Influenza

DEFINITION
- Acute respiratory viral infection with aerogenic transmission mechanism, antroponosis, characterized by lesions of the upper respiratory tract with the development of intoxication and catarrhal syndrome.
Virus is pneumotropic belongs the family Orthomyxoviridae;
- contains of RNA, nucleocapsid, lipoglycoprotein envelop;
has a rounded or oval shape;
nucleocapsid has S - antigen, H-antigen (hemagglutinin),
N-antigen (neuraminidase),
- has tropicity to the upper respiratory tract;
- resistant to low temperature;
- sensitive to heat, boiling, ultraviolet irradiation, disinfectants.

INFLUENZA: A SERIOUS THREAT
Influenza infection is associated with high morbidity, significant economic costs and mortality!
5-10 %
5-10 %
adults and
20-30 %
children
Die from complications:
250 – 500 th.
people
Economic costs:
1- 6 mln $ USA
on 100 000 population
According to WHO suffer from the influenza every year:

SUBTYPES OF INFLUENZA VIRUSES
INFLUENZA А
15 types of hemagglutinin (H1 - H15)
9 types of neuraminidase (N1 - N 9)
Viruses on the difference of specific antigens of the nucleoprotein and matrix protein are divided into 3 types:
A, B and C.
Subtypes of influenza virus are isolated by antigenic variants of the surface glycoprotein
hemagglutinin (H) and neuraminidase (N)
Every change in the antigenic structure of surface glycoproteins causes the development of new pandemics and epidemics!

INFLUENZA VIRUSES: A, B and C
PANDEMIA
frequent EPIDEMICS associated with high morbidity and mortality
associated primarily with the virus
А
seldom
В
С
as a rule, is asymptomatic and does not affect the incidence

NATURAL RESERVOIRS OF INFLUENZA VIRUSES
Influenza А
Influenza В
Influenza С
birds, rare animals
only people
in humans, pigs, dogs

SEASONAL prevalence of INFLUENZA
THE PEAK OF MORBIDITY
Outbreaks of influenza coincide with the increase in the incidence of other ARVI!
Revealed a clear dependence of the level of INFLUENZA morbidity of the population of the CITY:
> 1 MLN
FROM 500 TH TILL 1 MLN
LESS 500 TH
< 11,3 %
10,9 %
9,7 %
THE AUTUMN-WINTER PERIOD
THE BEST SURVIVAL OF VIRUS IN AEROSOLS AT LOW TEMPERATURE
A CROWDING OF PEOPLE IN ENCLOSED ROOMS

RISK GROUPS FOR INFLUENZA
The INFLUENZA poses a serious DANGER primarily to:
The INFLUENZA can occur without fever, with scanty pulmonary symptoms, but with rapid, sometimes catastrophic, development of toxicity and complications, therefore, these portions of the population require special attention and control.
children first year of life
the elderly
persons with concomitant diseases of the heart, lungs, diabetes, other chronic diseases

INFLUENZA
The core of the virus contains single-stranded negative chain of RNA consisting of 8 segments that encode 10 viral proteins
Fragments of RNA have a general protein envelope, which unites them, forming a nucleoprotein
Nucleoprotein permanent in its structure and determines the virus type (A, B or C).
The surface antigens (H and N), in contrast, is variable and define different strains of the same type of virus.

The replication cycle of influenza virus
The replication cycle of influenza virus in the human body lasts about 4 hours and can be described as follows:
Hemagglutinin on the surface of the virus, binds to sialic acid on epithelial cells lining the respiratory tract.
1
The virus enters the epithelial cell by endocytosis and starts to multiply
2
The synthesis of new viral RNA and proteins, which are collected into viral particles occurs via the structures of the host cell
3
Viral particles are transported to the surface cells in the sheath which contains the hemagglutinin, neuraminidase and M2 channels.
4
Collecting of virions is completed, but they remain bound to cell surface via hemagglutinin and sialic acid.
5
The neuraminidase releases new viruses
which infect other cells
6

INFLUENZA : THE DEVELOPMENT OF THE PATHOLOGICAL PROCESS
epithelium of the respiratory tract
«ENTRANCE GATE»
involvement of intact cells
replication of the virus in the cells
structural changes, degradation, rejection of cells
Do not sneeze!

