146B OS 213 Viral Respiratory Infections

8/14/2019 146B OS 213 Viral Respiratory Infections

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Page 5 of 5SSuperSSAugust 23, 2007

Exam 1Trans146B

Respiratory Viral InfectionsOS 213

Pulmo

Dr. Lilen Sarol

OutlineModes of TransmissionViruses Causing Respiratory Infections

AdenovirusesRhinovirusesParamyxoviridaeRespiratory Syncytial VirusParainfluenza VirusesInfluenza VirusesCoronaviruses

M o d e s o f T R A N S M I S S I O N same mode of transmission for respiratory infections

Figure 1. Routes of Transmitting Infection

Table 1. Comprarison of Modes ofTransmission

DIRECT MODES INDIRECT MODES

droplets(macrodroplets)

droplet nuclei (microdroplets:


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Dr. Lilen Sarol

B.

Classification

Table 2. Serotypes of FamilyAdenoviridae

Subgrp Representative Target organ Epidemiology

A 12, 18, 31 GIT EndemicB 3* , 7*, 11, 21 Pharynx, lungs,

UT, conjunctivaEpidemic

C 1, 2*, 5*, 6 Pharynx Latent throat

D 8, 9, 19 Eye Epidemic

E 4 Upper RT Epidemic

F 40, 41 GIT Endemic

*most common all over the world

Respiratory infections seen more in SubGrps B, C& E

Adenoviruses are not only seen in the respiratorytract but also in the GI tract(subgrp A & F) andconjunctival infections(subgrpD)

C. Pathogenesis Present with a dense central intranuclear inclusion

body in host cell

D. Laboratory Diagnosis Virus Isolation

methodof choice grapelike clusters type of cytopathic effect

intranulcear inlcusions ELISA (Enzyme-linked Immunosorbent Assay) Immunofluorescence

For directdetection in specimens like

nsopharyngeal aspirate For confirmation of viral isolates

R H I N O V I R U S E S

Major cause of upper respiratory tract infection

(causes 50% of common colds cases)

exclusive in RT

exclusive in humans

member of family Picornaviridae of which

Enteroviruses are also a member

Enteroviruseso Polioviruses (3)

o Coxsackieviruses A (24)o Coxsackieviruses B (6)

o Echoviruses (34)

o Enteroviruses (5)

o Enterovirus 72 (Hepatitis A)

A. Characteristics1. Small

measures around 1830 nm characteristic of the members of the family

Picornaviridae

2. Like adenoviruses, they have: Icosahedral symmetry Naked capsid Environmentally stable to:

Temperature

Acid

Proteases

Detergents

Drying Consequences:

Can be spread easily

Can dry out and retain infectivity

survive the adverse conditions of thegut

resistant to poor sewage treatment

3. Can be differentiated from adenovirusesbecause they have:

(+) single-stranded RNA can be used directly as mRNA

Consequences: mRNA is translated immediately to

proteins (polymerase)

RNA-polymerase is now used forsucceeding cycles of replication

Both the genome which acts as

mRNA and the complete virion areinfectious; unlike other viruses thatlose infectivity with removal ofcapsule

>100 serotypes (in some reports, around150 and still growing)

Difficult to produce vaccine

Difficult to diagnose specific serotype

B. Difference Between Enteroviruses &Rhinoviruses

Table. 3. Characteristics of Entero andRhino Viruses

Enteroviruses Rhinovirus

pH stability 3-9 >6

Buoyant density 1.43 g/ml 1.45 g/ml

Growth

requirements

37oC 33oC

Implications

Rhinoviruses can only grow in the RT, where pH>6,

and not in GIT where pH


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Exam 1Trans146B


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Dr. Lilen Sarol

P A R A M Y X O V I R I D A E

A. Classification1. Family Paramyxoviridae

Subfamily Paramyxoviridae

Respirovirus(paramyxovirus) Parainfluenza

1 & 3, Sendai virus

Rubulavirus Parainfluenza 2 & 4, Mumps

Morbillivirus Measles, Rinderpest Henipavirus Hendra virus, Nipah virus

Avulavirus Newcastle Disease virusSubfamily Pneumovirinae

Pneumovirus Respiratory SyncytialVirus (RSV)

Metapneumovirus

The Parainfluenza virus 1-4 are not grouped in thesame genera. Classification is primarily based onmolecular typing or sequencing of the viral agents.

B. Characteristics1. Envelope

Fusion protein (F) found in all Paramyxoviridae

responsible for viral entry whereenvelopd fuses with the plasmamembrane of the target cell

responsible for fusion of cells seen inculture or what is known as the formationof giant multinucleated cell

Attachment protein (G,H & N)- basis ofdifference among different groups.

