Pediatric Tuberculosis: Global Overview and ChallengesSoumya

Tuberculosis (TB) is among the top 10 causes of death among children worldwide; however, children with TB are given low priority in most national health programs and are neglected in this epidemic. Recent technological advancements in diagnosis of TB in adults have not been validated in children. Similarly, trials of new drugs and development of pediatric formulations of standard first- and second-line drugs are lagging behind. Among human immunodeficiency virus (HIV)-coinfected children, the optimal timing for highly active antiretroviral therapy initiation and drug combinations that have minimal interactions with anti-TB drugs need further study. Although bacille Calmette-Guérin vaccine, the only vaccine available for TB, protects against disseminated and severe forms of the disease in young children, its safety in the HIV-infected population has been questioned. Multicentric trials are urgently required to help develop improved diagnostic strategies and formulate shorter, more effective, safe, and evidence-based regimens for treatment and prevention of drugsusceptible and drug-resistant TB

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

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

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

Profile and response to anti-tuberculosis treatment among elderly tuberculosis patients treated under the TB control programme in South India

Introduction: The demographic transition in India has resulted in an increase in the elderly population. There is limited data on the profile of elderly tuberculosis (TB) patients and their treatment outcomes in India. Objective: To compare the clinical profile, presentation and response to anti-TB treatment among elderly (&#8805;60 yrs) and younger (15–59 yrs) TB patients treated under the Revised National TB Control programme. Methodology: Retrospective cohort analysis of TB patients treated from May 1999 to December 2004 in one Tuberculosis Unit of Tiruvallur district, South India. Results: Records of 865 elderly and 4343 younger TB patients were examined: elderly were more likely to be male (84% vs. 71%), smokers (46% vs.37%), illiterate (63% vs. 45%), identified by active case finding through survey (19% vs. 11%), have pulmonary TB (96% vs. 91%) and initial smear negative disease (46% vs. 36%) compared to younger (for all p&#60;0.001). Among a total of 352 elderly and 1933 younger new smear positive pulmonary TB, the elderly had higher loss to follow-up (15% vs. 11%; p = 0.03) and death rates (9% vs. 4%; p&#60;0.001). Mycobacterium tuberculosis susceptibility to first line anti-TB drugs did not differ (elderly 87% vs. younger 84%) (p = 0.20). Side effects related to anti-TB drugs were reported by a higher proportion of elderly patients (63% vs. 54%) (p = 0.005). Previously treated patients had similar treatment outcomes in both the groups. Conclusion: Elderly TB patients are less likely to have smear positive disease. Newly diagnosed elderly TB patients are more likely to be lost to follow-up or die and report drug side effects. Suitable interventions need to be developed for effective management and better treatment outcomes of TB in the elderly

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

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

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