Basics of the program

What is the program? What problem does it target?

Tuberculosis (TB) is an infectious disease that frequently results in death (about 2/3 of the time for the more severe form of the disease, and 10-15% for the less severe form). (More on tuberculosis.) DOTS refers to a broad TB control strategy outlined by the World Health Organization:1

1. Political commitment with increased and sustained financing
2. Case detection through quality-assured bacteriology
3. Standardized treatment, with supervision and patient support
4. An effective drug supply and management system
5. Monitoring and evaluation system, and impact measurement

DOTS is also sometimes used to refer more narrowly to "directly observed" tuberculosis treatment (i.e., the use of health workers to directly enforce compliance with drug regimens), but we use the term as the World Health Organization does.

What are the components required to implement this program - how does it work?

DOTS requires:

• Diagnosis. Diagnosis for TB is relatively involved, requiring laboratory analysis of results obtained by a trained clinician. In order to obtain an accurate diagnosis, individuals must have access to health services functioning at a relatively high level.2
• Drugs. TB treatment requires four drugs, often taken together in a single combination pill.3
• Patient adherence to treatment regimen, sometimes enforced by community health workers. There are multiple possible drug regimens; some countries use a six-month regimen, while others use an eight-month regimen.4 One approach to enforcing adherence is the use of health workers, who directly observe patients' swallowing their treatment each day to ensure adherence.5

Program track record

Micro evidence: Has this program been rigorously evaluated and shown to work?

There is no debate that the standard short-course chemotherapy regimen effectively cures TB.6 Because the treatment regimen lasts 6-8 months and many individuals do not strictly adhere to the treatment regimen,7 we focus here on whether interventions to improve access and adherence are effective. The evidence for the effectiveness of such efforts is primarily from national-level programs, discussed below.

Macro evidence: Has this program played a role in large-scale success stories?

DOTS has been credited with a number of large-scale, successful programs in the developing world to control TB. Below we summarize reports on China (Levine 2007) and Peru (Suarez et al. 2001).

• China. In 1990, TB was a major health problem in China, where it caused 360,000 deaths.8 In 1991, China implemented the DOTS strategy to control TB in 13 of its 31 provinces.9 China's program included a) case detection for patients seeking health services, b) standard treatment regimen for smear-positive patients, and c) a "consistent monitoring of the project" to ensure quality.10 In areas where the program was implemented, TB rates declined by 36%, and approximately 30,000 deaths have been averted each year.11 In western China, 5 provinces implemented DOTS and 7 did not. In the DOTS areas, TB rates declined by 33%; they only declined by 12% in non-DOTS areas,12 lending support to the idea that implementing DOTS, as opposed to other factors, caused a significant portion of the decline in TB.
• Peru. In 1990, Peru revised its National Tuberculosis Control Program to follow the World Health Organization's DOTS approach.13 The main components of Peru's program were a) case detection and diagnosis and b) directly observed therapy.14 Nurses administered the drugs in a health care facility, to which patients were encouraged to come through the offer of food packages, employment training, and free transport.15 The program had strong results. Between 1976 and 1990, reported cases of TB were relatively flat; they rose sharply between 1990 and 1993, possibly due to improved case detection in the early years of the program; and fell consistently from 1993 to 2000 (the last year the paper covers).16 Deaths from TB had been falling consistently since 1966 and fell slightly faster than this trend after the TB program was implemented.17 Suarez et al. (2001) estimates that 70% of deaths from smear-positive patients (those with the more severe form of the disease) were prevented between 1991 and 2000 because of Peru's program.18

Recommendations and concerns

Do expert reviews of the comparative merits of interventions endorse this one?

See this page for sources consulted.

• The Disease Control Priorities in Developing Countries report strongly supports the intervention writing, "short-course chemotherapy, delivered through the DOTS strategy, is ... the most cost-effective among current methods for the management of TB."19
• The Copenhagen Consensus ranks "Tuberculosis case finding and treatment" 13th on its list of the most cost-effective interventions, and fourth most cost-effective among interventions to control diseases.20
• The Copenhagen Consensus disease paper, Jamison, Jha, and Bloom (2008), ranks "Tuberculosis: appropriate case finding and treatment" as the most cost-effective intervention to control disease.21

What are the potential downsides of the intervention?

