Abstract
Despite major progress in the development of new strategies for diagnosing and treating tuberculosis, the disease still remains a major challenge for healthcare workers throughout the world. A number of causes are responsible for this threat but, unfortunately, many of these cannot be resolved easily because of cultural and social factors. Furthermore, not all countries throughout the world have enough financial resources to support educational and therapeutic programmes. The major challenges with tuberculosis are 2-fold: (i) to deal with the growing epidemic around the world (and especially in ‘low-income’ [developing] countries), and; (ii) to ensure correct use of antituberculosis medications in order to protect these drugs for future use. In ‘high-income’ countries, a major decline in the incidence of tuberculosis has been observed. Nevertheless, tuberculosis remains an important challenge in some risk groups, particularly the elderly patient, in these countries. The clinical and radiological presentations are often nonspecific, leading to delayed diagnosis and appropriate treatment, which often results in a large proportion of cases being discovered at autopsy only. Considering tuberculosis in the differential diagnosis remains the cornerstone of a fast and accurate diagnosis of this condition.
Management of active tuberculosis in the elderly does not differ fundamentally from that in younger patients with respect to outcomes or adverse effects of treatment. However, empirical treatment perhaps may be considered more readily in the elderly patient.
Elderly persons infected with tuberculosis at the beginning of the 20th century constitute a large reservoir of latent tuberculosis infection. Furthermore, these individuals are at increased risk of reactivation of this remote infection as their immunological status declines with aging. Compared with the past, modern guidelines are less reluctant to recommend use of tuberculin skin testing, treatment of latent tuberculosis infection in elderly persons, and prevention of transmission of tuberculosis in nursing homes.
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References
Herzog H. History of tuberculosis. Respiration 1998; 65: 5–15
Donoghue HD, Spigelman M, Greenblatt CL, et al. Tuberculosis: from prehistory to Robert Koch, as revealed by ancient DNA. Lancet Infect Dis 2004; 4: 584–92
Snider GL. Tuberculosis then and now: a personal perspective on the last 50 years. Ann Intern Med 1997; 126: 237–43
Rieder HL. Epidemiology of tuberculosis in Europe. Eur Respir J 1995; 20: 620s–32s
Young LS, Wormser GP. The resurgence of tuberculosis. Scand J Infect Dis 1994; 93: 9–19
Iseman MD. A clinician’s guide to tuberculosis. Philadelphia (PA): Lippincott Williams and Wilkins, 2000
Lauzardo M, Ashkin D. Phthisiology at the dawn of the new century: a review of tuberculosis and the prospects for its elimination. Chest 2000; 117: 1455–73
Rose AM, Watson JM, Graham C, et al. Tuberculosis at the end of the 20th century in England and Wales: results of a national survey in 1998. Thorax 2001; 56: 173–9
Dye C, Scheele S, Dolin P, et al. Consensus statement: global burden of tuberculosis — estimated incidence, prevalence and mortality by country. WHO global surveillance and monitoring project. JAMA 1999; 282: 677–86
Van den Brande P, Vanhoenacker F, Demedts M. Tuberculosis at the beginning of the third millenium: one disease, three epidemics. Eur Radiol 2003; 13: 1767–70
