Download INFLUENZA

chapter 24
viruses associated with
respiratory infections
Department of pathogenic biology
xie-shuixiang
1
ORTHOMYXOVIRUSES
• pleomorphic
• influenza types A,B,C
• febrile, respiratory
illness with systemic
symptoms
2
‘FLU’
• True influenza
– influenza virus A or influenza virus B (or
influenza virus C infections - much milder)
• Febrile respiratory disease with systemic
symptoms caused by a variety of other
organisms often called ‘flu’
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THE IMPACT OF INFLUENZA
PANDEMICS
Deaths:
1918-19 Spanish flu 500,000 US
20,000,000 world
1957-58 Asian flu
70,000 US
1968-69 Hong Kong 34,000 US
flu
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INFLUENZA VIRUS
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Composition of Influenza Virus
1.Core
RNA： -ssRNA, 8 fragments
NP (nucleoprotein)
RNA dependent RNA polymerase
2. envelope
M protein
lipid envelope
sipke hemagglutinin(HA)
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neuraminidase(NA) 1
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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
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Nomenclature
Host of origin
geographical origin
strain number
parentheses
antigenic description
of HA and NA
e.g.
A/swine/Iowa/3/70(H1N1)
A/Hong Kong/1/68(H3N2)
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Functions of Hemagglutinin
• HA causes agglutination of red blood cells.
• Viruses bind to the mucous membrane
cells by HA1 interacting with membrane
receptor.
• Virus’ envelope fuse with cell membrane
by HA2 forming a fusion pore.
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HA protein - attachment, fusion
S
S
S
S
S
S
cell enzymes
acid pH
10
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Functions of Neuraminidase
• NA help the virus to permeate mucin and
escape from “non-specific”inhibitor.
• NA can increase the number of free virus
particles, hence more virus spread from
the original site of infection.
• NA is important in the final stages of
release of the new virus particle from
infected cells.
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NA protein - neuraminidase
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ANTIGENIC DRIFT
• Minor changes in antigens due to gene
mutation in influenza virus.
• HA and NA accumulate mutations
– RNA virus
• immune response no longer protects fully
• sporadic outbreaks, limited epidemics
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ANTIGENIC SHIFT
• Major changes in antigens due to gene
reassortment in influenza virus.
• “new” HA or NA proteins
• pre-existing antibodies do not protect
• may get pandemics
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INFLUENZA A PANDEMICS
Ryan et al., in Sherris Medical Microbiology
18
where do “new” HA and NA
come from?
• 15 types HA
• 9 types NA
– all circulate in birds
• pigs
– avian and human
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where do “new” HA and NA
come from?
20
why do we not have influenza B
pandemics?
• so far no shifts
have been
recorded
• no animal
reservoir known
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TRANSMISSION
• AEROSOL
– 100,000 TO
1,000,000 VIRIONS
PER DROPLET
• 18-72 HR
INCUBATION
• SHEDDING
22
• DECREASED
CLEARANCE
• RISK BACTERIAL
INFECTION
• VIREMIA RARE
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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
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INTERFERON
25
INTERFERON
antiviral state
antiviral state
antiviral state
antiviral state
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INTERFERON
antiviral state
antiviral state
antiviral state
antiviral state
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INTERFERON
antiviral state
antiviral state
antiviral state
antiviral state
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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)
29
SYMPTOMS
• FEVER
• HEADACHE
• MYALGIA
• COUGH
• RHINITIS
• OCULAR SYMPTOMS
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CLINICAL FINDINGS
• SEVERITY
– VERY YOUNG
– ELDERLY
– IMMUNOCOMPROMISED
– HEART OR LUNG
DISEASE
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PULMONARY COMPLICATIONS
• CROUP (YOUNG CHILDREN)
• PRIMARY INFLUENZA VIRUS PNEUMONIA
• SECONDARY BACTERIAL INFECTION
– Streptococcus pneumoniae
– Staphlyococcus aureus
– Hemophilus influenzae
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DIAGNOSIS
• ISOLATION
– NOSE, THROAT SWAB
– TISSUE CULTURE OR EGGS
• SEROLOGY
• RAPID TESTS
• provisional - clinical picture + outbreak
33
VACCINE
• ‘BEST GUESS’ OF MAIN ANTIGENIC
TYPES
– CURRENTLY
• type A - H1N1
• type A - H3N2
• type B
• each year choose which variant of each subtype is
the best to use for optimal protection
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VACCINE
• inactivated
• egg grown
• sub-unit vaccine for children
• reassortant live vaccine approved 2003
– for healthy persons (those not at risk for
complications from influenza infection) ages
5-49 years
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live vaccine development
adapted from
36
Treanor JJ Infect. Med. 15:714
TREATMENT - DRUGS
• RIMANTADINE
(M2)
• AMANTADINE
(M2)
• type A only, needs to be given early
• 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
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NA protein - neuraminidase
.
