Evaluation of clinical, laboratory, radiographical and histopathological characteristics in patients with spinal tuberculosis in the context of HIV infection: An analysis of 52 patients from a South African tertiary hospital
DOI:
https://doi.org/10.7196/SAMJ.2024.v114i11.2065Keywords:
spinal tuberculosis, South Africa, tuberculous spondylodiscitis, cohort study, Pott`'s diseaseAbstract
Background. South Africa (SA) has the highest prevalence of people with tuberculosis (TB) and HIV coinfection globally. People living with HIV have an increased risk of TB infection, and are more likely to develop extrapulmonary TB. Approximately 10 - 20% of extrapulmonary TB accounts for skeletal TB, with spinal involvement in 50 - 60% of instances. Previous studies have shown highly heterogenic results regarding the effect of HIV status on clinical and laboratory characteristics in patients with spinal TB (STB).
Objective. To describe the clinical, laboratory, radiographical and histopathological characteristics of patients diagnosed with STB stratified by HIV status.
Methods. Data from patients who were treated for STB at the Division of Orthopaedic Surgery, Groote Schuur Hospital, SA, between 2013 and 2016 were analysed. We compared clinical, laboratory, radiographical and histopathological parameters of STB patients with HIV infection to those without HIV infection. To assess differences in means between the two groups, an independent samples t-test was used for normally distributed continuous data, and a χ2 test for categorical data. To assess correlations between continuous data groups, the Pearson correlation coefficient was used.
Results. We assessed 52 patients with STB (mean (standard deviation (SD) age 38 (15.2) years, range 17 - 80 years), of whom 55.8% were female, and 59.6% HIV infected. Five (9.6%) patients were identified with multidrug-resistant TB of the spine, with four (19.0%) in the HIV-infected cohort and one in the HIV-uninfected cohort (p=0.058). Significantly more STB patients without HIV infection presented with neurogenic symptoms (29%, p=0.029). The mean (SD) overall erythrocyte sedimentation rate was 69.3 (35.9) mm/h, with no significant difference between HIV-infected and HIV-uninfected patients (p=0.086). The rate of vertebral collapse was higher in the HIV-infected cohort (39% v. 67%, p=0.048). HIV-infected patients showed a higher count of involved vertebrae (mean 3.0 v. 3.85; p=0.034). There was no correlation between CD4 count and the number of involved vertebrae. The mean (SD) number of granulomata per low-power field was 10 (12.6), with no difference between the two cohorts. However, we found a positive correlation between granuloma count and CD4 cell count in HIV-infected STB patients (Pearson 0.503, p=0.02), with significantly higher formation of granulomata at a CD4 cell count >400 cells/μL (p=0.045).
Conclusion. In our cohort, HIV-infected patients with STB were more likely to present with vertebral collapse, and more vertebrae on average were diseased compared with HIV-uninfected patients with STB. CD4 cell count may affect granuloma formation, and it seems that HIV infection has a negative effect on cellular immunoresponse in STB, which emphasises the need for early antiretroviral therapy initiation.
References
1. World Health Organization. Global tuberculosis report 2023. Geneva: WHO, 2023.
2. World Health Organization. Global tuberculosis report 2020. Geneva: WHO, 2020.
3. Koch R. Die Aetiologie der Tuberkulose. Berliner Klinische Wochenschrift 1882;19:221-230.
4. Raviglione MC, O’Brien RJ. Tuberculosis. In: Loscalzo J, Fauci A, Kasper D, et al (eds). Harrison’s
Principles of Internal Medicine. New York: McGraw-Hill Companies, Inc, 2008:1012.
5. World Health Organization. Global tuberculosis report 2013. Geneva: WHO, 2014.
6. Diedrich CR, O’Hern J, Wilkinson RJ. HIV-1 and the Mycobacterium tuberculosis granuloma:
A systematic review and meta-analysis. Tuberculosis 2016;1(98):62-76. https://doi.org/10.1016/j.
tube.2016.02.010
7. Joint United Nations Programme on HIV/AIDS. Global HIV and AIDS statistics – fact sheet. UNAIDS, 2023. https://www.unaids.org/en/resources/fact-sheet (accessed 30 December 2023).
8. Bender BS, Davidson BL, Kline R, Brown C, Quinn TC. Role of the mononuclear phagocyte system in the immunopathogenesis of human immunodeficiency virus infection and the acquired immunodeficiency syndrome. Clin Infect Dis 1988;10(6):1142-1154.
9. Selwyn PA, Hartel D, Lewis VA, et al. A prospective study of the risk of tuberculosis among intravenous drug users with human immunodeficiency virus infection. N Engl J Med 1989;320(9):545-550.
10. Pitchenik AE, Cole C, Russell BW, Fischl MA, Spira TJ, Snider Jr DE. Tuberculosis, atypical mycobacteriosis, and the acquired immunodeficiency syndrome among Haitian and non-Haitian patients in South Florida. Ann Intern Med 1984;101(5):641-645.
