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Respiratory Viruses Flashcards

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1
Q

Viruses Covered

A

Respiratory Syncytial Virus

Parainfluenza Virus Types 1, 2, 3, 4,

Adenoviruses

Rhinoviruses

Enterovviruses

Coronaviruses

Human Metapneumovirus

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2
Q

Respiratory Tract Disease

A

More episodes of illness than any other organ system

  • 75-80% of all acute morbidity and visits to physicians
  • respiratory tract is main portal of entry for many organisms, so not surprising that it is the most common site of infection by microbial pathogens as in direct contact with the physical environment
  • wide range of organisms can infect the respiratory tract, including viruses, bacteria, fungi and parasites

Upper respiratory tract
- colds

Lower respiratory tract
- 4th most common cause of death in developed countries

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3
Q

Global Burden of Respiratory Disease

A

Public health issue!
Leading killer of children < 5 yrs old , especially RSV

Pediatric ALRI < 5 yrs old
RIV> Influenza> Pneumococcal > HiB

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4
Q

Acute viral respiratory disease

A

Viruses account 80% or more of RTI’s

All age groups

3 - 4 viral illnesses per year per person, mostly in young children!

Abx have no effect but 60% get them!

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5
Q

Who is at greatest risk for acute viral respiratory disease?

A

The very young

The elderly

Chronically ill

Immunocompromised!

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6
Q

Viral respiratory illness

Children vs Adults

A

Children: implicated in 40-70% CAP, >90% of bronchiolitis, over 90% asthma exacerbation

Adults: 30-50% of cap, > 80% asthma exacerbation, 20-60% exacerbation of COPD

infection messes with your epithelial cells so you are predisposed to secondary bacterial infections in respiratory tract and can affect other organ systems

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7
Q

Location in Respiratory Tract - relates specific site of infection to various symptoms

Where do most infections occur?

A

Most infections are limited to upper airways

LRTIs common in defined populations

Cough, runny nose, sneezing, sore throat, ear pain, congestion

Systemic manifestations of fever, headache, chills malaise, myalgia also common

Last 7-10 days in most, 2 - 3 weeks in many, longer in some

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8
Q

Common cold

Pharyngitis

Pneumonia

Laryngitis

Laryngotracheobronchitis in infants (croup))

Tracheobronchitis

Bronchiolitis

A

Common cold: nasal obstruction, nasal discharge

Pharyngitis: sore throat, red throat with or without exudate

Pneumonia: cough, chest pain, rales

Laryngitis: hoarseness

Laryngotracheobronchitis in infants (croup)): hoarseness, barking cough, stridor

Tracheobronchitis: nonproductive cough, substernal pain

Bronchioliti: cough, dyspnea, wheezing

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9
Q

Common complications of viral infections

A

Secondary bacterial infections causing otitis media, sinusitis, pneumonia

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10
Q

Diagnosis of respiratory viruses

A
  • clinical and epidemiological findings

Virus isolation in cell culture (time consuming, labor intensive and costly and not all respiratory viruses grow in culture): used to be gold standard but not anymore

Rapid antigen test

  • cheap easy but poor predictive value outside of peak season
  • IFA and EIA
  • not as sensitive as cell culture

Detection of nucleic acids

  • can test many viruses at the same time
  • PCR, feasible and most sensitivity GOLD STANDARD

Serology- retrospective, seldom done in clinical setting

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11
Q

Specimen collection for detection of respiratory viruses

A
  • close to clinical onset!
  • nasopharyngeal aspirates, washes, swabs in VTM, throat swabs in VTM
  • nasopharyngeal aspirates or nasal washes are good in young children
  • combined thorat and nasopharyngeal swabs are more practical for older children and adults
  • children shed virus at higher titers for longer periods of time than adults, upper airway specimens not always best for adults
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12
Q

Why test respiratory viruses?

A

Infection control

Individual patient management

  • help manage special populations
  • limit abx, lab tests, hospital procedures
  • reduce sequellae

Surveillance
- rapid outbreak identification!

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13
Q

Virus SEasonality at CHOP

A

Rhinovirus > RSV> adenovirus> influenza A> HMPV> HPV 3 etc

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14
Q

Flu Season is more than just flu

A

Even during peak influenza season (DEc-Feb)–> see RSV and HMPV at high levels

Incidence highest in winter and lowest in Sumer for respiratory viruses

BUT adenoviruses and rhinoviruses are endemic in the US and seen all year round

Also tropical and semitropical areas dont have same seasonality

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15
Q

Many different respiratory viruses

A

Heterogeneous group, a real mixed bag
Over 200 distinct viruses belonging to 6 major families can infect human respiratory tract

  • some viruses common and well established and you should recognize by name, some are newly identified and significance is still being established
  • differ due to size, symmetric, nucleic acid type, lability, mode of replication, and pathogenic and epidemiological behavior
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16
Q

Common respiratory viruses characteristics

A

Worldwide

Short incubation (1 - 4 days)

Person to person spread

Similar pathogenesis

Increased risk of bacterial superinfection

Immunity imperfect-> reinfection common

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17
Q

Respiratory Virus Transmission

A

Person to person normally!

