WHO Calls Tuberculosis a Global Emergency - latimes WHO Calls Tuberculosis a Global Emergency April 24, 1993 |Reuters LONDON — The World Health Organization on Friday declared tuberculosis a global emergency, saying the disease will claim more than 30 million lives in the next decade unless action is taken now. "Tuberculosis today is humanity's greatest killer, and it is out of control in many parts of the world," said Arati Kochi, manager of WHO's tuberculosis program, at a news conference announcing a plan to combat what has been dubbed the "forgotten epidemic." "The disease, preventable and treatable, has been grossly neglected and no country is immune to it." Once believed to be under control, TB, as tuberculosis is often called, is spreading worldwide because of the emergence of drug-resistant strains, changing research priorities and a link between TB and AIDS. MORE: WHO: Tuberculosis Tuberculosis Fact Sheet No 104 Revised August 2002 Tuberculosis (TB) kills approximately 2 million people each year. The global epidemic is growing and becoming more dangerous.

The breakdown in health services, the spread of HIV/AIDS and the emergence of multidrug-resistant TB are contributing to the worsening impact of this disease. In 1993, the World Health Organization (WHO) took an unprecedented step and declared tuberculosis a global emergency, so great was the concern about the modern TB epidemic. It is estimated that between 2002 and 2020, approximately 1000 million people will be newly infected, over 150 million people will get sick, and 36 million will die of TB - if control is not further strengthened. Infection and Transmission TB is a contagious disease. Like the common cold, it spreads through the air. Only people who are sick with pulmonary TB are infectious. When infectious people cough, sneeze, talk or spit, they propel TB germs, known as bacilli, into the air. A person needs only to inhale a small number of these to be infected. Left untreated, each person with active TB will infect on average between 10 and 15 people every year. But people infected with TB will not necessarily get sick with the disease.

The immune system 'walls off' the TB bacilli which, protected by a thick waxy coat, can lie dormant for years. When someone's immune system is weakened, the chances of getting sick are greater. Someone in the world is newly infected with TB every second. Nearly 1% of the world's population is newly infected with TB each year. Overall, one third of the world's population is currently infected with the TB bacillus. 5-10% of people who are infected with TB (but who are not infected with HIV) become sick or infectious at some time during their life. Global and Regional Incidence Each year, more people are dying of TB. In Eastern Europe and Africa, TB deaths are increasing after almost 40 years of decline. In terms of numbers of cases, the biggest burden of TB is in south-east Asia. Factors Contributing to the Rise in TB TB kills about 2 million people each year (including persons infected with HIV). More than 8 million people become sick with TB each year. About 2 million TB cases per year occur in sub-Saharan Africa. This number is rising rapidly as a result of the HIV/AIDS epidemic. Around 3 million TB cases per year occur in south-east Asia.

Over a quarter of a million TB cases per year occur in Eastern Europe. HIV is accelerating the spread of TB HIV and TB form a lethal combination, each speeding the other's progress. HIV weakens the immune system. Someone who is HIV-positive and infected with TB is many times more likely to become sick with TB than someone infected with TB who is HIV-negative. TB is a leading cause of death among people who are HIV-positive. It accounts for about 11% of AIDS deaths worldwide. In Africa, HIV is the single most important factor determining the increased incidence of TB in the past 10 years. Poorly managed TB programmes are threatening to make TB incurable Until 50 years ago, there were no drugs to cure TB. Now, strains that are resistant to a single drug have been documented in every country surveyed and, what is more, strains of TB resistant to all major anti-TB drugs have emerged. Drug-resistant TB is caused by inconsistent or partial treatment, when patients do not take all their drugs regularly for the required period because they start to feel better, doctors and health workers prescribe the wrong treatment regimens or the drug supply is unreliable.

A particularly dangerous form of drug-resistant TB is multidrug-resistant TB (MDR-TB), which is defined as the disease due to TB bacilli resistant to at least isoniazid and rifampicin  the two most powerful anti-TB drugs. Rates of MDR-TB are high in some countries, especially in the former Soviet Union, and threaten TB control efforts. From a public health perspective, poorly supervised or incomplete treatment of TB is worse than no treatment at all. When people fail to complete standard treatment regimens, or are given the wrong treatment regimen, they may remain infectious. The bacilli in their lungs may develop resistance to anti-TB drugs. People they infect will have the same drug-resistant strain. While drug-resistant TB is treatable, it requires extensive chemotherapy (up to two years of treatment) that is often prohibitively expensive (often more than 100 times more expensive than treatment of drug-susceptible TB), and is also more toxic to patients. WHO and its international partners have formed the DOTS-Plus Working Group , which is attempting to determine the best possible strategy to manage MDR-TB.

One of the goals of DOTS-Plus is to increase access to expensive second-line anti-TB drugs for WHO-approved TB control programmes in low- and middle-income countries. Movement of people is helping the spread of TB Global trade and the number of people travelling in aeroplanes have increased dramatically over the past 40 years. In many industrialized countries, at least one-half of TB cases are among foreign-born people. In the United States, nearly 40% of TB cases are among foreign-born people. The number of refugees and displaced people in the world is also increasing. Untreated TB spreads quickly in crowded refugee camps and shelters. It is difficult to treat mobile populations, as treatment takes at least six months and should ideally be suvervised. As many as 50% of the world's refugees could be infected with TB. As they move, they may spread TB. Effective TB Control The WHO-recommended treatment strategy for detection and cure of TB is DOTS. DOTS combines five elements: political commitment, microscopy services, drug supplies, surveillance and monitoring systems and use of highly efficacious regimes with direct observation of treatment.

