In the early 1990s, most TB control professionals, if asked to describe the best TB treatment, would produce a long list of interventions, including passive case-finding, short-course chemotherapy (SCC), patient compliance with treatment, adequate drug supply, sound reporting and recording systems.

The basic principles of the strategy were not new. The crucial innovation was the addition of the human element-having health workers or volunteers form a close bond with their patients to help them successfully complete treatment. In the United States, this was known as Directly Observed Therapy, or DOT. One fine autumn Sunday in 1994, WHO TB Programme Advocacy Officer Kraig Klaudt sat in a Geneva café, his work-in progress spread around in creative disarray. Looking across the table at the upside-down cover for his draft report entitled "Stop TB at its Source," it struck him that, when viewed from this viewpoint, the word "STOP" spelled "DO- T-S". Modifying the DOT acronym to include another key element of the strategy-the Short-course from SCC- gave meaning to "DOTS." Thus, the catchy brand name "DOTS" was born and Stop TB-Use DOTS became a clarion call for TB control programmes around the world. Because of its novelty, this health intervention quickly captured the attention of even those outside the international health community. The five major components of DOTS, as described by WHO, are:

• Political commitment and resources:
  TB control is a public health responsibility and top-down support is crucial. This component must be the strongest link in the chain.
• Microscopy:
  Accurate diagnosis using sputum smear microscopy among symptomatic patients is the first step in early detection of active TB infection. It sets the DOTS cure cycle in motion and protects others from infection;
• Treatment:
  Standardized 6-8 month regimens for all patients with active TB, with directly observed treatment for at least the first two months. The success of this phase is contingent upon a sound, functional health sector infrastructure and trained personnel;
• Medicines:
  Regular, uninterrupted supplies of the 4-6 most effective anti- TB drugs is essential. Full compliance with the drug regimen means nine out of ten patients can be cured;
• Monitoring:
  A standardized recording and reporting system allows assessment of each patient's treatment and progress. Rigorous overall record keeping also acts as early warning for emerging disease trends (e.g. MDR-TB).

DOTS is the most effective strategy available for controlling the TB epidemic today

• DOTS produces cure rates of up to 95 percent even in the poorest countries.
• A DOT prevents new infections by curing infectious patients.
• DOTS prevents the development of multidrug-resistant tuberculosis (MDR-TB) by ensuring the full course of treatment is followed.
• A six-month supply of drugs for DOTS costs US $11 per patient in some parts of the world. The World Bank has ranked the DOTS strategy as one of the "most cost-effective of all health interventions."

Since DOTS was introduced on a global scale in 1995, over 10 million infectious patients have been successfully treated under DOTS programmes. In half of China, cure rates among new cases are 96 percent. In Peru, widespread use of DOTS for more than ten years has led to the successful treatment of 91 percent of cases, and a reduction in incidence of new cases.

DOTS has FIVE key components:

• Government commitment to sustained TB control activities.
• Case detection by sputum smear microscopy among symptomatic patients self-reporting to health services.
• Standardized treatment regimen of six to eight months for at least all sputum smear- positive cases, with directly observed therapy (DOT) for at least the initial two months.
• A regular, uninterrupted supply of all essential anti-TB drugs.
• A standardized recording and reporting system that allows assessment of treatment results for each patient and of the TB control programme performance overall.
  

DOTS cures active TB. It is remarkably effective. Without treatment, seven in ten people with infectious TB will die of it, on an average within 4-5 years of onset even if they are young when they contract it. Though non-DOTS TB control programmes may decrease deaths considerably, they have less impact on curing TB. Many sufferers remain chronically ill and continue to unknowingly transmit the disease to family, friends and even strangers.

