Immune Dysfunction and Nontuberculous Mycobacterial Disease

  • Emily HenkleEmail author
  • Kevin L. Winthrop
Part of the Respiratory Medicine book series (RM)


The following chapter focuses on the epidemiology, prevention, diagnosis, and treatment of nontuberculous mycobacterial disease in different immunosuppressed and immunocompromised patient populations. Underlying causes of immunosuppression that increase the risk of nontuberculous mycobacterial disease include acquired immunodeficiency syndrome and certain types of primary immunodeficiency, cancer and its treatment, and solid organ and hematologic transplantation. More recently, evidence has suggested an increased risk with the use of immunosuppressive medications such as oral and inhaled corticosteroids, and biologic therapies used to treat autoimmune inflammatory diseases. In many immunocompromised patients, nontuberculous mycobacterial infections more commonly present as extrapulmonary disease (i.e., skin, soft tissue, or disseminated infections), although in some settings of immunosuppression (e.g., sarcoid, lung transplant), pulmonary presentations are common. Mycobacterium avium complex and rapid-growing mycobacteria (e.g., Mycobacterium abscessus and Mycobacterium fortuitum) cause the most disease, with several uncommon species (e.g., Mycobacterium haemophilum and Mycobacterium genavense) causing disease exclusively in immunocompromised patients. Treatment of those with nontuberculous mycobacterial infections and underlying immunosuppression frequently involves parenteral-based multidrug antimicrobial therapy and efforts to reduce immunosuppression. Treatment should be undertaken by experts per current American Thoracic Society/Infectious Disease Society of America treatment guidelines.


Nontuberculous mycobacteria Mycobacterium avium complex Mycobacterium abscessus Mycobacterium haemophilum Immunosuppression 


  1. 1.
    Andrejak C, Nielsen R, Thomsen VO, Duhaut P, Sorensen HT, Thomsen RW. Chronic respiratory disease, inhaled corticosteroids and risk of non-tuberculous mycobacteriosis. Thorax. 2013;68:256–62.PubMedGoogle Scholar
  2. 2.
    Winthrop KL, Baxter R, Liu L, et al. Mycobacterial diseases and antitumour necrosis factor therapy in USA. Ann Rheum Dis. 2013;72:37–42.PubMedGoogle Scholar
  3. 3.
    Cassidy PM, Hedberg K, Saulson A, McNelly E, Winthrop KL. Nontuberculous mycobacterial disease prevalence and risk factors: a changing epidemiology. Clin Infect Dis. 2009;49:e124–9.PubMedGoogle Scholar
  4. 4.
    Henkle E, Hedberg K, Schafer S, Novosad S, Winthrop KL. Population-based incidence of pulmonary Nontuberculous mycobacterial disease in Oregon 2007 to 2012. Ann Am Thorac Soc. 2015;12:642–7.PubMedPubMedCentralGoogle Scholar
  5. 5.
    Henkle E, Hedberg K, Schafer SD, Winthrop KL. Surveillance of Extrapulmonary Nontuberculous mycobacteria infections, Oregon, USA, 2007-2012. Emerg Infect Dis. 2017;23:1627–30.PubMedPubMedCentralGoogle Scholar
  6. 6.
    Position Statement 17-ID-07: Standardized Case Definition for Extrapulmonary Nontuberculous Mycobacteria Infections. Council of State and Territorial Epidemiologists. Available at, Last accessed 17 Nov 2017.
  7. 7.
    Jones D, Havlir DV. Nontuberculous mycobacteria in the HIV infected patient. Clin Chest Med. 2002;23:665–74.PubMedGoogle Scholar
  8. 8.
    Winthrop KL, Baddley JW, Chen L, et al. Association between the initiation of anti-tumor necrosis factor therapy and the risk of herpes zoster. JAMA. 2013;309:887–95.PubMedPubMedCentralGoogle Scholar
  9. 9.
    Knoll BM. Update on nontuberculous mycobacterial infections in solid organ and hematopoietic stem cell transplant recipients. Curr Infect Dis Rep. 2014;16:421.PubMedGoogle Scholar
  10. 10.
    Griffith DE, Aksamit T, Brown-Elliott BA, et al. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med. 2007;175:367–416.PubMedGoogle Scholar
  11. 11.
