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.     

A multi-state outbreak of tuberculosis among members of a highly mobile social network: implications for tuberculosis elimination.

SETTING: Baltimore, Maryland. OBJECTIVE: To describe a tuberculosis (TB) outbreak among a highly mobile population and the efforts required to control it. DESIGN: Epidemiologic outbreak investigation. RESULTS: Between June 1998 and January 2000, 20 TB outbreak cases were identified, of which 18 were culture-confirmed. Seventeen isolates of Mycobacterium tuberculosis had an identical 11-band DNA fingerprint; another isolate had one additional band and was considered a match. Two cases were diagnosed in New York City; another patient lived primarily in Atlanta, but was diagnosed in Baltimore. Persons in the outbreak were predominantly young (median age 24 years), black, male, infected with the human immunodeficiency virus (HIV), and gay, transvestite or transsexual. Activities common among many TB cases included attending two nightclubs, membership in one of three social 'Houses', attending balls or pageants in East Coast cities, marijuana use, and prostitution. Community outreach, extended contact tracing, DNA fingerprinting, directly-observed therapy, and expanded use of preventive therapy were utilized to assess and control the outbreak. During the outbreak period the Baltimore City TB rate declined by 10%. However, additional public health personnel were required to control the outbreak, resulting in a 17% increase in TB clinic staff. CONCLUSION: As TB rates decline, remaining cases are likely to occur in difficult-to-reach populations. Increased resources per case of TB treated will be required to eliminate TB.     

On the differences in attitude and awareness of clinical doctors, health administrators and other health workers to tuberculosis treatment in Japan and the US

Peculiarity of TB treatment in Japan is a higher rate and duration of hospitalization than in other developed countries. Improvement of the TB control policy in Japan necessitates reexamination of the issue of treatment policy, which requires consideration of recognition and understanding of the concept of TB infection, human rights and the protection of patients as well as the society. Therefore, this study aims at clarifying and analyzing the differences in TB treatment policies in Japan and the US. For the US, a questionnaire was sent to TB Directors of states and large cities in order to analyze TB control policies. Moreover, the author attended the NTCA meeting held in Chicago to interview 16 TB Directors. In Japan, the author sent the same questionnaire translated into Japanese to medical doctors in 54 National TB sanatoria. The hospitalization rates of new smear-positive TB patients were 100% (median) in Japan and 59% in the US. The periods of hospitalization of these patients were 150 days (median) in Japan and 10 days in the US. The total expenses of TB diagnosis and treatment per capita were approximately US $25,000 and 20,000, respectively in Japan and the US. If the DOT strategy were applied to the new smear-positive TB cases in Japan, those total expenses would be reduced to half. On the measures against the TB patients who pose a threat to the public, the US has the series of TB control strategies which contain the reporting system, home isolation, incarceration and penalties for violation, while Japan has only the strategy of hospitalization. The TB policies of Japan in future would need to focus more selectively and carry out thoroughly as seen in the US. The recommended TB policies for Japan obtained from this study are to set TB policies adapted to regional characteristics and to review the strategy against patients posing a threat to the public.     

Comparison of cost-effectiveness of tuberculosis screening of close contacts and foreign-born populations

Although tuberculosis (TB) screening of immigrants has been conducted for over 50 yr in many industrialized countries, its cost- effectiveness has never been evaluated. We prospectively compared the yield and cost-effectiveness of two immigrant TB screening programs, using close-contact investigation and passive case detection. Study subjects included all immigration applicants undergoing radiographic screening, already arrived immigrants requiring surveillance for inactive TB, and close contacts of active cases resident in Montreal, Quebec, Canada, who were referred from June 1996 to June 1997 to the Montreal Chest Institute (MCI), a referral center specializing in respiratory diseases. For all subjects seen, demographic data, investigations, diagnoses, and therapy were abstracted from administrative data bases and medical charts. Estimated costs of detecting and treating each prevalent active case and preventing future active cases, based on federal and provincial health reimbursement schedules, were compared with the costs for passively diagnosed cases of active TB. Over a period of 1 yr, the three programs detected 27 cases of prevalent active TB and prevented 14 future cases. As compared with passive case detection, close-contact investigation resulted in net savings of $815 for each prevalent active case detected and treated and of $2,186 for each future active case prevented. The incremental cost to treat each case of prevalent active TB was $39,409 for applicant screening and $24,225 for surveillance, and the cost of preventing each case was $33,275 for applicants and $65,126 for surveillance. Close-contact investigation was highly cost effective and resulted in net savings. Immigrant applicant screening and surveillance programs had a significant impact but were much less cost effective, in large part because of substantial operational problems.     

