The TB epidemic from 1992 to 2002
Introduction
The last decade has been characterized by a new understanding of the global tuberculosis (TB) epidemic and an acceleration in TB control efforts worldwide. Many key events took place in the 1990s and this resulted in intensified action in endemic countries towards the control of TB. However, even with our knowledge of today, a lot remains to be done if our generation has to leave a legacy of sustainable progress in TB control.
This paper aims to achieve four goals: first, to review the TB control situation in the early 1990s; second, to describe the key events for the international TB community during the decade 1992–2002; third, to assess the progress of TB control efforts and their achievements; and, fourth, to present an overview of the current situation of TB epidemiology and control.
In 1989, just before the establishment of a new TB unit at the World Health Organization, only two staff were responsible for WHO work on TB control worldwide.1 This was the result of several years of neglect of the TB epidemic by the international health community. It was felt, particularly in the industrialized countries, that the recent advances in TB chemotherapy had determined a quick disappearance of this disease as a public health problem. Very few had a clear notion of the huge impact that TB still had on the poorest people in developing countries. TB as a priority issue became less visible because of both WHO taking a strong step towards integration of programme functions and also as a consequence of the health sector reform movement.1 However, in this climate of general neglect, the International Union Against TB and Lung Disease (IUATLD) conducted key projects in the early 1980s in some of the least developed countries, showing that a standardized approach to TB control was feasible and effective in curing patients.2., 3.
Most believe that the global impetus to a renewed effort in TB control came largely from the observation of epidemiological anomalies in the United States of America (USA). For the fist time in decades, in 1984 TB notifications in this country did not fall at the same rate as the previous year.4 TB notifications, immediately thereafter, began to increase and generated what was called the “U-shaped curve of concern”.5 (Fig. 1). This observation prompted the awakening of public health and TB experts. The reasons for the increase were initially identified in the HIV epidemic and in the growth of poverty, especially in large metropolitan areas. However, it soon became clear that a growing percentage of cases notified yearly in the USA was among recent immigrants from developing countries.6., 7. This finding was a key factor in generating awareness that no sustainable TB control could be reached in the USA without properly addressing the global epidemic. Not only were notifications increasing, but serious outbreaks of multi-drug resistant TB (MDR-TB) were signalled in hospitals in New York City and Miami.8 Mostly involving HIV-seropositive patients in hospitals, these outbreaks were highly fatal. They also unveiled poor TB control practices. For instance, a study showed a 89% default rate among TB patients on treatment, proving the poor implementation of TB control policies.9 The finding of a high level of drug resistance and MDR-TB (23% and 7%, respectively) among never-treated patients in New York City10 confirmed the need of a complete rethinking of the approach adopted in the USA. This prompted major investment of financial and human resources which, a few years later, resulted in the adequate containment of the epidemic, although at the cost of 110 million US$.11 Certainly, the new epidemiological trends in the USA acted as a strong stimulus to WHO and other international agencies to focus attention on the TB problem.
The crisis in the USA was not the only one in the industrialized world. TB notification rates were increasing, although to a lesser extent, also in several European countries with reliable surveillance systems. The interruption of the secular decline in case rates occurred, in most cases, starting in the late 1980s and involved countries such as the Netherlands, Switzerland, Sweden, Norway and Denmark12 (Fig. 2). Other European countries were also reporting a stagnation in their case notification rates. There was general evidence that, like in the USA, increased poverty in urban settings and especially the recent waves of immigration from TB high-burden countries were responsible for the interruption of the previous declines.12 In the Netherlands and in the Scandinavian countries, more than half of the cases were occurring among non-nationals, thus fostering the need to address TB control globally, rather than with a limited view to the industrialized country in question.