    Lewis FM, Marsh BJ, von Reyn CF. Fish tank exposure and cutaneous infections due to Mycobacterium marinum: tuberculin skin testing, treatment, and prevention. Clin Infect Dis. 2003;37:390–7.PubMedGoogle Scholar
  12. 12.
    El Helou G, Hachem R, Viola GM, et al. Management of rapidly growing mycobacterial bacteremia in cancer patients. Clin Infect Dis. 2013;56:843–6.PubMedGoogle Scholar
  13. 13.
    Winthrop KL, Chang E, Yamashita S, Iademarco MF, LoBue PA. Nontuberculous mycobacteria infections and anti-tumor necrosis factor-alpha therapy. Emerg Infect Dis. 2009;15:1556–61.PubMedPubMedCentralGoogle Scholar
  14. 14.
    Wentworth AB, Drage LA, Wengenack NL, Wilson JW, Lohse CM. Increased incidence of cutaneous nontuberculous mycobacterial infection, 1980 to 2009: a population-based study. Mayo Clin Proc. 2013;88:38–45.PubMedGoogle Scholar
  15. 15.
    Doherty T, Lynn M, Cavazza A, Sames E, Hughes R. Mycobacterium haemophilum as the initial presentation of a B-cell lymphoma in a liver transplant patient. Case Rep Rheumatol. 2014;2014:742978.PubMedPubMedCentralGoogle Scholar
  16. 16.
    Ducharlet K, Murphy C, Tan SJ, et al. Recurrent Mycobacterium haemophilum in a renal transplant recipient. Nephrology. 2014;19(Suppl 1):14–7.PubMedGoogle Scholar
  17. 17.
    Lhuillier E, Brugiere O, Veziris N, et al. Relapsing Mycobacterium genavense infection as a cause of late death in a lung transplant recipient: case report and review of the literature. Exp Clin Transplant. 2012;10:618–20.PubMedGoogle Scholar
  18. 18.
    Turner RD, Chiu C, Churchyard GJ, et al. Tuberculosis infectiousness and host susceptibility. J Infect Dis. 2017;216:S636–S43.PubMedPubMedCentralGoogle Scholar
  19. 19.
    Cooper AM. Cell-mediated immune responses in tuberculosis. Annu Rev Immunol. 2009;27:393–422.PubMedPubMedCentralGoogle Scholar
  20. 20.
    Stenger S, Modlin RL. T cell mediated immunity to Mycobacterium tuberculosis. Curr Opin Microbiol. 1999;2:89–93.PubMedGoogle Scholar
  21. 21.
    Chan ED, Bai X, Kartalija M, Orme IM, Ordway DJ. Host immune response to rapidly growing mycobacteria, an emerging cause of chronic lung disease. Am J Respir Cell Mol Biol. 2010;43:387–93.PubMedGoogle Scholar
  22. 22.
    Lake MA, Ambrose LR, Lipman MC, Lowe DM. “Why me, why now?” Using clinical immunology and epidemiology to explain who gets nontuberculous mycobacterial infection. BMC Med. 2016;14:54.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Wu UI, Holland SM. Host susceptibility to non-tuberculous mycobacterial infections. Lancet Infect Dis. 2015;15:968–80.PubMedGoogle Scholar
  24. 24.
    Ehlers S. Role of tumour necrosis factor (TNF) in host defence against tuberculosis: implications for immunotherapies targeting TNF. Ann Rheum Dis. 2003;62(Suppl 2):ii37–42.PubMedPubMedCentralGoogle Scholar
  25. 25.
    Zumla A, James DG. Granulomatous infections: etiology and classification. Clin Infect Dis. 1996;23:146–58.PubMedGoogle Scholar
  26. 26.
    Gardam MA, Keystone EC, Menzies R, et al. Anti-tumour necrosis factor agents and tuberculosis risk: mechanisms of action and clinical management. Lancet Infect Dis. 2003;3:148–55.PubMedGoogle Scholar
  27. 27.
    Winthrop KL, Chiller T. Preventing and treating biologic-associated opportunistic infections. Nat Rev Rheumatol. 2009;5:405–10.PubMedGoogle Scholar
  28. 28.
