Skip to main content
Download PDF

Does tuberculosis threaten our ageing populations?

BMC Infectious Diseases volume 16, Article number: 119 (2016) Cite this article

Abstract

Background

The global population is ageing quickly and our understanding of age-related changes in the immune system suggest that the elderly will have less immunological protection from active tuberculosis (TB).

Discussion

Ongoing global surveillance of TB notifications shows increasing age of patients with active TB. This effect of age is compounded by changes to clinical manifestations of disease, confounding of diagnostic tests and increased rates of adverse reactions to antimicrobial treatment of TB. Future epidemiological surveillance, development of diagnostic tests and trials of treatment shortening should all include a focus on ageing people.

Summary

More detailed surveillance of TB notifications in elderly people should be undertaken and carefully evaluated. Risk stratification will help target care for those in greatest need, particularly those with comorbidities or on immunosuppressive therapies. Novel diagnostics and treatment regimes should be designed specifically to be used in this cohort.

Peer Review reports

Background

Ageing of global populations

The global population is ageing due to longer life expectancy and lower rates of child birth. By 2035, it is projected that those aged >65 years will constitute 23 % of the total UK population [1]. Worldwide, the number of people > 60 years is expected to increase by more than double, from 841 million people in 2013 to more than two billion people in 2050 [2]. It is projected that in 2047, older persons will exceed the number of children for the first time [2]. Currently most older people live in the developed world, but the older population is also growing rapidly in less developed regions such that projections for 2050 predict nearly 80 % of the world’s older population will be living in less developed countries [2].

Effects of age on immune protection against TB

Elderly people have an increased susceptibility to infectious diseases, particularly of the respiratory tract [3], and suffer greater morbidity and mortality compared to younger individuals [4]. Ageing has significant effects on both the innate and adaptive immune system [5–7], which may contribute to the increased risk of infection.

Immune protection against tuberculosis (TB) infection is primarily achieved by cell mediated immunity, through the coordinated action of phagocytic cells and adaptive immune T cell responses that serve to kill or contain the bacteria. In this context, macrophages represent the predominant phagocytic cells [8], CD4 T helper 1 cells are thought to enhance intracellular killing of bacteria through the action of interferon (IFN)γ and CD8 T cells may contribute to killing of infected macrophages by production of cell membrane porins such as granzyme and perforin [9].

Reduced T cell output by the thymus, T cell immune senescence, defined by reduced capacity for cell proliferation, and immune exhaustion, defined by reduced capacity to produce cytokines and other effector molecules are the most consistent reported effects of ageing on the immune system [10, 11]. In keeping with these data, ex vivo stimulation of peripheral blood mononuclear cells from elderly people with Mycobacterium tuberculosis (Mtb) antigens generates lower IFNγ responses, than in younger people [12], and older mice show increased susceptibility to Mtb infection, associated with impaired CD4 T cell-mediated immunity [13, 14]. However, others report exaggerated CD8 T cell responses in older mice which mediate a degree of increased host resistance to TB [15–17].

Age-related changes in the phenotype and function of macrophages are also reported, which might be expected to compromise their role in protection against TB. These include reduced expression of innate immune receptors, reduced production of tumour necrosis factor (TNF) and reduced phagocytosis [18]. Clear evidence for how these may impact the host-pathogen interactions between macrophages and Mtb is lacking. In one report, monocytes from older humans supported higher rates of bacterial growth [19] but others found no difference in cellular cytokine responses or bacterial growth in mouse macrophages from young and old mice [20].

The importance of well-calibrated mechanisms for regulation of inflammation to avoid or minimise the immunopathogenesis of TB are also increasingly recognised [21–23]. Persistently raised levels of proinflammatory cytokines are evident in older people [24, 25] and in pulmonary macrophages of older mice [26]. These data invite speculation that inflammage-ing may contribute to increased immunopathogenesis of TB and therefore more disease in the elderly.

Discussion

Evidence for the impact of ageing on TB

Currently the highest TB notification rates globally occur amongst 45–55 year olds, but in the Western Pacific Region, Eastern Mediterranean and South East Asia TB notifications are increasingly evident in older people, peaking amongst those aged ≥65 years old [27]. Similar observations have been reported in a recent review of all national TB prevalence studies in Asia which showed progressively increased TB prevalence rates amongst people over the age of 65 years [28], and this is echoed in reports from the Americas which also described the disease burden increasing amongst older adults in Central and South America [29] and North America [30].

