Practice of directly observed treatment (DOT) for tuberculosis in southern Thailand: comparison between different types of DOT observers.

SETTING: A government health system in southern Thailand where the directly observed treatment, short-course (DOTS) strategy has been implemented. OBJECTIVE: To compare the practice of actual directly observed treatment (DOT) and the observer sustainability for different types of observer. METHODS: During 1999-2000, 411 patients with new smear-positive pulmonary tuberculosis were followed up. The patients and/or their observers were interviewed about the presence of any person with the patient during drug intake and the practice of watching the patient swallowing the medicine (actual DOT). Data were recorded monthly and analysed by Cox and logistic regression models. RESULTS: For health personnel (HP), community member (CM), and family member (FM) observers, the proportions who did not practise actual DOT were respectively 11%, 23%, and 35%, and the proportions who changed to no observer or self administration were respectively 11%, 1%, and 2%, during the first 9 months of treatment. Health personnel had the lowest risk of not practising actual DOT (odds ratio HP/FM 0.1, 95%CI 0.1-0.2; CM/FM 0.9, 95%CI 0.5-1.6) but the highest risk for change to self administration. CONCLUSION: To increase the coverage of actual DOT, strategies are needed to maintain health personnel as the DOT observers and to promote actual DOT among family member observers.     

Review series: the politics of TB: the politics, economics and impact of directly observed treatment (DOT) in India

India harbors approximately one-third of the world's tuberculosis cases. The disease being multi-factorial; various political, social and economic factors play pivotal roles in causation and control. The country's policy-makers, via the Revised National Tuberculosis Programme (RNTCP), have embraced DOTS, i.e. Directly Observed Treatment; short course, as a means of combating the disease. Today, a decade after being launched, the DOTS programme in India is the largest in the world. The achievements of the programme have been significant in reaching out to the millions and having impressive cure rates, but the disease is far from eradicated. Social taboos, economic obstacles, and deficient infrastructure are impediments that hamper the success of the programme. With multidrug-resistant TB and HIV co-infection complicating the management of TB; the task has become more daunting. In a country as heterogeneous as India, novel holistic strategies that address individual needs will have to be developed to successfully curb the spread of the disease in the future.     

Cost-effectiveness analysis of directly observed therapy for patients with tuberculosis at low risk for treatment default.

To determine the incremental cost of directly observed therapy (DOT) for patients with tuberculosis at low risk for treatment default, we applied a model of DOT effectiveness to 1,377 low-risk patients in California during 1995. The default rate for this cohort, which consisted of those with no recent history of substance abuse, homelessness, or incarceration, was 1.7%. The model predicted that DOT and self-administered therapy (SAT) cured 93.1 and 90.8% of these patients, respectively. DOT would initially cost $1.83 million more than SAT, but avert $569,191 in treatment cost for relapse cases and their contacts, for a net incremental cost of $1.27 million ($919 per patient treated), or $40,620 per additional case cured. The cost-effectiveness of DOT was sensitive to the default rate and relapse rate after completing SAT. DOT would generate cost savings only when the default and relapse rates were more than 32.2 and 9.2%, respectively. Given the low default rate and resulting high incremental cost of DOT, provision of DOT to low-risk patients in California should be evaluated in the context of resource availability, competing program priorities, and program success in completing self-administered therapy with a low relapse rate.     

Effectiveness of urban community volunteers in directly observed treatment of tuberculosis patients: a field report from Haryana, North India.

A tuberculosis (TB) unit covering a population of 600000 in Gurgaon District of Haryana State, India, where the DOTS-based RNTCP has been implemented since April 2000. Treatment success rate, as recorded in the TB register, of new sputum smear-positive patients receiving directly observed treatment (DOT) from community volunteers was comparable with that of patients receiving DOT from government health workers (78% vs. 77%). The proportion of patients with community volunteers increased significantly with time (13% in 2000 to 25% in 2002), even in the absence of financial incentives. In this model of community volunteer involvement in an urban TB control programme, the primary responsibility for returning late patients to treatment was with the staff of the District TB Centre.     

