The PstS1 antigen is highly immunogenic, principally when combined with CFP10 during both latent and active TB infection. In the present study, a selected pstS1 gene fragment was cloned, fused with CFP10, and expressed in Escherichia coli. The product M ycobacterium tuberculosis, a highly successful parasite, is the cause of tuberculosis (TB). A major health care concern, the disease results in approximately 1.4 million annual deaths (990,000 among HIV-negative individuals), infecting roughly one-third of the world's population. Among the infected, 5% to 10% will develop active disease in their lifetimes and 90% will harbor the latent form. According to a recent mathematical projection of TB eradication, the treatment of latent TB infection (LTBI) and active TB is urgently required in order to lower and ultimately prevent the further spread of the disease at its present rate (1, 2).Two principal approaches based on the adaptive immune responses elicited by M. tuberculosis infection are currently used to identify TBI (3): the in vivo tuberculin skin test (TST) and the ex vivo gamma interferon (IFN-␥) release assay (IGRA).Developed in 1908, TST became the standard means of assessing the presence of TB infection. Via TST, prior TB exposure is measured by a type 4 delayed-type hypersensitivity reaction when a purified protein derivative (PPD) of M. tuberculosis is injected intradermally. Although TST has some biological limitations such as the occurrence of anergies in one-third of active TB cases, crossreactivity with M. bovis bacillus Calmette-Guérin (BCG) and non-TB mycobacteria does not, according to some authors, result in major sensibility differences in IGRAs (4).The IGRA was recently developed using antigens that are expressed in M. tuberculosis but not in BCG or M. bovis strains as stimuli. These antigens measure the production of IFN-␥ in peripheral blood mononuclear cells (3,5). According to a recent World Health Organization (WHO) report (1), the two currently commercially available IGRAs have yet to generate sufficient data or enough high-quality evidence regarding their performance in the low-and middle-income countries that typically have a high TB and/or HIV burden and where the coverage of BCG vaccination may cause some interference (5, 6).Both IGRAs are based on Mycobacterium tuberculosis-specific antigens, namely, early secretory antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP10) (5). These antigens must be validated in different scenarios, but other antigen combinations also need to be evaluated to improve IGRA coverage.The 38-kDa M. tuberculosis antigen, also known as phosphatespecific transporter-1 (PstS-1), coded by a pstS1 gene that composes one of the 3 putative pst operons, is a lipoprotein phosphate transport receptor on the cell surface. These operons probably constitute a subtle biochemical adaptation of M. tuberculosis, enabling it to grow and survive under different phosphate-limiting conditions during its infectious cycle. The PstS-1 protein is ac-
Assuming that the IS6110-restriction fragment length polymorphism (RFLP) changes at a constant rate of 3.2 years, this methodology was applied to demonstrate, for the first time, variant patterns of Mycobacterium tuberculosis (MTB) in multiple isolates obtained at short time intervals from sputum and blood of an HIV + patient with multiple admissions to the Emergency Room and to the multidrug-resistant tuberculosis (MDR-TB) Reference Center of a secondary-care hospital in Rio de Janeiro, Brazil. In sputum, the IS6110-RFLP appeared in isolates with two variant patterns with 10 and 13 IS6110 copies. However, blood presented only the pattern corresponding to 10 copies, suggesting compartmentalization. With regard to the exact match of 10 of 13 bands, this may be a subpopulation with the same clonal origin and this may be related to the IS6110 transposition. A susceptibility test demonstrated an MDR profile (INH R , RIF R , SM R , and EMB R ), with the sputum isolate also exhibiting EMB S (R = resistant; S = sensitive). A gene mutation confirmed resistance only to streptomycin. There was agreement between the results of the phenotypic test and the clinical response to MDR-TB treatment, suggesting serious implications with regard to treatment administration based exclusively on molecular methods, and calling attention to the fact that more effective control strategies against the emergence of MDR strains must be implemented by the TB control program to prevent transmission of MDR-MTB strains at health facilities in areas highly endemic for TB.
This retrospective molecular study involving restriction fragment length polymorphism, using insertion sequence 6110 as a marker, was conducted in order to provide an initial insight into the genetic diversity of Mycobacterium tuberculosis strains isolated in the slums of the Complexo de Manguinhos, located in the city of Rio de Janeiro, Brazil. Of the 67 strains evaluated, 23 (34.3%) were found to belong to clusters (total clusters, 10). Household and social chains of transmission were associated with clustering, in 20% and 60%, respectively. Living in the Conjunto Habitacional Programado 2 slum was associated with clustering. Although not significant, it is relevant that 26% of the clustered strains presented primary resistance. These findings, although possibly underestimating the prevalence due to the failure to analyze all strains, could help improve the local tuberculosis control program.
To highlight the transmission and major phylogenetic clades of Mycobacterium tuberculosis, a retrospective study was carried out at two health facilities in a small agro-industrial area in São Paulo, Brazil, that has a low tuberculosis incidence rate. IS6110-RFLP and spoligotyping were performed on the isolates, with the former revealing that 31.3% (35/112) of strains were clustered. Epidemiological links were found in 16 of the 35 clustered patients and were associated with transmission among patients living in public housing. Spoligotyping grouped 62.8% of the strains. The T genetic family predominated among the isolates. Of interest is that five strains had a pattern characteristic of African or Asian origin (ST535), and two others were of the rare localized type ST1888 (BRA, VEN). In addition, three new types--1889, 1890, and 1891--were identified. Spoligotyping showed that some ST may be circulating to or from Brazil, and RFLP revealed ongoing transmission in inadequately ventilated public-housing buildings. This may point to a failure in tuberculosis control policy.
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