Once patients with infectious TB (bacilli visible in a sputum smear) have been identified using microscopy services, health and community workers and trained volunteers observe patients swallowing the full course of the correct dosage of anti-TB medicines (treatment lasts six to eight months). The most common anti-TB drugs are isoniazid, rifampicin, pyrazinamide, streptomycin and ethambutol. Sputum smear testing is repeated after two months, to check progress, and again at the end of treatment. A recording and reporting system documents patients' progress throughout, and the final outcome of treatment. Since DOTS was introduced on a global scale in 1991, about 10 million patients have received DOTS treatment. In half of China, cure rates among new cases are 96%. In Peru, widespread use of DOTS for more than five years has led to the successful treatment of 91 %of cases and a decline in incidence. By the end of 2000, all 22 of the highest burden countries which bear 80% of the world's estimated incident cases had adopted DOTS.

Fifty-five percent of the global population had access to DOTS, double the fraction reported in 1995. In the same year, 27% of estimated TB patients received treatment under DOTS, two and a half times the fraction reported in 1995. DOTS produces cure rates of up to 95% even in the poorest countries. DOTS prevents new infections by curing infectious patients. DOTS prevents the development of MDR-TB by ensuring the full course of treatment is followed. A six-month supply of drugs for DOTS costs as little as US$ 10 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." WHO targets are to detect 70% of new infectious TB cases and to cure 85% of those detected. Ten countries had achieved these targets in 2000. Governments, nongovernmental organizations and civil society must continue to act to improve TB control if we are to reach these targets worldwide.

For more information contact: WHO | Lives saved by tuberculosis control and prospects for achieving the 2015 global target for reducing tuberculosis mortality Disclaimer Lives saved by tuberculosis control and prospects for achieving the 2015 global target for reducing tuberculosis mortality Philippe Glaziou a, Katherine Floyd a, Eline L Korenromp b, Charalambos Sismanidis a, Ana L Bierrenbach a, Brian G Williams a, Rifat Atun b & Mario Raviglione a a. World Health Organization, 20 avenue Appia 20, 1211 Geneva 27, Switzerland. b. Global Fund to Fight AIDS, Tuberculosis and Malaria, Geneva, Switzerland. Correspondence to Philippe Glaziou (e-mail: glazioup@who.int ). (Submitted: 21 February 2011 – Revised version received: 04 May 2011 – Accepted: 11 May 2011 – Published online: 31 May 2011.) Bulletin of the World Health Organization 2011;89:573-582.

doi: 10.2471/BLT.11.087510 Introduction In 1993, the World Health Organization (WHO) declared the tuberculosis (TB) epidemic a global public health emergency. 1 At that time few countries worldwide had well established systems of TB control. 2 Since then substantial efforts to improve TB care and control have been made by means of the DOTS Strategy (1995–2006, comprising five policy elements) 2 and its successor, the Stop TB Strategy. 3 From 1995 to 2006, two indicators were used to monitor progress in TB control at global and national levels: the case detection rate (i.e. the ratio of notified cases to incident cases) and the rate of treatment success among detected cases. Between 1995 and 2009, 49 million TB patients were treated in 127 national DOTS programmes, and 41 million of them were treated successfully.

The case detection rate increased from 46% (range: 43–49) in 1995 to 63% (range: 60–67) in 2009. The rate of treatment success among notified cases of smear-positive TB increased from 57% in 1995 to 86% in 2008. 4 More recently, attention has shifted to measuring progress towards achievement of global targets for reductions in disease burden (Box 1). The global target under the Millennium Development Goals (MDGs) is that TB incidence should be declining by 2015. The Stop TB Partnership has endorsed this MDG target and has also set two additional global targets, namely, to halve TB prevalence and mortality rates by 2015 compared with their level in 1990. 4 Methods for measuring trends in disease burden have been clearly described 5 , 6 and recommendations set out in a WHO policy paper. 7 Box 1.

Goals, targets and indicators for tuberculosis (TB) control set within the Millennium Development Goals (MDGs) and by the Stop TB Partnership, and related targets included in MDGs 4 and 5 Targets specific to TB control MDGs Goal 6: Combat HIV/AIDS, malaria and other diseases Target 6.C: Halt and begin to reverse the incidence of malaria and other major diseases Indicator 6.9: Incidence, prevalence and death rates associated with TB Indicator 6.10: Proportion of TB cases detected and cured under DOTS Stop TB Partnership targets By 2015: Global burden of TB (per capita prevalence and death rates) halved relative to 1990 baseline By 2050: Global annual incidence of active TB less than 1 case per million population Related 2015 targets under MDGs 4 and 5 Goal 4: Reduce child mortality Target 4.A: Reduce the under-five mortality rate by two thirds between 1990 and 2005 Goal 5: Improve maternal health Target 5.A: Reduce the maternal mortality ratio by three quarters between 1990 and 2005 AIDS, acquired immunodeficiency syndrome; HIV,

 human immunodeficiency virus.

In addition to assessing trends in disease burden, it has become increasingly important to determine the number of lives saved by health-care interventions and the contribution of disease control efforts to the broader goal of improving maternal and child health (MDGs 4 and 5, Box 1). 8 For example, the Global Fund to Fight AIDS, Tuberculosis and Malaria, 9 which has helped to finance the scale-up of TB control in 112 low- and middle-income countries since 2002, uses a performance management framework that links financial investments (about 2 billion United States dollars [US$] for TB control in 2003–2010, including US$ 512 million in 2010) to programmatic outcomes and the population coverage of key interventions, and then to their impact on morbidity and mortality and progress towards MDG targets. 5 , 9 In this paper we assess if the global target of halving TB mortality by 2015 compared with 1990 levels can be achieved, and we perform the first global assessment of the lives saved by the DOTS/Stop TB Strategy.