The situation in developing countries in 1990 was not entirely clear, mainly due to the lack of proper information systems in countries and of global assessment capacity. The first attempt to quantify the true extent of the problem resulted in the recognition that about 7.1 million new cases of TB and 2.5 million deaths were occurring annually in the developing world, with a large proportion of those in Asia and Africa.13 When WHO assessed the situation using a similar approach, it confirmed that nearly eight million cases and 2.9 million deaths occurred in 1990 worldwide.14 TB notification rates in the 1990s had doubled or tripled in some African countries such as Malawi, Tanzania and Zimbabwe, in as short a period as 10 years. This prompted alarmist views of what could be done in this region.15 There was no more excuse for inaction. The revitalized TB programme in WHO, as well as the entire international health community, had a formidable challenge to address. In 1991, a paper reviewed the TB situation.16 At the time, 1.7 billion people, i.e. a third of the human population, were estimated to be infected with the tubercle bacillus. Over 95% of the estimated 8 million new cases and 2.9 million deaths were occurring in the developing world. At the same time, less than 15 countries worldwide were capable of reporting on treatment outcomes, less than half of TB cases were covered by proper treatment services, and less than half of the cases treated were cured. These estimates clearly required a new global strategy to address TB control. WHO embarked on the promotion of an approach that was successfully implemented by K. Styblo of the IUATLD in some of the poorest African countries, like Tanzania and Malawi. The approach was based on the concepts expressed in the 9th Report of the WHO Expert Committee on TB that met in December 1973.17 Styblo first implemented the theoretical approach in Tanzania, perfecting it with the addition of the practical tools necessary to evaluate programme performance. The results showed that, even in a very poor country, it was possible to achieve high cure rates.2., 18. Inspired by these observations, WHO requested all countries to focus on cure rates and achieve 85%, and, later, expand TB services to detect more cases once cure rates were permanently high.16 The 44th World Health Assembly (WHA), that met in May 1991 in Geneva, immediately adopted a resolution (WHA 44.8) which (i) urged Member States to intensify tuberculosis control as an integral part of primary care using the new WHO strategy elaborated on the basis of the IUATLD approach; (ii) encouraged international partners to continue to help control TB by collaborating with National Programmes; and (iii) requested the establishment of global targets. These global targets were to cure 85% of sputum smear-positive patients under treatment and detect 70% of cases by the year 2000.19 These targets influenced the behaviour of the international community throughout the years, focusing country work and enforcing a policy of strict monitoring of achievements.
Following the adoption of this resolution, work began to implement the recommendations at country level in order to strengthen TB control efforts and achieve the set targets. In 1992, less than 20 countries were implementing a sound TB control strategy, that would be later called the DOTS strategy. These included the countries assisted by the IUATLD and the Royal Netherlands Anti-TB Association (KNCV), such as Tanzania, Mozambique, Malawi, Benin, Vietnam and Nicaragua. They also included countries with a long history of adequate control, such as Chile, Cuba, Uruguay and Algeria, or very committed to achieve it rapidly, like Guinea. Finally, there were two countries, China and Peru, in the initial phase of implementation of programmes that would become successful models later in the decade. By the mid-1990s, when the global monitoring system was put in place by WHO, 73 countries had already adopted the WHO strategy.20
The intensification of control efforts was further stimulated by the World Bank's Work Development Report issued in 1993. The report called TB chemotherapy “one of the most cost-effective of all interventions”.21 Data from Malawi, Mozambique and Tanzania showed an average incremental cost of US$80–110 per cure for ambulatory treatment of TB, with cost per total death averted between 20 and 100 US$. These figures meant that the cost per DALY saved was only between 1 and 3 US$.21., 22. The World Bank, therefore, officially endorsed the importance of investing in TB control, thus influencing financial policies in countries. In the same year, WHO declared TB a global emergency, an unprecedented step in public health.
