-
10-29-b: Viral Respiratory Tract Infections Part I
- Respiratory infections are the #1 cause of outpatient visits in the US
- Most are just a nuisance but often can be serious or fatal (extreme cas is hantabirus pulmonary syndrome > 50% fatality
- Role of vaccines
-
Types of Respiratory Infections
- Upper respiratory Infections: sinusitis, common cold, pharyngitis, epiglottitis, laryngotracheitis
- Loser respiratory infections: bronchitis, bronchiolitis, pneumonia – can sometimes be fatal
- The lower you go, the more serious it gets
-
Common cold
- Rhinoviruses
- Coronaviruses
- These two probably represent 80% or common cold infections, Rhino to Corona 4:1
-
Pharyngitis and tonsillitis
Begin to have bacteria as a large number of causes as well as viruses
-
Pneumonia
A lot of bacteria, viruses, as well as fungi
-
What contributes to disease symptoms in viral pathogenesis?
- Cell Killing and Immunopathology: respiratory epithelium, etc.
- Response to flu is to generate a cytokine floow, IL-1 fever
-
The Common Cold: Symptoms
Scratchy throat, nasal discharge, malaise, headache, cough; 1-2 day incubation period, no fever
-
Common cold: pathogenesis:
- infection of respiratory epithelium
- ciliary action stops
- mucous secretion increases
- inflammaroty reaction
- infection stopped by IFN and antibodies
-
Common cold: epidemiology
- Inhalation of infected droplets
- Infected mucous transfer to nose or eye
- Children initiate outbreaks due to poor hygiene
- Fomites
-
Common cold: prevention and treatment
- Hand washing
- Avoid people with colds
- Symptomatic
-
Rhinovirus
- Principal common cold virus
- Many different serotypes, makes vaccine development difficult
- But days of work lost because of symptoms
- Unenveloped; 4 structure proteins, VP1 important:
- Mimicking ICAM-1or the viral attachment site can prevent binding of virus to cell and prevent infection
- Can also target a protease that chops up the proteins into usable components that allow replication; if block protease, as in HIV as well, then block viral replication
-
Epidemiology of Rhinovirus Infections
- Resistant to drying and detergents
- Replication best at 33C
- Everyone at risk
- Worldwide, usually in winter
-
Adenovirus
- Not a major cause of common colds:
- Associated with pharyngitis and a range of other diseases, including som serious lower RIs
- NOT enveloped: knobs on the virus allow interactions, many treatment prevent interactions of those knobs with the cel
- Relatively cell-independent virus, so can also target early gene production to prevent replication.
-
Diseases caused by adenoviruses
- Able to cause a wide range of disease b/c can infect many different organs, unlike rhinovirus – only respiratory tract cells
- Endemic respiratory disease:
- Acute respiratory disease of military recruits: can be fatal
- Pneumonia:
- Pharyngoconjunctival fever: eye attacked
- Keratoconjunctivitis: eye
- Less common include: gastroenteritis, pertussis-like syndrome, hepatitis, acute hemorrhagic cystitis, etc.
-
Disease mechanisms of adenoviruses
- Spread by: aerosol, close contact,or fecal-oral means to establish pharyngeal infection, fingers spread to eyes
- Virus infects: mucoepithelial cells in the respiratory tract, GI tract, and conjuctive or cornea, causing cell damage directly
- Virus persists: in lymphoid tissue (e.g. tonsils, adenoids, Peyer’s patches)
- Antibody – important tof prophylaxis and resolution
-
Epidemiology of Adenoviruses
- Resistant to drying and GI tract (chlorine in pools)
- Asymmptomatically shed
- Day-care centers, military traning camps
- Worldwide, all seasons
- Live vaccine for military use
-
Other issues for Adenoviruses
- Viral pharyngitis (including adeno) can resemble strep throat
- Throat swab – rapid Ag test for strep; PCR for viruses
- Adenoviruses are popular vehicles for gene therapy
-
Coronaviruses
- Second most common cause of colds
- Also cause GI tract infections and SARS
- Positive-stranded virus
-
Coronavirus disease mechanisms
- Infects epithelial cells of upper respiratory tract
- Enveloped virus is able to survive the GI tract
- Reinfection occurs in presens of serum antibodies
-
SARS ( Severe Acute Respiratory Syndrome)
- Guangdong province, PRC, Nov 2002
- Flu-like symptoms+diarrhea
- 20% of overall fatality
- New corona virus: SARS CoV
- Source horseshoe bats (rhinolophidae species): source reservour for the virus
- Classic zoonosis
-
SARS – last group of cases
- In April 2004 when 9 people were diagnosed; linked to virology lab
- Who should be watched carefully?
- People with radiologically confirmed pneumonia, and a risk factor (visit to far east, hospital/lab contact):
-
Human metapneumovirus
- Recently-discovered paramyxovirus (2001)
- In Holland, 100% seroconversion by age 5
- Causes mild or severe URT and LRT infections in all age groups (particularly the elderly)
- Clinically similar to Respiratory Syncytial Virus (5-15 % of bronchiolitis in infants)
-
Recent U.D. study suggests about 6% of children in tertiary care setting have hMPV
- 12-15% of LRT (e.g. bronchiolitis) and URT infections in children may be due to the virus
- Complicates RSV infection and found in conjunction with HIV, too. (dual infections)
- Now found worldwide
- Serious enough to warrant vaccine development
|
|