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Paramyxo virus Classification Symptoms and Lab diagnosis
- 1. Paramyxovirus Neeraj Sharma Msc Microbiology PBPC Pokhara Nepal
- 2. Introduction Includes . RSV & Parainflunzavirus causing RTI in infants & Children . Measles & mumps , most contagious disease of child hood. ARI- cause of death of 4million children per year Paramyxoviruses – major respiratory pathogen in this age group. RSV & parainfluenzavirus ; limited to RT Measles & mumps disseminate throughout the body.
- 4. Properties Structure and composition Pleomorphic, enveloped Diameter occasionally 150 nm or more ranging up to 700 nm. The nucleocapsid consists of the negative-sense, single stranded non segmented RNA associated with the nucleoprotein (NP),polymerase phospho protein (P), and large (L) protein.
- 5. Contd.. The nucleocapsid associates with the matrix (M) protein lines the inside of the virion envelope. The envelope contains two glycoproteins, a fusion(F) protein, which promotes fusion of the viral and host cell membranes, and a viral attachment protein(hemagglutinin-neuraminidase [HN], hemagglutinin [H],or G protein)
- 6. The difference between the orthomyxo & paramyxoviruses Orthomyxoviruses Paramyxoviruses Diseases caused in humans Influenza types A, B and C Parainfluenza 1-4 infections, RSV diseaes, mumps and measles genome ssRNA 8 segmented, -ve sense ssRNA nonsegmented –ve sense Fusion of virus with cell Endosome Plasma membrane Transcription of viral RNA HOST CELL NUCLEUS Host cell cytoplasm Genetic reassortment frequent Rare Rate of antigentic change high low
- 7. Classification Paramyxoviridae family has 2 sub families Paramyxovirinae Respirovirus : Parainfluenza 1,3 Rubulavirus: Mumps, Parainfluenza 2, 4a,4b Morbili Virus: measles Henipavirus: Hendra, Nimph
- 8. Pneumovirinae Pneumo virus: RSV Metapneumovirus: human metapneumovirus
- 10. Replication Takes place in cytoplasm Virus attaches via hemagglutinin to sialic acid containing receptor on the cell surface. F protein fuses the viral envelope with the cell membrane releasing the nucleocapsid into the cell. RNA-dependent RNA polymerase carried within the virion produces subgenomic sized mRNA transcripts, which are translated to produce some of the early virus specific poly peptides.
- 11. Early proteins include a second RNA polymerase which copies the genome into full length positive complementary strand which is later copied back into negative strand for transcription of later mRNA (coding for structural proteins) and for incorporation into new virions.
- 12. Viral components are assembled beneath the cell membrane and the surface HN and F proteins are incorporated into a stretch of membrane converting it to viral envelope. This evaginates and buds off enclosing a nucleocapsid forming a new virion.
- 15. Para influenza virus Para influenza viruses are ubiquitous and cause common respiratory illness of varying severity in all age groups. Transmission: droplet TYPE 1,2,& 3 are particularly considered major pathogens of severe respiratory tract disease in infants & young children Type 4 does not cause severe disease even on primary infection
- 16. Primary infections in young children usually result in Rhinitis Pharyngitis However children with primary infection caused by serotypes 1,2 or 3 may have serious illness ranging from: Laryngeotracheobronchitis (croup) Bronchiolitis & pneumonia mainly type 3 age < 6month
- 17. Pathogenesis Incubation period 3 to 6 days. In immuno competent host, infection is limited to respiratory epithelia Type 1 &2 involve the infection of larynx and upper trachea resulting in croup. Croup: Respiratory obstruction caused by swelling of the larynx and related structure.
- 18. Type 3 infection may spread deeper to lower trachea and bronchi resulting in pneumonia or bronchiolitis. The duration of parainfluenza virus shedding is about 1 week after onset of illness. Type 3 may be excreated for up to 4 weeks, this persistent shedding from young children facilitates spread of infection.
- 20. Clinical findings Primary infection caused by parainfluenza virus type 1,2 & 3 may have serious illness which ranges from laryngitis and croup (Type 1 & 2) to bronchiolitis and pneumonia (Type3) Severe illness is associated with type3 mainly in infants younger than 6 months. Type 4 doesn’t cause serious disease even on first infection.
