Cargando…

An observational study identifying highly tuberculosis-exposed, HIV-1-positive but persistently TB, tuberculin and IGRA negative persons with M. tuberculosis specific antibodies in Cape Town, South Africa

BACKGROUND: Mycobacterium tuberculosis (Mtb) infection is inferred from positive results of T-cell immune conversion assays measuring Mtb-specific interferon gamma production or tuberculin skin test (TST) reactivity. Certain exposed individuals do not display T-cell immune conversion in these assays...

Descripción completa

Detalles Bibliográficos
Autores principales: Kroon, Elouise E., Kinnear, Craig J., Orlova, Marianna, Fischinger, Stephanie, Shin, Sally, Boolay, Sihaam, Walzl, Gerhard, Jacobs, Ashley, Wilkinson, Robert J., Alter, Galit, Schurr, Erwin, Hoal, Eileen G., Möller, Marlo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648124/
https://www.ncbi.nlm.nih.gov/pubmed/33038764
http://dx.doi.org/10.1016/j.ebiom.2020.103053
_version_ 1783607051434328064
author Kroon, Elouise E.
Kinnear, Craig J.
Orlova, Marianna
Fischinger, Stephanie
Shin, Sally
Boolay, Sihaam
Walzl, Gerhard
Jacobs, Ashley
Wilkinson, Robert J.
Alter, Galit
Schurr, Erwin
Hoal, Eileen G.
Möller, Marlo
author_facet Kroon, Elouise E.
Kinnear, Craig J.
Orlova, Marianna
Fischinger, Stephanie
Shin, Sally
Boolay, Sihaam
Walzl, Gerhard
Jacobs, Ashley
Wilkinson, Robert J.
Alter, Galit
Schurr, Erwin
Hoal, Eileen G.
Möller, Marlo
author_sort Kroon, Elouise E.
collection PubMed
description BACKGROUND: Mycobacterium tuberculosis (Mtb) infection is inferred from positive results of T-cell immune conversion assays measuring Mtb-specific interferon gamma production or tuberculin skin test (TST) reactivity. Certain exposed individuals do not display T-cell immune conversion in these assays and do not develop TB. Here we report a hitherto unknown form of this phenotype: HIV-1-positive persistently TB, tuberculin and IGRA negative (HITTIN). METHODS: A community-based case-control design was used to systematically screen and identify adults living with HIV (HIV+), aged 35–60 years, who met stringent study criteria, and then longitudinally followed up for repeat IGRA and TST testing. Participants had no history of TB despite living in TB hyper-endemic environments in Cape Town, South Africa with a provincial incidence of 681/100,000. Mtb-specific antibodies were measured using ELISA and Luminex. FINDINGS: We identified 48/286 (17%) individuals who tested persistently negative for Mtb-specific T-cell immunoreactivity (three negative Quantiferon results and one TST = 0mm) over 206±154 days on average. Of these, 97·2% had documented CD4 counts<200 prior to antiretroviral therapy (ART). They had received ART for 7·0±3·0 years with a latest CD4 count of 505·8±191·4 cells/mm(3). All HITTIN sent for further antibody testing (n=38) displayed  Mtb-specific antibody titres. INTERPRETATION: Immune reconstituted HIV+ persons can be persistently non-immunoreactive to TST and interferon-γ T-cell responses to Mtb, yet develop species-specific antibody responses. Exposure is evidenced by Mtb-specific antibody titres. Our identification of HIV+ individuals displaying a persisting lack of response to TST and IGRA T-cell immune conversion paves the way for future studies to investigate this phenotype in the context of HIV-infection that so far have received only scant attention.