INFECTION WITH INFLUENZA VIRUSES
From a sick person, who is the source of the infection, the virus through coughing and sneezing transmitted to healthy people by aerogenic mechanism through airborne, air–dust way
and by contact–household route
the replication cycle of 4-6 hours
isolation of virus from the respiratory tract
STARTS 1-2 days before onset of symptoms
ENDS after 5 –7days after the disappearance of clinical manifestations

CLINICAL PICTURE OF INFLUENZA INFECTION
The sudden rise of body temperature (38-40°C);
Chills, dizziness, muscle pain, headache, weakness;
Rhinorrhea usually not observed, patients often complain of a feeling of dryness in the nose and throat;
In some cases there is a dry, hard cough accompanied by pain behind the breastbone;
2 days
Incubation period
3-5 days
CLIMAX (febrile) period
The total duration of disease is 7-10 days

CLINICAL PERIODS OF INFLUENZA
1
2
3
4
5
PENETRATION
VIREMIA
LOCAL DEMIGE
BACTERIOLOGIC COMPLICATION
IMMUNIC
INCUBATION: ASIMPTOMATICAL
CLIMAX: DEVELOPMENT OF COMPLICATIONS
CLIMAX: SPESIFIC SDs – CATARRHAL AND INTOXICATION
INITIAL: NONSPESIFIC SD – GENERAL INTOXICATION
CONVALESCENCE: DISAPPEARANCE OF LIDING SDs;
ASTENOVEGETATIVE SD

CLINICAL CLASSIFICATION OF INFLUENZA
OBLITERATED
FULMINANT
SEVERE
COMPLICATED
INFLUENZA
TYPICAL FORM
ATYPICAL FORM
MILD
MODERATE
UNCOMPLICATED

SEVERITY OF INFLUENZA
MILD
MODERATE
SEVERE
increase of body temperature
in the range of 38.5–39°C,
moderate intoxication,
weakness, headache
Hypertoxic form occurs only in influenza, accompanied by expressed hyperthermic, meningo - encephalitic and hemorrhagic syndrome !
body temperature can to remain
normal or not rise above 38°C,
the symptoms of intoxication
less expressed or absent
Increase of body temperature
up to 40-40,5°C,
dizziness, delirium,
seizures, hallucinations, vomiting

INFLUENZA : OUTCOMES OF VIRUS INTRODUCTION
LESIONS OF EPITHELIUM OF RESPIRATORY TRACT
SUPPRESSION OF FUNCTION
of mucociliary clearance
macrophages
T - lymphocytes
INFLUENZA VIRUS
NEURAMINIDASE OF INFLUENZA VIRUS
modifies cell surface glycoproteins
promotes the formation of new places for bacteria adhesion and the development of secondary purulent infection !

INTOXICATION at the INFLUENZA
From a place of primary localization of the influenza virus gets into the blood, causing viremia that resulted in severe intoxication.
Is characterized by:
increased permeability and fragility of blood vessels of different severity
- HEMORRHAGIC SYNDROME
- BLEEDING
HEMORRHAGES OF DIFFERENT
LOCALIZATION
Disturbance of MICROCIRCULATION
(until the development of DIC –
syndrome, infectious-toxic shock!)
SEVERE CASES:
In the development of the neurotoxic syndrome in influenza plays an important role disorder of cerebral hemodynamics and cerebral edema!
Intoxication at the influenza

Complications of the INFLUENZA
THE MOST COMMON:
PNEUMONIA
ACUTE BRONCHITIS
BRONCHIOLITIS
Influenza infection leads to EXACERBATION: chronic bronchitis/
chronic obstructive
pulmonary disease;
bronchial asthma;
mucoviscidosis;
PNEUMONIA DEVELOPS:
5-38% with influenza A
10 % with influenza B
Distinguish
- primary viral pneumonia
(developed as a result of direct viral infection of the lungs) and
- secondary bacterial pneumonia (bacterial superinfection can complicate the course of primary viral pneumonia, and or to be independent late complication of the flu).