Currently in the United Kingdom (UK), the highest incidence of TB is amongst 15–44 year olds, representing nearly 60 % of all cases and those over the age of 65 years only accounted for 14 % [31]. Interestingly, the majority of the younger cases are in non-UK born individuals, most likely due to high immigration rates in younger people from TB endemic areas, confounding our perception of TB risk in the elderly population. Even in the UK, there is a comparatively high incidence of TB in UK born individuals, greater than 75 years old [31]. Birth cohort effects, such as higher childhood or early adulthood TB transmission rates amongst the current elderly may partly explain these observations [32] as it is has long been presumed that active TB in the elderly arises from reactivation of LTBI as protective immunity wanes [33–35]. However the emerging general consensus is that LTBI is most likely to reactivate within 18 months of infection, and disease resulting from reactivation more than 10 years after infection may be rare [36] and that most active disease represents relatively recent transmission events. Whether these observations are equally true in young and old people alike is not known and merits further investigation, particularly given the age-related immune changes and co-morbidities in older people, which may increase the risk of reactivation disease.

Effects of age on clinical presentation of TB

It has been argued that active TB infection in the elderly is “a different disease” than that occurring in younger people, due to the disparity in clinical presentation and laboratory tests [34]. Although pulmonary TB is the most common site of infection in elderly people, occurring in approximately 75 % of cases [37], many older patients with active TB may not exhibit the classic clinical features such as cough, hemoptysis, fever, night sweats and weight loss. Dyspnoea is more common and haemoptysis less common in the elderly [34, 38–40]. There may be very few symptoms, or the symptoms can mimic age-related illnesses such as reduced functional capacity, chronic fatigue, cognitive impairment, anorexia or pyrexia of unknown origin. An accurate history may be difficult to obtain due to poor memory, impaired hearing, sight or speech.

Extrapulmonary TB is more common with advancing age, and presentations may include TB meningitis, renal or bone and joint infection (particularly involving the thoracolumbar spine and large joints) [38, 41, 42]. Presentations of back and joint pain are sometimes dismissed as diseases of the elderly, such as degenerative arthritis or osteoporotic compression fractures [43], but associated constitutional symptoms (low grade fever, weight loss, fatigue and anorexia) can lead to the correct diagnosis.

The impact of age on diagnosis

Diagnosing TB can be difficult in all age groups and is often dependent on identifying those with compatible laboratory and radiological assessments, particularly when a microbiological diagnosis may be out of reach. By comparison to the young, elderly people with TB show higher frequencies of abnormal liver enzymes, hypoalbuminaemia, hyponatraemia and hypokalaemia, and about two-thirds of elderly patients with active TB exhibit a normocytic normochromic anaemia [34]. Less pulmonary cavitation is seen on plain radiographs [37], and fewer nodules, masses and cavities on chest computed tomography have been reported in the elderly [40], albeit not always consistently [39]. Rather than isolated apical shadowing, radiographs more often show mid zone and basal shadowing often accompanied by pleural effusions [34]. Moreover, mass-like lesions or nodules due to TB in the elderly can often be difficult to distinguish from malignant disease or more common bacterial pneumonias [35].

The age-related changes to the immune system described above may also compromise immunological tests for evidence of past exposure to TB, such as the tuberculin skin test (TST) or peripheral blood IFNγ release assays (IGRA) such as the T-SPOT.TB and QuantiFERON-TB Gold In-Tube. Lower rates of positive TST have been described in elderly populations, compared to younger people [37, 44], including a study of UK nursing home residents that showed a lower rate of TST positivity (3 %) in those aged over 90 years, compared to those under 70 years old (15 %) [45]. However other studies have not shown any age-related difference in TST positivity rate [40]. Studies of repeated TST in the elderly typically show reduced TST reactivity [46, 47], usually interpreted as evidence for waning immunity. Therefore the use of a boosted (two-step) TST is advocated in the elderly to improve sensitivity, though this is not predictive of active TB disease [48].

Data on the use of peripheral blood IGRAs in the elderly are limited. Some suggest indeterminate results may be more likely to occur [49, 50] and other reports show no effect of age [47]. However, discordance between TST and IGRA is more likely to occur in the elderly [47, 51].

