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 > or =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.

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.

Rapid decline in prevalence of pulmonary tuberculosis after DOTS implementation in a rural area of South India.

SETTING: Tiruvallur District in Tamilnadu, South India, where the World Health Organization-recommended DOTS strategy was implemented as a tuberculosis (TB) control measure in 1999. OBJECTIVE: To assess the epidemiological impact of the DOTS strategy on the prevalence of pulmonary tuberculosis (PTB). DESIGN: Surveys of PTB were undertaken on representative population samples aged > or =15 years (n = 83000-90000), before and at 2.5 and 5 years after the implementation of the DOTS strategy. The prevalence of PTB (smear-positive/culture-positive) was estimated. RESULTS: TB prevalence declined by about 50% in 5 years, from 609 to 311 per 100000 population for culture-positive TB and from 326 to 169/100000 for smear-positive TB. The annual rate of decline was 12.6% (95%CI 11.2-14.0) for culture-positive TB and 12.3% (95%CI 8.6-15.8) for smear-positive TB. The decline was similar at all ages and for both sexes. CONCLUSION: With an efficient case detection programme and the DOTS strategy, it is feasible to bring about a substantial reduction in the burden of TB in the community.

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).

Excess mortality and risk factors for mortality among a cohort of TB patients from rural south India.

OBJECTIVES: To estimate the excess general mortality among tuberculosis (TB) patients in a rural area (Tiruvallur) and identify risk factors for TB-related mortality. SETTING: The study population consisted of all TB patients aged >or=15 years who were registered under the Revised National Tuberculosis Control Programme (RNTCP) during the years 2000 to 2003 at Velliyur TB unit (TU) in south India. DESIGN: This is a retrospective cohort study of 3405 patients treated under the DOTS strategy, followed up from the date of start of treatment till the date of interview (for the survivors) or the date of death (for those who died). RESULTS: There were 2710 (79.6%) survivors and 695 (20.4%) deaths. The excess general mortalities for the cohort, expressed as standardised mortality ratio (SMR), was 4.2 (95%CI 3.9-4.5). High SMR values were obtained for patients belonging to the 15-44 years age group (12.1), patients on Category II regimen (9.3), treatment failures (9.1) and defaulters (7.8). The adjusted hazards ratios (aHR) were high for patients aged 45-59 years (1.9), >or=60 years (3.1) and with incomplete treatment due to default or failure (6.4). CONCLUSION: TB is one of the main causes of mortality in the younger age group. Among TB patients, the major risk factors for mortality are old age (>or=45 years) and incomplete treatment.

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.

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.

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.

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.

The prevalence of tuberculosis in different economic strata: a community survey from South India.

A cross-sectional socio-economic survey to assess the standard of living index (SLI) of a rural population in South India was undertaken along with a tuberculosis (TB) prevalence survey during 2004-2006. Of 32,780 households, the SLI was low, medium and high in 22%, 36% and 42%, and TB prevalence was 343, 169 and 92 per 100,000 population, respectively, a significant decrease in trend (P < 0.001); 57% of the TB patients had a low SLI and the prevalence of TB was higher amongst the landless (P < 0.001), those living below the poverty line (P < 0.01) and in katcha houses (P < 0.001), suggesting that TB disproportionately affects those with a low SLI.

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.

Additional risk of developing TB for household members with a TB case at home at intake: a 15-year study.

