Respiratory Tract Infection (Part –I)

1. Respiratory Tract Infection (Part –I) By: Dr. Mona Badr Assistant Professor & Consultant Virologist College of Medicine & KKUH

2. Viral Infection of Respiratory Tract • Influenza virus Orthomyxoviridae family • Rhinovirus Picornaviridae family • Coronavirus Coronaviridae family • Para – influenza viruses Paramyxoviridae family • Respiratory Synctial viruses Paramyxoviridae family. • Adenovirus Adenoviridae family.

3. Orthomyxoviridae Family Orthomyxoviruses Influenza Virus The Orthomyxoviruses are: 1) Single, Stranded negative sense RNA with 8helical segments 2) Helical capsid symmetry 3) Enveloped viruses which contains 2 projecting glycoprotein spikes. • Heamagglutinin HA attachment. • Neuroamindase NA an enzyme help in releasing progeny virus formation from infected cell.

5. Influenza Virus Epidemiology: • Winter months mostly • Influenza A can cause epidemic and pandemic which is usually associated with Antigenic shift. • Can cause epizootic in animal • Influenza B mainly cause outbreaks.

7. Wild birdsare the primary natural reservoir for all subtypes of influenza A virus and are thought to be the source of influenza A in all animals

8. Types of Influenza Viruses Influenza A Influenza B Influenza C • Infect human and animals. • Infect human only • Infect human only • Cause outbreaks • Cause mild illness • Antigenic drift • Can cause epidemic and pandemic in man • Can cause epizootic in animals • antigenic drift. • antigenic shift.

9. Epidemiology And Antigenic Variations in Influenza 1- Mutation/antigenic drift /minor change. • Can occur in influenza A or B. • It is due to spontaneous mutation in the haemaglutinin gene. • It occurs every 2- 3 years. • Can cause local outbreak. • 2. Re-assortment/ genetic recombination/ antigenic shift/ major change. • only in influenza A • co-infection of one cell with different strain at the same time causing genetic re-assortment of RNA segment that code for haemaglutinin. • Can cause epidemic and sometime pandemic every 10 years.

13. Past Antigenic Shifts 1918H1N1 “Spanish Influenza” 20-40 million deaths 1957H2N2 “Asian Flu” 1-2 million deaths 1968H3N2 “Hong Kong Flu” 700,000 deaths 1977H1N1 Re-emergence No pandemic • At least 15 HA subtypes and 9 NA subtypes occur in nature.

14. Pathogenesis And Immunity: • Influenza virus establish a local upper respiratory tract infection. • According to the immunity of the host, it can cause localized infection or spread to the lower respiratory tract infection. • Viremia usually occurs . • Influenza infection is self limiting condition.

15. Clinical Syndrome: • Transmission inhalation of respiratory secretion • Incubation period 1 - 4 days • Seasonal variation usually in winter • Symptoms:Sudden onset of fever Malaise – Headache Sneezing – sore throat - It takes 3 days. Severe myalgia - Then recoveryoccur within 7-10 days. Non-productive cough

16. Complication of Influenza: • Primary Influenza Pneumonia. • 2nd bacterial pneumonia [ Strep. pneumoniae, H.influenzae ] • Myositis (inflammation of the muscle). • Post influenza encephalitis. Reye’s Syndrome: • Encephalopathyand fatty degeneration. Of liver It occurs in children with viral infection and are taken Aspirin to reduce fever. The disease had been associated with several viruses; such as influenza A and B, Coxsackie B5, echovirus, HSV, VZV, CMV &adenov.

17. Laboratory Diagnosis: • Clinical diagnosis. • Laboratory investigation done to distinguish influenza viruses from other respiratory viruses and to identify the type and strain. • Specimen: Nasopharyngeal aspirate, nasal washing. • Rapid and direct detection of influenza A or B from nasopharyngeal aspirate by immunofluorescence &ELISA. This is the most common laboratory diagnosis. • RT-PCR (Nucleic acid testing)

18. Rapid antigen immunofluorescence assay • Assay performed on cells from a combined nose and throat swab, showing typical nuclear and cytoplasmic “apple-green” fluorescence after staining with monoclonal antibodies specific for influenza A.

19. Treatment: Amantadine: Is only effective against influenza A virus. inhibiting the un coating step of influenza A virus. It has both therapeutic and prophylactic . It significantly reduced the duration of fever and illness is given to high risk group of patients who are not vaccinated because they have allergy from egg.