There is also controversy in the literature about whether microbiological diagnosis of TB is affected by age, with reports of lower rates in the elderly [52, 53], no difference between groups [54] or higher rates of smear positive sputum in the elderly [40]. There are currently no published reports of the impact of age on GeneXpert molecular diagnostics for TB.

Age-related effects on anti-tuberculous treatment

Elderly people are more likely to develop adverse drug reactions from polypharmacy, existing co-morbidities and age-related physiological changes. Hepatotoxicity is a common adverse effect as a result of treatment with isoniazid, rifampicin and pyrazinamide, ranging from mild reversible abnormalities of transaminases to fulminant liver failure, and hepatotoxicity from anti-tuberculous drugs rises significantly with increasing age [38, 55, 56]. TB drug related hepatotoxicity in those older than 65 years incurs an odds ratio of 1.71 (CI 95 % 1.24–2.35) [56], although cessation of isoniazid therapy due to suspected hepatotoxicity is not associated with increasing age [57].

Although less common, acute kidney injury is also seen following anti-tuberculous therapy, particularly with rifampicin [58, 59]. This is more likely to occur with increasing age, and with co-morbidities of diabetes mellitus and chronic kidney disease [59].

In addition to increased adverse drug reactions, visual impairment, poor memory and reduced mobility may cause poor adherence to the drug regimen [35].

Comorbidities and therapies in an ageing population associated with increased risk of TB

Several co-morbidities that are prevalent in ageing populations may further increase the risk of developing active TB disease. Diabetes mellitus increases the risk of active TB by approximately three fold (relative risk 3.11, 95 % CI: 2.27–4.26), in all age groups but may contribute to age related TB as the prevalence of diabetes increases with age [60]. Similarly in chronic obstructive pulmonary disease (COPD), incidence and severity increases with age, and it is also associated with increased rates of active TB, albeit the effect also seems to be independent of age [61].

Furthermore elderly patients are more frequently treated with medication that may suppress protective immunity. The most common example of this is corticosteroids, especially in those with COPD. Both regular inhalers and short courses of high dose corticosteroids during exacerbations are associated with an increased risk of TB in younger and older patients, in a dose-dependent fashion [62–64]. Corticosteroid use (oral prednisolone > 7.5 mg daily) in other diseases is also an independent risk factor for active TB infection [65, 66]. In a study of older people with rheumatic conditions, those on immunosuppressive medication were at an increased risk of mycobacterial infection [67]. Amongst these immunosuppressive therapies, anti-TNF therapy particularly increases the risk of active TB [67–69].

Conclusions

Given the global ageing population and increasing incidence of active TB in the elderly, it would be prudent to undertake more detailed surveillance of this cohort. Of note there are no data that assess the differential effects of age on transmission of infection, likelihood of developing latent TB or progressing to active disease. Careful evaluation of de novo infection and reactivation of LTBI may help to risk stratify patients and target care to those at the highest risk of developing active TB, particularly to assess the role of comorbidities and immunosuppressive treatments. TB in the elderly also generates substantial diagnostic and treatment challenges. The performance of established and novel diagnostics, and new treatment regimens aiming to reduce the duration of treatment in TB should all be specifically evaluated in elderly populations, which have generally been avoided in the past because of practical difficulties in their inclusion and their comorbidities.

Ethics statement

Ethical approval was not required for this paper as it is a debate and not original research involving humans.

Abbreviations

CD4:

cluster of differentiation 4

CD8:

cluster of differentiation 8

COPD:

chronic obstructive pulmonary disease

IFNγ:

interferon gamma

IGRA:

interferon gamma release assay

LTBI:

latent tuberculosis infection

Mtb:

mycobacterium tuberculosis

TB:

tuberculosis

TNF:

tumour necrosis factor

TST:

tuberculin skin test

UK:

United Kingdom

References

  1. Population Ageing in the United Kingdom, its Constituent Countries and the European Union. In. http://www.ons.gov.uk/ons/dcp171776_258607.pdf: Office for National Statistics; 2012.