City tuberculosis control coordinators' perspectives of patient adherence to DOT in S?o Paulo State, Brazil, 2005.

SETTING: Thirty-six priority cities in S?o Paulo State, Brazil, with a high incidence of tuberculosis (TB) cases, deaths and treatment default. OBJECTIVE: To identify the perspectives of city TB control coordinators regarding the most important components of adherence strategies adopted by health care teams to ensure patient adherence in 36 priority cities in the State of S?o Paulo, Brazil. DESIGN: Qualitative research with semi-structured interviews conducted with the coordinators of the National TB Control Programme involved in the management of TB treatment services in the public sector. RESULTS: The main issues thought to influence adherence to directly observed treatment (DOT) by coordinators include incentives and benefits delivered to patients, patient-health care worker bonding and comprehensive care, the encouragement given by others to follow treatment (family, neighbours and health professionals), and help provided by health professionals for patients to recover their self-esteem. CONCLUSION: The main aspects mentioned by city TB control coordinators regarding patient adherence to treatment and to DOT in S?o Paulo are improvements in communications, relationships based on trust, a humane approach and including the patients in the decision-making process concerning their health.     

Community DOT for tuberculosis in a Brazilian favela: comparison with a clinic model.

SETTING: Rio de Janeiro City, Brazil. OBJECTIVE: To compare community-based directly observed treatment (DOT) for tuberculosis (TB), using community health workers (CHWs), with clinic-based DOT. DESIGN: In a longitudinal study in a cohort of TB patients in a region of Rio de Janeiro city, we evaluated treatment modalities and outcomes in 1811 patients diagnosed with TB between 1 January 2003 and 30 December 2004. Patients were offered DOT when they presented to out-patient clinics for an initial diagnosis. DOT was provided in the clinic or in the community, using CHWs, for patients living in a large favela. Outcomes of treatment were assessed using treatment registry databases. RESULTS: Of the 1811 TB patients, 1215 (67%) were treated under DOT; among these, 726 (60%) received clinic-based treatment and 489 (40%) community-based treatment. Patients offered community-based treatment were more likely to accept DOT (99%) than those offered clinic-based treatment (60%, P<0.001). Treatment success rates for new smear-positive and retreatment TB cases were significantly higher among those treated with community-based DOT compared to clinic-based DOT. CONCLUSION: We conclude that using CHWs to deliver DOT in the community may improve TB treatment outcomes in selected areas such as urban slums.     

Tuberculosis incidence, hospitalisation prevalence and mortality in Lazio, Italy, 1997-2003.

SETTING: Lazio region (5.15 million, including Rome, 2.8 million), Italy. OBJECTIVE: To monitor pulmonary tuberculosis (TB) epidemiology from 1997 to 2003. DESIGN: We used data from the mandatory National Infectious Diseases Surveillance system, the regional Hospital Information System and the regional Mortality Register. The number of prevalent pulmonary TB cases hospitalised was determined by linking notifications and hospitalisations. To estimate incidence, we excluded all cases with previous TB hospitalisations since 1995, and those reported as a secondary diagnosis in the Hospital Information System. Mortality rates were ascertained from mortality records reporting TB as the principal cause of death. RESULTS: The record linkage identified 4885 incident cases, 9010 hospital prevalent cases and 217 deaths. Incidence decreased from 15/100000 in 1997 to 11 in 2003, and consistent decreases were also observed in hospitalisation prevalence and mortality (P for trend <0.0005, <0.0005 and =0.063, respectively). The number of AIDS-related TB cases dropped from 85 to 49 (P < 0.0005). The number of incident cases in non-Italians increased significantly, from 171 to 267 (P < 0.0005). Notification underreporting was estimated at 39%. CONCLUSIONS: Despite a decreasing trend, TB incidence is still over 10/100000 in Lazio region. Targeted interventions for immigrant populations are essential for controlling TB.     

