Mendelian susceptibility to mycobacterial disease in tuberculosis-hyperendemic South Africa. Cornelissen, H. M., Glanzmann, B., Van Coller, A., Engelbrecht, C., Abraham, D. R., Reddy, K., Möller, M., Kinnear, C., Glashoff, R. H., & Esser, M. South African Medical Journal = Suid-Afrikaanse Tydskrif Vir Geneeskunde, 111(10):998–1005, October, 2021. doi abstract bibtex BACKGROUND: Severe infections in the absence of secondary immunodeficiency can alert clinicians to single-gene inborn errors of immunity/primary immunodeficiency disorders (PIDDs). Mendelian susceptibility to mycobacterial disease (MSMD) is characterised by selective susceptibility to mycobacterial infections due to inborn errors in the interleukin 12-interferon gamma pathway. The South African (SA) burden of hyperendemic tuberculosis (TB) infection provides an interesting context for the study of MSMD. OBJECTIVES: To evaluate whether severe, persistent, unusual or recurrent (SPUR) definitions of TB can be applied in the context of MSMD in SA. METHODS: This study is a retrospective review of an SA PIDD cohort. Patients aged 0 - 15 years with SPUR TB infections, assessed between 2013 and 2018, were identified using a proposed algorithm. HIV infection or other secondary causes for immunodeficiency were excluded. Basic investigations, then focused immunophenotyping and next-generation sequencing, were performed. RESULTS: A total of 20 patients with a clinical diagnosis of MSMD were identified. A further two, forming part of a family cohort, had pathogenic variants but remain asymptomatic. Infection with Mycobacterium tuberculosis complex predominated (64%), while 27% had BCG infection or non-tuberculous mycobacteria (NTM) infection. Molecular analysis revealed pathogenic variants in 41% of patients with SPUR mycobacterial infection, mainly in those with BCG/NTM infection. CONCLUSIONS: In the SA paediatric population, SPUR TB infections, particularly BCG/NTM, in the absence of secondary immunodeficiency, can alert to possible MSMD. The molecular diagnosis is pivotal, guiding disease classification and influencing clinical approach and management. The diagnosis is complex and requires a multidisciplinary approach with close collaboration between clinical immunologists, bioinformaticians, immunologists, clinical geneticists and genetic counsellors.
@article{cornelissen_mendelian_2021,
title = {Mendelian susceptibility to mycobacterial disease in tuberculosis-hyperendemic {South} {Africa}},
volume = {111},
issn = {2078-5135},
doi = {10.7196/SAMJ.2021.v111i10.15341},
abstract = {BACKGROUND: Severe infections in the absence of secondary immunodeficiency can alert clinicians to single-gene inborn errors of immunity/primary immunodeficiency disorders (PIDDs). Mendelian susceptibility to mycobacterial disease (MSMD) is characterised by selective susceptibility to mycobacterial infections due to inborn errors in the interleukin 12-interferon gamma pathway. The South African (SA) burden of hyperendemic tuberculosis (TB) infection provides an interesting context for the study of MSMD.
OBJECTIVES: To evaluate whether severe, persistent, unusual or recurrent (SPUR) definitions of TB can be applied in the context of MSMD in SA.
METHODS: This study is a retrospective review of an SA PIDD cohort. Patients aged 0 - 15 years with SPUR TB infections, assessed between 2013 and 2018, were identified using a proposed algorithm. HIV infection or other secondary causes for immunodeficiency were excluded. Basic investigations, then focused immunophenotyping and next-generation sequencing, were performed.
RESULTS: A total of 20 patients with a clinical diagnosis of MSMD were identified. A further two, forming part of a family cohort, had pathogenic variants but remain asymptomatic. Infection with Mycobacterium tuberculosis complex predominated (64\%), while 27\% had BCG infection or non-tuberculous mycobacteria (NTM) infection. Molecular analysis revealed pathogenic variants in 41\% of patients with SPUR mycobacterial infection, mainly in those with BCG/NTM infection.
