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Clinical Manifestations of HIV-Associated Tuberculosis in Adults

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HIV and Tuberculosis

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Abstract

HIV-associated tuberculosis is a heterogenous disease that confronts clinicians with substantial diagnostic challenge. Clinical syndromes are frequently non-specific in terms of symptoms, physical examination, routine laboratory testing, and chest radiography. Further complicating management is the possibility of co-infection with other severe opportunistic infections, all of which may have clinical presentations that mimic tuberculosis. Early recognition and treatment is urgent because of more severe manifestations and rapid progression, particularly at low CD4 counts. This chapter describes clinical manifestations and diagnostic approaches for HIV-associated tuberculosis in adults, with an emphasis on practice in resource-limited, high-burden settings. Advanced immunosuppression and disseminated disease are considered separately from ambulant patients with preserved CD4 cell counts in order to highlight differences in clinical phenotype, differential diagnosis, and management strategies. Clinical features and evaluation of common extra-pulmonary manifestations are also covered.

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References

  1. Barry CE 3rd, Boshoff HI, Dartois V et al (2009) The spectrum of latent tuberculosis: rethinking the biology and intervention strategies. Nat Rev Microbiol 7:845–855

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Gupta RK, Lucas SB, Fielding KL et al (2015) Prevalence of tuberculosis in post-mortem studies of HIV-infected adults and children in resource-limited settings: a systematic review and meta-analysis. AIDS (London, England) 29:1987–2002

    Google Scholar 

  3. Getahun H, Kittikraisak W, Heilig CM et al (2011) Development of a standardized screening rule for tuberculosis in people living with HIV in resource-constrained settings: individual participant data meta-analysis of observational studies. PLoS Med 8:e1000391

    PubMed  PubMed Central  Google Scholar 

  4. Hamada Y, Lujan J, Schenkel K et al (2018) Sensitivity and specificity of WHO’s recommended four-symptom screening rule for tuberculosis in people living with HIV: a systematic review and meta-analysis. The Lancet HIV 5:e515–ee23

    PubMed  Google Scholar 

  5. Wood R, Middelkoop K, Myer L et al (2007) Undiagnosed tuberculosis in a community with high HIV prevalence: implications for tuberculosis control. Am J Respir Crit Care Med 175:87–93

    PubMed  Google Scholar 

  6. Lawn SD, Kerkhoff AD, Vogt M et al (2013) Diagnostic and prognostic value of serum C-reactive protein for screening for HIV-associated tuberculosis. Int J Tuberc Lung Dis 17:636–643

    CAS  PubMed  Google Scholar 

  7. Drain PK, Mayeza L, Bartman P et al (2014) Diagnostic accuracy and clinical role of rapid C-reactive protein testing in HIV-infected individuals with presumed tuberculosis in South Africa. Int J Tuberc Lung Dis 18:20–26

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Wilson D, Badri M, Maartens G (2011) Performance of serum C-reactive protein as a screening test for smear-negative tuberculosis in an ambulatory high HIV prevalence population. PLoS One 6:e15248

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Nyamande K, Lalloo UG (2006) Serum procalcitonin distinguishes CAP due to bacteria, Mycobacterium tuberculosis and PJP. Int J Tuberc Lung Dis 10:510–515

    CAS  PubMed  Google Scholar 

  10. Yoon C, Davis JL, Huang L et al (2014) Point-of-care C-reactive protein testing to facilitate implementation of isoniazid preventive therapy for people living with HIV. J Acquir Immune Defic Syndr 1999 65(5):551–556

    CAS  Google Scholar 

  11. Mendelson F, Griesel R, Tiffin N et al (2018) C-reactive protein and procalcitonin to discriminate between tuberculosis, Pneumocystis jirovecii pneumonia, and bacterial pneumonia in HIV-infected inpatients meeting WHO criteria for seriously ill: a prospective cohort study. BMC Infect Dis 18:399

    PubMed  PubMed Central  Google Scholar 

  12. Van Dyck P, Vanhoenacker FM, Van den Brande P et al (2003) Imaging of pulmonary tuberculosis. Eur Radiol 13:1771–1785