• Poor adherence to the drug regimen may cause drug resistance;22 resistance has already caused resurgences in former Soviet republics.23
• Treatment may cause some relatively minor adverse reactions.24

What versions of the intervention are best?

As discussed above, a primary challenge of TB treatment is ensuring adherence to the treatment regimen. Approaches include:25

1. "Routinely reminding patients to keep an appointment and actions taken when patients fail to keep an appointment." A review of nine high-quality trials involving 5,257 participants found that "the included trials show significantly better outcomes among those tuberculosis patients for which late patient tracers and reminders are used."26
2. "Written or verbal agreements to return for an appointment or course of treatment." A recent review of thirty high-quality trials involving 4,691 participants living in high-income countries concluded that, "There is limited evidence that contracts can potentially contribute to improving adherence, but there is insufficient evidence from large, good quality studies to routinely recommend contracts for improving adherence to treatment or preventive health regimens."27
3. "Training and management processes that aim to improve how providers care for people with tuberculosis."
4. "Provision of information or one-to-one or group counseling about tuberculosis and the need to attend for treatment."
5. "Money or cash to reimburse expenses of attending services, or to improve the attractiveness of visiting the service."
6. "People from the same social group helping someone with tuberculosis return to the health service by prompting or accompanying them."

There is some evidence that approach #1 above achieves better results than standard directly-observed therapy. There is little evidence that other approaches are more effective.

What are the bottlenecks to increased coverage?

As noted above, implementing DOTS requires a relatively well-functioning health care system, which may make it difficult to expand to some areas.28

Are there additional reasons to support the intervention?

The "DOTS" approach may help prevent the emergence of MDR-TB (multidrug-resistant TB).29 MDR-TB is a type of tuberculosis that "is resistant to at least two of the best anti-TB drugs."30 Were MDR-TB to emerge, it could be a major public health problem as treatment costs could be orders of magnitude higher than treating conventional TB.31

Cost-effectiveness

The Disease Control Priorities in Developing Countries report states that cost-effectiveness varies with local factors;32 the range estimated for a sustained program is $5-$50 per disability-adjusted life-year (DALY) averted / $150-$750 per death averted.33 This places it among the most cost-effective programs.34 (More on the DALY metric.) DCP2"); ?>

Sources

• Bosch-Capblanch, Xavier, et al. 2007. Contracts between patients and healthcare practitioners for improving patients' adherence to treatment, prevention and health promotion activities. Cochrane Database of Systematic Reviews 2007, Issue 2. Summary available at http://www.cochrane.org/reviews/en/ab004808.html (accessed April 15, 2010). Archived by WebCite® at http://www.webcitation.org/5p0sImueW.
• CDC, Tuberculosis: fact sheet. http://www.cdc.gov/tb/publications/factsheets/drtb/mdrtb.htm (accessed July 8, 2010). Archived by WebCite® at http://www.webcitation.org/5r4p1KzC1.
• Copenhagen Consensus Center. Copenhagen Consensus 2008. http://www.copenhagenconsensus.com/Home.aspx (accessed April 15, 2010). Archived by WebCite® at http://www.webcitation.org/5p0sJczhJ.
• GiveWell. Interpreting the DALY metric.
• Jamison, Dean T. et al., eds. 2006. Disease control priorities in developing countries (PDF). 2nd ed. New York: Oxford University Press.
• Jamison, Dean, Prabhat Jha, and David Bloom. 2008. Copenhagen Consensus 2008 challenge paper: Diseases (PDF).
• Levine, Ruth. 2007. Case 3: Controlling tuberculosis in China (PDF). In Millions saved: Proven successes in global health. Washington DC: Center for Global Development.
• Liu, Qin, et al. 2008. Reminder systems and late patient tracers in the diagnosis and management of tuberculosis. Cochrane Database of Systematic Reviews 2008, Issue 4. Abstract available at http://www.cochrane.org/reviews/en/ab006594.html (accessed April 15, 2010). Archived by WebCite® at http://www.webcitation.org/5p0qvpD4o.
• Suarez, Pedro G., et al. 2001. The dynamics of tuberculosis in response to 10 years of intensive control effort in Peru (PDF). Journal of Infectious Diseases 184:473–8.
• TB Alert. Frequently asked questions. http://www.tbalert.org/general/faq.php (accessed April 15, 2010). Archived by WebCite® at http://www.webcitation.org/5p0sIxKbz.
• Volmink, Jimmy, and Paul Garner. 2007. Directly observed therapy for treating tuberculosis. Cochrane Database of Systematic Reviews 2007, Issue 4. Summary available at http://www.cochrane.org/reviews/en/ab003343.html (accessed April 15, 2010). Archived by WebCite® at http://www.webcitation.org/5p0sJ7qWd.
• World Health Organization. 2009a. Global tuberculosis control 2009: Epidemiology, strategy, financing (PDF). Geneva: World Health Organization.
• World Health Organization. 2009b. The five elements of DOTS (PDF).

