Feasibility and Acceptability of Undertaking Postmortem Studies for Tuberculosis Medical Research in a Low Income Country

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2023 Dec 22

PMID 38130719

Authors

Gift Ahimbisibwe

Marjorie Nakibuule

Marvin Martin Ssejoba

David Oyamo

Rose Mulwana

Josephine Nabulime

Febronius Babirye

Musana Abdusalaamu Kizito

Herve Monka Lekuya

Akello Suzan Adakun

Daisy Nalumansi

Stella Muryasingura

Robert Lukande

Andrew Kyazze

Joseph Baruch Baluku

Irene Andia Biraro

Stephen Cose

Affiliations

Soon will be listed here.

Abstract

Introduction: If we are to break new ground in difficult-to-treat or difficult-to-vaccinate diseases (such as HIV, malaria, or tuberculosis), we must have a better understanding of the immune system at the site of infection in humans. For tuberculosis (TB), the initial site of infection is the lungs, but obtaining lung tissues from subjects suffering from TB has been limited to bronchoalveolar lavage (BAL) or sputum sampling, or surgical resection of diseased lung tissue.

Methods: We examined the feasibility of undertaking a postmortem study for human tuberculosis research at Mulago National Referral Hospital in Kampala, Uganda.

Results: Postmortem studies give us an opportunity to compare TB-involved and -uninvolved sites, for both diseased and non-diseased individuals. We report good acceptability of the next-of-kin to consent for their relative's tissue to be used for medical research; that postmortem and tissue processing can be undertaken within 8 hours following death; and that immune cells remain viable and functional up to 14 hours after death.

Discussion: Postmortem procedures remain a valuable and essential tool both to establish cause of death, and to advance our medical and scientific understanding of infectious diseases.

References

Chakaya J, Petersen E, Nantanda R, Mungai B, Migliori G, Amanullah F . The WHO Global Tuberculosis 2021 Report - not so good news and turning the tide back to End TB. Int J Infect Dis. 2022; 124 Suppl 1:S26-S29. PMC: 8934249. DOI: 10.1016/j.ijid.2022.03.011. View

Lin P, Maiello P, Gideon H, Coleman M, Cadena A, Rodgers M . PET CT Identifies Reactivation Risk in Cynomolgus Macaques with Latent M. tuberculosis. PLoS Pathog. 2016; 12(7):e1005739. PMC: 4933353. DOI: 10.1371/journal.ppat.1005739. View

Biraro I, Egesa M, Toulza F, Levin J, Cose S, Joloba M . Impact of co-infections and BCG immunisation on immune responses among household contacts of tuberculosis patients in a Ugandan cohort. PLoS One. 2014; 9(11):e111517. PMC: 4221037. DOI: 10.1371/journal.pone.0111517. View

Dokgoz H, Arican N, Elmas I, Fincanci S . Comparison of morphological changes in white blood cells after death and in vitro storage of blood for the estimation of postmortem interval. Forensic Sci Int. 2001; 124(1):25-31. DOI: 10.1016/s0379-0738(01)00559-x. View

Sutherland J, Garba D, Fombah A, Mendy-Gomez A, Mendy F, Antonio M . Highly accurate diagnosis of pleural tuberculosis by immunological analysis of the pleural effusion. PLoS One. 2012; 7(1):e30324. PMC: 3266242. DOI: 10.1371/journal.pone.0030324. View

Ekberg-Jansson A, Arva E, Nilsson O, Lofdahl C, Andersson B . A comparison of the expression of lymphocyte activation markers in blood, bronchial biopsies and bronchoalveolar lavage: evidence for an enrichment of activated T lymphocytes in the bronchoalveolar space. Respir Med. 1999; 93(8):563-70. DOI: 10.1016/s0954-6111(99)90156-7. View

Cox J, Lukande R, Kateregga A, Mayanja-Kizza H, Manabe Y, Colebunders R . Autopsy acceptance rate and reasons for decline in Mulago Hospital, Kampala, Uganda. Trop Med Int Health. 2011; 16(8):1015-8. DOI: 10.1111/j.1365-3156.2011.02798.x. View

Ogongo P, Porterfield J, Leslie A . Lung Tissue Resident Memory T-Cells in the Immune Response to . Front Immunol. 2019; 10:992. PMC: 6510113. DOI: 10.3389/fimmu.2019.00992. View

Fliegert F, Tschernig T, Pabst R . Comparison of lymphocyte subsets, monocytes, and NK cells in three different lung compartments and peripheral blood in the rat. Exp Lung Res. 1996; 22(6):677-90. DOI: 10.3109/01902149609070037. View

10.

