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Biomedical subjects

T R Frieden

Publications and source records attributed to T R Frieden.

At least 19 recordsLinked to original sources

Value of dual testing for identifying tuberculous infection.

SETTING: A rural community in Chingleput district in Tamil Nadu state in south India. OBJECTIVE: To determine the value of dual testing with PPD-S and PPD-B for identifying subjects with a tuberculous infection. DESIGN: About 240,000 subjects in rural south India, all of whom were tested initially with PPD-S and PPD-B, were followed up for 15 years, mainly by total population survey once in every 212 years. The incidence of culture-positive tuberculosis was estimated using life-table technique. RESULTS: Among 17,530 subjects with an intermediate reaction (8-11 mm) to PPD-S at intake, 285 with an induration to PPD-S exceeding the induration to PPD-B by at least 2mm, had a significantly higher incidence of culture-positive tuberculosis than the remaining (154 and 93 per 100,000), and similarly 481 who had an induration of <10mm to PPD-B compared to those with >or=10 mm (131 and 93 per 100,000). These subjects may be regarded as having a tuberculous infection. Infection with non-tuberculous mycobacteria conferred protection of about 30% against the development of tuberculosis over a 15-year period. CONCLUSION: In subjects with an intermediate reaction (8-11 mm) to PPD-S, dual testing with PPD-B enabled identification of those with a tuberculous infection. Most of the reactions were due to non-tuberculous mycobacteria.

Adolescent↗

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.

Adolescent↗

Improved tuberculosis case detection through public-private partnership and laboratory-based surveillance, Kannur District, Kerala, India, 2001-2002.

BACKGROUND: Efforts to intensify global tuberculosis (TB) control are limited by difficulties in coordinating with private doctors. More than half of Indian TB patients may initially consult a private provider, but many are neither diagnosed accurately nor treated effectively. We established and evaluated a public-private partnership based on surveillance of TB detected in private laboratories and use of standardised directly observed treatment regimens. METHODS: In one district, the governmental TB control programme offered training in microscopy to all large private sector laboratories, and educated private physicians on the importance of microscopy for TB diagnosis. We reviewed records from participating private laboratories and all publicly diagnosed patients. RESULTS: Of 2328 pulmonary TB patients registered from July 2001 to December 2002, 404 (17%) were detected in the private sector. The annual new AFB-positive case notification rate increased by 21%, from 27.8/100,000 in 2000 to 33.5/100,000 in 2002. Surveillance at private laboratories found an additional 260 nonregistered AFB-positive patients. CONCLUSIONS: This public-private partnership substantially increased TB case detection and established a sustainable framework for private sector involvement in TB control. In the setting of a strong public sector programme, the combination of active surveillance of private laboratories along with physician sensitisation is a promising approach to improve TB case detection.

Humans↗

Reduced detection by Ziehl-Neelsen method of acid-fast bacilli in sputum samples preserved in cetylpyridinium chloride solution.

SETTING: Twelve health facilities implementing the DOTS strategy, and the Tuberculosis Research Centre (TRC), Chennai, India. OBJECTIVE: To determine the detection rates using Ziehl-Neelsen (ZN) and auramine-phenol to stain acid-fast bacilli (AFB) in sputum samples stored in cetylpyridinium chloride (CPC) solution. METHODS: Two smears were prepared from each of 988 sputum samples collected in CPC and randomly allocated, one to ZN and the other to auramine-phenol staining. All samples were processed for culture of Mycobacterium tuberculosis. RESULTS: A significantly higher proportion of samples were negative using the ZN method compared to the auramine-phenol method (74.5% vs. 61.8%, McNamara's paired chi2 test; P < 0.001). Among 377 samples that were positive using auramine-phenol, 44% were negative using ZN. There were more culture-positive, smear-negative samples in ZN (52.7%) than in auramine-phenol (30%); the difference attained statistical significance (McNemar's paired chi2 test; P < 0.00004). Using ZN, of the 104 smears made immediately after collection, 52 were positive for AFB, of which only 35 (67.3%) were positive after storage in CPC; the reduction in the number of positive smears attained statistical significance (McNemar's paired chi2 test; P = 0.004). CONCLUSION: Detection of AFB in sputum samples preserved in CPC is significantly reduced using ZN staining.

Benzophenoneidum↗

Gender disparities in tuberculosis: report from a rural DOTS programme in south India.

