INFLUENZA

Lecture was prepared by

Candidate of Medicine, assosiate professor of Sumy State University

Zakhlebaeva V.V.

INFLUENZA – sharp respiratory virus disease with the air-drop mechanism of the transfer, characterised by the sharp beginning, primary defeat of the upper respiratory ways and the general intoxication

Actuality:

• The Most widespread infection, is registered on all continents.

•Improbable speed of distribution - for 1,5-2 weeks - covers a city.

•During epidemic 30-50 % of the population fall ill.

•The Flu – an uncontrollable infection.

•Ability of a virus of a human flu to exchange the genetic information with agents of an avian flu and of an animals flu demands the further studying of a flu.

etiology• Belongs to the group of orthomyxoviruses.

• Has the spherical form, diameter of 80-120 nm;

The kernel contains RNA and ribonucleid, defining an accessory to types A, B, C.

• The kernel is surrounded by a membrane, which consists of a double lipid layer and of a membrane fiber.

• The Cover contains hemagglutinin (HA) and neuraminidase (NA).

• Hemagglutinin and neuraminidase are factors of aggression of a virus of a flu.

• Hemagglutinin defines an intoxication, neuraminidase renders immunosuppresive action.

• The flu Virus has 12 types НA and 9 types NA. HA 1,2,3 types and NA 1,2 types are peculiar to viruses of a flu of the person.

• NA and HA have high changeability. Antigene drift – little changes in structure HA, it is carried out continuously, from year to year. Full replacement НA and NA a new antigene variant is called as antigene shift. Shift registered 1 time in 10 - 12 years.

Viruses are unstable in an environment, and dies at a room temperature in couple hours. At 50-600С inactivated in few minutes, at freezing remains for years

Influenza A viruses:

Influenza A viruses includes avian,swine, equine and canine influenza viruses, as well as the human influenza A virus. Influenza A viruses are classified into 2 subtypes based on their surface antigens H and N proteins. There are 16 hemagglutinin antigens (H1-H16) and 9 Neuraminidase antigens( N1-N9). These 2 proteins are involved in cell attachments and released from cells, and are also major targets for new response. Only limited subtypes are found in each species of mammal. Influenza A viruses are also classified into strains. Strains of Influenza viruses are described by their type, host, place of first isolation, strain number, year of isolation and antigenic subtype.

Antigenic shift and drift in Influenza A viruses:

• Influenza A viruses change frequently. Strains evolve as they accumulate point mutations during virus replication; this process is sometimes called ‘antigenic drift’. A more abrupt change can occur during genetic reassortment. Reassortment is possible whenever 2 different influenza viruses infect a cell simultaneously. Reassortment between 2 subtypes can result in the emergence of a new subtype. Reassortment can also occur between avian, swine, equine, canine and human influenza A virus resulting in a ‘hybrid’ virus , for example both avian and human influenza virus proteins

• An abrupt change in the subtypes found in a host specie is called an “antigenic shift”

Antigenic shift can result from 3 mechanisms;

• Genetic reassortment between subtypes.

• The direct transfer of a whole virus from one host species to another.

• Re-emergence of a virus that was found previously in a specie, but is no longer in circulation. E.g Human viruses can continue to circulate in pigs and could re-emerge into human population

Antigenic shift and drift can result in periodic emergence of novel influenza viruses. By evading the immune response, these viruses can cause influenza epidemics and pandemics.

Avian influenza virusAvian influenza viruses circulates in a variety of domesticated and wild birds.

They are isolated occasionally from mammals including humans. They are classified as either high pathogenicity (HPAI) or low pathogenicity (LPAI) viruses based on genetic features of the virus and the severity of disease in experimentally inoculated chickens. HPAI viruses usually cause severe disease in poultry while LPAI are generally much milder. HPAI viruses contain the H5 or H7 hemagglutinin ; subtypes that contained other hemagglutinins have been found only in the LPAI form .

SWINE INFLUENZA VIRUSES• This mainly affects pigs but they can cause disease in turkeys. Outbreaks

have been described recently in FERRETS and MINK. One H1N1 swine influenza virus which was avirulent for both poultry and pigs was isolated from a dog in HONGKONG and experimental infections have been reported in calves. The most common subtypes currently found in pigs are H1N1, H1N2, H3N2; however the situation is complex as two or more viruses of each subtype are circulating in swine populations. One H1N1 virus found in North America is the “classical” H1N1 swine influenza virus. This virus, the first influenza virus known to have infected pigs was first detected in swine population in 1918. An “asian -like” H1N1 virus circulates mainly in European pigs.

