In this article we will discuss about Influenza Viruses:- 1. Occurrence of Influenza Viruses 2. Influenza Virus 3. Morphology 4. Antigenic Classification 5. Antigenic Variation 6. Pathogenesis 7. Clinical Features 8. Laboratory Diagnosis 9. Immunity 10. Epidemiology 11. Prophylaxis 12. Composition 13. Indication 14. Avian Influenza (Bird flu)-H5 N1 Virus 15. Prophylaxis 16. Swine Flu (H1N1 Virus).
Contents:
- Occurrence of Influenza Viruses
- Influenza Virus
- Morphology of Influenza Viruses
- Antigenic Classification of Influenza Virus
- Antigenic Variation of Influenza Viruses
- Pathogenesis of Influenza Viruses
- Clinical Features of Influenza Viruses
- Laboratory Diagnosis of Influenza Viruses
- Immunity
- Epidemiology of Influenza Viruses
- Prophylaxis Influenza Viruses
- Composition of Vaccine
- Indication
- Avian Influenza (Bird flu)-H5 N1 Virus
- Prophylaxis
- Swine Flu (H1N1 Virus)
1. Occurrence of Influenza Viruses:
These viruses have a unique antigenic variation occurring continuously within type A; in type B it is lesser, but in type C it is stable. They cause influenza, an acute respiratory illness. Animals (pigs, horses, birds) are also infected by Influenza virus type A strains.
The term myxo virus was at first proposed for a large group of enveloped RNA viruses which get attached to cell surface receptors of RBC and have affinity to mucin. They are now separated into two distinct families—Ortho-myxovirus and Para-myxovirus—because of their difference in replication pattern, structures and other properties.
2. Influenza Virus:
Smith et al (1933) first isolated influenza type A from throat washing of a patient and in 1940 Type B virus was isolated along with type A in cell culture; Influenza virus type C, the third serotype, was isolated by Taylor (1949).
3. Morphology of Influenza Viruses:
Types A and B are morphologically identical but Type C differs from them in some aspects.
They are pleomorphic:
1. Spherical Particle:
Diameter 80-100 nm.
2. A lipid envelope derived from the host cell membrane separates the spikes from the inner core.
3. Attached to lipid layer of the envelope are densely arranged radial projections of two types of peplomers-haemagglutinin (HA) spikes and neuraminidase (NA)-mushroom shaped. Distal tip of HA contains sites for binding to host cell.
4. Single stranded RNA genome is segmented.
4. Antigenic Classification of Influenza Virus:
Influenza virus possesses four antigens (structural proteins):
(1) The internal or nucleocapsid (nucleo-protein-NP) is closely associated with ss-RNA protein core);
(2) Matrix protein of the viral envelope (M); and (3) two surface glycoproteins (HA, haemaggludnin; NA, neuroaminidase). Three polymerase polypeptides, PA, PB and PB2 are also present.
Influenza viruses are divided into three types—A, B, C—on the basis of antigenic structure differences of NP and M proteins. Again, the types are divided into subtypes on the basis of antigenic variation of HA and NA.
Till now, 15 types of HA (H1-H13) and 9 types of NA (N1-N9) in different combination have been isolated from influenza viruses of birds, animals or humans. Human viruses have 3 HA (H1, H2, H3) and 2 NA (N1 N2) types. Type A human virus has 2 main subtypes; A1 (H1 N1) and A2 (H2 N2).
Non-human influenza viruses belong to type A whereas human influenza viruses belong to type A, B and C.
Non-human viruses do not infect man but play an important role in the emergence of pandemic influenza by genetic re-assortment with human viruses.
Nomenclature system of influenza virus:
Type/host origin/strain number/year of isolation and subtypes of HA and NA in parenthesis e.g. A/Hong Kong / 03/68 (H3 N2).
1. Haemagglutinins:
These are glycoprotein spikes on the surface of each influenza virus particle. Each virus contains 500 haemagglutinin spikes. When influenza virus is mixed with a suspension of fowl erythrocytes, the virus is adsorbed on to the mucoprotein receptor on the surface of red cells by its haemagglutinin spikes and also with adjacent red cells causing haemagglutination—an important property of influenza virus.
2. Neuraminidase:
The enzyme neuraminidase, a glycoprotein, is present on viral surface. Neuraminidase of influenza A and B viruses hydrolyses specific glycoprotein on the cell receptor and splits off N-acetyl muramic acid from the receptor and causes Haemagglutination and elution.
Due to enzymatic action of neuraminidase, (Receptor Destroying Enzyme, RDE) the virus is eluted from RBCs and remain free in the solution. Haemagglutination action can be inhibited (HIT) by specific homologous anti-serum.
5. Antigenic Variation of Influenza Viruses:
Influenza viruses show remarkable ability to undergo variation due to frequent changes in the antigenicity of HA and NA. The variation is highest in Type A and less in Type B but none in Type C. This antigenic variation is of great importance in the epidemiology of the disease.
Two antigenic variation forms are:
(1) Antigenic rift; and
(2) Antigenic shift.
(1) Antigenic rift refers to minor antigenic changes in haemagglutinin and neuraminidase, or both, and results from mutation in the HA and NA genome.
(2) Antigenic shift is major antigenic changes in NA and HA and results in emergence of new subtype.