  2. Organisation WH. World Population Aging 2013. In: United Nations. 2013.

    Google Scholar 

  3. Gardner ID. The effect of aging on susceptibility to infection. Rev Infect Dis. 1980;2(5):801–10.

    Article  CAS  PubMed  Google Scholar 

  4. Bellmann-Weiler R, Weiss G. Pitfalls in the diagnosis and therapy of infections in elderly patients--a mini-review. Gerontology. 2009;55(3):241–9.

    Article  PubMed  Google Scholar 

  5. Stervbo U, Meier S, Malzer JN, Baron U, Bozzetti C, Jurchott K, et al. Effects of aging on human leukocytes (part I): immunophenotyping of innate immune cells. Age (Dordr). 2015;37(5):9828.

    Google Scholar 

  6. Stervbo U, Bozzetti C, Baron U, Jurchott K, Meier S, Malzer JN, et al. Effects of aging on human leukocytes (part II): immunophenotyping of adaptive immune B and T cell subsets. Age (Dordr). 2015;37(5):9829.

    Google Scholar 

  7. Shaw AC, Joshi S, Greenwood H, Panda A, Lord JM. Aging of the innate immune system. Curr Opin Immunol. 2010;22(4):507–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Flynn JL, Chan J, Lin PL. Macrophages and control of granulomatous inflammation in tuberculosis. Mucosal Immunol. 2011;4(3):271–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Cooper AM. T cells in mycobacterial infection and disease. Curr Opin Immunol. 2009;21(4):378–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Akbar AN, Fletcher JM. Memory T cell homeostasis and senescence during aging. Curr Opin Immunol. 2005;17(5):480–5.

    Article  CAS  PubMed  Google Scholar 

  11. Akbar AN, Henson SM. Are senescence and exhaustion intertwined or unrelated processes that compromise immunity? Nat Rev Immunol. 2011;11(4):289–95.

    Article  CAS  PubMed  Google Scholar 

  12. Bodnar Z, Steger MM, Saurwein-Teissl M, Maczek C, Grubeck-Loebenstein B. Cytokine production in response to stimulation with tetanus toxoid, Mycobacterium tuberculosis and influenza antigens in peripheral blood mononuclear cells and T cell lines from healthy elderlies. Int Arch Allergy Immunol. 1997;112(4):323–30.

    Article  CAS  PubMed  Google Scholar 

  13. Orme IM. Aging and immunity to tuberculosis: increased susceptibility of old mice reflects a decreased capacity to generate mediator T lymphocytes. J Immunol. 1987;138(12):4414–8.

    CAS  PubMed  Google Scholar 

  14. Orme IM, Griffin JP, Roberts AD, Ernst DN. Evidence for a defective accumulation of protective T cells in old mice infected with Mycobacterium tuberculosis. Cell Immunol. 1993;147(1):222–9.

    Article  CAS  PubMed  Google Scholar 

  15. Rottinghaus EK, Vesosky B, Turner J. Interleukin-12 is sufficient to promote antigen-independent interferon-gamma production by CD8 T cells in old mice. Immunology. 2009;128(1 Suppl):e679–90.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Vesosky B, Flaherty DK, Turner J. Th1 cytokines facilitate CD8-T-cell-mediated early resistance to infection with Mycobacterium tuberculosis in old mice. Infect Immun. 2006;74(6):3314–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Vesosky B, Rottinghaus EK, Davis C, Turner J. CD8 T Cells in old mice contribute to the innate immune response to Mycobacterium tuberculosis via interleukin-12p70-dependent and antigen-independent production of gamma interferon. Infect Immun. 2009;77(8):3355–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Shaw AC, Goldstein DR, Montgomery RR. Age-dependent dysregulation of innate immunity. Nat Rev Immunol. 2013;13(12):875–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Guerra-Laso JM, Gonzalez-Garcia S, Gonzalez-Cortes C, Diez-Tascon C, Lopez-Medrano R, Rivero-Lezcano OM. Macrophages from elders are more permissive to intracellular multiplication of Mycobacterium tuberculosis. Age (Dordr). 2013;35(4):1235–50.

    Article  CAS  Google Scholar 

  20. Rhoades ER, Orme IM. Similar responses by macrophages from young and old mice infected with Mycobacterium tuberculosis. Mech Ageing Dev. 1998;106(1–2):145–53.