Super contagious

Direct contact, aerosolization of infective droplets during coughing and sneezing or indirectly by hand transfer of contaminated secretions or from contaminated objects to nasal or conjunctival epithelium

Eg RSV stable 3 - 30 hours on countertops

Eyes and nose major portals of entry

WASH HANDS

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18
Q

RV pathogenesis

A

Viruses enter via nose and eyes

–> infect ciliated respiratory epithelial cell slining upper and lower airways, multiply locally no systemic infection

–> cytolytic causing cell damage and death–> clearance mechanisms compromised (damage creates susceptibility to bacterial superinfections)

–> local and circulating Ab response and T cell recognition with release of cytokines

–> recruitment of neutrophils, NK cells, CD4+ and CD8+ T cells, macrophages, mononuclear cells, eosinophils

–> viruses have ways of evading the immune system

–> certain viruses interact with the immune system to promote immediate hypersensitivity reactions leading to virus-induced wheezing and asthma - CYTOKINE STORM

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19
Q

Cytokine storm

A

Immune mediated injury caused by immediate hypersensitivity reaction to virus

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20
Q

Respiratory Syncytial Virus (RSV) - who does it affect

A

Most common cause of bronchiolitis and pneumonia in infants and young children <1 yo

Most important agent of respiratory disease in infancy

Infects virtually everyone by 2 - 3 years of age and reinfections are common throughout life

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21
Q

RSV function and structure

A

Paramyxovirus family

Enveloped: single stranded RNA

120-300 nm

G and F proteins (surface glycoproteins mediate attachment of the virus to the host cell and fusion, respectively)
- F protein also mediates syncytium formation

Virus contains an RNA dependent RNA polymerase for transcription and replication

Other paramyxoviruses = measles, human parainfluenza, mumps, metapneumovirus

Two subgroups - antigenic types A and B

Significance of variants unknown

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22
Q

What proteins mediate RSV attachment, and fusion to host cell and synctitium formation?

A

G (attach)

F(form and syncytium)

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23
Q

Antigenic Subgroups of RSV

A

A - associated with more severe
B - less severe

Significance of variants is unknown

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24
Q

RSV epidemiology

Outbreaks?

Source of infection?

Who is infected?

Episodes?

Immunity?

A

Humans= only source of infections

Annual community outbreaks

50% of all families with children

Circulation is effeicient (2/3 of infants infected in 1st yr, all children by 2 - 3 yr)

Age peak of 2 - 5 mo

50% children have 2 + episodes, 40% infx produce lower respiratory tract diseases

Re infx common for all age groups, immunity imperfect and not completely cross protective against two strains

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25
Q

Serious RSV illness

A

Very young infants, premature infants

Children <2 - 3 yo

Elderly

Children and adults with chronic illness and compromised immune systems

Mortality = .5-1% but > 15% in impaired host

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26
Q

What is the single most important agent in respiratory disease in infancy?

Leading cause of lower respiratory illness in infants and young children worldwide?

A

RSV

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27
Q

RSV mortality

A

Leading viral cause of mortality in infancy

10x morality of influenza in infants < 1 yr

500 deaths per year
- 80% in infants < 1 yo

28
Q

Syndromes of RSV infections in children

A

Bronchiolitis (most common)

Pneumonia

Tracheobronchitis

Croup

Asymptomatic

(Ascending–> descending, most common–> leas common)

29
Q

Clinical Presentation of RSV disease

URI?

LRI?

Clinical findings?

Other?

Duration of illness?