SETTING: Tiruvallur District, south India. OBJECTIVES: To examine gender differences in tuberculosis among adults aged >14 years with respect to infection and disease prevalence, health care service access, care seeking behaviour, diagnostic delay, convenience of directly observed treatment (DOT), stigma and treatment adherence. METHODS: Data were collected from 1) community survey, 2) self-referred out-patients seeking care at governmental primary health institutions (PHIs), 3) tuberculosis suspects referred for sputum microscopy at PHIs, and 4) tuberculosis patients notified under DOTS. Community survey results were compared with those for patients notified at PHIs. RESULTS: In the community, 66% of males and 57% of females had tuberculosis infection. The prevalence of smear-positive tuberculosis was 568 and 87/100,000, respectively, among males and females. Fewer males than females attended PHIs (68 men for every 100 women). Females constituted 13% of all smear-positive patients detected in the community survey, and 20% of those detected at PHIs (P < 0.05). The probability of notification decreased significantly with age among both males and females. Significantly more females than males felt inhibited discussing their illness with family (21% vs. 14%) and needed to be accompanied for DOT (11% vs. 6%). Males had twice the risk of treatment default than females (19% vs. 8%; P < 0.01). CONCLUSIONS: Despite facing greater stigma and inconvenience, women were more likely than men to access health services, be notified under DOTS and adhere to treatment. Men and elderly patients need additional support to access diagnostic and DOT services.

Adolescent↗

A survey of tuberculosis hospitals in India.

SETTING: Hospitals with beds for tuberculosis (TB) in India. OBJECTIVES: To assess diagnostic and treatment practices at institutions offering secondary or tertiary level care for TB patients, and to determine the resources being used at these institutions. DESIGN: Countrywide cross-sectional survey of TB hospitals using a mailed semi-structured questionnaire sent to all 105 hospitals with 100 or more beds and to all State Directorate Health Services. RESULTS: The 94 hospitals that returned the questionnaire had 15773 TB beds, one third of the total TB beds in the country. Nearly 1 million patients sought treatment in the TB hospitals and one third were diagnosed with TB; the ratio of smear-positive to smear-negative patients was 1:2.7. Sixty-four per cent of hospitals prescribed unobserved rifampicin in the continuation phase, and 56% of sputum smear-positive patients were hospitalised. The annual expenditure for the TB hospitals was more than the total annual budget for the TB control programme of the country. CONCLUSIONS: In view of the high number of patients seen and the suboptimal practices observed, urgent steps should be taken to ensure implementation of correct diagnostic and treatment policies in hospitals with TB beds.

Cross-Sectional Studies↗

Are community surveys to detect tuberculosis in high prevalence areas useful? Results of a comparative study from Tiruvallur District, South India.

BACKGROUND: In Tiruvallur District, South India, tuberculosis cases are detected at health facilities (HF) as part of a DOTS programme, and by screening adults through community survey (CS) as part of ongoing epidemiological research. OBJECTIVE: To compare socio-demographic, clinical and bacteriological characteristics and treatment outcomes of all patients detected at HF with those of all patients detected by CS during a 12-month period. RESULTS: Of 32,663 adults surveyed, 100 had smear-positive and 116 had smear-negative tuberculosis; of 65 smear-positive patients who began treatment, 44 were cured. Compared to HF patients, CS patients were significantly more likely to be older (AOR = 1.9), male (AOR = 2.7), non-literate (AOR = 1.7), and living in poor quality housing (AOR = 2.0), and were less likely to have cough >3 weeks (AOR = 3.4) or smear-positive tuberculosis (AOR = 4.2). Of 61 new smear-positive CS patients, 40 reported chest symptoms; of these, 32 (80%) had already consulted a health-care provider, but remained undiagnosed. CONCLUSIONS: The community survey was of little value in tuberculosis case detection even in this high-prevalence setting. Patients identified by the survey were less symptomatic and less infectious, and less than half were cured. Diagnostic services should be made more accessible to the elderly, the non-literate and men.

Adult↗

Impact of national consultants on successful expansion of effective tuberculosis control in India.

