Rifampicin-induced renal toxicity during retreatment of patients with pulmonary tuberculosis

Rifampicin is a crucial component of treatment regimens for tuberculosis and has been in use since the early 1970’s. It is usually considered safe. Rarely life-threatening complications like acute renal failure or acute thrombocytopaenia may manifest during treatment with rifampicin. In our experience at the Tuberculosis Research Centre of treating more than 8000 pulmonary and extrapulmonary tuberculosis patients with rifampicin-containing regimens over the last 30 years, we are reporting 3 cases of probably rifampicininduced acute renal failure. Despite extreme therapeutic safety of this drug the clinician must be aware of this rare complication, which if detected early is completely reversible

Rifampicin-induced acute thrombocytopenia.

Rifampicin is an essential component of the treatment regimen for tuberculosis. Extensive clinical experience has shown that the drug is well tolerated, but on rare occasions it can cause life threatening adverse reactions like acute renal failure and thrombocytopenia. At the Tuberculosis Research Centre, we have treated more than 8000 patients with pulmonary and extra-pulmonary tuberculosis with rifampicin-containing regimens over the past 30 years and we are reporting a case of acute thrombocytopenia probably rifampicin induced, in a patient who was retreated for tuberculosis. The physician treating tuberculosis patients must be aware of this rare life threatening complication, which if detected early, is completely reversible

Contact screening and chemoprophylaxis in India’s Revised Tuberculosis Control Programme: a situational analysis

BACKGROUND: India’s Revised National Tuberculosis Control Programme (RNTCP) recommends screening of all household contacts of smear-positive pulmonary tuberculosis (PTB) cases for tuberculosis (TB) disease, and 6-month isoniazid preventive therapy (IPT) for a symptomatic children aged <6 years. OBJECTIVE: To assess the implementation of child contact screening and IPT administration under the RNTCP. METHODS: A cross-sectional study conducted in four randomly selected TB units (TUs), two in an urban (Chennai City) and two in a rural (Vellore District) area of Tamil Nadu, South India, from July to September 2008. The study involved the perusal of TB treatment cards of source cases (new or retreatment smear-positive PTB patients started on treatment), interview of source cases and focus group discussions (FGDs) among health care workers. RESULTS: Interviews of 253 PTB patients revealed that of 220 contacts aged <14 years, only 31 (14%) had been screened for TB, and that of 84 household children aged <6 years, only 16 (19%) had been initiated on IPT. The treatment cards of source cases lacked documentation of contact details. FGDs revealed greater TB awareness among urban health care workers, but a lack of detailed knowledge about procedures. CONCLUSION: Provision for documentation using a separate IPT card and focused training may help improve the implementation of contact screening and IPT. KEY WORDS: contact screening; IPT; RNTCP; chemoprophylaxi

Promoter polymorphism of IL-8 gene and IL-8 production in pulmonary tuberculosis

Interleukin-8 (IL-8) is a chemokine which functions as a potent chemo attractant for the recruitment of leucocytes to the inflammatory sites. A polymorphism in position –251 in the promoter region of the IL-8 gene has been shown to be associated with altered IL-8 production. IL-8-251A promoter polymorphism was studied in 127 pulmonary tuberculosis (PTB) patients and 124 normal healthy subjects (NHS). IL-8 gene variants were correlated with IL-8 levels from peripheral blood mononuclear cells stimulated with phytohaemagglutinin, culture filtrate antigen (CFA) of Mycobacterium tuberculosis and live M. tuberculosis. No difference was observed in the variant genotype frequencies of IL-8 gene and IL-8 levels between NHS and PTB patients. NHS positive for TT genotype showed a higher spontaneous IL-8 production than AA genotype (P = 0.05). Similarly, PTB patients with TT genotype showed significantly higher IL-8 production to CFA (P = 0.009) and live M. tuberculosis (P = 0.022), compared to patients with AA genotype. The study suggests that the variant genotypes of –251 promoter polymorphism of the IL-8 gene are not associated with susceptibility to PTB. Probably, TT genotype may be associated with higher IL-8 production and increased leucocyte accumulation and inflammation at the site of M. tuberculosis infection

Sputum conversion at the end of intensive phase of Category-1 regimen in the treatment of pulmonary tuberculosis patients with diabetes mellitus or HIV infection: An analysis of risk factors

Background & objectives: New smear-positive pulmonary tuberculosis (PTB) patients in the Revised National Tuberculosis Control Programme (RNTCP) are treated with a 6-month short-course chemotherapy (SCC) regimen irrespective of co-morbid conditions. We undertook this retrospective analysis to compare sputum conversion rates (smear, culture) at the end of intensive phase (IP) of Category-1 regimen among patients admitted to concurrent controlled clinical trials: pulmonary tuberculosis alone (PTB) or with type 2 diabetes mellitus (DM-TB) or HIV infection (HIV-TB), and to identify the risk factors influencing sputum conversion. Methods: In this retrospective analysis sputum conversion rates at the end of intensive phase (IP) in three concurrent studies undertaken among PTB, DM-TB and HIV-TB patients, during 1998 – 2002 at the Tuberculosis Research Centre (TRC), Chennai, were compared. Sputum smears were examined by fluorescent microscopy. HIV infected patients did not receive anti-retroviral treatment (ART). Patients with DM were treated with oral hypoglycaemic drugs or insulin (sc). Results: The study population included 98, 92 and 88 patients in the PTB, DM-TB and HIV-TB studies. At the end of IP the smear conversion (58, 61, and 62%) and culture conversion (86, 88 and 92%) rates were similar in the three groups respectively. The variables associated with lack of sputum smear or culture conversion were age >45 yr, higher pre-treatment smear and culture grading, and extent of the radiographic involvement. Interpretation & conclusions: Our findings confirm that the current policy of the control programme to treat all pulmonary TB patients with or with out co-morbid conditions with Category-I regimen appears to be appropriate

