PARAMYXOVIRUSES

1. PARAMYXOVIRUSES DR SATHYA ANANDAM

2. Myxo = affinity to mucin Myxoviruses Paramyxo viruses Orthomyxo viruses • Smaller • Segmented RNA genome • Liable to Agic variation • Larger • Single piece of RNA • Not liable to Agic variation - Parainfluenza - Mumps virus - Measles virus - Respiratory syncytial virus Influenza viruses

3. Large Spherical enveloped • Unsegmented –ve sense RNA • The lipid envelope is associated with 2-virus specific glycoproteins; Haemagglutinin-Neuraminidase (HN) protein & fusion (F) protein • F protein responsible for fusion of viral envelope with host plasma membrane

4. CLASSIFICATION • Family parayxoviridae is divided into 4 genera • Rubula virus- mumps virus • Parainfluenza virus- parainfluenza types 1-4 • Pneumovirus- Respiratory synctial virus • Morbillivirus- measles virus

5. Mumps Virus • Acute infectious diseases of children • Causes epidemic parotitis ( non suppurative inflammation of parotid) • Mode of transmission: Via aerosols & fomites • The virus is secreted in urine so urine is a possible source of infection saliva

6. CULTURES • Possess both HN and F proteins • Chick embryos- in amniotic cavity and allantoic cavity • Cell cultures- primary monkey kidney cells- synctium formation and acidophilic cytoplasmic inclusions

7. Pathogenesis & clinical picture • Infects children 5-15years • Replicates in the nasopharynx & cervical LNs • Incubation period: 12-25 days Lasts 3-5 d viremia • Salivary • Pancreas • Testes • ovaries glands meninges Long life immunity due to IgG neutralizing Abs

9. Complications • Severe aseptic meningitis in adults- deafness as sequelae • Epididymo-Orchitis in adult males which might cause sterility • Pancreatitis • Oophritis • Arthritis • Nephritis • Myocarditis & thyroiditis

10. Epidemiology • Humans are the only natural hosts • Affects children 5-15 years of age • Source: patient in late incubation period or early clinical stage of illness • No human carriers or animal reservoir • One attack of mumps confers lasting immunity

11. Laboratory Diagnosis Specimens: - saliva(4-5 days) - CSF(8-9 days) - urine(upto 2 wks) 1- Direct virus demonstration: - RT-PCR for detection of viral RNA 2- Viral isolation: - Specimens are inoculated onto (MKTC) or chick embryo - Growth is recognized by hemadsorption or by direct IF & by characteristic CPE giant cell formation

13. 3- serology: • ELISA is used for detection of IgM or IgG • For IgG, paired acute & convalescent sera are necessary • Four fold or more rise in IgG titer indicates infection

14. Prevention Mumps vaccine Active immunization • Live attenuated • TheJeryl-Lynn strain of mumps virus, attenuated by passage in eggs and grown on fibroblast culture • Given by subcutaneous injection single dose • Long term immunity(10 yrs) • Monovalent form or MMR vaccine

15. MEASLES VIRUS • Causes measles (rubeola) • One of the most contagious respiratory infections • It can nearly affect every person (in a given population) by adolescence, in the absence of immunization programs • Mode of transmission: • - Large respiratory droplet • -airborne Most infectious in the early stage: Before the rash appears

16. Measles virus • Spherical 120-250 nm, pleomorphic • Heamagglutinin (H) and Fusion(F) protein on surface • Grows well on monkey kidney cells and human amnion cultures • Cytopathic effects are multinucleate synctium formation with acidophilic nuclear and cytoplasmic inclusion bodies • Multinucleate gaint cells (Warthin–Finkeldey cells) in lymphoid tissue of patients

17. Epidemiology • Endemic throughout world • Epidemics every 2-3 yrs in late winter and early spring • 1-5 yr children are commonly affected • Humans are only natural hosts • Patients are infectious from 3 days before onset of symptoms until rash desquamates • Spread by direct contact, aerosols

18. Pathogenesis & clinical picture • Replication initially in the upper & lower respiratory tract or conjunctiva • Followed by LNs replication • Viremia to RES • Secondary viremia& growth in a variety of epithelial tissue • Incubation period:1-2 wks • In 2-3 days, no rash but fever, running nose, cough & conjunctivitis

