1. Viral Infections of the Respiratory System

2.  Common cold (rhinitis).  Sinusitis & otitis media.  Pharyngitis & tonsillitis.  Croup (acute laryngotracheobronchitis).  Acute bronchitis & acute bronchiolitis.  Viral pneumonia. Respiratory infections caused by viruses:

3. Name of the virusDisease RhinovirusesURT infection Human metapneumovirusLRT infection AdenovirusesURT and eye infections Influenza virusesURT & LRT infection Parainfluenza virusesURT & LRT infection Respiratory syncytial virusURT & LRT infection CoronavirusesURT & LRT infection Common respiratory viruses  URTI: common cold, tonsillitis, pharyngitis.  LRTI: croup, bronchitis, bronchiolitis, pneumonia.

4. Some viruses cause pneumonia as part of a multisystem syndrome, e.g. Measles, Varicella-zoster virus, Epstein - Barr virus, Cytomegalo virus (CMV) and Herpes simplex virus.

5. Rhinoviruses The most common cause of common cold. Family: Picornaviridae. Structural features: Non-enveloped Ss RNA viruses. more than 100 serotypes. Transmission: -Inhalation of infectious aerosol droplet -Contaminated fingers or fomites. Treatment and prevention: self-limiting, no specific treatment & no vaccine available.

6. Adenovirus  Family: Adenoviridae > 50 serotypes.  Virology: Non-enveloped, Ds DNA virus.  Pathogenesis: Adenoviruses infect the epithelial cells of respiratory tract, conjunctiva, urogenital tract & GIT.  Clinical syndromes:  Pharyngitis and tonsillitis.  Epidemic pharyngioconjunctivitis (pink eye).  Pneumonia.  Gastroenteritis (diarrhoea & vomiting)  Acute hemorrhagic cystitis & urethritis.  No specific treatment or vaccine.

7.  Family: Paramyxoviridae.  Structural features: Enveloped viruses with Ss RNA genome. There are 4 types (1-4)  Transmission: Inhalation of infected droplets.  Clinical syndrome: Croup (or laryngotracheobronchitis). Fever, harsh cough, difficult inspiration. Bronchiolitis (cough, fever & wheeze ≤ 2 years). Pneumonia.  No specific treatment or vaccine. Parainfluenza Virus

8. Respiratory Syncytial Virus (RSV)  Family: Paramyxoviridae.  Virology: Enveloped, Ss RNA virus.  Transmission: Inhalation of infectious aerosols mainly in winter.  Clinical syndromes: Bronchiolitis. Pneumonia. These conditions can be fatal in neonates, prematures and in infants with congenital defects or who are immunodeficient.

9.  Treatment: Inhaled ribavirin for infants with severe cases.  Vaccine:  No vaccine available.  Specific immunoglobulin can be given for high risk infants.

11.  Family: Orthomyxoviridae  Genome: Enveloped Ss RNA with 8 Segments.  The envelop contains two glycoproteins:  Haemagglutinin (HA)  Neuraminidase (NA)  Three Types (Genera): Type A: infects Man, and animals (birds, pigs). Causes epidemics and pandemics. Type B, C: infects Man only.  Influenza viruses are highly susceptible to mutations and reassortment within the infected hosts.

13. Haemagglutinin (HA):  Attachment to the cell surface receptors.  Antibodies to the HA is responsible for immunity.  16 haemagglutinin antigenic type, H1 – H16, human associated H antigenic type are H1, H2, H3. H5, H7, H9. Neuraminidase (NA):  Responsible for release of the viruses from the infected cell.  9 neuraminidase antigenic type, N1 – N9  Human associated N antigenic type are N1, N2. N7.

14.  Antigenic drift: accumulated mutations lead to chemical changes in HA or NA antigens. Partial protective immunity in population.  Antigenic shift: Genetic re-assortment between two viruses results in production of a new virus with different NA-HA combinations. › Usually in Influenza A virus and lead to pandemics because there is no previous population immunity.

18.  Before 1968; H2N2 (Asian flu ; human; killed 1.5 million).  Since 1968; H3N2 (Hong Kong flu; Avian; killed 1 million),  2004- 2009; H5N1 (Hong Kong, Avian); 718 cases and 413 deaths. Rarely spread between humans.  In the last years: › H1N1 (Swine flu; Animal-Human) (five genes from swine, two from avian, one from human). 12,000 deaths. › H7N9 (avian, China)no human to human spread

19. Transmission:  Respiratory droplets, aerosols and fomites.  Some subtypes can be transmitted from animals to human e.g. H1N1, H5N1. Pathogenesis:  Tropism: viral hemagglutinin (H) bind to sialic acid containing glycoproteins on columnar cells of the throat, bronchi and lungs. Certain subtypes (H5N1, H1N1) bind to lower cells at a higher rate (sever pneumonia).  Up-take of virus into endocytic vesicle.

20.  Uncoating and release of the viral genome segments into the cytoplasm.  Replication of viral RNA in the nucleus & release from the cell by the NA.

21.  Tissue Damage:  Infected columnar cells produce interferon-α; monocytic and lymphocytic attraction.  Massive inflammation with edema formation.  In sever cases (e.g. H1N1): hemorrhagic and necrotizing bronchitis and tracheobronchitis and later: bronchopneumonia & alveolar damage with extensive fibrosis can happen.

22. Symptoms: starts as URTI then LRT:  Fever, dry cough, muscle pain, and generalized pain.  In sever cases: bleeding from mouth and throat with symptoms of acute respiratory distress syndrome (ARDS). Prognosis:  Seasonal influenza is usually a self-limiting disease but epidemic and pandemic influenza are severe and may be fatal.

23. Diagnosis:  Usually clinical.  Specimens: nasopharyngeal swabs, throat swabs or other respiratory secretions.  Laboratory diagnosis: o Direct detection of viral antigens by rapid test, direct immunofluorescent or ELISA. o Detection of viral RNA by PCR.

26.  Transmission: inhalation of respiratory aerosols.  Clinical manifestations: › Upper respiratory infection: 10-30% of common cold cases. › Lower respiratory infection: by the new viruses known as SARS-CoV; and MERS- CoV.  Immunity is short lived and reinfection can happen within few months.

27.  Sever Acute Respiratory Syndrome (SARS- CoV): jumped from bats to civet cats and then to human after mutation.  The virus became able to spread between human in 2003 and caused a large outbreak in china which spread world wide with high mortality. (29 countries, 8273 cases, 775 deaths)  Super spreader: one patient with SARS can transmit the disease to > 10 persons.  Interact with lungs-cellular receptor (angiotensin- converting enzyme 2).  Symptoms: fever, dry cough, myalgia, diarrhea followed by tachypnea and respiratory distress.

28.  Was first identified in Saudi Arabia in 2012 then other cases were discovered inside & outside the Arabian Peninsula.  Symptoms: fever, cough, and shortness of breath, diarrhoea. Severe illness can cause respiratory failure & requires mechanical ventilation.  Mortality rate ≈ 27%.  Camels may be the source of infection.

29.  Tell 2 nd February 2015 there were 971 laboratory-confirmed cases of MERS- CoV reported to WHO, including at least 356 deaths.  No specific treatment or vaccine is available for coronaviruses.