Trends in the prevalence of Pulmonary Tuberculosis over a period of seven and half years in a rural community in south India with DOTS.

Setting: Tiruvallur district In Tamil Nadu where DOTS was implemented by the State Government as the tuberculosis control measure in 1999, and monitored by the National Institute for Research in Tuberculosis for over five years. Objective: To estimate trends in TB prevalence in a rural community with DOTS. Design: Surveys of pulmonary tuberculosis were undertaken in representative samples of subjects aged >15 years (N = 83,000 – 92,000), initially and after two and half, five and seven and half years of implementation of DOTS. Sputa were collected from those with abnormal radiograph and/or presence of chest symptoms, and examined by direct smear and culture. Results: The prevalence of culture-positive tuberculosis was 607, 454, 309 and 388 per 100,000 in the four surveys, and that of smear-positive tuberculosis was 326, 259, 168 and 180. In the first five years; annual decrease was 12.4% (95% CI 10.4 - 14.4%) for culture-positive tuberculosis, and 12.2% (95% CI 8.0–16.2) for smear-positive tuberculosis. This was, however, followed by a significant increase in the next two and half years. The average new smear-positive case-notification rate was 75 per 100,000 during first four years but declined to 49 in subsequent years. There were no methodological differences during this period and information on changes in socio-economic indicators and nutritional standards was unavailable. Conclusion: Despite the average annual success rate (78%) in this tuberculosis unit being lower than the expected rate of 85%, the implementation of DOTS was followed by a substantial decrease in the prevalence of pulmonary tuberculosis over the seven and half year period. Our findings suggest that sustaining the high effectiveness of DOTS programme needs vigilant supervision.

Knowledge and behaviour of chest symptomatics in urban slum populations of two states in India towards care-seeking.

Background: Little information is available on triggers and barriers for seeking appropriate healthcare among chest symptomatics (CS) from slum populations in India. Methods: Urban slums in Uttar Pradesh (UP) and Karnataka (KA) were selected based on case detection rate (2008), population size and geographic distribution. A door-to-door survey was conducted in 2010 and CS were identified and interviewed. Action taking patterns were collected and factors influencing these among behavers (CS visiting qualified providers) and non-behavers (CS not taking action or resorting to self-medication) compared. Results: Of 1526 CS in UP and 1515 in KA interviewed, 75% in UP and 58% in KA sought care; of them 79% in UP and 99% in KA visited a qualified provider. More than 80% in both UP and KA underwent recommended tests within a week (mean days: UP-1.8; KA-2.4). Only 16% of respondents in UP and 48% in KA reported that private qualified providers recommended sputum microscopy. Important triggers of visiting a qualified provider were being females; of higher economic status, self-efficacy, suspicion of having TB when suffering from persistent cough and that sputum microscopy should be done to diagnose TB. Additional triggers included knowledge that TB is caused by germs and can affect anyone (UP) and perceptions of quality of care and knowledge that TB is curable (KA). Implications: There is need to carry out targeted area-specific communication in slums to improve appropriate treatmentseeking behaviour and demand creation for DOTS by CS. The study recommends investments to focus on changing private provider behaviour.

DOTS Reacdes Socially Marginalized Population in the Community a Study from a Rural Area of South India.

We report here that the Directly Observed Treatment, Short course (DOTS) is reaching all tuberculosis patients in the community irrespective of social classification based on the analysis from the tuberculosis prevalence survey and programme performance during 1999-2003 from a rural area in Tamilnadu, South India. New smear- positive cases treated under a DOTS programme were classified in two groups namely; scheduled caste living in colony and other population. The prevalence of smear- positive cases among the scheduled caste population was 1.9 times higher than the other population and this was reflected in the notification also. The successful treatment outcome was also similar in these two groups (75% and 78% respectively; overall 77%). From these findings it is concluded that people living in colony have equal access to DOTS as those in the village.

DOTS reaches socially marginalized population in the community: a study from a rural area of South India.