19. Koplik spots: pathognomonic, slightly raised bluish-white dots, 2-3 mm in diameter are seen on the buccal mucosa opposite the lower molars shortly before rash onset persist for 1-3 days • A characteristic maculopapular rash extending from face(forehead) to extremities involving palms & soles : this seems to be associated with T-cells attacking virally infected endothelial cells in small blood vessels • The rash lasts from 3-7 d & may be followed by skin exfoliation

21. 1-Respiratory symptoms 2-3 days 2-Koplick spots 3-Maculopapular rash Persist 1-3 days Disappear after the rash onset Lasts for 3-7 days 4-Skin exfoliation Long life immunity due to IgG neutralizing Abs

23. complications I- Respiratory • Otitis media & bacterial pneumonia: common • Virus laeds to croup or bronchitis • Giant cell pneumonia in patients with impaired CMI or malnutrition( rare but fatal) II- Neurological • Postinfectiousmeningoencephalitis. Few days after the rash (1:1000) • Subacutesclerosingpanencephalitis (SSPE) (1:100.000)

24. Complications • Protracted diarrhoea in developing countries • Suppression of delayed hypersensitivity- worsens TB and eczema • Induces labour in some pregnant women leading to spontaneous abortion or premature labour

25. Laboratory Diagnosis Specimens: nasal secretions-nasopharyngeal aspirate or swab- urine 1- Direct virus demonstration: - Demonstration of multinucleated gaint cells in Giemsa stained smears - DIF: for detection of viral Ag - RT-PCR for detection of viral RNA 2- Viral isolation: - nasal secretions inoculated onto (MKTC) - Growth is recognized by development of CPE in the form of multinucleated giant cells containing both intranuclear & intracytoplasmic IBs

26. 3- serology: • ELISA is used for detection of IgM or IgG • For IgM single serum specimen 1-2 wks after the rash onset • For IgG, paired acute & convalescent sera are necessary • Four fold or more rise in IgG titer indicates infection

27. Passive immunization Measles IGs Prevention • - For immunocompromised patients • Intramuscular within 6 days of exposure • Prevent measles symptoms in 80% of cases Active immunization MMR vaccine • Live attenuated,Edmonston-Zagreb strain • Given by subcutaneous injection • Long term immunity(upto 20 yrs) • Monovalent form or MMR vaccine

28. Respiratory Syncytial Virus • Commonest cause of bronchitis & pneumoniaamong infants< 1yr. • Causes repeated infections throughout life, usually associated with moderate- to severe cold –like symptoms • Otitis media in young children • Severe lower respiratory tract disease may occur at any age, especially elderly & those with compromised immune systems

29. Laboratory Diagnosis Specimens: nasal secretions-nasopharyngeal aspirate 1- Direct virus demonstration: - DIF: for detection of viral Ag - RT-PCR for detection of viral RNA 2- Viral isolation: - nasal secretions inoculated onto (HeLa) - Growth is recognized by development of CPE in the form of giant cells & syncytia

30. Treatment No vaccine is yet available • Symptomatic treatment for mild disease • Oxygen therapy & may be mechanical ventilation in children with severe disease • Ribavirin aerosol

31. Human Parainfluenza Viruses(1,2,3,4) • HPIVs are second to RSV as a common cause of lower respiratory tract disease in young children • Similar to RSV, HPIVs can cause repeated infections throughout life. • Can also cause severe lower respiratory tract infections among immuno-compromised patient

32. The most distinctive clinical feature of HPIV-1& HPIV-2 is croup • HPIV-3 is more associated with bronchiolitis & pneumonia • HPIV-4 is infrequently detected, because it is less likely to cause severe disease Croup (laryngotracheobronchitis) Difficulty in breathing, hoarseness and a seal bark-like coughing

33. Laboratory Diagnosis Specimens: nasal secretion-nasopharyngeal aspirate- bronchoalveolarlavage 1- Direct virus demonstration: - DIF: for detection of viral Ag - RT-PCR for detection of viral RNA 2- Viral isolation: - Specimens are inoculated onto (MKTC) - Growth is recognized by hemadsorption using guinea pig RBCs or by direct IF