11. Sunderam G, McDonald RJ, Maniatis T, Oleske J, Kapila R, Reichman LB. Tuberculosis as a manifestation of the acquired immunodeficiency syndrome (AIDS). JAMA 1986;256(3):362-366.
12. Chaisson RE, Schecter G, Theuer C, Rutherford G, Echenberg D, Hopewell P. Tuberculosis in patients
with the acquired immunodeficiency syndrome. Am Rev Respir Dis 1987;136:570-574.
13. Theuer CP, Hopewell PC, Elias D, Schecter GF, Rutherford GW, Chaisson RE. Human
immunodeficiency virus infection in tuberculosis patients. J Infect Dis 1990;162(1):8-12.
14. Kramer F, Modilevsky T, Waliany AR, Leedom JM, Barnes PF. Delayed diagnosis of tuberculosis in
patients with human immunodeficiency virus infection. Am J Med 1990;89(4):451-456.
15. Pitchenik AE, Burr J, Suarez M, Fertel D, Gonzalez G, Moas C. Human T-cell lymphotropic virus-III (HTLV-III) seropositivity and related disease among 71 consecutive patients in whom tuberculosis was
diagnosed: A prospective study. Am Rev Respir Dis 1987;135(4):875-879.
16. Barnes PF, Bloch AB, Davidson PT, Snider DE, Jr. Tuberculosis in patients with human
immunodeficiency virus infection. N Engl J Med 1991;324(23):1644-1650. https://doi.org/10.1056/
NEJM199106063242307
17. Sharma SK, Mohan A. Extrapulmonary tuberculosis. Indian J Med Res 2004;120(4):316-353.
18. Kaya A, Topu Z, Fitoz S, Numanoglu N. Pulmonary tuberculosis with multifocal skeletal involvement.
Monaldi Arch Chest Dis 2004;61(2):133-135. https://doi.org/10.4081/monaldi.2004.714
19. Turgut M. Spinal tuberculosis (Pott’s disease): Its clinical presentation, surgical management, and
outcome. A survey study on 694 patients. Neurosurg Rev 2001;24(1):8-13.
20. Garg RK, Somvanshi DS. Spinal tuberculosis: A review. J Spinal Cord Med 2011;34(5):440-454. https://
doi.org/10.1179/2045772311Y.0000000023
21. Esteves S, Catarino I, Lopes D, Sousa C. Spinal tuberculosis: Rethinking an old disease. J Spine 2017;6(358):2.
22. Trecarichi EM, Di Meco E, Mazzotta V, Fantoni M. Tuberculous spondylodiscitis: Epidemiology, clinical features, treatment, and outcome. Eur Rev Med Pharmacol Sci 2012;16(Suppl 2):S58-S72.
23. Flamm ES. Percivall Pott: An 18th century neurosurgeon. J Neurosurg 1992;76(2):319-326. https://doi.
org/10.3171/jns.1992.76.2.0319
24. Batirel A, Erdem H, Sengoz G, et al. The course of spinal tuberculosis (Pott disease): Results of the multinational, multicentre Backbone-2 study. Clin Microbiol Infect 2015;21(11):1009-e1018. https:// doi.org/10.1016/j.cmi.2015.07.013
25. Ansari S, Amanullah MF, Ahmad K, Rauniyar RK. Pott’s spine: Diagnostic imaging modalities and technology advancements. N Am J Med Sci 2013;5(7):404-411. https://doi.org/10.4103/1947- 2714.115775
26. Diedrich CR, O’Hern J, Wilkinson RJ. HIV-1 and the Mycobacterium tuberculosis granuloma: A systematic review and meta-analysis. Tuberculosis 2016;98:62-76. https://doi.org/10.1016/j. tube.2016.02.010
27. Anley CM, Brandt AD, Dunn R. Magnetic resonance imaging findings in spinal tuberculosis: Comparison of HIV positive and negative patients. Indian J Orthop 2012;46 (2):186-190. https://doi. org/10.4103/0019-5413.93688
28. Marais S, Roos I, Mitha A, Mabusha SJ, Patel V, Bhigjee AI. Spinal tuberculosis: Clinicoradiological findings in 274 patients. Clin Infect Dis 2018;67(1):89-98. https://doi.org/10.1093/cid/ciy020
29. Held M, Laubscher M, Zar HJ, Dunn RN. GeneXpert polymerase chain reaction for spinal tuberculosis: An accurate and rapid diagnostic test. Bone Joint J 2014;96-B(10):1366-1369. https://doi. org/10.1302/0301-620X.96B10.34048
30. World Medical Association. Declaration of Helsinki: Ethical principles for medical research involving human subjects. JAMA 2013;310(20):2191-2194. https://doi.org/10.1001/jama.2013.281053
31. Truzzi JC, de Almeida FG, Sacomani CA, Reis J, Rocha FET. Neurogenic bladder – concepts and treatment recommendations. Int Braz J Urol 2022;48(2):220-243. https://doi.org/10.1590/s1677-5538. Ibju.2021.0098