OBJECTIVE: To assess the additional risk to household contacts from an infectious case of tuberculosis (TB) at home in a rural community in south India. METHODS: In all, 3506 contacts of smear-positive (S+C+) and 2910 contacts of smear-negative TB cases (S-C+) and 246 845 persons with no TB case at home were followed for 15 years, with a repeat survey every 2.5 years consisting of radiographic and sputum examination, selective follow-up of high-risk individuals and passive surveillance. If a case developed during follow-up, all household members were subsequently considered as contacts. Cox's proportional hazards model (multivariate) was employed to compare incidences. RESULTS: The annual incidence of culture-positive TB was respectively 526 and 271 per 100000 population for contacts of smear-positive and smear-negative patients, and 198/100000 in non-contacts. The adjusted hazard rate was 3.4 for contacts of smear-positive patients (95% CI 3.0-3.9) and 1.7 for contacts of smear-negative patients (95% CI 1.4-2.0) as compared to non-contacts. Of 3942 incident cases, 337 (8.5%) came from households with a TB case. CONCLUSION: Although family contacts had a significantly higher incidence, their contribution to total new caseload was meagre. Contact chemoprophylaxis as a public health measure would therefore have limited impact on community TB incidence.

Health-seeking behaviour of new smear-positive TB patients under a DOTS programme in Tamil Nadu, India, 2003.

BACKGROUND: Although case detection is above 70% in Tamil Nadu after DOTS implementation, an assessment of the timeliness of patient diagnosis and treatment is still needed. OBJECTIVE: To study the health-seeking behaviour of new smear-positive pulmonary tuberculosis (PTB) patients treated at government facilities. METHODS: New smear-positive patients diagnosed and treated between January and March 2003 in government facilities of randomly selected blocks in Tamil Nadu were interviewed using a semi-structured interview schedule. RESULTS: Of 601 patients interviewed, 65% contacted a provider within 28 days. The first contact was governmental for 47% and non-governmental for 53%. Median total, patient and provider delays were respectively 62, 28 and 28 days; provider delay was 9 days with government and 50 with private provider. In multivariate analysis, patient delay was significantly associated with smoking (P < 0.001) and mode of travel (P < 0.01), and provider delay with first consultation with a private provider (P < 0.001) and distance > 5 km from the health facility (P < 0.01). Twenty-five per cent of patients took more than two actions before diagnosis. CONCLUSION: Community awareness of TB needs to be increased. Greater private sector involvement in the Revised National Tuberculosis Control Programme is essential to reduce provider delay. Referral and sputum transportation to the diagnostic facility should be given priority.

Active community surveillance of the impact of different tuberculosis control measures, Tiruvallur, South India, 1968-2001.

BACKGROUND: Tuberculosis is curable, but community surveys documenting epidemiological impact of the WHO-recommended DOTS strategy on tuberculosis prevalence have not been published. We used active community surveillance to compare the impact of DOTS with earlier programmes. METHODS: We conducted tuberculosis disease surveys using random cluster sampling of a rural population in South India approximately every 2.5 years from 1968 to 1986, using radiography as a screening tool for sputum examination. In 1999, DOTS was implemented in the area. Prevalence surveys using radiography and symptom screening were conducted at the start of DOTS implementation and after 2.5 years. RESULTS: From 1968 to 1999, culture-positive and smear-positive tuberculosis declined by 2.3 and 2.5% per annum compared with 11.9 and 5.6% after DOTS implementation. The 2.5 year period of DOTS implementation accounted for one-fourth of the decline in prevalence of culture-positive tuberculosis over 33 years. Multivariate analysis showed that prevalence of culture-positive tuberculosis decreased substantially (10.0% per annum, 95% CI: 2.8-16.6%) owing to DOTS after only slight declines related to temporal trends (2.1% annual decline, 95% CI: 1.1-3.2%) and short-course chemotherapy (1.5% annual decline, 95% CI: -9.7% to 11.5%). Under DOTS, the proportion of total cases identified through clinical care increased from 81 to 92%. CONCLUSIONS: Following DOTS implementation, prevalence of culture-positive tuberculosis decreased rapidly following a gradual decline for the previous 30 years. In the absence of a large HIV epidemic and with relatively low levels of rifampicin resistance, DOTS was associated with rapid reduction of tuberculosis prevalence.

Effects of amlodipine and valsartan on oxidative stress and plasma methylarginines in end-stage renal disease patients on hemodialysis.