Usefulness of directly observed therapy (DOT) during hospitalization as DOTS in Japanese style

Many patients with smear positive tuberculosis were hospitalized during the initial phase of chemotherapy but DOT was not applied to patients with tuberculosis in Japan. We tried randomized clinical study to evaluate the usefulness of DOT during admission. 135 culture positive TB patients were administered by DOT and 124 culture positive TB patients were self-administered during admission. There was no significant difference between 2 groups in the clinical background factors, treatment and the incidence of adverse reactions. Treatment completion rate was 94.1% in DOT group and 87.9% in non-DOT group. Default rate was significantly lower in DOT group (4.4%) than in non-DOT group (11.3%). We concluded that "DOT during admission" was useful to improve the outcome of chemotherapy for tuberculosis and it is preferable to apply DOT throughout treatment course for patients with tuberculosis in Japan.     

Using treatment failure under effective directly observed short-course chemotherapy programs to identify patients with multidrug-resistant tuberculosis.

SETTING: Public ambulatory care centers in three districts of northern metropolitan Lima, Peru. OBJECTIVE: To document drug resistance patterns of isolates of Mycobacterium tuberculosis from patients identified as treatment failures under a model tuberculosis (TB) control program based on directly observed, short-course chemotherapy (DOT-SCC). DESIGN: Case series. RESULTS: In a referred, consecutive sample of 173 patients identified as treatment failures on DOT-SCC, 160 (92.5%) had culture-positive TB. Of those 160, 150 (93.8%) had active, pulmonary multidrug-resistant TB (MDR-TB, resistance to at least isoniazid [INH] and rifampicin [RIF]). Sixty of the 150 (40.0%) had isolates resistant to at least INH, RIF, ethambutol (EMB) and pyrazinamide (PZA), the initial first-line empiric treatment regimen used locally. Forty-four (29.3%) had isolates resistant to at least INH, RIF, EMB, PZA and streptomycin (SM), the first retreatment regimen. This series of patients had isolates resistant to a mean of 4.5 of the ten drugs tested. The local profile of multidrug resistance is very different from that obtained from national data from Peru. CONCLUSION: In this setting, treatment failure on DOT-SCC is strongly predictive of active MDR-TB. Because of existing local drug resistance patterns in northern Lima, 89.3% of MDR-TB patients identified as treatment failures will receive ineffective therapy with two or fewer secondary TB drugs if they are given the five-drug empiric retreatment regimen endorsed by the World Health Organization. Further short-course chemotherapy for these patients would only serve to amplify ominous existing drug resistance patterns.     

Twice-weekly, directly observed treatment for HIV-infected and uninfected tuberculosis patients: cohort study in rural South Africa.

OBJECTIVE: To determine the effectiveness of twice-weekly directly observed therapy (DOT) for tuberculosis (TB) in HIV-infected and uninfected patients, irrespective of their previous treatment history. Also to determine the predictive value of 2-3 month smears on treatment outcome. METHODS: Four hundred and sixteen new and 113 previously treated adults with culture positive pulmonary TB (58% HIV infected, 9% combined drug resistance) in Hlabisa, South Africa. Daily isoniazid (H), rifampicin (R), pyrazinamide (Z) and ethambutol (E) given in hospital (median 17 days), followed by HRZE twice a week to 2 months and HR twice a week to 6 months in the community. RESULTS: Outcomes at 6 months among the 416 new patients were: transferred out 2%; interrupted treatment 17%; completed treatment 3%; failure 2%; and cured 71%. Outcomes were similar among HIV-infected and uninfected patients except for death (6 versus 2%; P = 0.03). Cure was frequent among adherent HIV-infected (97%; 95% CI 94-99%) and uninfected (96%; 95% CI 92-99%) new patients. Outcomes were similar among previously treated and new patients, except for death (11 versus 4%; P = 0.01), and cure among adherent previously treated patients 97% (95% CI 92-99%) was high. Smear results at 2 months did not predict the final outcome. CONCLUSION: A twice-weekly rifampicin-containing drug regimen given under DOT cures most adherent patients irrespective of HIV status and previous treatment history. The 2 month smear may be safely omitted. Relapse rates need to be determined, and an improved system of keeping treatment interrupters on therapy is needed. Simplified TB treatment may aid implementation of the DOTS strategy in settings with high TB caseloads secondary to the HIV epidemic.     