- 21. The most common complication of parainfluenza virus infection is ottitis media. Immuno compromised children and adults are susceptible to severe infection. Newcastle disease virus is an avian paramyxovirus that produce pneumoencephalytis in young chicken and influenza in other birds .
- 22. In humans it may produce inflammation of conjunctiva. Disease is limited to workers handling the infected birds. Recovery is complete in 10-14 days.
- 23. Widely distributed geographically, Type 3 is most pravalent 1&2 occur at lower rate.
- 24. Lab Diagnosis Nucleic acid detection: Preferred diagnostic method because of their sensitivity and specificity. Reverse transcription PCR (RT- PCR) assays can be used to detect viral RNA in nasopharyngeal washes or nose and throat swabs.
- 25. Antigen Detection : Direct identification of the viral antigen is commonly done. Antigen is detected in exfoliated nasopharengeal cells by direct or indirect immuno fluorescence test.
- 26. Isolation & Identification: Rapid cell culture technique Slow to produce results. Serology: Neutralization test, Hemagglutination or ELISA
- 27. Treatment and prevention Isolation of the infected patient. Gowning and hand washing by medical persons Ribavirin is used in treatment of immuno compromised patient with lower respiratory tract disease No vaccine available.
- 29. RSV Structure
- 30. Most important cause of LRT infection in infants and young children Major cause of bronchiolitis and pneumonia in infants and below 1 year. Labile paramyxovirus, produces a characteristic syncytial effect. ( Fusion of human cells in human cell culture) Slightly smaller(80-120 nm) than other paramyxovirus.
- 32. Pathogenesis Localised infection of RT Not causing Viremia Pneumonia from cytopathologic spread Bronchiolitis from host immune response Narrow airways of infants obstructed by virus-induced pathologic effect Maternal antibody does not protect infant from infection
- 33. Pathogenesis Replication occurs initially in epithelial cells of nasopharynx. May also spread to LRT and cause bronchiolitis or pneumonia. I.P. 3-5 days. Viral shedding may persist for 1-3 weeks from infants and young children but adults shed virus for only 1-2 days. Viremia occurs rarely
- 34. Intact immune system seems to be important in resolving the infection. The spectrum of respiratory illness caused by RSV ranges from inapperant infection or the common cold through pneumonia to bronchiolitis in the very young children. Bronchiolitis is the distinct clinical syndrome associated with the virus.
- 35. One third of the primary infection involve the LRT severely enough to rewuire the medical attention. Progression of the symptoms may be very rapid resulting in death. Reinfection is common in both young and adults.
- 36. It accounts for about one third of the respiratory infection in the bone marrow transplanted patients. Infection in elderly adults may cause symptoms similar to influenza virus disease.
- 37. Clinical Features Upper Respiratory Infection Fever Rhinitis Pharyngitis Lower Respiratory Infection- Bronchiolitis, Pneumonia Cough Poor feeding, lethargy Hypoxemia Respiratory Distress (tachypnea, retractions) Apnea
- 38. Lab diagnosis Nucleic acid detection: Reverse transcription PCR (RT- PCR) assays can be used to detect viral RNA in nasopharyngeal washes or nose and throat swabs. Antigen Dectation: Detected in exfoliated nasopharengeal cells by direct or indirect immuno fluorescence test.
- 39. Treatment and prevention Treatment of serious RSV depends primiraly on supportive care Ribavirin is approved for treatment of LRT, administered in aerosoles. No vaccine is available.
- 40. Mumps Virus
- 42. Introduction It causes mumps; an acute contagious disease characterised by non suppurative enlargement of one or both of the parotid glands. It is a typical paramyxovirus. Mostly causes mild childhood disease but in adults complications including meningitis and orchitis are sometimes seen.
- 43. Time course of Mumps infection Local replication Systemic infection Inoculation EC of URT Viremia Virus multiplies in ductal epithelial cells. local inflammation causes Marked swelling Parotid glandpancreas Testes Ovaries Peripheral nerves Eye Inner ear CNS
- 44. Pathogenesis Humans are the only natural host Primary replication occurs in nasal or upper respiratory tract epithelial cells. Viremia dissiminates the virus to salivary glands and parotid gland. Incubation period is 2-4 weeks.
- 45. Virus sheds in the saliva from about 3 days before to 9 days after the onset of salivary gland swelling. About one third of infected individuals do not exhibit symptoms but are equally capable of transmitting the infection. Systemic viral disease with propensity to replicate in epithelial cells of various visceral organs.