It soon became apparent that WHO needed to disseminate its strategy in a simple and understandable manner. In 1994, the “Framework for effective TB control” was launched, defining the five essential elements of a TB control policy package.23 These elements, now universally accepted, are: (i) government commitment to sustainable TB control; (ii) diagnosis through sputum-smear microscopy mainly among symptomatic patients self-referring to health services; (iii) standardized short-course chemotherapy provided under proper case management conditions, including direct observation of treatment (DOT); (iv) a functioning drug supply system; and (v) a recording and reporting system allowing assessment of treatment results. A year later, in 1995, this package was branded under the name “DOTS”. Thanks to an aggressive campaign, the adoption of “DOTS” quickly spread, and it soon became one of the most well-known brands in health.24 The number of countries adopting the five elements of the DOTS strategy continued to grow throughout the 1990s, favoured by both the demonstration that it was effective in achieving high cure rates25 and by an increasing media interest in TB. At this time there was a rapid increase in external resources made available to developing countries.1 The number of articles mentioning TB in some leading media increased dramatically after the WHO's advocacy efforts began.24 At the same time, probably related to the increasing media interest, the number of million US dollars for external financing of TB control, inclusive of aid funds and bank loans, went from 16 in 1990 to 50 in 1996 and, eventually, to 190 in 2000.1
The establishment of the global surveillance and monitoring system in the second half of the 1990s showed that despite the rapid adoption of DOTS and the increased finances available, the targets set for the year 2000 were not in reach. The first global monitoring report by WHO in 199726 showed that only 11% of all estimated cases were treated under DOTS programmes, leaving nearly nine out of 10 either untreated or managed through other TB control practices. The cure rate among the cases treated under DOTS was 78% in 1995.26 Thus, it became evident that the 2000 targets, especially the 70% detection target, could not be reached on time. This was largely due to a very slow pace of DOTS expansion in the 22 highest-burden countries responsible for 80% of the global TB incidence.
In the light of the slow pace of the implementation of DOTS, an “Ad-hoc Committee on the TB Epidemic” was convened by the WHO Global TB Programme in March 1998 to give urgent attention to the global epidemic.27 The Committee analysed the general constraints to progress against TB and the possible solutions. There were six major issues: the first was insufficient political will and commitment, and a “global charter” among all key partners and the endemic countries was proposed as a way to coordinate efforts. The second issue was lack of financing or ineffective use of financial resources. Several ideas were proposed on how financing for TB control could be maximized. The third constraint identified was lack of trained human resources, the solution of which lies mostly in endemic countries and might need the support of WHO and IUATLD. Incentives could be explored to attract and retain staff. The fourth constraint was that good management at programme level was lacking in many countries. This was made more complex by recent trends in health system organization following reforms. The Committee called for a proper balance between integration and specificity, and between decentralization and centralized functions. It also supported the involvement of the private sector and the communities in TB control. The fifth constraint was the problem experienced by many countries in quality and supply of anti-TB drugs. As a consequence, the Committee recommended the creation of a “global drug facility” that would procure and distribute quality TB drugs. The sixth main issue was the weakness of information systems; without them, no effective monitoring could take place, and the Committee recommended proper strengthening. Finally, the Committee recognized that HIV-associated TB and MDR-TB represented two key epidemiological challenges that needed to be faced urgently with effective interventions.27
The report of the Committee was key to influence policy decisions during the following years and, today, most of the recommendations have been implemented. For instance, a global coalition, named Stop TB Partnership, exists that comprises governments, non-governmental organizations (NGOs), donors and various institutions. Financial support to endemic countries has increased dramatically in the past few years and is bound to further increase in the future, due to the newly created Global Fund against AIDS, TB and Malaria (GFATM). A Global Drug Facility (GDF) has been established to deliver free quality drugs to countries in need. Surveillance and monitoring systems have been further improved allowing a clear understanding of the TB epidemic, a situation that is almost unique in public health.
Towards the middle of the last decade, it became more and more evident that the TB situation was deteriorating rapidly in a few regions. Case rates continued to increase in Sub-Saharan Africa, largely due to the HIV epidemic (Fig. 3), and in the former Soviet republics, mostly due to the social-economic crisis that followed the collapse of the Soviet Union20 (Fig. 4). In the case of the TB/HIV epidemic, a major effort was made to define the most effective way of combining control efforts targeting TB and HIV/AIDS. A new philosophy was encapsulated in a “Strategic framework to decrease the burden of TB/HIV”.28 This framework promotes identification of feasible interventions to be delivered jointly by the two specified control programmes.
