Nothing

1. Influenza and ARVI
Department of Infectious Diseases, Epidemiology and Immunology
JSC "Astana Medical University"
Prepared by senior lecturer Konkaeva M.

2. Title
Term «influenza» appeared due to astrologers:
–Italian «sotto l’influenza delle stelle» means «under
the influence of stars»
–First it was used in Italy in 1358 and meant diseases
under «influence» of stars or cold weather

3. History of influenza
• Firstly it was described by Hippocrates in fifth
century BC
• The earliest mention was appeared in 1770 in
English chronics
• Term “Influenza” was naturalized by the British
people during the epidemic in 1782
• The Russian name of disease- «грип(п)» -
was borrowed from French – “grippe”

4. Definition
• Acute respiratory viral
infection (ARVI) is a
widespread disease develops
in people of all ages with
variety of forms and severity of
clinical manifestations
depending on the degree of
intoxication and the level of
lesion of the respiratory tract.
• Influenza - an acute viral
infection characterized by
intoxication and defeat of
the upper respiratory tract
mucosa with prevalence of
tracheitis.

5. • SEASONAL INFUENZA - the influenza that occurs every year with
the gradual mutation of surface protein of the last year virus
(antigenic drift).
• BIRD INFLUENZA: The disease of birds that sometimes "jumps" to
other species and infect humans. In the near future, it is the source
of a new type of virus A, which can lead to a pandemic.
• PANDEMIC INFLUENZA: The outbreak of diseases in the whole
world, caused by the sudden new variation of surface protein of
virus A (antigenic shift, profound changes). Potentially affecting
hundreds of thousands of people.

6. Seasonal influenza (morbidity)
• Influenza is highly contagious
• 5% – 20% of population is infected with seasonal
influenza every year
– ~13% of patients are hospitalized
– Young, elder people and people with chronic
diseases are a strong group of risk
• Economic losses: morbidity with temporal disability,
disease incidence, mortality, medical expenses
– increased burden on the health care system

7. Virus of influenza Haemagglutinin
(15 subtypes)
Neuraminidase
(9 subtypes)
RNA of virus
M2
protein

8. Designation of influenza virus
A /Hong Kong/ 03/ 68 (H1N1)
Type
Detachment place
Strain number
Detachment year
Description of antygens

9. The influenza virus under the electronic microscope

10. Influenza A
• Causes the epidemic and pandemic
– 3-5 million cases of serious diseases every year and 300000-500000 of them
are fatal cases.
• Subtypes of influenza A are distinguished by a combination of two surface
glycoproteins:
– Haemaglutinin (HA) = 15 types
– Neuraminidase (NA) = 9 types
• All subtypes of virus A are circulating among wild birds
• Often people suffer from:
– H1N1, H1N2, H3N2 – are circulating among people at the present time

11. Influenza B and C
• Influenza B (mainly affects people)
– It may cause epidemic, but less dangerous that influenza A
– Serious outbreaks every 2-3 years
– Does not cause pandemic
– Influenza С has mild coarse, does not cause epidemic and
pandemic
• Antigenic changes continuously occur in the group of type A and
less in the group of type B, while type C is antigenically stable.

12. Potential reservoir of different subtypes of
influenza A
H15,16
H14
H13
H12
H11
H10
H3
H2
H1
H9
H8
H7
H6
H5
H4
N9
N8
N7
N6
N5
N3
N4
N2
N1

13. TRANSMISSION WAYS:
- Air-borne (in coughing when drop path length -1 meter)
- contact (through common use items infected by patients)
- Contagiosity peak – first 3 days after onset of disease

14. Transmission ways of seasonal
influenza
Direct aerosol contamination of
the respiratory tract mucus
through sneezing, coughing.
Indirect infection through
contaminated objects, people,
hands with following contact
entry of the virus in the nose
and eyes

15. The natural reservoir of all influenza A viruses are wild waterfowl birds.
The mortality rate from bird influenza is 40-65%
from pig influenza is - 0,007%

16. • SARS (Severe Acute
Respiratory Syndrome):
• SARS is diagnosed when the
disease has arisen during the
previous 7 days, requires
hospitalization and is
characterized by the following
symptoms:
• - fever ≥ 38ºC – in anamnesis,
• - cough,
• - shortness of breath or rough
breathing.
• INFLUENZA LIKE DISEASE:
• Acute respiratory disease
appeared in the preceding 7
days and characterized by the
following symptoms:
• - body temperature ≥ 38ºC (on
the results of measuring), and
also
• - cough .