Conversely, good DOTS programmes rapidly reduce both death and disease, curing over 85% of patients. In human terms, DOTS gives young people marked for premature TB death a chance to lead full and productive lives, raise their children to adulthood, and make their contribution to their communities and society. Additionally:

• DOTS saves lives.
  Modelling suggests that achievement of WHO's 2005 targets would avert 15.5 million TB deaths during the period 2001-2005 period, in addition to the 4.2 million lives saved through ongoing DOTS expansion programmes. Even today, in China alone, DOTS has prevented 46% of deaths that would otherwise have occurred in the provinces in which it is being applied. This translates into 30,000 lives saved each year.
• DOTS stops the chain reaction oftransmission.
  Curing people with TB prevents them from infecting others. For example, introducing DOTS in Peru has accelerated the decline in notified TB incidence to about 7% per year.
• DOTS prevents treatment failure and the emergence of even more deadly strains of drug resistant TB.
  For example, the China Tuberculosis Coalition (CTC) reported that the failure rate in previously treated patients fell from 17.6% to 6.2% following the introduction of DOTS in World Bankassisted provinces in China.
• DOTS reduces TB recurrence rates.
  For example, in the US state of Texas, TB recurrence rates fell from 20.9% to 5.5% within six years when a DOTSbased TB control strategy was introduced.
• DOTS indirectly alleviates poverty.
  Saving lives, reducing periods of illness, and prevention of new infections means fewer years of productive work life lost.
• DOTS overcomes TB's stigma.
  Effective treatment, combined with a positive approach, reduces the fear of death and disability that has fuelled the profound stigma often associated with TB. In Nepal, for example, the introduction of DOTS has led to a general awareness that TB is curable. As a result, it is now less feared; no longer 'khapate'-the disease that dries you up before you die.
• DOTS provides a model for strengthening health services.
  Remarkably successful in promoting the development of peripheral health services, the DOTS strategy can serve as a model for expanded use of HIV antiretrovirals, as proposed in Malawi. If adaptations of DOTS strategy were shown to be effective in AIDS treatment, then networks linked to DOTS TB treatment programmes could be rapidly set up, since up to a third of all AIDS patients ultimately die of tuberculosis.
• DOTS saves taxpayers' money-and lives.
  The World Bank has hailed DOTS as "one of the most cost-effective interventions available." Country studies in the early 1990s from Malawi, Mozambique and Tanzania showed the cost of TB interventions ranging from US$ 19-52 (in 2000 US$) per life saved. But drugs cost up to four times as much at that time. Today the DOTS drug package can be had for as little as US$ 10. This means that investing in TB control will save lives, starting right now. Over time, it will also "turn a profit" as it reduces the disease burden on society.

Tackle TB.
There is really no other choice. The right to disease prevention, diagnosis, treatment and cure is not only a fundamental human right; it also makes sound economic, social and public health sense.

The means are there.
Affordable and effective interventions are available to save lives, prevent drug resistance and reduce TB transmission.

The targets are clear and consensual,
adopted by all countries that are committed to achieve them by 2005. They are to diagnose 70% of estimated new active TB patients and to successfully treat
85% of those patients.

Afghanistan, Bangladesh, Brazil, Cambodia, China, DR Congo, Ethiopia, India, Indonesia, Kenya, Myanmar, Nigeria, Pakistan, Peru, Philippines, Russia, South Africa, Thailand, Tanzania, Uganda, Vietnam, Zimbabwe.

Starting with the 22 TB high-burden countries (HBCs) that together account for 80% of the global TB burden, it is clear that successful DOTS expansion in these countries will make an enormous contribution to global elimination of TB.

Afghanistan, Bangladesh, Brazil, Cambodia, China, DR Congo, Ethiopia, India, Indonesia, Kenya, Myanmar, Nigeria, Pakistan, Peru, Philippines, Russia, South Africa, Thailand, Tanzania, Uganda, Vietnam, Zimbabwe.

Several of those countries have already introduced DOTS and taken it to scale.
For example:

