Aleyamma Thomas

Role of QuantiFERON-TB Gold, Interferon Gamma Inducible Protein-10 and Tuberculin Skin Test in Active Tuberculosis Diagnosis

Background The measurement of Interferon gamma or Interferon gamma inducible protein (IP)-10 in antigen stimulated blood samples is suggested as an alternative method for latent tuberculosis (TB) diagnosis. Nonetheless, their role in active TB diagnosis, particularly in TB endemic settings is yet to be defined. In this study, the sensitivities and specificities of Interferon gamma release assay (IGRA), IP-10 assay and tuberculin skin test (TST) in detecting active TB cases were assessed in human immunodeficiency virus (HIV) sero-negative TB patients and healthy controls respectively. Methods/Principal Findings A total of 177 adult TB patients and 100 healthy controls were included for this study. QuantiFERON-TB Gold In-tube (QFT-IT) method was used to analyze the sensitivity and specificity of IGRA. QFT-IT, IP-10 and TST yielded the diagnostic sensitivities of 90.6% (95%CI: 86.3%–94.9%), 92.5% (95%CI: 88.6%–96.4%) and 68.9% (95%CI: 60.6%–77.2%) and specificities of 55% (95% CI: 35.2%–54.8%), 48% (95% CI: 38.2%–57.8%) and 75.5% (95% CI: 66.8%–84.2%), respectively. The extent of pulmonary involvement or presence of diabetes mellitus did not appear to influence the sensitivities of any of these tests. The combination of any of the two tests among QFT-IT, IP-10 and TST showed >98% sensitivity among smear negative cases and particularly the combination of IP-10, TST and smear microscopy showed 100% sensitivity, however, the specificity was decreased to 44.8%. Conclusions/Significance QFT-IT and IP-10 were highly sensitive in detecting active TB cases. The combination with TST improved the sensitivity of QFT-IT and IP-10 significantly. Although the higher sensitivity of combination of QFT-IT/IP-10 and TST may be useful in active TB diagnosis, they are limited by their poor specificity due to the high prevalence of latent TB in our settings.

Feasibility of Provider-Initiated HIV Testing and Counselling of Tuberculosis Patients Under the TB Control Programme in Two Districts of South India

Background Provider-initiated HIV testing and counselling (PITC) is internationally recommended for tuberculosis (TB) patients, but the feasibility, effectiveness, and impact of this policy on the TB programme in India are unknown. We evaluated PITC of TB patients across two districts in India considered to have generalized HIV epidemics, Tiruchirappalli (population 2.5 million) and Mysore (population 2.8 million). Methodology/Principal Findings Starting June 2007, healthcare providers in both districts were instructed to ascertain HIV status for all TB patients, and refer those with unknown HIV status to the nearest Integrated Counselling and Testing Centre (ICTC)—often in the same facility—for counselling and voluntary HIV testing. All TB patients registered from June 2007 to March 2008 were followed prospectively. Field investigators assessed PITC practices and abstracted data from routine TB programme records and HIV counselling registers to determine the proportion of TB patients appropriately evaluated for HIV infection. Patient records were traced to determine the efficiency of referral links to HIV care and antiretroviral treatment (ART). Between July 2007 and March 2008, 5299 TB patients were registered in both study districts. Of the 4701 with unknown HIV status at the time of TB treatment initiation, 3368 (72%) were referred to an ICTC, and 3111 (66%) were newly tested for HIV. PITC implementation resulted in the ascertainment of HIV status for 3709/5299 (70%) of TB patients, and detected 200 cases with previously undiagnosed HIV infection. Overall, 468 (8.8%) of all registered TB patients were HIV-infected; 177 (37%) were documented to have also received any ART. Conclusions With implementation of PITC in India, HIV status was successfully ascertained for 70% of TB patients. Previously undiagnosed HIV-infection was detected in 6.4% of those TB patients newly tested, enabling referral for life-saving anti-retroviral treatment. ART uptake, however, was poor, suggesting that PITC implementation should include measures to strengthen and support ART referral, evaluation, and initiation.

Perceptions of Tuberculosis Patients on Provider-Initiated HIV Testing and Counseling - A Study from South India

