TB control: role of DOTS

Tuberculosis is a major cause of morbidity and mortality, particularly in many developing countries with significant public-health problems. Nearly a third of the world’s population is infected with Mycobacterium tuberculosis or is at risk of developing TB in the future. There was an estimated incidence of 9.27 million new cases of TB in 2007 (139 per 100,000 population), which has steadily increased from 9.24 million cases in 2006 (140 per 100,000 population), 8.3 million in 2000 and 6.6 million cases in 1990. A total of 1.32 million TB-related deaths occurred in HIV-negative people, with an additional 0.46 million TB deaths in HIV-positive individuals. The prevalence of TB cases worldwide is 13.7 million, 687,000 of which were HIV-positive cases. The majority of TB infections occur in Asia and Africa, contributing 55 and 31% of the total TB cases, respectively. Of these 9.27 million new cases, approximately 44% or 4.1 million (61 per 100,000 population) were new smear-positive cases. India, China, Indonesia, Nigeria and South Africa rank first to fifth in terms of the total number of cases. Of these cases in 2007, an estimated 1.37 million individuals (14.8%) were HIV positive. The African region accounts for most (79%) of HIV/TB coinfection cases, followed by the southern and eastern Asia regions, mainly India, with 11% of total cases [1]. More than 90% of global TB cases and deaths occur in the developing world, where approximately three-quarters of these cases affect the most economically productive age group (15–54 years), with significant socioeconomic impacts [101].

In the prechemotherapy era, it was estimated that, on average, one infectious case would transmit infection to approximately 20 others over a period of 2 years before death or self-cure. Accordingly, if 50 new smear-positive TB cases occur in 1 year in a population of 100,000 people, it would produce 100 infectious cases in the population at any given time, leading to 1000 new infections annually; that is, 1% of the population will become infected every year. Of these infected individuals, approximately 5% will develop active TB within 5 years of primary infection, and the other 95% will later be at risk to progress to opportunistic infections, depending on the status of immune system. Therefore, approximately 10% of infected individuals will eventually develop active TB in their lifetimes. However, with HIV infection, the risk increases to approximately 50–60% [2].

The main reasons for the increasing burden of TB worldwide are poverty and the widening gap between rich and poor in various populations, particularly in developing countries; neglect of the disease owing to inadequate case detection, diagnosis and cure; inadequate national control programs and a collapse of the health infrastructure due to economic crises or civil unrest; and the impact of the HIV pandemic. Governments in many high-burden countries have neglected TB control in the past. The existing TB programs have failed to achieve high detection and cure rates for infectious, smear-positive patients. The WHO declared TB a global emergency in 1993 and, realizing its growing importance as a public-health problem, it developed the Directly Observed Treatment, Short Course Strategy (DOTS) in 1994 as the new framework for effective TB control [3,4]. The global strategy has five components:

• • Sustained political commitment;

• • Access to quality-assured sputum microscopy;

• • Standardized short-course chemotherapy for all cases of TB under proper case management conditions, including the direct observation of treatment;

• • Uninterrupted supply of quality-assured drugs;

• • Recording and reporting systems, enabling the outcome assessment of all patients and the assessment of overall program performance.

By using a 6-month course of treatment that included rifampicin, the WHO has mobilized finance, manpower and implementing systems in countries to tackle this global problem, with good progress currently being made [5]. The successful treatment of TB depends on patient compliance to complete the prescribed treatment regimen. The interruption of treatment results in ongoing transmission of the disease. Owing to a longer duration of therapy and other socioeconomic factors, the patient often fails to complete therapy, resulting in the persistence of TB and ongoing transmission to the community. In addition, if treatment is not properly supervised, drug resistance may develop. Thus, DOTS represents the basic minimum necessity for the control of TB. This strategy has been adopted in many countries with flexibility and adaptation to the existing needs of the community [6,7]. The total number of countries implementing DOTS has increased steadily from 1995 to 2003, and has since remained stable at around 180. All the 22 high-burden countries fortunately have the DOTS program since 2000. By the end of 2007, approximately 94% of the world’s population lived in countries that had adopted DOTS and the population was reported to exceed 90% in all regions except Europe. However, 100% DOTS coverage does not mean that all providers in a country, such as the various networks of health facilities, other public, voluntary, corporate and private providers (public–private mix [PPM] approaches), are implementing the DOTS strategy.