• In North America some of the most important swine influenza viruses are the triple reassortant H3N2 viruses. These viruses first emerged in the US pigs in the late 1990s, mainly in the mid-west and they have been detected in Canada since 2005. The H3N2 triple reassortant viruses contain hemagglutinin and neuraminidase proteins from a human influenza virus and internal proteins from the classical swine influenza virus, an avian influenza virus and a human influenza virus. The particular combination of internal genes carried by these viruses is known as the triple reassortment internal gene (TRIG) cassette..

• The H1N2 viruses in the US is a reassortant of the classical H1N1 swine influenza virus and the North American triple reassortant H3N2 virus. The H1N2 virus in Europe is a reassortant of a human H1N1 virus and the human-like European H3N2 virus.

• New subtypes have also been found in some swine populations. The novel subtype H3N1 has recently been isolated from pigs in the US. This subtype appears to contain genes from human, swine and avian influenza viruses. A different H3N1 influenza virus containing human and swine influenza virus genes has been found in Korea.

The NOVEL H1N1 VIRUS OF SWINE ORIGIN.• In 2009, a novel H1N1 virus which seems to have originated from one or

more swine influenza viruses emerged in human populations. This virus appears to be a reassortant between north America and Eurasian swine influenza viruses. It contains a hemagglutinin gene that is most closely related to swine influenza virus in North America, a neuraminidase gene that is related to swine influenza viruses in Eurasia and internal genes from two or more swine influenza viruses including the North America triple reassortant H3N2 viruses and the Eurasian virus.

HUMAN INFLUENZA A VIRUS.

• These are mainly found in people , but they can also infect ferrets and sometimes swines.

• Human viruses can also replicate to a limited extent in the nasal epithelium of experimentally infected horses. H1N1,H1N2 and H3N2 viruses are currently in general circulation in humans. H1N2 viruses were first seen in human population in 2001, probably as a result of genetic reassortment between the H3N2 and H1N1 viruses. H2N2 viruses circulated in the human population between 1957 and 1968. A novel H1N1 virus emerged in human population in 2009.

• Human influenza viruses change frequently as a result of antigenic drift, and occasionally as a result of antigenic shift. Human pandemics resulting from antigenic shifts were most recently reported in 1918, 1957, 1968 and 2009.

Influenza A viruses in other species .

• These viruses are occasionally isolated from outbreaks or isolated cases in other species of mammals.

• Avian influenza viruses have infected pinnipeds, cetaceans and mink; and swine influenza viruses have caused outbreak in mink and ferrets. Antibodies to influenza viruses have been detected in other species including raccoons, cattle , yak, sheep, goats , reindeers, and deer and a variety of mammals have been infected experimentally.

INFLUENZA B VIRUS.• Influenza B viruses are known to circulate only in human populations.

• These viruses can cause epidemics, but they have not till date been responsible for pandemics.

• They have also been found occasionally in animals. Influenza B viruses are categorized into lineages rather than subtypes. They are also classified into strains. These viruses undergo antigenic drift, though it occurs more slowly than in influenza A viruses. Until recently, the B/Victoria/2/87 lineage predominated in the human populations, and influenza B viruses were said not to undergo antigenic shift. In the 1990s, viruses of the B/Yamagata/16/88 lineage circulated to a very limited extent in Asia. This lineage emerged in various parts of the world in 2001 and it is now co-circulating with the B/Victoria/2/87. Recent evidence suggests that recombination between this two lineages is resulting in antigenic shifts.

INFLUENZA C VIRUSES• These viruses circulate in human [populations and are mainly associated

with diseases in people. Until recently, they had never been linked to large scale epidemics. However, a nation-wide epidemic of influenza C was reported in Japan between January and July 2004. These viruses have also been found in animals. They are not classified into subtypes but into strains. Each strain is antigenically stable , and accumulates few changes over time. Recent evidence suggest that reassortment occurs frequently between different strains of influenza C viruses.

Epidemiology:• An infection Source – the sick person or a virus carrier (that is not proved).

• The person in the first 2 days of disease is most infectious.

• The Virus of a flu A have most changeable antigen. It causes annual seasonal lifting the diseases everyone of 2-3 years – the epidemic flashes everyone of 10-30 years – pandemics (owing to antigene shift).

• The flu Virus B does not cause a pandemic. Causes disease lifting once in 3-4 years, epidemics – in 5-7 years.

• The Virus of a flu C causes sporadic cases.