34. 3- Serological tests: • Based on Neutralisation, HI, or ELISA for detection of IgM or IgG • Paired acute & convalescent sera are necessary for IgG detection • A four fold or more rise in the titre indicates infection

35. Newcastle Disease virus • Avian paramyxovirus type 1 • In India called as Ranikhet virus • In poultry pneumoencephalitis or Influenza with high mortality • Control by vaccination & slaughter of affected birds • Human infection – self limited conjunctivitis

36. Nipah & hendra virus • Zoonotic paramyxovirus • Fruit bats are natural hosts • Nipah virus caused severe encephalitis • Hendra virus: morality in human and horses

37. Rubella virus

38. Rubella Virus • Causes German measles which is the mildest of common viral exanthems • It is a member of rubiviruses family Togaviridae • Enveloped +ve sense ss RNA • Possesses hemaglutinating ability

39. Diseases • 1- German measles: acute febrile illness with rash & lymphadenopathy affecting children & young adults • 2- Congenital Rubella Syndrome: Serious abnormalities of the fetus as a consequence of maternal infection during early pregnancy

40. Postnatal rubella (German measles) Pathogenesis & clinical picture • Mode of transmission: droplet • Initial viral replication occurs in the respiratory mucosa followed by multiplication in the cervical lymph nodes • Viremia develops with spread to other tissues. As a result the disease symptoms develop in 50% of cases after an incubation period of 12-23 days • Possibly 50% of infections are apparently subclinical

41. Fever & malaise (prodromal symptoms) for 1-2 days • Maculopapular rash appears on the face, then the trunk, then the extremities sparing palms and soles and disappears within 3 days • Suboccipital and postauricular-lymphadenopathy • Extremely rare complications, self limiting encephalopathy

42. complications • Arthralgia and arthritis in women • Extremely rare (1/6000) • Rubella encephalopathy • 6 days after the rash appears • Complete recovery with no sequelae

43. Laboratory Diagnosis Specimens: nasal secretions-nasopharyngeal aspirate or swab 1- Direct virus demonstration: - DIF: for detection of viral Ag - RT-PCR for detection of viral RNA 2- Viral isolation: - nasal secretions inoculated onto (MKTC) - Growth is recognized by interferencewith coxsackie virus

44. 3- serology: • ELISA is used for detection of IgM or IgG • For IgM single serum specimen • For IgG, paired acute & convalescent sera are necessary • Four fold or more rise in IgG titre indicates infection

45. Congenital rubella • Congenital rubella is a group of physical problems that occur in an infant when the mother is infected with the virus that causes German measles. • Very early pregnancy: abortion • First trimester: 90% congenital malformations • Later on: subtle, communication defects or developmental retardation

46. Congenital rubella is caused by the destructive action of the rubella virus on the fetus at a critical time in development. • Triad includes cataract, deafness and cardiac defects • Hepatosplenomegaly, thromocytopenicpurpura, myocarditis and bone lesions- expanded rubella syndrome • The rate of congenital rubella has decreased dramatically since the introduction of the rubella vaccine.

47. Risk factors for congenital rubella include: • Not getting the recommended rubella immunization • Contact with a person who has rubella (also called the 3-day measles or German measles)

48. Clinical picture • Transient symptoms:growth retardation, anemia & thrombocytopenia • Permanent defects: congenital heart diseases, total or partial blindness, deafness & mental retardation • Progressive rubella panencephalitis:Extremely rare slow virus disease, develops in teens with death within 8 yrs

49. Laboratory Diagnosis During Pregnancy After Birth • Detection of maternal IgM or rising IgG in serum • Then, detection of rubella Ag in the amniotic fluid by DIF • TORCH panel • Live newborn: detection of IgMantirubella Abs in the serum of the baby by ELISA • Stillbirth: virus isolation on MKTC

50. Prevention of congenital rubella vaccinate • Women in the childbearing age • School age children Pregnancy should be avoided 3 months after vaccination Maternal rubella infection confirmed during the first trimester???? Therapeutic abortion