Table 4. Attachment Proteins of

ParamyxoviridaeAttachment Protein Genus

Examples

G Protein (G) Pneumovirus RSV

Hemagglutinin (H) Morbilivirus Measles

Hemagglutinin &Neuraminidase (HN)

Paramyxovirus1-4

All promote cell attachment and necessary toinfect a cell.

Hemagglutinin (in H and HN) agglutinates RBCs

(hemagglutination and hemadsorption),

G protein for attachment only, NO agglutination

For diagnostic purposes. If RBCs do notagglutinate, the more probable causative agentsare those that do not have H protein.

2. Nucleic acid Negative ssRNA

have RNA-dependent RNA-polymerase:

RNA is transcribe first to mRNA beforebeing translated to early proteins

Non-segmented3. Nucleocapsid

Helical symmetryo Can have different forms

o Can undergo pleiomorphism

Genome of Rhinovirus is associated with capsid so itis not possible for them to produce an empty capsid

C. Paramyxoviridae in RT causes repeated infections No available vaccine

1. Respiratory syncytial virus (RSV)

One antigenic type

In children


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Dr. Lilen Sarol

negative ssRNA

Viruses having segmented nucleic acid have biggercapacity to mutate or be reassorted, so thissegmentation of the nucleic acid augments the

inherent capacity of the RNA to undergo minormutation. With segmented nucleic acid, they can havemajor mutations (2010 trans).

B. Attachment proteins

1. H spike ( hemagglutinin)

binds to host cell receptors (sialic acid) in the host

respiratory cell

allows entry into cell

Antibodies agiants H prevents infection

Figure 3. Envelope Antigens of InfluenzaVirus.The neuraminades and hemagglutininoccur at different spikes, unlikeparamyxovirus where H & N are on samespikes

2. N spike ( neuraminidase) hydrolyzes the mucus of the respiratory tract

cleaves neuramic acid in mucin and exposes

other host cell receptors (sialic acid) whichthen assists in the viral budding and release

Antibodies to N does not prevent infection, itonly helps to limit its spread

Responsible for exit of virus

Table 5. Occurrence of H and N Serotypes ofInfluenza

Hemagglutinin Neuraminidase

Serotypes 16 types 9 types

Found in humans 1,2,3 1,2

Found in birds All All

C. Segmentation of Genome each segment corresponds to one viral protein

Influenza A and B have 8 segmentations ascompared to influenza C (7 only) because thehemagluttinin and neuraminidase are combinedtogether in influenza C.

Influenza viruses can undergo major mutations

(antigenic shift resulting to oandemics)

Segment 1 translation into transcriptase

Segment 4 for translation of hemaggultinin

Segment 6- for translation of neuraminidase

Nucleoprotein coded by segment 5 and matrix proteincoded by segment 7 are the basis for differentiation fortypes A,B, and C.

D. ANTIGENECITY in Influenza Virus

Influenza have both group-specific and type-

specific antigens

Antigenic changes (2 types):

Antigenic Drift

minor mutations in the hemagglutinin antigen

due to lack of proofreading capability (ascompared with DNA dependent viruses)

related to polymerase error and selectivepressure of antibody

accumulation of point mutations in HA or NA

makes prior immunity less effective and ensuresthat enough susceptible people are available forthe survival of the virus

it is advisable to have influenza shots every yearbecause of accumulation of mutations in thevirus in a short period of time

Antigenic Shift

will produce a totally different subtype, virus

strains appear more different antigenically frompreviously seen strains

occur when two separate strains of influenzainfect the same cell simultaneously reassortment of segments occur

2 different species from human and avianpopulation affect the human cell anynumber of segments can reassort suddenappearance of a new antigenic type

major mutations that can occur

cause of pandemics

only influenza A can undergo antigenic shiftbecause it is the only one that can infect both

humans and animals

Figure 4. Antigenic Shift and Drift inInfluenza virus

Table 6. Comparison of Antigenic Shift andAntigenic Drift

Antigenic Shift Antigenic DriftMajor change, new subtype Minor change, w/in subtype

Exchange of gene segments Point mutation

Occurs in A subtypes only Occurs in A&B subtypes

Occurs infrequently Occur continuosly

E. Laboratory Diagnosis

Virus Isolation Seldom show cytopathic effect

Hemadsorption Presumptive test for the presence of virus

Hemeagglutination Presumptive test for the presence of virus

Internal ribunucleoprotein: group specificantigen and distinguishes Influenza A,B, andC (internal location)

