Extensively drug-resistant tuberculosis: 2 years of surveillance in Iran.

BACKGROUND: Extensively drug-resistant (XDR) tuberculosis (TB) is a cause of concern, because it renders patients untreatable with available drugs. In this study, we documented the existence and transmission of XDR TB among patients with multidrug-resistant TB. These patients were referred to the National Research Institute of Tuberculosis and Lung Diseases (Tehran, Iran) for treatment and diagnosis from 2003 to 2005. METHODS: The sputum specimens from a total of 2030 patients with TB were digested, examined microscopically for acid-fast bacilli, and inoculated into Lowenstein-Jensen slants by standard procedures. Testing of susceptibility to first-line drugs was performed for 1284 Mycobacterium tuberculosis isolates. Subsequently, the strains that were identified as multidrug-resistant M. tuberculosis (113 isolates) were subjected to susceptibility testing for second-line drugs. Spoligotyping and restriction fragment-length polymorphism were performed for strains that were identified as XDR M. tuberculosis. RESULTS: A total of 12 (10.9%) of 113 multidrug-resistant M. tuberculosis strains were resistant to all 8 second-line drugs tested and, therefore, were denoted as XDR M. tuberculosis. Retrospective analysis of the cases of XDR TB showed that all of them belonged to 1 of 2 epidemiological clusters, either a single-family cluster (4 cases) or a cluster of close contacts (8 cases). The strains were identified as belonging to the M. tuberculosis superfamilies Haarlem 1 and East African Indian 3. CONCLUSIONS: The emergence of XDR TB cases in Iran highlights the need to reinforce the Iranian TB policy with regard to control and detection strategies.

Increased activation and expansion of a CD57+ subset within peripheral CD8+ T lymphocytes in Mycobacterium tuberculosis-infected patients.

BACKGROUND: Mycobacterium tuberculosis-specific CD8+ and CD4+ T lymphocyte responses restrict the spread of extracellular pathogens by limiting M.tuberculosis replication. Alterations in cytolytic function, inappropriate maturation/differentiation, and limited proliferation could reduce their ability to control M.tuberculosis replication. METHODS: In an attempt to further characterize the immune responses during M.tuberculosis infection, we enumerated gamma-delta and alpha-beta receptor-bearing T cells expressing CD8 or CD4 phenotype and analyzed the differentiation phenotypes of CD8+ and CD4+ T lymphocyte subpopulations in 47 cases (23 new cases and 24 multidrug resistant patients) and 20 control subjects, using flowcytometry. RESULTS: We found that the CD4/CD8 ratio was significantly lower in newly-diagnosed M.tuberculosis patients compared to multidrug resistant and control subjects (P < 0.003). Also, we found that a large proportion of CD8+ T lymphocytes in newly-diagnosed patients was defined by increased surface expression of CD57 as compared to the two other settings (P < 0.002). This increase was more profound in patients with an inverted CD4/CD8 ratio. Analysis of the late activation antigen revealed that this was predominantly HLA-DR+ (P < 0.003). No significant changes were observed in the percentages of CD8+CD57+ T cells between the different settings. Moreover, the co-stimulatory molecule CD28+ tended to be underexpressed by CD8+ T cells in multidrug resistant patients when compared to newly-diagnosed subjects (P < 0.002), but not to the control subjects. In contrast, the frequency of CD28+ marker on CD4+ T cells was higher in the setting of multidrug resistant compared with those of new cases (P < 0.0001). No significant changes were observed in percentages of gamma-delta receptor-bearing T cells between different groups. CONCLUSION: We suggest that the increase in the proportion of CD57+ within CD8+ T cells in newly-diagnosed patients results from M.tuberculosis antigenic stimulation, which is a hallmark of many infections and that the protracted accumulation of CD57+ T lymphocytes might reflect an end-stage differentiation phenotype.

Radiographic manifestations of Tuberculosis in HIV positive patients: Correlation with CD4+ T-cell count.

BACKGROUND: Observations on Tuberculosis/HIV co-infection in addition to epidemiologic molecular studies have recently provided strong evidence for the state of immune system as the major determinant of the TB imaging spectrum. However, the presence of any correlation between radiographic findings and the degree of immunosuppression in HIV+ patients still remains controversial. The present study aimed to investigate the TB radiographic manifestation in HIV+ patients and its relationship to the CD4 cell count. METHOD AND MATERIAL: Chest radiography of 15 HIV+ patients with a definite diagnosis of pulmonary Tuberculosis in Masih Daneshvari Hospital, between 2013 and 2014, were retrospectively reviewed. Radiographic findings and severity were categorized as typical (upper lobe infiltration/cavity) and atypical (middle/lower lobe opacity, adenopathy, pleural effusion and normal X-ray). Demographics and CD4+ cell count were also recorded. Data analysis was performed using SPSS version 23 (frequency and mean for descriptive quantitative variables and Logistic regression analysis for correlation, p<0.05). RESULTS: Of a total 15 patients (86.7% men and 13.3% women), 78.6% had CD4+ counts <350 (mean±SD; 229.15±199.45). The most common radiographic findings in descending order of frequency were adenopathy (53.3%), pleural effusion (26.7%) and cavitation (6.7%) with an overall atypical presentation of 93.3%. This study failed to reveal any statistically significant correlation between CD4+ cell count and radiographic manifestation as well as severity. CONCLUSION: In CD4+ cell count <500, the dominant radiographic pattern of Tuberculosis is atypical presentation. At this level of immunity, CD4+ T cell dysfunction may play a deterministic role in TB radiographic manifestation.

Treatment of multiple drug-resistant tuberculosis (MDR-TB) in Iran.

SETTING: Masih Daneshvari Hospital, Tehran, Iran, 2000-2002. OBJECTIVE: To evaluate the effectiveness of multiple drug-resistant tuberculosis (MDR-TB) treatment for the first time in Iran. DESIGN: All cases of MDR-TB with complete follow-up data were recruited and results of their treatments were evaluated. RESULTS: MDR-TB treatment was initiated with 5.23 drugs, on average. Isoniazid, amikacin, and ofloxacin were present in the drug regimen of all patients. Average duration of the treatment was 18.5 months (range, 7-36). Over 76% of the patients responded to the treatment (negative smear and culture). Cure and probable cure were documented in seven (41.2%) and four (23.5%) of the patients, respectively. No failure in the treatment occurred when cycloserine was present in the treatment regimen. CONCLUSION: A majority of the MDR-TB patients in Iran can be cured with the use of appropriate treatment regimens. An even greater success could be achieved by providing more second-line drugs.