    PubMed  Google Scholar 

  13. Perlman DC, el-Sadr WM, Nelson ET et al (1997) Variation of chest radiographic patterns in pulmonary tuberculosis by degree of human immunodeficiency virus-related immunosuppression. Clin Infect Dis 25:242–246

    Google Scholar 

  14. Pedro-Botet J, Gutierrez J, Miralles R et al (1992) Pulmonary tuberculosis in HIV-infected patients with normal chest radiographs. AIDS (London, England) 6:91–93

    CAS  Google Scholar 

  15. Organization WH (2007) Improving the diagnosis and treatment of smear-negative pulmonary and extrapulmonary tuberculosis among adults and adolescents. WHO, Geneva

    Google Scholar 

  16. Ngwira LG, Corbett EL, Khundi M et al (2019) Screening for tuberculosis with Xpert MTB/RIF versus fluorescent microscopy among adults newly diagnosed with HIV in rural Malawi: a cluster randomized trial (Chepetsa). Clin Infect Dis 68(7):1176–1183

    PubMed  Google Scholar 

  17. Hermans SM, Babirye JA, Mbabazi O et al (2017) Treatment decisions and mortality in HIV-positive presumptive smear-negative TB in the Xpert MTB/RIF era: a cohort study. BMC Infect Dis 17:433

    PubMed  PubMed Central  Google Scholar 

  18. Calligaro GL, Theron G, Khalfey H et al (2015) Burden of tuberculosis in intensive care units in Cape Town, South Africa, and assessment of the accuracy and effect on patient outcomes of the Xpert MTB/RIF test on tracheal aspirate samples for diagnosis of pulmonary tuberculosis: a prospective burden of disease study with a nested randomised controlled trial. Lancet Respir Med 3:621–630

    PubMed  Google Scholar 

  19. Sigel K, Makinson A, Thaler J (2017) Lung cancer in persons with HIV. Curr Opin HIV AIDS 12:31–38

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Hanifa Y, Toro Silva S, Karstaedt A et al (2019) What causes symptoms suggestive of tuberculosis in HIV-positive people with negative initial investigations? Int J Tuberc Lung Dis 23(2):157–165

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Kaplan R, Hermans S, Caldwell J et al (2018) HIV and TB co-infection in the ART era: CD4 count distributions and TB case fatality in Cape Town. BMC Infect Dis 18:356

    PubMed  PubMed Central  Google Scholar 

  22. Osler M, Hilderbrand K, Goemaere E et al (2018) The continuing burden of advanced HIV disease over 10 years of increasing antiretroviral therapy coverage in South Africa. Clin Infect Dis 66:S118–Ss25

    PubMed  PubMed Central  Google Scholar 

  23. Crump JA, Reller LB (2003) Two decades of disseminated tuberculosis at a university medical center: the expanding role of mycobacterial blood culture. Clin Infect Dis 37:1037–1043

    PubMed  Google Scholar 

  24. Janssen S, Schutz C, Ward A et al (2017) Mortality in severe human immunodeficiency virus-tuberculosis associates with innate immune activation and dysfunction of monocytes. Clin Infect Dis 65:73–82

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Griesel R, Stewart A, van der Plas H et al (2018) Optimizing tuberculosis diagnosis in HIV-infected inpatients meeting the criteria of seriously Ill in the WHO algorithm. Clin Infect Dis 66(9):1419–1426

    CAS  PubMed  Google Scholar 

  26. Gupta-Wright A, Corbett EL, van Oosterhout JJ et al (2018) Rapid urine-based screening for tuberculosis in HIV-positive patients admitted to hospital in Africa (STAMP): a pragmatic, multicentre, parallel-group, double-blind, randomised controlled trial. Lancet 392:292–301

    Google Scholar 

  27. Maartens G, Willcox PA, Benatar SR (1990) Miliary tuberculosis: rapid diagnosis, hematologic abnormalities, and outcome in 109 treated adults. Am J Med 89:291–296

