Respiratory Viruses and Atypical Respiratory Pathogens

Question 1

Name the types of respiratory infections

Answer 1

Surface: local spread
- Short incubation, e.g. common cold, Candida

Systemic: spreads from mucosal site of entry to other site in the body

• returns to surface for final shedding stage
• longer incubation- weeks
• e.g. measles, mumps, rubella

Question 2

Name the types of respiratory pathogens

Answer 2

Professional invaders:- infect healthy respiratory tract

Secondary invaders: - infect compromised tract

Question 3

What causes infections of the nasopharynx (rhinitis and sinusitis - the common cold)?

Answer 3

Various viruses
Transmission by aerosol
Self-limiting and not systemic in healthy people
No need for identification unless LRT spread

Question 4

How does the virus infect the nasopharynx?

Answer 4

Adheres to ciliated epithelium
Enters cells, spreading to neighbouring areas
Inflam response = cold symptoms

Question 5

Adenovirus features?

Answer 5

Icosohedral symmetry, non-enveloped resistant to desiccation
Attach via adhesions on the end of penton fibres
dsDNA
Cause pharyngitis: conjunctivitis, bronchitis

Question 6

What is pharyngitis and tonsilitis?

Answer 6

Complication of colds due to surrounding infecs
Site of entry of EBV (Herpes) and mumps virus
70% caused by viruses - rhinoviruses, adenoviruses, influenza viruses

Question 7

Mumps features?

Answer 7

Paramyxovirus
Air-borne spread
Common in school age children - most vaccinated (MMR)
Complications - Orchitis = inflam of testicles

Question 8

What causes laryngitis and tracheitis?

Features?

Answer 8

Parainfluenza viruses, adenovirus and influenza
Burning pain in larynx and trachea, easily obstructed in children
Cough with stridor inhalation

Question 9

Causes of bronchitis and bronchioitis?

Answer 9

Viral causes - rhinoviruses, coronaviruses, adenoviruses, influenza
Atypical pathogens - mycoplasma pneumoniae
Many 2ndry infecs - especially in children - narrow airways - leading to bronchiolitis and pneumonia

Question 10

What causes 75% of bronchiolitis?

Answer 10

Respiratory syncytial virus

Question 11

RSV (Resp syncytial virus) features?

Answer 11

Aerosol and surface transmission
Pathology creates large fused cells
Outbreaks in winter
Nearly all children infected by 2yrs old but only as common cold
Severe in young infants - peak mortality 3 months of age
Infants - coughs, cyanosis, rapid resp rate, pneumonia and bronchiolitis
Older = more like common cold

Question 12

Treatment of RSV?

Answer 12

Supportive
Hydration
Bronchodilators
Severe cases require ribavirin antiviral or palivizumab-prophylactic

Question 13

Name the influenza virus?

Answer 13

Orthomyxoviridae

Question 14

How does orthomyxoviridae cause influenza?

Answer 14

Transmitted by aerosol droplet
Restricted to coldest months of the year
Initial infec: virus attaches to sialic acid receptors on epithelial cells via viral HA protein
1-3 days: liberated cytokines result in systemic chills, malaise, fever, muscle aches, runny nose and cough
Recover after 1 week but some get pneumonia and bronchitis
2ndry invaders = lethal infections: pneumococci, staphylococci

Question 15

Describe the structure of the influenza virus?

Answer 15

2 surface glycoproteins:
- HA - Haemagglutinin
- NA - Neuraminadase
Host derived viral envelope
ssRNA genome: 8 segments
Nucleoprotein and polymerases

Question 16

What do the major antigens of the influenza virus do?

Answer 16

HA: major antigenic determinant:

• HA binds sialic acid receptors on epithelial cell surface
• Major source of antigenic variation

NA: second antigen determinant:
- Involved in release of the virus from host cells during budding

Question 17

Name the types of influenza?

Answer 17

A - Yearly epidemics and occasional worldwide epidemics - animal reservoir
B - Yrly epidemics - no animal reservoir
C - Minro respiratory illness - no epidemics

Question 18

How to classify influenza?