CONCLUSIONS: In the SA paediatric population, SPUR TB infections, particularly BCG/NTM, in the absence of secondary immunodeficiency, can alert to possible MSMD. The molecular diagnosis is pivotal, guiding disease classification and influencing clinical approach and management. The diagnosis is complex and requires a multidisciplinary approach with close collaboration between clinical immunologists, bioinformaticians, immunologists, clinical geneticists and genetic counsellors.},
language = {eng},
number = {10},
journal = {South African Medical Journal = Suid-Afrikaanse Tydskrif Vir Geneeskunde},
author = {Cornelissen, H. M. and Glanzmann, B. and Van Coller, A. and Engelbrecht, C. and Abraham, D. R. and Reddy, K. and Möller, M. and Kinnear, C. and Glashoff, R. H. and Esser, M.},
month = oct,
year = {2021},
pmid = {34949297},
keywords = {Adolescent, Algorithms, Child, Child, Preschool, Female, Genetic Predisposition to Disease, High-Throughput Nucleotide Sequencing, Humans, Immunophenotyping, Infant, Infant, Newborn, Interleukin-12, Male, Mycobacterium Infections, Retrospective Studies, South Africa},
pages = {998--1005},
}
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{"_id":"EMLijSFgMyWHdjyeR","bibbaseid":"cornelissen-glanzmann-vancoller-engelbrecht-abraham-reddy-mller-kinnear-etal-mendeliansusceptibilitytomycobacterialdiseaseintuberculosishyperendemicsouthafrica-2021","author_short":["Cornelissen, H. M.","Glanzmann, B.","Van Coller, A.","Engelbrecht, C.","Abraham, D. R.","Reddy, K.","Möller, M.","Kinnear, C.","Glashoff, R. H.","Esser, M."],"bibdata":{"bibtype":"article","type":"article","title":"Mendelian susceptibility to mycobacterial disease in tuberculosis-hyperendemic South Africa","volume":"111","issn":"2078-5135","doi":"10.7196/SAMJ.2021.v111i10.15341","abstract":"BACKGROUND: Severe infections in the absence of secondary immunodeficiency can alert clinicians to single-gene inborn errors of immunity/primary immunodeficiency disorders (PIDDs). Mendelian susceptibility to mycobacterial disease (MSMD) is characterised by selective susceptibility to mycobacterial infections due to inborn errors in the interleukin 12-interferon gamma pathway. The South African (SA) burden of hyperendemic tuberculosis (TB) infection provides an interesting context for the study of MSMD. OBJECTIVES: To evaluate whether severe, persistent, unusual or recurrent (SPUR) definitions of TB can be applied in the context of MSMD in SA. METHODS: This study is a retrospective review of an SA PIDD cohort. Patients aged 0 - 15 years with SPUR TB infections, assessed between 2013 and 2018, were identified using a proposed algorithm. HIV infection or other secondary causes for immunodeficiency were excluded. Basic investigations, then focused immunophenotyping and next-generation sequencing, were performed. RESULTS: A total of 20 patients with a clinical diagnosis of MSMD were identified. A further two, forming part of a family cohort, had pathogenic variants but remain asymptomatic. Infection with Mycobacterium tuberculosis complex predominated (64%), while 27% had BCG infection or non-tuberculous mycobacteria (NTM) infection. Molecular analysis revealed pathogenic variants in 41% of patients with SPUR mycobacterial infection, mainly in those with BCG/NTM infection. CONCLUSIONS: In the SA paediatric population, SPUR TB infections, particularly BCG/NTM, in the absence of secondary immunodeficiency, can alert to possible MSMD. The molecular diagnosis is pivotal, guiding disease classification and influencing clinical approach and management. The diagnosis is complex and requires a multidisciplinary approach with close collaboration between clinical immunologists, bioinformaticians, immunologists, clinical geneticists and genetic counsellors.","language":"eng","number":"10","journal":"South African Medical Journal = Suid-Afrikaanse Tydskrif Vir