Patients with end-stage renal disease (ESRD) receiving hemodialysis (HD) treatment have a markedly shortened life expectancy in large part owing to cardiovascular disease (CVD), not explained by established risk factors. We tested the hypothesis that therapy with valsartan, an angiotensin receptor blocker and amlodipine, an antioxidant calcium channel blocker will reduce oxidative stress and the plasma levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase. We confirmed that compared with age- and gender-matched healthy controls, ESRD patients have excessive oxidative stress and arginine methylation as indexed by elevated plasma levels of oxidation products of lipids (13-hydroxyoctadecadienoic acid (13-HODE)), thiols (oxidized:reduced glutathione, oxidized glutathione (GSSG):GSH), proteins, and nucleic acids, and the methylation products ADMA and symmetric dimethylarginine (SDMA). We undertook a double blind, crossover study of equi-antihypertensive treatment with amlodipine and valsartan for 6 weeks each to test our hypothesis. Both treatments significantly reduced GSSG:GSH, 8-hydroxy 2-deoxyguanosine, ADMA, and SDMA levels and amlodipine reduced 13-HODE. We conclude that hypertensive patients with ESRD receiving HD have evidence of extensive oxidation of lipids, thiols, proteins, and nucleic acids and methylation of arginine that could contribute to CVD. Many of these changes can be reduced by short-term treatment with amlodipine and valsartan.

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.

Status of bacillary tuberculosis cases identified in a community survey under different control programmes.

We report the status of bacillary tuberculosis (TB) cases identified in community surveys undertaken at 2.5-year intervals. We observed three cohort periods to represent the different TB control programmes, namely 12-18 months of treatment (pre-short-course chemotherapy [pre-SCC]), 6-8 months SCC and DOTS in the area. There was a significant reduction in deaths from 23% to 17%, and an increase in the proportion of cases negative by smear and/or culture for Mycobacterium tuberculosis, from 54% to 58% in the pre-SCC and SCC cohorts to 80% in the DOTS cohort. These findings suggest that the DOTS strategy could have a significant influence on TB epidemiology.

Initial drug susceptibility profile of M. tuberculosis among patients under TB programme in South India.

SETTING: Pulmonary tuberculosis (PTB) patients enrolled for treatment at government health facilities in a sub-district of Thiruvallur district, Tamil Nadu, India. OBJECTIVES: To determine the drug susceptibility profile among PTB patients admitted to treatment according to the Revised National Tuberculosis Control Programme (RNTCP). METHODOLOGY: From May 1999 to December 2003, two additional sputum samples were collected from all patients at the start of anti-tuberculosis treatment under DOTS and were transported to a central laboratory for Mycobacterium tuberculosis culture and drug susceptibility testing (DST). RESULTS: DST results were available for 1603 new sputum smear-positive patients; 85% of patients had organisms fully susceptible to streptomycin (S), isoniazid (H) and rifampicin (R), 10.4% any resistance to H and 1.7% to HR. Of 443 patients with history of previous anti-tuberculosis treatment, 59% had organisms susceptible to S, H and R, 37% had any resistance to H and 11.7% to HR. CONCLUSION: The DST profile showed that the vast majority of patients have drug-susceptible organisms, and that currently recommended regimens under the RNTCP would be effective in the treatment of TB.

Relationship of ARTI to incidence and prevalence of tuberculosis in a district of south India.

OBJECTIVE: To validate the currently used empirical relationship between annual risk of tuberculous infection (ARTI) and incidence and prevalence of smear-positive cases. SETTING: Two disease surveys to estimate the prevalence and incidence of tuberculosis (TB) among adults in Tiruvallur district, south India, and a tuberculin survey to estimate the ARTI among children. RESULTS: The incidence of TB was estimated to be 82 and prevalence 210 per 100,000 population and ARTI 1.6%. We estimated that 1% ARTI corresponded to 51 new and 131 prevalent cases. CONCLUSION: The currently used empirical relationship between ARTI and incidence can be used by programme managers as an effective monitoring tool.

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.