We report here that the Directly Observed Treatment, Short course (DOTS) is reaching all tuberculosis patients in the community irrespective of social classification based on the analysis from the tuberculosis prevalence survey and programme performance during 1999-2003 from a rural area in Tamilnadu, South India. New smear- positive cases treated under a DOTS programme were classified in two groups namely; scheduled caste living in colony and other population. The prevalence of smear- positive cases among the scheduled caste population was 1.9 times higher than the other population and this was reflected in the notification also. The successful treatment outcome was also similar in these two groups (75% and 78% respectively; overall 77%). From these findings it is concluded that people living in colony have equal access to DOTS as those in the village.

Impact of improved treatment success on the prevalence of TB in a rural community based on active surveillance.

OBJECTIVE: To study the impact of improved treatment outcome of a cohort of patients treated under DOTS strategy on the prevalence of pulmonary tuberculosis (TB) in the community. DESIGN: The data from TB register of one Tuberculosis Unit (TU) in Tiruvallur district of Tamilnadu, and two TB disease surveys conducted in the same area during 1999-2003 were analysed. The successful treatment outcome was compared to the prevalence of TB in the subsequent cohort. RESULTS: The proportion of patients who completed treatment successfully was 75.3% in the first cohort period. This higher proportion of treatment success among patients treated under DOTS in the first cohort period (1999-2001) compared to the 51-55% reported during SCC, resulted in a lower prevalence of smear-positive cases, irrespective of culture results observed in the survey conducted during 2001-2003 compared to that in the survey conducted during 1999-2001 (252 vs. 323 per 100,000; annual decline of 9%). Similarly, a decline in culture-positive cases, irrespective of smear results, was also observed (443 vs. 605; annual decline 11%). CONCLUSION: The higher proportion of successful completion of treatment after DOTS implementation was associated with a substantial decline in the prevalence of TB. These findings showed that we are in the direction towards achieving the Millennium Development Goals (MDGs).

Status of smear-positive TB patients at 2-3 years after initiation of treatment under a DOTS programme.

OBJECTIVE: To describe the status of cases 2-3 years after the initiation of treatment under DOTS. SETTING: After DOTS implementation in Tiruvallur district, south India, we followed up a cohort of smear-positive TB patients registered during 2002-03 after initiation of treatment. RESULTS: The overall mortality rate was 15.0% and among the remaining 18.6% had active disease. In multivariate analysis, a higher mortality rate was independently associated with age, sex, occupation, treatment outcome and initial body weight of patients. CONCLUSION: The mortality and morbidity rates are still high during follow-up and needs to be curtailed by addressing these issues effectively in TB control programme.

Reasons for non-compliance among patients treated under Revised National Tuberculosis Control Programme (RNTCP), Tiruvallur district, south India.

OBJECTIVES: To elicit reasons for treatment default from a cohort of TB patients under RNTCP and their DOT providers. METHODS: A total of 186 defaulters among the 938 patients registered during 3rd and 4th quarters of 1999 and 2001 in one Tuberculosis Unit (TU) of Tiruvallur district, Tamil Nadu and their DOT providers were included in the study. They were interviewed using a semi-structured interview schedule. RESULTS: Sixteen (9%) had completed treatment, 25 (13%) died after defaulting, and 4 (2%) could not be traced. Main reasons given by the remaining 141 patients and their DOT providers were: drug related problems (42%, 34%), migration (29%, 31%), relief from symptoms (20%, 16%), work related (15%, 10%), alcohol consumption (15%, 21%), treatment from other centers (13%, 4%), respectively. Risk factors for default were alcoholism (P<0.001), category of treatment (P<0.001), smear status (P<0.001), type of disease (P<0.001) and inconvenience for DOT (P<0.01). CONCLUSION: This study has identified group of patients vulnerable to default such as males, alcoholics, smear positive cases, and DOT being inconvenient. Intensifying motivation and counselling of this group of cases are likely to improve patient compliance and reduce default.