    CAS  PubMed  Google Scholar 

  28. Jacob ST, Pavlinac PB, Nakiyingi L et al (2013) Mycobacterium tuberculosis bacteremia in a cohort of HIV-infected patients hospitalized with severe sepsis in Uganda-high frequency, low clinical suspicion [corrected] and derivation of a clinical prediction score. PLoS One 8:e70305

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Muchemwa L, Shabir L, Andrews B et al (2017) High prevalence of Mycobacterium tuberculosis bacteraemia among a cohort of HIV-infected patients with severe sepsis in Lusaka, Zambia. Int J STD AIDS 28:584–593

    PubMed  Google Scholar 

  30. Gleeson LE, Sheedy FJ, Palsson-McDermott EM et al (2016) Cutting edge: Mycobacterium tuberculosis induces aerobic glycolysis in human alveolar macrophages that is required for control of intracellular bacillary replication. J Immunol 196:2444–2449

    CAS  PubMed  Google Scholar 

  31. Keiper MD, Beumont M, Elshami A et al (1995) CD4 T lymphocyte count and the radiographic presentation of pulmonary tuberculosis. A study of the relationship between these factors in patients with human immunodeficiency virus infection. Chest 107:74–80

    CAS  PubMed  Google Scholar 

  32. Greenberg SD, Frager D, Suster B et al (1994) Active pulmonary tuberculosis in patients with AIDS: spectrum of radiographic findings (including a normal appearance). Radiology 193:115–119

    CAS  PubMed  Google Scholar 

  33. Wasserman S, Engel ME, Griesel R, Mendelson M (2016) Burden of pneumocystis pneumonia in HIV-infected adults in sub-Saharan Africa: a systematic review and meta-analysis. BMC Infect Dis 16:482

    PubMed  PubMed Central  Google Scholar 

  34. Rupali P, Abraham OC, Zachariah A et al (2003) Aetiology of prolonged fever in antiretroviral-naive human immunodeficiency virus-infected adults. Natl Med J India 16:193–199

    PubMed  Google Scholar 

  35. Kerkhoff AD, Meintjes G, Burton R et al (2016) Relationship between blood concentrations of hepcidin and anaemia severity, mycobacterial burden and mortality in patients with HIV-associated tuberculosis. J Infect Dis 213(1):61–70

    CAS  PubMed  Google Scholar 

  36. Andrews B, Semler MW, Muchemwa L et al (2017) Effect of an early resuscitation protocol on in-hospital mortality among adults with sepsis and hypotension: a randomized clinical trial. JAMA 318:1233–1240

    PubMed  PubMed Central  Google Scholar 

  37. Kerkhoff AD, Meintjes G, Opie J et al (2016) Anaemia in patients with HIV-associated TB: relative contributions of anaemia of chronic disease and iron deficiency. Int J Tuberc Lung Dis 20:193–201

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Kerkhoff AD, Lawn SD, Schutz C et al (2015) Anemia, blood transfusion requirements and mortality risk in human immunodeficiency virus-infected adults requiring acute medical admission to hospital in South Africa. Open Forum Infect Dis 2:ofv173

    PubMed  PubMed Central  Google Scholar 

  39. Janssen S, Schutz C, Ward AM et al (2017) Hemostatic changes associated with increased mortality rates in hospitalized patients with HIV-associated tuberculosis: a prospective cohort study. J Infect Dis 215:247–258

    CAS  PubMed  Google Scholar 

  40. World Health Organization (2017) Guidelines for treatment of drug-susceptible tuberculosis and patient care, 2017 update. WHO, Geneva

    Google Scholar 

  41. Griesel R, Stewart A, van der Plas H et al (2018) Optimizing tuberculosis diagnosis in human immunodeficiency virus-infected inpatients meeting the criteria of seriously ill in the World Health Organization algorithm. Clin Infect Dis 66:1419–1426

