Randomized controlled trial of directly observed treatment (DOT) for patients with pulmonary tuberculosis in Thailand

While directly observed treatment (DOT) has been recommended as the standard approach to tuberculosis control, empirical data on its feasibility and efficiency are still scarce. We conducted a controlled trial of DOT at 15 health care facilities at various levels of the government health care system in Thailand. A total of 836 patients diagnosed between August 1996 and October 1997 were randomly assigned to be treated either under DOT or self-supervised using monthly drug supplies (SS). Options for treatment supervisors were health staff, community members or members of the patients' families. Treatment outcomes were compared on the basis of cure, treatment-completion, default and death rates. In both study arms, treatment outcomes were improved compared to pre-study conditions. Cure and treatment-completion rates were significantly higher in the DOT cohort (76% and 84%) than in the SS group (67% and 76%). The benefits of DOT were more pronounced at district and provincial hospitals (DOT cure rate 81% vs. 69% in the SS group), while differences for patients treated at referral centres were non-significant (DOT cure rate 72% vs. 66% in the SS group). No significant differences in outcomes could be observed between patient groups receiving DOT under the various options for treatment supervisors. DOT appears especially suited for treatment at decentralized facilities. While a general focus on programme performance can improve outcomes, DOT provides significant additional benefits. If basic conditions are met, a DOT strategy can be tailored to country-specific conditions by exploring multiple observation options, without decreasing its effectiveness.     

Directly observed therapy and treatment completion for tuberculosis in the United States: is universal supervised therapy necessary?

OBJECTIVES: This study examined the relationship between directly observed therapy and treatment completion rates in the years before and after infusion of federal funding for tuberculosis (TB) control in 1993. METHODS: An ecological study of estimated directly observed therapy rates and 12-month treatment completion rates from 1990 through 1994 was undertaken for TB control programs in all 25 cities and counties across the nation with 100 or more incident TB cases in any year from 1990 to 1993. Three cohorts were formed: high treatment completion, intermediate completion, and low completion. RESULTS: In 1990, the median 12-month treatment completion rate was 80% for the entire study population, with a median estimated directly observed therapy rate of 16.8%. By 1994, those rates had increased to 87% and 49.4%, respectively, and increases were shown in all 3 cohorts. CONCLUSIONS: Directly observed therapy has had a marked impact on treatment completion rates in jurisdictions with historically low rates. But TB treatment completion rates of more than 90% can be attained with directly observed therapy rates far lower than those proposed by advocates of universal supervised therapy.     

Directly observed highly active antiretroviral therapy for HIV-infected children in Cambodia

Antiretroviral medications are becoming available for HIV-infected children in resource-limited settings. Maryknoll, an international Catholic charity, provided directly observed antiretroviral therapy to HIV-infected children in Phnom Penh, Cambodia. Child care workers administered generic antiretroviral drugs twice daily to children, ensuring adherence. Treatment began with 117 late-stage HIV-infected children; 22 died of AIDS during the first 6 months. The rest were treated for at least 6 months and showed CD4 count increases comparable to those achieved in US and European children. Staffing cost for this program was approximately US $5 per child per month, or 15% more than the price of the medications. Drug toxicities were uncommon and easily managed. Directly observed antiretroviral therapy appears to be a promising, low-cost strategy for ensuring adherent treatment for HIV-infected children in a resource-limited setting.     

Costs and cost-effectiveness of different DOT strategies for the treatment of tuberculosis in Pakistan. Directly Observed Treatment

An economic study was conducted alongside a clinical trial at three sites in Pakistan to establish the costs and effectiveness of different strategies for implementing directly observed treatment (DOT) for tuberculosis. Patients were randomly allocated to one of three arms: DOTS with direct observation by health workers (at health centres or by community health workers); DOTS with direct observation by family members; and DOTS without direct observation. The clinical trial found no statistically significant difference in cure rate for the different arms. The economic study collected data on the full range of health service costs and patient costs of the different treatment arms. Data were also disaggregated by gender, rural and urban patients, by treatment site and by economic categories, to investigate the costs of the different strategies, their cost-effectiveness and the impact that they might have on patient compliance with treatment. The study found that direct observation by health centre-based health workers was the least cost-effective of the strategies tested (US dollars 310 per case cured). This is an interesting result, as this is the model recommended by the World Health Organization and International Union against Tuberculosis and Lung Disease. Attending health centres daily during the first 2 months generated high patient costs (direct and in terms of time lost), yet cure rates for this group fell below those of the non-observed group (58%, compared with 62%). One factor suggested by this study is that the high costs of attending may be deterring patients, and in particular, economically active patients who have most to lose from the time taken by direct observation. Without stronger evidence of benefits, it is hard to justify the costs to health services and patients that this type of direct observation imposes. The self-administered group came out as most cost-effective (164 dollars per case cured). The community health worker sub-group achieved the highest cure rates (67%), with a cost per case only slightly higher than the self-administered group (172 dollars per case cured). This approach should be investigated further, along with other approaches to improving patient compliance.     

Barriers to care seeking in directly observed therapy short-course (DOTS) clinics and tuberculosis control in southern Nigeria: a qualitative analysis

An understanding of the socioeconomic and cultural realities of persons infected with tuberculosis (TB) in communities is important to re-strategizing control programs because these realities often come as constraints to the use of the directly observed therapy short-course (DOTS) in Nigeria. In-depth interviews and focus group discussion were used to study barriers to attendance at DOTS clinics for both prompt diagnosis and treatment of smear positive cases in Nigerian communities. A number of common and interrelated factors form barriers to use of DOTS clinics. These include perceived causes of the infection, for example witchcraft, that mitigate against an orthodox solution to TB and thereby affect perceived efficacy of DOTS. Another factor is perceived high cost in resource poor settings. Facility staff were noted to have demanded money from patients in spite of the fact that DOTS is advertised as free treatment. Furthermore, community members complain of the hostile attitude of health staff toward poor people as a barrier to community use of the facilities. It follows, therefore, that the attitude of health workers must be addressed if community members will use the DOTS clinics.     

