INFLUENZA VIRUS INFLUENZA VIRUS CDC WEBSITE http://www.cdc.gov/ncidod/diseases/flu/fluinfo.htm 1
THE IMPACT OF INFLUENZA Deaths: PANDEMICS 1918-19 S p a n is h flu 5 0 0,0 0 0 U S 2 0,0 0 0,0 0 0 w o rld 1957-58 A s ia n flu 7 0,0 0 0 U S 2
THE IMPACT OF INFLUENZA In the United States, on average: 36,000 deaths per year 114,000 hospitalizations per year CDC: MMWR 53:8-11, 2004 3
4
ORTHOMYXOVIRUSES HA - hemagglutinin NA - neuraminidase helical nucleocapsid (RNA plus NP protein) lipid bilayer membrane polymerase complex M1 protein type A, B, C : NP, M1 protein sub-types: HA or NA protein 5
Hemaggulutinin(HA) Virus hemagglutinin sticks new virus particle to sialic acid on cell surface
7
Replication 8
Neuraminidase(NA) hemagglutinin binds to sialic acid on other virus particles: virus clumps OR virus sticks to mucous in respiratory tract
Neuraminidase of virus removes sialic acid from cell surface thereby releasing virus
TRANSMISSION AEROSOL 100,000 TO 1,000,000 VIRIONS PER DROPLET 18-72 HR INCUBATION SHEDDING 11
12
NORMAL TRACHEAL MUCOSA 3 DAYS POST-INFECTION 7 DAYS POST-INFECTION Lycke and Norrby Textbook of Medical Virology 1983 13
DECREASED CLEARANCE RISK BACTERIAL INFECTION VIREMIA RARE 14 Lycke and Norrby Textbook of Medical Virology 1983
RECOVERY INTERFERON - SIDE EFFECTS INCLUDE: FEVER, MYALGIA, FATIGUE, MALAISE CELL-MEDIATED IMMUNE RESPONSE TISSUE REPAIR CAN TAKE SOME TIME 15
SIDE EFFECTS OF INTERFERONS FEVER MALAISE FATIGUE MUSCLE PAINS 16
PROTECTION AGAINST RE-INFECTION IgG and IgA IgG less efficient but lasts longer antibodies to both HA and NA important antibody to HA more important (can neutralize) 17
SYMPTOMS FEVER HEADACHE MYALGIA COUGH RHINITIS OCULAR SYMPTOMS 18
CLINICAL FINDINGS SEVERITY VERY YOUNG ELDERLY IMMUNO- COMPROMISED HEART OR LUNG DISEASE 19
PULMONARY COMPLICATIONS CROUP (YOUNG CHILDREN) PRIMARY INFLUENZA VIRUS PNEUMONIA SECONDARY BACTERIAL INFECTION Streptococcus pneumoniae Staphlyococcus aureus Hemophilus influenzae 20
NON-PULMONARY COMPLICATIONS myositis (rare, > in children, > with type B) cardiac complications recent studies report encephalopathy 2002/2003 season studies of patients younger than 21 yrs in Michigan - 8 cases (2 deaths) liver and CNS Reye s syndrome peripheral nervous system Guillian-Barré syndrome 21
Reye s syndrome liver - fatty deposits brain - edema vomiting, lethargy, coma risk factors youth certain viral infections (influenza, chicken pox) aspirin 22
Guillian-Barré syndrome 1976/77 swine flu vaccine 35,000,000 doses 354 cases of GBS 28 GBS-associated deaths recent vaccines much lower risk 23
MORTALITY MAJOR CAUSES OF INFLUENZA VIRUS- ASSOCIATED DEATH BACTERIAL PNEUMONIA CARDIAC FAILURE 90% OF DEATHS IN THOSE OVER 65 YEARS OF AGE 24
DIAGNOSIS ISOLATION NOSE, THROAT SWAB TISSUE CULTURE OR EGGS SEROLOGY PCR RAPID TESTS provisional - clinical picture + outbreak 25
ANTIGENIC DRIFT HA and NA accumulate mutations RNA virus immune response no longer protects fully sporadic outbreaks, limited epidemics 26
ANTIGENIC SHIFT new HA or NA proteins pre-existing antibodies do not protect may get pandemics 27
Decreasing serologic relatedness Antigenic shift and drift Antigenic drift Antigenic shift HA or NA HA Or NA NP Years One year 28
29
30
Where do new HA and NA come from - can new bird flu directly infect humans? Bird flu H5N1? 31
H5N1 in birds Avian H5N1 has spread to humans So far human cases in Asia and Africa 256 cases (12-1-03 through 10-16-06) 151 (59%) fatal Have been a few instances where may have spread human-to-human So far no sustained spread in humans Surveillance continues 32
why do we not have influenza so far no shifts have been recorded no animal reservoir known B pandemics? 33
VACCINE BEST GUESS OF MAIN ANTIGENIC TYPES CURRENTLY type A - H1N1 type A - H3N2 type B each year choose which strain of each subtype is the best to use for optimal protection 34
VACCINE inactivated egg grown some formulations licensed for children reassortant live vaccine approved 2003 for healthy persons (those not at risk for complications from influenza infection) ages 5-49 years 35
PREVENTION - DRUGS RIMANTADINE (M2) type A only AMANTADINE (M2) type A only 2005-6 season H3N2 virus - 92% isolates resistant to rimantadine and amantadine in US, so these drugs not recommended until % resistance in major circulating type drops ZANAMIVIR (NA) types A and B OSELTAMIVIR (NA) types A and B 36
TREATMENT - DRUGS RIMANTADINE (M2) type A only, needs to be given early AMANTADINE (M2) type A only, needs to be given early ZANAMIVIR (NA) types A and B, needs to be given early OSELTAMIVIR (NA) types A and B, needs to be given early 37
OTHER TREATMENT REST, LIQUIDS, ANTI-FEBRILE AGENTS (NO ASPIRIN FOR AGES 6MTHS-18YRS) BE AWARE OF COMPLICATIONS AND TREAT APPROPRIATELY 38
TYPE A TYPE B TYPE C severity of illness ++++ ++ + animal reservoir yes no no human pandemics yes no no human epidemics yes yes no (sporadic) antigenic changes shift, drift drift drift segmented genome yes yes yes amantadine, rimantidine (sensitive) no effect no effect zanamivir,oseltamivir sensitive sensitive surface glycoproteins 2 2 (1) 39