On the epidemiology of influenza

John J Cannell¹ , Michael Zasloff² , Cedric F Garland³ , Robert Scragg⁴ and Edward Giovannucci⁵

¹Department of Psychiatry, Atascadero State Hospital, 10333 El Camino Real, Atascadero, CA 93423, USA

²Departments of Surgery and Pediatrics, Georgetown University, Washington, D.C., USA

³Department of Family and Preventive Medicine, University of California San Diego, La Jolla, CA, USA

⁴Department of Epidemiology and Biostatistics, University of Auckland, Auckland, New Zealand

⁵Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, MA, USA

author email corresponding author email

Virology Journal 2008, 5:29doi:10.1186/1743-422X-5-29


Published:	25 February 2008

Abstract

The epidemiology of influenza swarms with incongruities, incongruities exhaustively detailed by the late British epidemiologist, Edgar Hope-Simpson. He was the first to propose a parsimonious theory explaining why influenza is, as Gregg said, "seemingly unmindful of traditional infectious disease behavioral patterns." Recent discoveries indicate vitamin D upregulates the endogenous antibiotics of innate immunity and suggest that the incongruities explored by Hope-Simpson may be secondary to the epidemiology of vitamin D deficiency. We identify – and attempt to explain – nine influenza conundrums: (1) Why is influenza both seasonal and ubiquitous and where is the virus between epidemics? (2) Why are the epidemics so explosive? (3) Why do they end so abruptly? (4) What explains the frequent coincidental timing of epidemics in countries of similar latitude? (5) Why is the serial interval obscure? (6) Why is the secondary attack rate so low? (7) Why did epidemics in previous ages spread so rapidly, despite the lack of modern transport? (8) Why does experimental inoculation of seronegative humans fail to cause illness in all the volunteers? (9) Why has influenza mortality of the aged not declined as their vaccination rates increased? We review recent discoveries about vitamin D's effects on innate immunity, human studies attempting sick-to-well transmission, naturalistic reports of human transmission, studies of serial interval, secondary attack rates, and relevant animal studies. We hypothesize that two factors explain the nine conundrums: vitamin D's seasonal and population effects on innate immunity, and the presence of a subpopulation of "good infectors." If true, our revision of Edgar Hope-Simpson's theory has profound implications for the prevention of influenza.