Answer 18

Influenza type, location of isolation, strain number, yr of isolation, antigen

H-antigens (HA)
- 16 types but only 3 human adapted (H1-3)

N-antigens (NA)
- 9 serotypes but only 2 are human adapted (N1-2)

Question 19

How does the viral uptake of HA occur?

Answer 19

1. HA mediates binding to sialic acid containing receptors
2. Internalised by endocytosis
3. Endosome acidified- HA conformation alters, M2 ion channel important here
4. HA mediates fusion of viral envelope and endosome membrane
   Viral RNA and polymerases delivered into the cell
   REPLICATION

Question 20

What causes antigenic DRIFT?

Answer 20

Small point mutations in HA and NA that accumulate = new variant viruses that can re-infec individuals
Source of yrly flu epidemics
All types of influenza

Question 21

Antigenic SHIFT features?

Answer 21

Cause major shift in viral composition
Major gene reassortment = new HA and NA types formed
Cause of major world pandemics
Only influenza A

Question 22

How does antigenic shift occur?

Answer 22

Simultaneous infection of human/ animal with Human and ‘other’ influenza virus
Reassortment of genes due to homologous recombination with existing human virus
Dissemination through immunologically naïve population
WORLDWIDE PANDEMIC

Question 23

Where did HINI swine flue come from?

Answer 23

Re-assortment of existing swine flu viruses
Contain genes of Human, Swine and Avian origin
Amantidine resistant and some oseltamivir resistant
VACCINE has been widely distributed globally

Question 24

What is the global action plan for influenza?

Answer 24

Increase in seasonal vaccine use
Increase in vaccine production capacity
Research and development

Question 25

How to combat a pandemic?

Answer 25

Vaccines Antiviral drugs: - Resistance a problem - tamiflu, relenza

Question 26

What causes pneumonia?

Answer 26

Organisms less than 5mm enter the alveoli Often 2ndry to preceding damage - CF or influenza Influenced by immunocompromisation e.g HIV Children: - Viral causes - RSV, parainfluenza - 2ndry bacterial infections Adults: - Bacterial causes more common - strep. pneumoniae

Question 27

Viral causes of pneumonia?

Answer 27

``` Influenza A/B Parainfluenza Measles Resp syncytial virus Adenovirus ```

Question 28

What do atypical resp pathogens: atypical pneumonia cause?

Answer 28

Chest pain, cough, SOB

Question 29

Examples of atypical resp pathogens that cause atypical pneumonia?

Answer 29

Mycoplasma pneumoniae Chlamydophila Legionella pneumophila

Question 30

Mycoplasma pneumoniae features?

Answer 30

Small bacterium with minimalist genome (0.5Mbp) No peptidoglycan- cholesterol- penicillin resistant ‘walking’ pneumonia- sick but not hospitalised Major cause of pnuemonia in young adults and students Efficient binding to cilial epithelial cells via a special cytadherence organelle rich in a cytadhesin (P1) for sialic acid rich glycolipids.

Question 31

Chlamydophila pneumoniae features?

Answer 31

Small, obligate Gram-negative intracellular pathogen Complex life-cycle: - Elementary body- akin to a spore - Reticulate body- intracellular growth and replication No peptidoglycan (Pen Flu-like illness Detection by ELISA or MicroImmunofluorescence

Question 32

Legionnaires disease caused by?

Answer 32

Legionella pneumophila No human-human transmission Acquired form environmentally derived aerosols Aircon, heating, showers Common in hospital, high rise blocks, hotels, student accom Causes confusion and pneumonia symptoms Intracellular invasion of lung cells and phagosomes

Question 33

Legionella pneumophila features?

Answer 33

Motile aerobic Gram-negative rod Isolation on BCYE medium (Buffered Charcoal Yeast Extract) Urinary antigen test

Question 34

Rhinovirus attachment mechanism?

Answer 34

Caspid protein binds to ICAM-1 type molecule on a cell = common cold