Mortality from influenza and its complications takes the first place among all infectious diseases!
5-10 %
80 - 90 %
of patients older than 65 years in the structure of mortality from the flu
6 %
of deaths due to influenza in adults, young patients without apparent risk factors!
1/3
complications associated with influenza occur among people, healthy in all other indicators
Most cases of influenza in hospitalized patients are younger than 65 years
INFLUENZA : THE RISK OF COMPLICATIONS

ETIOLOGICAL DIAGNOSIS OF INFLUENZA
METHODS:
Etiologic diagnosis for most patients
in clinical practice is not possible (!),
due to technical difficulties, the complexity and relative high cost of virological and immunological methods.
During epidemics of influenza the performance of clinical diagnosis is high and reaches 70%!
the method of direct immunofluorescence
polymerase chain reaction – PCR
reaction of complement binding
enzyme-linked immunosorbent assay
virological method

DIFFERENTIAL DIAGNOSIS of colds and influenza
Non-specific diagnosis of influenza:
GBC: leukopenia, shift to the left formula, increased ESR;
urinalysis: leukocyturia, proteinuria, microhematuria,
cylindruria;
biochemical blood: the increase of urea, creatinine;
coagulogramm changes in severe forms;

DIFFERENTIAL DIAGNOSIS of colds and influenza

DIFFERENTIAL DIAGNOSIS of colds and influenza

DIFFERENTIAL DIAGNOSIS of colds and influenza

ways of influence the infectious process
IMMUNOCORRECTIVE THERAPY
PATHOGENETIC THERAPY
SYMPTOMATIC THERAPY
LEADING ROLE
have a direct effect
on the reproduction of the virus
and some
virus-specific target in its cycle
1st generation – amantadine and rimantadine
2 generation – zanamivir and oseltamivir
ETIOTROPIC DRUGS
SPECIFIC TREATMENT

RIMANTADINE
Limitation:
MECHANISM of ACTION: inhibition of the synthesis of M-protein of influenza virus, disrupts the process of reproduction and formation of complete virions.
rapid development of resistance in viruses (resistance);
narrow spectrum of activity (only influenza A);
common side effects;
SPECIFIC TREATMENT

one of the main enzymes involved in replication of
influenza viruses A and B.
Violates penetration of the virus into healthy cells
inhibites further spread of the virus in the body
THE ATTACK ON NEURAMINIDASE
INHIBITION
Reduces production of proinflammatory cytokines;
Prevents development of local inflammatory reaction;
Attenuates systemic symptoms of influenza (fever, myalgia);
SPECIFIC TREATMENT

mechanism of action of neuraminidase inhibitors
Primary
infection
Replication
viruses
Blockade of
neuraminidase
Violation of viral
replication and
distribution
NА
the sooner the better
NА
NА
NА

OSELTAMIVIR
Selective inhibitor of neuraminidase;
Inhibits the release of formed virus;
It is used to treat influenza A and B;
It is used to prevent influenza A or B in people
who had contact with patients
NEUROAMINIDASE
OSELTAMIVIR
SPECIFIC TREATMENT

TREATMENT
(Patients with mild forms can be treated ambulatory, with severe forms- should be hospitalized)
1. Bed rest;
2. Diet № 15, drink plenty of liquids;
3. Etiotropic treatment:
- anti-influenza gamma-globulin (3ml) - i/m in the first 3 days,
- interferon 2-3 drops every 1-2 h for 3 days,
- rimantadine – 1-st day: 0,1 g × 3 t/d,
2-nd day and 3-rd day: 0,1 g × 2 t/d;
- oseltamivir – 0,75 g × 2 t/d (5 days);
- zanamivir - 1 inhalation × 2 t/d
4. Pathogenic therapy: - desintoxication; - desensitization;
- angioprotectors; - metabolites;
5. Symptomatic treatment: antipyretics, vitamins, local antiseptics;
6. Antitussive drugs, mucolytics, vasoconstrictor nasal drops;
7. Antibiotics - in complications, exacerbation of chronic diseases

DIFFERENTIAL DIAGNOSIS of ARVI

DIFFERENTIAL DIAGNOSIS of ARVI

DIFFERENTIAL DIAGNOSIS of ARVI

DIFFERENTIAL DIAGNOSIS of ARVI