• Chinawas one of the first. Its DOTS programmes covered over half a billion people by 1994, and had treated over 110 000 patients a year.
• India has also progressed rapidly. Between 1997-99, the Revised National TB Control Programme expanded DOTS coverage from 22 to 135 million people, providing treatment
  to nearly 150,000 TB patients. WHO monitors the global TB epidemic. According to its annual report on the state of the world's TB epidemic, this was the situation at the end of 1999:
• 127 countries, including all 22 TB highburden countries, had adopted DOTS and 66 of them were already implementing this strategy for over 90% of their populations;
• 1.7 million patients with TB were treated in DOTS programmes in 1998; 870 000 of them-23% of the cases estimated to have occurred that year-had active TB;
• Eight out of ten patients treated in DOTS programmes in 1997 were reported successfully treated, compared with less than four out of 10 in non-DOTS programmes. Most of the 66 countries implementing DOTS on a wide scale are relatively small. Progress in large-population countries has been generally slow, with a few notable exceptions, such as Viet Nam and Peru. These are the only two large countries to achieve the global targets for TB control. Worldwide, national TB programmes would need to add an additional 470 000 new case detections each year, 300 000 of which would be active and thus contagious-to
  reach these targets by the year 2005. TB comprises perhaps the greatest health paradox of our times. Despite the proven effectiveness of a low-cost strategy:
• Less than one quarter of all TB patients worldwide receive care in accordance with the international guidelines for diagnosis, treatment, and monitoring;
• Many receive inadequate treatment in poorly organized and insufficiently monitored programmes in the public and private sectors. This poses a grave danger by encouraging the development of drug-resistant strains, one of the greatest threats to TB control. Finally, some people receive no treatment at all.
• It is not only paradoxical-but also perverse-that children born in the third millennium, as well as at risk adults who have inherited this "dark legacy", should continue to be plagued with this entirely preventable disease.

Geographic obstacles:
On the one hand, remote, rural areas (e.g. mountainous Himalayan countries, isolated Pacific island communities, nomadic East African tribes) pose obvious problems in terms of the accessibility of TB treatment. Not only is detection thwarted; even when diagnosed, patients living in such remote rural communities cannot easily travel to distant health facilities. This means that community-based approaches will be necessary. Access can also be a significant problem in urban areas, today home to half the world's population-up from only 24% in 1950. The challenges for TB control in urban areas include: higher rates of TB infection; drug resistance; the growing risk of HIV co-infection; difficulties providing continuity of care to mobile populations and socially disadvantaged groups (e.g. homeless people and slum dwellers); and the complexities inherent in large-scale and/or problematic settings (e.g. health-service providers in mega-city private hospitals and clinics, university hospitals, industries, prisons and the military).

Social obstacles:
Such as the stigma attached to the disease, remain a problem in many societies, and health systems do not always respond to patients' needs in a supportive manner. The WHO World Health Report 2000 analyzed the level of 'responsiveness' of public health services: 15 of the 22 countries with the highest TB burden were in the bottom half of the table. If we are to reach the four million people with TB who currently lack access to treatment, we will need swift and massive global DOTS expansion.

The potential impact of accelerating DOTS expansion is dramatically emonstrated below. Increasing DOTS coverage to provide effective treatment to just 70% of people with active infectious TB by 2005 would save millions of lives and jump-start a decline in TB that could lead to future elimination. Investing in accelerated DOTS expansion can clearly have a profound impact:

• 22 million people can be cured of TB by 2005-six million more than with the current level of TB control; and
• 15.5 million lives can be saved by 2010-4.2 million more than with the current level of TB control. Momentum is already being generated at the highest political levels. As indicated earlier, when Ministers and senior officials from 20 of the TB highestburden countries met for the March, 2000 Conference on TB and Sustainable Development, delegates committed their countries to reaching specific, imebound global targets by 2005; i.e.: Expanding DOTS to all countries; Diagnosing 70% of all people with nfectious TB; and
• Successfully treating 85% of those diagnosed. Reaching TB's global targets by even as late as 2010 would prevent 48 million cases (23% of the predicted total) by 2020. The percentage of deaths averted would be even greater. Indeed, most TB deaths could be prevented immediately if all patients took a full course of anti-TB drugs now. Further evidence of political commitment to accelerated action is visible in the outcome of the G8 Summit in July, 2000 in Okinawa, Japan. There, the G8 Heads of State committed their countries to a massive increase in funding for action against infectious diseases. The goal they set was to halve the TB burden- both the number of people living with the disease and the number dying from it- within a decade. The European Union and the US Government also pledged to work together "in partnership with the countries concerned" to combat communicable diseases such as HIV/AIDS, malaria, and TB. Now, concrete follow-up action is needed in three areas to realize DOTS' full potential. We must increase the supply of funds for DOTS programmes, increase the demand for DOTS programmes, and build the capacity for implementing DOTS. These activities must be advocacy-driven to ensure high-level political commitment. They need operational research to improve the effectiveness and efficiency of mechanisms for action, and close monitoring and surveillance to demonstrate the impact of the interventions.