    Mirsaeidi M, Machado RF, Garcia JG, Schraufnagel DE. Nontuberculous mycobacterial disease mortality in the United States, 1999-2010: a population-based comparative study. PLoS One. 2014;9:e91879.PubMedPubMedCentralGoogle Scholar
  29. 29.
    Lee WI, Huang JL, Yeh KW, et al. Immune defects in active mycobacterial diseases in patients with primary immunodeficiency diseases (PIDs). J Formos Med Assoc. 2011;110:750–8.PubMedGoogle Scholar
  30. 30.
    Sexton P, Harrison AC. Susceptibility to nontuberculous mycobacterial lung disease. Eur Respir J. 2008;31:1322–33.PubMedGoogle Scholar
  31. 31.
    Bustamante J, Boisson-Dupuis S, Abel L, Casanova JL. Mendelian susceptibility to mycobacterial disease: genetic, immunological, and clinical features of inborn errors of IFN-gamma immunity. Semin Immunol. 2014;26:454–70.PubMedPubMedCentralGoogle Scholar
  32. 32.
    Haverkamp MH, van de Vosse E, van Dissel JT. Nontuberculous mycobacterial infections in children with inborn errors of the immune system. J Infect. 2014;68(Suppl 1):S134–50.PubMedGoogle Scholar
  33. 33.
    Phoompoung P, Ankasekwinai N, Pithukpakorn M, et al. Factors associated with acquired anti IFN- gamma autoantibody in patients with nontuberculous mycobacterial infection. PLoS One. 2017;12:e0176342.PubMedPubMedCentralGoogle Scholar
  34. 34.
    Browne SK, Burbelo PD, Chetchotisakd P, et al. Adult-onset immunodeficiency in Thailand and Taiwan. N Engl J Med. 2012;367:725–34.PubMedPubMedCentralGoogle Scholar
  35. 35.
    Browne SK, Zaman R, Sampaio EP, et al. Anti-CD20 (rituximab) therapy for anti-IFN-gamma autoantibody-associated nontuberculous mycobacterial infection. Blood. 2012;119:3933–9.PubMedPubMedCentralGoogle Scholar
  36. 36.
    Czaja CA, Merkel PA, Chan ED, et al. Rituximab as successful adjunct treatment in a patient with disseminated nontuberculous mycobacterial infection due to acquired anti-interferon-gamma autoantibody. Clin Infect Dis. 2014;58:e115–8.PubMedGoogle Scholar
  37. 37.
    Vinh DC, Patel SY, Uzel G, et al. Autosomal dominant and sporadic monocytopenia with susceptibility to mycobacteria, fungi, papillomaviruses, and myelodysplasia. Blood. 2010;115:1519–29.PubMedPubMedCentralGoogle Scholar
  38. 38.
    Hsu AP, Sampaio EP, Khan J, et al. Mutations in GATA2 are associated with the autosomal dominant and sporadic monocytopenia and mycobacterial infection (MonoMAC) syndrome. Blood. 2011;118:2653–5.PubMedPubMedCentralGoogle Scholar
  39. 39.
    Hsu AP, McReynolds LJ, Holland SM. GATA2 deficiency. Curr Opin Allergy Clin Immunol. 2015;15:104–9.PubMedPubMedCentralGoogle Scholar
  40. 40.
    Horsburgh CR Jr. Mycobacterium avium complex infection in the acquired immunodeficiency syndrome. N Engl J Med. 1991;324:1332–8.PubMedGoogle Scholar
  41. 41.
    Havlik JA Jr, Horsburgh CR Jr, Metchock B, Williams PP, Fann SA, Thompson SE 3rd. Disseminated Mycobacterium avium complex infection: clinical identification and epidemiologic trends. J Infect Dis. 1992;165:577–80.PubMedGoogle Scholar
  42. 42.
    Varley CD, Ku JH, Henkle E, Schafer SD, Winthrop KL. Disseminated Nontuberculous mycobacteria in HIV-infected patients, Oregon, USA, 2007-2012. Emerg Infect Dis. 2017;23:533–5.PubMedPubMedCentralGoogle Scholar
  43. 43.
    Kaplan JE, Hanson D, Dworkin MS, et al. Epidemiology of human immunodeficiency virus-associated opportunistic infections in the United States in the era of highly active antiretroviral therapy. Clin Infect Dis. 2000;30(Suppl 1):S5–14.PubMedGoogle Scholar
  44. 44.