H and N: type specific antigens located on cellsurface; Antibody against hemagglutinin

neutralizes the infectivity (prevents disease) of thevirus whereas antibody against group-specificantigen does not. Antibody against neuraminidasedoes NOT neutralize infectivity but reduce disease,


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Titer can be determined Hemeagglutination Inhibition Test

Confirmatory test Can be used to ID type of influenza virus

Immunofluorescence For direct detection in specimens like

nasopharyngeal aspirate and for confirmationviral isolates

Possible mechanisms for emergence of pandemic virus

1. Human and bird virus reassort gene sequence in pigresulting in banded virus in pig and normal humansubject (genetic reassortment between human &animal viruses)

2. alteration of receptor specificity during replication ofan avian virus in pigs may occur both before afterreassortment with a human virus

3. direct transmission between animals and humansand reassortment in humans

e.g. outbreak in HK in 19974. will result in a pandemic since new transmission is

very fast and before antibodies can be produced,many people are already infected

Why is it more important to become vaccinated withvaccine against human influenza ?

If youre protected against influenza, reassortmentwill not be possible since you need both avian andhuman influenza for reassortment of genes to occur

One should have a good surveillance system inorder to determine the type of strain coming out. It isbased on laboratory diagnosis. The Philippines hasa good one by the way.

Vaccines or immunity promote point mutation

because of the pressure exerted by the antibodies(like Darwins natural selection) thus cannot becompletely eliminated.

Vaccines are also needed because it would take 1week to produce neutralizing antibodies if one getsinfected and apparently has no pre-existingantibodies against the infecting agent. So basically,vaccines will spare you from getting sick, feeling ill,or worse experiencing the complications for 1 weekwhile your body is producing the antibodies againstthe virus.

COMPLICATIONS Primary viral pneumonia Secondary Bacterial pneumonia Myositis and cardiac involvement Neurologic syndromes Guillain- Barre syndrome Encephalopathy Encephalitis Reyes syndrome

C O R O N A V I R U S E S tetromers are crownlike thats why theyre called

coronaviruses

A. Characteristics Enveloped virus with + sense ssRNA

Have club-shaped surface spikes

helical capsid

viral particle is pleomorphic

13 serotypes

3 human, including SARS

10 animals and birds

Infect humans, animals and birds

All human coronaviruses (2 serotypes) causerespiratory infections

Infection is confined to the ciliary epithelium ofthe trachea, nasal mucosa and alveolar cells ofthe lungs.

B. Severe acute respiratory syndrome (SARS)

1. Etiologic AgentOrder Nidovirales

Family CoronaviridaeTorovirusCoronavirus

(Group I, Group II, Group III)

2. Case Definition

Suspect Case Respiratory disease of unknown etiology

after 2-01-2003

Fever (>100.4F) and cough or shortness ofbreath

>1 of cough, shortness of breath, dyspnea,hypoxia, or X-ray of pneumonia or ARDS

AND Exposure History - Recent travel to anarea with SARS transmission or closecontact with a suspected SARS case

MOST IMPT, OTHERWISE dont consider

this infection)

Probable Case Suspect case with chest X-ray or autopsy

findings of pneumonia or unexplainedARDS

3. Transmission

Observations Preponderance of cases in HCW or

household contract workers

Infrequent instances of communitytransmission

Super-spreading events

Prolonged detection of virus

Modes of Transmission Close contact droplet, fomites, direct

contact

Airborne

Fecal-oral - vs influenza which is throughrespiratory secretions

4. Risk Factors for Severe Outcome

Age - estimated mortality rate nearly 50% if>60 years; 13.2% if


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Pulmo

Dr. Lilen Sarol

Milder infection in younger children

Table 7. Comparison between SARS andInfluenza

Influenza SARSAffects community Health care workers

Best isolated during start ofacute phase (first weekform onset)

Best diagnosed duringcovalescent phase (1-2weeks form onset)

Exclusively in RT Can be isolated in stool

end of trans

SELF-ASSESMENT

1. Each of the following statements regardinginfluenza is correct EXCEPT:a. Major epidemics of the disease are caused byInfluenza A rather than Influenza B and C

b Likely sources of new antigens for Influenza A virus areviruses that cause influenza in animals

c.Major antigenic changes (shifts) occur primarily inInfluenza A rather than influenza B and C

d. Antigenic changes that occur with antigenic drift are dueto reassortment of the multiple pieces if the influenzavirus genome

Each of the following statements regarding in rhinovirusesis correct EXCEPT:

Picornaviruses i.e small non-enveloped RNA virusImportant cause of lower respiratory esp. in COPDDo not infect the GI tract because they are inactivated by

acid pH in the stomach.

No vaccine against rhinoviruses since they have too many

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146B OS 213 Viral Respiratory Infections