Community-based treatment of advanced HIV disease: introducing DOT-HAART (directly observed therapy with highly active antiretroviral therapy).

In 2000, acquired immunodeficiency syndrome (AIDS) overtook tuberculosis (TB) as the world's leading infectious cause of adult deaths. In affluent countries, however, AIDS mortality has dropped sharply, largely because of the use of highly active antiretroviral therapy (HAART). Antiretroviral agents are not yet considered essential medications by international public health experts and are not widely used in the poor countries where human immunodeficiency virus (HIV) takes its greatest toll. Arguments against the use of HAART have mainly been based on the high cost of medications and the lack of the infrastructure necessary for using them wisely. We re- examine these arguments in the setting of rising AIDS mortality in developing countries and falling drug prices, and describe a small community-based treatment programme based on lessons gained in TB control. With the collaboration of Haitian community health workers experienced in the delivery of home-based and directly observed treatment for TB, an AIDS-prevention project was expanded to deliver HAART to a subset of HIV patients deemed most likely to benefit. The inclusion criteria and preliminary results are presented. We conclude that directly observed therapy (DOT) with HAART, "DOT-HAART", can be delivered effectively in poor settings if there is an uninterrupted supply of high-quality drugs.     

A novel approach to directly observed therapy for tuberculosis in an HIV-endemic area

OBJECTIVES: This study evaluated a novel approach to the delivery of directly observed therapy (DOT) for tuberculosis in Haiti. METHODS: A total of 194 patients (152 HIV seropositive, 42 HIV seronegative) received daily unsupervised triple-drug therapy for 4 to 8 weeks, followed by twice-weekly 2-drug therapy for the remainder of the 6-month period. DOT was deferred until initiation of the twice-weekly phase. RESULTS: A total of 169 of 194 patients (87.1%) completed the 6-month course. The program of deferred DOT had an effectiveness of 85%. Overall cost was reduced by approximately 40%. CONCLUSIONS: Flexible approaches to DOT, integrating behavioral knowledge, cost considerations, and practicality may improve completion rates and program effectiveness.     

Tuberculosis, HIV disease, and directly observed therapy.

Directly observed therapy (DOT) to enable completion of antituberculous therapy works. DOT is largely responsible for the recent improvement in tuberculosis case rates in New York City. Despite this favorable trend, the factors of significant HIV disease rates and of multidrug resistant forms of tuberculosis bacteria in the population are of grave concern. Therefore, in addition to DOT other means of preventing tuberculosis spread should be encouraged. These include directly observed preventive therapy (DOPT) programs, use of masks, improved ventilation in crowded settings such as homeless shelters, and ultraviolet light germicidal irradiation of upper room air in such locations.     

School-based tuberculosis testing and treatment program: comparing directly observed preventive therapy with traditional preventive therapy.

A high-school-based health center instituted a tuberculosis testing and treatment program. Compliance of purified protein derivative (PPD) positive students with isonicotine hydrazine (INH) preventive therapy was compared for two groups of students: those in directly observed preventive therapy (DOPT) and those in traditional therapy. Four hundred thirty six students were tested and 429 returned for a reading: 209 (49 percent) students had a positive PPD test. The rate of positivity did not vary by age, sex, or years in the United States. There was no relationship between bacille Calmette-Guérin (BCG) vaccination and rate of positivity or mean size of induration. The compliance rate for all courses of DOPT was significantly higher (54 percent) than that for traditional therapy (26 percent). The compliance rates for the first and second attempts to complete a course of DOPT was 71 percent. Completion of therapy did not differ by age, sex, or years in the United States. Haitian students completed therapy more often than students from Jamaica. We believe it is effective and efficient to base tuberculosis testing and treatment with DOPT in the school setting.     

Implications of directly observed therapy in tuberculosis control measures among IDUs.

Tuberculosis (TB) is a rapidly growing problem among injecting drug users (IDU), especially those infected with human immunodeficiency virus. The authors review IDUs'' responses to current TB control strategies and discuss the implications of their findings for the proposed implementation of directly observed therapy (DOT), a method for ensuring that patients take prescribed medication. Field workers carried out 210 ethnographic interviews with 68 IDUs in a Brooklyn, NY, community during 1990-93. Case studies suggested that many IDUs are uninformed about TB and often misinformed about their personal TB status. Ethnographic interviews and observations indicated that the threat of TB-related involuntary detainment may lead IDUs to avoid TB diagnostic procedures, treatment for TB, or drug abuse treatment, and to avoid AIDS outreach workers and other health-related services. IDUs who tested positive for the purified protein derivative (PPD) of TB sometimes have left hospitals before definitive diagnoses were made, because of a perceived lack of respectful treatment, fear of detention, or lack of adequate methadone therapy to relieve the symptoms of withdrawal from drugs. Current TB diagnosis and treatment systems are, at best, inadequate. The threat of TB-related detention discourages some IDUs from seeking any type of health care. There is an urgent need to educate IDUs about TB and to educate and sensitize health care providers about the lifestyles of IDUs. DOT may help in servicing this difficult-to-serve population, particularly if techniques are incorporated that have been developed for other successful public health interventions for IDUs.