Management of multi drug resistance tuberculosis in the field: Tuberculosis Research Centre experience.

SETTING: Multi-drug TB resistant (resistant to isoniazid and rifampicin) patients identified from a rural and urban area. OBJECTIVE: To study the feasibility of managing MDR TB patients under field conditions where DOTS programme has been implemented. METHODS: MDR TB Patients identified among patients treated under DOTS in the rural area and from cases referred by the NGO when MDR TB was suspected form the study population. Culture and drug susceptibility testing were done at Tuberculosis Research Centre (TRC). Treatment regimen was decided on individual basis. After a period of initial hospitalization, treatment was continued in the respective peripheral health facility or with the NGO after identifying a DOT provider in the field. Patients attended TRC at monthly intervals for clinical, sociological and bacteriological evaluations. Drugs for the month were pre-packed and handed over to the respective center. RESULTS: A total of 66 MDR TB patients (46 from the rural and 20 from the NGO) started on treatment form the study population and among them 20 (30%) were resistant to one or more second line drugs (Eto, Ofx, Km) including a case of "XDR TB". Less than half the patients stayed in the hospital for more than 10 days. The treatment was provided partially under supervision. Providing injection was identified to be a major problem. Response to treatment could be correctly predicted based on the 6-month smear results in 40 of 42 regular patients. Successful treatment outcome was observed only in 37% of cases with a high default of 24%. Adverse reactions necessitating modification of treatment was required only for three patients. IMPLICATIONS: Despite having reliable DST and drug logistics, the main challenge was to maintain patients on such prolonged treatment by identifying a provider closer to the patient who can also give injection, have social skills and manage of minor adverse reactions.

Status of re-registered patients for tuberculosis treatment under DOTS programme.

OBJECTIVE: To assess the proportion of patients re-registered after default, failure or successful treatment, completion and evaluate their treatment outcome. Setting: Tuberculosis patients diagnosed were registered for treatment under DOTS in rural area, South India. Patients reregistered during 1999-2004 identified from the TB register were considered for analysis. RESULTS: Among 273 Category-I patients 'defaulted' 23% and among 112 'failure' cases 68% were re-registered. After 'successful treatment completion' of 1796 cases 6.5% were re-registered as relapse. Corresponding figures for Category II were 20% of 281 defaulters; 23% of 60 failures; 12.9% of 302 'successful treatment completion' patients. Among patients re-registered as 'default', subsequent default was also high (57% vs 37%). Failure in Category II treatment was similar among patients who were re-registered for Category II and initially registered in it for treatment. Median delay for reregistration was >200 days for 'defaulters' and 18 days for 'failures'. CONCLUSION: Our findings emphasise the need for continuing motivation and prompt defaulter retrieval action to reduce default at all stages of treatment. 'Defaulters' need to be contacted so that they can be started on treatment without delay. Patients declared as 'successful treatment completion' should be encouraged to report if chest symptoms recur.

Influence of drug susceptibility on treatment outcome and susceptibility profile of failures to category II regimen.

Objective: To assess the influence of drug resistance on treatment outcome among patients treated with Category-II regimen and document drug susceptibility pattern of “Failures” to this regimen. Design: A retrospective analysis of patients registered from May 1999 through December 2004. Results: Treatment success was 42% among 572 patients and was similar among patients with fully susceptible or resistant but non-MDR organisms (41% of 254 and 40% of 128 patients, respectively). Among 49 MDR-TB patients, 27% had successful treatment outcome. The failure rates among patients with fully susceptible, resistant but non-MDR and MDR bacilli, were 6%, 12% and 27% respectively. Default was significantly higher among males (53% vs. 34%: p<0.01) smokers (57% vs. 36%: p <0.001), alcoholics (58% vs. 39%: p <0.001) and patients with higher initial smear grading (2+ or 3+, 56% vs. scanty or 1+, 44%: p <0.01). DST results were available for 60% (31 of 52) of failures and 10 had MDR-TB. Conclusion: The low success rate to the re-treatment regimen was mainly due to non-compliance. Failure was observed among 9% of patients and MDR-TB was 32% among Category II failures. The currently recommended Category II regimen appears to be adequate for majority of re-treatment cases.

