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.

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.

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.

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.

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.

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.

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 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.

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.

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.

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.

Application of lot sampling of sputum AFB smears for the assessment of microscopy centres.

SETTING: Designated microscopy centres (DMC) and additional microscopy centres (AMC) performing sputum acid-fast bacilli (AFB) microscopy, the District TB Centre (DTC) and a reference laboratory (RL). OBJECTIVES: To ascertain the feasibility of adopting lot sampling of AFB smears and to assess the performance of MCs employing Senior Tuberculosis Laboratory Supervisors (STLS) with no knowledge about the principles of quality assurance of AFB microscopy and RL-based laboratory technicians with training on quality assurance for blinded checking of AFB smears. METHODS: Slides from MCs were transported to the DTC and the RL; 20 smears per month per MC were selected systematically; 1547 slides from DMCs and 726 from AMCs were checked, respectively, by STLSs at the DTC and by RL laboratory technicians. Discrepancies were resolved by referee. RESULTS: The discrepancy between MC laboratory technicians and STLSs at the DTC was 4.7%, compared to 1% at the RL. The STLSs and RL-based laboratory technicians had 70 and 2 errors, respectively. CONCLUSIONS: Lot sampling of AFB smears is feasible under field conditions. Assessment of MCs was more valid with RL-based technicians trained in principles of quality assurance of sputum AFB microscopy than with STLSs with no such training and working in the field.

Predictors of relapse among pulmonary tuberculosis patients treated in a DOTS programme in South India.

OBJECTIVE: To identify risk factors associated with relapse among cured tuberculosis (TB) patients in a DOTS programme in South India. DESIGN: Sputum samples collected from a cohort of TB patients registered between April 2000 and December 2001 were examined by fluorescence microscopy for acid-fast bacilli and by culture for Mycobacterium tuberculosis at 6, 12 and 18 months after treatment completion. RESULTS: Of the 534 cured patients, 503 (94%) were followed up for 18 months after treatment completion. Of these, 62 (12%) relapsed during the 18-month period; 48 (77%) of the 62 relapses occurred during the first 6 months of follow-up. Patients who took treatment irregularly were twice more likely to have a relapse than adherent patients (20% vs. 9%; adjusted odds ratio [aOR] 2.5; 95% CI 1.4-4.6). Other independent predictors of relapse were initial drug resistance to isoniazid and/or rifampicin (aOR 4.8; 95% CI 2.0-11.6) and smoking (aOR 3.1; 95% CI 1.6-6.0). The relapse rate among non-smoking, treatment adherent patients with drug-sensitive organisms was 4.8%. CONCLUSIONS: The relapse rate under the DOTS programme may be reduced by ensuring that patients take their treatment regularly and are counselled effectively about quitting smoking.

Comparison of cough of 2 and 3 weeks to improve detection of smear-positive tuberculosis cases among out-patients in India.

SETTING: Governmental health facilities in six districts of India. OBJECTIVE: To estimate the prevalence of cough and to compare the detection of smear-positive tuberculosis (TB) among out-patients with cough of > or =2 or > or =3 weeks. DESIGN: Trained health workers questioned each out-patient for presence of cough. Those with cough > or =2 weeks underwent sputum microscopy. RESULTS: Of 55561 out-patients interviewed, 2210 (4%) had cough > or =2 weeks, of whom 267 had sputum-positive TB, compared to 182/1370 with cough > or =3 weeks. The 31% who did not spontaneously complain of cough were less likely to be sputum-positive than those who did (45/680 [7%] vs. 222/1530 [15%], P < 0.001), but they accounted for 45/267 smear-positive cases. Using cough > or =2 weeks as the screening criterion, the estimated number of smears performed per day at each primary and secondary health care facility was respectively 8 and 19, compared to 5 and 12 using cough > or =3 weeks. CONCLUSION: The detection of smear-positive TB cases can be substantially improved by actively eliciting history of cough from all out-patients, and by changing the screening criterion for performing sputum microscopy among out-patients from cough > or =3 weeks to > or =2 weeks. Before implementing this change nationally, its programmatic feasibility should be assessed.

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.

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.

Shifting the focus of tuberculosis research in India.

India has a long and distinguished tradition of research in the field of tuberculosis (TB). Pioneering studies from India demonstrated the efficacy and safety of domiciliary treatment, the necessity of direct observation of treatment, the feasibility of case detection through sputum smear microscopy in primary health care institutions, and the effectiveness of intermittent short-course chemotherapy. These findings laid the foundation of directly observed treatment, short course (DOTS), which has been adopted by nearly 150 countries worldwide. Today, India has the second-largest and the fastest-growing DOTS programme in the world. A strong component of programme evaluation and operational research is needed to sustain and expand DOTS in the context of a suboptimal primary health care system, a large and unregulated private health care system, and the dual threats of HIV and multidrug-resistant TB (MDR-TB). Therefore, the focus of TB research in India has shifted to the following operational research areas: evaluating models to involve the private health sector; assessing the role of incentives in increasing treatment compliance; examining gender differentials in the access to TB services; assessing risk factors for delay in diagnosis; evaluating diagnosis, treatment and prevention of TB among HIV-infected persons; monitoring MDR-TB; estimating cost-effectiveness of the DOTS programme; monitoring the quality of smear microscopy services; and measuring the current burden of TB. Research for developing newer diagnostic tools, drugs and vaccines remains a long-term priority. Greater networking is needed among national researchers, programme managers and policy-makers to translate the findings of research into policies and programmes to make TB control in India more effective and efficient.

Washing of new microscopic glass slides in dichromate solution does not influence sputum AFB smear results.

SETTING: Microscopy centres in Tiruvallur District, Tamil Nadu, India, implementing DOTS. OBJECTIVE: To know whether washing new glass slides in dichromate solution is essential for effective sputum acid-fast bacilli microscopy. METHODS: Two direct smears were prepared from each of 1750 sputum samples. One was made on dichromate solution-cleaned new glass slides and the other was made on unwashed new glass slides. The smears were blinded and examined. RESULTS: Of the 1750 specimens, 13.5% and 13.08% were positive for AFB using washed and unwashed slides, respectively (P = 0.12). The concordance between these two (including one grade above and one below) was 98.7%. CONCLUSION: Washing of new glass slides in dichromate solution is not essential for AFB microscopy.

Late onset paraplegia--a sequela to Pott's disease. A report on imaging, prevention and management.

Late onset paraplegia is a neurological complication that develops after a variable period in a patient with healed tuberculous disease of the vertebrae. In this retrospective analysis clinical features, imaging in diagnosis and treatment of this condition are described among 5 cases seen over a period of 5 years. This complication occurred even after successful treatment of initial spinal lesions with rifampicin-containing regimens. Magnetic resonance imaging was useful in pinpointing the exact pathology; one case had syrinx and two cases had marked internal gibbus with cord atrophy. Of the two cases who accepted surgical treatment, one improved.