• 1. World Health Organization 2009b.
• 2. "Bacteriology remains the recommended method of TB case detection, first using sputum smear microscopy and then culture and drug susceptibility testing (DST), as indicated below...A wide network of properly equipped laboratories with trained personnel is necessary to ensure access to quality-assured sputum smear microscopy." World Health Organization 2009b.
• 3. "The treatment regimen recommended by the World Health Organisation includes at least three and preferably four specific antibiotics. They are called isoniazid, rifampicin, pyrazinamide and ethambutol. For convenience they may be given in a combination tablet which combines the antibiotics in a single tablet." TB Alert, "Frequently Asked Questions."
• 4. "In 2007, all of the 146 countries reporting data, including all HBCs, provided treatment with standardized short-course chemotherapy (SCC). There were 105 countries using the six-month Category I regimen and 23 countries using an eight-month regimen that does not include rifampicin in the continuation phase of treatment." World Health Organization 2009a, Pg 40.
• 5. "Directly observed therapy (DOT): an appointed agent (health worker, community volunteer, family member) directly monitors people swallowing their antituberculous drugs." Volmink and Garner 2007, Pg 3.
• 6. "Effective drugs for tuberculosis have been available since the 1940s." Volmink and Garner 2007, Pg 3.
• 7. "People with tuberculosis require treatment for at least six to eight months. Many find it difficult to complete their course of treatment and this serves as a major constraint to eradicating the disease (Fox 1958; Addington 1979; Cuneo 1989). Poor adherence to treatment can lead to prolonged infectiousness, drug resistance, relapse of tuberculosis, or even death. Incomplete treatment thus poses a serious risk for the individual as well as the community." Volmink and Garner 2007, Pg 3.
• 8. "In 1990, according to vital registration data, 360,000 people died from TB, making it the leading cause of death among adults." Levine 2007, Pg 3.
• 9. "In 1991, with $58 million in financial support from the World Bank, China embarked on a 10-year Infectious and Endemic Disease Control (IEDC) project to help curb its TB epidemic in 13 of its 31 mainland provinces. The project adopted the DOTS strategy and short-course chemotherapy." Levine 2007, Pg 3.
• 10. "Free diagnosis was offered, and patients' lungs were examined with chest fluoroscopy...New patients with smear-positive pulmonary TB were started on a course of directly observed treatment of antibiotics, every other day for at least two months and up to six months...Quarterly reports summarizing the case findings, treatment outcomes, and other program activities were submitted from each county to the province, the central government, and the newly formed National Tuberculosis Project Office, allowing for consistent monitoring of the project." Levine 2007, Pg 4-5.
• 11. "From 1990 to 2000, the number of people with TB in the DOTS area declined by 36.1 percent, about 4.1 percent each year, compared with a decline of 3.1 percent in non-DOTS areas...Since DOTS was introduced in China, more than 1.5 million patients have been treated, and approximately 30,000 TB deaths have been prevented each year." Levine 2007, Pg 5.
• 12. "In western China, for example, where five provinces implemented DOTS and seven provinces did not, the prevalence in the DOTS area decreased by 33.3 percent while the prevalence in the non-DOTSarea decreased by just 11.7 percent." Levine 2007, Pg 5.
• 13. "In August 1990, the National Tuberculosis Control Program (NTP) in Peru was revised, and the revised NTP (RNTP) follows the WHO DOTS strategy." Suarez et al. 2001, Pg 473.
• 14. "The main tenets of TB control under the RNTP are early case detection and diagnosis, followed by DOT of patients." Suarez et al. 2001, Pg 473.
• 15. "DOT is provided by nursing staff in special areas within health facilities reserved for this purpose. Patients are encouraged to come for treatment by being given food packages and employment support (e.g., training in handicrafts), and their transport costs are paid." Suarez et al. 2001, Pg 474.