Performance of a DOTS programme: Administrative and Technical Challenges - A field report from a district in south India.

Background: Performance of tuberculosis (TB) control programme depends on the functioning of health facilities (HFs). TB control programmes have been evaluated based on the programme indicators of conversion and cure. We have attempted to correlate the programme performance based on the availability of staff and their performance at the HF level. Objective: To correlate the performance of HFs to programme indicators, conversion and cure of patients treated under DOTS, in a district of south India. Design: Analysis of the data on new sputum smear-positive cases registered in 17 HFs during 1999-2003 was undertaken using TB register. The HFs with a low conversion or cure rates were identified and the reasons for the same were analysed. A scoring system was designed for the functioning of the HFs based on staff availability, supervision and review meetings which was correlated with programme performance. Univariate and multivariate analyses were performed. Results: Of 1893 new smear-positive patients registered during the study period, conversion was 1582 (83.6%) with cure rate of 76.4% (1447 of 1893), 254 (13.4%) default, 94 (5.0%) failure and 85 (4.5%) death. The conversion rates increased from 76% in 1999 to 87% in 2003; a statistically significant trend (c2 = 15.9; P<0.001). Similarly, a significant increase in trend (c2 = 4.0; P < 0.05) was observed in cure rates also (71 to 80%). The HFs were broadly classified into four groups namely; poor, fair, good and very good based on functioning scores .Correlation co-efficient was 0.77 between functioning of the HFs and conversion, and 0.76 between functioning and cure (P<0.01). Lack of regular review meetings was found to be independently associated with poor programme performance. Conclusion: Availability of staff such as Medical Officer, Laboratory Technician, and regular supervisory visits and review meetings are essential for a well functioning of programme. There is significant impact on DOTS with good functioning of HFs.

Association of conversion & cure with initial smear grading among new smear positive pulmonary tuberculosis patients treated with Category I regimen.

BACKGROUND & OBJECTIVES: Early diagnosis of tuberculosis (TB) is important for initiating treatment to gain cure. The present investigation was undertaken to study the association of conversion and cure with initial smear grading among pulmonary tuberculosis (TB) patients registered in a directly observed treatment - short course (DOTS) programme in Tiruvallur district, south India. METHODS: All new smear positive cases registered from May, 1999 to December, 2002 were analysed for conversion and cure related to initial smear grading. RESULTS: Of the 1463 patients, 1206(82.4%) were converted at the end of the intensive phase and 1109 (75.8%) were declared 'cured' after the completion of treatment. The cure rate decreased as the initial smear grading increased and the decrease in trend was statistically significant (P=0.01). Similarly, a significant decrease in conversion rate was also observed with increase in initial smear grading (P<0.001). In multivariate analysis, lower cure rate was significantly associated with patient's age (AOR=1.5, 95% CI=1.1-2.1), alcoholism (AOR=1.7, 95% CI 1.2- 2.4) and conversion at the end of intensive phase (AOR=3.5, 95% CI= 2.6-4.8). INTERPRETATION & CONCLUSION: Cure and conversion rates were linearly associated with initial smear grading. High default and death rates were responsible for low cure and conversion. The proportion of patients who required extension of treatment and those who had an unfavourable treatment outcome were significantly higher among patients with a 3+ initial smear grading. This reiterates the need to pay more attention in motivating these patients to return to regular treatment and sustained commitment in the control of tuberculosis. There is a need to extend the treatment for one more month in the intensive phase of treatment.

Sputum examination at 2-months into continuation phase - How much does it contribute to define treatment outcome.

