Non-tuberculosis Mycobacteria Infection Research Articles

Non tuberculosis mycobacteria isolates among new and previously treated pulmonary tuberculosis patients in Nigeria

ObjectiveTo determine the prevalence of non tuberculosis mycobacteria (NTM) among new and previously treated tuberculosis (TB) patients in Nigeria. MethodsIt was a retrospective study. A total of 102 sputum smear positive samples/culture isolates from pulmonary TB patients (41 new smear positive and 61 smear positive retreatment cases) were sent to the Institute of Tropical Medicine, Antwerp Belgium between 2007-2009. Data on patients' characteristics were retrieved from their treatment cards. ResultsAmong the 102 samples, 25 isolates results (20 were culture negative while 5 were contaminated) were excluded from the study. Data were available for 77 mycobacterium isolates. 70 (90.9%) were identified as Mycobacterium tuberculosis and 7 (9.1%) as atypical mycobacteria. Among the atypical mycobacteria, three of them were Mycobacterium fortuitum, two Mycobacterium intracellulare and two Mycobacterium chelonae. Of the seven isolates with atypical mycobacteria, 4 (57.1%) were from previously treated patients, while 3 (42.9%) were new sputum positive patients. There was no statistically significant difference in NTM infection between new and previously treated pulmonary TB patients (P =0.97). ConclusionsThe study shows the involvement of atypical mycobacterium in pulmonary infection in both new and previously treated TB patients. Therefore, there is a need to carry out culture and drug susceptibility testing in all pulmonary TB patients especially those who had failed conventional DOTS treatment to rule out NTM infections.

Nontuberculous Mycobacteria Among Patients Who are Suspected for Multidrug-Resistant Tuberculosis—Need for Earlier Identification of Nontuberculosis Mycobacteria

BackgroundIn this study, we intended to find the prevalence of nontuberculosis mycobacteria (NTM) among patients who are referred as suspected multidrug-resistant tuberculosis (MDR-TB) cases to the only referral center in Iran. MethodsAll patients referred to our center in 2002–2006 as MDR-TB with histories of treatment with standard and CAT II World Health Organization regimens were included in the study. Sputum smear and culture for acid-fast bacilli were performed for all patients 3 times. Sputum polymerase chain reaction was also performed for all patients. Mycobacterial identification was performed via polymerase chain reaction and routine identification tests for all culture-positive cases. ResultsOf the 105 patients in the study, 12 (11.43%) were identified to have NTM infection. The identified mycobacteria were classified in order of prevalence as Chelonae (8 cases), Simiae (2 cases), Aloei (1 case), and Farcinogen (1 case). Based on radiologic findings, most of the cases demonstrated bilateral nodularity (83.3%) and also multifocal bronchiectasis (75%). Notably, cavitary lesions were present in 41.7% of the cases. ConclusionBased on the findings of this study, it is essential that such cases be identified before commencing MDR-TB treatment.

A Novel Mutation 774del4 in IFNGR1, Which Produces Truncated Form of Interferon γ Receptor 1, Causes a Dominant-Negative Effect on Interferon γ Signal Transduction.

Patients with interferon γ receptor 1 (IFNγR1) deficiency are characterized by disseminated Bacilli Calmette-Guérin (BCG) infections and severe non-tuberculosis mycobacterium infections, and show remarkable genetic heterogeneity. It is known as one of inherited immunodeficiency disorders with recessive or dominant form. So far known dominant forms of IFNγR1 deficiency are associated with heterozygous mutation in the intracellular domain of IFNγR1, among of which 818del4 is known as a major mutation in IFNGR1, leading to frameshift and premature stop codon. We describe here a novel heterozygous IFNGR1 mutation in a patient with recurrent mycobacterium infections, resulting in impairment of receptor degradation. The proband, a 12-year old Japanese girl, developed multiple osteomyelitis due to M. avium infection. She had suffered from BCG lymphadenitis, which occurred 2 months after BCG vaccination, for 3 years. DNA sequence analysis of IFNGR1 demonstrated that the patient had a heterozygous mutation 774del4, producing a truncated protein lacking intracellular component of IFNγR1. IFNγR1 was overexpressed on the surface of CD14-positive cells in the peripheral blood of the patient, and STAT1 phosphorylation was partially defected in response to high dose IFN-γ stimulation. Impaired TNF-α production in response to IFN-γ stimulation was also observed. T cells from the patient presented decreased IFN-γ production in response to IL-12 stimulation.In order to define the characterization of this truncated form of IFNγR1, we cloned 774del4 and 818del4 mutations as well as the wild-type into mammalian expression vector. These constructs were transfected into HEK293 cells. Cycloheximide (CHX) treatment enabled detection of IFNγR1 expression by flow cytometry and Western blot analysis. In contrast to the wild-type IFNγR1 protein, which rapidly disappeared after CHX treatment, 774del4 mutant protein was stably retained on the cell surface as was observed in 818del4 mutant. These observations suggest that 774del4 mutant causes overexpression of dominant-negative form of IFNγR1 on the cell surface through impairment of receptor degradation.

Pathogeny of archaic mycobacteria at the emergence of urban life in Egypt (3400 bc)

In a previous study, we extracted, amplified and sequenced a DNA fragment from bone lesions similar to those of bone tuberculosis in a predynastic skeleton (Egypt, around 3400 bc). This 65 kDa gene fragment encodes the surface of the mycobacterium responsible for the lesions. In the present study, we reconstructed the phylogenetic tree of the Mycobacterium family using this fragment and 51 sequences of pathogens and environmental mycobacteria. This reconstruction enabled us to polarise the phylogenic tree and to confirm the originality of the sequence and its ancestral character. According to a recent evolutionary scenario for the Mycobacterium tuberculosis complex, these data suggest the pathogenicity of an archaic mycobacterium at the emergence of urban life. This result could lead to a better understanding of present day evolutionary processes, especially the emergence or re-emergence of non-tuberculosis mycobacteria infection and disease.