We also include estimates of the lives saved among children and women of childbearing age (the focus of MDGs 4 and 5, respectively) and discuss the actions needed to improve the measurement of TB mortality and the impact of TB control. Methods Estimates of TB incidence, prevalence and mortality are published annually by WHO using data from national surveillance systems (case notifications and registered deaths) and special studies such as national surveys of the prevalence of disease. 5 The methods used are regularly peer-reviewed and published in both the scientific literature and in annual reports. 5 , 7 , 10 , 11 The last full update of the methods was completed in 2009 following an 18-month review by an expert group convened by the WHO Global Task Force on TB Impact Measurement. 5 These methods have also been scrutinized by a separate group of experts responsible for updating the estimated global burden of disease.

5 , 12 , 13 Following the International classification of diseases (ICD), which defines deaths from TB among those who are infected with the human immunodeficiency virus (HIV+) as deaths from acquired immunodeficiency syndrome (AIDS), WHO estimates of TB mortality are reported separately for the HIV-negative (HIV−) and HIV+ populations. Tuberculosis mortality since 1990 There are two major ways to estimate TB mortality: (i) to use mortality records from vital registration (VR) systems that code causes of death according to the last two revisions of the ICD (underlying cause of death: ICD-10 A15-A19, equivalent to ICD-9: 010–018); 14 and (ii) to estimate TB mortality as the product of TB incidence 5 and the TB case fatality rate (CFR). In countries where VR systems meet coverage and quality criteria, VR data provide a direct measurement of TB mortality among HIV− people and are thus preferable to indirect estimates derived from TB incidence and CFRs.

Data from VR systems are seldom suitable for estimating TB deaths among HIV+ people because, in compliance with ICD coding, TB deaths among HIV+ people are registered as AIDS deaths. Although TB can be recorded as a contributory cause, one third of countries with VR systems do not report contributory causes of death to WHO. In 2009, 90 countries had well functioning VR systems, defined as: (i) coverage of ≥ 80% of the population, and (ii) < 20% ill-defined causes (ICD-9 code B46, ICD-10 codes R00-R99). 15 These countries (Table 1) included four of the 22 high-burden countries (defined by WHO in 2000 as those accounting for about 80% of the world's estimated TB cases at the time): Brazil, the Philippines, the Russian Federation and South Africa. We used VR data from 89 of these 90 countries to estimate TB mortality among HIV− people. We excluded South Africa because in that country large numbers of HIV-related deaths were miscoded as TB deaths.

14 Among the 89 countries, 602 country–years of VR data on TB mortality (of a total of 1765 country–years) met the above criteria. 5 We assumed that in countries with a VR system the proportion of TB deaths was the same among deaths with no recorded cause as among deaths with a recorded cause. 5 html, 4kb In 2009, 124 countries (2448 country–years) lacked VR data of the necessary coverage and quality for every year since 1990. For these country–years and for the entire HIV+ population, TB mortality was estimated as the product of TB incidence (using time series published by WHO) 5 and the CFR (Box 2). CFRs were estimated for six groups of cases (Table 2) according to the findings of recent systematic reviews, cohort data and expert consensus. 5 , 10 , 11 Using Bayesian models, CFRs for HIV− cases were further refined for this study to obtain the best fit to the TB death rates recorded in VR systems (i.e. the death rates derived for 602 country–years across 89 countries).

Details are provided in Box 2. Box 2. Estimates of tuberculosis (TB) incidence and mortality TB incidenceNo country has ever undertaken a nationwide survey of TB incidence because of the large samples and logistic and financial challenges involved. As a result, no direct measurement of the incidence of TB is available. However, routine TB surveillance systems within health systems that have high coverage and good performance can capture all or nearly all incident cases of TB. TB underreporting (i.e. the percentage of diagnosed TB cases that are not notified) can be measured through special studies, 7 but few countries have conducted such studies on a nationally representative scale (examples include Egypt, the United Kingdom of Great Britain and Northern Ireland, the Syrian Arab Republic and Yemen). In the absence of direct measurements of the level of underreporting, plausible ranges are obtained through national consultations in which expert opinion is elicited based on an analysis of all available data according to the so-called “onion model”, a framework used by the Global Task Force on TB Impact Measurement of the World Health Organization (WHO) (described in detail elsewhere).

5 , 7 Between April 2009 and December 2010, consultations were conducted with 90 countries and incidence estimates were updated. Indirect methods for measuring incidence from the results of national tuberculin surveys are no longer recommended because there is very large uncertainty about the relationship between the annual risk of infection measured in such surveys and the incidence of TB. It was formerly assumed that one smear-positive case infected 10 people per year and remained infectious for an average period of 2 years, such that a 1% annual risk of infection translated into an incidence of smear-positive TB of 50 cases per 100 000 population (under the further assumption that the TB epidemic was in a stable state). These assumptions were based on data from the early or pre-chemotherapy era and no longer hold in settings with modern TB control. 16 It is theoretically possible to derive TB incidence from measurements of TB mortality or TB prevalence. However, quality measurements of TB mortality are generally not available in countries with a high burden of TB (Table 1). Furthermore, no accurate country-specific data on the duration of disease can be used to derive incidence from prevalence with reasonable confidence.

Measurements of illness duration during national surveys of the prevalence of TB disease do not represent the duration distribution throughout the country because survey investigations shorten the national history of disease in previously undetected prevalent cases. In this study we used incidence estimates published by WHO 4 and accounted for the uncertainty in incidence estimates when deriving indirect mortality estimates. Bayesian model for estimating TB case fatality rates in countries with no vital registration dataThe prior probability distribution of case fatality rates (CFRs) is the probability distribution representing one’s uncertainty about the true value of CFRs before VR data are observed. The posterior distribution is the conditional probability distribution of the value of the CFR that is assigned after VR data are taken into account. Therefore, posterior CFR distributions account for both prior knowledge, formalized in a prior probability distribution of the true value of the CFR, as well as for VR data. We estimated CFRs in a way that yielded the best fit to the VR-recorded TB death rates (within their uncertainty ranges) across the 602 country–years of data from the 89 countries with functioning VR systems, in conjunction with WHO estimates of the distributions of TB incidence in those countries.

