Презентация на тему: INFLUENZA

INFLUENZA
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mechanism of action of neuraminidase inhibitors
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INFLUENZA

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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.

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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:

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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!

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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

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

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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 % 1 0,9 % 9,7 % THE AUTUMN-WINTER PERIOD THE BEST SURVIVAL OF VIRUS IN AEROSOLS AT LOW TEMPERATURE A CROWDING OF PEOPLE IN ENCLOSED ROOMS

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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

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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.

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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

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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!

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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

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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

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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

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

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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

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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 !

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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

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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).

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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

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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

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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;

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DIFFERENTIAL DIAGNOSIS of colds and influenza SIGN ARVI INFLUENZA ONSET GRADUAL ACUTE SOMETIMES SUDDEN FEVER MILD INCREASE OF TEMPERATURE TO 38.5º THE MAXIMUM LEVEL (HECTIC) IS ACHIEVED IN A FEW HOURS. PERSISTS FOR 3-4 DAYS INTOXICATION MODERATE OR ABSENT EXPRESSED, INCREASES RAPIDLY: CHILLS, SWEATING HEADACHE MILD, MODERATE SEVERE, LOCALIZED IN THE FRONTO-TEMPORAL REGION MYALGIA ARTHRALGIA MILD OR ABSENT SEVERE FATIGUE WEAKNESS MILD OR ABSENT EXPRESSED, PAIN IN THE SMALL AND MEDIUM JOINTS

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DIFFERENTIAL DIAGNOSIS of colds and influenza SIGN ARVI INFLUENZA RUNNY NOSE TYPICAL ABSENT NASAL CONGESTION SELDOM OFTEN SNEEZING OFTEN NONTYPICAL CATARRHAL SYNDROME OF THE OROPHARYNX GRAININESS, MODERATE REDNESS AND SWELLING ON THE 2-3-d DAY BRIGHT HYPEREMIA OF OROPHARYNX AND SOFT PALATE SORE THROAT MODERATE SEVERE EYE SYMPTOMS LACRIMATION PAIN WHEN MOVING THE EYEBALLS, PHOTOPHOBIA, BURNING, SCLERITIS, CONJUNCTIVITIS

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DIFFERENTIAL DIAGNOSIS of colds and influenza SIGN ARVI INFLUENZA COUGH DRY, LATER MOIST APPEARS ON 2ND DAY DRY PAINFUL, ACCOMPANIED BY PAIN BEHIND THE BREASTBONE ASTHENOVEGETATIVE SYNDROME INSIGNIFICANT FATIGUE, WEAKNESS, HEADACHE, INSOMNIA FOR 2-3 WEEKS DURATION 5-7 DAYS 7-10 DAYS COMPLICATION RARELY: ACUTE SINUSITIS OTITIS OFTEN ACUTE BRONCHITIS PNEUMONIA

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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

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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

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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

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Слайд 37: 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

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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

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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

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DIFFERENTIAL DIAGNOSIS of ARVI SIGN INFLUENZA PARAINFLUENZA ADENOVIRUS INFECTION RESPIRATORY SYNCYTIAL INFECTION RHINOVIRUS INFECTION LEADING SYNDROME OF DAMAGE TRACHEITIS LARYNGITIS RHINOPHARYNGITIS CONJUNCTIVITIS TONSILLITIS BRONCHIOLITIS RHINITIS INCUBATION A FEW HOURS TO 1-2 DAYS 2-7 DAYS OFTEN 3-4 DAYS 4-14 DAYS 3-6 DAYS 2-3 DAYS ONSET ACUTE GRADUAL GRADUAL GRADUAL ACUTE CURRENT ACUTE SUBACUTE LINGERING, WAVY SUBACUTE SOMETIMESLINGERING ACUTE INTOXICATION SEVERE MILD MODERATE MODERATE MODERATE MILD OR ABSENT

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SIGN INFLUENZA PARAINFLUENZA ADENOVIRUS INFECTION RESPIRATORY SYNCYTIAL INFECTION RHINOVIRUS INFECTION DURATION OF INTOXICATION 2-5 DAYS 1-3 DAYS 8-10 DAYS 2-7 DAYS 1-2 DAYS BODY TºC HECTIC 37-38C MAY LONG REMAIN FEBRILE SUBFEBRILE NORMAL OR SUBFEBRILE CATARRHAL SYNDROME MODERATE EXPRESSED EXPRESSED FROM THE 1-st DAY, HOARSENESS EXPRESSED FROM THE 1-st DAY EXPRESSED INCREASE GRADUALLY EXPRESSED FROM THE 1-st DAY RINITIS NASAL CONGESTION NASAL CONGESTION ABUNDANT SEROUS DISCHARGE DIFFICULTY IN NASAL BREATHING SCUNTY SEROUS DISCHARGE STUFFY NOSE ABUNDANT SEROUS DISCHARGE DIFFICULTY IN NASAL BREATHING DIFFERENTIAL DIAGNOSIS of ARVI

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SIGN INFLUENZA PARAINFLUENZA ADENOVIRUS INFECTION RESPIRATORY SYNCYTIAL INFECTION RHINOVIRUS INFECTION COUGH DRY WITH PAIN BEHIND THE BREASTBONE UP TO 7-10 DAYS, ON 3-d DAY MOIST DRY BARKING COUGH UP TO 12-21 DAY MOIST DRY PAROXYSMAL COUGH UNTIL 3 WEEKS ABSENT OR TICKLE THE CHANGE IN THE OROPHARYNGEAL CAVITY NJECTION OF VESSELS OF MODERATE HYPEREMIA MILD OR MODERATE HYPEREMIA MODERATE HYPEREMIA EDEMA HYPERPLASIA OF THE FOLLICLES OF THE TONSILS, POSTERIOR PHARYNGEAL WALL MILD HYPEREMIA MILD HYPEREMIA DIFFERENTIAL DIAGNOSIS of ARVI

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SIGN INFLUENZA PARAINFLUENZA ADENOVIRUS INFECTION RESPIRATORY SYNCYTIAL INFECTION RHINO-VIRUS INFECTION LYMPHADENOPATHY ABSENT NONTYPICAL GENERALIZED INCREASE PARATRACHEAL AND PARABRONCHIAL LYMPH NODES ABSENT HEPATOSPLENOMEGALY ABSENT ABSENT PRESENT ABSENT ABSENT EYE DAMAGE NJECTION OF VESSELS, SCLERITIS, BILATERAL CONJUNCTIVITIS ABSENT ONE-SIDED CONJUNCTIVITIS ABSENT ABSENT DIFFERENTIAL DIAGNOSIS of ARVI

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Последний слайд презентации: INFLUENZA

Strict adherence to sanitary-hygienic regime in the epidemic and pre-epidemic period, regular general wet cleaning, bactericidal air disinfection. 2. The use of personal protective equipment ( disposable masks ). 3. Specific prevention (vaccination). Routine immunization can be carried out throughout the year, but the greatest its effectiveness in the autumn before the influenza season. 4. Nonspecific prevention of influenza and ARVI aimed at increasing the general resistance of the human body: - improvement of immune status with immunomodulators ; - promotion of healthy lifestyle, tempering; - creation of favourable temperature in the room; PROFILAXIS OF INFLUENZA

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