The results of DOTS strategy

Tuberculosis control in Japan is now on the stage of program transition since the declaration of emergency of tuberculosis in 1999. The "21st century DOTS, Japan version" has been proposed under the influence of DOTS experiences in the United States, where drastic reduction of tuberculosis was observed after the introduction of universal DOT. We cannot copy the experiences of US, considering the difference of epidemiological situation of tuberculosis, social background of TB cases and the difference of health infrastructure for TB patients. In the United States, many tuberculosis patients are treated under government health system with DOT. In Japan, TB cases are treated at clinics and hospitals under the integrated health system and public health centers mainly provide prevention services including contact examination of TB and cohort analysis of TB cases. 21st century DOTS, Japan version, is not the universal system at present but it is on the process of implementation and various kind of new activities have been tried including activities to assure the close collaboration between public health centers and clinics, and DOT activities including hospital based DOT, ambulatory intermittent DOT at pharmacies. Here are presented with various experiences both in the field of collaboration between public health centers and clinics, and in the field of DOT. Also here are presented with the calculation which shows the reduction of total cost of tuberculosis treatment by the introduction of ambulatory DOT, considering the influence of recurrence of defaulter cases which would have occurred without DOT. We consider that this symposium is the interim report of the expansion of Japanese DOTS.     

Auditing the new decentralised oral treatment regimens in Malawi.

SETTING: All 44 non-private hospitals in Malawi treating tuberculosis (TB) cases in which oral regimens were used allowing patients during the initial phase to receive directly observed treatment (DOT) from health centres or guardians at home. OBJECTIVES: A country-wide audit of the oral regimens to determine: 1) TB ward bed occupancy rates, 2) patient DOT options, 3) patients' knowledge of treatment and 4) treatment outcomes compared to those obtained with previous treatment regimens. DESIGN: Retrospective data collection using registers and treatment cards. Prospective interviews with patients. Inspections of TB wards. RESULTS: There were 1513 TB beds occupied by 807 (53%) TB patients. Over 50% of 4793 patients registered with different types of TB chose guardian-based DOT. For 266 patients with pulmonary TB the correct knowledge about total duration of treatment (45%), all three DOT options (62%) and the months for giving follow-up sputum (16%), was poor. There were differences in treatment outcomes between TB patients on oral compared with previous regimens. With oral regimens, rates of unknown outcome were high. CONCLUSION: Oral treatment regimens are associated with reduced bed occupancy rates on TB wards. However, rates of unknown outcome are increased, and TB control is therefore weakened.     

Administrative monitoring of tuberculosis treatment in Switzerland.

SETTING: Treatment of tuberculosis (TB) is critically dependent on adherence. Directly observed treatment (DOT) has been shown to be effective. OBJECTIVE: To determine operational treatment outcome using administrative treatment monitoring (ATM) to assess the need for more vigorous promotion of DOT. DESIGN: Cohort study in eastern Switzerland, where ATM was started in 2002. Bi-monthly progress forms and a treatment outcome form (after 6 months) were sent to the treating doctors. Forms not returned within 6 weeks were followed up with phone calls. RESULTS: Between 2002 and 2004, 98 (87.5%) of 112 new TB patients completed a 6-month treatment course. Eight elderly patients died of causes other than TB while on treatment, four travelled out of the region and two were lost to follow-up. Treating doctors opted for DOT in only seven cases. CONCLUSION: Given the high success rate of 87.5% in our cohort, more vigorous promotion of DOT is not a priority for TB case management in eastern Switzerland. In our setting, ATM in collaboration with the family doctors offers a valuable alternative to the more time-consuming universal DOT.     

