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LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00006644naa a2200613 4500
001oai:lup.lub.lu.se:a211da20-0268-42e7-aca5-18210427d482
003SwePub
008210517s2021 | |||||||||||000 ||eng|
0247 a https://lup.lub.lu.se/record/a211da20-0268-42e7-aca5-18210427d4822 URI
0247 a https://doi.org/10.1016/S2666-5247(21)00043-42 DOI
040 a (SwePub)lu
041 a engb eng
042 9 SwePub
072 7a art2 swepub-publicationtype
072 7a ref2 swepub-contenttype
1001 a Belay, Mulugetau University of Oslo,Queen Mary University,Armauer Hansen Research Institute4 aut
2451 0a Detection of Mycobacterium tuberculosis complex DNA in CD34-positive peripheral blood mononuclear cells of asymptomatic tuberculosis contacts : an observational study
264 1c 2021
520 a Background: Haematopoietic stem cells expressing the CD34 surface marker have been posited as a niche for Mycobacterium tuberculosis complex bacilli during latent tuberculosis infection. Our aim was to determine whether M tuberculosis complex DNA is detectable in CD34-positive peripheral blood mononuclear cells (PBMCs) isolated from asymptomatic adults living in a setting with a high tuberculosis burden. Methods: We did a cross-sectional study in Ethiopia between Nov 22, 2017, and Jan 10, 2019. Digital PCR (dPCR) was used to determine whether M tuberculosis complex DNA was detectable in PBMCs isolated from 100 mL blood taken from asymptomatic adults with HIV infection or a history of recent household or occupational exposure to an index case of human or bovine tuberculosis. Participants were recruited from HIV clinics, tuberculosis clinics, and cattle farms in and around Addis Ababa. A nested prospective study was done in a subset of HIV-infected individuals to evaluate whether administration of isoniazid preventive therapy was effective in clearing M tuberculosis complex DNA from PBMCs. Follow-up was done between July 20, 2018, and Feb 13, 2019. QuantiFERON-TB Gold assays were also done on all baseline and follow-up samples. Findings: Valid dPCR data (ie, droplet counts >10 000 per well) were available for paired CD34-positive and CD34-negative PBMC fractions from 197 (70%) of 284 participants who contributed data to cross-sectional analyses. M tuberculosis complex DNA was detected in PBMCs of 156 of 197 participants with valid dPCR data (79%, 95% CI 74–85). It was more commonly present in CD34-positive than in CD34-negative fractions (154 [73%] of 197 vs 46 [23%] of 197; p<0·0001). Prevalence of dPCR-detected M tuberculosis complex DNA did not differ between QuantiFERON-negative and QuantiFERON-positive participants (77 [78%] of 99 vs 79 [81%] of 98; p=0·73), but it was higher in HIV-infected than in HIV-uninfected participants (67 [89%] of 75 vs 89 [73%] of 122, p=0·0065). By contrast, the proportion of QuantiFERON-positive participants was lower in HIV-infected than in HIV-uninfected participants (25 [33%] of 75 vs 73 [60%] of 122; p<0·0001). Administration of isoniazid preventive therapy reduced the prevalence of dPCR-detected M tuberculosis complex DNA from 41 (95%) of 43 HIV-infected individuals at baseline to 23 (53%) of 43 after treatment (p<0·0001), but it did not affect the prevalence of QuantiFERON positivity (17 [40%] of 43 at baseline vs 13 [30%] of 43 after treatment; p=0·13). Interpretation: We report a novel molecular microbiological biomarker of latent tuberculosis infection with properties that are distinct from those of a commercial interferon-γ release assay. Our findings implicate the bone marrow as a niche for M tuberculosis in latently infected individuals. Detection of M tuberculosis complex DNA in PBMCs has potential applications in the diagnosis of latent tuberculosis infection, in monitoring response to preventive therapy, and as an outcome measure in clinical trials of interventions to prevent or treat latent tuberculosis infection. Funding: UK Medical Research Council.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Infektionsmedicin0 (SwePub)302092 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Infectious Medicine0 (SwePub)302092 hsv//eng
7001 a Tulu, Begnau Bahir Dar University,Addis Ababa University4 aut
7001 a Younis, Sidrau Queen Mary University,National University of Medical Sciences (NUMS)4 aut
7001 a Jolliffe, David A.u Queen Mary University4 aut
7001 a Tayachew, Dawitu Armauer Hansen Research Institute4 aut
7001 a Manwandu, Hanau Armauer Hansen Research Institute4 aut
7001 a Abozen, Tenagneworku Armauer Hansen Research Institute4 aut
7001 a Tirfie, Emawayish A.u Armauer Hansen Research Institute4 aut
7001 a Tegegn, Metasebiau Armauer Hansen Research Institute4 aut
7001 a Zewude, Abomau Addis Ababa University4 aut
7001 a Forrest, Sallyu University of Cambridge4 aut
7001 a Mayito, Jonathanu Makerere University4 aut
7001 a Huggett, Jim F.u University of Surrey,LGC Group4 aut
7001 a Jones, Gerwyn M.u LGC Group4 aut
7001 a O'Sullivan, Denise M.u LGC Group4 aut
7001 a Martineau, Henny M.u University College London4 aut
7001 a Noursadeghi, Mahdadu University College London4 aut
7001 a Chandran, Aneeshu University College London4 aut
7001 a Harris, Kathryn A.u Great Ormond Street Hospital4 aut
7001 a Nikolayevskyy, Vladu Public Health England4 aut
7001 a Demaret, Julieu Lille University Hospital4 aut
7001 a Berg, Stefanu Animal and Plant Health Agency4 aut
7001 a Vordermeier, Martinu Animal and Plant Health Agency4 aut
7001 a Balcha, Taye T.u Lund University,Lunds universitet,Klinisk infektionsmedicin,Forskargrupper vid Lunds universitet,Clinical infection medicine,Lund University Research Groups4 aut0 (Swepub:lu)med-ttb
7001 a Aseffa, Abrahamu Armauer Hansen Research Institute4 aut
7001 a Ameni, Gobenau Addis Ababa University,United Arab Emirates University4 aut
7001 a Abebe, Markosu Armauer Hansen Research Institute4 aut
7001 a Reece, Stephen T.u University of Cambridge,Kymab Ltd4 aut
7001 a Martineau, Adrian R.u Queen Mary University4 aut
7102 a University of Oslob Queen Mary University4 org
7730 t The Lancet Microbeg 2:6, s. 267-275q 2:6<267-275x 2666-5247
8564 u http://dx.doi.org/10.1016/S2666-5247(21)00043-4x freey FULLTEXT
8564 8u https://lup.lub.lu.se/record/a211da20-0268-42e7-aca5-18210427d482
8564 8u https://doi.org/10.1016/S2666-5247(21)00043-4

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