    Article  CAS  PubMed  Google Scholar 

  21. Tobin DM, Roca FJ, Oh SF, McFarland R, Vickery TW, Ray JP, et al. Host genotype-specific therapies can optimize the inflammatory response to mycobacterial infections. Cell. 2012;148(3):434–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Mayer-Barber KD, Andrade BB, Oland SD, Amaral EP, Barber DL, Gonzales J, et al. Host-directed therapy of tuberculosis based on interleukin-1 and type I interferon crosstalk. Nature. 2014;511(7507):99–103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Gideon HP, Phuah J, Myers AJ, Bryson BD, Rodgers MA, Coleman MT, et al. Variability in tuberculosis granuloma T cell responses exists, but a balance of pro- and anti-inflammatory cytokines is associated with sterilization. PLoS Pathog. 2015;11(1), e1004603.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Franceschi C, Bonafe M, Valensin S, Olivieri F, De Luca M, Ottaviani E, et al. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci. 2000;908:244–54.

    Article  CAS  PubMed  Google Scholar 

  25. Franceschi C, Capri M, Monti D, Giunta S, Olivieri F, Sevini F, et al. Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech Ageing Dev. 2007;128(1):92–105.

    Article  CAS  PubMed  Google Scholar 

  26. Canan CH, Gokhale NS, Carruthers B, Lafuse WP, Schlesinger LS, Torrelles JB, et al. Characterization of lung inflammation and its impact on macrophage function in aging. J Leukoc Biol. 2014;96(3):473–80.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Organisation WH. Global Tuberculosis Report 2014. In: World Health Organisation, Geneva, Switzerland. 2014.

    Google Scholar 

  28. Onozaki I, Law I, Sismanidis C, Zignol M, Glaziou P, Floyd K. National tuberculosis prevalence surveys in Asia, 1990–2012: an overview of results and lessons learned. Trop Med Int Health. 2015;20(9):1128–45.

    Article  PubMed  Google Scholar 

  29. Organisation PAH. Tuberculosis in the Region of the Americas Regional Report 2011: Epidemiology, Control and Financing. In: Pan American Health Organisation, Washington DC. 2011.

    Google Scholar 

  30. CDC Reported tuberculosis in the United States, 2013. http://www.cdc.gov/tb/statistics/reports/2013/pdf/report2013.pdf.

  31. Tuberculosis in the UK 2014 report. https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/360335/TB_Annual_report__4_0_300914.pdf.

  32. Winston CA, Navin TR. Birth cohort effect on latent tuberculosis infection prevalence, United States. BMC Infect Dis. 2010;10:206.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Wang S-H, Carruthers B, Turner J. The Influence of Increasing Age on Susceptibility of the Elderly to Tuberculosis. Open Longevity Sci. 2012;6:73–82.

    Article  Google Scholar 

  34. Morris CD. Pulmonary tuberculosis in the elderly: a different disease? Thorax. 1990;45(12):912–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Schaaf HS, Collins A, Bekker A, Davies PD. Tuberculosis at extremes of age. Respirology. 2010;15(5):747–63.

    Article  PubMed  Google Scholar 

  36. Esmail H, Barry 3rd CE, Young DB, Wilkinson RJ. The ongoing challenge of latent tuberculosis. Philos Trans R Soc Lond Ser B Biol Sci. 2014;369(1645):20130437.

    Article  CAS  Google Scholar 

  37. Perez-Guzman C, Vargas MH, Torres-Cruz A, Villarreal-Velarde H. Does aging modify pulmonary tuberculosis?: A meta-analytical review. Chest. 1999;116(4):961–7.

    Article  CAS  PubMed  Google Scholar 

  38. Schluger NW. Tuberculosis and nontuberculous mycobacterial infections in older adults. Clin Chest Med. 2007;28(4):773–81. vi.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Korzeniewska-Kosela M, Krysl J, Muller N, Black W, Allen E, FitzGerald JM. Tuberculosis in young adults and the elderly. A prospective comparison study. Chest. 1994;106(1):28–32.

    Article  CAS  PubMed  Google Scholar 

  40. Kwon YS, Chi SY, Oh IJ, Kim KS, Kim YI, Lim SC, et al. Clinical characteristics and treatment outcomes of tuberculosis in the elderly: a case control study. BMC Infect Dis. 2013;13:121.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Rajagopalan S. Tuberculosis and aging: a global health problem. Clin Infect Dis. 2001;33(7):1034–9.