The global targets for TB control, adopted by the World Health Assembly, are to cure 85% of newly detected sputum smear-positive TB cases and to detect 70% of the estimated incidence of sputum smear-positive TB cases [8]. This strategy will rapidly reduce TB mortality, prevalence and transmission, and gradually reduce TB and acquired drug-resistance incidence. An effective national TB program has a high cure rate, a low level of acquired drug resistance and ultimately a high case detection rate. Although many countries have achieved this target, the case detection rate was 63% worldwide in 2007 through the DOTS programs, while for all cases it was 56%. A cumulative total of 37.3 million new and relapse cases have been treated in the DOTS program over 13 years (1995–2007). The treatment success rate was 85% in the 2006 global cohort, although this figure varies from region to region [1]. Even if the total number of global cases is still increasing in absolute terms as a result of population growth, the incidence per 100,000 population is decreasing. While the global incidence of TB appears to have been slowly declining since 2004, and treatment success met the target in 2006, the case detection rate for sputum smear-positive TB was stagnating at 64% in 2007 [1]. Thus, only 52% of the estimated new smear-positive pulmonary cases are treated successfully [9]. However, one must be very careful about the accuracy and validity of the routine data generated by TB programs, as well as the uncertainties about the estimates of TB incidence [10]. Doubts have been raised before on this issue. The WHO also emphasizes the need for better estimates and reporting [11].

The global targets and indicators for TB control were developed within the frameworks of the Millennium Development Goals (MDGs) in 2006. The targets are to cease and reduce the incidence of TB by 2015, and reach a 50% reduction in prevalence and mortality rates by 2015 relative to 1990 levels (goal 6, target 6c) [12,13]. The Stop TB Partnership targets the achievement of the case detection rates of 70% and a cure rate of at least 85% for such cases as established by the World Health Assembly in 1991. The ultimate goal of eliminating TB is the occurrence of less than one case per million populations per year by 2050 [13,14].

Two landmark strategies were launched in 2006 for global TB control [14] – the Stop TB Strategy and the Global Plan to Stop TB [13]. The Stop TB Strategy, launched by the WHO, sets out six major components/interventions to be implemented to achieve the MDG, Stop TB Partnership goals and World Health Assembly targets. These six broad components are:

• • To pursue high-quality DOTS expansion and enhancement through the aforementioned five technical elements;

• • To address TB–HIV coinfection, multidrug-resistant (MDR)-TB, and the needs of poor and vulnerable populations by: a) scaling up collaborative TB/HIV activities; b) scaling up the prevention and management of MDR-TB; and c) addressing the needs of TB contacts and of poor and vulnerable populations, including women, children, prisoners, refugees, migrants and ethnic minorities;

• • To contribute to health system strengthening based on primary healthcare by: a) helping to improve health policies, human resource development, financing, supplies, service delivery and information; b) strengthening infection control in health services, other congregate settings and households; c) upgrading laboratory networks, and implementing the Practical Approach to Lung Health (PAL); and d) adapting successful approaches from other fields and sectors, and foster action on the social determinants of health;

• • To engage all healthcare providers by: a) involving all public, voluntary, corporate and private providers through PPM approaches; and b) promoting the use of the International Standards for TB Care (ISTC);

• • To empower people with TB and communities through partnership by: a) pursuing advocacy, communication and social mobilization; b) fostering community participation in TB care; and c) promoting use of the Patients’ Charter for TB Care;

• • To enable and promote research by: a) conducting program-based operational research, and introducing new tools into practice; and b) advocating for and participating in research to develop new diagnostics, drugs and vaccines.

The Global Plan to Stop TB, developed by the Stop TB Partnership, sets out how and at what scale the strategy should be implemented from 2006 to 2015. The WHO has advised countries to report on the implantation of TB control activities according to the major components of the strategy. The implementation by countries components-wise varied widely. The first component and the important foundation of the strategy – DOTS – is the most widely implemented, and progress has been made which is the closest to matching the expectations contained in the global plan.