17. Clinical classification of influenza and other acute respiratory
diseases (ARD):
• 1.1. Etiology.
• 1.1.1. Influenza of type А.
• 1.1.2. Influenza of type В.
• 1.1.3. Influenza of type С.
• 1.1.4. Parainfluenzal infection.
• 1.1.5. Adenovirus infection.
• 1.1.6. Respiratory-syncytial infection.
• 1.1.7. Rhinovirus infection.
• 1.1.8. Coronaviral infection.
• 1.1.9. Mycoplasmal infection.
• 1.1.10. ARD of bacterial etiology
• 1.1.11. ARVI of combined etiology (viral, viral-mycoplasmal,
viral-bacterial, mycoplasmal-bacterial).

18. Pathogenesis (1)
• The influenza virus is transmitted from person to person by airborne droplets or
by contact way through contaminated hands or surfaces.
• Epithelial cells of respiratory system are contaminated if the virus particles are
neutralized by immunoglobulin A or nonspecific inhibitors in mucous
secretions.
• Virions affect the adjacent cell, where the reproduction cycle is repeated.
• Viral neuraminidase decreases viscosity of mucous layer, opening the cell
surface receptors and contributing to the spread of liquid containing the virus in
the lower respiratory tract.
• Within a short time a large number of airway cells are affected and destroyed
by the virus.

19. Pathogenesis(2)
• The incubation period: from 1 to 4 days depending on the dose of virus
and host immune status.
• Spreading of the virus begins the day before the onset of symptoms,
peaks for 24 hours and remains high during 1-2 days, then decreases
over the next 5 days.
• Typically, the recovery occurs in about a week
• But can develop serious complications and death
• The virulent virus is very rarely isolated from blood.

20. Pathogenesis(3)
• Recovery occurs due to the action of interferon.
• Interferon is detected in the respiratory secretions of about
one day after the start of spreading the virus.
• Specific antibodies and cellular immune response are
detected during the following 1-2 weeks.

21. Pathogenesis(4)
• The virus destroys the cells on the surface of the respiratory tract
mucosa, but does not affect on the basic layer of the epithelium.
• Full restoration of cellular damage occurs within 1 month.
• Viral damage of airway epithelium reduces its resistance to
secondary bacterial infections, especially the invasion of
staphylococci, streptococci and Haemophilus influenzae.
• Develops edema and infiltration with mononuclear cells
• Severe intoxication is associated with cytokine production.

22. Forms of clinical course of disease
• Asymptomatic.
• Mild.
• Moderate.
• Severe.
• Extra severe.
FORMS: typical, atypical (acatarrhal, apyretic)

23. Protection
• It correlates with both antibodies in serum and with the
immunoglobulin class antibodies in nasal secretions.
• Serum antibodies persist up to several years, while secretory
antibodies persist for several months.
• Antibodies also change the course of the disease.
– A person with low antibody titer can be infected but the disease
has a mild coarse in this case.
• Immunity can not protect against new infections, there are cases of
reinfection with the same virus.

24.  pregnant women, patients with influenza and
ARVI, regardless of severity, in any stage of
pregnancy:
 pregnant women up to 30 weeks hospitalized in
the infectious hospital,
 pregnant women for more than 30 weeks should
hospitalized in perinatal center or if she has
signs of pneumonia - in the pulmary department.

25. Diagnostic measures carried out by emergency medical
care department:
• complaints and anamnesis;
• epidemiological anamnesis;
• physical examination.