format Online
Article
Text
id pubmed-7648124
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-76481242020-11-16 An observational study identifying highly tuberculosis-exposed, HIV-1-positive but persistently TB, tuberculin and IGRA negative persons with M. tuberculosis specific antibodies in Cape Town, South Africa Kroon, Elouise E. Kinnear, Craig J. Orlova, Marianna Fischinger, Stephanie Shin, Sally Boolay, Sihaam Walzl, Gerhard Jacobs, Ashley Wilkinson, Robert J. Alter, Galit Schurr, Erwin Hoal, Eileen G. Möller, Marlo EBioMedicine Research Paper BACKGROUND: Mycobacterium tuberculosis (Mtb) infection is inferred from positive results of T-cell immune conversion assays measuring Mtb-specific interferon gamma production or tuberculin skin test (TST) reactivity. Certain exposed individuals do not display T-cell immune conversion in these assays and do not develop TB. Here we report a hitherto unknown form of this phenotype: HIV-1-positive persistently TB, tuberculin and IGRA negative (HITTIN). METHODS: A community-based case-control design was used to systematically screen and identify adults living with HIV (HIV+), aged 35–60 years, who met stringent study criteria, and then longitudinally followed up for repeat IGRA and TST testing. Participants had no history of TB despite living in TB hyper-endemic environments in Cape Town, South Africa with a provincial incidence of 681/100,000. Mtb-specific antibodies were measured using ELISA and Luminex. FINDINGS: We identified 48/286 (17%) individuals who tested persistently negative for Mtb-specific T-cell immunoreactivity (three negative Quantiferon results and one TST = 0mm) over 206±154 days on average. Of these, 97·2% had documented CD4 counts<200 prior to antiretroviral therapy (ART). They had received ART for 7·0±3·0 years with a latest CD4 count of 505·8±191·4 cells/mm(3). All HITTIN sent for further antibody testing (n=38) displayed  Mtb-specific antibody titres. INTERPRETATION: Immune reconstituted HIV+ persons can be persistently non-immunoreactive to TST and interferon-γ T-cell responses to Mtb, yet develop species-specific antibody responses. Exposure is evidenced by Mtb-specific antibody titres. Our identification of HIV+ individuals displaying a persisting lack of response to TST and IGRA T-cell immune conversion paves the way for future studies to investigate this phenotype in the context of HIV-infection that so far have received only scant attention. Elsevier 2020-10-07 /pmc/articles/PMC7648124/ /pubmed/33038764 http://dx.doi.org/10.1016/j.ebiom.2020.103053 Text en © 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Paper
Kroon, Elouise E.
Kinnear, Craig J.
Orlova, Marianna
Fischinger, Stephanie
Shin, Sally
Boolay, Sihaam
Walzl, Gerhard
Jacobs, Ashley
Wilkinson, Robert J.
Alter, Galit
Schurr, Erwin
Hoal, Eileen G.
Möller, Marlo
An observational study identifying highly tuberculosis-exposed, HIV-1-positive but persistently TB, tuberculin and IGRA negative persons with M. tuberculosis specific antibodies in Cape Town, South Africa
title An observational study identifying highly tuberculosis-exposed, HIV-1-positive but persistently TB, tuberculin and IGRA negative persons with M. tuberculosis specific antibodies in Cape Town, South Africa
title_full An observational study identifying highly tuberculosis-exposed, HIV-1-positive but persistently TB, tuberculin and IGRA negative persons with M. tuberculosis specific antibodies in Cape Town, South Africa
title_fullStr An observational study identifying highly tuberculosis-exposed, HIV-1-positive but persistently TB, tuberculin and IGRA negative persons with M. tuberculosis specific antibodies in Cape Town, South Africa
title_full_unstemmed An observational study identifying highly tuberculosis-exposed, HIV-1-positive but persistently TB, tuberculin and IGRA negative persons with M. tuberculosis specific antibodies in Cape Town, South Africa
title_short An observational study identifying highly tuberculosis-exposed, HIV-1-positive but persistently TB, tuberculin and IGRA negative persons with M. tuberculosis specific antibodies in Cape Town, South Africa
title_sort observational study identifying highly tuberculosis-exposed, hiv-1-positive but persistently tb, tuberculin and igra negative persons with m. tuberculosis specific antibodies in cape town, south africa
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648124/
https://www.ncbi.nlm.nih.gov/pubmed/33038764
http://dx.doi.org/10.1016/j.ebiom.2020.103053
work_keys_str_mv AT kroonelouisee anobservationalstudyidentifyinghighlytuberculosisexposedhiv1positivebutpersistentlytbtuberculinandigranegativepersonswithmtuberculosisspecificantibodiesincapetownsouthafrica