A

URI = cough, rhinitis pharyngitis, fever

LRI = expiration wheezing, air trapping, tachpnea, dyspnea, rales (clicking rattling in lungs), rhonchi (snoring sound in lungs), retractions (sinking in of the chest wall above collarbone, between ribs and below rib cage), nasal flaring, grunting hypoxemia (low oxygenation of blood), irritability, dehydration, respiratory distress

Clinical findings: Hyperexpansion of lungs and hypercapnia (carbon dioxide retention- especially bad when young)

Other; otitis media, vomiting, conjunctivitis

Duration: 10 - 14 days

30
Q

Retractions

A

Look at pic slide 26 of respiratory lecture

  • see child with suprasternal and intercostal retractions and nasal flaring–> child cant breathe
31
Q

Chest X ray: RSV bronchiolitis - children

A

Slide 27 of respiratory lecture

Hyperinflation of lungs (due to airtrapping tachypnea) with flattened diaphragm, horizontal ribs and increased hilar bronchial markings

See pulmonary insterstitial infiltrates with areas of pulmonary collapse

RSV pathogenesis: infx in respiratory tract - no viremia, respiratory epithelial cells killed by virus and cellular immune response–> necrosis of epithelium in medium to small airways–> mucus/fibrin plugs impeding airflow gas exchange and leading to pulmonary infiltrates

32
Q

RSV in adults

A

Healthy adults frequent, mild influenza like

In elderly and immunocompromised (CHF, immune suppression, bronchiopulmonary insuffiency) it can the serious

2- 4% pneumonia deaths among elderly

Suspect RSV in all adults who present with fever and pulmonary infiltrates

33
Q

Hospital associated infections - RSV spread

A

Concern in pediatric wards, nurseries, nursing homes, adult medical wards

Controlling spread can be difficult

Recovered rom counter tops for 3 - 30 h

Cloth gowns, gloves, paper tissue for 1 h

Skin 30 min

Max period of viral shedding is 3 - 8 days for immune competent and 3 - 4 weeks in young infants

WASH HANDS

34
Q

RSV treatment

A

Supportive, maintain hydration and oxygenation and keep airways clear of mucus and debris

No vaccine

Palivizumab(synagogue) - humanized mouse monoclonal Ab for HIGH RISK children
- IM injections 1x/mo during RSV season, 5 doses given

Aersolized - Ribavirin

  • drug to treat RSV lower respiratory tract, cost and risk of aersolized administration, used selectively
  • generic antiviral for lower respiratory tract, not suggested for routine use
35
Q

Human Metapneumovirus (HMPV)

What family?

Age?

Location?

What type of particles

RNA vs DNA?

Enveloped vs not enveloped?

Genotype?

A

Family: paramyxovirus

Not a new virus

All age groups all over the world

Pleomorphic particles, spherical, filamentous

SsRNA, single stranded negative sense RNA virus

Enveloped

No hemagglutin

4 genotypes of the virus that can be found in two major groups (A and B)

36
Q

SEasonality of HMPV

A

Mid January – mid June

37
Q

HMPV epidemiology/disease

A

Symptoms similar to RSV

Acute respiratory illness in children, elderly, those with underlying immune compromise and cardiopulmonary disease

Virtually all children infected by 5 to 10 yo, new infections throughout life

Clinical presentation from URI to severe bronchiolitis and pneumonia

38
Q

HMPV treatment or vaccine?

A

None

39
Q

Parainfluenza viruses

Family?

Size?

Enveloped/not enveloped?
Genetic material?

Proteins involved ?

A

Paramyxovirus family (with RSV, HMPV, mumps and measles)

120-300 mm

Enveloped

Nonsegments, ssRNA genome

Paramyxoviruses have hemagglutinin and neuraminidase activity (HN protein) and fusion (F protein)
- positive hemagglutination tests are parainfluenza and negative are HMPV

40
Q

What is the major cause of croup, and an important cause of lower respiratory tract infection in infants and young children?

A

Parainfluenza virus

41
Q

Parainfluenza virus antigenic types

Serotypes?

A

Four serotypes: 1, 2, 3, 4 (A&B)

Individual types are antigenically stable
- unlike influenza, no antigenic shift or drift

Differ in frequency of occurrence, disease spectrum, and epidemic patterns

Cause disease in larger airways of LRT

Important cause of LRI in infants and children (15-20%( of all non bacterial respiratory disease causing hospitalization

42
Q

Differences in parainfluenza antigenic subtypes

A

PIV1 - major cause of acute viral croup, mostly in the fall and early winter, 6 - 12 mo yo

PIV3 and 2 (second and 3rd most frequent cases)

PIV2 - fall and early winter but not concurrent with PIV1
- less significant, 6 - 12 mo yo

PIV3 - mostly in the spring and summer- common cause of pneumonia and bronchiolitis , all throughout the year
- highest attack rates in 3 - 6 mo

PIV4 is least common and infrequent cause of acute LRtract disease and associated with mild URI

Viruses
1 & 2: Croup, 6 mo - 12 yr, Autumn
3: Bronchiolitis, Pnejmonia, < 6 mo, Endemic (spring)
4: URI, children, endemic

43
Q

Parainfluenza croup

A

Virus infects epithelial cells of upper airways

Begins as URI with thin nasal discharge, sore throat, mild cough

Within 1 - 2 d, inspiration stridor, retractions, worsening barking cough (hoarseness due to narrowing in region of larynx and subglottic trachea)

Symptoms exacerbated at nigh, children wake up gasping for breath

Self limited, last 3 - 7 days in most and up to 7 - 14 days

STEEPLE SIGN - see pic on slide 42

44
Q

Treatment of parainfluenza croup

Immunity?

