Abstract
Purpose
HIV/AIDS is a known risk factor for the development of pulmonary tuberculosis (PTB). However, the association is less clear between HIV and extrapulmonary tuberculosis (EPTB). We conducted a systematic review to determine the association between HIV and EPTB.
Methods
We searched the electronic databases Medline, Embase, and relevant conference literature using defined search terms for EPTB and HIV. Only publications in English and only studies reporting adjusted estimates were included, while our search criteria did not include restriction by age or geographic location of study participants. Qualitative and quantitative analyses (including I 2 test for heterogeneity) were performed.
Results
Sixteen studies (15 cross-sectional and 1 case–control) conducted from 1984 to 2016 were included in the final analyses after screening 5163 articles and conference abstracts. Our qualitative analysis showed heterogeneity in study design and study population characteristics along with a medium/high risk of bias in the majority of studies. While most of the individual studies showed increased odds of EPTB compared with PTB among HIV-infected individuals, we did not provide an overall pooled estimate, as the I 2 value was high at 93% for the cross-sectional studies.
Conclusions
While an association between HIV and EPTB is observed in most individual studies, the high heterogeneity and risk of bias in these studies highlight the need for further well-designed prospective cohort studies to assess the true risk of EPTB in the HIV-infected patient population.
Similar content being viewed by others
References
UNAIDS. Fact sheet 2016 http://www.unaids.org/en/resources/fact-sheet. Accessed 1 Aug 2016.
WHO. Tuberculosis fact sheet http://www.who.int/mediacentre/factsheets/fs104/en/. 2015 http://www.who.int/mediacentre/factsheets/fs104/en/. Accessed 1 Aug 2016.
WHO. Global tuberculosis report 2014. http://apps.who.int/iris/bitstream/10665/137094/1/9789241564809_eng.pdf. Accessed 1 Aug 2016.
WHO. Improving the diagnosis and treatment of smear-negative pulmonary and extrapulmonary tuberculosis among adults and adolescents. 2007 http://www.who.int/hiv/pub/tb/pulmonary/en/. Accessed 5 Feb 2015.
Adada H, Valley MA, Nour SA, Mehta J, Byrd RP Jr, Anderson JL, et al. Epidemiology of extra-pulmonary tuberculosis in the United States: high rates persist in the post-HIV era. Int J Tuberc Lung Dis. 2014;18:1516–21. doi:10.5588/ijtld.14.0319.
Sandgren A, Hollo V, van der Werf MJ. Extrapulmonary tuberculosis in the European union and European economic area 2002 to 2011. Euro Surveill 2013;18:1–9.
Peto HM, Pratt RH, Harrington TA, LoBue PA, Armstrong LR. Epidemiology of extrapulmonary tuberculosis in the United States, 1993–2006. Clin Inf Dis. 2009;49:1350–7. doi:10.1086/605559.
WHO. WHO case definition of HIV for surveillance and revised clinical staging and immunological classification of HIV-related disease in adults and children. 2007 http://www.who.int/hiv/pub/guidelines/HIVstaging150307.pdf. Accessed 5 Feb 2015.
Naing C, Mak JW, Maung M, Wong SF, Kassim AI. Meta-analysis: the association between HIV infection and extrapulmonary tuberculosis. Lung. 2013;191:27–34. doi:10.1007/s00408-012-9440-6.
Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6:e1000097. doi:10.1371/journal.pmed.1000097.
Yang Z, Kong Y, Wilson F, Foxman B, Fowler AH, Marrs CF, et al. Identification of risk factors for extrapulmonary tuberculosis. Clin Infect Dis. 2004;38:199–205. doi:10.1086/380644.
Wells GA SB, O’Connell D, Peterson J, Welch V, Losos M, Tugwell P. The Newcastle–Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. 2014 http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed 5 Feb 2015.
Hayden JA, Cote P, Bombardier C. Evaluation of the quality of prognosis studies in systematic reviews. Ann Int Med. 2006;144:427–37.
Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of observational studies in epidemiology (MOOSE) group. JAMA. 2000;283:2008–12.
von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP. The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007;370:1453–7. doi:10.1016/S0140-6736(07)61602-X.
Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60. doi:10.1136/bmj.327.7414.557.
Fiske CT, Griffin MR, Erin H, Warkentin J, Lisa K, Arbogast PG, et al. Black race, sex, and extrapulmonary tuberculosis risk: an observational study. BMC Infect Dis. 2010;10:16. doi:10.1186/1471-2334-10-16.
Gomes T, Reis-Santos B, Bertolde A, Johnson JL, Riley LW, Maciel EL. Epidemiology of extrapulmonary tuberculosis in Brazil: a hierarchical model. BMC Infect Dis. 2014;14:9. doi:10.1186/1471-2334-14-9.