Assessment of long term status of sputum positive pulmonary TB patients successfully treated with short course chemotherapy

Background: Long term status of pulmonary tuberculosis (PTB) patients treated with short course chemotherapy (SCC) regimens remains unknown. Objective: To assess the clinical, bacteriological, radiological status and health related quality of life (HRQoL) of PTB patients 14 -18 years after successful treatment with SCC. Methodology: In a cross-sectional study, cured PTB patients treated during 1986 – 1990 at the Tuberculosis Research Centre (TRC) were investigated for their current health status including pulmonary function tests (PFT). The St Georges respiratory questionnaire (SGRQ) was used to assess the HRQoL Results: The mean period after treatment completion for the 363 eligible participants was 16.5yrs (range 14-18 yrs, 84% coverage) ; 25 (7 %) had been re-treated and 52 (14%) died. Among the investigated, 58 (29%) had persistent respiratory symptoms; 170(86%) had radiological sequelae but none had active disease. Abnormal PFT was observed in 96 (65%) with predominantly restrictive type of disease in 66(45%). The SGRQ scores for activity and impact were high implying impairment in HRQoL. Conclusion: Assessment of long term status of cured PTB patients showed an impairment of lung functions and HRQoL highlighting the need to address these issues in the management of TB that may provide added value to patient care

Quality indicators in a mycobacteriology laboratory supporting clinical trials for pulmonary tuberculosis

AbstractBackgroundDocumentation of structured quality indicators for mycobacteriology laboratories supporting exclusively controlled clinical trials in pulmonary tuberculosis (PTB) is lacking.ObjectiveTo document laboratory indicators for a solid (Lowenstein–Jensen medium) culture system in a mycobacteriology laboratory for a period of 4years (2007–2010).MethodsThe sputum samples, collected from PTB suspects/patients enrolled in clinical trials, were subjected to fluorescence microscopy, culture and drug sensitivity testing (DST). Data was retrospectively collected from TB laboratory registers and computed using pre-formulated Microsoft Office Excel. Laboratory indicators were calculated and analyzed.ResultsThe number of samples processed in a calendar year varied from 6261 to 10,710. Of the samples processed in a calendar year, specimen contamination (4.8–6.9%), culture positives (78.4–85.1%) among smear positives, smear positives (71.8–79.0%) among culture positive samples, smear negatives among culture negative samples (95.2–96.7%), and average time to report DST results (76–97days) varied as shown in parentheses.ConclusionValues of quality indicators in mycobacteriology laboratories supporting exclusively clinical trials of PTB have to be defined and used for meaningful monitoring of laboratories

Antigen detection as a point-of-care test for TB: the case of lipoarabinomannan

The limitations of sputum smear microscopy, routine chest radiology for HIV-associated TB and culture-based diagnosis are well recognized, especially in resource-limited settings. The diagnostic accuracy of a new point-of-care lateral-flow urine strip test for lipoarabinomannan (Determine(®) TB-LAM; Alere, MA, USA), which costs US$3.50 per test strip and provides results within 30 min, was evaluated in a cohort of South African patients for HIV-associated TB before starting anti-retroviral therapy in South Africa. Prevalence of culture-positive TB cases was 17.4%, among which 28.2% had sputum smear positivity. Determine(®) TB-LAM (Alere, MA, USA) had highest sensitivity at low CD4 cell counts: 66.7, 51.7 and 39.0% at <50 cells, <100 cells and <200 cells per µl, respectively; specificity was greater than 98% for all strata. There was an incremental sensitivity when Determine TB-LAM was combined with smear microscopy, which did not differ statistically from the sensitivities obtained by testing a single sputum sample with the Xpert(®) MTB/RIF (Cepheid; CA, USA) assay. Determine TB-LAM is a simple, low-cost alternative to existing diagnostic assays for TB screening in HIV-infected patients with very low CD4(+) cell counts

Rifampicin-induced acute thrombocytopenia

Rifampicin is an essential component of the treatment regimen for tuberculosis. Extensive clinical experience has shown that the drug is well tolerated, but on rare occasions it can cause life threatening adverse reactions like acute renal failure and thrombocytopenia. At the Tuberculosis Research Centre, we have treated more than 8000 patients with pulmonary and extra-pulmonary tuberculosis with rifampicin-containing regimens over the past 30 years and we are reporting a case of acute thrombocytopenia probably rifampicin induced, in a patient who was retreated for tuberculosis. The physician treating tuberculosis patients must be aware of this rare life threatening complication, which if detected early, is completely reversible