20. Tamiflu: • It is Neuraminidase inhibitor that act by blocking the viral enzyme neuraminidase which help the influenza virus invade respiratory tract cells. • It has to be given within the first 48 hours after the exposure of cases or appearance of symptoms. • Recommended dose is 75 mg twice daily for 5 days.

21. PREVENTION • Vaccine • killed influenza A (HINI and H3N2 isolates) and B viruses • Protection lasts only 6 months. • Yearly boosters are recommended • Should be given to people: • Older than 65 years • With chronic respiratory diseases • With chronic cardiovascular and kidney diseases • With diabetes • With lowered immunity. • Immunity to Influenza • Antibody against hem agglutinin (H) is the most important component in the protection against influenza viruses.

22. AVIAN INFLUENZA • Avian influenza A viruses usually do not infect humans • Rare cases of human infection with avian influenza viruses have been reported since 1997 with avian influenza A (H5N1) viruses. • All strains of the infecting virus were totally avian in origin and there was no evidence of reassortment. • Infection in humans are thought to have resulted from direct contact with infected poultry or contaminated surfaces. • To date, human infections with avian influenza A viruses have not resulted in sustained human-to-human transmission.

24. PICORNAVIRUSES • Small (20 – 30 nm) non–enveloped viruses, ssRNA with positive polarity. • Includes two groups: • Enteroviruses • Enteroviruses include poliovirus, coxsackie viruses, echovirus and hepatitis A virus. • replicate optimally at 37 ºC • Enteroviruses are acid resistance (pH 3 – 5). • Rhinoviruses • Rhinoviruses grow better at 33 ºC in accordance with the lower temperature of the nose. • Rhinoviruses are acid – labile.

25. RHINOVIRUSES • Common cold accounts for 1/3 to 1/2 of all acute respiratory infections in humans. • Rhinoviruses are responsible for 50% of common colds, coronaviruses for 10%, adenoviruses, enteroviruses, RSV, influenza, parainfluenza can also cause common cold . • Common cold is a self-limited illness. • More than 100 serologic types of rhinoviruses (No vaccine) • Transmitted directly from person to person by respiratory droplet.

26. Clinical Syndrome: • Symptoms as runny nose, sneezing and nasal obstruction, mild sore throat, headache and malaise that last for one week. • Complication: Usually due to secondary bacterial infection which can lead to: • Acute sinusitis 2) Acute otitis media. • 3) Exacerbation of chronic bronchitis. • Laboratory Diagnosis: • Usually no need. Treatment and Prevention: • No specific treatment. • No vaccine available.

27. Coronaviruses • The name Coronavirus means Crown – like projection on • its surface (when viewed with an electron microscope). • ssRNA enveloped with positive polarity. • Coronavirus are the second cause of common cold which usually mild but can lead to pneumonia in children and adult. • Coronavirus – particles have been seen by electron micrography of stool specimen from adult and children with diarrhea and gastro-entritis.

29. Clinical Syndrome: • The viruses spread by respiratory droplets. • Infection usually occur in winter and early spring. • Incubation period is short 2 –4 days. • Coronavirus causes an upper respiratory tract infection (common cold) as Rhinovirus.

30. DIAGNOSIS AND TREATMENT • Laboratory diagnosis is not attempted. • Coronaviruses have fastidious growth requirement in cell culture. • No antiviral drugs against coronaviruses are available.

31. Severe Acute Respiratory Syndrome SARS • SARS is a viral infection, causes Atypical pneumonia, can infect all age groups, and can lead to death especially among people with existing chronic condition. • SARS suspected to be originated in China and Hong Kong. • What we know about the causative agent of SARS? • A new mutation of coronavirus, apparently a zoonosis of which the animal reservoir may be the cat. • Coronavirus is difficult to isolate and not easily grown in tissue culture. • Coronavirus is able to survive in dry air for up to 3 hours, but can be killed by exposure to ultra-violet light.

33. OTHER CAUSES OF COMMON COLD SYNDROME • Coxsackievirus • Herpangina (severe sore throat with vesiculoulcerative lesions) • Pleurisy • common cold syndrome • Adenovirus • Pharyngitis • common cold syndrome • Bronchitis • pneumonia (types 3, 4, 7 and 21) • Influenza C

34. Thank you

35. Viral Infection of Respiratory Tract (Part –II) By: Dr. Mona Badr Assistant Professor & Consultant Virologist College of Medicine & KKUH

36. Viral Infection of Respiratory Tract: • Influenza virus Orthomyxoviridae Family. • Rhinovirus Picronaviridae Family. • Coronavirus Coronaviridae Family • Para – influenza viruses Paramyxoviridae Family. • Respiratory Synctial viruses Paramyxoviridae Family. • Adenovirus Adenoviridae Family.

