Influenza is an acute respiratory infection of specific viral etiology characterized by sudden onset of headache, myalgia, fever, and prostration. The term influenza and “flu” should be restricted to those cases with clear-cut epidemiologic or laboratory evidence of infection with influenza virus.
The etiological agent
The viruses of A and B influenza constitute one antigenic type and the virus of influenza C another type. Infection with one type confers no immunity to the other two. The designation of the influenza viruses of type A, B or C is based on the antigenic identification of the nucleoprotein (NP) and of the internal matrix proteins (M). The three types are grouped in a virus family named Orthomyxoviridae. The influenza A viruses are further subdivided (subtypes) on the basis of the surface antigens: hemagglutinin (H) and neuraminidase (N); the single subtype are denominated according to the place and year of their isolation, for example A/Sydney/5/97 (H3N2). The influenza B and C viruses are classified following the same criteria but they are not divided into subtypes because the H and N antigens do not show very significant variations in the type B and can even be lacking in type C. The influenza B and C viruses do not usually cause significant complications.
The etiological agent
Influenza A viruses are the cause of outbreaks of desease almost annually. With the exception of the last two decades, world epidemics or pandemics have happened about every 10-15 years starting from the pandemic in 1957-1958. Influenza A viruses infect pigs, horses, and fowl, expecially ducks and turkeys. A summary of the appearance of antigen subtypes of influenza A associated with various pandemics or epidemics.
|Year||Subtype of influenza A||Extension of the epidemic|
|1889-90||H2N8 (a)||Serious pandemic|
|1900-03||H3N8 (a)||Moderate epidemic|
|1918-19||H1N1 (b)||Spanish or swine influenza - serious pandemic|
|1933-35||H1N1- in precedenza HswN1||Light epidemic|
|1946-47||H1N1- in precedenza HoN1||Light epidemic|
|1957-58||H2N2 - Asiatica||Serious pandemic|
|1968-69||H3N2 - Hong Kong||Moderate epidemic from horses virus|
|1977-78||H1N1 (c)||Light epidemic|
(a) From retrospective serological investigations on people living in those
(b) The hemagglutinins once denominated Hsw and HO are now classified as H1 variants.
(c) From then up until now (1999-2000), viruses of the subtypes H1N1 or H3N2 have shown themselves in alternate years or together.
The most extensive and serious epidemics are caused by the viruses of influenza A. This is partly due to the notable capacity of the hemagglutinin and neuraminidase antigens of the virus of influenza A to undergo periodical antigenic modifications. The greatest variations are recognised as antigenic shifts (antigenic variants), are limited to influenza A viruses and sometimes are related to influenza pandemics. Minor variations are defined as antigenic drifts (antigenic modifications). These changes may regard only the hemagglutinin or the hemagglutinin and the neuraminidase. In human infections three major antigenic subtypes of hemagglutinins (H1,H2,H3) and two neuroaminidases (N1,N2) have been identified. The hemagglutinins, once denominated Ho and Hsw, are now classified as variants of H1 (see the summary). An example of antigenic variant which affected hemagglutinin and neuraminidase took place in 1957, when the subtype of the predominant influenza A virus changed from H1N1 to H2N2 with the appearance of a serious epidemic which caused in the United States alone 70,000 deaths more than those forecast. In 1968 there was an interesting antigenic variant affecting only the hemagglutinin (from H2N2 to H3N2) and the consequent pandemic was less serious than the one in 1957. In 1977 a H1N1 virus emerged which was responsible for a pandemic affecting above all young people born after 1957. As can be observed in the summary, the H1N1 viruses appeared from 1918 to 1956 and so it was foreseeable that those born before 1957 would possess a certain degree of immunity towards the H1N1 virus. During the main influenza epidemics only one viral subtype circulated at a time. And yet, starting from 1977, the viruses H1N1 and H3N2 circulated together causing epidemics of varying gravity. In some epidemics also viruses of influenza type B circulated simultaneously with the viruses of influenza type A. The origin of the pandemics is of avian origin. Given the notable difference in the primary structures of the hemagglutinins of the various subtypes of the influenza virus (H1, H2 or H3), it can be considered improbable that the antigenic variations are the fruit of spontaneous mutations of the gene of the hemagglutinin. As the segmented genome of the influenza virus may show a strong indication of rearrangement, it has been assumed that the pandemic stocks may derive from the gene rearrangement between human and animal influenza viruses. It is held that such a gene rearrangement could have happened in 1997 in Hong Kong where some cases of infection by the virus of influenza A/H5N1 were discovered in human beings during an extensive epidemic of avian influenza caused by A/H5N1 in poultry. Pandemics represent the most dramatic expression of influenza; and yet, the cases of illness which take place between the pandemic periods are responsible for a high total mortality and morbidity, even if observed over a longer period. The viruses of influenza A which circulate between the pandemic periods show antigenic drift of the H antigen; these variations are apparently the result of punctiform mutations which involve the segment of RNA which codifies the hemagglutinin. Significant stocks from the epidemiological point of view, that is those which can cause large epidemics, show amino acid modifications in at least two greater antigenic sites in the hemagglutinin molecule. As two punctiform mutations hardly ever happen together, it is thought that antigenic drifts derive from punctiform mutations, which have happened sequentially during the diffusion of the virus from person to person. Antigenic drifts took place almost every year from 1977 onwards for H1N1 viruses, and from 1968 onwards for H3N2 viruses.