• The transfer Mechanism – air-drop.

• The Susceptibility – very high in all age groups.

• Seasonal prevalence - in winter months.

Pathogenesis:1. Penetration and virus reproduction into cells of the upper respiratory ways. The main target of a virus – cylindrical ciliated epithelium. The virus overcomes factors of nonspecific resistance of the upper respiratory ways:

• Viscous properties of slime;

• Constant movement of ciliated epithelium;

• Nonspecific inhibitors of a virus replication;

• Macrophages;

• Ig A;

• Interferons.

2. A virus exit in intercellular space, destruction of the damaged cells – catarrhal syndrome, virusaemia;

3. virusaemia, toxaemia – neurotoxic action, a fever, capillarotoxicosis, immunosuppresion, defeats of organs, a secondary infection, complications;

4. recovering, immunity formation.

Flu classification1. Serological virus type: A (H1N1, H2N2, H3N2), B, C.

2. Clinical forms:

• Typical (intoxication syndromes, catarrhal)

• The atypical:

a) without high temperature;

b) without catarrhal sympthoms;

c) fulminant.

3. On severity of disease: light, medium, hard, hypertoxic.

4. On presence of complications:

• With complications: a sinusitis, an otitises, a meningitis, an encephalitis, a myocarditis, a pneumonia, a bronchiolitis, a bronchitis, a pyelonephritis.

• Without complications.

The diagnosis:

Flu A (H2N2), the typical form, an easy current.

Clinic1. The incubatory period from several hours till 1 days;

2. Allocate 2 basic of a syndrome – intoxication and catarrhal;

3. The beginning is sharp; a fever;

4. The temperature raises to 39-40 0C;

5. The maximum expressiveness of illness in the first day;

6. A headache sharp in fronto-temporal and eyebrow areas;

7. A photophobia, a pain in the eyeballs, amplifying at their movement;

8. Muscular pains, weakness, adinamia;

9. Hyperemia of face, an injection of vessels of white of the eye;

10. A herpetic rash on lips and nose wings;

11. Bright hyperemia of mucous of oropharinx;

12. Granularity of a back wall of pharynx (Morozkin’s symptom);

13. A tachycardia, systolic noise on a top of the heart, a hypotonia;

14. Since 2-3rd day moderately expressed a catarrhal syndrome;

15. A tracheitis;

16. The temperature keeps 2-3 days, then decreases critically or by truncated lisis

• Uncomplicated infections with human influenza A or B viruses are usually characterized by upper respiratory symptoms, which may include fever, chills, anorexia, headache, myalgia, weakness, sneezing, rhinitis, sore-throat and non-productive cough.

• Diarrhea , abdominal pain and photophobia are also possible. Most people recover in 1-7 days, but in some cases the symptoms may last up to two weeks or longer.

• More severe symptoms including pneumonia can be seen in some individuals especially those with chronic respiratory or heart disease. Secondary bacterial or viral infections may also occur. In addition, influenza A had been associated with encephalopathy, transverse myelitis, Reye syndrome, myocarditis , pericarditis and myositis. Because influenza C viruses are difficult to isolate, there are few reports on their clinical features.

• Some recent descriptions suggests that clinical cases may be indistinguishable from influenza A or B. In one recent study, the most common clinical signs were fever, cough and rhinorrhea, but 29 of 179 children were hospitalized with more serious illnesses such as pneumonia, bronchitis or bronchiolitis. Serious disease was most common in children less than 2years of age. Fever and cough were the most common signs in 14 patients from France, with rhinitis, pharyngitis, wheezing, and otitis in some individuals.

• In most people , the novel H1N1 virus causes a relatively mild illness which resembles the disease caused by other human influenza viruses. Vomiting and diarrhea have been reported in a significant number of cases. Most people have self limiting illness , and recover within a week . Severe primary viral pneumonia or acute respiratory distress syndrome occur in a small percentage of cases and maybe fatal. Patients who become severely ill usually begin to deteriorate 3-5 days after the onset of the symptoms, and their condition rapidly becomes serious, often progressing to respiratory failure within 24 hours.

• Multiple organ failure may be seen. Like other influenza viruses, the novel H1N1 virus can also exacerbate chronic medical conditions, especially respiratory diseases such as asthma or COPD and some cases maybe complicated by secondary bacterial infection.

