Dr TR Frieden, Commissioner of Health, Department of Health, 125 Worth Street, CN28, Room 331, New York, NY 10013, USA. E-mail: tfrieden{at}health.nyc.gov
![]() |
Abstract |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Methods We reviewed data for the amenability of TB to control. We considered separately control of deaths, prevalence, rate of infection and incidence.
Results Tuberculosis mortality can be reduced by more than 80% in less than 5 years. The prevalence of TB can be reduced by 30% or more annually; sustained annual decreases of 17% have been documented in a developing country. The TB infection rate can be reduced by 15% annually. In the absence of human immunodeficiency virus (HIV), TB incidence can be decreased by as much as 25% per year and up to 10% annually in developing countries. A high prevalence of untreated HIV infection in the adult population of a developing country will inevitably result in a significant increase in TB incidence despite optimal use of currently available technologies.
Conclusions Tuberculosis can be controlled if appropriate policies are followed, effective clinical and public health management is ensured, and there are committed and co-ordinated efforts from within and outside the health sector. However, in the context of a large epidemic of AIDS, TB incidence will inevitably increase. By 2001, less than 30% of global TB cases were reported to have received effective diagnosis, treatment and monitoring. Rapid expansion of effective TB control services is urgently required, both to avert the continued high burden of morbidity and mortality from TB and because of the HIV pandemic.
Keywords Tuberculosis, short-course chemotherapy, disease control, burden of disease
Accepted 17 January 2002
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
![]() |
Methods |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
![]() |
Results |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
In countries where baseline data exist, it is possible to make a reasonable estimate of the reduction in mortality achieved through DOTS implementation. Peru has been able to implement a highly effective DOTS programme, with a striking 80% reduction in mortality within just 3 years (Figure 1). This has been achieved by reducing the case fatality rate among treated patients through prompt diagnosis, effective and directly observed treatment, and increasing the proportion of patients treated. In India, mortality among smear-positive patients in the previous programme was 2030%, compared with 4% in the DOTS programmeapproximately a sevenfold reduction.11,13 Considering both smear-positive and smear-negative cases in India, DOTS reduces the case fatality rate by about 80%, even if neither secondary cases and their mortality, nor the increased detection rate, is taken into account. By early 2002, the Indian DOTS programme will have treated more than a million patients (see www.tbcindia.org), thereby saving nearly 200 000 lives. In China, national coverage with DOTS would prevent more than 60 000 deaths per year.14
|
|
Rate of infection
For the long-term control of TB, the rate of decline of the risk of infection with the TB bacteria is the most important indicator. If infection rates consistently decline, TB will eventually disappear.22 In industrialized countries, the risk of infection with TB bacteria decreased by approximately 5% or more per year even before the introduction of chemotherapy. With the introduction of effective treatment, the rate of infection decreased by 15% or more per year.23 In contrast, in developing countries, unless effective TB treatment services are in place, there is little or no decline in the annual risk of TB infection.24
Effective diagnosis and treatment of TB can rapidly reduce the risk of infection. With effective treatment, the risk of infection in developed countries can be reduced by 1015% per year.3 In Alaska, under rudimentary conditions not dissimilar to those in developing countries today, an intensive treatment programme resulted in a dramatic decline in the annual risk of infection by 1015% per year.25 However, few studies have attempted to document this in developing countries. Such studies are difficult logistically, and are further complicated by difficulties in the interpretation of tuberculin tests in the same population over time. One such survey in the Republic of Korea found an annual decrease in the risk of TB infection of 814% between the years 1965 and 1995, even though the treatment success rate (the proportion of patients cured plus those completing treatment)26 did not quite reach 85%.27 At a constant rate of BCG vaccination, the incidence of tuberculous meningitis in infants reflects the annual risk of infection. In Beijing, tuberculous meningitis decreased from 2.1 to 0.1 per 100 000 between 1986 and 1996, a decrease of 26% per year.20 However, some of this decrease may have been due to improved vaccination practices.
