Role of bacille Calmette-Guérin in preventing tuberculous infection.

SETTING: Rural community in South India. OBJECTIVE: To determine the role of bacille Calmette-Guérin (BCG) in preventing tuberculous infection in children. DESIGN: A prevalence survey was undertaken in 1999-2001 in a representative rural population in Tiruvallur District in South India using cluster sampling. Tuberculin testing was performed among all children aged <15 years, and all adults aged 15 years were questioned about chest symptoms and underwent radiography, followed by sputum examinations, if indicated. RESULTS: In children living in households with a tuberculosis case, the proportion with evidence of tuberculous infection was 35.5% of 200 in the absence of a BCG scar and 27.0% of 100 in its presence, a reduction of 24% (P = 0.14). In very young children (age <5 years), the corresponding proportions were 29.1% of 55 and 11.9% of 42, a reduction of 59%; the difference was statistically significant (P = 0.048). CONCLUSION: There is a possible role for BCG in preventing tuberculous infection in very young children.

Trend in the incidence of smear-positive tuberculosis in a district in South India after DOTS implementation.

SETTING: One baseline and three repeat surveys of the prevalence of tuberculosis (TB) disease were conducted in 1999-2008 in rural South India, where the DOTS strategy was implemented in 1999. The impact of DOTS on prevalence was documented, but not its impact on incidence. OBJECTIVE: To ascertain epidemiological trends in the incidence of smear-positive TB. DESIGN: All persons aged ⩾15 years (range 83 000-92 000) were examined using chest radiography (CXR); chest symptoms and history of anti-tuberculosis chemotherapy were noted in all four surveys. Sputum was collected from eligible participants and tested using direct smear and culture, and for drug susceptibility. As follow-up surveys were not frequent, survey cases and cases directly notified under DOTS were combined to estimate the incidence of smear-positive TB. RESULTS: Coverage was consistently high in all the repeat surveys, at ⩾80% for CXR and symptom recording, and at ⩾95% for sputum examination. The annual incidence of smear-positive TB was respectively 112, 80 and 76 per 100 000 population in 2001-2003, 2004-2006 and 2006-2008. The overall decline observed was 7.5% per annum. CONCLUSION: A well-implemented DOTS strategy can lead to a reduction in the TB burden in the community.

Tuberculosis mortality in a rural population from South India.

BACKGROUND: General mortality rate (GMR) is an essential indicator for assessing the health status of a community. Tuberculosis (TB) mortality is an indicator for the Millennium Development Goal for 2015. METHODS: This community-based retrospective survey was conducted in 2007-2008 on a sample of 114,605 rural populations living in 56 villages randomly selected from 218 villages in Tiruvallur district, South India, where the DOTS strategy was implemented in 1999. All the permanent residents of the households were registered and information on occurrence of death was recorded. All the deaths were investigated by verbal autopsy (VA) using standardized methods. RESULTS: A total of 719 deaths were registered. The GMR and tuberculosis mortality rate (TMR) were 648 (95% CI: 568-727) and 39 (95% CI: 25-52) per 100,000 p-yrs, respectively. The GMR increased with age, and was higher in males than females at all ages. The TMR was higher in males than females and the overall male:female ratio was 5:1. CONCLUSION: TB was the 6th leading cause of death overall and the 2nd leading cause among men in this area. Strategies to reduce TB death should be implemented and the impact should be monitored by repeat VA studies.

General and tuberculosis mortality in two states of India: A population-based survey.

BACKGROUND: General and cause-specific mortality data for causes of death are not available for the states of Andhra Pradesh (AP) and Orissa in India. OBJECTIVES: To estimate general mortality rate (GMR) and the tuberculosis mortality rate (TMR) among the general population in the two states. METHODS: All permanent residents in households of selected districts of AP and Orissa states were registered in the survey in 2005-2006. A sample size of 380,000 persons was selected from each state. Health workers carried out house-to-house enumeration. Demographic and occurrence of death data were collected. The cause of death was determined using the instrument of verbal autopsy. RESULTS: The GMR for AP and Orissa was 636 (95% CI: 610-662) and 616 (95% CI: 588-643) per 100,000 person years (p-ys) respectively. The TMR for AP and Orissa was 76 (95% CI: 67-85) and 41 (95% CI: 34-48) per 100,000 p-ys respectively. The difference in TMR between the states was statistically significant (P<0.0001). CONCLUSION: The GMRs are similar in AP and Orissa states. Tuberculosis accounted for 12% and 7% of deaths in AP and Orissa respectively. Focused strategies are needed to reduce mortality due to tuberculosis.

