Adobe Systems Department of infectious diseases, Masaryk univerzity, Univerzity hospital Brno 1 Influenza Avian influenza Tomáš Gergel Adobe Systems 2 Influenza •segmented RNA viruses, family Orthomyxoviridae •Influenzavirus A - seasonal epidemics and pandemics •Influenzavirus B - milder, small epidemics •Influenzavirus C - pigs, dogs, less common, „common cold“ •Influenzavirus D - pigs, cattle, no human infection was reported • Image of the influenza virus Adobe Systems 3 Epidemiology •the illness occurs in outbreaks and epidemics worldwide •mainly during the winter season •self-limited infection in the general population •associated with increased morbidity and mortality in certain high-risk populations (cardiovascular ilnesses, chronic respiratory tract illnesses, immunocompromised patients,…) • •CDC + WHO track influenza virus isolates throughout the world → monitor disease activity → predict the appropriate components for the annual influenza vaccine ̶ Adobe Systems 4 •infected >10% world population anually •5 millions of sever cases / year •0,5 million deaths / year •in Czech republic 3000 deaths / year Image of the influenza virus Adobe Systems 5 https://en.wikipedia.org/wiki/File:Viruses-12-00504-g001.webp Adobe Systems 6 •2 large surface antigens - glycoproteins • •Hemagglutinin - HA (H1-H18, humans only H1-H3) •binding the viral particle to the host cell • •Neuraminidase - NA (N1-N11, humans only N1-N2) •internalization of particle into the host cell, release the new particles from the cell • • Subtype f.e. : H1N1 ̶ Adobe Systems 7 Antigenic drift •minor antigenical change •occurs almost annually •results in outbreaks of variable extent and severity •outbreaks less extensive and severe than the epidemics or pandemics associated with antigenic shifts • • •point mutations in the RNA gene segments that code for the hemagglutinin or the neuraminidase Adobe Systems 8 Antigenic shift •major antigenical change •segmented genome can be reassorted among viruses coinfecting the same cell •reassortment between animal and human viruses - may result in the emergence of pandemic strains •caused the pandemics of 1957, 1968 and 2009 • • •reassortment, switching the genom segments, among viruses coinfecting the same cell •great role of pig and bird (avian) influenzaviruses • Adobe Systems Define footer – presentation title / department 9 Adobe Systems Define footer – presentation title / department 10 chřipka mutace Adobe Systems 11 Outbreak characteristics •2-3 different strains circulate in a influenza season, 1 dominant • •Seasonality — exclusively during the winter months in the Northern and Southern hemispheres (occur at different times of the year) •!!! traveling to tropical regions •persistance between outbreaks - poorly understood - import from geographically distant sites ?? •Factors determining the severity of an outbreak •not fully understood •the susceptibility of the population = prevalence of antibodies to circulating virus = major role. Adobe Systems 12 Outbreak characteristics •Time course of an outbreak •begin abruptly •peak ober 2-3 weeks •last for 2-3 months •earliest indicator of outbreak = increase in febrile respiratory illnesses in children → increases in influenza-like illnesses in adults •outbreaks attack rates = 10-20% in the general population, ˃50 % in pandemics, extraordinarily high attack rates in institutionalized and semiclosed populations. ̶ ̶ Adobe Systems 13 Transmission •large amounts of influenza virus in respiratory secretions → cough, sneezing → large dropplets (˃5um) - small distance (up to 2 m/6 feet) → small particle aerosols - long distances → contact with contaminated surface → respiratory tract → (ocular mucousa) •Incubation period: 1-4 days •Duration of shedding: detected 24 to 48 hours before illness onset, 5 days after onset of symptoms in avarage Adobe Systems Ghebrehewet Sam, MacPherson Peter, Ho Antonia. Influenza BMJ 2016; 355 :i6258 14 Clinical manifastation Uncomlicated influenza •abrupt onset of fever (37.8-40.0°C), headache, myalgia, and malaise •respiratory tract illness - nonproductive cough, sore throat, and nasal discharge •GIT - vomiting, diarrhea (ussualy children) •patient appears hot and flushed •oropharyngeal hyperemia, mild cervical lymphadenopathy •physical examination is unremarkable •Lab: unspecific, leukocyte normal, leukopenia in the early state, >15,000 cells/microL suggest bacterial superinfection •improvenment usually 2-5 days •postinfluenza asthenia - persistent symptoms of weakness, fatigability, last for several weeks Adobe Systems Ghebrehewet Sam, MacPherson Peter, Ho Antonia. Influenza BMJ 2016; 355 :i6258 15 Clinical manifastation Complicated influenza •Pneumonia - most common complication of influenza •Primary influenza pneumonia •severe pneumonia •symptoms persist and increase instead of resolving •high fever, dyspnea, cyanosis •X-ray, CT •Secondary bacterial pneumonia •↑morbidity and mortality ≥65 years •exacerbation symptoms after initial improvement , production of purulent sputum, pulmonary infiltrates •bacterial pathogens: S. pneumoniae , S.aureus, (S.pyogenes, P.aeruginosa, H.influenzae, K.pneumoniae, M.catarrhalis, E.coli •Mixed viral and bacterial pneumonia Adobe Systems Ghebrehewet Sam, MacPherson Peter, Ho Antonia. Influenza BMJ 2016; 355 :i6258 16 Clinical