{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:10:07Z","timestamp":1787163007307,"version":"build-2736575974"},"update-to":[{"DOI":"10.12688\/f1000research.14184.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2018,4,30]],"date-time":"2018-04-30T00:00:00Z","timestamp":1525046400000}}],"reference-count":155,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2018,4,30]],"date-time":"2018-04-30T00:00:00Z","timestamp":1525046400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p>Although several factors are known to increase the risk of tuberculosis, the occurrence of tuberculosis disease in an infected individual is difficult to predict. We hypothesize that active human cytomegalovirus infection due to recent infection, reinfection or reactivation plays an epidemiologically relevant role in the aetiology of tuberculosis by precipitating the progression from latent tuberculosis infection to disease. The most compelling support for this hypothesis comes from the striking similarity in age-sex distribution between the two infections, important because the age-sex pattern of tuberculosis disease progression has not been convincingly explained. Cytomegalovirus infection and tuberculosis have other overlapping risk factors, including poor socio-economic status, solid organ transplantation and, possibly, sexual contact and whole blood transfusion. Although each of these overlaps could be explained by shared underlying risk factors, none of the epidemiological observations refute the hypothesis. If this interaction would play an epidemiologically important role, important opportunities would arise for novel approaches to controlling tuberculosis.<\/ns4:p>","DOI":"10.12688\/f1000research.14184.2","type":"journal-article","created":{"date-parts":[[2018,4,30]],"date-time":"2018-04-30T05:30:26Z","timestamp":1525066226000},"page":"280","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":30,"title":["The convergent epidemiology of tuberculosis and human cytomegalovirus infection"],"prefix":"10.12688","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4367-1133","authenticated-orcid":false,"given":"Frank","family":"Cobelens","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nico","family":"Nagelkerke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0435-1006","authenticated-orcid":false,"given":"Helen","family":"Fletcher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2018,4,30]]},"reference":[{"key":"ref-1","article-title":"Global tuberculosis report 2017.","year":"2017"},{"key":"ref-2","first-page":"28-106","article-title":"Controlled chemoprophylaxis trials in tuberculosis. 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Strang, Institute for Infection\u00a0and\u00a0Immunity, St George's, University of London, London, UK, 14 Mar 2018, version 1, 1 approved, 1 approved with reservations","URL":"https:\/\/f1000research.com\/articles\/7-280\/v1#referee-response-31552","order":0,"name":"referee-response-31552","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Frank Cobelens<\/b>; <i>Posted: 22 Apr 2018<\/i>; We thank Dr. Strang for his valuable comments.Here we respond point-by-point, referring to the revised version of our paper.1. &quot;(... )Indeed, the authors should have done more to highlight very resent work from one of their laboratories on this topic. This study, mentioned in the opening paragraphs, shows a clear association of the presence of T cells recognizing HCMV and an increased risk of MTB disease early in life. What is especially interesting about this study is the possibility that development of MTB disease is related to the impairment of NK cell function. Much recent work in HCMV pathogenesis by Wilkinson and colleagues has highlighted the many and diverse mechanisms that HCMV employs to evade NK cells. It is interesting to consider that HCMV evasion of the immune response to infection is directly related to development of MTB disease.&quot; <b>Response<\/b>: We agree that the possible role of impairment of NK cell function deserves more attention. We now elaborate on this aspect in the section entitled &quot;Human Cytomegalovirus Infection&quot;.2. &quot;The authors mention that the lung may be a reservoir for HCMV. However, this is based on studies in mice using murine cytomegalovirus (MCMV). The pathology of MCMV does not accurately mirror that of HCMV. Thus, more compelling evidence relating the presence of HCMV in the lung with disease must be presented. Based on the data discussed above, co-incident infection of HCMV and MTB in lung tissue may not be required for disease, but, perhaps, modulation of the immune system.&quot; <b>Response<\/b>: We added the following references: Gordon et al, J Exp Med 2017 (a study of donor organs that showed the lung is a major site for CMV DNA) and Poole et al. J Infect Dis 2015 (that found CMV in alvealoar macrophages). But it is also true that CMV may not need to be present in the lung as it impacts the systemic immune response and therefore has an indirect effect still relevant for lung immunity. It is possible that both co-infection of lung AND CMV impact on systemic immune response contribute to TB risk in the CMV infected individual. We added this consideration to the in the section entitled &quot;Human Cytomegalovirus Infection&quot;.3. &quot;It must be noted, however, that there is currently no widely available HCMV vaccine and it is unclear if vaccines based on HCMV in humans will offer similar protection to those based on RhCMV in non-human primates.&quot;&nbsp; <b>Response<\/b>: We agree with this caveat that we added to the text.","URL":"https:\/\/f1000research.com\/articles\/7-280\/v2#referee-comment-3608","order":1,"name":"referee-comment-3608","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.16087.r33563, Maziar Divangahi, McGill Internation TB Center, University of McGill, Montr\u00e9al, QC, Canada, 03 May 2018, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/7-280\/v2#referee-response-33563","order":2,"name":"referee-response-33563","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"The author(s) declared that no grants were involved in supporting this work","order":3,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}