Could repeated prevalence surveys lead to decreasing tuberculosis prevalence in a community?

SETTING: Tiruvallur District, South India, where one baseline tuberculosis (TB) disease prevalence survey followed by three repeat prevalence surveys were conducted every 2.5 years between 1999 and 2008, and where the DOTS strategy was implemented in 1999. OBJECTIVE: To rule out the possibility that the observed decline in TB prevalence was influenced by conducting repeat prevalence surveys, we compared the findings from two surveys: the third repeat survey conducted in 2006-2008 and an independent single survey in a neighbouring area conducted in 2008-2009. DESIGN: An independent survey was conducted to estimate the prevalence of TB in the same district in 2008-2009 using a different set of villages and employing repeat survey methodology. The independent survey findings were compared with those of the third repeat survey. RESULTS: The estimated prevalence rate of culture- and smear-positive TB was respectively 401 per 100,000 and 186 per 100,000 population in the third repeat survey area. The corresponding rates were 340 and 184/100,000 in the independent survey area. The difference in prevalence was not significant (culture P = 0.09; smear P = 0.93). CONCLUSION: The estimated prevalence rates in the two different sample survey areas were comparable, indicating that the repeated prevalence surveys in the study area did not influence the observed decline in TB disease prevalence.

Does effect of BCG vaccine decrease with time since vaccination and increase tuberculin skin test reaction?

The protective efficacy of BCG was studied for over 15 years, from 1968, in South India. A secondary analysis of data was performed to investigate the relationship between Bacille Calmette-Guérin (BCG) and tuberculosis (TB) disease and between BCG and positive tuberculin skin test for different time periods among children aged less than 10 years. A randomized controlled trial was conducted, where 281,161 persons were allocated to receive BCG 0.1mg, BCG 0.01mg or placebo. Tuberculin skin test was performed at baseline and at 4 years after BCG vaccination. Surveys were conducted every 2.5 years to detect all new cases of culture-positive/smear-positive TB occurring in the community over a 15-year period. Relative risk (RR) was obtained from the ratio of incidence among the vaccinated and the placebo groups. Among those children vaccinated with 0.1mg of BCG, the RR for TB was 0.56 (95% CI: 0.32-0.87, P=0.01) at 12.5 years but increased to 0.73 later. Similar pattern was seen with 0.01mg. The increase in the number of skin test positives with 0.1mg of BCG was 57.8%, 49.4% and 34% for cut-off points at ≥10mm, ≥12mm and ≥15mm, respectively. The study suggests that the effect of BCG may decrease since vaccination and the tuberculin positive was higher at post-vaccination test period due to BCG.

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.

Trend in tuberculosis infection prevalence in a rural area in South India after implementation of the DOTS strategy.

SETTING: Three tuberculin surveys were conducted at intervals of 5 years following the implementation of a DOTS-based programme in 1999 in Tiruvallur District, South India. OBJECTIVE: To estimate the trend in the prevalence of tuberculosis (TB) infection among children and to evaluate the impact of the DOTS strategy. METHODS: Children aged 1-9 years in the sample for each survey were registered and administered 1 tuberculin unit of purified protein derivative RT 23 with Tween 80 by intradermal injection on the volar aspect of the left forearm. The induration diameter of the reaction was measured in mm after 72 h (3 days) and the prevalence of TB infection estimated. RESULTS: The induration data of bacille Calmette-Guérin (BCG) vaccinated and non-vaccinated children were analysed using the mixture model. The estimated prevalence of TB infection among non-BCG-vaccinated children in the three tuberculin surveys were respectively 19.4%, 13.8% and 11.4%, with an average annual decline of 5.2% (95%CI 3.6-6.8). The prevalence of TB infection among BCG-vaccinated children decreased, with an average annual decline of 5.4% (95%CI 10.0-18.6). CONCLUSION: A significant declining trend in the prevalence of TB infection among children was observed following the implementation of the DOTS strategy in the area.

Weight gain in patients with tuberculosis treated under directly observed treatment short-course (DOTS).

