Respiratory viruses and 'atypical' respiratory pathogens Flashcards
-The complexity of the various compartments of the respiratory tract, and the microbial agents which cause infections in this system. -The types of infection presenting in the respiratory system and their causes. (including common cold, laryngitis, tracheitis, bronchiolitis) -Influenza as a major respiratory disease with worldwide significance. Focussing on: Nature of the disease, viral biology and complications. Classification of flu viruses Influenza as a recurring epidemic disease, due to
Types of respiratory infection
Surface
Systemic
Professional invaders
Secondary invaders
Surface respiratory infection plus example
Local spread
Short incubation
E.g. common cold, candida
Systemic respiratory infection plus example
Spreads from mucosal site of entry to other site in body
Returns to surface for final shedding stage
Longer incubation - weeks
E.g. measles, mumps, rubella
Professional invaders
Infect healthy respiratory tract
Secondary invaders
Infect compromised tract
Infections of the nasopharynx
Rhinitis and sinusitis: the common cold
- caused by various viruses
- self-limiting and not systemic in healthy people
- identification usually not necessary unless clinical symptoms worsen - involvement of LRT
- molecular methods most common for ID, epidemiological info only
Treatment of Rhinitis and sinusitis
No vaccines
Treatment symptomatic
Mechanism infection of the nasopharynx (SEE PIC)
lytic infection
I. Adhere to cilia or microvilli on mucosal epithelial cells - avoid flushing
II. Infect cells, spread to neighbouring area
III. Inflammatory response results in classic ‘cold’ symptoms
Common cold viruses
Rhinoviruses (>100 types) Coxackie virus A Influenza virus Parainfluenza virus Respiratory syncytial virus Coronaviruses Adenovirus Echovirus
Attachment mechanism rhinoviruses
Capsid protein binds to ICAM-1 type molecule on cell
Attachment mechanism influenza virus
Hemagglutinin binds to neuraminic acid-containing glycoprotein on cell
Adenovirus
Icosohedral symmetry, non-enveloped - resistant to desiccation
-resistance to environment promotes efficient transmission
Attach via adhesins on end of penton fibres
dsDNA
Pharyngitis and tonsilitis
70% caused by viruses
-similar viruses as common cold
Common complication of common colds due to surrounding infections
Also site of entry of EBV and mumps virus (before dispersal around body)
Mumps
Paramyxovirus
Air-borne spread (saliva etc.)
Commonly spread and contracted in school age children
Most children now vaccinated - MMR
MMR fear > occurrence in UK for number of years
Complications of mumps
Include Orchitis
- inflammation of testicles
- painful especially in adult men
Laryngitis and tracheitis
Often caused by parainfluenza viruses, adenovirus and influenza
Burning pain in larynx and trachea
Can become obstructed easily in children - croup
-specific type of cough with stridor inhalation
Caused by serious narrowing of airway
Bronchitis and bronchiolitis causes
Several viral causes: Rhinoviruses, coronaviruses (SARs), adnoviruses and influenza
Atypical pathogens: Mycoplasma pneumoniae
Many 2. infections
-especially in children
-narrow airways
- –> bronchiolitis and pneumonia
75% bronchiolitis caused by Respiratory Synctial Virus
Respiratory Syncytial Virus (RSV) transmission
Aerosol and hand-hand/ surfaces
Respiratory Syncytial Virus (RSV) pathology
Creates large fused cells
Respiratory Syncytial Virus (RSV) epidemiology
Outbreaks in winter months
Nearly all children have been infected by age 2- but often nothing more serious than common cold
Severe in young infants- peak mortality 3 months of age (why?)