Corbett EL, Watt CJ, Walker N, et al. The growing burden of tuberculosis: global trends and interactions with the HIV epidemic. Arch Intern Med 2003; 163: 1009–21
Davies PD. The effects of poverty and ageing on the increase in tuberculosis. Monaldi Arch Chest Dis 1999; 54: 168–71
Raviglione MC. The TB epidemic from 1992 to 2002. Tuberculosis 2003; 83: 4–14
Dolin PJ, Raviglione MC, Koch A. Estimates of future global tuberculosis morbidity and mortality. MMWR Morb Mortal Wkly Rep 1993; 42: 961–4
Van den Brande P, Uydebrouck M, et al. Tuberculosis in asylum seekers in Belgium. Eur Respir J 1997; 10: 610–4
Chaimowicz F. Age transition of tuberculosis incidence and mortality in Brazil. Rev Saude Publica 2001; 35: 81–7
Devereaux Hutton M, Cauthen GM, et al. Results of a 29-state survey of tuberculosis in nursing homes and correctional facilities. Public Health Rep 1993; 108: 305–14
Kearney MT, Wanklyn PD, Goldman JM. Urban deprivation and tuberculosis in the elderly. Respir Med 1994; 88: 703–4
Stead WW. Tuberculosis among elderly persons: an outbreak in a nursing home. Ann Intern Med 1981; 94: 606–10
Ijaz K, Dillaha JA, Yang Z, et al. Unrecognized tuberculosis in a nursing home causing death with spread of tuberculosis to the community. J Am Geriatr Soc 2002; 50: 1213–8
Van den Brande P, Demedts M. Four-stage tuberculin testing in elderly subjects induces age-dependent progressive boosting. Chest 1992; 101: 447–50
Ben-Yehuda A, Weksler ME. Host resistance and the immune system. Clin Geriatr Med 1992; 8: 701–11
Castle S, Uyemura K, Wong W, et al. Evidence of enhanced type 2 immune response and impaired upregulation of a type 1 response in frail elderly nursing home residents. Mech Ageing Dev 1997; 94: 7–16
Kurashima C, Utsuyama M, Kasi M, et al. The role of thymus in the aging of TH cell subpopulations and age-associated alteration of cytokine production by these cells. Int Immunol 1995; 7: 97–104
Menzies D. Interpretation of repeated tuberculin tests: boosting, conversion and reversion. Am J Respir Crit Care Med 1999; 159: 15–21
Finucane TE. The American Geriatrics Society Statement on two-step PPD testing for nursing home patients on admission. J Am Geriatr Soc 1988; 36: 77–8
Stead WW, Kerby GR, Schlueter DP, et al. The clinical spectrum of primary tuberculosis in adults. Ann Intern Med 1968; 68: 731–45
Van den Brande P, Vijgen J, Demedts M. Clinical spectrum of pulmonary tuberculosis in older patients: comparison with younger patients. J Gerontol 1991; 46: M204–9
Miller RA. The aging immune system: primer and prospectus. Science 1996; 273: 70–4
Perez-Guzman C, Vargas MH, Torres-Cruz A, et al. Does aging modify pulmonary tuberculosis: a meta-analytical review. Chest 1999; 116: 961–7
Rajagopalan S. Tuberculosis and aging: a global health problem. Clin Infect Dis 2001; 33: 1034–9
Korzeniewska-Kosela M, Krysl J, Müller N, et al. Tuberculosis in young adults and the elderly. Chest 1994; 106: 28–32
Leung CC, Yew WW, Chan CK, et al. Tuberculosis in older people: a retrospective and comparative study from Hong Kong. J Am Geriatr Soc 2002; 50: 1219–26
American Thoracic Society. Diagnostic standards and classification of tuberculosis in adults and children. Am J Respir Crit Care Med 2000; 161: 1376–95
Rieder HL. How to combat tuberculosis in the year 2000? Respiration 1998; 65: 423–31
Patel YR, Mehta JB, Harvill L. Flexible bronchoscopy as a diagnostic tool in the evaluation of pulmonary tuberculosis in an elderly population. J Am Geriatr Soc 1993; 41: 629–32