The issue of MDR-TB was finally faced when it became clear, through the WHO/IUATLD Global Drug Resistance Surveillance Project, that a few settings, named “hot spots”, had a major drug resistance burden. These included the Baltic republics of Estonia and Latvia, parts of Russia and China, Iran and the Dominican Republic.29., 30. After a tumultuous debate, the international community established a global working group responsible for identifying solutions to MDR-TB control. The “DOTS-Plus” strategy began to be implemented in some countries to test the feasibility of MDR-TB management in resource-poor settings.31 Currently, projects are implemented in Peru, Latvia, Estonia, the Philippines and three oblasts in Russia. The results of a country-wide project in Peru are promising and suggest that MDR-TB can be effectively managed under routine programme conditions, using long regimens with second-line drugs with reasonable compliance and cure rates.32
Following the restructuring of WHO in 1998, the previous Global TB Programme was dismantled.1 This influenced international politics and policies in TB control. A new approach based on partnership was promoted by the historical agencies involved in TB control, such as WHO, IUATLD, KNCV, the USA Centers for Disease Control (CDC), the American Thoracic Society (ATS), and the American Lung Association (ALA). The end-result was the creation of a global partnership called Stop TB, which was launched in October 1998 by WHO and its partners. This partnership grew slowly at the beginning. However, while WHO regained its leadership role in international TB control after a transitional, uncertain 2-year period, the aims and the structure of the Stop TB Partnership were better defined and the coalition began to accelerate operations. Today, the Partnership counts over 150 partners. Its organization is based on a governing body, called Stop TB Coordinating Board, and various working groups and task forces addressing all major issues in TB, from control to research, from advocacy to financial assessment. The Stop TB Partnership convened a ministerial conference in Amsterdam in March 2000 that was attended by governmental authorities of the top high-burden countries and all stake-holders in international TB work. The “Amsterdam Declaration to Stop TB” was the outcome of the meeting.33 This Declaration confirmed the commitment of high-burden countries and the international partners to achieve the global targets set by the World Health Assembly: to mobilize all necessary resources in order to expand DOTS and detect at least 70% of infectious cases by the year 2005. The momentum arising from this Declaration originated the establishment of a Global DOTS Expansion Plan (GDEP)34 and of the Global Drug Facility (GDF). The GDEP promotes national inter-agency coordination committees and formulation of 5-year DOTS expansion plans in line with the global targets. In addition, the GDEP has produced a coordination scheme for technical agencies supporting national programmes, in such a way that all countries receive the necessary assistance. Furthermore, an assessment of global financial needs has been conducted within the GDEP. It is estimated that at least US$1.2 billion a year are necessary to support TB control efforts globally. Sixty-nine per cent of this sum is committed by governments of endemic countries, and 4% is presently in the form of grants from a variety of donors, thus leaving a gap of at least 300 million US$ that must be mobilized.35 In October 2001, the entire Stop TB Partnership was convened at a Partners' Forum in Washington to launch the Global Plan to Stop TB (GPSTB). The GPSTB consists of the various plans of the Partnership working groups and addresses the future work and the financial needs for TB control and research. It estimates that US$9.1 billion will be necessary between 2001 and 2005 to expand DOTS, adapt it to the challenges of HIV and MDR-TB, develop new tools, and strengthen the global movement to stop TB.36
At the beginning of the new millennium, the Stop TB Partnership is still facing a formidable challenge. The latest set of estimates of the global situation suggests that 8.2 million new TB cases occurred worldwide in the year 2000.37 The sub-Saharan African countries have the highest incidence rates, with an average for the region of about 300 per 100,000 population. However, in absolute terms, 60% of all cases were in Asia. More than 1.8 million deaths occurred in the same year, and more than 95% of those were in developing countries. Twenty-two countries suffered 80% of the global case burden and are priority for action if the global 2005 targets are to be achieved20 (Table 1).