37. Para –Infuenza Viruses • Para –Infuenza Viruses can cause wide spectrum of respiratory syndromes from sever life threatening lower respiratory infection to mild self limiting upper respiratory tract infection .

38. Para – Influenza Viruses • paramyxoviridae family which also includes measles, mumps, respiratory syncytial viruses(RSV) and human metapneumovirus. • Enveloped SS RNA, with negative polarity. • There are four para–influenza viruses: Type 1, 2, 3, 4 . • Para - influenza virus are ubiquitous and infection occur mainly • in winter month. • Transmitted by respiratory droplets. • Envelop surface projection presents as Heamagglutinin HA, Neuroamindase NA and F-glucoprotins which cause cell TO cell membrane to fuse syncytia

39. Clinical Syndromes: 1- Croup or Acute Laryngotracheobronchitis: parainfulenza Type I,II seen in infants & young children < 5 years. Croup: Harsh cough, inspiratory stridor with Hoarse voice and difficult inspiration which can lead to airway obstruction which need hospitalization to do tracheotomy. 2- Bronchiolitis and pneumonia: Sometime parainfluenza type 3 can cause bronchiolitis and pneumonia in young children. 3- Common Cold: Seen in older children and adult. 4- Immunocompromized: Parainfluenza type 3 very dangerous, especially in bone marrow transplant patient.

40. Laboratory Diagnosis: • Direct detection of parainfluenza virus from • nasopharyngeal aspirate by direct immunofluorescent. • Anti-body rising titer using ELISA of little value. • Isolation by culture from mouth wash on monkey kidney cells. • Treatment and Prevention: • Hospital admission for infant having Croup for careful monitoring of upper airway (endotracheal intubation and tracheotomy) • No specific antiviral treatment, no vaccine available.

41. Respiratory Syncytial Virus (RSV) • One of the paramyxoviridae family. • Enveloped ,ss RNA withy negative polarity. • F-protein which responsible for cells to fuse forming multinucleated giant cells ( syncitia). • The virus transmitted by respiratory droplets, virus is very • contagious with( I.P. 3-6 days) infection mainly in winter. • The importance of RSV lies in its tendency to invade the lower respiratory tract in infant under one year causing pneumonia, bronchiolitis.

42. Clinical Syndromes: • RSV can cause any respiratory tract illness from commoncoldpneumonia • In old children and adult can cause common cold . • Bronchiolitis an important and life –threatening disease in infant especially under 6 months of life, started with fever, nasal discharge, rapid breathing, respiratory distress and cyanosis, it may be fatal in premature infant or infant with underlying disease or immunocompromised infant, also can lead to chronic lung disease in later life. • Pneumonia: also an important and life threatening disease in infant with case fatality rate of 2-5% .

44. Complications • Apnea • occurs in approximately 20% of cases (premature infants). Alterations in pulmonary function, which may lead to chronic lung disease in later life.

45. Laboratory Diagnosis: • Isolation of the virus from nasopharyngeal aspirate OR mouth wash in cell culture will appear as multinucleated giant cell (synctia). • ELISA and immunofluorescent for direct detection from nasopharyngeal aspirate. • Serology: by detection 4 fold rise in Ab titer.

46. Immunoflurescence on smears of respiratory secretions

47. Isolation in cell culture (multinucleated giant cells or syncytia)

48. Treatment and Prevention: Infant will be hypoxic and need hospitalization (oxygen inhalation). • Ribavirinby inhalation to treat severe Bronchiolitis and pneumonia. • Passive immunization with anti-RSV immunoglobulin is available for premature infant. • Hospital staff caring for these isolated infants have to follow control measure as hand washing, wearing of gowns, goggles and mask. • No vaccine is available.

49. Family Adenoviridae (Adenoviruses) • dsDNA, non-enveloped viruses with 47serogroup, , grouped into 6 group from A –F. • Adenoviruses infect epithelial cells lining respiratory tract, • conjunctiva, gastrointestinal tract, and genital tract • Viremia may occur after this local replication of the viruses • so virus can spread to other visceral organs… e.g. Urinary bladder • The Adenoviruses have the tendency to becomelatentin • lymphoid tissue and can be reactivated if immunity become low.

50. The fibers possess hemagglutinating activity and mediate the attachment of the virus to cellular receptors.