A rapid and low-cost microscopic observation drug susceptibility assay for detecting TB and MDR-TB among individuals infected by HIV in South India.

BACKGROUND: The converging epidemics of HIV and tuberculosis (TB) pose one of the greatest public health challenges of our time. Rapid diagnosis of TB is essential in view of its infectious nature, high burden of cases, and emergence of drug resistance. OBJECTIVE: The purpose of this present study was to evaluate the feasibility of implementing the microscopic observation drug susceptibility (MODS) assay, a novel assay for the diagnosis of TB and multi-drug-resistant tuberculosis (MDR-TB) directly from sputum specimens, in the Indian setting. MATERIALS AND METHODS: This study involved a cross-sectional, blinded assessment of the MODS assay on 1036 suspected cases of pulmonary TB in HIV-positive and HIV-negative patients against the radiometric method, BD-BACTEC TB 460 system. RESULTS: Overall, the sensitivity, specificity, positive predictive value, and negative predictive value of the MODS assay in detecting MTB among TB suspected patients were 89.1%, 99.1%, 94.2%, 95.8%, respectively. In addition, in the diagnosis of drug-resistant TB, the MODS assay was 84.2% sensitive for those specimens reporting MDR, 87% sensitivity for those specimens reporting INH mono-resistance, and 100% sensitive for specimens reporting RIF mono-resistance. The median time to detection of TB in the MODS assay versus BACTEC was 9 versus 21 days (P<0.001). CONCLUSION: Costing 5 to 10 times lesser than the automated culture methods, the MODS assay has the potential clinical utility as a simple and rapid method. It could be effectively used as an alternative method for diagnosing TB and detection of MDR-TB in a timely and affordable way in resource-limited settings.

HIV coinfection among multidrug resistant and extensively drug resistant tuberculosis patients--a trend.

Infection with human immunodeficiency virus (HIV) is found to increase the occurrence of drug resistant tuberculosis. The data for HIV and multidrug resistant tuberculosis (MDR-TB) coinfection is scarce in India. The study aims to find out the prevalence of MDR-TB and extensively drug resistant tuberculosis (XDR-TB) among chronic TB patients and to identify their trend with HIV coinfection over time. Non-responding chronic pulmonary tuberculosis patients were selected for the study from 2004 to 2007. They were all subjected to HIV screening and drug susceptibility testing (DST) for anti-TB drugs. In all 2927 chronic tuberculosis patients were assessed for DST and HIV coinfection; 2156 patients (73.7%) had culturable Mycobacterium tuberculosis in their sputum specimens; 1651 patients (56.4%) were found to have drug resistant mutants to one or more anti-TB drugs; 993 patients (33.9%) had MDR-TB and 48 (1.6%) had XDR-TB. Significantly, 17.9% of 1651 patients with drug resistance were found to have fluoroquinolone (ofloxacin) resistant strain. HIV was found to coexist with 141 (14.2%) of 993 MDR-TB patients. Three XDR-TB patients had HIV coinfection. The HIV coinfection was observed among MDR-TB patients to the tune of 12.3%, 14.7%, 17% and 12.6% during 2004, 2005, 2006 and 2007 respectively (p = 0.81). Prevalence of HIV coinfection with MDR-TB was found to be high among chronic TB patients. It would be appropriate to screen all the chronic TB patients for HIV coinfection apart from their sputa examined for drug resistant tuberculosis, especially in HIV high prevalent states. Indiscriminate use of fluoroquinolone should be stopped.

Post-HAART tuberculosis in adults and adolescents with HIV in India: incidence, clinical and immunological profile.

BACKGROUND: Highly Active Antiretroviral Therapy (HAART) was introduced in National AIDS Control Programme in 2004 to reduce the morbidity and mortality among those affected with HIV/AIDS. Tuberculosis, being an important coinfection, its emergence/occurrence in post-HAART period has potential implications. OBJECTIVE: Primary objectives were to study the incidence of post-HAART tuberculosis in HIV patients and to identify the possible risk factors. It was also intended to understand the clinical and immunological profile of this important condition. METHODOLOGY: Eligible adults and adolescents with HIV disease enrolled on HAART at Government Hospital of Thoracic Medicine, Tambaram Sanatorium, Chennai, from April, 2004 to March, 2007, formed the study population. They were monitored and screened for the occurrence of tuberculosis after commencing HAART. Clinical details and immunological profile of these patients were analysed. RESULTS: Two hundred and sixty-two patients (5.1%) of 5099 patients followed-up for one to four years were found to have Post HAART TB with 100-person year risk of 2.83. Post HAART TB occurred predominantly in men (67.6%) and in 31-44 years age group (69.8%) with 100-person year risk being 3.26 and 2.83 respectively. Pulmonary, Extra-pulmonary and disseminated tuberculosis were found to occur in the frequencies of 78%, 16% and 6% respectively. A total of 144 patients (54.9%) developed tuberculosis within six months and this number increased to 202 (77%) by 12 months. 230 patients (87.7%) had base level CD4 cell count < 200 / mm3. CONCLUSION: Tuberculosis was found to occur pre-dominantly in adult male patients with HIV during the first year after the initiation of HAART. Significantly, occurrence of Post HAART TB remained almost the same (5%) among patients treated for TB prior to the initiation of HAART.

Manifestation of tuberculosis in patients with human immunodeficiency virus: a large Indian study.