SETTING: India, during a period of rapid expansion of DOTS services. DOTS expansion has been slow in many countries. OBJECTIVE: To document use of consultants to expand DOTS effectively. DESIGN: Staff were contracted to monitor DOTS expansion and implementation. To estimate the impact of these staff, we compared areas with and without consultants, and individual areas before and after consultants were assigned. Consultants were preferentially assigned to the more difficult areas; the temporary absence of consultants reflected non-availability of candidates. RESULTS: Areas with consultants met pre-defined criteria and began DOTS service delivery faster (median 9 vs. 18 months of preparation) than areas without consultants. Rates of sputum conversion (87% vs. 83%, P < 0.001) and treatment success (83% vs. 78%, P < 0.001) were significantly higher in areas with consultants present. CONCLUSION: Assignment of consultants resulted in much more rapid implementation of the DOTS strategy, and better quality performance. Continued effective performance in these areas will rely on many factors, but the need for consultants appears to be decreasing, suggesting that they have provided sustainable improvements. The effectiveness of local consultants may have important implications for efforts to scale up public health interventions for tuberculosis, malaria, AIDS and other diseases in developing countries.

Communicable Disease Control↗

A baseline survey of the prevalence of tuberculosis in a community in south India at the commencement of a DOTS programme.

OBJECTIVE: To determine the baseline prevalence of culture-positive and smear-positive tuberculosis and the annual risk of tuberculous infection (ARTI) in a community in south India where DOTS is being implemented. METHODS: Using cluster sampling, 50 rural panchayats (villages) and three urban units in Tiruvallur district were selected randomly. All adults aged > or = 15 years underwent symptom and radiographic examination, and those with abnormal shadows and/or chest symptoms had sputum smear and culture examination. In another cluster sample of 73 villages and three urban units, all children aged < 10 years were tuberculin tested. RESULTS: The prevalence of culture-positive and smear-positive tuberculosis was respectively 605 and 323/100,000. Both increased appreciably with age, and were substantially higher in males than in females at all ages; the overall male:female ratio was 5.5 for culture-positive and 6.5 for smear-positive tuberculosis. The ARTI in children aged under 10 years was 1.6%, and was unaffected by sex. Over three decades there was an overall decline of 1.8% per annum in the prevalence of culture-positive and 2.1% for smear-positive tuberculosis. CONCLUSION: Tuberculosis is a major problem in this rural community in south India, with a prevalence of 605/100,000 for culture-positive tuberculosis and 323/100,000 for smear-positive tuberculosis.

Adolescent↗

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.

Caustics↗

Risk factors associated with default, failure and death among tuberculosis patients treated in a DOTS programme in Tiruvallur District, South India, 2000.

OBJECTIVE: To identify risk factors associated with default, failure and death among tuberculosis patients treated in a newly implemented DOTS programme in South India. DESIGN: Analysis of all patients registered from May 1999 through April 2000. A community survey for active tuberculosis was underway in the area; patients identified in the community survey were also treated in this programme. RESULTS: In all, 676 patients were registered during the period of the study. Among new smear-positive patients (n = 295), 74% were cured, 17% defaulted, 5% died and 4% failed treatment. In multivariate analysis (n = 676), higher default rates were associated with irregular treatment (adjusted odds ratio [AOR] 4.3; 95%CI 2.5-7.4), being male (AOR 3.4; 95%CI 1.5-8.2), history of previous treatment (AOR 2.8; 95%CI 1.6-4.9), alcoholism (AOR 2.2; 95%CI 1.3-3.6), and diagnosis by community survey (AOR 2.1; 95%CI 1.2-3.6). Patients with multidrug-resistant tuberculosis (MDR-TB) were more likely to fail treatment (33% vs. 3%; P < 0.001). More than half of the patients receiving Category II treatment who remained sputum-positive after 3 or 4 months of treatment had MDR-TB, and a large proportion of these patients failed treatment. Higher death rates were independently associated with weight <35 kg (AOR 3.8; 95%CI 1.9-7.8) and history of previous treatment (AOR 3.3; 95%CI 1.5-7.0). CONCLUSIONS: During this first year of DOTS implementation with sub-optimal performance, high rates of default and death were responsible for low cure rates. Male patients and those with alcoholism were at increased risk of default, as were patients identified by community survey. To prevent default, directly observed treatment should be made more convenient for patients. To reduce mortality, the possible role of nutritional interventions should be explored among underweight patients.

Adult↗

TB prevention in HIV clinics in New York City.

