PMID- 29548281 OWN - NLM STAT- MEDLINE DCOM- 20180619 LR - 20181114 IS - 1471-2334 (Electronic) IS - 1471-2334 (Linking) VI - 18 IP - 1 DP - 2018 Mar 16 TI - Mycobacterium tuberculosis thymidylate kinase antigen assays for designating incipient, high-risk latent M.tb infection. PG - 133 LID - 10.1186/s12879-018-3007-y [doi] LID - 133 AB - BACKGROUND: Precise designation of high risk forms of latent Mycobacterium tuberculosis-M.tb infections (LTBI) is impossible. Delineation of high-risk LTBI can, however, allow for chemoprophylaxis and curtail majority cases of active tuberculosis (ATB). There is epidemiological evidence to support the view that LTBI in context of HIV-1 co-infection is high-risk for progression to ATB relative to LTBI among HIV-ve persons. We recently showed that assays of M.tb thymidylate kinase (TMKmt) antigen and host specific IgG can differentiate ATB from LTBI and or no TB (NTB, or healthy controls). In this study, we aimed to expose the differential levels of TMKmt Ag among HIV+ve co-infected LTBI relative to HIV-ve LTBI as a strategy to advance these assays for designating incipient LTBI. METHODS: TMKmt host specific IgM and IgG detection Enzyme Immuno-Assays (EIA) were conducted on 40 TB exposed house-hold contacts (22 LTBI vs. 18 no TB (NTB) by QunatiFERON-TB GOLD(R)); and TMKmt Ag detection EIA done on 82 LTBI (46 HIV+ve vs 36 HIV-ve) and 9 NTB (American donors). Purified recombinant TMKmt protein was used as positive control for the Ag assays. RESULTS: IgM levels were found to be equally low across QuantiFERON-TB GOLD(R) prequalified NTB and TB exposed house-hold contacts. Higher TMKmt host specific IgG trends were found among TB house-hold contacts relative to NTB controls. TMKmt Ag levels among HIV+ve LTBI were 0.2676 +/- 0.0197 (95% CI: 0.2279 to 0.3073) relative to 0.1069 +/- 0.01628 (95% CI: 0.07385 to 0.14) for HIV-ve LTBI (supporting incipient nature of LTBI in context of HIV-1 co-infection). NTB had TMKmt Ag levels of 0.1013 +/- 0.02505 (5% CI: 0.0421 to 0.1606) (intimating that some were indeed LTBI). CONCLUSIONS: TMKmt Ag levels represent a novel surrogate biomarker for high-risk LTBI, while host-specific IgG can be used to designate NTB from LTBI. FAU - Wayengera, Misaki AU - Wayengera M AUID- ORCID: 0000-0001-7239-8079 AD - Department of Pathology, Unit of Genetics & Genomics, School of Biomedical Sciences, Makerere University College of Health Sciences, P o Box 7072, Kampala, Uganda. wmisaki@yahoo.com. AD - Department of Immunology &Molecular Biology, School of Biomedical Sciences, Makerere University College of Health Sciences, P o Box 7072, Kampala, Uganda. wmisaki@yahoo.com. FAU - Kateete, David P AU - Kateete DP AD - Department of Immunology &Molecular Biology, School of Biomedical Sciences, Makerere University College of Health Sciences, P o Box 7072, Kampala, Uganda. AD - Department of Medical Microbiology, School of Biomedical Sciences, Makerere University College of Health Sciences, P o Box 7072, Kampala, Uganda. FAU - Asiimwe, Benon AU - Asiimwe B AD - Department of Medical Microbiology, School of Biomedical Sciences, Makerere University College of Health Sciences, P o Box 7072, Kampala, Uganda. FAU - Joloba, Moses L AU - Joloba ML AD - Department of Immunology &Molecular Biology, School of Biomedical Sciences, Makerere University College of Health Sciences, P o Box 7072, Kampala, Uganda. AD - Department of Medical Microbiology, School of Biomedical Sciences, Makerere University College of Health Sciences, P o Box 7072, Kampala, Uganda. LA - eng GR - D43-TW009607-01/NIH Forgarty/International GR - D43 TW009607/TW/FIC NIH HHS/United States GR - R24 TW008886/TW/FIC NIH HHS/United States GR - N/A/Sida Makerere University/International GR - 5R24TW008886/GF/International PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. DEP - 20180316 PL - England TA - BMC Infect Dis JT - BMC infectious diseases JID - 100968551 RN - 0 (Antibodies, Bacterial) RN - 0 (Biomarkers) RN - 0 (Immunoglobulin G) RN - 0 (Immunoglobulin M) RN - EC 2.7.4.4 (Nucleoside-Phosphate Kinase) RN - EC 2.7.4.9 (dTMP kinase) SB - IM MH - Adult MH - Antibodies, Bacterial/analysis MH - Biomarkers/analysis MH - Coinfection MH - *Disease Progression MH - Female MH - HIV Infections/complications MH - HIV-1 MH - Humans MH - Immunoglobulin G/analysis MH - Immunoglobulin M/analysis MH - Latent Tuberculosis/complications/*diagnosis/microbiology MH - Male MH - Mycobacterium tuberculosis/*enzymology/isolation & purification MH - Nucleoside-Phosphate Kinase/*metabolism MH - Risk Assessment MH - Tuberculin Test/*methods PMC - PMC5857104 OTO - NOTNLM OT - Latent M.tb infections (LTBI);Thymidylate Kinase OT - Mycobacterium tuberculois OT - Serodiagnosis OT - Tuberculosis COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: This protocol was approved by the School of Biomedical Sciences Institutional Review & Ethics Committee (SBS-IREC) at the College of Health Sciences, Makerere University Kampala, Uganda as protocol # SBS 263 titled "Exploration of Mycobacterium tuberculosis thymidylate kinase based culture- and immunodiagnostic- assays towards rapid and easy detection of Tuberculosis". Since the study used broadly consented serum of TB house-hold contacts and LTBI previously collected by the Makerere University-Case-Western Reserve University (MU-CWRU) TB Research Unit Project, the need for participant consent was waived by the SBS-IREC. CONSENT FOR PUBLICATION: Not Applicable COMPETING INTERESTS: "Tehe authors declare that they have no competing interests." M.W has previously filed a related patent # UG/P/2013/000006 at the Uganda Registration Services Bureau (URBS) and African Regional Intellectaul Property Organization (ARIPO). PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2018/03/20 06:00 MHDA- 2018/06/21 06:00 PMCR- 2018/03/16 CRDT- 2018/03/18 06:00 PHST- 2017/11/30 00:00 [received] PHST- 2018/02/21 00:00 [accepted] PHST- 2018/03/18 06:00 [entrez] PHST- 2018/03/20 06:00 [pubmed] PHST- 2018/06/21 06:00 [medline] PHST- 2018/03/16 00:00 [pmc-release] AID - 10.1186/s12879-018-3007-y [pii] AID - 3007 [pii] AID - 10.1186/s12879-018-3007-y [doi] PST - epublish SO - BMC Infect Dis. 2018 Mar 16;18(1):133. doi: 10.1186/s12879-018-3007-y.