Treatment outcome of tuberculosis patients under directly observed treatment in Addis Ababa,Ethiopia

BackgroundTuberculosis is one of the leading causes of mortality among infectious diseases worldwide. For effective tuberculosis control, it is a pre-requisite to detect the cases as early as possible, and to ensure that the tuberculosis patients complete their treatment and get cured. However, in many resource-constrained settings treatment outcome for tuberculosis has not been satisfactory.ObjectiveThe aim of the study was to assess the treatment outcome of tuberculosis patients and investigate the association of demographic and clinical factors with treatment success of patients enrolled in Directly Observed Treatment Short Course program in government owned health centers over the course of five consecutive years in Addis Ababa, Ethiopia.MethodsA register based historical cohort study covering the period of July 2004 to June 2009 was conducted to determine the treatment outcome of Directly Observed Treatment Short Course in government owned health centers in Addis Ababa. Sex and age of tuberculosis patients, health center at which the patient was treated, year of treatment, type of tuberculosis for which the patient was treated, type of treatment offered to the patient, follow-up status and documented treatment outcome were extracted from the Directly Observed Treatment Short Course clinics of three randomly selected health centers.ResultRecords of 6450 registered tuberculosis patients (n = 3147 males and 3433 females) were included in this document review. Of these patients 18.1% were reported as being cured, 64.6% were documented as treatment completed, 3.7% died during follow-up, 5.1% were reported as defaulters, 0.4% were documented as treatment failure and 8.2% were transferred out to another health institution. Treatment center and year of enrollment were significantly associated with treatment success.ConclusionYear of enrollment and treatment center were significantly associated with treatment success. Although the overall treatment success obtained in this study is in line with the World Health Organization (WHO) target, continuous follow-up of patients with frequent supportive supervision during the course of treatment, and further investigate the cause for the observed difference in treatment success across treatment centers are recommended.     

Effectiveness of community-based directly observed treatment for tuberculosis in an urban setting in Tanzania: a randomised controlled trial.

SETTING: An urban district in Dar es Salaam city with a high tuberculosis (TB) caseload. OBJECTIVE: To evaluate the effectiveness of community-based direct observation of treatment (DOT) using guardians and former TB patients compared to hospital-based DOT in an urban setting in Tanzania. DESIGN: Unblinded randomised control trial conducted in five sites under operational conditions in Temeke district. No changes to existing treatment delivery were made other than randomisation. The main outcome measure was treatment success. Analysis was by intention to treat. FINDINGS: A total of 587 new tuberculosis patients were enrolled. Among enrolled patients, 260 were assigned to community-based DOT using guardians and former TB patients and 327 to health facility-based DOT. Both DOT options gave similar treatment outcomes. Treatment success rate among patients under community and health facility-based DOT were 85% and 83%, respectively (OR 1.17, 95%CI 0.75-1.83). CONCLUSION: Community-based DOT is as effective as health facility-based DOT and can achieve good treatment outcomes, even in countries with well functioning National Tuberculosis Programmes.     

Emergence of multidrug-resistant tuberculosis in a community-based directly observed treatment programme in rural South Africa.

OBJECTIVE: Although little studied in developing countries, multidrug-resistant tuberculosis (MDR-TB) is considered a major threat. We report the molecular epidemiology, clinical features and outcome of an emerging MDR-TB epidemic. METHODS: In 1996 all tuberculosis suspects in the rural Hlabisa district, South Africa, had sputum cultured, and drug susceptibility patterns of mycobacterial isolates were determined. Isolates with MDR-TB (resistant to both isoniazid and rifampicin) were DNA fingerprinted by restriction fragment length polymorphism (RFLP) using IS6110 and polymorphic guanine-cytosine-rich sequence-based (PGRS) probes. Patients with MDR-TB were traced to determine outcome. Data were compared with results from a survey of drug susceptibility done in 1994. RESULTS: The rate of MDR-TB among smear-positive patients increased six-fold from 0.36% (1/275) in 1994 to 2.3% (13/561) in 1996 (P = 0.04). A further eight smear-negative cases were identified in 1996 from culture, six of whom had not been diagnosed with tuberculosis. MDR disease was clinically suspected in only five of the 21 cases (24%). Prevalence of primary and acquired MDR-TB was 1.8% and 4.1%, respectively. Twelve MDR-TB cases (67%) were in five RFLP-defined clusters. Among 20 traced patients, 10 (50%) had died, five had active disease (25%) and five (25%) were apparently cured. CONCLUSIONS: The rate of MDR-TB has risen rapidly in Hlabisa, apparently due to both reactivation disease and recent transmission. Many patients were not diagnosed with tuberculosis and many were not suspected of drug-resistant disease, and outcome was poor.     

Lack of toxicity from concomitant directly observed disulfiram and isoniazid-containing therapy for active tuberculosis.