26. Laryngitis (parainfluenza virus)
ss (-) RNA viruses
Enveloped viruses with hemagglutinin and
neuraminidase spikes and fusion (F) protein
Helical symmetry
4 types: 1, 2, 3, 4a, 4b

27. Clinical features of parainfluenza (PIV)
Incubation period is 2 to 6 days.
Clinical symptoms: Rhinitis, pharyngitis, cough, fever, croup
(laryngotracheobronchitis), bronchiolitis, and pneumonia.
Croup - the subglottic region becomes narrower and results in
difficulty with breathing, a seal bark-like cough and hoarseness.
There is clinical variation between the different PIV types.
PIV-1 and 2: croup in children ages 2-6 years in autumn/early winter.
PIV-3: bronchiolitis and pneumonia, and croup sporadically, without a
particular seasonal occurrence.
PIV-4: mild upper respiratory infections.

28. LABORATORY DIAGNOSIS OF PARAINFLUENZA
1. Detection of antigen from nasopharyngeal aspirates and
throat swab by IF and PCR.
2. The virus isolation in cell culture.
Indication: Haemadsorption of erythrocytes on the surface
of cells infected with virus.
Identification: HadsI, HAI, NtT, CFT.
3. Serology – detection of rise in titer of IgG in pared sera:
NtT, ELISA, CFT, HAI.

29. Unique features of Adenoviruses
• Double-stranded linear(+)DNA.
• Naked icosahedral capsid has fibers (viral attachment
proteins) and vertices.
• 47 human serotypes Viruses cause: lytic, persistent,
latent infections in humans, some strain can immortalize
certain animal cells.

31. Pathogenesis of adenoviruses infections
• Virus is spread: by aerosol, direct contact, fecal-oral.
Virus infects: epithelial cells in respiratory and
gastrointestinal tract, conjunctiva and cornea.
• Virus persists in lymphoid tissue (tonsils, adenoids,
Peyer’s patches).

37. Drug-free treatment
- Bed rest for a period of fever, then the regime can be
extended when symptoms of intoxication decrease;
- Diet - easily digestible food and plenty of drink.

38. Drug treatment (on the stage of out-patient department)
Treatment of influenza (administered in the first 2-3 days during onset
of disease): Antiviral drugs are not related to the neuraminidase
inhibitors (administered in the first 2-3 days of the onset of the disease,
one of the following):
• - Imidazolyl ethanamide pentandioic acid (Ingavirin) 90 mg daily during 5
days;
- Inosine pranobex (groprinosin) 0.5 in the first 2 days of the onset of illness
(2 tab. x 3-4 times per day during 5 days);
- Rimantadine – the first day - 100 mg x 3 times per day, the second and
third days 100 mg x 2 times, 4-5 days 1 x 100 mg once;
- Oxolinic ointment 0.25% - lubrication of the nasal passages from the first
days of the disease;

39. Interferon and inductors of endogenous interferon synthesis (administered
in the first 2-3 days after onset of disease):
• - Tilorona the first two days of the disease - 125mg once a day, then 125 mg
every 48 hours. Course dose is 750 mg (6 tablets);
• - Interferon alfa-2b, recombinant 500,000 IU 1 suppository x 2 times per day
every 12 hours daily. The course of treatment - 5-10 days;
• -Affinity purified antibodies to human interferon gamma - (a combination of
homeopathic dilutions C12, C30 and C200) 1 tablet sublingually 3 times per
day up to 6 (5 days).

40. ARVI Treatment (administered in the first 2-3 days of onset):
Antiviral drugs are not related to the neuraminidase inhibitors:
• - Imidazolyl ethanamide pentandioic acid (Ingavirin) 90 mg daily during
5 days;
• - Inosine pranobex (tab. 500mg) in the first 2 days of the onset of
disease; 2 tab. x 3-4 times per day during 5 days;
• - Oxolinic ointment 0.25% - lubrication of the nasal passages from the
first days of the disea
Interferon and inductors of endogenous interferon synthesis
(administered in the first 2-3 days of onset of disease): as well as in
infuenza.