Gomes T, Vinhas SA, Reis-Santos B, Palaci M, Peres RL, Aguiar PP, et al. Extrapulmonary tuberculosis: mycobacterium tuberculosis strains and host risk factors in a large urban setting in Brazil. PLoS One. 2013;8:e74517. doi:10.1371/journal.pone.0074517.
Gonzalez OY, Adams G, Teeter LD, Bui TT, Musser JM, Graviss EA. Extra-pulmonary manifestations in a large metropolitan area with a low incidence of tuberculosis. Int J Tuberc Lung Dis. 2003;7:1178–85.
Kung HC, Sun HY, Chen MY, Hsieh SM, Sheng WH, Chen YC, Hung CC, Chang SC. Human immunodeficiency virus testing among patients with tuberculosis at a university hospital in Taiwan, 2000 to 2006. J Formos Med Assoc. 2009;108:108320327. doi:10.1016/S0929-6646(09),60072-3.
Namme LH, Marie-Solange D, Hugo Bertrand MN, Elvis T, Achu JH, Christopher K. Extrapulmonary tuberculosis and HIV coinfection in patients treated for tuberculosis at the Douala General Hospital in Cameroon. Ann Trop Med Publ Health. 2013;6:100–4.
Prado TN, Caus AL, Marques M, Maciel EL, Golub JE, Miranda AE. Epidemiological profile of adult patients with tuberculosis and AIDS in the state of Espirito Santo, Brazil: cross-referencing tuberculosis and AIDS databases. J Bras Pneumol. 2011;37:93–9.
Rieder HL, Cauthen GM, Bloch AB, Cole CH, Holtzman D, Snider DE Jr, et al. Tuberculosis and acquired immunodeficiency syndrome—Florida. Arch Int Med. 1989;149:1268–73.
Wilkinson D, Moore DA. HIV-related tuberculosis in South Africa–clinical features and outcome. S Afr Med J. 1996;86:64–7.
Bates M, Mudenda V, Shibemba A, Kaluwaji J, Tembo J, Kabwe M, et al. Burden of tuberculosis at post mortem in inpatients at a tertiary referral centre in sub-Saharan Africa: a prospective descriptive autopsy study. Lancet Infect Dis. 2015;15:544–51. doi:10.1016/S1473-3099(15)70058-7.
Culqui-Levano DR, Rodriguez-Valin E, Donado-Campos JM, Analysis of extrapulmonary tuberculosis in Spain: 2007–2012 national study. Enferm Infecc Microbiol Clin. 2016. doi:10.1016/j.eimc.2016.06.002.
Fortun J, Martin-Davila P, Gomez-Mampaso E, Gonzalez-Garcia A, Barbolla I, Gomez-Garcia I, et al. Extra-pulmonary tuberculosis: differential aspects and role of 16S-rRNA in urine. Int J Tuberc Lung Dis. 2014;18:478–85. doi:10.5588/ijtld.13.0555.
Sama JN, Chida N, Polan RM, Nuzzo J, Page K, Shah M. High proportion of extrapulmonary tuberculosis in a low prevalence setting: a retrospective cohort study. Publ Health. 2016;138:101–7. doi:10.1016/j.puhe.2016.03.033.
Sanches I, Carvalho A, Duarte R. Who are the patients with extrapulmonary tuberculosis? Rev Port De Pneumol. 2015;21:90–3. doi:10.1016/j.rppnen.2014.06.010.
Tesgaye F, Defar A, Beyene T, Shafi O, Klinkenberg E, Howe R. Documentation and treatment outcomes of smear-negative and extra-pulmonary tuberculosis in Ethiopia. Public health action. 2014;4(Suppl 3):S25–30. doi:10.5588/pha.14.0052.
Acknowledgements
We would like to thank Kay Dickerson, Tianjing Li and especially Ian Saldanha for helpful discussion and advice on the paper. We would also like to thank Natasha Chida and Matthew Bates, authors from the selected papers, for providing us with added information and analyses for this publication. RS was supported by a training grant from the National Institute of Health (K99HD089753). Otherwise, this work did not have any funding sources.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
On behalf of all authors, the corresponding author states that there is no conflict of interest.
Additional information
Rupak Shivakoti, Davina Sharma, and Kiemanh Pham have contributed equally to this work.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Shivakoti, R., Sharma, D., Mamoon, G. et al. Association of HIV infection with extrapulmonary tuberculosis: a systematic review. Infection 45, 11–21 (2017). https://doi.org/10.1007/s15010-016-0960-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s15010-016-0960-5