This statistical fitting used Bayesian linear models defined separately for the following three groups of countries: (i) high-income; (ii) eastern Europe; (iii) all other countries. 5 We fitted the models separately to account for differences among these three groups in the ratio of reported TB mortality to TB case notification rates (data not shown). To fit the models we used Gibbs sampling and assumed that the value of the random error followed a normal distribution with a mean of zero: where y is TB mortality from VR data, I denotes TB incidence excluding HIV-positive (HIV+) people, N denotes TB notifications excluding HIV+ people, parameters β1 and 2 denote the CFRs in non-notified and notified cases, respectively, and indices i, j, k denote country, year and grouping, respectively. Semi-conjugate priors were set with an uninformative inverse gamma prior on the conditional error variance: Priors b and their precision B were defined as shown in Table 2. Convergence of Markov chains was assessed graphically and using convergence diagnostic tests.

Within each case category for 1990–2009, mortality estimates were computed by taking the product of posterior distributions of the CFR, assumed to be time-independent (Table 2), and country-year specific distributions of estimated incidence. 5 Within the same grouping by HIV and notification status, we assumed that CFRs in countries with no VR system were similar to CFRs in countries with functioning VR systems. We also assumed that CFRs specific to each case category were constant over time in the absence of any evidence to the contrary for any category. html, 6kb TB mortality was projected for 2010–2015 by fitting a log-linear model to the estimated time trend for 2006–2009. This was done separately for HIV+ and HIV− cases within each country. Projections of TB mortality among HIV+ people did not account for anticipated increases in coverage with antiretroviral therapy (ART).

Lives saved with the DOTS/Stop TB Strategy The lives saved through implementation of the DOTS/Stop TB Strategy were calculated as the difference between: (i) actual or projected TB deaths estimated according to the methods described above, and (ii) estimated TB deaths in a counterfactual (without DOTS) scenario in which TB control continued to perform at the levels observed in 1995, the year DOTS was introduced. This performance was defined in terms of the proportion of incident cases detected and notified in 1995, estimated to be 46% (range: 43–50) at best, much less than the 60–67% achieved by 2009 with the DOTS/Stop TB Strategy. 5 There were fewer deaths under the DOTS/Stop TB Strategy because the CFR is lower among notified cases (Table 2). We conservatively assumed that annual TB incidence rates were the same under both scenarios (i.e. that the DOTS/Stop TB Strategy had no effect on transmission and hence on TB incidence rates).

17 Uncertainty All estimates allowed for sampling uncertainty in the underlying measurements of TB mortality and incidence and in the prevalence of HIV infection among incident and notified TB cases, as well as for parameter uncertainty in the Bayesian models. Uncertainty bounds were defined as centiles 2.5 and 97.5 of outcome distributions. Global mortality rates for every year were computed by aggregating country–year mortality rate distributions through simulations. 18 Results In 2009, an estimated 1.3 million (range: 1.2–1.5) TB deaths occurred among HIV− people. This is equivalent to 20 deaths (range: 17−22) per 100 000 population, or 36% lower than the estimated 30 (range: 25−36) per 100 000 population that occurred in 1990 (Fig. 1). Between 2006 and 2009, the decline averaged 3.4% per year (range: 3.1−3.7). If this rate is sustained until 2015, TB-attributable deaths (i.e.

TB deaths among HIV− individuals) will be halved by 2015 compared with 1990 and the Stop TB Partnership target will be reached. Fig. 1. Global trends in tuberculosis (TB) mortality, 1990–2009 estimates and 2010–2015 forecast Note: Shaded areas represent uncertainty bands. The black horizontal line represents the Stop TB Partnership target of a 50% reduction in the 1990 mortality rate by 2015. Forecast expected values (dashed) were predicted by fitting log-linear models of time series for the years 2006–2009. In 2009 there were 0.38 million (range: 0.31–0.45 million) deaths among HIV+ individuals, compared with 0.073 million (range: 0.059 – 0.089) in 1990.

Overall, TB mortality (among HIV+ and HIV− people combined) fell from 31 (range: 26−37) per 100 000 population in 1990 to 25 (range: 22−28) per 100 000 population in 2009 (Fig. 1). The average annual decline was 3.7% (range: 3.3−4.2) between 2006 and 2009. If this rate is sustained, overall TB mortality will have fallen by around 32% between 1990 and 2015. TB mortality rates are falling in all WHO regions (data not shown), but in sub-Saharan Africa they have fallen relatively little since 1990 because of the sharp HIV-related increase in TB incidence in the 1990s. TB incidence and mortality rates in Africa levelled off and began to fall only around 2004.