Incidence of disease
The incidence of TB is the combination of (i) recurrent TB in patients who have had previous episodes of disease, (ii) rapid progression to TB disease among individuals infected or re-infected within a relatively short period (e.g. 2 years) of infection, and (iii) reactivation of TB infection contracted many years previously. Recent developments in molecular epidemiology, along with conventional epidemiological investigations, have helped to determine the relative proportion of cases arising from each of these groups. A comprehensive study of TB epidemiology in South India found that, in 1972, only 37% of all smear-positive cases of TB arose from individuals who had a normal chest radiograph at the outset of the survey. Within 12 years, this fraction had increased to two-thirds, suggesting that a much higher proportion of cases arose from recent infection.15
The amenability of TB incidence to control, even in the absence of an epidemic of HIV, depends to a great extent on local epidemiology. At one extreme are situations in which the vast majority of TB cases arise from remote infection. A recent survey in Norway has shown that fewer than one in five patients developed TB as the result of recent infection; the overwhelming majority of cases arose from remote infection or recurrent TB.28 Most such cases will not be prevented with current technologies. Many individuals with remotely acquired infections will not be candidates for preventive treatment, and, even if preventive treatment is attempted on a mass scale, its success is far from assured because adherence may be low. At the other extreme are populations in which as many as half of all TB cases arise from infection or re-infection within the preceding 2 years. In such a context, the application of effective TB control measures can result in a very rapid decline in TB cases. For example, in New York City the incidence of TB among people born in the US declined by 25% annually over the 5-year period of 19921996; incident cases of multidrug-resistant TB, many of which were linked to ongoing transmission in health facilities, declined by 34% annually in the same time period.29 Similarly, an elegant study in San Francisco documented that more than one-third of cases resulted from recent transmission, as indicated by clustering of DNA fingerprints. With improved control measures, the overall case rate declined by 7% per year; the rate of clustered cases declined by 15% per year while non-clustered cases declined by only 5% per year.30 In New York City, molecular epidemiological studies documented a 26% decline in the estimated incidence of clustered smear-positive TB between 1991 and 1997 (ref. 31 and New York City Department of Health, unpublished data, 1997).
A limited number of surveys in developing countries suggest that the proportion of new cases caused by recent infection may range from 29% to 48%.3235 Such cases can be rapidly decreased by effective treatment. In addition, cases arising from reactivation of TB may decline steadily over a longer period of time. Thus, on theoretical grounds, it should be possible to control incidence even in developing countries. This prediction has been borne out by experience.
In developing countries where effective treatment practices have not been implemented, the incidence of TB remains essentially static.15 In contrast, rapid declines in TB incidence have been documented in the developing world when effective TB control measures are applied. In underdeveloped parts of Alaska and Canada, incidence decreased by 15% annually when the government devoted sufficient resources to ensure effective treatment. In Beijing, during a period when the proportion of incident cases that was notified was believed to be high and constant, a 9% annual decrease in new smear-positive cases was documented between 1986 and 1996.20 In Cuba, with application of directly observed treatment and efficient treatment organization achieving high rates of treatment success, the reported rate of new smear-positive cases decreased by 10% per year over a 26-year period.6 In Peru, cases of TB declined by approximately 8% per year from 1994 to 2000.5 An 810% annual reduction will cut the number of cases by half in 7 years. Thus, in the absence of an HIV epidemic, the incidence of TB can be significantly reduced even in developing countries.
![]() |
Tuberculosis control in the context of HIV |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
An HIV epidemic increases the incidence of TB by increasing the risk of reactivation in patients already infected with the TB bacteria, as well as by rapid and widespread dissemination of TB in HIV-infected populations. As a result, the incidence of TB will inevitably increase in most areas of the world if the rate of HIV infection in the adult population is high (e.g. 5%) (Table 1
). Hence, in the presence of a significant proportion of untreated HIV infection among adults, TB incidence cannot be reduced with current technologies.
|
An effective TB control programme can blunt the impact of HIV-associated TB, and can also prevent the related emergence of multidrug-resistant TB.36 Tuberculosis has increased explosively in areas of the world where HIV is endemic; these increases have been significantly less in areas with effective TB control services.37
Experience in the United Republic of Tanzania may be somewhat encouraging in this regard. Although the country is in the midst of a substantial epidemic of HIV, systematic surveys for annual risk of infection over the past 15 years have documented continued stable or even slightly declining (2% annually) rates of TB infection.38 This suggests that an effective TB control programme can, by means of prompt diagnosis and effective treatment, limit the number of secondary infections and cases.
Theoretically, preventive treatment for HIV-infected patients who also have TB infection could dramatically reduce the impact of HIV on TB epidemiology. However, since most individuals with HIV infection in developing countries do not know their infection status, and because of the logistic difficulties of giving preventive treatment for latent TB infection to a large number of patients who have no clinical symptoms, the practical applicability of treatment of latent TB infection may be limited to individual rather than public health interventions.