Value of antimicrobials in the prevention and treatment of tuberculosis in the United States.

OBJECTIVE: To estimate the economic value of antimicrobials for the prevention and treatment of tuberculosis in the United States from 1954 through 1997. DESIGN: Published sources were used to estimate the burden of illness (direct medical costs, reductions in quality of life, and years of life lost) from active tuberculosis (TB) cases diagnosed between 1954 and 1997. Published literature concerning the pre-antimicrobial incidence rate and treatment of TB were extrapolated to estimate the burden of illness that would have occurred in the absence of antimicrobials. RESULTS: Between 1954 and 1997, the use of antimicrobials reduced the number of newly diagnosed cases of active TB by 32% (relative to the number that would have occurred in the absence of antimicrobials), the number of mortalities by 81%, the number of life-years lost by 87%, and the cost of medical treatment by 76%. The total financial burden of illness over this time period (including the value of lost life-years) was reduced from $894 billion (in 1997 dollars) to $128 billion. CONCLUSION: TB antimicrobials had a substantial health impact in the US from 1954 to 1997. This quantitative assessment of the economic impact of innovative biopharmaceutical products demonstrates the importance of continuing medical innovation.     

Future savings from measles eradication in industrialized countries

Estimates are made of monetary savings associated with measles eradication in seven industrialized countries. Three scenarios were studied: First, changing from the present two-dose measles-mumps-rubella (MMR) immunization schedule to one-dose of MMR; second, the use of an MMR and mumps-rubella schedule; or third, continuing the present schedule. Results show that the largest savings (US $623 million) would be achieved by changing to a one-dose MMR schedule with an assumption of a 3% discount rate and measles eradication in 2010. The smallest overall savings would result from option 3, by use of a 5% discount rate and the assumption that measles eradication occurs in 2020 ($10 million). These savings are less than previously estimated for the United States, partly because of the assumption that measles vaccines will continue to be delivered in response to possible bioterrorism threats.     

Directly observed therapy (DOT) is not the entire answer: an operational cohort analysis.

SETTING: New Jersey Medical School National Tuberculosis Center-Lattimore Clinic, a TB Clinic for an inner city population of Newark, New Jersey, USA. OBJECTIVE: Directly observed therapy (DOT) is the recommended standard of TB care. Recent reports suggest that DOT may not be any better than self-administered therapy (SAT). To quantify the impact of different levels of SAT, DOT, and active case management on outcomes of TB treatment at our location, we reviewed the outcomes of six TB patient-cohorts from Newark between 1 January 1994 and 31 December 1996. STUDY DESIGN: A retrospective cohort study of the outcomes of 343 tuberculosis patients treated during the years 1994-1996. The three treatment strategies were 1) self-administered with occasional selective directly observed therapy, 2) universal directly observed therapy alone (universal DOT), and 3) universal DOT with nurse case management (NCM). RESULTS: The first two cohorts who began treatment during the transition may have received more than one treatment strategy. However, universal DOT did not significantly improve the TB treatment completion rates of Cohort 2 over SAT therapy with selective DOT given to Cohort 1. Universal DOT with NCM, Cohorts 3, 4, 5, and 6, significantly increased the TB treatment completion rates by three to six times. A cohort-specific step-wise reduction in duration of treatment from a median of 11.6-7.5 months and an increase in completion rates from 57-81% resulted. The most desirable and optimal (shortest) duration of treatment completion coincided with the application of universal DOT combined with NCM.     

DOT in rural China: experience from a case study in Shandong Province, China.