In the counterfactual scenario (no introduction of DOTS), TB deaths would have increased from 1.5 million in 1995 to 2.0 million in 2009 among HIV− individuals, and from 0.2 million to 0.5 million among HIV+ individuals (Fig. 2). This means that between 4.1 and 5.7 million lives were saved between 1995 and 2009 among HIV− people (best estimate: 4.8 million, Table 3), and an additional 0.29 to 0.88 million lives were saved among HIV+ people. In total, 5.4 million (range: 4.6–6.3 million) lives were saved. Fig. 2. Estimated global number of tuberculosis (TB) deaths, 1995–2015 Note: Shaded areas represent uncertainty bands. Forecast expected values (dashed) were predicted by fitting log-linear models of time series for 2006–2009. We assumed that trends during 2006–2009 remained constant.

html, 2kb If the average annual decline in TB mortality between 2006 and 2009 can be sustained from 2010 to 2015, the global number of lives saved per year by 2015 (including among HIV+ people) will be more than 1 million (range: 0.8–1.2 million, Fig. 3) compared with the counterfactual scenario. Cumulatively, 5.5 million (range: 4.9–6 million) additional lives will have been saved between 2010 and 2015. Fig. 3. Lives saved by the DOTS/Stop TB Strategy during the period 1995–2015 at the global level, overall and by human immunodeficiency virus (HIV) infection status Note: Shaded areas represent uncertainty bands. Forecast expected values (dashed lines) were predicted by fitting log-linear models of the factual and counterfactual time series for 2006–2009.

In 2009, 47 000 to 57 000 HIV− children (aged 0–14 years) died of TB, and more girls died (range 28 000–36 000) than boys (range 17 000–22 000). In the same year, 0.43–0.55 million HIV− women of childbearing age (aged 15–45 years) died of TB. From 1995 to 2009, 0.23–0.28 million lives were saved among children and 1.4–1.7 million lives were saved among women of childbearing age. The cumulative number of additional lives that could be saved from 2010 to 2015 (if HIV+ people are excluded) includes those of 0.18–0.20 million children and of 1.5–1.7 million women of childbearing age.

Discussion This is the first study to assess whether the global target of halving TB mortality by 2015 relative to 1990 can be achieved and to estimate the lives saved by improved TB care and control since 1995. Our findings suggest that the introduction and expansion of the DOTS/Stop TB Strategy, whose application grew from a negligible level in 1995 to over 99% of all notified TB cases by 2009, saved 4.6–6.3 million lives between 1995 and 2009. Around one third of the lives saved were among women of childbearing age and children. By 2009 the average annual number of TB-attributable deaths per capita among HIV− people had dropped by 36% compared with 1990; by 2015 it will have fallen by 50% if the recent rate of decline is sustained. Our study has two major limitations. The first is that for most countries, we indirectly estimated trends in TB mortality since 1990 from time series data on TB incidence and CFRs, rather than directly from VR data.

This was the best that could be done given that VR data of the necessary coverage and quality were only available for countries that account for 32% of the world's population and 8% of all estimated TB deaths globally, and that VR data generally lack the detail and accurate coding required to estimate TB mortality among HIV+ people. 14 , 19 – 23 Moreover, although estimates of CFRs and estimates of TB incidence are uncertain, 6 we based our assumptions on recent literature reviews, expert consensus, consultations with 90 countries and reported treatment outcomes in national DOTS cohorts. 5 , 10 , 11 Second, we may have underestimated the effectiveness of the DOTS/Stop TB Strategy. Given the impossibility of having a control group for assessing the impact of better practices in TB control worldwide, we had to make several assumptions about what would have occurred if DOTS had never been introduced. We assumed the same trends in overall TB incidence and a constant CFR among cases that were not notified in both the actual and counterfactual scenarios (and implicitly assumed that economic growth and improvements in socioeconomic status had had no effect on TB incidence or CFRs in either scenario).

However, transmission of TB and TB incidence rates would probably have been higher in the absence of DOTS and the Stop TB Strategy. It is also possible that under the DOTS/Stop TB Strategy the application of good practices to an increasingly large fraction of TB cases had a positive influence on treatment among cases that were not notified. An example of this is the promotion of the International Standards of TB Care in both the public and private sectors as part of the Stop TB Strategy, which may have helped to improve the diagnosis and treatment of TB cases, especially in the private sector. 24 If so, CFRs among cases that were not notified could have improved instead of remaining unchanged. Finally, our projections for 2010 to 2015 did not account for the impact of ART scale-up in reducing deaths among HIV+ TB patients. In 2009, one third of HIV+ TB patients were started on ART. 5 We can directly compare our estimates with the results of only one study: an evaluation of the lives saved by DOTS programmes co-financed by the Global Fund.

In that study, the 3.3 million DOTS treatments delivered between 2003 and the end of 2007 in 68 countries were found to have saved around 0.4 million lives (95% confidence interval, CI: 0.26–0.55) compared with the pre-DOTS standard of treatment. 25 Although the methods differed, these results, equivalent to an average of 0.12 lives saved per DOTS treatment, are consistent with our findings. In addition to analyses at the global level, several country-specific examples illustrate the impact of good TB control. In Peru, improved TB case-finding and treatment following the introduction of DOTS saved an estimated 91 000 lives between 1991 and 2000, equivalent to 0.44 lives per treatment when the estimated impact of DOTS on transmission is also taken into account. 26 The impact of DOTS on the number of incident or prevalent TB cases has been demonstrated in China, 27 Cuba, 28 southern India 29 and Morocco.

30 Our results show that while TB-attributable mortality will be halved by 2015 among HIV− people, it will not be halved among HIV+ people at current rates of decline. To accelerate progress in reducing TB mortality, especially in Africa, where approximately 80% of the world's cases of HIV+ TB patients are found, 5 three interventions need to be expanded: ART for the treatment of HIV+ TB patients; 31 , 32 TB case-finding among people in HIV care; 33 and isoniazid chemoprophylaxis to prevent TB in people who are HIV+. 34 – 38 Elsewhere, expanding the diagnosis and treatment of multidrug-resistant TB (MDR-TB) could accelerate reductions in TB mortality. 39 – 41 In 2009, less than 5% of patients with MDR-TB were treated in accordance with international guidelines, and VR data from eastern Europe show that a higher prevalence of MDR-TB is associated with higher mortality (results not shown). In all parts of the world, TB control efforts will be sustained and expanded only if there is sustained and increased financing from domestic as well as international sources.