    Kaplan JE, Masur H, Holmes KK, Usphs, Infectious Disease Society of A. Guidelines for preventing opportunistic infections among HIV-infected persons--2002. Recommendations of the U.S. Public Health Service and the Infectious Diseases Society of America. MMWR Recomm Rep. 2002;51:1–52.PubMedGoogle Scholar
  45. 45.
    McCarthy KD, Cain KP, Winthrop KL, et al. Nontuberculous mycobacterial disease in patients with HIV in Southeast Asia. Am J Respir Crit Care Med. 2012;185:981–8.PubMedGoogle Scholar
  46. 46.
    Corbett EL, Blumberg L, Churchyard GJ, et al. Nontuberculous mycobacteria: defining disease in a prospective cohort of south African miners. Am J Respir Crit Care Med. 1999;160:15–21.PubMedGoogle Scholar
  47. 47.
    Kaplan JE, Masur H, Holmes KK, et al. USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus: an overview. USPHS/IDSA prevention of opportunistic infections working group. Clin Infect Dis. 1995;21(Suppl 1):S12–31.PubMedGoogle Scholar
  48. 48.
    Horsburgh CR Jr, Havlik JA, Ellis DA, et al. Survival of patients with acquired immune deficiency syndrome and disseminated Mycobacterium avium complex infection with and without antimycobacterial chemotherapy. Am Rev Respir Dis. 1991;144:557–9.PubMedGoogle Scholar
  49. 49.
    Miguez-Burbano MJ, Flores M, Ashkin D, et al. Non-tuberculous mycobacteria disease as a cause of hospitalization in HIV-infected subjects. Int J Infect Dis. 2006;10:47–55.PubMedGoogle Scholar
  50. 50.
    Lawn SD, Bekker LG, Miller RF. Immune reconstitution disease associated with mycobacterial infections in HIV-infected individuals receiving antiretrovirals. Lancet Infect Dis. 2005;5:361–73.PubMedGoogle Scholar
  51. 51.
    Sitapati AM, Kao CL, Cachay ER, Masoumi H, Wallis RS, Mathews WC. Treatment of HIV-related inflammatory cerebral cryptococcoma with adalimumab. Clin Infect Dis. 2010;50:e7–10.PubMedGoogle Scholar
  52. 52.
    Meintjes G, Scriven J, Marais S. Management of the immune reconstitution inflammatory syndrome. Curr HIV/AIDS Rep. 2012;9:238–50.PubMedGoogle Scholar
  53. 53.
    Wallace RJ Jr, Brown BA, Onyi GO. Skin, soft tissue, and bone infections due to Mycobacterium chelonae chelonae: importance of prior corticosteroid therapy, frequency of disseminated infections, and resistance to oral antimicrobials other than clarithromycin. J Infect Dis. 1992;166:405–12.PubMedGoogle Scholar
  54. 54.
    Jick SS, Lieberman ES, Rahman MU, Choi HK. Glucocorticoid use, other associated factors, and the risk of tuberculosis. Arthritis Rheum. 2006;55:19–26.PubMedGoogle Scholar
  55. 55.
    Dirac MA, Horan KL, Doody DR, et al. Environment or host?: A case-control study of risk factors for Mycobacterium avium complex lung disease. Am J Respir Crit Care Med. 2012;186:684–91.PubMedPubMedCentralGoogle Scholar
  56. 56.
    Brode SK, Jamieson FB, Ng R, et al. Increased risk of mycobacterial infections associated with anti-rheumatic medications. Thorax. 2015;70:677–82.PubMedGoogle Scholar
  57. 57.
    Hojo M, Iikura M, Hirano S, Sugiyama H, Kobayashi N, Kudo K. Increased risk of nontuberculous mycobacterial infection in asthmatic patients using long-term inhaled corticosteroid therapy. Respirology. 2012;17:185–90.PubMedGoogle Scholar
  58. 58.
    Bigbee CL, Gonchoroff DG, Vratsanos G, Nadler SG, Haggerty HG, Flynn JL. Abatacept treatment does not exacerbate chronic Mycobacterium tuberculosis infection in mice. Arthritis Rheum. 2007;56:2557–65.PubMedGoogle Scholar
  59. 59.