UNLABELLED: SET UP: One Tuberculosis Unit (TU) in Tiruvallur district, Tamil Nadu, India where Tuberculosis (TB) patients treated under Directly Observed Treatment Short Course (DOTS) programme. OBJECTIVE: To identify the effects of weight gain among TB patients at the end of treatment on different factors such as socio-economic and demographic characteristics, smoking and drinking habits, treatment under supervision, the type of DOTS centres and problems in taking drugs. METHODS: TB patients registered between May 1999 and December 2004 formed the study population. Multiple regression method was used for the analysis. RESULTS: Among 1557 smear-positive TB patients registered under DOTS programme, the changes in weight ranged from a loss of 4 kgs to a gain of 20 kgs at the end of TB treatment; the average change in weight was 3.22 kgs. The gain in weight at the end of treatment was associated with age (<45 years), DOT at government centres, no problems in taking drugs as reported by patients and cure rate. CONCLUSION: The findings showed that there is an association between gain in weight with DOT at government centres and cure of patients.

Association between biomass fuel and pulmonary tuberculosis: a nested case-control study.

OBJECTIVE: To quantify the association between biomass fuel usage and sputum-positive pulmonary tuberculosis. METHODOLOGY: A tuberculosis prevalence survey was conducted in a random sample of 50 rural units (villages) and three urban units in the Tiruvallur district of Tamilnadu, India during the period 2001-2003. Additional data regarding exposure to tobacco smoking, alcohol consumption, biomass fuel usage and Standard of Living Index (SLI) were also collected from the study participants. A nested case-control study was carried out in this population. Cases are defined as bacteriological-positive cases diagnosed by either sputum smear or culture examination. For each case, five age- (within +/-5 years of age) and sex-matched controls were selected randomly from the non-cases residing in the same village/unit. Thus, 255 cases and 1275 controls were included in this study. RESULTS: The unadjusted OR measured from univariate analysis for biomass fuel is 2.9 (95% CI 1.8 to 4.7). The adjusted OR measured from multivariate analysis using Cox regression is 1.7 (95% CI 1.0 to 2.9). Thirty-six percent of cases are attributable to biomass fuel usage. CONCLUSION: The findings from this case-control study add to the evidence for an independent association between biomass smoke and pulmonary tuberculosis. Improvement in standards of living brought about by economic development will lead to more people using cleaner fuels for cooking than biomass fuel which in turn will lead to a reduction in the occurrence of pulmonary tuberculosis in the community.

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.

Annual risk of tuberculosis infection among tribal population of central India.

OBJECTIVE: To estimate the annual risk of tuberculosis infection (ARTI) among tribal children of Madhya Pradesh, central India. METHODS: Community-based, cross-sectional tuberculin survey among children aged 1-9 years in the tribal population of Madhya Pradesh. Multistage stratified cluster sampling was used to select a representative random sample of villages predominated by tribal population from selected districts. A total of 4802 children were tuberculin-tested with 1TU of PPD RT 23 and the reaction sizes read after 72 h. RESULTS: A total of 3062 (64%) children had no BCG scar. The frequency distribution of children by reaction sizes indicated a fair mode at 18 mm in the right hand side of the distribution. By mirror-image technique, the prevalence of infection among children with no recognizable BCG scar was estimated as 6.8% (95% CI: 4.8-8.9%). The ARTI was computed as 1.3% (0.9-1.7%). The corresponding figures for children irrespective of scar status were 7.1% (95% CI: 5.5-8.8%) and 1.3% (1.0-1.7%) respectively. CONCLUSIONS: The risk of tuberculosis infection in tribal population of Madhya Pradesh, central India is not different from other areas of the country. There is, however, a need to further intensify tuberculosis control measures on a sustained and long-term basis.

Evaluation of different types of chest symptoms for diagnosing pulmonary tuberculosis cases in community surveys.