Maternal mortality and under-5 mortality remain major global challenges. 42 , 43 In 2008, deaths in children < 5 years old fell to 8.8 million, representing a 30% reduction from the 12.4 million deaths estimated in 1990. 4 At this rate of decline, the MDG 4 target of a 67% reduction will not be achieved by 2015, especially in sub-Saharan Africa, where under-5 mortality is declining more slowly than in other regions. 43 – 45 Nonetheless, improved TB control efforts saved an estimated 0.23–0.28 million lives in children < 15 years of age between 1990 and 2009 and 0.18 to 0.2 million additional lives could be saved by 2015.

We estimate that 1.4–1.7 million TB deaths were averted among women of childbearing age from 1995 to 2009 and that a further 1.5–1.7 million could be averted through TB control efforts between 2010 and 2015. In comparison, a cumulative total of 6.5–9.3 million maternal deaths occurred from 1990 to 2008. Declining TB mortality in women of childbearing age will continue to contribute to MDG 5, even though few low- and middle-income countries are currently on track to achieve the target of reducing the 1990 maternal mortality ratio by 75% by 2015. 46 Estimates of mortality trends and of the lives saved by health-care interventions are needed by policy-makers and for advocacy. However, the investment of resources needed to ensure high-quality data is often lacking. If good VR systems with high coverage were available in all countries, or at least in the 22 countries with the highest burden of TB, global trends both overall and among HIV+ and HIV− people could be much more accurately assessed than is currently feasible.

Measuring mortality through standardized VR systems and/or through validated interim mortality measurement systems with ICD coding of causes of death must be a priority for global health agencies. 14 , 22 , 47 – 49 Improvements in TB care and control since 1995 have saved millions of lives and brought within reach the global target of halving the 1990 TB mortality rate by 2015. To sustain progress, intensified efforts are needed to plan, finance and implement the full range of interventions recommended in the Stop TB Strategy, including research on new diagnostics, ART for HIV+ TB patients, TB prophylaxis in HIV+ individuals, prompt diagnosis and treatment of cases of MDR-TB, and accelerated research on new diagnostics, vaccines and treatments. 50 In addition, greater investments in national surveillance would make it possible to more accurately monitor progress in reducing TB incidence and mortality rates.

Competing interests: Rise in TB declared a global emergency | The Independent Rise in TB declared a global emergency Friday 23 April 1993 23:02 BST Click to follow The Independent Online THE World Health Organisation yesterday declared tuberculosis a global emergency which will claim 30 million lives within the next decade unless action is taken to halt its spread. TB is the leading cause of death world-wide from a single infectious agent and three million people die from it each year, although drugs which cure it are readily available and cheap. Eight million people develop the disease annually. Most cases are in developing countries but there has been an upsurge in the illness in industrialised countries, linked to the spread of Aids, increasing homelessness, drug misuse and poverty. These factors are largely responsible for renewed interest in Europe and America in a disease which many thought had been dealt with by modern medicine. The appearance of strains of Mycobacterium tuberculosis which are resistant to several drugs is also causing concern. In Britain, the decline stopped in the late 1980s - when incidence was about 6,000 cases a year. It is now running at 7,000 cases a year.

There was a 12 per cent increase in the US between 1986 and 1991, a 28 per cent rise in Italy between 1988 and 1990, and and a 33 per cent rise in Switzerland between 1986 and 1990. All three countries have a high proportion of HIV-infected individuals. Professor Richard Feacham, Dean of the London School of Hygiene and Tropical Medicine, said TB killed far more people than Aids, and equivalent money should be spent on research and prevention. He urged governments not to abandon school vaccination programmes. More about: NIH Fact Sheets - Tuberculosis Tuberculosis YESTERDAY Tuberculosis (TB) is one of the oldest human diseases. Mummies from ancient Egypt show signs of tubercular decay, and TB was common in both ancient Greece and Imperial Rome. Physicians identified TB by its hallmark symptoms: dry, persistent cough, bloody sputum, intermittent fevers, and flushed complexion. Emaciation often preceded a difficult death, giving TB the name “consumption”.

In 1882, the German physician Robert Koch announced his discovery that a microbe he called Mycobacterium tuberculosis (Mtb) causes TB. He also demonstrated that TB can be spread from person to person, carried by droplets expelled when an infected person coughs, sneezes, speaks, or laughs. A century ago, TB was a leading cause of death in the United States and in many European countries. TB disease and deaths have declined steadily from the early 1900s due largely to the introduction of effective antibiotics and improvements in living conditions. There is an inexpensive TB vaccine available known as Bacille Calmette Guerin, but its effectiveness is limited. More than one billion people have been inoculated since the vaccine was introduced in 1921. It can prevent severe forms of TB in young children but it is not reliable in preventing adult pulmonary TB. Before antibiotics became an effective treatment for TB in the 1940s, patients were treated in sanatoria, where therapy included plenty of fresh air, sleep, wholesome food, and exercise. TODAY In 1993, the World Health Organization (WHO) declared TB a “global health emergency”.

While improvements in global control have been implemented, TB continues to be a leading cause of death from an infectious disease in many countries of the world. It is estimated that one-third of the world’s population is infected with the TB bacterium, and that 16.2 million people currently have TB. TB remains one of the leading causes of death and illness in the world. Approximately 9.4 million new cases were reported in 2008 by the WHO. For 2008, the WHO reported an estimated 1.8 million deaths from TB, including 500,000 people who were also infected with HIV. The greatest number of deaths from TB per capita occurs in Africa, where HIV has led to rapid growth of the TB epidemic, and increases the likelihood of dying from TB. From 1985-1992, rates of TB in the United States increased, due largely to the HIV epidemic, cutbacks in public health infrastructure and treatment programs, increasing poverty, homelessness, and drug abuse. Since 1992, a large influx of Federal funds and renewed emphasis on TB therapy, prevention, and control again led to TB to decline in the United States.