.
.
.
.
. . .
.
.
..
...
.
.
.
.
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OTHER TREATMENT
• REST, LIQUIDS, ANTI-FEBRILE AGENTS
(NO ASPIRIN FOR AGES 6MTHS-18YRS)
• BE AWARE OF COMPLICATIONS AND
TREAT APPROPRIATELY
39
CORONA VIRUSES
COLDS AND SARS
40
Severe acute
respiratory
syndrome
(SARS)
41
SARS Coronavirus, SARS CoV
• Severe Acute Respiratory Syndrome(SARS)
• 2002/11
42
SARS symtom
• Droplet or osculation
• Latent period：2~12d，usually4~5d
• Centralization in family and hospital apparently
43
Biological
properties
• 60-130nm，envelope
with spikes
• +ssRNA，29.7KB，14
ORF:RNA polymer- ase、
S、E、M、N
• Vero cell--CPE
• Infected quadrumana –
typical SARS symptom
44
SARS Genome
45
Transmission and
Epidemiology
46
Chinese SARS epidemiology
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Diagnosis
• Mainly depend on the clinic and
epidemiologic data
• Pathogen diagnosis
– Isolation and identification of virus
– RT-PCR
– Immunofluorescence、ELISA
• P3 laboratory
• Pathogen diagnosis is immature
49
Prevention
• SARS CoV比普通CoV抵抗力强，室温下痰、
粪便、尿中可稳定存活1~2d
• 对温度敏感，37oC存活4d，56oC存活90m，
75oC30m
• 对含氯消毒剂、过氧乙酸及UV均敏感，
• WHO推荐中效以上的消毒剂，如过氧乙酸
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Pathologic cytoarchitectural changes indicative of diffuse
alveolar damage, as well as a multinucleated giant cell
with no conspicuous viral inclusions.
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Paramyxoviridae
-ssRNA
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measles (rubeola)
Koplik's spots on mucosal membranes
Maculopapular rash (extends
from face to extremities)
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Measles virus
measles (rubeola)
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SUB-ACUTE SCLEROSING
PANENCEPHALITIS (SSPE)
•
•
•
•
Very rarely (7 in 1,000,000 cases)
1-10 years after initial infection.
progressive, fatal disease.
defective forms of the virus in the brain
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Lab Diagnosis
Histopathology of measles pneumonia. Giant cells.
61
Prevention
MMR
• (mumps, measles, rubella) vaccine
contains live, attenuated forms of all three
of these viruses.
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MUMPS VIRUS
Mumps
• British "to mump" - to
•
grimace or grin, from
the appearance of the
patient as a result of
parotid gland swelling.
(Note: Other agents can
also cause parotitis).
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• very contagious
64
RESPIRATORY SYNCYTIAL VIRUS
spherical or
pleomorphic
enveloped viruses
(100-350 nm) with
single-stranded,
negative sense linear
RNA
65
• Upper respiratory
infection (‘bad cold’) in
older children and adults
• Lower respiratory
• Infection of cells
results in syncytium
formation
infection- Bronchiolitis
and/or pneumonia may
occur after the upper
respiratory infection
• Severe infections occur
in infants (2-6m)
66
Others
67
ADENOVIRUS
• non-enveloped
• linear double-stranded (ds)
•
•
DNA
Icosahedral capsid,
capsomeres
hexons;
at the vertices are 12 pentons,
from which a fiber with a
terminal knob projects. This
complex is toxic to cells causing rounding and death of
cells through inhibition of
protein synthesis.
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• Eye
•
•
•
Epidemic Keratoconjunctivitis (EKC), acute follicular
conjunctivitis, pharyngoconjunctival fever
Respiratory system
Common cold (rhinitis), pharyngitis (with or without fever),
tonsillitis, bronchitis, pharyngoconjunctival fever, acute
respiratory disease (LRI)
Genitourinary
Acute hemorrhagic cystitis
Gastrointestinal
Gastroenteritis.
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RUBELLA
cataracts
Rash
Congenital rubella
70
RUBELLA (GERMAN MEASLES) VIRUS
• Togavirus
• +ssRNA
• Fetal
damage
• live vaccine
(attenuated
strain)
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