Abstract

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.

Highlights

  • With 10.4 million new cases and 1.7 million deaths per year, tuberculosis (TB) remains a major global health problem[1]

  • We have phrased some of the conclusions more cautiously, and added immunological detail on the role of Type I IFN and the effect of human CMV on natural killer (NK) cell function

  • 5%–15% of individuals infected with Mycobacterium tuberculosis (Mtb) ever develop TB disease, and over 50% of these do so within two years after infection[2]

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Summary

30 Apr 2018

Any reports and responses or comments on the article can be found at the end of the article. This article is included in the World TB Day collection. We have revised the article in accordance with the suggestions made by the reviewers. We have phrased some of the conclusions (with regard to congruent risk factors and CMV vaccination) more cautiously, and added immunological detail on the role of Type I IFN and the effect of human CMV on NK cell function. See detailed responses to the reviewers’ comments

Introduction
Ferebee SH
11. Comstock GW
24. Fares A
32. Chou S
53. Nagelkerke NJ
Findings
96. Frost WH
Full Text
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