The Centers for Disease Control and Prevention reported nearly 13,000 cases of TB, a reduction of 3.8% from the previous year. The TB crisis is intensified by the emergence of drug-resistant forms of the pathogen. Because of the long duration and associated side effects of standard TB drug treatment, patients often do not complete the full course of therapy. This fosters emergence of single- and multi-drug resistant TB (MDR-TB) strains. The treatment course for drug-resistant TB is even longer, sometimes more than two years. This therapy usually includes the use of costly second-line drugs that are often less effective and more toxic. In addition, patients with drug-resistant TB may remain infectious for long periods, thereby increasing the chance for transmission of resistant strains. A virtually untreatable form of MDR-TB, called extensively drug resistant TB (XDR-TB), was first defined in 2006. Global incidence of XDR-TB is difficult to determine.

However, in 2008, it was estimated that out of 10,000 TB patients, between 300 and 400 have drug-resistant TB and of those, 5-6 patients have the more resistant form, XDR-TB. The devastating global impact of TB makes it a high priority research area. NIH is supporting research to develop novel TB vaccines, drugs, and diagnostics through studies to characterize how the bacterium and host interact and to better understand how drug resistance develops and can be avoided in the future. NIH is expanding its existing HIV/AIDS clinical trial networks for TB studies, which may result in novel collaborations and critical data to improve TB control and care strategies. Recent advances in NIH supported TB research that may improve control of TB worldwide: Diagnostics A new diagnostic test that can identify TB and drug resistance directly from patient samples within 2 hours is being evaluated in late stage clinical testing. Currently available diagnostics take several months to diagnose drug resistant TB. Characterization of antibodies and other components of the immune response may help identify people who are infected with Mtb and are at the highest risk of developing active disease.

The NIAID Tuberculosis Clinical Diagnostics Research Consortium ( ) provides expertise and infrastructure to help evaluate early stage diagnostics for their potential to make significant contributions to TB diagnosis in high burden countries. Treatment Several promising new drug candidates have entered clinical trials and other drug candidates are being tested in the laboratory and in animals. Researchers are evaluating shorter treatment regimens that may make it easier for people to complete drug therapy. Several antibiotics that are already approved by the FDA for other infections are being evaluated as additions to current TB drug regimens to improve treatment of drug-resistant TB. NIAID researchers are conducting two new clinical trials In South Korea that will address how drugs penetrate into lesions of TB patients undergoing lung surgery. The researchers also will evaluate new drugs for XDR-TB. Vaccines Several new vaccine candidates are in advanced clinical trials, and additional candidates are being analyzed in animal studies. Research is underway to better understand how the Bacille Calmette Guerin vaccine provides protection against TB in children to help improve the effectiveness of this vaccine. TOMORROW These and future priority research areas will improve our understanding of TB and its various manifestations and improve our ability to prevent and treat this deadly disease.

Areas of interest include: the basic biology of TB in humans and the development and spread of MDR- and XDR-TB; technologies to rapidly diagnose drug resistance in TB patients; the interplay between TB, HIV, and other co-infections; and the development of effective strategies to prevent infection with Mtb or the development of active TB disease. Additional information about TB and NIH-supported TB research can be found at: Or, contact the National Institute of Allergy and Infectious Diseases (NIAID) Strategic Planning and Evaluation Branch: 301-496-6752 Download Readers: Global TB targets | DOTS & DOTS-Plus, failed Global Plans Global TB Control – DOTS & DOTS-Plus, failed Global Plans DOTS DOTS sign In 1994 the World Health Organisation (WHO) announced a new strategy, called DOTS, for the worldwide control of TB. DOTS was the Directly Observed Treatment Short course strategy. All countries with a TB problem were to provide standardized short course drug treatment to, at least, all sputum smear positive TB patients. Until 2006 DOTS was to be the internationally recommended approach to global TB control.

DOTS had five components which were initially as follows.1“What is DOTS? WHO Tuberculosis Factsheet”, WHO, 2006 What is dots? Sustained political and financial commitment. Diagnosis of TB by quality ensured sputum smear microscopy. Standardized short course anti TB treatment (SCC) given under direct and supportive observation (DOTS). A regular uninterrupted supply of high quality anti TB drugs. Standardized recording and reporting. Upside down DOTS sign In 1996 the WHO claimed that “where the health system is working even moderately well, the DOTS strategy is extraordinarily effective achieving cure rates over 90%.” But where in sub-Saharan Africa were there TB programs reliably implementing all five parts of DOTS? There were certainly some places where DOTS was remarkably effective. For example, with the control of TB in China where the country achieved cure rates of more than 85% although case detection barely climbed above 50%.2C McMillen, “Discovering Tuberculosis”, Yale University Press, 2015 DOTS was not however the “magic bullet” it was thought to be, and a universal solution had not been found.

However, the World Bank made support of TB programs contingent on the adoption of DOTS, and the “gospel” of DOTS spread far and wide. Five years after its emergence 120 countries had at least nominally adopted DOTS. When it was first introduced DOTS did not take any account of HIV. In a 2006 interview Arata Kochi the former director of TB programs at the WHO said: One thing that I didn’t do well is develop an additional strategy in addition to DOTS for HIV/TB . That is my regret. Multi drug resistant TB DOTS also did not take any account of drug resistant TB . Where resistance already exists to first line drugs such as isoniazid and rifampin, the DOTS program reverts to a short course of pyrazinamide and ethambutol. These are at doses insufficient to treat active TB, but in doses large enough to boost resistance. Further, if a patient’s TB was not cured, DOTS also called for retreatment with rifampin and isoniazid. So in these circumstances the DOTS programme could actually cause a worsening of the MDR TB situation.