If we are to reach the four million people with TB who currently lack access to treatment, we will need swift and massive global DOTS expansion.

5.1 Increase access to drug treatment and care
Increasing access to accurate diagnosis and swift treatment for people with TB can be achieved by:

• Expanding DOTS coverage through public health health services;
• Securing sustainable supplies of quality TB drugs for NTPs; and
• Involving other health service providers, including the private sector and not-for-profit providers such as nongovernmental organizations (NGOs).

DOTS …: Most TB high-burden countries have gained considerable experience in introducing DOTS, but may face difficulties in reaching 100% population coverage. This may be specific to certain national TB control programmes (e.g. human and financial resource constraints) or more applicable to health services in general (e.g. providing services to "hard to reach" population groups). In addition, in some instances much-needed health sector reforms have been introduced without ensuring maintenance of an effective TB control programme, with catastrophic results for patients. The key to successful TB control is "broader, better and bolder" use of drugs to ensure that all TB sufferers in all countries have uninterrupted access to effective treatment. Frequent interruptions in the TB drug supply are common in many countries.… and drugs: Participants in the Amsterdam Conference 2000 called for a global facility to increase access to highquality TB drugs. In response, the Global Drug Facility (GDF) was launched on World TB Day 2001 by the Global Partnership to Stop TB. It provides free drugs for people in the poorest countries and emergency supplies to assist countries facing stock-outs. Managed by the Stop TB Partnership Secretariat in WHO, the GDF has received initial funding of US$ 10 million from the Canadian government, and, within less than a year after its creation, had already awarded grants in kind of TB drugs to 12 countries in Africa, Asia, and Eastern Europe. The GDF is living proof of just how quickly and effectively Stop TB partners can work together to respond to an urgent need faced by many countries. However, it will require a substantial increase in funding to meet its goal of supplying drugs to an additional 10 million patients over the next five years. In most countries where TB is common, its diagnosis and treatment are not restricted to public health services. NGOs and private medical practitioners often provide a substantial proportion of care. Successful DOTS expansion will require close collaboration between these different health care service providers to ensure that all patients get access to effective and affordable care. Models of public-private sector collaboration in health service delivery are being developed in many countries, but need to be rapidly scaled up.

The WHO recommended strategy for curing “ordinary” TB (known as “DOTS”) is a proven success. But in those places in which MDR-TB is already common and increasing, it can be like shutting the stable door after the horse has bolted.

“DOTS does what it’s designed for – it cures ordinary TB,” agrees Stop TB scientist Rajesh Gupta. “But trying to treat MDR-TB requires going beyond ordinary methods – you need something extraordinary.” So in 1998 WHO and several of its partner organizations around the world conceived DOTS-Plus, a strategy that is still under continuous development and testing, for the management of MDR-TB.

DOTS-Plus works as a supplement to standard DOTS-based TB programmes already in place. “It is not intended as a ‘catchall’ strategy,” emphasizes Thelma Tupasi, director of the Philippine Coalition Against Tuberculosis (PCAT), a nongovernmental organization and Stop TB’s partner in the Philippines.

“DOTS-Plus is meant for areas with significant incidences of MDR-TB … but within those areas, standard TB cases continue to be treated with standard DOTS procedures, and those procedures must be followed through to the finish – how else can we stop more drug-resistant TB occurring?”

DOTS-Plus is needed in areas where MDR-TB has emerged due to previous inadequate TB control programmes. Therefore, DOTS-Plus pilot projects are only recommended in settings where the standard DOTS strategy is fully in place to protect against the creation of further drug resistance.

DOTS-Plus is designed to cure MDR-TB using second-line TB drugs. These drugs should be stored and dispensed at specialized health centers with appropriate facilities and well-trained staff. It is vital that DOTS-Plus pilot projects follow WHO recommendations in order to minimize the risk of creating drug resistance to second line TB drugs.