Conde MB, Soares SL, Mello FC, et al. Comparison of sputum induction with fiberoptic bronchoscopy in the diagnosis of tuberculosis. Am J Respir Crit Care Med 2000; 162: 2238–40
Drobniewski FA, Caws M, Gibson A, et al. Modern laboratory diagnosis of tuberculosis. Lancet Infect Dis 2003; 3: 141–7
Lim TK, Zhu D, Gough A, et al. What is the optimal approach for using a direct amplification test in the routine diagnosis op pulmonary tuberculosis? A preliminary assessment. Respirology 2002; 7: 351–7
Van den Brande P, Verniest T, Verwerft J, et al. Impact of age and radiographie presentation on the presumptive diagnosis of tuberculosis. Respir Med 2002; 96: 979–83
American Thoracic Society. American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: treatment of tuberculosis. Am J Respir Crit Care Med 2003; 167: 603–62
Migliori GB, Raviglione MC, Schaberg T, et al. Tuberculosis management in Europe: Task Force of the European Respiratory Society (ERS), the World Health Organisation (WHO) and the International Union against Tuberculosis and Lung Disease (IUATLD) Europe Region. Eur Respir J 1999; 14: 978–92
Pabloz-Méndez A, Sterling TR, Frieden TR. The relationship between delayed or incomplete treatment and all-cause mortality in patients with tuberculosis. JAMA 1996; 276: 1223–8
Rothe TB, Karrer W. Short-course therapy of pulmonary tuberculosis: doctor’s compliance. Tuber Lung Dis 1996; 77: 93–7
Vlaamse Vereniging voor Respiratoire Gezondheiszorg en Tuberculosebestrijding. Tuberculoseregistratie en opsporing in 1994. Berichten 1995; 5: 3–10
Ormerod LP, Prescott RJ. The management of pulmonary and lymph node tuberculosis notified in England and Wales in 1998. Clin Med 2003; 3: 57–61
Oursler KK, Moore RD, Bishai WR, et al. Survival of patients with pulmonary tuberculosis: clinical and molecular epidemiologic factors. Clin Infect Dis 2002; 34: 752–9
Rajogopalan S, Yoshikawa TT. Tuberculosis in long-term-care facilities. Infect Control Hosp Epidemiol 2000; 21: 611–5
Frieden TR, Sterling TR, Munsiff SS, et al. Tuberculosis. Lancet 2003; 362: 887–99
Horsburgh Jr CR, Feldman S, Ridzon R. Practice guidelines for the treatment of tuberculosis. Clin Infect Dis 2000; 31: 633–9
Grosset J. Bacteriologic basis of short-course chemotherapy for tuberculosis. Clin Chest Med 1980; 1: 231–41
Jindani A, Doré CJ, Mitchison DA. Bactericidal and sterilizing activities of antituberculosis drugs during the first 14 days. Am J Respir Crit Care med 2003; 167: 1348–54
Zhang Y, Mitchison D. The curious characteristics of pyrazinamide: a review. Int J Tuberc Lung Dis 2003; 7: 6–21
Douglas JG, McLeod M-J. Pharmacokinetic factors in the modern drug treatment of tuberculosis. Clin Pharmacokinet 1999; 37: 127–46
Joint Tuberculosis Committee of the British Thoracic Society. Chemotherapy and management of tuberculosis in the United Kingdom: recommendations 1998. Thorax 1998; 53: 536–48
Turnheim K. When drug therapy gets old: pharmacokinetics and pharmacodynamics in the elderly. Exp Gerontol 2003; 38: 843–53
Acocella G, Nonis A, Gialdroni-Grassi G, et al. Comparative bioavailability of isoniazid, rifampicin and pyrazinamide in free combination and in a fixed triple formulation designed for daily use in antituberculosis chemotherapy. Am Rev Respir Dis 1988; 136: 882–5
Peloquin CA. Therapeutic drug monitoring in the treatment of tuberculosis. Drugs 2002; 62: 2169–83
Parkin DP, Vandenplas S, Botha FJ, et al. Trimodality of isoniazid elimination: phenotype and genotype in patients with tuberculosis. Am J Respir Crit Care Med 1997; 155: 1717–22