    Schiff M, Keiserman M, Codding C, et al. Efficacy and safety of abatacept or infliximab vs placebo in ATTEST: a phase III, multi-centre, randomised, double-blind, placebo-controlled study in patients with rheumatoid arthritis and an inadequate response to methotrexate. Ann Rheum Dis. 2008;67:1096–103.PubMedGoogle Scholar
  60. 60.
    Novosad SA, Winthrop KL. Beyond tumor necrosis factor inhibition: the expanding pipeline of biologic therapies for inflammatory diseases and their associated infectious sequelae. Clin Infect Dis. 2014;58:1587–98.PubMedGoogle Scholar
  61. 61.
    Lee SK, Kim SY, Kim EY, et al. Mycobacterial infections in patients treated with tumor necrosis factor antagonists in South Korea. Lung. 2013;191:565–71.PubMedGoogle Scholar
  62. 62.
    Yoo JW, Jo KW, Kang BH, et al. Mycobacterial diseases developed during anti-tumour necrosis factor-alpha therapy. Eur Respir J. 2014;44(5):1289–95.PubMedGoogle Scholar
  63. 63.
    Mori S, Tokuda H, Sakai F, et al. Radiological features and therapeutic responses of pulmonary nontuberculous mycobacterial disease in rheumatoid arthritis patients receiving biological agents: a retrospective multicenter study in Japan. Mod Rheumatol. 2012;22:727–37.PubMedGoogle Scholar
  64. 64.
    Lutt JR, Pisculli ML, Weinblatt ME, Deodhar A, Winthrop KL. Severe nontuberculous mycobacterial infection in 2 patients receiving rituximab for refractory myositis. J Rheumatol. 2008;35:1683–5.PubMedGoogle Scholar
  65. 65.
    Cohen SB, Tanaka Y, Mariette X, et al. Long-term safety of tofacitinib for the treatment of rheumatoid arthritis up to 8.5 years: integrated analysis of data from the global clinical trials. Ann Rheum Dis. 2017;76:1253–62.PubMedPubMedCentralGoogle Scholar
  66. 66.
    Cortet B, Flipo RM, Remy-Jardin M, et al. Use of high resolution computed tomography of the lungs in patients with rheumatoid arthritis. Ann Rheum Dis. 1995;54:815–9.PubMedPubMedCentralGoogle Scholar
  67. 67.
    Yamakawa H, Takayanagi N, Ishiguro T, Kanauchi T, Hoshi T, Sugita Y. Clinical investigation of nontuberculous mycobacterial lung disease in Japanese patients with rheumatoid arthritis receiving biologic therapy. J Rheumatol. 2013;40:1994–2000.PubMedGoogle Scholar
  68. 68.
    U.S. Department of Health & Human Services Organ Procurement and Transplantation Network. Transplant: Organ by Transplant Year (2015–2061). Found at Last accessed 11/6/2017.
  69. 69.
    Yoo JW, Jo KW, Kim SH, et al. Incidence, characteristics, and treatment outcomes of mycobacterial diseases in transplant recipients. Transpl Int. 2016;29:549–58.PubMedGoogle Scholar
  70. 70.
    Huang HC, Weigt SS, Derhovanessian A, et al. Non-tuberculous mycobacterium infection after lung transplantation is associated with increased mortality. J Heart Lung Transplant. 2011;30:790–8.PubMedPubMedCentralGoogle Scholar
  71. 71.
    Knoll BM, Kappagoda S, Gill RR, et al. Non-tuberculous mycobacterial infection among lung transplant recipients: a 15-year cohort study. Transpl Infect Dis. 2012;14:452–60.PubMedGoogle Scholar
  72. 72.
    Longworth SA, Vinnard C, Lee I, Sims KD, Barton TD, Blumberg EA. Risk factors for nontuberculous mycobacterial infections in solid organ transplant recipients: a case-control study. Transpl Infect Dis. 2014;16:76–83.PubMedGoogle Scholar
  73. 73.
    Baker AW, Lewis SS, Alexander BD, et al. Two-phase hospital-associated outbreak of Mycobacterium abscessus: investigation and mitigation. Clin Infect Dis. 2017;64:902–11.PubMedPubMedCentralGoogle Scholar
  74. 74.