6. Pathogenesis of Influenza Viruses:
The portal of entry of influenza virus is respiratory tract. Ciliated cells of respiratory tract are mainly susceptible, because its mucous membrane contains the specific mucoprotein receptors, for influenza virus. After entry they encounter respiratory secretions with mucoprotein. Viral neuraminidase lowers viscosity of the mucus. Then a large number of cells are infected and killed.
7. Clinical Features of Influenza Viruses:
Usually the incubation period is 1 to 4 days; subclinical infection are common. Influenza is an acute respiratory illness and clinical manifestations vary from a mild coryza to fulminating pneumonia. During acute illness, due to necrosis of virally infected cells, there is extensive desquamation of respiratory epithelium.
Influenza is characterised by fever, chills, headache, dry cough, and generalized myalgia. Fever lasts for about 3 days and respiratory symptoms last for 3 to 4 days. An uncomplicated case usually resolves within 7 days. It is self-limiting disease secondary bacterial pneumonia due to staphylococcus aureus and Haemophilus influenzae is usually observed in 10% cases.
8. Laboratory Diagnosis of Influenza Viruses:
Very frequently Influenza is diagnosed clinically:
1. Isolation of virus:
Nasal and throat washings or secredon (within 3 days of illness) are inoculated into amniotic sac of 11-13 days old chick embryo or on monolayers of monkey kidney tissue culture.
2. Immuno-fluorescence:
Can detect the viral antigen. ELISA and RIA have also been developed to detect viral antigen.
3. Serology:
Haemagglutination inhibition test (HI) is a convenient and widely used technique for identification of the strain of the virus. CFT is sensitive.
4. Antigens:
Immuno-fluorescence, ELISA, RIA have been developed to detect influenza antigens in the clinical material.
9. Immunity:
An attack of influenza produces active immunity against the strain. Local secredon of Ig A plays the dominant role. The short duration of immunity is due to antigenic variation of influenza virus.
10. Epidemiology of Influenza Viruses:
Its patterns are variable in three types of influenza virus. Type A causes severe and wide spread epidemics; B causes sporadic and sometimes epidemics, but C does not cause epidemics, but does cause in-apparent infections.
Epidemics and pandemics of influenza is associated with antigenic shift which is exhibited by only Type A virus. Periodical epidemics can be caused by antigenic drift also, which is exhibited by all three types. Type B, and C are confined to humans, while Type A viruses circulate in ecosystem (birds, swine, horses). These animal viruses infect man.
Since antiquity epidemics occurred at regular intervals. Influenza epidemic starts abruptly, spreads rapidly and often distributed worldwide.
11. Prophylaxis Influenza Viruses:
Artificial immunization is the primary means of prevention of influenza. Its efficiency is about 80%. Vaccine is prepared by incorporating the circulating latest strains of Type A and B virus specified by WHO.
12. Composition of Vaccine:
Types A and B viruses, grown in allantoic cavity of chick embryos, are inactivated by formalin or beta-propiolactone. This vaccine administrated is in a single dose but requires to be repeated each winter.
13. Indication:
Vaccine is administrated in cold countries to protect elderly people with pre-existing cardiovascular or renal disease. Side effects are few and mild, but few cases of polyneuritis are reported. Chemo-prophylaxis with antiviral amantadine and rimantadine inhibits absorption of all influenza A viruses, but it is without any effect on B viruses.
14. Avian Influenza (Bird flu)-H5 N1 Virus:
Avian Influenza is normally known as bird flu affecting human with influenza striking the lungs.
Malik Peiris, a top microbiologist in Hong Kong, battled the bird flu virus since 1997 when it made its first known jump to humans in Hong Kong and killed six people.
After interaction of bird flu from wild birds to poultry it was not a major risk, but it becomes endemic—that is a big problem.
Once the virus multiple in poultry, there is a golden opportunity for continued interaction with human population. WHO reported 20 cases contracted bird flu virus, directed from poultry, which caused 50% mortality in humans. The virulent strain H5N1 of bird flu has been isolated from migratory bird in Canada.
It was also reported from Iraq, China, Turkey. Gujarat (India) got the first suspected case of bird flu who later died (human death) in February 16, 2006, when 27 year old poultry farmer from Navapur of neighbouring Maharashtra State died in Surat Hospital (Gujarat). It was confirmed that it was due to Avian Flu virus.
India has become the first country in South Asia to report H5N1 virus, a deadly bird flu virus strains—after 36,000 birds died in Maharashtra (India). It was also reported by high security Laboratory, Bhopal (Madhya Pradesh) India, where samples (blood, stool) were tested and confirmed eight birds and diagnosed the H5N1 virus on February 18, 2006.
15. Prophylaxis:
A prophylactic dose of Tamiflu was given to those who are undertaking the culling of birds. This drug has side effects.
16. Swine Flu (H1N1 Virus):
This novel Influenza 2009A/H1N1 virus contains a combination of 2 swine, one avian and one human influenza virus genes. Initially recognised in Mexico, swine flu or H1N1 influenza was declared as a pandemic by WHO on June 11, 2009. The virus had killed more than 19,633 people worldwide, whereas 1,632,258 laboratory confirmed cases were reported.
The global infection rate was 11-21% and case fatality ratio was 0.03%. Number of cases steeply declined since May 2010 and on 10th August, 2010 WHO announced the end of H1N1 pandemic. India had reported a widespread, low intensity epidemic with 29,599 confirmed cases and 2024 deaths. Cases occurred mainly in Maharashtra, Kerala, Karnataka, Andhra Pradesh and Delhi.