New York City demonstrated that it is possible to control an outbreak of TB even in the context of HIV, and even in an area where multidrug resistance has become common.4 This was achieved by ensuring prompt diagnosis, high-quality laboratory work, standardized treatment, direct observation as the standard of care, and rigorous cohort analysis with accountability for every patient diagnosed. In addition, the spread of TB in hospitals was curtailed. However, the prevalence of HIV infection among adults in New York City probably did not exceed 3%, in contrast with more than 30% HIV prevalence among adults in some countries of Africa.
![]() |
Conclusions |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Thus, the answer to the question, Can tuberculosis be controlled? is Yesif appropriate policies are followed, effective clinical and public health management is ensured, and there are committed and co-ordinated efforts for its control from within and outside of the health sector.41 Rapid expansion of effective TB control services is urgently required, both to avert the continued high burden of morbidity and mortality from TB and because of the HIV pandemic.
KEY MESSAGES
|
![]() |
Acknowledgments |
---|
![]() |
Notes |
---|
Centers for Disease Control and Prevention, Atlanta, GA, USA.
Columbia University School of Public Health, New York City, NY, USA.
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
2 Frieden TR. Tuberculosis control and social change. Am J Public Health 1994;84:172123.[ISI][Medline]
3 Styblo K, Bumgarner JR. Tuberculosis can be controlled with existing technologies: evidence. Tuberculosis Surveillance Research Unit, Progress Report, 1991, pp. 6072.
4 Frieden TR, Fujiwara PI, Washko RM, Hamburg MA. Tuberculosis in New York Cityturning the tide. New Engl J Med 1995;333:22933.
5 Suarez PG, Watt CJ, Alarcon E et al. The dynamics of tuberculosis in response to 10 years of intensive control effort in Peru. J Infect Dis 2001;184:47378.[CrossRef][ISI][Medline]
6 Marrero A, Caminero JA, Rodriguez R, Billo NE. Towards elimination of tuberculosis in a low-income country: the experience of Cuba, 196297. Thorax 2000;55:3945.
7 World Health Organization. Treatment of Tuberculosis, Guidelines for National Programmes. Geneva: World Health Organization, 1997.
8 Hinshaw HC, Feldman WH. Streptomycin in the treatment of clinical tuberculosis: a preliminary report. Proc Staff Meet Mayo Clinic 1945; 20:31318.[ISI]
9 Crofton J. The contribution of treatment to the prevention of tuberculosis. Bull Int Union Tuberc 1962;32:64353.
10 Styblo K. Epidemiology of Tuberculosis. Vol. 24. The Hague, Royal Netherlands Tuberculosis Association, 1984.
11 Datta M, Radhamani MP, Selvaraj R et al. Critical assessment of smear-positive pulmonary tuberculosis patients after chemotherapy under the district tuberculosis programme. Tuberc Lung Dis 1993;74:18086.[ISI][Medline]
12 Global Tuberculosis Control: WHO Report 2001. Geneva: World Health Organization, 2001 (WHO/CDS/TB/2001.287).
13 www.tbcindia.org/method.asp
14 Dye C, Fengzeng Z, Scheele S, Williams BG. Evaluating the impact of tuberculosis control: number of deaths prevented by short-course chemotherapy in China. Int J Epidemiol 2000;29:55864.
15 Tuberculosis Research Centre, Chennai. Trends in the prevalence and incidence of tuberculosis in South India. Int J Tuberc Lung Dis 2001; 5:14257.[ISI][Medline]
16 Khatri GR, Frieden TR. The status and prospects of tuberculosis control in India. Int J Tuberc Lung Dis 2000;4:193200.[ISI][Medline]
17 Styblo K, Dankova D, Drapela J et al. Epidemiological and clinical study of tuberculosis in the district of Kolín, Czechoslovakia. Bull World Health Org 1967;37:81974.[ISI][Medline]
18 Frieden TR, Sterling T, Pablos-Mendez A, Kilburn JO, Cairthen GM, Dooley SW. The emergence of drug resistant tuberculosis in New York City. N Engl J Med 1993;328:52126.