DOTS-Plus In 1999 WHO and their partners launched DOTS-Plus. DOT-Plus was to be developed as a comprehensive initiative that was to build upon the five elements of DOTS. However it would take into account specific issues such as the use of second line anti TB drugs, that needed to be used in resource limited settings where there were significant levels of MDR TB . This new approach of DOTS Plus needed rapid assessment of its feasibility and effectiveness under programme conditions. So in 2000 the first DOTS-Plus pilot projects were launched and the Stop TB Working Group on DOTS-Plus for MDR-TB was also set up. One of the difficulties with the implementation of some of the DOTS-Plus pilot projects, was the need for quality second line anti TB drugs. These were normally very expensive and difficult to obtain. WHO and their partners made an arrangement with the pharmaceutical industry for preferential prices for the second line drugs used for the pilot projects. A ward for patients being treated under DOTS Plus However, it was considered important that these beneficial prices were only used in projects that were organised according to certain standards.

So the Green Light Committee was established to review project applications.They had to decide whether the applications were sufficiently in accordance with the guidelines that had been established for the pilot projects.3“DOTS-Plus & the Green Light Committee”, If programs were approved the drug purchasing took place through the Global Drug Facility.4“What is the GDF?”, By July 2005 36 DOTS-Plus pilot projects had been established in 27 countries for the treatment of more than 10,000 MDR-TB patients. With the ending of the piloting phase of DOTS-Plus it was believed that there was evidence that MDR-TB management was both feasible and effective in resource limited settings. With additional resources being available for MRD-TB control, there was then a rapid increase in the number of countries implementing DOTS-Plus. The Global Plan to Stop TB 2001–2005 By the year 2000 some global TB targets set in 1991 had still not been met. So further international meetings were held, and a new declaration was the Amsterdam Declaration to Stop TB.

The same goals were once again set, but this time to be achieved by 2005.5“Amsterdam Declaration to Stop TB”, Amsterdam, The Netherlands, 24th March 2000 The Stop TB Partnership was set up in 2001 following the Amsterdam Conference in 2000. Initially the partnership comprised just six organisations. Three of its working groups were: DOTS Expansion TB/HIV DOTS-Plus By the time the first Stop TB Partners’ Forum took place in October 2001 the partnership had grown from six to over 120 organisations. At the Forum the launch took place of the Global Plan to Stop TB 2001–2005.

Its aim was to provide a “roadmap” towards a TB free world, and it was considered that the 2005 TB control targets were realistic.6“First Stop TB Partners’ Forum”, Washington, 22 October 2001, 6 The Global Plan to Stop TB 2001–2005 made a number of commitments including that:7“First Stop TB Partners’ Forum”, Washington, 22 October 2001, 6 Within the next 50 months — by the end of 2005: A global DOTS case detection rate of at least 70% would have been achieved, while maintaining a treatment success rate of at least 85% Effective responses to TB/HIV and MDR TB would have been developed and scaled up A Global Plan to Stop TB for the period 2006–2010 would have been developed. The ending of DOTS Plus In 2006 WHO decided on an expansion of DOTS. This was not though a geographical expansion. This was effectively a redefinition of DOTS. In future DOTS would be about the provision of diagnosis, treatment and care for all patients.

This would include those with drug resistant TB, and also patients co-infected with TB and HIV. Effectively DOTS Plus would no longer exist, as its various parts for drug resistant TB, and for TB/HIV co-infection were included in a redefined DOTS program. The Global Plan to Stop TB 2006–2015 Once again the targets set in a Global Plan to Stop TB had not been reached. This time it was the targets in the Global Plan to Stop TB 2001–2005. These targets had been considered realistic back when they were set in 2001. In the new global plan for 2006–2015, the targets were no longer set in terms of the percentage of people reached in case detection rates, or a treatment success rate of at least 85%. Instead there were a range of targets covering specific areas such as the development of improved diagnostics and drugs, and the targets set in the Millenium Development Goals.

The Global Plan to Stop TB 2011–2015 Global Plan to Stop TB In 2009 the Stop TB Partnership produced a report on the progress that had been made in global TB control between 2006 and 2008.8“The Global Plan to Stop TB 2006-2015: Progress Report 2006-2008”, WHO, 2009 Many different areas were highlighted and in some, significant progress had been made, whereas in others, such as screening HIV positive people for TB, it was noted that much less progress had been made. It was particularly noted that the provision of funding for TB was an area of particular difficulty with a funding gap still existing of over US$1 billion per year.

The Global Plan was subsequently updated in 2010, to become the “Global Plan to Stop TB 2011–2015”.9“The Global Plan to Stop TB 2011-2015”, WHO, Geneva, 2010 After 2015 — Another Global Plan This time the plan was to end TB, with the WHO End TB Strategy, and the Global Plan to End TB 2016 – 2020. Meetings were held, documents were written and targets set. It was said that there needed to be a paradigm shift, that there needed to be a radical change in how TB was viewed. A belief that this time it was different. The WHO End TB Strategy and the Global Plan to End TB 2016 – 2020 set out as other plans had before the resources needed and how the targets could be met. Why is it going to be different? However, what they did not explain was why this time it would be different. Except that at some point those people who can implement these changes might decide that they care. They care about the 1.5 million people who die each year from a curable disease.

Resources were made available for Ebola, and how many people died? The answer is a fraction of the people who died in the same period from TB. This time lets all show that we care. Read more You can read more about the new plans to end TB . References

Question: In April 1993, the World Health Organisation declared which disease ‘A global health emergency’?
Answer: Tuberculosis