A history of influenza.

Abstract

1. Summary, 572 2. Introduction, 572 3. Influenza epidemics, 572 3.1. History, 572 3.2. Antigenic drift, 573 4. Influenza pandemics, 574 4.1. History, 574 4.2. Pandemics before 1700, 574 4.3. Pandemics from 1700 to 1830, 574 4.4. Pandemics since 1830–3, 575 4.4.1. Pandemic of 1918–20, 575 4.4.2. Pandemic of 1957–8, 577 4.5. Features of pandemic influenza, 578 5. References, 578 From the history of influenza epidemics and pandemics, which can be traced back with some accuracy for the past three hundred years, and with less certainty before this time, it is apparent that outbreaks occur somewhere in the world in most years. Annual epidemics are due to antigenic drift; and pandemics, occurring at 10 to 50 years intervals, are due to new virus subtypes resulting from virus reassortment. Nothing has been introduced during the past 100 years to affect the recurrent pattern of epidemics and pandemics; and our future in the new century is clearly indicated by our past. This past experience is reviewed in the present paper. Since 1932, when the influenza virus was first isolated in the laboratory, the history of this infection can be recorded and confirmed by laboratory diagnosis. In the two centuries before this time, infections can be identified by the known signs and symptoms of disease and the explosive nature of outbreaks. Thus, although sharing many symptoms with other respiratory infections, influenza presents in addition as a sudden onset of three-day fever, with muscle pain and a degree of prostration out of all proportion with the severity of other symptoms. Secondly, epidemics usually occur suddenly without warning, infecting a large percentage of people, and disappear after a few weeks or months; these epidemics are commonly heralded by an increase in hospital admissions of elderly patients with bronchopneumonia, particularly associated with Staphylococcus aureus, and an excess of deaths, mainly in the elderly and those suffering from chronic heart and lung disease. From these observations outbreaks can be identified in the historical record without difficulty, although this identification becomes less secure as one goes back further in time; and reference to influenza can be found in both scientific and lay publications since 1650. More dramatically, pandemics of influenza occur: these appear suddenly in a specific geographical area, spread throughout the world infecting millions and cause a large numbers of deaths. Evidence of pandemics is also present in the historical record which include 10 probable and three possible pandemics since AD 1590 (30); and allusion to earlier possible pandemics is suggested throughout history. With the above in mind, it is not surprising that influenza remained the most studied of viruses and virus diseases, until the advent of HIV two decades ago. It has focused the interests of researchers, epidemiologists, physicians and the pharmaceutical industry, whose studies are reported in a vast literature. Despite this, little has been done in the past century to change the pattern of influenza infections; and our future is clearly indicated by the past. Epidemics of influenza occur in most countries in some years, and in some countries in most years: for many they are common annual events, unpredictable in time and severity. However, history indicates certain features which make influenza epidemics more likely. Firstly, epidemics tend to occur in winter months when cold, crowding of people and higher humidities are a feature: indeed, in areas where continuous high humidity is a characteristic, infections may occur throughout the year. Secondly, in more recent times epidemics are often first seen in Eastern or Southern Hemisphere countries, and later spread to Europe and North America in the winter months of these areas: seeding of infection may occur prior to epidemics, to be followed by epidemics when conditions are optimal. Thirdly, epidemics are more likely to occur when a variant virus appears which shows antigenic changes from previous strains, and cross-reacting antibody, acquired by previous infection, is low in both percentage positive and titre. The influenza virus has radiating from the surface multiple copies of two glycoproteins termed haemagglutinin (HA) and neuraminidase (NA): it is antibody to these proteins which equates with immunity, and it is accumulating mutations in these glycoproteins, particularly the haemagglutinin, which constitutes the virus variation termed antigenic drift. The monitoring of antigenic variation in the influenza virus is a key factor in anticipating epidemics, and in vaccine design where for any year the prevalent virus strain(s) must be incorporated into the current vaccines. The responsibility for monitoring virus variation rests with the World Health Organization who have commissioned over a hundred research laboratories in various parts of the world to monitor antigenic changes in the infecting viruses and the incidence and sprea