RSV in infants - symptoms
Cough
Cyanosis
Rapid RR
–> Penumonia and bronchiolitis
RSV in older children and adults - symptoms
More like common cold
RSV treatment
Supportive
-hydration
-bronchiodilators
Severe cases require ribavirin antiviral or Palivizumab-prophylactic in at risk groups (e.g. prem babies at risk (heart defect, lung disease, immunodef., in season)
Influenza virus name
Orthomyxoviridae
Influenza virus transmission
Aerosol droplet
Influenza virus epidemiology
Occurs worldwide- restricted to coldest months of year
Influenza virus mechanism
Initial infection: virus attaches to sialic acid receptors on epithelial cells via viral HA protein
1-3 days: liberated cytokines result in systemic chills, malaise, fever and muscle aches, runny nose and cough
Usually recover after 1 week, but some develop pneumonia and bronchitis and have lingering symptoms.
Influenza virus secondary invaders
Can cause lethal infections: pneumococci, staphylococci
Influenza virus - structure
Two surface glycoproteins: -HA- Haemagglutinin -NA- Neuraminadase Host-derived viral envelope ssRNA genome: 8 segments Nucleoprotein and polymerases
Influenza virus - major antigens (and classification)
HA: major antigenic determinant -HA binds sialic acid receptors on epithelial cell surface -major source of antigenic variation -16 avian and mammalian types -only 3 are human adapted (HI-3) NA : second antigen determinant -involved in release of the virus from host cells during budding -9 known serotypes -2 human adapted (NI-2)
Three types of influenza
A: yearly epidemics and occasional serious worldwide epidemics - important animal reservoirs in birds and pigs
B: yearly epidemics - no animal reservoir
C: minor respiratory illness - no epidemics
Viral uptake - HA
- HA mediates binding to sialic acid containing receptors
- Internalised by endocytosis
- Endosome acidified
- HA conformation alters, M2 iron channel important here - HA mediates fusion of viral envelope and endosome memrane
- viral RNA and polymerases delivered into cell
- replication
Antigenic drift influenza virus
Small point mutations in HA and NA that accumulate in population over time
Result in new variant viruses that can re-infect individuals
Source of yearly flu epidemics worldwide
All types of influenza
Flu vaccines
Yearly epidemic cover
Vaccine strains chosen in February for northern hemisphere
Strains grown in embryonated hen eggs: not applicable to individuals with Egg allergy
Formalin killed, detergent treated viral ‘split’ vaccines
Southern hemisphere strains used to predict next years northern strains- yearly vaccines of at-risk (current dominant strains are H3N2-types)
Vaccine contains one H3N2 strain, one H1N1 and one B strain
Administered in October each year
Do not cover pandemics - they come from unexpected strains
Current flu vaccine
A/Michigan/45/2015 (H1N1)pdm09-like virus;
A/Hong Kong/4801/2014 (H3N2)-like virus;
B/Brisbane/60/2008-like virus.
Antigenic shift
Less common
Results in major shift in viral composition
Major gene reassortment resulting in new HA and NA types
Little immunity in population
CAUSE OF MAJOR WORLD PANDEMICS
-only influenza A
Antigenic shift - how?
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
HINI ‘Swine’ Flu - where did that come from? A/ California/ 2009/ H I N I
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
- has proven safe and effective
Brief history of pandemics
1918- source unknown- likely to be avian- WORST EVER: 20-40 million
-influenza
-pre-antibiotics - 2. infections unable to be treated
-public health measures not as good
1957- Recombinant 1918 virus with avian sequences: H2N2
1968- Recombinant between H2N2 and unknown avian source: H3N2
2010-11 Novel H1N1- ‘swine’ flu
1918 ‘Spanish flu’ Pandemic: H I N I
think Edward Cullen!!
Killed up to 40 million people worldwide in a very short period 1918-19 (directly after Great War)
Extremely virulent
Resulted in 10-year drop in life expectancy in USA
Many deaths from secondary infections
- remember pre-antibiotic!