32. Wippold FJ II. Focal neurologic deficit. Am J Neuroradiol 2008;29(10):1998-2000.
33. Godlwana L, Gounden P, Ngubo P, Nsibande T, Nyawo K, Puckree T. Incidence and profile of spinal tuberculosis in patients at the only public hospital admitting such patients in KwaZulu-Natal. Spinal
Cord 2008;46(5):372-374. https://doi.org/10.1038/sj.sc.3102150
34. Dunn R, Zondagh I, Candy S. Spinal tuberculosis: Magnetic resonance imaging and neurological
impairment. Spine (Phila Pa 1976) 2011;36(6):469-473. https://doi.org/10.1097/brs.0b013e3181d265c0 35. Danaviah S, Sacks JA, Kumar KP, et al. Immunohistological characterisation of spinal TB granulomas from HIV-negative and -positive patients. Tuberculosis 2013;93(4):432-441. https://doi.org/10.1016/j.
tube.2013.02.009
36. Churchyard GJ, Mametja LD, Mvusi L, et al. Tuberculosis control in South Africa: Successes, challenges and recommendations. S Afr Med J 2014;104(3 Suppl 1):S244-S248. https://doi.org/10.7196/samj.7689 37. Polley P, Dunn R. Noncontiguous spinal tuberculosis: Incidence and management. Eur Spine J
2009;18(8):1096-1101.
38. Weinstein MA, Eismont FJ. Infections of the spine in patients with human immunodeficiency virus.
J Bone Joint Surg Am 2005;87(3):604-609. https://doi.org/10.2106/JBJS.C.01062
39. Dunn RN, Castelein S, Held M. Impact of HIV on spontaneous spondylodiscitis. Bone Joint J
2019;101-B(5):617-620. https://doi.org/10.1302/0301-620X.101B5.BJJ-2018-0960.R1
40. Govender S, Annamalai K, Kumar KP, Govender UG. Spinal tuberculosis in HIV positive and negative patients: Immunological response and clinical outcome. Int Orthop 2000;24(3):163-166. https://doi.
org/10.1007/s00264000012541. Wang P, Liao W, Cao G, Jiang Y, Rao J, Yang Y. Characteristics and management of spinal tuberculosis in tuberculosis endemic area of Guizhou Province: A retrospective study of 597 patients in a teaching hospital. Biomed Res Int 2020:1468457. https://doi.org/10.1155/2020/1468457
42. Jain AK. Tuberculosis of spine: Research evidence to treatment guidelines. Indian J Orthop 2016;50(1):3-9. https://doi.org/10.4103/0019-5413.173518
43. Sagane SS, Patil VS, Bartakke GD, Kale KY. Assessment of clinical and radiological parameters in spinal tuberculosis: Comparison between human immunodeficiency virus-positive and human immunodeficiency virus-negative patients. Asian Spine J 2020;14(6):857-863. https://doi.org/10.31616/ asj.2019.0251
44. Geldmacher C, Zumla A, Hoelscher M. Interaction between HIV and Mycobacterium tuberculosis: HIV-1-induced CD4 T-cell depletion and the development of active tuberculosis. Curr Opin HIV AIDS 2012;7(3):268-275. https://doi.org/10.1097/COH.0b013e3283524e32
45. Hilhorst M, Shirai T, Berry G, Goronzy JJ, Weyand CM. T cell-macrophage interactions and granuloma formation in vasculitis. Front Immunol 2014;5:432. https://doi.org/10.3389/fimmu.2014.00432
46. Di Perri G, Cazzadori A, Vento S, et al. Comparative histopathological study of pulmonary tuberculosis in human immunodeficiency virus-infected and non-infected patients. Tuber Lung Dis 1996;77(3):244-249. https://doi.org/10.1016/s0962-8479(96)90008-8
47. Heyderman RS, Makunike R, Muza T, et al. Pleural tuberculosis in Harare, Zimbabwe: The relationship between human immunodeficiency virus, CD4 lymphocyte count, granuloma formation and disseminated disease. Trop Med Int Health 1998;3(1):14-20. https://doi.org/10.1046/j.1365- 3156.1998.00167.x
48. Kennedy DJ, Lewis WP, Barnes PF. Yield of bronchoscopy for the diagnosis of tuberculosis in patients with human immunodeficiency virus infection. Chest 1992;102(4):1040-1044. https://doi.org/10.1378/ chest.102.4.1040
49. Scherer J, Mukasa SL, Wolmarans K, et al. Comparing gene expression profiles of adults with isolated spinal tuberculosis to disseminated spinal tuberculosis identified by 18FDG-PET/CT at time of diagnosis, 6- and 12-months follow-up: Classifying clinical stages of spinal tuberculosis and monitoring treatment response (Spinal TB X cohort study). J Orthopaedic Surg Res 2024;19(1):376. https://doi.org/10.1186/s13018-024-04840-7
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