19 Fujiwara PI, Cook SV, Rutherford CM et al. A continuing survey of drug-resistant tuberculosis, New York City, April 1994. Arch Int Med 1997;157:53136.[CrossRef][ISI]
20 Zhang LX, Tu DH, Enarson DA. The impact of directly-observed treatment on the epidemiology of tuberculosis in Beijing. Int J Tuberc Lung Dis 2000;4:90410.[ISI][Medline]
21 Frimodt-Moller J. A community wide tuberculosis study in a south Indian rural population, 195055, Bull World Health Organ 1960;22: 61170.[Medline]
22 Frost WH. How much control of tuberculosis? Am J Public Health 1937;27:75966.
23 Styblo K. Overview and epidemiologic assessment of the current global tuberculosis situation with an emphasis on control in developing countries. Rev Infect Dis 1989;11:S33946.[ISI][Medline]
24 Styblo K. Epidemiology of Tuberculosis. Vol. 24. The Hague, Royal Netherlands Tuberculosis Association, 1984, p. 97.
25 Kaplan GJ, Fraser RI, Comstock GW. Tuberculosis in Alaska, 1970. The continued decline of the tuberculosis epidemic. Am Rev Respir Dis 1972;105:92026.[ISI][Medline]
26 World Health Organization, International Union Against Tuberculosis and Lung Disease, Royal Netherlands Tuberculosis Association. Revised international definitions in tuberculosis control. Int J Tuberc Lung Dis 2001;5:21315.[ISI][Medline]
27 Neuenschwander BE, Zwahlen M, Kim SJ, Engel RR, Rieder HL. Trends in the prevalence of infection with Mycobacterium tuberculosis in Korea from 1965 to 1995: an analysis of seven surveys by mixture models. Int J Tuberc Lung Dis 2000;4:71929.[ISI][Medline]
28 Heldal E, Docker H, Caugant DA et al. Pulmonary tuberculosis in Norwegian patients. The role of reactivation, re-infection and primary infection assessed by previous mass screening data and restriction fragment length polymorphism analysis. Int J Tuberc Lung Dis 2000;4: 30007.[ISI][Medline]
29 Tuberculosis Information Summary1999. New York, New York City Department of Health, 2000.
30 Jasmer RM, Hahn JA, Small PM et al. A molecular epidemiologic analysis of tuberculosis trends in San Francisco, 19911997. Ann Intern Med 1999;130:97178.
31 Frieden TR, Woodley CL, Crawford JT, Lew D, Dooley S. The molecular epidemiology of tuberculosis in New York City: the importance of nosocomial transmission and laboratory error. Tuber Lung Dis 1996; 77:40713.[ISI][Medline]
32 Diaz R, Kremer K, de Haas PE et al. Molecular epidemiology of tuberculosis in Cuba outside of Havana, July 1994June 1995: utility of spoligotyping versus IS6110 restriction fragment length polymorphism. Int J Tuberc Lung Dis 1998;2:74350.[ISI][Medline]
33 Yang ZH, Mtoni I, Chonde M et al. DNA fingerprinting and phenotyping of Mycobacterium tuberculosis isolates from human immunodeficiency virus (HIV)-seropositive and HIV-seronegative patients in Tanzania. J Clin Microbiol 1995;33:106469.[Abstract]
34 Garcia-Garcia M, Palacios-Martinez M, Ponce-de-Leon A et al. The role of core groups in transmitting Mycobacterium tuberculosis in a high prevalence community in Southern Mexico. Int J Tuberc Lung Dis 2000;4:1217.[ISI][Medline]
35 Wilkinson D, Pillay M, Crump J, Lombard C, Davies GR, Sturm AW. Molecular epidemiology and transmission dynamics of Mycobacterium tuberculosis in rural Africa. Trop Med Int Health 1997;2:74753.[ISI][Medline]
36 Kenyon TA, Mwasekaga MJ, Huebner R, Rumisha D, Binkin N, Maganu E. Low levels of drug resistance amidst rapidly increasing tuberculosis and human immunodeficiency virus co-epidemics in Botswana. Int J Tuberc Lung Dis 1999;3:411.[ISI][Medline]
37 Cantwell MF, Binkin NJ. Tuberculosis in sub-Saharan Africa: a regional assessment of the impact of the human immunodeficiency virus and national tuberculosis control program quality. Tuber Lung Dis 1996;77:22026.[ISI][Medline]
38 Royal Netherlands Tuberculosis Association and International Tuberculosis Surveillance, The Hague. Tuberculosis control in the era of the HIV epidemic: risk of tuberculosis infection in Tanzania, 19831998. Int J Tuberc Lung Dis 2001;5:10312.[ISI][Medline]
39 Styblo K. Eradication of tuberculosis in developed countries in the HIV era. Bull Int Union Tuber Lung Dis 1989;64:5864.
40 Brudney K, Dobkin J. Resurgent tuberculosis in New York City: human immunodeficiency virus, homelessness, and the decline of tuberculosis control programs. Am Rev Respir Dis 1991;144:74549.[ISI][Medline]
41 Dye C. Tuberculosis 20002010: control, but not elimination. Int J Tuberc Lung Dis 2000;4(Suppl.):S14652.[ISI][Medline]