Unusually high mortality rate in
young people
W-shaped death curve contrasts normal U-shaped curve
Notably less deaths in over age 34 than might have been expected from completely naïve pop
Hints at history………….. Similar virus pre 1
Evolution of Spanish Flu
In 1918 the cause of Flu was not even known, not until 1930 was an influenza virus isolated (remember Haemophilus influenzae)
Thus evidence is thin on H1N1 origins
But, 1957 and 1968 pandemics came about by re-assortment with avian viruses
1918/H1N1 likely to have come from reassortment or directly by adaptation to human habitation
Geographical origin of Spanish flu (controversial)
Army camps in Kansas, USA – Spread to Europe when American soldiers entered Great War in Europe
Etaples British Army Camp, Northern France- Disease became established and quickly spread, demobilised troops spread disease worldwide
Are we safe from pandemics for now?
Global Action Plan:
- > in seasonal vaccine use
- > in vaccine production capacity
- research and development
Bird flu
Any of these could recombine with present H I N I and H3N2 strains to create new pandemic
-H5N1 strains (around 50% of people die)
A new threat: H7N9 (and H7N7)
571 cases with 212 deaths in China since discovery in March 2013 (22%)
Evolved from bird strains in Live Poultry market environment
No human-human transmission
Combatting a pandemic
Vaccines
Antiviral drugs
Combatting a pandemic: vaccines
Would require knowing which virus to create a vaccine against
Recombinant techniques should speed this process- difficult but best option
Combatting a pandemic: antiviral drugs
Resistance a problem Tamiflu, Relenza, peramivir, H5N1 Vietnam resistant to amantidine (as is New H1N1 !)
Pneumonia
Many organisms cause identical symptoms
Only organisms less than 5mm can enter the alveoli
Often secondary to preceding damage- Cystic Fibrosis or influenza
Influenced by Immunocompromisation
- e.g. HIV and pneumocystis infections
Pneumonia in children
Mainly viral causes – RSV, parainfluenza
- secondary bacterial infections
Neonates may acquire Chlamydia from mother in birth
Pneumonia in adults
Bacterial causes more common-: e.g. Strep. Pneumoniae formerly most common
Atypical respiratory pathogens: atypical pneumonia
Term originally coined as pneumonia caused by Penicillin resistant organisms
‘Walking pneumonia’- not hospitalised
Typically report chest pain, cough, shortness of breath
On the rise in comparison with pneumococcus
Atypical pneumonia mainly caused by
Mycoplasma pneumoniae
Chlamydophila (formerly Chlamydia)
Legionella pneumophila
AIDS associated atypical pneumonia
Pneumocystis spp (fungus) Aspergillus spp (fungus)
Mycoplasma pneumonia
Very small bacterium with minimalist genome (0.5Mbp)- possibly smallest of any free-living organism in nature (Ventner)- made artificially- SYNTHIA (related spp.)
No peptidoglycan- cholesterol- penicillin resistant…
‘walking’ pneumonia- sick but not hospitalised
Efficient binding to cilial epithelial cells via a special cytadherence organelle rich in a cytadhesin (P1) for sialic acid rich glycolipids
Major cause of pneumonia in young adults and students
Mycoplasma pneumoniae
Chlamydophila pneuoniae
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
Related C. psittaci from parrots !!!!
Legionnaires disease
Pneumonia symptoms often accompanied by neurological presentations such as confusion
No human-human transmission
Ubiquitous in environment (symbiosis with amoeba)
Intracellular invader of phagosomes and lung cells
Legionnaires disease acquired from/ in
From environmentally derived aerosols -air-con -spa-baths -hot-air heating -shower systems -cooling tower reservoirs Commonly in hospitals, high rise blocks, hotels, student residences, factory air-con sources
Legionella pneumophilia
- type of bacteria
- isolation
- test
Motile aerobic Gram-negative rod
Isolation on BCYE medium (Buffered Charcoal Yeast Extract)
Urinary antigen test
Transmission of rhinitis/ sinusitis
Transmission by aerosol