manifastation Complicated influenza •Acute respiratory distress syndrome (ARDS) and multisystem organ failure (MOF) •Myositis and rhabdomyolysis •most frequently in children •extreme tenderness of affected muscles (legs) •elevated serum creatine phosphokinase, myoglobinuria with associated renal failure •Cardiac •↑risk acute coronary syndrome, myocarditis and pericarditis •Central nervous system •encephalopathy, encephalitis, transverse myelitis, aseptic meningitis and Guillain-Barré syndrome Adobe Systems 17 Diagnosis •during season/outbreak • •clinical dg. •uncomplicated acute respiratory ilness •not requiring hospitalization •↓risk of complications ̶ ̶ Adobe Systems 18 Diagnosis •whom to test: •symptomatic immunocompromised patients / patients at ↑risk • •patients requiring hospitalization with acute respiratory illness, including pneumonia, with or without fever • •patients requiring hospitalization with acute worsening of chronic cardiopulmonary disease (eg, COPD, asthma, coronary artery disease, or congestive heart failure) • •acute onset of respiratory symptoms with or without fever, or respiratory distress, after hospital admission ̶ ̶ Adobe Systems 19 Diagnosis •RT-PCR •golden standard, genome identification •most sensitive and specific •rapid results (1-8 hours) •differentiates between influenza types and subtypes •nasopharyngeal aspirates, bronchoalveolar lavage fluid, nasal and throat swabs • •Rapid antigen tests •influenza A and B viral nucleoprotein antigens in respiratory specimens •qualitative results (+/-) •results in approximately 15 minutes or less •but much lower sensitivity than RT-PCR Adobe Systems 20 Diagnosis •Viral culture •nasal washes, throat swabs, sputum, bronchoalveolar lavage specimens •results available in 48-72 hours • •Serologic testing •useful primarily for research purposes •not useful for the diagnosis of acute illness - paired acute and convalescent are required •to establish the diagnosis of influenza retrospectively • • Adobe Systems 21 Treatment •Nonspecific •fluids •vitamins •antipyretics/analgetics •antitusics... ̶ Adobe Systems 22 Treatment •Antivirals: •neuraminidase inhibitors: zanamivir (inhalation 10 mg 1-0-1, 5 days), oseltamivir (p.o. 75 mg 1-0-1, 5 days), peramivir (i.v. 600 mg 1xdaily) • active against both influenza A and B • •inhibitor of influenza cap-dependent endonuclease: baloxavir • active against influenza A and B • •adamantanes: amantadine, rimantadine • only active against influenza A • increase in resistant isolates, adverse effects → ↓ of use Adobe Systems 23 Prevention •Preexposing measures •hand washing, aerosols (masks) •Vaccinaton •Profylactic drug use •Oseltamivir (75 mg 1xdaily) •Zanamivir (5 mg 1-0-1) Vaccination Adobe Systems 24 Prevention Vaccination •most effective prevention •against hemagglutinine •every year due to antigenic drifts • •i.m. - inactivated vac., reccombinant vac. •nasaly - live attenuated vac. (not available in CR) • •quadrivalent vac. - influenza A Ag x2 + influenza B Ag x2 •trivalent vac. - influenza A Ag x2 + influenza B Ag x1 • •elderly, chronicly ill, healthcare workers, long term facility workers, ... Adobe Systems 25 Avian influenza •influenza viruses adapted to birds •mostly influenza A virus •high pathogenic avian influenza (HPAI), low pathogenic avian influenza (LPAI) •H1-16, N1-9 = many subtypes •only H5N1, H7N3, H7N7, H7N9, H9N2 were confirmed in human •new strains typically emerge in Southeast Asia (close contact of human, bird and swine) •↑ pandemic potential, ↑ case fatality rate ̶ Adobe Systems Define footer – presentation title / department 26 china_market55 Adobe Systems 27 Transmission •Bird-to-human •handling dead infected birds •contact with infected (animal) fluids •contaminated surfaces and droppings •close contact, ↓hygiene • •Human-to-human •rare, only prolonged contact •spreading after mutation is ↑concern • •Role of pigs •infected by avian and human strains → reassortement → new strain • ̶ Adobe Systems 28 Why so dangerous ? •avian influenza viruses attach cells via diferent receptors than human strains → these reseptors are in lower respiratory tract in human → severe pneumonia with ARDS • •↓ effect of host antiviral cytokines, ↑ proinflammatory mediators → SIRS → ARDS •predominance of children and young adults Adobe Systems 29 Clinical manifestation •Incubation period: 2-5 days •respiratory illness •GIT •CNS • •Complications: pneumonia, MOF, renal dysfunction, cardiac compromise, pulmonary hemorrhage, pneumothorax, pancytopenia •Lab: leukopenia, neutropenia, lymphopenia, thrombocytopenia, ↑ aminotransferases (AST>ALT), ↑LDH, ↑ CK, ↓ albumin ̶ ̶ Adobe Systems 30 Diagnosis, treatment DG: •PCR •antigen detection •serology •viral isolation • Treatment •nonspecific •only oseltamivir is recommended in specific treatment of avian flu Adobe Systems 31 Prevention •Infection control measures •appropriate biosafety precautions when handling suspected specimen •higher level of infection control than for seasonal influenza viruses - eye protection and respirators (eg, N95 masks, FFP2) in addition •patients in airborne infection isolation rooms • •postexposition profylaxis – oseltamivir, zanamivir • •vaccine against H5N1 is available - ??? Efficiency after 10 years ??? ̶ ̶ Adobe Systems COVID-19 pandemic, 1.wave 32 Thank you for your attention !