    Floto RA, Olivier KN, Saiman L, et al. US Cystic Fibrosis Foundation and European cystic fibrosis society consensus recommendations for the management of non-tuberculous mycobacteria in individuals with cystic fibrosis: executive summary. Thorax. 2016;71:88–90.PubMedPubMedCentralGoogle Scholar
  75. 75.
    Brodhie M. et al. Journal of Heart and Lung Transplantation April 2017 [abstract] NonTuberculous Mycobacteria Infection and Lung Transplantation in Cystic Fibrosis: A Worldwide Survey of Clinical Practice.Google Scholar
  76. 76.
    Lobo LJ, Chang LC, Esther CR Jr, Gilligan PH, Tulu Z, Noone PG. Lung transplant outcomes in cystic fibrosis patients with pre-operative Mycobacterium abscessus respiratory infections. Clin Transpl. 2013;27:523–9.Google Scholar
  77. 77.
    Doucette K, Fishman JA. Nontuberculous mycobacterial infection in hematopoietic stem cell and solid organ transplant recipients. Clin Infect Dis. 2004;38:1428–39.PubMedGoogle Scholar
  78. 78.
    Daley CL. Nontuberculous mycobacterial disease in transplant recipients: early diagnosis and treatment. Curr Opin Organ Transplant. 2009;14:619–24.PubMedGoogle Scholar
  79. 79.
    Pasquini MC, Wang Z. Current use and outcome of hematopoietic stem cell transplantation: CIBMTR Summary Slides. (2013). Available at:
  80. 80.
    Busam KJ, Kiehn TE, Salob SP, Myskowski PL. Histologic reactions to cutaneous infections by Mycobacterium haemophilum. Am J Surg Pathol. 1999;23:1379–85.PubMedGoogle Scholar
  81. 81.
    Kiehn TE, White M, Pursell KJ, et al. A cluster of four cases of Mycobacterium haemophilum infection. Eur J Clin Microbiol Infect Dis. 1993;12:114–8.PubMedGoogle Scholar
  82. 82.
    Straus WL, Ostroff SM, Jernigan DB, et al. Clinical and epidemiologic characteristics of Mycobacterium haemophilum, an emerging pathogen in immunocompromised patients. Ann Intern Med. 1994;120:118–25.PubMedGoogle Scholar
  83. 83.
    White MH, Papadopoulos EB, Small TN, Kiehn TE, Armstrong D. Mycobacterium haemophilum infections in bone marrow transplant recipients. Transplantation. 1995;60:957–60.PubMedGoogle Scholar
  84. 84.
    Weinstock DM, Feinstein MB, Sepkowitz KA, Jakubowski A. High rates of infection and colonization by nontuberculous mycobacteria after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 2003;31:1015–21.PubMedGoogle Scholar
  85. 85.
    Chen CY, Sheng WH, Lai CC, et al. Mycobacterial infections in adult patients with hematological malignancy. Eur J Clin Microbiol Infect Dis. 2012;31:1059–66.PubMedGoogle Scholar
  86. 86.
    Feld R, Bodey GP, Groschel D. Mycobacteriosis in patients with malignant disease. Arch Intern Med. 1976;136:67–70.PubMedGoogle Scholar
  87. 87.
    Rolston KV, Jones PG, Fainstein V, Bodey GP. Pulmonary disease caused by rapidly growing mycobacteria in patients with cancer. Chest. 1985;87:503–6.PubMedGoogle Scholar
  88. 88.
    Gallo JH, Young GA, Forrest PR, Vincent PC, Jennis F. Disseminated atypical mycobacterial infection in hairy cell leukemia. Pathology. 1983;15:241–5.PubMedGoogle Scholar
  89. 89.
    Weinstein RA, Golomb HM, Grumet G, Gelmann E, Schechter GP. Hairy cell leukemia: association with disseminated atypical mycobacterial infection. Cancer. 1981;48:380–3.PubMedGoogle Scholar
  90. 90.
    Bennett C, Vardiman J, Golomb H. Disseminated atypical mycobacterial infection in patients with hairy cell leukemia. Am J Med. 1986;80:891–6.PubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.OHSU-PSU School of Public Health, Oregon Health and Science UniversityPortlandUSA

Personalised recommendations