Objective: To assess the usefulness of sputum examination at 2-months into Continuation Phase (CP) to declare treatment outcome. Methodology: It is a retrospective study conducted in one tuberculosis unit, Tiruvallur district of Tamilnadu among smear positive patients treated with Category I and Category II regimens from May, 1999 – December, 2003. Results: Sputum was collected at 2-months into CP from 70% of 1551 Category I and 74% of 292 Category II patients declared cure, failed or treatment completed. Result at 2-months CP was used for giving outcome in 112 (10.3%) of 1088 Category I patients and 37 (17%) of 217 Category II patients. Conclusion: In practice, sputum needs to be collected for 7.8% of the patients with smear positive at the end of Intensive Phase. By doing so, there will be a delay of 1 month for 3.6% of the patients in declaring ‘failure’. By deferring the sputum examination at 2 months into CP, workload of laboratory technicians can be reduced by about 30%.

Is migration a factor leading to default under RNTCP.

Objective: To study the contribution of migration to treatment default among tuberculosis patients treated under RNTCP Methods: Retrospective study by interviewing the defaulters using semi-structured interview schedule to elicit the reasons for default including migration. Results: Of the 531 patients registered under TB programme in 3rd and 4th quarters of 2001, 104 (20%) had defaulted for treatment. Among defaulters, 24% had migrated. The reasons for migration were: occupational (48%), returning to the native place (28%), domestic problems (12%) and other illnesses (12%). Conclusion: After initiation of treatment, patients should be encouraged to report to the provider, if they are leaving the area, to transfer treatment to the nearest centre to ensure continuity of treatment. These measures will help to reduce default on account of migration and achieve the desired outcome in RNTCP. Availability of treatment under the DOTS strategy should be popularized among patients, providers and community.

Course of action taken by smear negative chestsymptomatics a report from a rural area in south India.

Objective: To evaluate adherence to diagnostic algorithm of Revised National Tuberculosis Control Programme (RNTCP) and course of action taken by smear-negative chest symptomatics (CSs). Method: Interviewing smear-negative chest symptomatics. Results: Of the 423 smear-negative CSs interviewed, 85 (20%) were not prescribed antibiotics and only 133 (39%) received it for more than seven days. Of the 148 patients with persistence of symptoms, 83 (56%) returned for further investigations and only 39% were X-rayed. Main reasons for not returning were: ‘not aware’ or ‘consulted another health provider.’ Conclusion: Strict adherence to diagnostic algorithm and proper counselling of patients are important for diagnosing smear-negative pulmonary tuberculosis (PTB) cases.

Is it worth treating Category I failure patients with Category II regimen.

Background: Very little information is available on the drug susceptibility profile among patients who are treated with standardized short-course chemotherapy regimens under programme conditions. Methods: Sputum samples were collected from new sputum smear-positive patients declared ‘failure’ after treatment with Category I regimen under tuberculosis control programme using DOTS strategy from a rural area of Tamil Nadu. Results: Of 1463 patients started on Category I regimen between May1999 and December 2002, 74 cases were declared as ‘failures’ (smear positive at 5/6 months of treatment). We collected sputum samples from 60 (81%) of 74 ‘failures’ and 27% (16 of 60) of them were culture-negative for M tuberculosis and 17% (10 of 60) had organisms resistant to Isoniazid and Rifampicin (MDR TB). Conclusion: Based on the drug susceptibility profile at the time of ‘failure’, treating Category I ‘failures’ with Category II regimen with close monitoring appears to be justified.

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 rifampicin-induced 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.

Estimation of burden of tuberculosis in India for the year 2000.