SETTING: Ten hospital-based human immunodeficiency virus (HIV) clinics in New York City. OBJECTIVE: To evaluate tuberculosis (TB) prevention in HIV clinics based on the prevalence and incidence of TB and the efficacy of preventive therapy with isoniazid (INH). DESIGN: The medical records of 2393 HIV-infected patients with a first clinic visit in 1995 were reviewed retrospectively. Deaths and TB cases through December 1997 were ascertained through a match with the TB and AIDS registries. RESULTS: At first visit, 92 patients (4%) had a history of TB, 98 (4%) were being treated for TB, and six (<1%) were diagnosed with TB. During follow-up, 23 cases were diagnosed, an incidence of 0.53 per 100 person-years (py) (95%CI 0.34-0.77). Among 439 tuberculin skin test (TST) positive patients, the incidence of TB/100 py was 1.63 (95%CI 0.27-5.02) in patients with no INH, 1.28 (95%CI 0.40-2.98) in patients with <12 months of INH, and 1.06 (95%CI 0.38-2.28) in patients with 12 months of INH. The incidence/100 py was 0.0 (95%CI 0.0-0.78) in TST-negative patients and 0.37 (95%CI 0.09-0.95) in anergic patients. The relative risk of TB was 0.65 (95%CI 0.14-4.56) in TST-positive patients with 12 months of INH (vs. none). CONCLUSIONS: The benefits of TB prevention efforts in these HIV clinics from 1995 to 1997 were limited because most TB occurred before the first clinic visit. Methods for reaching HIV-infected patients earlier should be identified.

Adult↗

Trends in the prevalence and incidence of tuberculosis in south India.

OBJECTIVE: To study trends in the prevalence and incidence of tuberculosis in south India. METHODS: In 1968-1970, about 100,000 subjects were surveyed for tuberculosis and followed thereafter for 15 years, mainly by repeat survey once every 2.5 years. New entrants were inducted at every repeat survey. Radiographic examination of subjects aged 5 years or more and sputum smear and culture examinations of those with an abnormal shadow were undertaken; tuberculin tests were done initially on all, and at 4, 10 and 15 years in selected samples of those aged 1-9 years. RESULTS: The prevalence of culture-positive tuberculosis decreased by 1.4% per annum to 694/100,000, while that of smear-positive tuberculosis showed no significant decrease from 457/100,000. The annual incidence of culture-positive tuberculosis decreased by 4.3%/annum to 189/100,000 and that of smear-positive tuberculosis decreased by 2.3%/annum to 113/100,000. Decreases in incidence occurred exclusively in those with abnormal radiographic findings suggestive of tuberculosis at the start of the period. The annual risk of tuberculosis infection (ARTI) was initially 2%, and showed no sign of decline over the period. CONCLUSION: The prevalence of tuberculosis and ARTI showed little or no decrease over the 15-year period. A significant decrease in incidence occurred, but exclusively in those with abnormal radiograph suggestive of tuberculosis at the start of the period.

Adolescent↗

Public-private partnership in tuberculosis control: experience in Hyderabad, India.

SETTING: Hyderabad, India. OBJECTIVE: To determine whether private practitioners and the government can collaborate with a nongovernmental intermediary to implement DOTS effectively. DESIGN: A non-profit hospital provided DOTS services to a population of 100000 for 3 years, then expanded coverage to 500000 in October 1998. A hospital physician visited all private practitioners, encouraged them to refer patients, and gave feedback on each patient referred. After diagnosis, patients received directly observed treatment free of charge at the trust hospital or at 30 conveniently located small hospitals operated by local private practitioners. No financial incentives were used to encourage physicians to refer patients or to provide treatment observation. Diagnosis, treatment, and case and outcome definitions were performed as per DOTS policies; medicines and laboratory reagents were provided by the government. RESULTS: All 244 allopathic and 114 non-allopathic physicians practising in the area agreed to participate; 59% referred at least one patient. Of 2244 persons referred, 969 (43%) had tuberculosis. Physicians had obtained chest radiographs on 80% of patients before referral for sputum microscopy. The detection rate increased from 50 to 200/100000 over the first 2-3 years of the project, and has increased gradually since expansion; 90% of new smear-positive patients and 77% of re-treatment patients were successfully treated. Compared with those treated at a neighbouring government DOTS centre, patients in this project paid less for diagnosis ($5 vs. $20) and treatment ($1 vs. $11), largely due to lower transport costs. CONCLUSIONS: Collaborative efforts between private practitioners and the government can achieve moderate-high rates of case detection and high rates of treatment success. Public-private services appeared to be more convenient to patients, who paid less for care and were less likely to miss work in order to participate in DOTS. Clearly defined roles and expectations and frequent communication are essential to success. An institution such as a non-profit hospital can serve as an effective intermediary between the government DOTS programme and private practitioners.

Adolescent↗

Rates and risk factors for discontinuation of rifampicin.