Pea F, Milaneschi R, Baraldo M, et al. Isoniazid and its hydrazine metabolite in patients with tuberculosis. Clin Drug Invest 1999; 17: 145–54
Sbarbaro JA, Iseman MD, Crowle AJ. The combined effect of rifampin and pyrazinamide within the human macrophage. Am Rev Respir Dis 1992; 146: 1448–51
Jain A, Mehta VL, Kulshrestha S. Effect of pyrazinamide on rifampicin kinetics in patients with tuberculosis. Tuber Lung Dis 1993; 74: 87–90
Plets MW, De Roux A, Roth A, et al. Early bactericidal activity of moxifloxacin in treatment of pulmonary tuberculosis: a prospective, randomized study. Antimicrob Agents Chemother 2004; 48: 780–2
Ginsburg AS, Grosset JH, Bishai WR. Fluoroquinolones, tuberculosis and resistance. Lancet Infect Dis 2003; 3: 432–42
Pablos-Méndez A, Knirsch CA, Barr RG, et al. Nonadherence in tuberculosis treatment: predictors and consequences in New York City. Am J Med 1997; 102: 164–70
Kimerling M. Low serum antimycobacterial drug levels in non-HIV-infected tuberculosis patients. Chest 1998; 113: 1178–83
Iseman MD, Cohn DL, Sbarbaro JA. Directly observed treatment of tuberculosis: we can’t afford not to try it. N Engl J Med 1993; 328: 576–8
Weis SE, Slocum PC, Biais FX, et al. The effect of directly observed therapy on the rates of drug resistance and relapse in tuberculosis. N Engl J Med 1994; 330: 1179–84
Goble M, Iseman MD, Madsen LA, et al. Treatment of 171 patients with pulmonary tuberculosis resistant to isoniazid and rifampin. N Engl J Med 1993; 328: 527–9
Burman WJ, Cohn DL, Rietmeijer CA, et al. Noncompliance with directly observed therapy for tuberculosis: epidemiology and effect on the outcome of treatment. Chest 1997; 111: 1168–73
Geerligs WA, Van Altena R, De Lange WCM, et al. Multidrug-resistant tuberculosis: long-term treatment outcome in the Netherlands. Int J Tuberc Lung Dis 2000; 4: 758–64
Colebunders R, Bastian I. A review of the diagnosis and treatment of smear-negative pulmonary tuberculosis. Int J Tuberc Lung Dis 2000; 4: 97–107
Dutt AK, Moers D, Stead WW. Smear-and culture-negative pulmonary tuberculosis: four-month short-course chemotherapy. Am Rev Respir Dis 1989; 139: 867–70
Van den Brande P, Demedts M. Empiric anti-tuberculous treatment of smear-negative pulmonary tuberculosis in elderly patients [abstract]. S Afr Respir J 2000; 6: 108
Small PM, Fujiwara PI. Management of tuberculosis in the United States. N Engl J Med 2001; 345: 189–200
Telzak EE, Fazal BA, Pollard CL, et al. Factors influencing time to sputum conversion among patients with smear-positive pulmonary tuberculosis. Clin Infect Dis 1997; 25: 666–70
Morris CD. The duration of excretion of viable bacilli in elderly patients on treatment for cavitating pulmonary tuberculosis. South Afr Med J 1996; 86: 958–60
Narita M, Hisada M, Thimmappa B, et al. Tuberculosis recurrence: multivariate analysis of serum levels of tuberculosis drugs, human immunodeficiency virus status, and other risk factors. Clin Infect Dis 2001; 32: 515–7
Yee D, Valiquette C, Pelletier M, et al. Incidence of serious side effects from first-line antituberculosis drugs among patients treated for active tuberculosis. Am J Respir Crit Care Med 2003; 167: 1472–7
Van den Brande P, Van Steenbergen W, Vervoort G, et al. Aging and hepatotoxicity of isoniazid and rifampin in pulmonary tuberculosis. Am J Respir Crit Care Med 1995; 152: 1705–8
American Thoracic Society. Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med 2000; 161: S221–47
Jasmer RM, Nahid P, Hopewell PC. Latent tuberculosis infection. N Engl J Med 2002; 347: 1860–6
