-called Beijing, Haarlem, and African clusters (5, 13, 21, 23). These major strain groups have been classified based on repetitive element IS6110 genotyping and spoligotyping patterns and have been described as the predominant pathotypes in the world. Although the M. tuberculosis genome contains several repetitive elements, only a few are polymorphic and these have not been rigorously studied (18). The abundance of polymorphisms related to the mobility of repetitive elements, coupled with the restricted number of single-nucleotide polymorphisms, indicates that transposition and homologous recombination are the major events contributing to the diversity of M. tuberculosis strains (21). In addition, polymorphisms seen with ...
Using real-time technology, we reliably identified chronic hepatitis C virus (HCV) infection and quantified virus from reflex samples originally submitted for serologic testing. There was no need to process specimens obtained directly for quantitation separately. Whether the initial source is a reflex sample or one obtained directly, a repeat HCV RNA test is needed before starting treatment.
The combination therapy of ledipasvir/sofosbuvir was approved by the Food and Drug Administration in 2014 for the treatment of chronic hepatitis C. Although hyperglycemia is not well known to occur with its use, we present 2 cases of new-onset diabetes mellitus and a review of the literature suggesting an adverse event association. In the first patient with HIV, we postulate that ledipasvir/sofosbuvir increased the levels of tenofovir and thereby potentiated hyperglycemia. In the second case of a patient with prediabetes, ledipasvir/sofosbuvir appeared to increase insulin resistance. A literature review further supported an association of hyperglycemia and the use of ledipasvir/sofosbuvir. Hence, clinicians should be cautious about worsening of glucose intolerance, and more studies are warranted to explore the underlying mechanism.
Infection with HCV is one of the most challenging co-morbidities emerging in HIV-infected patients in the post-antiretroviral therapy era. The co-infected population differs from the HCV mono-infected population in several aspects. HIV accelerates hepatic fibrosis progression, cirrhosis, end-stage liver disease, the development of hepatocellular carcinoma and death. Co-infected patients have a lower likelihood of achieving sustained virological response to treatment compared with mono-infected ones. A growing number of co-infected patients have a past history of nonresponse or relapse along with advanced liver disease. The simultaneous treatment of HCV and HIV may be associated with the occurrence of drug interactions, overlapping toxicities, and increased incidence and severity of side effects. This population is sorely in need of treatment. State-of-the-art management requires different strategies to achieve a cure with minimal adverse events. This review focuses on specific treatment challenges encountered in the current treatment of HCV in HIV-seropositive individuals.
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