SETTING: All patients with culture-confirmed, rifampin-susceptible Mycobacterium tuberculosis diagnosed during a 20-month period in New York City, who were started on a rifampin-containing regimen and received > or =60 days of treatment. OBJECTIVE: To identify rates of and reasons for rifampin discontinuation. DESIGN: Retrospective case-control study using surveillance data and medical record reviews. Discontinuation due to thrombocytopenia, creatinine >2.0 mg/dl, bilirubin >2.0 mg/dl or severe reactions (generalized rash, persistent drug fever, or severe interference with methadone metabolism) were defined as appropriate for discontinuation of rifampin. All other reactions were classified as inappropriate. RESULTS: Of 3,520 patients, rifampin was discontinued in 68 (1.9%); of these, 57% had rifampin discontinued unnecessarily. Treatment by an inexperienced provider (adjusted odds ratio [ORadj] 4.0; 95% confidence interval [CI] 1.9-8.5), race (ORadj 3.1; 95%CI 1.4-6.9), history of previous treatment (ORadj 4.8; 95%CI 1.9-12.5), and history of methadone drug treatment (ORadj 12.6; 95%CI 5.3-29.9) were all associated with inappropriate rifampin discontinuation. CONCLUSION: True intolerance was rare, even among those patients infected with the human immunodeficiency virus. Most patients with minor reactions can successfully complete treatment with rifampin, particularly if managed by a physician experienced in the treatment of tuberculosis.

Adolescent↗

The status and prospects of tuberculosis control in India.

SETTING: India, where much of the global strategy for tuberculosis control was established, but where, every year, there are an estimated 2 million cases of tuberculosis. OBJECTIVE: To describe the policies, initial results, and lessons learned from implementation of a Revised National Tuberculosis Control Programme using the principles of DOTS (Directly Observed Treatment, Short-course). DESIGN: A Revised National Tuberculosis Control Programme (RNTCP) was designed and implemented starting in 1993. With funding from the Government of India, State Governments, the World Bank and bilateral donors, regular supply of drugs and logistics was ensured. Persons with chest symptoms who attend health facilities are referred to microscopy centres for diagnosis. Diagnosed cases are categorized as per World Health Organization guidelines, and treatment is given by direct observation. Systematic recording and cohort reporting is done. RESULTS: From October 1993 through mid-1999, 146,012 patients were put on treatment in the programme. The quality of diagnosis was improved, with the ratio of smear-positive to smear-negative patients being maintained at 1:1. Case detection rates varied greatly between project sites and correlated with the percentage of patients who were smear-positive among those examined for diagnosis, suggesting heterogeneous disease rates. Treatment success was achieved in 81% of new smear-positive patients, 82% of new smear-negative patients, 89% of patients with extra-pulmonary tuberculosis, and 70% of re-treatment patients. CONCLUSION: The RNTCP has successfully treated approximately 80% of patients in 20 districts of 15 states of India. Treatment success rates are more than double and death rates are less than a seventh those of the previous programme. Starting in late 1998, the programme began to scale up and now covers more than 130 million people. Maintaining the quality of implementation during the expansion phase is the next challenge.

Adolescent↗

Directly observed treatment, short-course (DOTS): ensuring cure of tuberculosis.

The WHO-recommended strategy for tuberculosis control is known as DOTS (Directly Observed Treatment, Short-course). Of importance here are description of WHO recommendations for tuberculosis control, of the scientific basis for these recommendations, and of outcomes in areas which have implemented these recommendations. Standardized definitions and reporting formats allow for systematic analysis of the quality of diagnosis and treatment, including international comparisons. As of 1999, more than 110 countries are implementing the DOTS strategy. Quality of both diagnosis and treatment are markedly better than in previous programmes. In DOTS areas, a majority of adult patients have smear-confirmed disease. Nearly 8 out of 10 patients treated in DOTS areas completed treatment and had negative smears at the end of treatment. However, less than one fourth of tuberculosis patients globally undergo treatment consistent with the principles of DOTS. The DOTS strategy for tuberculosis control allows for standardized, accurate diagnosis and effective treatment. By curing infectious patients and thereby stopping tuberculosis at the source, DOTS protects children and communities from spread of the disease. DOTS policies for diagnosis and treatment are easily adaptable to a pediatric population. India and other countries are in the process of rapid expansion of the DOTS strategy. Constructive cooperation from all sectors will be required for success of the programme.

Adult↗