Geneeskunde","author":[{"propositions":[],"lastnames":["Cornelissen"],"firstnames":["H.","M."],"suffixes":[]},{"propositions":[],"lastnames":["Glanzmann"],"firstnames":["B."],"suffixes":[]},{"propositions":[],"lastnames":["Van","Coller"],"firstnames":["A."],"suffixes":[]},{"propositions":[],"lastnames":["Engelbrecht"],"firstnames":["C."],"suffixes":[]},{"propositions":[],"lastnames":["Abraham"],"firstnames":["D.","R."],"suffixes":[]},{"propositions":[],"lastnames":["Reddy"],"firstnames":["K."],"suffixes":[]},{"propositions":[],"lastnames":["Möller"],"firstnames":["M."],"suffixes":[]},{"propositions":[],"lastnames":["Kinnear"],"firstnames":["C."],"suffixes":[]},{"propositions":[],"lastnames":["Glashoff"],"firstnames":["R.","H."],"suffixes":[]},{"propositions":[],"lastnames":["Esser"],"firstnames":["M."],"suffixes":[]}],"month":"October","year":"2021","pmid":"34949297","keywords":"Adolescent, Algorithms, Child, Child, Preschool, Female, Genetic Predisposition to Disease, High-Throughput Nucleotide Sequencing, Humans, Immunophenotyping, Infant, Infant, Newborn, Interleukin-12, Male, Mycobacterium Infections, Retrospective Studies, South Africa","pages":"998–1005","bibtex":"@article{cornelissen_mendelian_2021,\n\ttitle = {Mendelian susceptibility to mycobacterial disease in tuberculosis-hyperendemic {South} {Africa}},\n\tvolume = {111},\n\tissn = {2078-5135},\n\tdoi = {10.7196/SAMJ.2021.v111i10.15341},\n\tabstract = {BACKGROUND: Severe infections in the absence of secondary immunodeficiency can alert clinicians to single-gene inborn errors of immunity/primary immunodeficiency disorders (PIDDs). Mendelian susceptibility to mycobacterial disease (MSMD) is characterised by selective susceptibility to mycobacterial infections due to inborn errors in the interleukin 12-interferon gamma pathway. The South African (SA) burden of hyperendemic tuberculosis (TB) infection provides an interesting context for the study of MSMD.\nOBJECTIVES: To evaluate whether severe, persistent, unusual or recurrent (SPUR) definitions of TB can be applied in the context of MSMD in SA.\nMETHODS: This study is a retrospective review of an SA PIDD cohort. Patients aged 0 - 15 years with SPUR TB infections, assessed between 2013 and 2018, were identified using a proposed algorithm. HIV infection or other secondary causes for immunodeficiency were excluded. Basic investigations, then focused immunophenotyping and next-generation sequencing, were performed.\nRESULTS: A total of 20 patients with a clinical diagnosis of MSMD were identified. A further two, forming part of a family cohort, had pathogenic variants but remain asymptomatic. Infection with Mycobacterium tuberculosis complex predominated (64\\%), while 27\\% had BCG infection or non-tuberculous mycobacteria (NTM) infection. Molecular analysis revealed pathogenic variants in 41\\% of patients with SPUR mycobacterial infection, mainly in those with BCG/NTM infection.\nCONCLUSIONS: In the SA paediatric population, SPUR TB infections, particularly BCG/NTM, in the absence of secondary immunodeficiency, can alert to possible MSMD. The molecular diagnosis is pivotal, guiding disease classification and influencing clinical approach and management. The diagnosis is complex and requires a multidisciplinary approach with close collaboration between clinical immunologists, bioinformaticians, immunologists, clinical geneticists and genetic counsellors.},\n\tlanguage = {eng},\n\tnumber = {10},\n\tjournal = {South African Medical Journal = Suid-Afrikaanse Tydskrif Vir Geneeskunde},\n\tauthor = {Cornelissen, H. M. and Glanzmann, B. and Van Coller, A. and Engelbrecht, C. and Abraham, D. R. and Reddy, K. and Möller, M. and Kinnear, C. and Glashoff, R. H. and Esser, M.},\n\tmonth = oct,\n\tyear = {2021},\n\tpmid = {34949297},\n\tkeywords = {Adolescent, Algorithms, Child, Child, Preschool, Female, Genetic Predisposition to Disease, High-Throughput Nucleotide Sequencing, Humans, Immunophenotyping, Infant, Infant, Newborn, Interleukin-12, Male, Mycobacterium Infections, Retrospective Studies, South Africa},\n\tpages = {998--1005},\n}\n\n","author_short":["Cornelissen, H. M.","Glanzmann, B.","Van Coller, A.","Engelbrecht, C.","Abraham, D. R.","Reddy, K.","Möller, M.","Kinnear, C.","Glashoff, R. 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