To face this situation, there has been a remarkable expansion of the DOTS strategy during the last decade. The latest information shows that in 2000, 148 out of 210 countries and territories had adopted DOTS, and that 55% of the human population lived in areas where DOTS was potentially available20 (Fig. 5). Essentially, all of the 22 highest-burden countries were implementing DOTS, although with different coverage ranging from a mere 7% in Brazil to 100% in countries such as Kenya, Tanzania and Uganda.20 However, this rapid adoption of DOTS has not necessarily meant full geographical coverage in all settings, nor has it fully translated into universal access to services ready to manage TB patients appropriately. Today, only Vietnam is consistently reaching the targets, while Peru, the other high-burden country that reached the targets, left the high-burden country list in 2000 thanks to a regular decline in incidence. However, most of the 22 high-burden countries, especially the largest ones, have neither achieved full service coverage, nor, more importantly, the WHA targets. India has expanded impressively between July 1998 and mid-2002, reaching a coverage of nearly half a billion (Fig. 6). However, more than half of its population (9% of the global population) is still to be covered with DOTS. In the case of China, about one-third of the population (7% of the global population) still needs to be covered. There are also high-burden countries which still cover less than 20% of their population; these include Pakistan, Russia, Brazil and Afghanistan (Table 1).
Geographical coverage, however, is not all. Even countries with full DOTS implementation suffer from low detection rate under DOTS (i.e., the ratio between number of cases reported from DOTS areas and number of cases estimated for that country). For instance, Indonesia has a case detection under DOTS of only 19%; Bangladesh of 24%; Kenya of 43%; Tanzania of 45%; Uganda of 50%; Mozambique of 40% and Zimbabwe of 52%20 (Table 1). This is one of the main issues for TB control today: how to ensure that countries with full DOTS coverage detect at least 70% of the estimated infectious cases? In global terms, the DOTS case detection rate has progressed steadily during the last 7 years, going from 11% in 1995 to 27% in 2000, thanks to the nearly 2 million cases notified from DOTS areas in 2000. However, this is far from the 2005 70% target. Furthermore, the trend in DOTS case detection has been very regular over the past several years, with an average 130,000 additional cases having been enrolled annually. However, if this trend continues, the 70% global target will not be reached before 2013. It is estimated that nearly 350,000 additional cases must be recruited under DOTS if the case detection target has to be reached in 200520 (Fig. 7).
Therefore, the great challenge today is to accelerate the geographical expansion of DOTS within governmental services and, at the same time, to identify innovative ways through which case detection can increase rapidly while maintaining high cure rates.
Some of the constraints identified by the London Ad-hoc Committee in 199827 are now being addressed through the new Stop TB Partnership, the Global Drug Facility and the recent increase in financial aid to poor countries. Others remain to be properly tackled, especially the lack of human resources and managerial capacity in programmes. At the same time, attention must now be paid to country-specific obstacles impeding wider access to DOTS. In many settings, weaknesses of the general health systems, rather than of specific TB activities, are emerging as major constraints.