A

Supportive care for mild disease

Oxygen, nebulized epinephrine and corticosteroids for severe infection

Immunity short lived so reinfections throughout life are common though less severe

45
Q

Croup clinical pearls

A

Symptoms from inflamed larynx and subglottic airway, may close the airway in severe case

Dry barking seal life cough

6mo - 12 yrs, peak incidence at 2, more common in boys

Fall or early winter

10pm - 4 am ED visits, worst ending symptoms at night

Self-limited condition - last 3 - 7 days, up to 7 - 14 days in some

See treatment slide for treatment

46
Q

Adenovirus: composition

Enveloped/ non enveloped

DNA vs RNA

A

Nonenveloped viruses

80 - 90 mm in size

Icosahedral capsid of. Hexon and Peyton capsomers

DsDNA (encodes 30 - 40 genes)

Fibers project from capsid at Peyton base and are major attachment for proteins (knobbed viruses–> classic shape)

Peyton base and fiber proteins determine serotypes, tissue tropism and disease

47
Q

ADenovirus: Antigenic types

A

~ 100 types, 57 affect humans

Species A to G (varied tissue tropism)

  • mainly b and C, some E: infect respiratory tract
  • B and D: ocular
  • primarily F, some a and G–> GI disease

Ubiquity and persistence in host tissues for days to years (prolonged infx without disease!)

Only 45% of infx result in disease

Serotypes 1-5, 7, 8, 21 important respiratory agents, 14 associated with sever pneumonia in civilian and military communities

48
Q

ADenovirus epidemiology

A

Endemic in US, sporadic outbreaks

Children: 6 mo - 5 yrs and grade school and junior high

Epidemics occur in military recruits (primarily AdV types 4 & 7)

Spread by respiratory and fecal route

  • resist drying, detergents, GI secretion
  • aerosols, fingers, fomites (including medical instruments), poorly chlorinated swimming pools
  • in day care, hospitals, clinics, children’s homes, physicians offices, industrial settings
49
Q

Adenovirus multiple syndromes

Infants, young children,

School age children

Military recruits

Transplant recipients, AIDS patients, other immunocompromised

A

Many common diseases including multiple respiratory and GI syndromes, significant cause of conjunctivitis (pink eye)

Cause disseminated disease and high morbidity and mortality in immunocompromised patients, transplant reciepients and are a significant cause of nonstreptococcal exudative pharyngitis < 3 yo

Infants, young children,

  • acute febrile pharyngitis
  • **pneumonia
  • pertussis like syndromes

School age children

  • pharyngoconjunctivial fever
  • pic on slide 49

Military recruits
- acute respiratory disease

Transplant recipients, AIDS patients, other immunocompromised

  • disseminated diseas
  • acute hemorrhagic cystitis
50
Q

Pharyngoconjunctival fever

A

Slide 49
- foreign body sensation in right eye

Conjunctiva was injected and red with clear discharge

No foreign body–> give anti-inflammatories for possible allergic reaction–> next day eye was swollen and appearance of pale real conjunctiva was intensely red and granular

Patient complained of severe eye pain and burning, photophobia, and eye was constantly tearing

Over the next 2 - 3 days, develop:

  • sore throat, cough, Coryza, stiff neck, malaise aches and pains, fever, vomiting, diarrhea, anorexia, lymphadenopathy, left eye conjunctivitis
  • adenovirus from respiratory tract, persisted for 14 days infected from children
51
Q

Rhinovirus Characteristics

Family? Genetic material? Enveloped? Size? Viral proteins? Proteins? Serotypes?

A

Picornaviridae: small RNA virus

Genus: enterovirus

Naked, nucleocapsid,

Capsid has 4 viral proteins: VP1, VP2, VP3, VP4

Attach to intracellular adhesion molecule 1(ICAM-1) on cells (member of Ig super family(

SsRNA genome (single stranded negative sense RNA)

> 100 sero/genotypes in three groups (A-C); 3 - 4 circulate at a time

Common cold virus

Acid labile (unlike enteroviruses) so they cannot replicate in GI tract

52
Q

What is the common cold virus?
/ What is the most commonly identified virus from persons experiencing acute respiratory illness; seen in all age groups ?