    Article  CAS  PubMed  Google Scholar 

  42. Negin J, Abimbola S, Marais BJ. Tuberculosis among older adults--time to take notice. Int J Infect Dis. 2015;32:135–7.

    Article  PubMed  Google Scholar 

  43. Dass B, Puet TA, Watanakunakorn C. Tuberculosis of the spine (Pott’s disease) presenting as ‘compression fractures’. Spinal Cord. 2002;40(11):604–8.

    Article  CAS  PubMed  Google Scholar 

  44. Dorken E, Grzybowski S, Allen EA. Significance of the tuberculin test in the elderly. Chest. 1987;92(2):237–40.

    Article  CAS  PubMed  Google Scholar 

  45. Nisar M, Williams CS, Ashby D, Davies PD. Tuberculin testing in residential homes for the elderly. Thorax. 1993;48(12):1257–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Perez-Stable EJ, Flaherty D, Schecter G, Slutkin G, Hopewell PC. Conversion and reversion of tuberculin reactions in nursing home residents. Am Rev Respir Dis. 1988;137(4):801–4.

    Article  CAS  PubMed  Google Scholar 

  47. Hochberg NS, Rekhtman S, Burns J, Ganley-Leal L, Helbig S, Watts NS, Brandeis GH, Ellner JJ, Horsburgh CR, Jr.: The complexity of diagnosing latent tuberculosis infection in older adults in long-term care facilities. Int J Infect Dis. 2016;44:37–43.

  48. Chan-Yeung M, Dai DL, Cheung AH, Chan FH, Kam KM, Tam CM, et al. Tuberculin skin test reaction and body mass index in old age home residents in Hong Kong. J Am Geriatr Soc. 2007;55(10):1592–7.

    Article  PubMed  Google Scholar 

  49. Tebruegge M, de Graaf H, Sukhtankar P, Elkington P, Marshall B, Schuster H, et al. Extremes of age are associated with indeterminate QuantiFERON-TB gold assay results. J Clin Microbiol. 2014;52(7):2694–7.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Kobashi Y, Mouri K, Miyashita N, Okimoto N, Matsushima T, Kageoka T, et al. QuantiFERON TB-2G test for patients with active tuberculosis stratified by age groups. Scand J Infect Dis. 2009;41(11–12):841–6.

    Article  PubMed  Google Scholar 

  51. Weinfurter P, Blumberg HM, Goldbaum G, Royce R, Pang J, Tapia J, et al. Predictors of discordant tuberculin skin test and QuantiFERON(R)-TB Gold In-Tube results in various high-risk groups. Int J Tuberc Lung Dis. 2011;15(8):1056–61.

    Article  CAS  PubMed  Google Scholar 

  52. Velayutham BR, Nair D, Chandrasekaran V, Raman B, Sekar G, Watson B, et al. Profile and response to anti-tuberculosis treatment among elderly tuberculosis patients treated under the TB Control programme in South India. PLoS ONE. 2014;9(3), e88045.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Wang CS, Chen HC, Yang CJ, Wang WY, Chong IW, Hwang JJ, et al. The impact of age on the demographic, clinical, radiographic characteristics and treatment outcomes of pulmonary tuberculosis patients in Taiwan. Infection. 2008;36(4):335–40.

    Article  PubMed  Google Scholar 

  54. Lee JH, Han DH, Song JW, Chung HS. Diagnostic and therapeutic problems of pulmonary tuberculosis in elderly patients. J Korean Med Sci. 2005;20(5):784–9.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Pande JN, Singh SP, Khilnani GC, Khilnani S, Tandon RK. Risk factors for hepatotoxicity from antituberculosis drugs: a case–control study. Thorax. 1996;51(2):132–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Hosford JD, von Fricken ME, Lauzardo M, Chang M, Dai Y, Lyon JA, et al. Hepatotoxicity from antituberculous therapy in the elderly: a systematic review. Tuberc (Edinb). 2015;95(2):112–22.

    Article  CAS  Google Scholar 

  57. Vinnard C, Gopal A, Linkin DR, Maslow J. Isoniazid Toxicity among an Older Veteran Population: A Retrospective Cohort Study. Tuberc Res Treat. 2013;2013:549473.