Clinical manifestations of influenza
Influenza epidemics take place almost every winter beginning brusquely and reaching their climax in a two week period; they generally last from 2 to 3 weeks and often disappear with the same rapidity with which they appeared. Influenza is an acute respiratory disease caused by an infection of influenza viruses; the illness affects the high/low respiratory tracts and is often accompanied by systemic signs and symptoms such as headache, temperature from 38° to 41°C, headache in the forehead, sensation of coldness, shivering, widespread myalgia, bodily discomfort, pain when moving the eyeballs, photophobia and burning of the eyes; the respiratory symptoms are characterised by coughing and pharyngodinia. Influenza without complications usually reaches a solution of the acute illness in a period going from 2 to 5 days and most patients get completely better in a week.
These epidemics have a high morbidity rate (illness rate: the relation between the number of ill people and healthy people in a community) in the general population. On the other hand, one has a high mortality rate if the influenza caused by the influenza A virus causes a primary pneumonia; pneumonia is more frequent in elderly people suffering from chronic respiratory, cardiovascular, metabolic and immune-depressive diseases and it often worsens ending in death. Pneumonia must be suspected in all cases of influenza when the temperature does not come down 5 days after the onset. The differential diagnosis of parainfluential pneumonia of bacterial etiology should be made after laboratory tests and radiological enquiries. The main indications of phlogosis (VES, leucocytosis, mucoproteins, reactive C protein) are normally higher in pneumonia of bacterial etiology; in the latter, moreover, chest X-rays will show single or multiple zones of parenchymal thickening. Pulmonary affection can even be verified 24-48 hours after the onset of the influenza; in this case it is characterised by coughing, hemoptysis, plain dyspnoea, hyperpnea and, at the end, cyanosis. During auscultation there are appreciable rhonchi, whistling and widespread rattles or the presence of hypophonia. X-rays will show an evident widespread interstitial bronchopneumonia and/or an acute respiratory distress syndrome (ARDS) whose homeopathic therapy has been described in “SARS, a proposition for its treatment” *
In these cases a strong hypoxia is noticed in the arterial hemogasanalysis. Hystopathological reports, in cases of lethal primary influential pneumonia, consist of a strong inflammatory reaction in the alveolar septa, with edema and infiltrates of lymphocytes, macrophages and plasma cells. In the alveolar capillaries there are fibrin thrombi, together with necrosis; the alveoli and the alveolar ducts may be covered with eosinophilic hyaline membranes. In direct immunofluorescence the antigens of the influenza virus are noticeable in the macrophages and alveoli. The therapy is aimed above all at ensuring good respiratory functioning; in the most serious cases intensive care treatment is necessary.
In other cases the clinical course of viral pneumonia A leads to death caused by a “hemorrhagic pneumonia” (see for the therapy, canine influenza).
* As the expected pandemic fortunately did not take place, the book “SARS, a proposition for its treatment” did not receive the clinical confirmation it deserved, but the corona virus responsible for SARS is only sleeping in its natural “reservoir”, the zibet, which is still a popular dish on Chinese tables, and also in the raccoon dog. In order to fight this corona virus we have at our disposal a vaccine which was synthetized in record time in 2004. However, should there be an epidemic or pandemic, we cannot forecast immunity induced by a vaccine prepared with the 2003 type; patients at risk even if vaccinated could meet with serious complications even leading to death.