41. Pathogenetic and symptomatic treatment - according to
indications:
- detoxication therapy: mild and moderate coarse of disease – plenty of
drinking (20-40 ml / kg per day in the form of tea, fruit and vegetable
juices, fruit drinks and water).
- antipyretic drugs (NSAIDs);
- vasoconstrictor nasal drops and sprays;
- antitussives and expectorants.

42. Development of bacterial complications
• When we cannot hospitalize a patient.
• We should prescribe antibiotic therapy with the inclusion of semi-
synthetic penicillins, cephalosporins of III-IV generation,
ftoroquinolones and carbapenems. In the cases with a high
probability of complications of staphylococcal etiology, antibiotic
of choice is vancomycin.

43. Specific guidance for antiviral treatment of pregnant women
 Treatment should be started as soon as possible: within 48 hours after onset of
disease.
 Laboratory confirmation of influenza is not important.
 Oseltamivir (Tamiflu) - drug of choise from the group of neuraminidase
inhibitors - 75 mg (1 capsule) two times per day during 5 days; in severe /
complicated forms of influenza the dose can be increased up to 150 mg x 2
times per day (in this case - coarse of treatment up to 10 days).
 Treatment with antiviral drugs of pregnant women with severe or progressive
course of the disease in the cases when they visited a doctor after long period
of time after onset of disease should be started later.

44. • If we cannot use oseltamivir, we should use zanamivir (powder for
inhalation 5 mg / dose); (starting from the 12th week of pregnancy); 2
inhalations (2 × 5 mg) 2 times per day during 5 days.
• The use of antibiotics in pregnancy is possible only in cases where the
effect of therapy outweighs the potential risk for the fetus. In
hospitalized patients the choice of route of administration is determined
by the severity of the condition and characteristics of the drug: for non-
severe infections possibly oral administration of antibiotics, in severe
cases, patients should receive antibiotics intravenously.

45. Recommended dosages of some antiboitics
- Amoxycillin/clavulanate – i/v 1,2 g every 8 hours; 1,0г х 2 times
per day, enteral or 0,625 х 3 times per day.
- Cefoperazone/sulbactam – 1-2 g, every 8-12 hours;
- Josamycin 1,0 х 2 times per day
- Ceftriaxone – 1-2 g, one time per day i/v;
- Cefotaxime – 1-2 g, 2-3 times per day i/v;

46. Preventive measures
Seasonal vaccination against influenza virus.
- Epidemiology:
 isolation of patients.
 Ventilation of room.
 Wet cleaning with using a 0.5% solution of chlorine,
 in medical institutions, pharmacies, shops and other service facilities,
staff should work in masks.
 The staff should systematically turn on ultraviolet lamps and ventilate
rooms of hospitals, doctors' offices and hospital corridors.
 For patients in hospitals are organized separate compartments with
separate entrance and own wardrobe.

47. Patient I., 21 years old, student. In the past, she was not sick. On the eve I felt
satisfactory, on the day of the disease I was in class. The first clinical symptoms
were chills, headache, fever up to 40 ºС, anxiety, vomiting, pain in bones and joints.
She spent the night very restless: she threw herself around, drank water eagerly,
complained of pain in her whole body, especially in her legs.
By morning, excitement, confusion appeared. A rash was noticed by others. An
ambulance was called.
Objectively: the temperature is 39.4 ºС, the consciousness is preserved, restless,
the limbs are cold, the nails are blue, large blue spots on the body and face. Against
them is a profuse rash in the form of major hemorrhages.
The pulse is not palpable. BP is not determined. Stiff neck no.
You are an emergency doctor. Justify and formulate a preliminary diagnosis. Make a
therapy plan.

48. Treatment efficacy indicators:
- Relief of symptoms of intoxication and catarrhal
syndrome;
- Relief of exacerbations

49. THANK YOU FOR ATTENTION!