For instance, community participation in patient care is still lacking, despite demonstration of cost-effectiveness of community workers' involvement, compared to old practices of hospitalization, by a multi-centric project in districts of seven African countries.38 As a consequence of this project, Uganda has adopted a community-care approach for TB and other important public-health threats. Wide social mobilization is necessary to stimulate people and communities, and render health policy rooted within social movements. Second, primary care is often too poorly supported to guarantee adequate diagnosis and treatment of a variety of diseases, including TB. A response to this is a standardized, syndromic management of common respiratory complaints. While improving diagnostic capacity for TB, the WHO-sponsored Practical Approach to Lung Health (PAL) ensures proper, cost-effective treatment of priority respiratory diseases as required in modern times.39 This may be the natural evolution of well structured DOTS programmes towards supporting primary care in countries with good health services, such as Morocco and Chile. Third, other public systems that manage TB outside of the scheme of a national programme are often unlinked to regular programmes, thus adopting approaches which are neither standardized, nor effective. Urban administrations, prisons, public hospital systems, army health services, social security systems are examples of unlinked service providers. The solution is better coordination and, when necessary, enforcement of legal measures. Finally, the private sector is almost universally excluded from standard TB control practices and collaboration with governmental services. Private practitioners, academic institutions and non-governmental organizations need to be enlisted by national programmes and not marginalized, if comprehensive country-wide control is our target. Exclusion of the private sector often results in continuation of bad practices: misdiagnosis, high-defaulting, lack of notifications and ultimately, perpetuation of transmission and, likely, onset of drug resistance.40
Section snippets
Conclusions
In the last decade, the TB community has achieved a lot in global TB control. A clear strategic approach, DOTS, has been developed and promoted. DOTS has been shown to be effective in reducing TB mortality41 and incidence42 in all countries that have adopted it. Yet, there is no room for complacency, since the 2005 targets are still not at reach. The top priority for action remains geographical DOTS expansion within governmental structures. This must be coupled with innovative approaches to
References (42)
- et al.
Evolution of WHO policies for tuberculosis control, 1948–2001
Lancet
(2002) The International Union Against Tuberculosis and Lung Disease model national tuberculosis programme
Tuberc Lung Dis
(1995)- et al.
Is Africa lost?
Lancet
(1991) The global tuberculosis situation and the new control strategy of the World Health Organization
Tubercle
(1991)- et al.
Cost-effectiveness of chemotherapy for pulmonary tuberculosis in three sub-Saharan African countries
Lancet
(1991) - et al.
Assessment of worldwide tuberculosis control
Lancet
(1997) - et al.
Feasibility and cost-effectiveness of standardized second-line drug treatment for chronic tuberculosis patientsa national cohort study in Peru
Lancet
(2002) - et al.
Private practitioners and public healthweak links in tuberculosis control
Lancet
(2001) The mutual assistance programme of the IUATLD. Development, contribution and significance
Bull Int Union Tuberc Lung Dis
(1991)Tuberculosis—United States, First 39 weeks, 1985
MMWR
(1985)
The U-shaped curve of concern
Am Rev Respir Dis
Epidemiology of tuberculosis in the United States
Epidemiol Rev
The epidemiology of tuberculosis among foreign-born persons in the United States, 1986–1993
N Engl J Med
Nosocomial transmission of multidrug-resistant tuberculosis among HIV-infected persons—Florida, New York, 1988–1991
MMWR
Resurgent tuberculosis in New York Cityhuman immunodeficiency virus, homelessness, and the decline of tuberculosis control programs
Am Rev Respir Dis
The emergence of drug-resistant tuberculosis in New York City
N Engl J Med
Tuberculosis in New York City—turning the tide
N Engl J Med
Secular trends of tuberculosis in Western Europe
Bull World Health Organ
Tuberculosis in developing countriesburden, intervention and cost
Bull Int Union Tuberc Lung Dis
Tuberculosisa global overview of the situation today
Bull World Health Organ
Ninth Report. Technical Reports Series No. 552
Cited by (248)
Wearable microfluidic-based e-skin sweat sensors
2022, RSC AdvancesDrug-resistant tuberculosis in eastern Europe and central Asia: a time-series analysis of routine surveillance data
2020, The Lancet Infectious DiseasesPolymorphisms in the prostaglandin receptor EP2 gene confers susceptibility to tuberculosis
2016, Infection, Genetics and EvolutionCitation Excerpt :An estimated one-third of the world's population is infected with the tubercle bacillus Mycobacterium tuberculosis (M.tb). However, only 10% infected with M.tb actually develops active tuberculosis (TB), suggesting that innate immunity often contains the infection (Raviglione, 2003). It is well known that innate susceptibility to TB has a genetic component, but the exact mechanism of this genetic component remains unknown (Bellamy, 2003).
Tuberculosis Epidemiology
2016, International Encyclopedia of Public Health