A Study of an Unexplained and Large Increase in Respiratory Deaths in England and Wales: Is the Pattern of Diagnoses Consistent with the Potential Involvement of Cytomegalovirus?

Aims: To determine if the ubiquitous herpes virus, cytomegalovirus (CMV), could be involved in a large and unexplained increase in all-cause mortality in England and Wales in 2012, and more specifically if this involvement was via a respiratory etiology.
Study Design: Analysis of respiratory system cause of death in England and Wales and of respiratory system emergency hospital admissions in England.
Place and Duration of Study: Cause of death statistics with primary respiratory system involvement in England and Wales in 2011 and 2012. Trends in emergency hospital admissions in England where there is a respiratory system primary diagnosis over the period 2000/01 to 2012/13.
Methodology: Respiratory diagnoses which show a statistically significant increase as cause of death in 2012 were identified, as were diagnoses showing a statistically significant increase as the primary cause of an emergency hospital admission in 2012/13. These diagnoses were then compared with medical case studies for hospitalization and death due to CMV.
Results: Deaths in England and Wales showed a sudden and unexplained increase in early 2012 which continued for 18 months before abating. The increase was equivalent to a large influenza epidemic, although higher levels attributable to influenza were absent. The increase was age and gender specific, and highest among those with neurodegenerative diseases (+15%); however, due to the way in which the primary cause of death is coded the role of respiratory diseases as the trigger for decease can be obscured. The next highest increase was for respiratory conditions, the most notable for bronchiectasis (+19%), asthma (female +14%), lung diseases due to external agents (+12%), interstitial pulmonary diseases (female +12%), chronic pulmonary disease (+7%) and a range of other conditions with >4% increases. After adjusting for the way in which deaths in the dementia group are coded the increase due to pneumonia rises to +8% for males and +15% for females. For the whole of the respiratory group augmented with the dementia group the increase in deaths was specific to those aged over 65 (average for 65+ of male +8.3%, female + 8.7%) with a peak at 90-94 (male + 15%, female + 17%). A corresponding large increase in respiratory admissions accompanies the increase in deaths. Given that the increase in admissions and deaths moved across England and Wales in a time-based spread, indicative of an infectious agent, with spurts of rapid local spread compatible with respiratory transmission, the increase in respiratory deaths were examined to see if the nature of any putative infectious agent could be discerned. There was a striking match with the known clinical effects of CMV.
Conclusion: In an aged population lifelong exposure to the immune erosive effects of CMV presents the potential for the emergence of diseases reliant on immune impairment for their modus operandi. The lung is a primary reservoir for permanent CMV infection in humans and conditions/diagnoses showing a large increase in both death and hospital admissions in 2012 are all potentially CMV-mediated. In view of the very large increase in death for particular respiratory diagnoses further research is urgently required.