SETTING: Four counties at varying levels of economic development in Shandong Province were sampled. All offered tuberculosis (TB) directly observed treatment (DOT) treatment at the County TB Dispensary (CTBD). OBJECTIVE: To empirically document how DOT and home visits were implemented in rural China and to shed light on whether DOT is one of the key elements through which China achieves its high cure rates for TB. DESIGN: A total of 404 rural smear-positive TB patients registered in the CTBDs were interviewed face-to-face with structured questionnaires. Village doctors and key informants from the CTBDs were also interviewed. RESULTS: The majority of TB patients in rural areas do not receive DOT from village doctors and rarely get support, such as visits as required, from the CTBDs or township health providers in Shandong, China. CONCLUSION: The lack of DOT in Shandong does not have a negative effect on TB treatment outcomes. Given that the DOTS strategy is still the core measure of TB control in China, implementation of other programme elements apart from DOT is necessary to ensure a successful TB treatment programme.     

DOT and timely treatment completion among Asian-born immigrant tuberculosis patients.

SETTING: A large urban tuberculosis (TB) control program. OBJECTIVES: To identify factors associated with directly observed therapy (DOT) participation and to quantify how early use of DOT affected treatment duration. DESIGN: A retrospective study of 731 Asian-born patients with drug-susceptible Mycobacterium tuberculosis isolates who were verified in New York City between 1993 and 1997 and completed treatment. RESULTS: Overall, 297 (41%) of 731 patients in the study participated in DOT for some or all of their TB treatment. DOT participation was significantly associated with TB disease in a pulmonary site (adjusted odds ratio [aOR] 2.85, 95% CI 1.86-4.35), more recent year of diagnosis (aOR 1.70, 95% CI 1.50-1.94) and male sex (aOR 1.86, 95% CI 1.30-2.66). Patients who received > or = 70% of their TB treatment at a health department chest clinic were also significantly more likely to participate in DOT (aOR 3.83, 95% CI 2.55-5.74). Among 297 DOT patients, those who completed treatment by 9 months received a greater amount of treatment by DOT during the first 4 months of treatment than those who took longer to complete treatment. CONCLUSION: Earlier DOT participation can lead to overall shorter treatment duration. Health care providers should encourage TB patients to participate in DOT as early as possible in their TB treatment.     

Extensive transmission of an isoniazid-resistant strain of Mycobacterium tuberculosis in Sweden.

SETTING: City of Stockholm, Sweden. BACKGROUND: The incidence of tuberculosis (TB) in Sweden increased by 40% between 2003 and 2005. The spread of a unique TB strain resistant to isoniazid (INH) contributed to this increase. OBJECTIVE: To describe outbreaks of TB caused by this single strain, elucidate possible causes for its extensive spread and identify shortcomings of the TB control programme in Sweden. RESULTS: We identified a cluster consisting of 102 culture-confirmed TB cases with identical DNA fingerprints and 26 epidemiologically related cases, not confirmed by culture, all diagnosed between 1996 and 2005. Five partly separate outbreaks of this strain were discovered. Epidemiological links were established for 56% of the culture-confirmed cases and for all cases not confirmed by culture. Three patients died while receiving treatment, four became failures and eight defaulted or were lost to follow-up. Only eight patients received directly observed treatment (DOT) up to a period of 3 months, although 40% had poor adherence. CONCLUSIONS: Shortcomings of the national TB programme were revealed. Improved contact tracing and case holding, including DOT, is crucial to reduce TB transmission in Sweden.     

The epidemiology of tuberculosis in Ottawa, Canada, 1995-2004

BACKGROUND: In Ottawa (population 774,072), active tuberculosis (TB) cases are reported to Ottawa Public Health. There has been no comprehensive local epidemiological analysis to date. We report the epidemiology of TB in Ottawa and identify areas of improvement. METHODS: We reviewed TB cases reported to the Reportable Disease Information System from 1995 to 2004 to determine epidemiological characteristics, drug resistance, use of directly observed treatment (DOT) and rates of human immunodeficiency virus (HIV) co-infection. RESULTS: A total of 584 TB cases (79% foreign-born) were analyzed (average annual incidence 7.5/100,000). Anatomical site of disease followed national trends, with 58% being pulmonary TB. DOT was applied in 49% of total cases. Culture results were available for 385 (66%) and resistance was found in 46 (12%) cases. HIV testing results were available for only 139 cases: 24% were positive. CONCLUSION: Overall, Ottawa TB rates are slightly higher than national rates, yet they reflect national trends. The surveillance data were imperfect, with poor or no recording of aboriginal origin, adverse events and treatment outcomes. Reported resistance patterns may be underestimated, as only 66% had cultures. HIV testing was underutilized. Given the high mortality with TB-HIV co-infection, testing should be routine. Correcting these limitations will improve surveillance data and TB control in the future.     