    CAS  PubMed  Google Scholar 

  42. Lawn SD, Kerkhoff AD, Burton R et al (2015) Rapid microbiological screening for tuberculosis in HIV-positive patients on the first day of acute hospital admission by systematic testing of urine samples using Xpert MTB/RIF: a prospective cohort in South Africa. BMC Med 13:192

    PubMed  PubMed Central  Google Scholar 

  43. Gupta-Wright A, Corbett EL, Wilson D et al (2019) Risk score for predicting mortality including urine lipoarabinomannan detection in hospital inpatients with HIV-associated tuberculosis in sub-Saharan Africa: derivation and external validation cohort study. PLoS Med 16:e1002776

    PubMed  PubMed Central  Google Scholar 

  44. Kerkhoff AD, Barr DA, Schutz C et al (2017) Disseminated tuberculosis among hospitalised HIV patients in South Africa: a common condition that can be rapidly diagnosed using urine-based assays. Sci Rep 7:10931

    PubMed  PubMed Central  Google Scholar 

  45. Gupta-Wright A, Peters JA, Flach C et al (2016) Detection of lipoarabinomannan (LAM) in urine is an independent predictor of mortality risk in patients receiving treatment for HIV-associated tuberculosis in sub-Saharan Africa: a systematic review and meta-analysis. BMC Med 14:53

    PubMed  PubMed Central  Google Scholar 

  46. Shah M, Variava E, Holmes CB et al (2009) Diagnostic accuracy of a urine lipoarabinomannan test for tuberculosis in hospitalized patients in a High HIV prevalence setting. J Acquir Immune Defic Syndr (1999) 52:145–151

    Google Scholar 

  47. Lawn SD, Kerkhoff AD, Burton R et al (2017) Diagnostic accuracy, incremental yield and prognostic value of Determine TB-LAM for routine diagnostic testing for tuberculosis in HIV-infected patients requiring acute hospital admission in South Africa: a prospective cohort. BMC Med 15:67

    PubMed  PubMed Central  Google Scholar 

  48. World Health Organization (2015) Guidelines on the management of latent tuberculosis infection. WHO, Geneva

    Google Scholar 

  49. Lawn SD, Kerkhoff AD, Vogt M et al (2013) HIV-associated tuberculosis: relationship between disease severity and the sensitivity of new sputum-based and urine-based diagnostic assays. BMC Med 11:231

    PubMed  PubMed Central  Google Scholar 

  50. Iseman MD (2000) A clinician’s guide to tuberculosis. Lippincott Williams & Wilkins, Philadelphia

    Google Scholar 

  51. World Health Organization. Automated real-time nucleic acid amplification technology for rapid and simultaneous detection of tuberculosis and rifampicin resistance: Xpert MTB/RIF assay for the diagnosis of pulmonary and extrapulmonary TB in adults and children. Policy update. Geneva, 2013

    Google Scholar 

  52. Lawn SD, Mwaba P, Bates M et al (2013) Advances in tuberculosis diagnostics: the Xpert MTB/RIF assay and future prospects for a point-of-care test. Lancet Infect Dis 13:349–361

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Batungwanayo J, Taelman H, Allen S et al (1993) Pleural effusion, tuberculosis and HIV-1 infection in Kigali, Rwanda. AIDS (London, England) 7:73–79

    CAS  Google Scholar 

  54. Aljohaney A, Amjadi K, Alvarez GG (2012) A systematic review of the epidemiology, immunopathogenesis, diagnosis, and treatment of pleural TB in HIV-infected patients. Clin Dev Immunol 2012:842045

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Luzze H, Elliott AM, Joloba ML et al (2001) Evaluation of suspected tuberculous pleurisy: clinical and diagnostic findings in HIV-1-positive and HIV-negative adults in Uganda. Int J Tuberc Lung Dis 5:746–753

    CAS  PubMed  Google Scholar 

  56. Aggarwal AN, Agarwal R, Sehgal IS et al (2019) Adenosine deaminase for diagnosis of tuberculous pleural effusion: a systematic review and meta-analysis. PLoS One 14:e0213728

