CH 105 - Chemistry and Society

Following a typical incubation period of 48 hours, the typical symptoms of influenza appears. The onset is abrupt with a marked fever, headache, photophobia, shivering, a dry cough, malaise, myalgia, and a dry tickling throat. The fever is continuous and lasts around 3 days. Influenza B infection is similar to influenza A, but infection with influenza C is usually subclinical or very mild in nature.

Complications

1. 1. Tracheobronchitis and bronchiolitis - A small proportion of patients develop more sever respiratory symptoms where rales and rhonchi are heard but the chest is radiologically clear. These symptoms are more commonly seen in the elderly and patients with COAD.
    
2. 2. Pneumonia - primary viral pneumonia or a secondary bacterial pneumonia may develop. Primary viral pneumonia is relatively uncommon, but cases have been demonstrated in many influenza epidemics. It may occur in previously young and healthy persons, but are commonly associated with patients with preexisting cadiovascular disease such as Rheumatic fever. Secondary bacterial pneumonia is more common than primary viral pneumonia. It was speculated that the high incidence of deaths in young people during the Spanish influenza pandemics of 1917-1918 may have been due to secondary bacterial pneumonia in a population generally debilitated by the effects the WWI.
    
3. Secondary bacterial pneumonia - usually occurs late in the course of disease, after a period of improvement has been observed for the acute disease. The symptoms and signs are that of a typical bacterial pneumonia. S. aureus is most commonly involved although S. pneumoniae and H. influenzae may be found. There appears to be a good reason why S. aureus is so commonly found in cases of secondary bacterial pneumonia. Infection of cells by influenza A requires cleavage of the virus haemagglutinin by proteases, and some strains of S. aureus produces such enzymes. Thus S. aureus and influenza may promote infection by the other. Influenza A by damage to the healthy respiratory epithelium.
    
4. Myositis and myoglobinuria - In addition to myalgia, which is characteristic of acute influenza infection, clinical myositis and myoglobinuria may occur.
    
5. Reye's syndrome - Reye's syndrome is characterized by encephalopathy and fatty liver degeneration. The disease has a 50% mortality amongst hospitalized cases and had been associated with several viruses; such as influenza A and B, Coxsackie B5, echovirus, HSV, VZV, CMV and adenovirus.
    
6. Other complications - influenza infection have been implicated in acute viral encephalitis and Guillain-Barre syndrome. Influenza A was also associated with the cot death syndrome.
    

E. Laboratory Diagnosis

During epidemics, a presumptive diagnosis can be made on the basis of the clinical symptoms. However, influenza A and B can co-circulate, and mixed infections of influenza and other viruses have been reported. Isolated cases of suspected influenza should be investigated for these may represent the first cases of an impending epidemic.

1. Virus Isolation - Throat swabs, NPA and nasal washings may be used for virus isolation. It is reported that nasal washings are the best specimens for virus isolation. The specimen may be inoculated in embryonated eggs or tissue culture. 10-12 day embryonated eggs are used for virus isolation. The specimen is inoculated into the amniotic cavity. The virus replicates in the cells of the amniotic membrane and large quantities are released back into the amniotic fluid. After 2-3 days incubation, virus in the amniotic fluid can be detected by adding aliquots of harvested amniotic fluid to chick, guinea pig, or human erythrocytes. Pathological specimens can be inoculated on to tissue cultures of kidney, chicks or a variety of other species. Rhesus monkey cells are the most sensitive. Although no CPE is produced, newly produced virus can be recognized by haemadsorption using the cells in the tissue culture, and haemagglutination using the culture medium which contains free virus particles. Influenza B virus and occasionally influenza A will produce a CPE in MDCK cells. Influenza viruses isolated from embryonated eggs or tissue culture can be identified by serological or molecular methods. Influenza viruses can be recognized as A, B, or C types by the use of complement fixation tests against the soluble antigen. (A soluble antigen is found for all influenza A, B or C type virus but antibody against one type does not cross react with the soluble antigen of the other. The further classification of influenza isolates into subtypes and strains is a highly specialized responsibility of the WHO reference laboratories. The HA type is identified by HAI tests, the NA type is also identified.

2. Rapid Diagnosis by Immunofluorescence - cells from pathological specimens may be examined for the presence of influenza A and B antigens by indirect immunofluorescence. Although many workers are convinced of the value of this technique, others have been disappointed with the specificity of the antisera and the level of background fluorescence that makes the test difficult to interpret. EIA tests for the detection of influenza A viral antigens are available that are easier to interpret than immunofluorescence. PCR assays for the detection of influenza RNA have also been developed but there usefulness in a clinical setting is highly questionable.
    
3. Serology - Virus cannot be isolated from all cases of suspected infection. More commonly, the diagnosis is made retrospectively by the demonstration of a rise in serum antibody to the infecting virus. CFT is the most common method used using the type specific soluble antigen. However, the CF test is thought to have a low specificity. A more specific test is the HAI test. Infection by influenza viruses results in a rise in serum antibody titre, but the requirement for a 4-fold or greater rise in titre of HI of CF antibody reflects the inaccuracy of these tests for detecting smaller increases in antibody. A more precise method for measuring antibody is by SRH. SRH is more sensitive than CF or HAI tests and has a greater degree of precision. A 50% increase in zone area represents a rise in antibody and is evidence of recent infection. Sera do not have to be pretreated to remove non-specific inhibitors which plaque the HAI test. SRH may well replace CF and HAI tests in diagnostic laboratory in future.

Sia α(2,6) Gal  (Human)

Sia α(2,3) Gal (Avian and some Swine)

(made with Sweet, with an OH, not AcNH on sialic acid on C5)

(made with Sweet, with an OH, not AcNH on sialic acid on C5)