Multidrug-resistant TB has come as a major challenge to the global effort to control TB [15]. The most recent estimates based on data from different countries of the world on drug resistance surveys or routine surveillance suggest that 510,545 cases of MDR-TB occurred in 2007 [1]. Cases are unevenly distributed, with 27 countries (of which 15% are in eastern Europe) accounting for 85% of all cases. These 27 countries have been identified as priorities for the improved diagnosis and management of MDR-TB on the global level. By 2008, 55 countries and territories reported at least one case of extremely drug-resistant (XDR)-TB, including five that reported cases for the first time in 2007. India, China and Russia account for approximately two-thirds of such cases. Unfortunately case detection and the diagnosis of MDR-TB in these resource-limited countries pose significant problems in the management of these cases. It is also to be realized that the management of MDR- and XDR-TB is more complex and difficult. Besides establishing accredited, quality-assured laboratories, the duration of treatment, and cost of second-line drugs complicate the issue further. The availability of good-quality drugs is also an issue. We have to hold a MDR-TB patient for 24–27 months, who has failed to comply with 6–8 months of treatment under DOTS, and treatment will now include 6–9 months of injectable drugs. The current strategy to manage MDR-TB is DOTS-Plus, which is a method of managing MDR-TB patients within the existing DOTS program. Many countries are scaling up their DOTS-Plus strategy to manage such cases. However, it is also to be remembered that the treatment outcomes of these cases are not very encouraging [16,17]. Health ministers from 27 high-burden countries met in Beijing (China) under the auspicies of The Stop TB Partnership (WHO), The Ministry of Health of the People’s Republic of China and the Bill and Melinda Gates Foundation on 1–3 April 2009, and resolved to tackle MDR/XDR-TB, which is known as the ‘Beijing Call for Action’. This resolution is essentially a consensus building process and political committment globally and in countries with a high burden of MDR/XDR-TB, with emerging economies taking the lead and to stimulate immediate action to scale-up the prevention and management of MDR-TB and start developing 5-year national strategic plans for MDR-TB embedded within national TB and health sector plans [102].

Other strategies for TB control besides DOTS implementation and DOTS-Plus include collaborative TB/HIV activities, particularly HIV testing of TB patients and the provision of cotrimoxazole prophylaxis and antiretroviral therapy to HIV-positive TB patients. Case notification of MDR-TB is very important. Globally, just under 30,000 cases were reported to the WHO in 2007, which is only 8.5% of the global estimate. Of this number, only 3700 individuals were put on treatment with high-quality drugs. Most countries have integrated the diagnosis and treatment of TB into primary healthcare services along with the PAL approach. However, the issues of human resource development and infection control measures are less than desired in most developing countries. PPM and ISTC are being introduced and expanded in more and more countries. In fact, countries such as India, Pakistan and The Philippines have demonstrative the potential of PPM to contribute increased case detection, referral and treatment of cases [18]. The involvement of medical colleges is another step towards better implementation of the DOTS program [18]. Advocacy, communication and social mobilization is a new and exciting area for many countries. Operational research and the introduction of new tools are being adopted by many countries that will be of immense help in the early and improved diagnosis of TB. Molecular diagnostic methods such as the line probe assay and liquid culture methods [19] will be of help in diagnosing MDR-TB cases early so that treatment can be initiated sooner. Other issues include the management of pediatric TB; for instance, India has an existing program for children with TB [20].

The other important issue for the implementation of the various aforementioned strategies for TB control around the world is that of accurate budgeting and financing. The mobilization of funding and rational spending of available funds is essential. Financial monitoring began in 2002, which shows that funding for TB control has increased every year since then. The available funding reached US$3.0 billion in 2009. Most of this funding (87%) will be provided by the national governments, with the remainder provided by the Global Fund (9%) and other donors (4%). In recent years, there has been an increase in the funding for TB control. However, large gaps in funding still remain. Therefore, additional resources will need to be mobilized and arranged. This will, however, be a major challenge in the context of the recent global financial crisis. In addition, unless socioeconomic development reaches disadvantaged sections of society, we may not be able to eradicate TB in the near future. Besides good TB control programs with national, international and public–private efforts, other benefits in the form of socioeconomic development need to reach the vulnerable section of society to improve their standard of living, nutrition status, and so on [21]. It is not clear at this moment whether the development of new drugs and regimens, including newer vaccines, will have any impact on global TB control in the future [22].

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.