Nadal D. Is the in vitro Interferon-γ release assay an adequate replacement for the tuberculin skin test? Clin Infect Dis 2002; 34: 1457–9
Joint Tuberculosis Committee of the British Thoracic Society. Control and prevention of tuberculosis in the United Kingdom: code of practice 2000. Thorax 2000; 55: 887–901
Stevens JP, Daniel TM. Chemoprophylaxis of multidrug-resistant tuberculous infection in HIV uninfected individuals using ciprofloxacin and pyrazinamide: a decision analysis. Chest 1995; 108: 712–7
Gardam MA, Keystone EC, Menzies R, et al. Anti-tumor necrosis factor agents and tuberculosis risk: mechanisms of action and clinical management. Lancet Infect Dis 2003; 3: 148–55
Stead WW, To T, Harrison RW, et al. Benefit-risk considerations in preventive treatment for tuberculosis in elderly persons. Ann Intern Med 1987; 107: 843–5
Rose DN, Schechter CB, Silver AL. The age threshold for isoniazid chemoprophylaxis: a decision analysis for low-risk tuberculin reactors. JAMA 1986; 256: 2709–13
Sorresoo DJ, Metha JB, Harvill LM, et al. Underutilization of isoniazid chemoprophylaxis in tuberculosis contacts 50 years of age and older: a prospective analysis. Chest 1995; 108: 706–11
Segal-Maurer S, Kalkut GE. Environmental control of tuberculosis: continuing controversy. Clin Infect Dis 1994; 19: 299–308
Centers for Disease Control and Prevention. Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care facilities. MMWR Morb Mortal Wkly Rep 1994; 43(RR13): 1–132
LoBue PA, Catanzaro A. Effectiveness of a nosocomial tuberculosis control program at an urban teaching hospital. Chest 1998; 113: 1184–9
Centers for Disease Control and Prevention. Prevention and control of tuberculosis in facilities providing long-term care to the elderly. MMWR Morb Mortal Wkly Rep 1990; 39(RR10): 7–20
Marchand R, Tousignant P, Chang H. Cost-effectiveness of screening compared to case-finding approaches to tuberculosis in long-term care facilities for the elderly. Int J Epidemiol 1999; 28: 563–70
Stead WW. Management of health care workers after inadvertent exposure to tuberculosis: a guide for the use of preventive therapy. Ann Intern Med 1995; 122: 906–12
Stevens JP, Daniel TM. Bacille Calmette Guérin immunisation of health care workers exposed to multidrug-resistant tuberculosis: a decision analysis. Tuber Lung Dis 1996; 77: 315–21
International Union Against Tuberculosis and Lung Disease. Criteria for discontinuation of vaccination programs using Bacille Calmette-Guérin (BCG) in countries with a low prevalence of tuberculosis. Tuber Lung Dis 1994; 75: 179–80
Dye C, Garnett GP, Sleeman K, et al. Prospects for worldwide tuberculosis control under the WHO DOTS strategy: directly observed short-course therapy. Lancet 1998; 352: 1886–91
Citron KM. BCG vaccination against tuberculosis: international perspectives. BMJ 1993; 306: 222–3
Tascon RE, Colston MJ, Ragno S, et al. Vaccination against tuberculosis by DNA injection. Nat Med 1996; 2: 888–92
Stanford JL. Immunotherapy with Mycobacterium vaccae in the treatment of mycobacterial disease. J Infect 1999; 39: 179–82
Barnes PF. Immunotherapy for tuberculosis: wave of the future or tilting at windmills? Am J Respir Crit Care Med 2003; 168: 142–3
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Van den Brande, P. Revised Guidelines for the Diagnosis and Control of Tuberculosis. Drugs Aging 22, 663–686 (2005). https://doi.org/10.2165/00002512-200522080-00004
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DOI: https://doi.org/10.2165/00002512-200522080-00004