20 chapter viruses associated with respiratory infections

1
20 chapter viruses associated with respiratory
infections
Department of pathogenic biology xie-shuixiang
2
ORTHOMYXOVIRUSES

• pleomorphic
• influenza types A,B,C
• febrile, respiratory illness with systemic
  symptoms

3
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

4
THE IMPACT OF INFLUENZAPANDEMICS
Deaths
5
INFLUENZA VIRUS
6
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) 5
• neuraminidase(NA) 1

7
type A, B, C NP, M1 protein sub-types HA or
NA protein
8
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)

9
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.

10
HA protein - attachment, fusion
11
(No Transcript)
12
Functions of Neuraminidase

• NA help the virus to permeate mucin and escape
  from non-specificinhibitor.
• 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.

13
NA protein - neuraminidase
14
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

15
(No Transcript)
16
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

17
(No Transcript)
18
INFLUENZA A PANDEMICS
Ryan et al., in Sherris Medical Microbiology
19
where do new HA and NA come from?

• 15 types HA
• 9 types NA
• all circulate in birds
• pigs
• avian and human

20
where do new HA and NA come from?
21
why do we not have influenza B pandemics?

• so far no shifts have been recorded
• no animal reservoir known

22
TRANSMISSION

• AEROSOL
• 100,000 TO 1,000,000 VIRIONS PER DROPLET
• 18-72 HR INCUBATION
• SHEDDING

23

• DECREASED CLEARANCE
• RISK BACTERIAL INFECTION
• VIREMIA RARE

Lycke and Norrby Textbook of Medical Virology 1983
24
RECOVERY

• INTERFERON - SIDE EFFECTS INCLUDE
• FEVER, MYALGIA, FATIGUE, MALAISE
• CELL-MEDIATED IMMUNE RESPONSE
• TISSUE REPAIR
• CAN TAKE SOME TIME

25
INTERFERON
26
INTERFERON
27
INTERFERON
28
INTERFERON
29
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)

30
SYMPTOMS

• FEVER
• HEADACHE
• MYALGIA
• COUGH
• RHINITIS
• OCULAR SYMPTOMS

31
CLINICAL FINDINGS

• SEVERITY
• VERY YOUNG
• ELDERLY
• IMMUNO-COMPROMISED
• HEART OR LUNG DISEASE

32
PULMONARY COMPLICATIONS

• CROUP (YOUNG CHILDREN)
• PRIMARY INFLUENZA VIRUS PNEUMONIA
• SECONDARY BACTERIAL INFECTION
• Streptococcus pneumoniae
• Staphlyococcus aureus
• Hemophilus influenzae

33
DIAGNOSIS

• ISOLATION
• NOSE, THROAT SWAB
• TISSUE CULTURE OR EGGS
• SEROLOGY
• RAPID TESTS
• provisional - clinical picture outbreak

34
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

35
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

36
live vaccine development
adapted from Treanor JJ Infect. Med. 15714
37
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

38
NA protein - neuraminidase
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
39
OTHER TREATMENT

• REST, LIQUIDS, ANTI-FEBRILE AGENTS (NO ASPIRIN
  FOR AGES 6MTHS-18YRS)
• BE AWARE OF COMPLICATIONS AND TREAT APPROPRIATELY

40
CORONAVIRUSES

• COLDS AND  SARS

41
Severe acute respiratory syndrome (SARS)
42
SARS Coronavirus, SARS CoV

• Severe Acute Respiratory Syndrome(SARS)
• 2002/11

43
SARS symtom

• Droplet or osculation
• Latent period212d,usually45d
• Centralization in family and hospital apparently

44
Biological properties

• 60-130nm,envelope with spikes
• ssRNA,29.7KB,14 ORFRNA polymer- ase?S?E?M?N
• Vero cell--CPE
• Infected quadrumana typical SARS symptom

45
SARS Genome
46
Transmission and Epidemiology
47
Chinese SARS epidemiology
48
(No Transcript)
49
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

50
Prevention

• SARS CoV???CoV????,???????????????12d
• ?????,37oC??4d,56oC??90m,75oC30m
• ????????????UV???,
• WHO??????????,?????

51
(No Transcript)
52
(No Transcript)
53
(No Transcript)
54
(No Transcript)
55

• Pathologic cytoarchitectural changes
  indicative of diffuse alveolar damage, as well as
  a multinucleated giant cell with no conspicuous
  viral inclusions.

56
(No Transcript)
57
Paramyxoviridae
-ssRNA
58
measles (rubeola)
Koplik's spots on mucosal membranes
Maculopapular rash (extends from face to
extremities)
59
Measles virusmeasles (rubeola)
60
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

61
Lab Diagnosis
62
Prevention

• MMR 
• (mumps, measles, rubella) vaccine contains live,
  attenuated forms of all three of these viruses.

63
MUMPS VIRUSMumps 

• 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).

64

• very contagious

65
RESPIRATORY SYNCYTIAL VIRUS

• spherical or pleomorphic enveloped viruses
  (100-350 nm) with single-stranded, negative sense
  linear RNA

66

• Upper respiratory infection (bad cold) in older
  children and adults
• Lower respiratory infection- Bronchiolitis and/or
  pneumonia may occur after  the upper respiratory
  infection
• Severe infections occur in infants (2-6m)

• Infection of cells results in syncytium formation

67
Others
68
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.

69

• 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.

70
RUBELLA
71
RUBELLA (GERMAN MEASLES) VIRUS

• Togavirus
• ssRNA
• Fetal damage
• live vaccine (attenuated strain)