    PubMed  PubMed Central  Google Scholar 

  58. De Vriese AS, Robbrecht DL, Vanholder RC, Vogelaers DP, Lameire NH. Rifampicin-associated acute renal failure: pathophysiologic, immunologic, and clinical features. Am J Kidney Dis. 1998;31(1):108–15.

    Article  PubMed  Google Scholar 

  59. Chang CH, Chen YF, Wu VC, Shu CC, Lee CH, Wang JY, et al. Acute kidney injury due to anti-tuberculosis drugs: a five-year experience in an aging population. BMC Infect Dis. 2014;14:23.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Jeon CY, Murray MB. Diabetes mellitus increases the risk of active tuberculosis: a systematic review of 13 observational studies. PLoS Med. 2008;5(7), e152.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Inghammar M, Ekbom A, Engstrom G, Ljungberg B, Romanus V, Lofdahl CG, et al. COPD and the risk of tuberculosis--a population-based cohort study. PLoS ONE. 2010;5(4), e10138.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Lee CH, Kim K, Hyun MK, Jang EJ, Lee NR, Yim JJ. Use of inhaled corticosteroids and the risk of tuberculosis. Thorax. 2013;68(12):1105–13.

    Article  PubMed  Google Scholar 

  63. Kim JH, Park JS, Kim KH, Jeong HC, Kim EK, Lee JH. Inhaled corticosteroid is associated with an increased risk of TB in patients with COPD. Chest. 2013;143(4):1018–24.

    Article  CAS  PubMed  Google Scholar 

  64. Shu CC, Wu HD, Yu MC, Wang JT, Lee CH, Wang HC, et al. Use of high-dose inhaled corticosteroids is associated with pulmonary tuberculosis in patients with chronic obstructive pulmonary disease. Medicine (Baltimore). 2010;89(1):53–61.

    Article  CAS  Google Scholar 

  65. Lai CC, Lee MT, Lee SH, Lee SH, Chang SS, Lee CC. Risk of incident active tuberculosis and use of corticosteroids. Int J Tuberc lung Dis. 2015;19(8):936–42.

    Article  PubMed  Google Scholar 

  66. Jick SS, Lieberman ES, Rahman MU, Choi HK. Glucocorticoid use, other associated factors, and the risk of tuberculosis. Arthritis Rheum. 2006;55(1):19–26.

    Article  PubMed  Google Scholar 

  67. Brode SK, Jamieson FB, Ng R, Campitelli MA, Kwong JC, Paterson JM, et al. Increased risk of mycobacterial infections associated with anti-rheumatic medications. Thorax. 2015;70(7):677–82.

    Article  PubMed  Google Scholar 

  68. Dixon WG, Hyrich KL, Watson KD, Lunt M, Galloway J, Ustianowski A, et al. obotBB: Drug-specific risk of tuberculosis in patients with rheumatoid arthritis treated with anti-TNF therapy: results from the British Society for Rheumatology Biologics Register (BSRBR). Ann Rheum Dis. 2010;69:522–8.

  69. Tubach F, Salmon D, Ravaud P, Allanore Y, Goupille P, Breban M, et al. Risk of tuberculosis is higher with anti-tumor necrosis factor monoclonal antibody therapy than with soluble tumor necrosis factor receptor therapy: The three-year prospective French Research Axed on Tolerance of Biotherapies registry. Arthritis Rheum. 2009;60(7):1884–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Supported by an Arthritis Research UK clinical research fellowship (RBM) and NIHR Biomedical Research Centre funding to University College London Hospitals and UCL (MN).

Author information

Authors and Affiliations

  1. Division of Infection and Immunity, University College London, Cruciform Building, Gower Street, London, WC1E 6BT, UK

    Rachel Byng-Maddick & Mahdad Noursadeghi

Authors
  1. Rachel Byng-Maddick
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mahdad Noursadeghi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rachel Byng-Maddick.

Additional information

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

RBM wrote the manuscript with input from MN. Both authors read and approved the final manuscript.

Rights and permissions

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Byng-Maddick, R., Noursadeghi, M. Does tuberculosis threaten our ageing populations?. BMC Infect Dis 16, 119 (2016). https://doi.org/10.1186/s12879-016-1451-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12879-016-1451-0

Keywords

BMC Infectious Diseases

ISSN: 1471-2334

Contact us