BACKGROUND: Prevalence of tuberculosis (TB) is an important epidemiological index to measure the load of the disease in a community. A series of disease surveys were undertaken in rural community in Tiruvallur district in Tamilnadu, south India OBJECTIVE: To investigate the yield of pulmonary tuberculosis (TB) cases by different symptoms status and suggest predominant symptoms for detection of cases in the community based surveys. METHODS: Three disease surveys were conducted during 1999-2006, in a random sample of 82,000 adults aged > or = 15 years to estimate the prevalence and incidence of pulmonary TB. All subjects were screened for chest symptoms and chest radiography. Sputum examination was done among those who were either symptomatic or abnormal on X-ray or both. Cases observed through symptom inquiry were included for analysis. RESULTS: In survey-I, 65.6% had cough of > or = 14 days and yielded 79.1% of the total cases. In surveys II and III, symptomatic subjects with cough contributed 69.5% and 69.2% of the cases respectively. In survey I, 26.8% had symptoms without cough but with at least chest pain > or = 1 month contributed 8.4% of total cases. The corresponding proportions in subsequent surveys were 29.3, 11.5%; and 23.4, 11.2% respectively. The number of symptomatics without cough and chest pain but with fever > or = 1 month was negligible. CONCLUSION: The relative importance of cough as a predominant symptom was reiterated. The yield of pulmonary TB cases from symptomatics having fever of > or = 1 month was negligible. Fever may be excluded from the definition of symptomatics for screening the population in community surveys.

Annual risk of tuberculosis infection in Chennai city.

AIM: To study the proportion of children infected with Mycobacterium Tuberculosis in Chennai city. METHODOLOGY: A cluster sampling methodology was adopted to select an estimated sample size of 7000 children from five corporation zones selected systematically from ten zones of the city. A total of 7098 children aged 1-9 years were subjected to Mantoux and test read; 1897 (27%) from slum area and 5201 (73%) from non-slum area. RESULTS: The prevalence of infection among children without BCG scar was estimated to be 10.5 % (ARTI of 2.0%) and was similar to that among children irrespective of scar status. The prevalence of infection was higher among children in slum areas (11.1%; ARTI 2.1%) compared to non-slum areas (8.9%; ARTI 1.7%); but the difference was not statistically different. CONCLUSION: The tuberculosis situation in Chennai as measured by risk of infection was higher in urban city area than rural areas and comparable to that found in other cities as reported from earlier studies. This information can be used as baseline information for monitoring the epidemiological trends in Chennai city in future.

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.

Tuberculous infection in Saharia, a primitive tribal community of Central India.

A cross-sectional tuberculin survey was carried out to estimate the prevalence of tuberculous infection and the annual risk of tuberculosis infection (ARTI) among children of Saharia, a primitive ethnic group in Madhya Pradesh, Central India. A total of 1341 children aged 1-9 years were subjected to tuberculin testing with 1 TU of PPD RT 23 and the reaction sizes were read after 72 h. The proportion of BCG scar-positive children was 34.6%. The frequency distribution of children by reaction sizes indicated a clear-cut anti-mode at 11 mm and a mode at 18 mm at the right-hand side of the distribution. The prevalence of infection among children irrespective of BCG scar was estimated as 20.4% (95% CI 18.2-22.5%) and the ARTI was 3.9% (95% CI 3.5-4.3%). The corresponding figures were 21.1% (95% CI 18.3-23.8%) and 3.9% (95% CI 3.4-4.5%) among BCG scar-negative children and 19.0% (95% CI 15.4-22.5%) and 4.0% (95% CI 3.2-4.8%) among BCG scar-positive children. The findings of the present study show a high prevalence of tuberculous infection and high ARTI in this primitive ethnic group. There is an urgent need to further intensify tuberculosis control measures on a sustained and long-term basis in this area.

Survival of tuberculosis patients treated under DOTS in a rural Tuberculosis Unit (TU), south India.

OBJECTIVE: To estimate survival probabilities and identify risk factors for death of tuberculosis (TB) patients during treatment period. METHODS: TB patients registered during May 1999 to December 2004 from a rural TB unit (TU) with a population of 580,000 in Tiruvallur district, South India, formed study population. Life table and Cox's regression methods were used. RESULTS: Of the 3818 TB patients who were initiated on treatment, 96, 94 and 97% of category--I, II and III respectively, were surviving after completion of treatment. Higher death rates were independently associated with patient's age (45 years), previous history of treatment, alcoholism and initial body weight (<35 kgs). CONCLUSION: The survival probability was found to be similar in all patients irrespective of categorization. Necessary actions need to be initiated in the programme to improve body weight and abstain from alcoholism.

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.