AT kinnearcraigj anobservationalstudyidentifyinghighlytuberculosisexposedhiv1positivebutpersistentlytbtuberculinandigranegativepersonswithmtuberculosisspecificantibodiesincapetownsouthafrica
AT orlovamarianna anobservationalstudyidentifyinghighlytuberculosisexposedhiv1positivebutpersistentlytbtuberculinandigranegativepersonswithmtuberculosisspecificantibodiesincapetownsouthafrica
AT fischingerstephanie anobservationalstudyidentifyinghighlytuberculosisexposedhiv1positivebutpersistentlytbtuberculinandigranegativepersonswithmtuberculosisspecificantibodiesincapetownsouthafrica
AT shinsally anobservationalstudyidentifyinghighlytuberculosisexposedhiv1positivebutpersistentlytbtuberculinandigranegativepersonswithmtuberculosisspecificantibodiesincapetownsouthafrica
AT boolaysihaam anobservationalstudyidentifyinghighlytuberculosisexposedhiv1positivebutpersistentlytbtuberculinandigranegativepersonswithmtuberculosisspecificantibodiesincapetownsouthafrica
AT walzlgerhard anobservationalstudyidentifyinghighlytuberculosisexposedhiv1positivebutpersistentlytbtuberculinandigranegativepersonswithmtuberculosisspecificantibodiesincapetownsouthafrica
AT jacobsashley anobservationalstudyidentifyinghighlytuberculosisexposedhiv1positivebutpersistentlytbtuberculinandigranegativepersonswithmtuberculosisspecificantibodiesincapetownsouthafrica
AT wilkinsonrobertj anobservationalstudyidentifyinghighlytuberculosisexposedhiv1positivebutpersistentlytbtuberculinandigranegativepersonswithmtuberculosisspecificantibodiesincapetownsouthafrica
AT altergalit anobservationalstudyidentifyinghighlytuberculosisexposedhiv1positivebutpersistentlytbtuberculinandigranegativepersonswithmtuberculosisspecificantibodiesincapetownsouthafrica
AT schurrerwin anobservationalstudyidentifyinghighlytuberculosisexposedhiv1positivebutpersistentlytbtuberculinandigranegativepersonswithmtuberculosisspecificantibodiesincapetownsouthafrica
AT hoaleileeng anobservationalstudyidentifyinghighlytuberculosisexposedhiv1positivebutpersistentlytbtuberculinandigranegativepersonswithmtuberculosisspecificantibodiesincapetownsouthafrica
AT mollermarlo anobservationalstudyidentifyinghighlytuberculosisexposedhiv1positivebutpersistentlytbtuberculinandigranegativepersonswithmtuberculosisspecificantibodiesincapetownsouthafrica
AT kroonelouisee observationalstudyidentifyinghighlytuberculosisexposedhiv1positivebutpersistentlytbtuberculinandigranegativepersonswithmtuberculosisspecificantibodiesincapetownsouthafrica
AT kinnearcraigj observationalstudyidentifyinghighlytuberculosisexposedhiv1positivebutpersistentlytbtuberculinandigranegativepersonswithmtuberculosisspecificantibodiesincapetownsouthafrica
AT orlovamarianna observationalstudyidentifyinghighlytuberculosisexposedhiv1positivebutpersistentlytbtuberculinandigranegativepersonswithmtuberculosisspecificantibodiesincapetownsouthafrica
AT fischingerstephanie observationalstudyidentifyinghighlytuberculosisexposedhiv1positivebutpersistentlytbtuberculinandigranegativepersonswithmtuberculosisspecificantibodiesincapetownsouthafrica
AT shinsally observationalstudyidentifyinghighlytuberculosisexposedhiv1positivebutpersistentlytbtuberculinandigranegativepersonswithmtuberculosisspecificantibodiesincapetownsouthafrica
AT boolaysihaam observationalstudyidentifyinghighlytuberculosisexposedhiv1positivebutpersistentlytbtuberculinandigranegativepersonswithmtuberculosisspecificantibodiesincapetownsouthafrica
AT walzlgerhard observationalstudyidentifyinghighlytuberculosisexposedhiv1positivebutpersistentlytbtuberculinandigranegativepersonswithmtuberculosisspecificantibodiesincapetownsouthafrica
AT jacobsashley observationalstudyidentifyinghighlytuberculosisexposedhiv1positivebutpersistentlytbtuberculinandigranegativepersonswithmtuberculosisspecificantibodiesincapetownsouthafrica
AT wilkinsonrobertj observationalstudyidentifyinghighlytuberculosisexposedhiv1positivebutpersistentlytbtuberculinandigranegativepersonswithmtuberculosisspecificantibodiesincapetownsouthafrica
AT altergalit observationalstudyidentifyinghighlytuberculosisexposedhiv1positivebutpersistentlytbtuberculinandigranegativepersonswithmtuberculosisspecificantibodiesincapetownsouthafrica
AT schurrerwin observationalstudyidentifyinghighlytuberculosisexposedhiv1positivebutpersistentlytbtuberculinandigranegativepersonswithmtuberculosisspecificantibodiesincapetownsouthafrica
AT hoaleileeng observationalstudyidentifyinghighlytuberculosisexposedhiv1positivebutpersistentlytbtuberculinandigranegativepersonswithmtuberculosisspecificantibodiesincapetownsouthafrica
AT mollermarlo observationalstudyidentifyinghighlytuberculosisexposedhiv1positivebutpersistentlytbtuberculinandigranegativepersonswithmtuberculosisspecificantibodiesincapetownsouthafrica