BACKGROUND AND OBJECTIVE: Data on the burden of tuberculosis (TB) in India are vital for programme planners to plan the resource requirements and for monitoring the nation-wide TB control programme. There was a need to revise the earlier estimate on the burden of TB in India based on the increase in population and current epidemiological data. This study estimates the burden of disease for the year 2000 based on recent prevalence of TB and annual risk of tuberculosis infection (ARTI) estimates. METHODS: Data on prevalence generated among adults by the Tuberculosis Research Centre (TRC), Chennai, among children by National Tuberculosis Institute (NTI), Bangalore, and the ARTI estimates from the nation-wide sample survey by NTI and TRC were used for the estimation. The prevalence of disease corresponding to 1 per cent ARTI was extrapolated to different parts of the country using the estimates of ARTI and the population in those areas and added together to get the total cases. Abacillary cases that required treatment were estimated from X-ray abnormals. The estimates of bacillary, abacillary and extrapulmonary cases were then combined to get the national burden. RESULTS: The estimated number of bacillary cases was 3.8 million (95% CI: 2.8-4.7). The number of abacillary cases was estimated to be 3.9 million and that for extrapulmonary cases was 0.8 million giving a total burden of 8.5 million (95% CI: 6.3-10.4) for 2000. INTERPRETATION AND CONCLUSION: The present estimate differs from the earlier estimates because we have included the disease burden of X-ray cases that are likely to breakdown to bacillary cases in a one year period, and extrapulmonary TB cases. The current estimates provided baseline information for advocacy and planning resource allocation for TB control activities. Also, these estimates can be compared with that in future years to measure the long term impact of TB control activities in India.

Evaluation of Directly Observed Treatment Providers in the Revised National Tuberculosis Control Programme.

Background: Non-governmental personnel such as Anganwadi workers and community volunteers have been used as directly observed treatment (DOT) providers in the Revised National Tuberculosis Control Programme (RNTCP), but their effectiveness has not been documented. Aim: To assess the treatment outcome and problems encountered by patients managed by different DOT providers in the RNTCP. Material and Methods: Patients diagnosed with tuberculosis at 17 Primary Health Institutions (PHIs) in Tiruvallur District during a 3-year period received DOT from one of the four types of trained DOT providers (PHI staff, governmental outreach workers, Anganwadi workers, community volunteers), and their treatment outcomes were compared. Of the 1131 new smear-positive patients treated between May 1999 through June 2002, 199 (18%) received DOT from PHI staff, 238(21%) from outreach workers, 496 (44%) from Anganwadi workers, and 170 (15%) from community volunteers. Twenty-eight patients (2%) collected drugs for self-administration. Results: Treatment success rates among patients treated by different DOT providers, Anganwadi workers (80%), governmental outreach workers (81%), community volunteers (76%) and PHI staff (76%), were statistically similar. Patients who received drugs for self-administration were significantly more likely to fail to treatment or die than patients who were treated by a DOT provider (5/28 versus 84/1103; odds ratio=4.1; 95% confidence interval=1.2-12.6; p=0.02). Conclusion: In addition to governmental staff, Anganwadi workers and community volunteers can be effectively utilized as DOT providers.

Induction of rifampicin metabolism during treatment of tuberculous patients with daily and fully intermittent regimens containing the drug.

Self-induction of rifampicin metabolism during daily and intermittent chemotherapy was studied by monitoring the changes in the serum half-life of the drug over a 4-week period in patients with pulmonary tuberculosis. Rifampicin 450 mg was administered to 8 patients who received treatment daily, 7 on thrice-weekly and 7 others on twice-weekly treatment. Serum half-life was computed from concentrations of the drug determined at 3, 4 1/2 and 6 hours after drug administration, on admission and at 1, 2 and 4 weeks after start of treatment. In the daily series, the mean serum half-life decreased from 4.9 hours on admission to 3.6 hours at 1 week (P = 0.02), and treatment beyond this had no further effect. In the thrice-weekly series, maximal induction was observed at the 2nd week, the mean values on admission and at 2 weeks being 5.8 and 3.7 hours, respectively (P less than 0.01). In the twice-weekly series, maximal induction was observed only at the 4th week, the mean values on admission and at 4 weeks being 4.9 and 3.7 hours, respectively (P less than 0.01). Serum activity of gamma glutamyl transferase was not found to be a suitable in vivo marker to monitor induction of the hepatic microsomal enzymes as no significant changes were observed in the activity of this enzyme in any of the 3 series during the 4-week period.