We retrospectively evaluated the use of disulfiram among alcoholic patients being treated for active tuberculosis. There were 13 alcoholics treated with disulfiram, 105 alcoholics not on disulfiram, and 249 non-alcoholics. Rates of toxicity were higher among alcoholics than among non-alcoholics (58% vs. 32%), but there was no difference between alcoholics taking and those not taking disulfiram (61% vs. 57%). There were no neurological side effects in the disulfiram group. Disulfiram appeared to be safe when added to intermittent, directly observed isoniazid-containing tuberculosis treatment, and was useful in managing complications of alcohol abuse. However, the small number of patients on disulfiram limits the strength of this negative finding.     

Treatment costs of directly observed therapy and traditional therapy for Mycobacterium tuberculosis: a comparative analysis.

OBJECTIVE: Treatment of tuberculosis is a time-consuming and expensive process, often complicated by patient non-adherence. Directly observed therapy (DOT), an out-patient management strategy designed to ensure adherence, is not widely used because it is perceived to be too expensive. This study compared costs of tuberculosis treatment in DOT to the same factors in traditional therapy. DESIGN: A retrospective economic evaluation of 659 tuberculosis cases was reported to a major metropolitan county public health department between 1980 and 1994. Out-patient costs, in-patient costs and the cost impact of relapse and acquired resistance were estimated in 1995 dollars. RESULTS: Treatment costs were lower with DOT: $15,670 per case for in-patient care and $700 per case for out-patient care (P < 0.001). These cost differences resulted from shorter therapy duration (334 vs 550 days), fewer patient hospitalizations (58 vs 75%) and shorter hospital stays (26 vs 55 days per hospitalized patient). Relapse or acquired resistance occurred in 10.9% of patients and accounted for 35.7% of cost with traditional therapy, as compared to 1.2% of patients and 6.0% of cost with observed therapy. CONCLUSIONS: Directly observed therapy is less costly than traditional therapy.     

The effects of increasing incentives on adherence to tuberculosis directly observed therapy.

SETTING: Six New York State Department of Health tuberculosis (TB) directly observed therapy (DOT) programs in public, private and community facilities in New York City. OBJECTIVE: A key feature of the TB DOT program was provision of incentives to motivate patients and increase adherence to therapy. The study hypothesis was that adherence will improve as the value of incentives increases and bonuses are added in a schedule of increasing rewards. DESIGN: The study population consisted of 365 patients in six inner city TB DOT programs. Interviews, clinical data and attendance records for 3+ years were analyzed. RESULTS: Patients who adhered (attending 80% of prescribed DOT visits each month of treatment) and those who did not were similar on seven demographic factors (e.g., age and sex), but were significantly different on clinical and social variables. Previous TB, resistance to rifampin, human immunodeficiency virus infection, psychiatric illness, homelessness, smoking and drug use were related to non-adherence. High adherence was significantly associated with fewer months in treatment (P < 0.016). Logistic regression showed that the odds that a patient would adhere to therapy were greater with increased incentives. Odds of adherence were significantly lower with rifampin resistance and psychiatric illness. CONCLUSION: Increasing incentives is associated with improved adherence to therapy in inner city TB populations.     

Risk factors for defaulting from anti-tuberculosis treatment under directly observed treatment in Hong Kong.

OBJECTIVE: To identify risk factors for defaulting from anti-tuberculosis treatment. SETTING: Directly observed treatment in Hong Kong Government chest clinics. DESIGN: Defaulters were recruited from a cohort of tuberculosis patients registered from 1 January to 31 March 1999. Three controls per case, matched for age and sex, were selected randomly from the cohort. Patient factors, initial tuberculosis characteristics and treatment-related variables were collected by review of medical records. RESULTS: On matching 102 defaulters and 306 controls, a logistic risk model of default that considered patient factors, initial disease characteristics and treatment-related factors identified seven risk factors: current smoking (OR 3.00, 95% CI 1.41-6.39), past TB with default (OR 6.23, 95% CI 1.95-19.91), poor initial adherence (OR 117.21, 95% CI 13.52-1015.92), fair initial adherence (OR 11.02, 95% CI 2.15-56.43), unknown initial adherence (OR 6.59, 95% CI 3.47-12.49), treatment side effects (OR 13.30, 95% CI 3.23-54.79), and subsequent hospitalisation (OR 0.27, 95% CI 0.11-0.67). Its predictive power was 85%. Another model that considered only factors on registration for treatment gave a lower predictive power of 70%. CONCLUSIONS: Treatment default could be predicted fairly accurately by considering patient and treatment-related factors.