• 16. "The number of reported pulmonary TB cases per capita remained roughly steady between 1976 and 1990 after an earlier decline (figure 2)...The case report rate increased sharply between 1990 and 1993, coincident with the improvement in diagnostic effort. Since 1993, reported new smear-positive cases have declined in all departments of the country (figure 3A)." Suarez et al. 2001, Pg 475.
• 17. Suarez et al. 2001, Pg 475, Figure 2.
• 18. "This elevated rate of decline suggests that 27% (19%–34%) of cases (158,000) and 70% (63%–77%) of deaths (91,000) among smear-positive patients were averted between 1991 and 2000." Suarez et al. 2001, Pg 473.
• 19. Jamison et al. 2006, Pgs 304-305.
• 20. Copenhagen Consensus Center, "Copenhagen Consensus 2008." Tuberculosis case finding and treatment is defined in Jamison, Jha, and Bloom 2008, Pgs 41-42 as the DOTS program.
• 21. Jamison, Jha, and Bloom 2008, Pg 51, Table 7.
• 22. "Poor adherence to treatment can lead to prolonged infectiousness, drug resistance, relapse of tuberculosis, or even death. Incomplete treatment thus poses a serious risk for the individual as well as the community." Volmink and Garner 2007, Pg 3.
• 23. "The biggest resurgences of TB in recent history have been driven by the spread of HIV in Africa and are linked to the rise of drug resistance in former Soviet republics." Jamison et al. 2006, Pg 299.
• 24. "Can the TB treatment cause side effects? Rifampicin will turn urine and other body secretions such as tears orangy-red. It also interacts with other medicines, in particular it reduces the effectiveness of the contraceptive pill. It is therefore important to warn your doctor when prescribing other medicines that you are on TB treatment. The tablets may rarely cause some of these:
  • Rash
  • Giddiness
  • Sickness
  • Pins and Needles
  • Jaundice"
  TB Alert, "Frequently Asked Questions."
• 25. Unless otherwise noted, the following list is quoted from Vomink and Garner 2007, Pg 3.
• 26. Liu et al. 2008, Pg 2.
• 27. Bosch-Capblanch et al. 2007, Pg 2.
• 28. "Disease Control Priorities for Developing Countries" reports some evidence of this: "Observations on the way DOTS is presently implemented suggest that a ceiling on case detection might be reached at about 50 to 60 percent (Dye and others 2003; WHO 2005). This fraction is about the same as the percentage of all cases reported annually to WHO from all sources (that is, from DOTS and non-DOTS programs). The problem is that, as DOTS programs have expanded geographically, they have not yet reached far beyond existing public health reporting systems." Jamison et al. 2006, Pg 294.
• 29. "Relatively simple, the DOTS approach can improve patient compliance, cure the vast majority of new TB patients, and prevent transmission of the disease and the emergence of MDR-TB (Balasubramanian, Oommen, and Samuel 2000; Dye and others 2002)." Jamison, et al. 2006, Pg 1041.
• 30. CDC, "Tuberculosis: Fact Sheet."
• 31. "Because many patients either are treated outside the DOTS regimen or do not adhere to the long-term chemotherapy necessary to eradicate the causative organism,MDR-TB is likely to emerge and treatment costs are likely to escalate to as high as 1,000 times the cost of conventional treatment of drug-sensitive infection." Jamison, et al. 2006, Pg 1041.
• 32. "The cost effectiveness of TB control depends not only on local costs but also on the local characteristics of TB epidemiology (for example, epidemic or endemic, low or high rates of HIV infection and drug resistance) and on the rate of application of any chosen intervention." Jamison et al. 2006, Pg 301.
• 33. "For a 10-year program of treatment for infectious TB, the cost per death prevented is typically US$150 to US$750, and the cost per DALY gained is US$5 to US$50 for all regions except Europe and Central Asia (figure 16.1)." Jamison et al. 2006, Pg 299.
• 34. See Jamison et al. 2006, Pgs 41-42, Figures 2.2 and 2.3 for a chart of the cost-effectiveness range (measured in cost per DALY) for many programs.