Hinks T, Wallington J, Williams A, Djukanovic R, Staples K, Wilkinson T . Steroid-induced Deficiency of Mucosal-associated Invariant T Cells in the Chronic Obstructive Pulmonary Disease Lung. Implications for Nontypeable Haemophilus influenzae Infection. Am J Respir Crit Care Med. 2016; 194(10):1208-1218. PMC: 5114442. DOI: 10.1164/rccm.201601-0002OC. View

11.

Kizza F, List J, Nkwata A, Okwera A, Ezeamama A, Whalen C . Prevalence of latent tuberculosis infection and associated risk factors in an urban African setting. BMC Infect Dis. 2015; 15:165. PMC: 4392742. DOI: 10.1186/s12879-015-0904-1. View

12.

Thome J, Farber D . Emerging concepts in tissue-resident T cells: lessons from humans. Trends Immunol. 2015; 36(7):428-35. PMC: 4491028. DOI: 10.1016/j.it.2015.05.003. View

13.

Ardain A, Domingo-Gonzalez R, Das S, Kazer S, Howard N, Singh A . Group 3 innate lymphoid cells mediate early protective immunity against tuberculosis. Nature. 2019; 570(7762):528-532. PMC: 6626542. DOI: 10.1038/s41586-019-1276-2. View

14.

Klemm A, Tschernig T, Krug N, Pabst R . Lymphocyte subsets in distinct lung compartments show a different ability to produce interferon-gamma (IFN-gamma) during a pulmonary immune response. Clin Exp Immunol. 1998; 113(2):252-7. PMC: 1905029. DOI: 10.1046/j.1365-2249.1998.00657.x. View

15.

Ogongo P, Steyn A, Karim F, Dullabh K, Awala I, Madansein R . Differential skewing of donor-unrestricted and γδ T cell repertoires in tuberculosis-infected human lungs. J Clin Invest. 2019; 130(1):214-230. PMC: 6934215. DOI: 10.1172/JCI130711. View

16.

Kumar B, Ma W, Miron M, Granot T, Guyer R, Carpenter D . Human Tissue-Resident Memory T Cells Are Defined by Core Transcriptional and Functional Signatures in Lymphoid and Mucosal Sites. Cell Rep. 2017; 20(12):2921-2934. PMC: 5646692. DOI: 10.1016/j.celrep.2017.08.078. View

17.

Coleman M, Chen R, Lee M, Lin P, Dodd L, Maiello P . PET/CT imaging reveals a therapeutic response to oxazolidinones in macaques and humans with tuberculosis. Sci Transl Med. 2014; 6(265):265ra167. PMC: 6413515. DOI: 10.1126/scitranslmed.3009500. View

18.

Maixenchs M, Anselmo R, Zielinski-Gutierrez E, Odhiambo F, Akello C, Ondire M . Willingness to Know the Cause of Death and Hypothetical Acceptability of the Minimally Invasive Autopsy in Six Diverse African and Asian Settings: A Mixed Methods Socio-Behavioural Study. PLoS Med. 2016; 13(11):e1002172. PMC: 5119724. DOI: 10.1371/journal.pmed.1002172. View

19.

Marakalala M, Raju R, Sharma K, Zhang Y, Eugenin E, Prideaux B . Inflammatory signaling in human tuberculosis granulomas is spatially organized. Nat Med. 2016; 22(5):531-8. PMC: 4860068. DOI: 10.1038/nm.4073. View

20.

Martinez L, Cords O, Liu Q, Acuna-Villaorduna C, Bonnet M, Fox G . Infant BCG vaccination and risk of pulmonary and extrapulmonary tuberculosis throughout the life course: a systematic review and individual participant data meta-analysis. Lancet Glob Health. 2022; 10(9):e1307-e1316. PMC: 10406427. DOI: 10.1016/S2214-109X(22)00283-2. View