The great influenza centennial—what have we learned about the epidemiology and prevention of transmission?
Authors: L.A. Mermel
Journal: Clinical Microbiology and Infection (2018)

At Camp Devens in Massachusetts, Dr Roy Grist described influenza in 1918: ‘These men start with what appears to be an ordinary attack of LaGrippe or Influenza, and when brought to the hospital they very rapidly develop the most vicious type of Pneumonia that has ever been seen. Two hours after admission they have the Mahogany spots over their cheek bones, and a few hours later you can begin to see the Cyanosis extending from their ears and spreading all over their face…’ [[1]Barry J.M. The great influenza. Viking Penguin, New York2004Google Scholar]. Insights have been gained into the pathogenesis of the 1918 H1N1 influenza virus [[2]Tumpey T.M. Belser J.A. Resurrected pandemic influenza viruses.Annu Rev Microbiol. 2009; 63: 79-98Crossref PubMed Scopus (54) Google Scholar]. However, as witnessed in the 2018 flu season, we have much work ahead to mitigate risk of seasonal and pandemic influenza. There is now a more concerted effort to develop a universal influenza vaccine [[3]Nachbagauer R. Krammer F. Universal influenza virus vaccines and therapeutic antibodies.Clin Microbiol Infect. 2017; 23: 222-228Abstract Full Text Full Text PDF PubMed Scopus (132) Google Scholar]. A Phase 2 trial of an investigational universal influenza vaccine has begun in the USA and plans for a Phase 3 trial are underway in Europe. In the interim, preventing influenza requires improved seasonal influenza vaccines and precautions reflecting current knowledge regarding modes of transmission. Infection prevention strategies have been based on large droplet spread of influenza. However, a long-forgotten seminal article published 77 years ago revealed airborne transmission of influenza in an animal model [[4]Andrewes C.H. Glover R.E. Spread of infection from the respiratory tract of the ferret. I. Transmission of influenza A virus.Br J Exp Pathol. 1941; 22: 91-97Google Scholar], and now, there is proof of infectious seasonal influenza virus in fine aerosols (≤5 μm) exhaled from individuals with influenza [[5]Yan J. Grantham M. Pantelic J. Jacob Bueno de Mesquita P. Albert B. Liu F. et al.Infectious virus in exhaled breath of symptomatic seasonal influenza cases from a college community.Proc Natl Acad Sci USA. 2018; 115: 1081-1086Crossref PubMed Scopus (333) Google Scholar], supporting the potential for transmission beyond large droplets in humans. Most influenza shedding from infected individuals occurs shortly after symptom onset [[5]Yan J. Grantham M. Pantelic J. Jacob Bueno de Mesquita P. Albert B. Liu F. et al.Infectious virus in exhaled breath of symptomatic seasonal influenza cases from a college community.Proc Natl Acad Sci USA. 2018; 115: 1081-1086Crossref PubMed Scopus (333) Google Scholar], a time when infected adults have upper respiratory tract symptoms but often no fever [[6]Ridgway J.P. Bartlett A.H. Garcia-Houchins S. Cariño S. Enriquez A. Marrs R. et al.Influenza among afebrile and vaccinated healthcare workers.Clin Infect Dis. 2015; 60: 1591-1595Crossref PubMed Scopus (38) Google Scholar]. Hence, for influenza control planning, it is important to consider removing people from work and school environments soon after onset of symptoms suggestive of a respiratory viral infection (i.e. otherwise unexplained cough, rhinorrhoea, sore throat), particularly in healthcare settings [[7]Chow E.J. Mermel L.A. More than a cold: hospital-acquired respiratory viral infections, sick leave policy and a need for culture change.Infect Contr Hosp Epidemiol. 2018; 39: 861-862Crossref PubMed Scopus (11) Google Scholar]) and when the predominant circulating influenza virus is a poor match with the seasonal influenza vaccine or a novel influenza virus. If infected individuals are in proximity to others, such as at home, then source control, if tolerated, can be done by having an infected individual don a surgical mask [[8]Johnson D.F. Druce J.D. Birch C. Grayson M.L. A quantitative assessment of the efficacy of surgical and N95 masks to filter influenza virus in patients with acute influenza infection.Clin Infect Dis. 2009; 49: 275-277Crossref PubMed Scopus (144) Google Scholar]. Some people are super spreaders of influenza virus [[9]Bischoff W.E. Swett K. Leng I. Peters T.R. Exposure to influenza virus aerosols during routine patient care.J Infect Dis. 2013; 207: 1037-1046Crossref PubMed Scopus (163) Google Scholar], but unfortunately, we cannot yet identify such individuals when they present to emergency departments or clinics. In toto, evidence published to date suggests that the most robust transmission reduction during the next pandemic will be afforded by early removal of ill individuals from workplace or school settings, school closure in some circumstances [[10]Bin Nafisah S. Alamery A.H. Al Nafesa A. Aleid B. Brazanji N.A. School closure during novel influenza: a systematic review.J Infect Publ Health. 2018; (pii: S1876-0341(18)30004-2. (Epub ahead of print))Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar], symptomatic individuals donning a surgical mask when around others, frequent hand hygiene, and healthcare workers donning respirators (surgical masks will not prevent inhalation of virus in fine aerosols), eye protection [[11]Belser J.A. Gustin K.M. Katz J.M. Maines T.R. Tumpey T.M. Influenza virus infectivity and virulence following ocular-only aerosol inoculation of ferrets.J Virol. 2014; 88: 9647-9654Crossref PubMed Scopus (30) Google Scholar], and gowns when examining patients with influenza [[12]Mermel L.A. Pandemic avian influenza.Lancet Infect Dis. 2005; 5: 666-667Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar], as well as careful removal of personal protective equipment [[13]Tomas M.E. Kundrapu S. Thota P. Sunkesula V.C. Cadnum J.L. Mana T.S. et al.Contamination of health care personnel during removal of personal protective equipment.JAMA Intern Med. 2015; 175: 1904-1910Crossref PubMed Scopus (178) Google Scholar] and hand hygiene thereafter. The great hope for the Great Influenza is a universal vaccine. Until then, vigilance will save lives. The author has no conflicts of interest and has not received funding related to this manuscript.