BACKGROUND: Government Hospital of Thoracic Medicine, Tambaram Sanatorium, Chennai, is the largest HIV-care center in South East Asia. As many as 29,300 HIV patients visited this center at least once in the year 2005 for care and support. OBJECTIVES: Clinical manifestations and the modes of presentation of tuberculosis were assessed among 12,750 adult and adolescent patients with human immunodeficiency virus (HIV) attending the hospital for the first time. MATERIALS AND METHODS: Database of Hospital Information System, specially evolved for managing patients afflicted with tuberculosis and HIV, was utilized. The particulars confined to patients with tuberculosis and HIV co-infection who visited the hospital for the first time from January to December 2005 were considered for the analysis. Proportion test and Chi-square test with Yates correction were done. RESULTS: As many as 12,750 adult and adolescent HIV-confirmed patients were screened for the possible presence of tuberculosis. Out of them, 4,383 (34.4%) patients had tuberculosis. Among them, 2,448 (55.9%) had pulmonary tuberculosis, and the remaining 1,935 (44.1%) had either disseminated or extra-pulmonary tuberculosis (P<0.001). Positive sputum-smear microscopy for acid fast bacilli was evident in 1,363 (31.1%) patients; however, it was significantly lower compared to positive smear rate of 44% in HIV patients (P< 0.001). CONCLUSION: Tuberculosis was found to be the predominant co-infection among the symptomatic patients infected with HIV attending the largest care center for the first time in India. Advanced tuberculosis, disseminated tuberculosis and sputum smear negative pulmonary tuberculosis were the presenting clinical manifestations in 44% of the patients, as they had moderate to advanced immunosuppression. Early detection of tuberculosis co-infection is absolutely necessary.

Decreased bioavailability of rifampin and other antituberculosis drugs in patients with advanced human immunodeficiency virus disease.

We evaluated the effects of human immunodeficiency virus (HIV) disease on pharmacokinetics of antituberculosis medications by measuring concentrations of isoniazid and rifampin in blood and of pyrazinamide and ethambutol in urine. Peak concentration and exposure were reduced for rifampin, and rapid acetylators of isoniazid had lower drug levels. HIV and HIV-tuberculosis patients who have diarrhea and cryptosporidial infection exhibit decreased bioavailability of antituberculosis drugs.

Prevalence of acquired MDR-TB and HIV co-infection.

BACKGROUND: Mounting prevalence of primary and acquired multidrug-resistant tuberculosis in India is a sorry reminder of all round failure in our fight against tuberculosis and also of the necessity for new effective strategies. OBJECTIVES: (1) To assess the prevalence and pattern of drug resistant pulmonary tuberculosis among treated patients or on those on treatment without adequate response and (2) to evaluate HIV seropositivity among MDR-TB patients. METHODS: Pulmonary TB patients, who had at least six months of unsuccessful anti-tuberculous treatment were selected for the study. Their sputum specimens were examined for M. tuberculosis culture and drug sensitivity pattern and serological examinations for HIV infection were carried out. RESULTS: Sputum specimens of 618 patients' (61.8%) of a total of 1000 examined had shown culturable M. tuberculosis. Four hundred ninty-five patients (49.5%) were found to expectorate tubercle bacilli resistant to one or more anti TB drugs. MDR-TB was detected in 339 patients (33.9%). HIV seropositivity among MDR-TB was 4.42%. Significantly, 245 patients (24.5%) had tubercle bacilli resistant to one or more reserve drugs too (ethionamide, kanamycin and/or ofloxacin). CONCLUSIONS: Prevalence of MDR-TB was high in the study population. It is essentially an acquired condition. Its association with HIV disease was at present on the lower side, an observation contrary to published western literature. Higher rates of resistance for reserve drugs (ethionamide, kanamycin and/or ofloxacin) in patients who never had these drugs in their earlier treatment schedules suggest the possibility of emerging spontaneous drug resistant mutants.

Angiographic correlates of anterior ST segment depression in acute inferior wall myocardial infarction.

This study was conducted prospectively to assess the correlation between the pattern of anterior ST segment depression on the admission electrocardiogram and the in-hospital morbidity and mortality in patients with acute inferior wall myocardial infarction. Coronary angiography was also done to assess its correlation, if any, with pattern of anterior ST segment depression. Our study cohort comprised of 165 consecutive patients with acute inferior wall myocardial infarction divided into four groups based on admission electrocardiogram. Group I (n = 33): patients with no anterior ST segment depression; group II (n = 16): patients with ST segment depression in leads V1-V3; group III (n = 71): patients with ST segment depression in leads V4-V6, I and aVF, and; group IV (n = 45): patients with ST segment depression in all anterior leads (V1-V6, I, aVL). The outcomes were analysed in terms of high grade atrioventricular block, Killip class II or higher failure, and in-hospital mortality. Coronary angiography was performed to analyse coronary anatomy. Group IV patients had increased incidence of complete heart block (37.8% vs 15.2% in the total group) (p < 0.001) and increased mortality (11.1% vs 4.2% in the total group) (p < 0.05). This group also had greater incidence of triple vessel disease (76.7%) (p < 0.001). Group II patients had greater incidence of double vessel disease (88.9%) (p < 0.05) and had no triple vessel disease. Group III patients had double vessel disease (76.5%) (p < 0.05) or triple vessel disease (23.5%) (p = NS) and no single vessel disease. Coronary angiography in group II showed greater incidence of involvement of left circumflex artery and right coronary artery while in group III there was left anterior descending artery and right coronary artery disease. We conclude that patients with anterior ST segment depression in group III and group IV categories are in high risk subset with acute inferior wall myocardial infarction.