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Baba K, Hoosen AA, Langeland N et al (2008) Adenosine deaminase activity is a sensitive marker for the diagnosis of tuberculous pleuritis in patients with very low CD4 counts. PLoS One 3:e2788

    PubMed  PubMed Central  Google Scholar 

  58. Heyderman RS, Makunike R, Muza T et al (1998) Pleural tuberculosis in Harare, Zimbabwe: the relationship between human immunodeficiency virus, CD4 lymphocyte count, granuloma formation and disseminated disease. Tropical Med Int Health 3:14–20

    CAS  Google Scholar 

  59. Sharma MP, Bhatia V (2004) Abdominal tuberculosis. Indian J Med Res 120:305–315

    CAS  PubMed  Google Scholar 

  60. Riquelme A, Calvo M, Salech F et al (2006) Value of adenosine deaminase (ADA) in ascitic fluid for the diagnosis of tuberculous peritonitis: a meta-analysis. J Clin Gastroenterol 40:705–710

    CAS  PubMed  Google Scholar 

  61. Magula NP, Mayosi BM (2003) Cardiac involvement in HIV-infected people living in Africa: a review. Cardiovasc J South Afr 14:231–237

    Google Scholar 

  62. Mayosi BM, Wiysonge CS, Ntsekhe M et al (2006) Clinical characteristics and initial management of patients with tuberculous pericarditis in the HIV era: the Investigation of the Management of Pericarditis in Africa (IMPI Africa) registry. BMC Infect Dis 6:2

    PubMed  PubMed Central  Google Scholar 

  63. Mayosi BM, Wiysonge CS, Ntsekhe M et al (2008) Mortality in patients treated for tuberculous pericarditis in sub-Saharan Africa. S Afr Med J 98:36–40

    PubMed  Google Scholar 

  64. Reuter H, Burgess LJ, Doubell AF (2005) Role of chest radiography in diagnosing patients with tuberculous pericarditis. Cardiovasc J South Afr 16:108–111

    CAS  Google Scholar 

  65. George S, Salama AL, Uthaman B et al (2004) Echocardiography in differentiating tuberculous from chronic idiopathic pericardial effusion. Heart 90:1338–1339

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Liu PY, Li YH, Tsai WC et al (2001) Usefulness of echocardiographic intrapericardial abnormalities in the diagnosis of tuberculous pericardial effusion. Am J Cardiol 87:1133–1135. a10

    CAS  PubMed  Google Scholar 

  67. Pandie S, Peter JG, Kerbelker ZS et al (2014) Diagnostic accuracy of quantitative PCR (Xpert MTB/RIF) for tuberculous pericarditis compared to adenosine deaminase and unstimulated interferon-γ in a high burden setting: a prospective study. BMC Med 12:101

    PubMed  PubMed Central  Google Scholar 

  68. Mayosi BM, Burgess LJ, Doubell AF (2005) Tuberculous pericarditis. Circulation 112:3608–3616

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, Department of Medicine, University of Cape Town, Cape Town, South Africa

    Sean Wasserman & Graeme Meintjes

  2. Division of Infectious Diseases and HIV Medicine, Department of Medicine, University of Cape Town, Cape Town, South Africa

    Sean Wasserman & Graeme Meintjes

  3. Institute of Infection and Global Health, University of Liverpool, Liverpool, UK

    David Barr

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  1. Sean Wasserman
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  2. David Barr
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  3. Graeme Meintjes
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Correspondence to Sean Wasserman .

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Editors and Affiliations

  1. National Institute of Health, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA

    Irini Sereti

  2. Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    Gregory P. Bisson

  3. Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, Department of Medicine, University of Cape Town, Division of Infectious Diseases and HIV Medicine, Department of Medicine, University of Cape Town, Cape Town, South Africa

    Graeme Meintjes

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Wasserman, S., Barr, D., Meintjes, G. (2019). Clinical Manifestations of HIV-Associated Tuberculosis in Adults. In: Sereti, I., Bisson, G.P., Meintjes, G. (eds) HIV and Tuberculosis. Springer, Cham. https://doi.org/10.1007/978-3-030-29108-2_5

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