结核病和结核病/艾滋病病毒双重感染的负担与挑战:尼日利亚的案例研究

目的: 了解尼日利亚结核病与结核病/艾滋病病毒(TB/HIV)双重感染的负担和结核病综合防治措施的落实情况,以确定尼日利亚结核病防控所面临的挑战,为尼日利亚消除结核病提供参考依据。方法: 利用2010—2020年世界卫生组织的全球结核病报告数据描述尼日利亚的结核病与TB/HIV双重感染负担趋势。结果: 尼日利亚是结核病与TB/HIV双重感染高负担国家,HIV感染者结核病发病率从2010年的54/10万下降至2020年的17/10万;2020年结核病确诊患者数为13.5万例,估计发病例数为45.2万,结核病治疗覆盖率仅为30%;TB/HIV双重感染患者抗逆转录病毒治疗覆盖率从2010年的6.9%增加至2020年的26.0%;结核病成功治疗率从2010年的81%提高至2019年的88%,TB/HIV双重感染患者成功治疗率从2012年的78.9%提高至2019年的81.1%;尼日利亚结核病资金总量增加,TB/HIV项目资金变化小,从2010年的450万美元增长至2020年的540万美元。结论: 尼日利亚与2020年“终止结核病战略”的目标有很大的差距。尼日利亚要减轻并消除结核病和TB/HIV双重感染负担,必须优先考虑落实结核病综合防治措施,增加必要的结核病防治资源和经费,提高结核病诊断能力。     

Economic implications of extended-release metoprolol succinate for heart failure in the MERIT-HF trial: a US perspective of the MERIT-HF trial

BACKGROUND: The MERIT-HF trial demonstrated improved survival and fewer hospitalizations for worsening heart failure with extended-release (ER) metoprolol succinate in patients with heart failure. This study sought to estimate the economic implications of this trial from a US perspective. METHODS AND RESULTS: A discrete event simulation was developed to examine the course of patients with heart failure. Characteristics of the population modeled, probabilities of hospitalization and death with standard therapy, and risk reductions with ER metoprolol succinate were obtained from Metoprolol CR/XL Randomized Intervention Trial in Chronic Heart Failure (MERIT-HF) and evaluated in weekly cycles. Direct medical costs were estimated from US databases in 2001 US dollars. Uncertainty in inputs was incorporated and analyses were carried out to estimate events prevented total and net costs. The model predicts that ER metoprolol succinate will prevent approximately 7 deaths and 15 hospitalizations from heart failure per 100 patients over 2 years. Compared with standard therapy alone, this translates to a cost reduction between $395 and $1112 per patient, depending on whether the costs of hospitalizations for other causes are included. Savings were maintained in 90% of the simulations. CONCLUSION: This analysis predicts that the positive effect of ER metoprolol succinate on mortality and morbidity demonstrated in MERIT-HF leads to substantial savings.     

A spoonful of sugar...: improving adherence to tuberculosis treatment using financial incentives.

OBJECTIVE: To determine whether incentives increase adherence to directly observed therapy (DOT) for tuberculosis (TB) treatment. METHODS: The TB program gave a five-dollar grocery coupon for each DOT appointment kept to 55 patients who had missed at least 25% of DOT doses over a 4-week period. Treatment completion rates were compared with an historic control group of 52 patients who began treatment a year earlier, who would have been eligible for incentives but did not receive them. RESULTS: Incentive program patients were more likely than control patients to complete therapy within 32 weeks (OR 5.73, 95%CI 2.25-14.84) and 52 weeks (OR 7.29, 95%CI 2.45-22.73). CONCLUSION: Patient incentives can increase adherence to DOT in TB programs.