Flu complications

1. The complications caused by direct action of a virus: toxic hemorrhagic hypostasis of lungs, a false croup, glomerulonephritis, a brain hypostasis, arachnoiditis, a Rey’s syndrome; a syndrome of sudden death;

2. The Complications caused by a secondary infection: a pneumonia, diseases of LOR-ORGANS (a sinusitis, an otitis, a pharyngitis, an antritis, etc.).

CRITERIA OF THE DIAGNOSIS

Flu Diagnostics1. The REEF (slime from oropharynx);2. Virologic research on a chicken embryo;3. Serological research – HAR, RHAI,CB;4. The immunefluorescent method.

1.

1. The epidemiological diagnosis (disease lifting in a cold season);2. A sharp, sudden onset of the illness;3. Prevalence intoxication over a catarrhal syndrome (tracheitis);4. Appearance of the patient («face of the tear-stained child»);5. Poured hyperemia an oral cavity mucous membrane;6. Leucopenia with relative lymphocytosis at normal ERS.

Flu treatmentHospitalisation – on epidemical indications (hotel accommodation, a hostel) and clinical (a heavy current with hypertermia, meningeal symptoms, vomiting, spasms, etc.,).

Etiotropic therapy:

Remantadin: 1 days 0,1 г х 3 times, 2 and 3 days on 0,1 g х 2 times a day;

Antiinfluenza gamma-globulin – on 3-6 ml х 2 times a day in muscle;

Interferon leukocytic or recombinant α - interferon (inhalations, drops in a nose);

0,25 % oxolini ointment in nasal courses.

• Children of first 2 years of a life and elder people

•Supportive care for uncomplicated Influenza in humans include fluids and rest. More severe cases or infectious that have an elevated risk of complications may be treated with anti viral drugs.

Four(4) drugs are used to treat Influenza, they are Amantadine, Rimantadine, Zanamivir, and Oseltamivir.

•Amantadine and Rimantadine (Adamantanes) are active against human influenza A viruses if treatment is begun within the first 48 hours.

•Zanamivir and Oseltamivir are effective for both Influenza A and B. Side effects including neuropsychiatric events may occur.

• Testing must be done to determine each individual drug susceptibility. Drug resistance develops rapidly in viruses exposed to Amantadine and Rimantadine and may emerge during treatment.

• During the 2006 to 2008 flu seasons, human influenza viruses circulating in the US and Canada exhibited high resistance to Rimantadine and Amantadine. The CDC recommends that this two (2) drugs be avoided until the circulating strains become susceptible again.

• Laboratory studies have shown that influenza viruses can also become resistant to Zanamivir and Oseltamivir, however this appears to be less common than resistance to Rimantadine.

• The novel (swine origin)H1N1 virus circulating among humans in 2009 is resistant to Amantadine and Rimantadine but sensitive to Oseltamivir and Zanamivir.

• Oseltamivir appears to increase the chance of survival in patients infected with asian lineage H5N1 viruses, particularly if it is given early. These viruses are resistant to Amantadine and Rimantadine. Although resistance to Zanamivir and Oseltamoivir has also been reported in H5N1 viruses, it is currently uncommon

Pathogenetic therapy:

• Light febrifugal at very high temperature (analginum, мефенамовая acid, ibuprofen,paracetamol);

• Plentiful drink (2-2,5 l a day) from broths and infusions of medicinal grasses (lime colour, tea with a lemon, a raspberry, a cranberry);

• Mustard plasters (is reflex improve blood circulation in respiratory organs);

• Ascorbic acid, ascorutin;

• Antihistaminic preparations (Tavegil, Diasolin);

• Immunomodulators (Methyluracil 0,5 г х 4 times a day, 4-5 days; Amizon 0,25 г х 3 times a day, 5 days; Arbidol, etc.);

• Mucolytic (a grass of thermopsis, mucaltin, АCC, etc.)

Indications for prescription of antibiotics at flu:

• Chronic centre of an infection;

• Signs of joining of a secondary infection (complication);

• The long fever (more than 5 days);

Flu preventive maintenance

Nonspecific seasonal preventive maintenance: training, vitamins, adaptogens (tincture элеутерококка, заманихи, эхинацеи), immunomodulators (мефенамовая acid, Arbidol, Amozon, Interferon, Amixin, etc.).

Specific preventive maintenance: an antiinfluenza vaccine "Vaksigripp" (France), "Fljuariks" (Belgium), "Influvak" (Netherlands), "Grippol" (Russia), «Infiksal In» (Switzerland). The vaccine contains epidemicaly actual types a virus of a flu of 3 types, recommended the CART for an epidemic season.

Thank You for Thank You for attention!attention!