A

Rhinovirus

53
Q

Salient characteristics of rhinovirus

A

Antigenic diversity!
3 - 4 serotypes circulate at one time

Infection with one type appears to confer lasting type specific immunity but offers no protection against other types

By adulthood, we have Ab to about half the serotypes

Infections throughout the year but peak in the fall/ spring

54
Q

When do rhinoviruses occur and in what population

A

All ages, especially older children and adults

All throughout the year, peak activity in fall and spring

55
Q

Where is most viral infection in the rhinovirus?

A

Most viral replication is in nose; release of bradykinin and histamine causes “runny nose”

56
Q

Rhinovirus Serious disease

A

Flu like illness
- significant cause of lower respiratory tract disease, more common than expected

Indirectly or directly cause many cases of acute sinusitis and otitis media

Important role of rhinoviruses as a cause of

  • bronchiolitis in infancy,
  • childhood pneumonia
  • exacerbation of asthma, COPD, cystic fibrosis,

Enterovirus respiratory infections - associated with respiratory illness, seen in late summer/early fall

57
Q

Treatment of rhinovirus

A

Zicam!

58
Q

Corona virus characteristics

Enveloped/nonenveloped?

Shape/size

Genome?

Infection site?

Serotypes?

A

Enveloped virus

Petal or club shaped spikes (solar corona) created by spike protein peplomers

SsRNA genome, positive sense single stranded RNA

Phenotypically and genotypically diverse

Infect respiratory and GI tracts of mammals and birds

4 respiratory serotypes in man

SARS coV in 2003; MERs coV in 2012

59
Q

SEasonality of common cold

A

In the winter corona virus is more common the cause

In the summer rhinovirus more commonly causes the common cold

60
Q

What does RNA genome code for in the coronavirus?

A

Two non structural replicate polyproteins and four structural proteins

structural proteins

  • spike (S): responsible for receptor binding
  • envelop (E): virus assembly
  • membrane (M) glycoproteins : virus assembly
  • nucleocapsid (N) protein: internal protein binds to viral RNA to form ribonucleoprotein complexes

Replicate polyproteins directly translated from viral genome and used in viral transcription and replication

61
Q

Coronavirus characteristics

A

Common viruses, people get in their life time

10-30% common colds

Can cause more serious LRTI

Can also cause enteric, hepatic, or neurological diseases

Can be found in other species, birds cats dogs pigs mice, horses whales and are widespread in bats!

62
Q

Respiratory Viruses: prognosis and complications

A

Excellent for healthy individuals

Increased risk: young children, elderly, ill chornically ill, immunocompromised

Complications

  • exacerbation of underlying respiratory disease
  • development of chronic lung disease
  • possible secondary bacterial infections
  • apnea, respiratory failure
  • acute otitis media
  • sudden infant death syndrome in immunocompromised children
63
Q

Respiratory Viruses: Immunity

A

Infection induces immunity only partially protective and of short duration

Ab acquired early in life but reinfection is common

Cell mediated immunity is likely to be pivotal in clearance of RVs and in recovery

  • resistance to infection of upper respiratory tract due to secretory antibody
  • resistance of lower respiratory tract due to circulating antibody

Illness is. Milder with reinfection

Ag variants may exist for which immunity is not completely cross protective

Only vaccines for influenza

64
Q

RV treatment

A

No vaccines or therapeutics for most respiratory viruses

Good supportive care

Treatment

  • aersolized ribavirin (RSV) for select patients,
  • amantadine, rimantadine (influenza A)
  • Zane I IR, oseltamivir (influenza A and B)

RSV: treat with aersolized ribavirin and prevent with palivizumab (humanized monoclonal ab)

Parainfluenza: ribavirin (limited studies)

Adenovirus: ribavirin, cidofovir - anecdotal

Rhinovirus: limited, pleconaril an dother canyon inhibitors

65
Q

RV prevention

A

Immunoglobulin: Palivizumab (synagogue) humanized monoclonal antibody against RSV

Vaccine and antivirals (influenza)

66
Q

RV control

A

Interrupt transmission: contact isolation, cohorting, gowns and gloves, HANDWASHING

67
Q

Other causes of respiratory diseases

A

Certain bacteria and fungi but at lesser frequency than viruses discussed today

Bacterial infections may result of secondary infection following viral illness
- symptoms may persist longer than expected 10-14 days of viral illness and fever worse and get worse after a few days

Secondary infections: sinusitis, ear infections, pneumonia (productive cough for bacterial infections with more discrete foci unlike the diffuse interstitial infiltrates of viruses)

Microbiology (10 decks)

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