Background The acceptability and feasibility of provider-initiated HIV testing and counseling (PITC) in many settings across Asia with concentrated HIV epidemics is not known. A pilot study of the PITC policy undertaken within the public health care systems in two districts in India offered the opportunity to understand patients perspectives on the process of referral for HIV testing and linking to HIV treatment and care. Methods We conducted a cross-sectional study of randomly selected TB patients registered by the TB control program between July and November 2007 in two districts in south India. Trained interviewers met patients shortly after TB diagnosis and administered a structured questionnaire. Patients were assessed regarding their experience with HIV status assessment, referral for counseling and testing, and for HIV-infected patients the counseling itself and subsequent referral for HIV treatment and care. Results Of the 568 interviewed TB patients, 455 (80%) reported being referred for HIV testing after they presented to the health facility for investigations or treatment for TB. Over half the respondents reported having to travel long distances and incurred financial difficulties in reaching the Integrated Counselling and Testing Centre (ICTC) and two-thirds had to make more than two visits. Only 48% reported having been counseled before the test. Of the 110 HIV-infected patients interviewed, (including 43 with previously-known positive HIV status and 67 detected by PITC), 89 (81%) reported being referred for anti-retroviral treatment (ART); 82 patients reached the ART centre but only 44 had been initiated on ART. Conclusions This study provides the first evidence from India that routine, provider-initiated voluntary HIV testing of TB patients is acceptable, feasible and can be achieved with very high efficiency under programmatic conditions. While PITC is useful in identifying new HIV-infected patients so that they can be successfully linked to ART, the convenience and proximity of testing centres, quality of HIV counseling, and efficiency of ART services need attention.

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 (≥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<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<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.

High Rates of Ofloxacin Resistance in Mycobacterium tuberculosis among Both New and Previously Treated Patients in Tamil Nadu, South India

Periodic drug resistance surveillance provides useful information on trends of drug resistance and effectiveness of tuberculosis (TB) control measures. The present study determines the prevalence of drug resistance among new sputum smear positive (NSP) and previously treated (PT) pulmonary TB patients, diagnosed at public sector designated microscopy centers (DMCs) in the state of Tamil Nadu, India. In this single-stage cluster-sampling prevalence survey, 70 of 700 DMCs were randomly selected using a probability-proportional to size method. A cluster size of 24 for NSP and a varying size of 0 to 99 for PT cases were fixed for each selected DMC. Culture and drug susceptibility testing was done on Lowenstein-Jensen medium using the economic variant of proportion sensitivity test for isoniazid (INH), rifampicin (RMP), ofloxacin (OFX) and kanamycin (KAN). Human Immunodeficiency Virus (HIV) status was collected from patient records. From June 2011 to August 2012, 1524 NSP and 901 PT patients were enrolled. Any RMP resistance and any INH resistance were observed in 2.6% and 15.1%, and in 10.4% and 30% respectively in NSP and PT cases. Among PT patients, multi drug resistant TB (MDR-TB) was highest in the treatment failure (35%) group, followed by relapse (13%) and treatment after default (10%) groups. Extensively drug resistant TB (XDRTB) was seen in 4.3% of MDR-TB cases. Any OFX resistance was seen in 10.4% of NSP, 13.9% of PT and 29% of PT MDR-TB patients. The HIV status of the patient had no impact on drug resistance levels. RMP resistance was present in 2.6% of new and 15.1% of previously treated patients in Tamil Nadu. Rates of OFX resistance were high among NSP and PT patients, especially among those with MDR-TB, a matter of concern for development of new treatment regimens for TB.

Evaluation of a diagnostic algorithm for sputum smear-negative pulmonary tuberculosis in HIV-infected adults.

Background:The Revised National TB Control Program bases diagnosis of tuberculosis (TB) on sputum smear examination and response to a course of antibiotics, whereas World Health Organization recommends early chest radiography [chest x-ray (CXR)] for HIV-infected symptomatic patients. We evaluated the utility of initial CXR in the diagnostic algorithm for symptomatic HIV-infected patients with negative sputum smears. Methods:HIV-infected ambulatory patients with cough or fever of ≥2 weeks and 3 sputum smears negative for acid-fast bacilli were enrolled in Chennai and Pune, India, between 2007 and 2009. After a CXR and 2 sputum cultures, a course of broad-spectrum antibiotics was given and patients were reviewed after 14 days. Sensitivity, specificity, positive and negative predictive values of symptoms, CXR, and various combinations for diagnosing pulmonary tuberculosis (PTB) were determined, using sputum culture as gold standard. Results:Five hundred four patients (330 males; mean age: 35 years; median CD4: 175 cells per cubic millimeter) were enrolled. CXR had a sensitivity and specificity of 72% and 57%, respectively, with positive predictive value (PPV) of 21% and negative predictive value (NPV) of 93% to diagnose PTB. TB culture was positive in 49 of 235 patients (21%) with an abnormal initial CXR and 19 of 269 patients (7%) with a normal CXR (P < 0.001). Sensitivity and specificity of cough ≥2 weeks for predicting PTB was 97% and 6%, with PPV and NPV of 14% and 94%, respectively. Conclusions:Although moderately sensitive, basing a diagnosis of TB on initial CXR leads to overdiagnosis. An absence of weight loss had a high NPV, whereas none of the combinations had a good PPV. A rapid and accurate diagnostic test is required for HIV-infected chest symptomatic.

Estimation of content of anti-TB drugs supplied at centres of the Revised National TB Control Programme in Tamil Nadu, India.

To determine the content of certain antituberculosis (TB) drugs supplied at TB treatment centres of the Revised National TB Control Programme (RNTCP) in the state of Tamil Nadu, India.