- 46. Virus frequently infects kidney and can be detected in urine of most patients. The central nervous system is also commonly infected.
- 47. Lab diagnosis Nucleic acid detection: By Reverse transcription polymerase chain reaction. Antigen detection: by ELISA or HI test Isolation of the virus from saliva CSF and urine Monkey kidney cells are preferred for viral isolation.
- 48. Treatment and prevention Immunization with attenuated mumps virus vaccine is the best approach for control. Vaccine is available in combination with measles and rubella. (MMR) Two doses of MMR vaccine are recommended.
- 49. Measles
- 50. Measles
- 51. Introduction Measles is a morbilli virus, morphologically indistinguishable from parainfluenza virus, mumps virus and NDV. Glycoprotein spike carries hemagglutinin but not nuraminidase function. F protein and M protein also present. There is only one serotype of measles no subtypes have been recognised.
- 52. Measles Serious and highly contagious Usually found in non-immunized or partially-immunized (single vaccine, no booster) Most born before 1957 have had measles Measles virus is spread easily Through air by coughs or sneezes By direct contact with nose or throat secretions Symptoms Rash that starts on the face and neck, then spreads High fever Runny nose Red, watery eyes Cough
- 53. Measles Symptoms start about 10 days after exposure Average 10 days from exposure to onset of fever Average 14 days from exposure to onset of rash Other symptoms and complications Ear infection Pneumonia CNS/ brain infection (as SSPE, subacute sclerosing panencephalitis) Complications may be lethal More serious in infants and adults, less in children and teens Vaccine Measles (Paramyxoviridae), mumps (Paramyxoviridae), rubella (Togaviridae, + sense) (MMR) vaccine is a live vaccine Has been very effective in limiting spread Links of vaccine to autism have been proposed but not shown Management Antibiotics should be used to combat side-effects such as ear infetions pneumonia. Giving vitamin A at the time of diagnosis can help to prevent blindess
- 54. Measles pathogenesis Lymphatic spread Wide dissemination Virus- infected endothelial cells+ immune T cell
- 55. Incubation period 7-14 days. Human are the only natural host. Entry via respiratory tract,multplies locally infection spreads to the regional lymphoid tissue where further multplication occurs. Primary viremia disseminates the virus which then multplies in reticuloendothelial system. Finally second viremia seeds the epithelial surface of the body (skin, respiratory tract, conjunctiva)
- 56. Clinical features Prodromal stage Eruptive stage Post-measles stage
- 57. Prodromal phase starts with high fever and 3C’s - Coryza - Conjunctivitis - Cough
- 58. Eruptive phase Presence of koplik’s spot Koplik’s spot: Red spot with bluish white centre on the buccal mucosa just above the lower molars.
- 61. With decline of acute symptoms in 1 to 2 days typical wide spread maculopapular rashes (morbiliform) rash appear on skin Begins on face and thorax and spreads preipherally. The rash last approximately for 5 days. Skin rash is due to cytotoxic T cells attacking the measles virus infected vascular endothelial cellsin skin.
- 62. Lab diagnosis Same as other paramyxoviruses
- 64. Rubella virus is a member of Togaviridae family. Although its morphologic feature and physiologic properties place it in togavirus group its is not transmitted by arthropods. Causes Postnatal and congenital infections.
- 65. The name rubella is derived from a Latin term meaning "little red." Rubella is sometime called German Measles or 3-day Measles. The synonym "3-day measles" derives from the typical course of rubella exanthema that starts initially on the face and neck and spreads centrifugally to the trunk and extremities within 24 hours. It then begins to fade on the face on the second day and disappears throughout the body by the end of the third day. It is a generally mild disease caused by the rubella virus.
- 66. Source of infection – Respiratory secretion Transmission – droplet, vertical transmission I.P – 2-3 weeks average 18 days
- 67. Clinical Symptoms. • Eye pain on lateral and upward eye movement (a particularly troublesome complaint) • Conjunctivitis • Sore throat • Headache • General body aches • Low-grade fever • Chills • Anorexia • Nausea • Tender lymphadenopathy (particularly posterior auricular and suboccipital lymph nodes)
- 68. Forchheimer sign (an enanthem observed in 20% of patients with rubella during the prodromal period; can be present in some patients during the initial phase of the exanthem; consists of pinpoint or larger petechiae that usually occur on the soft palate)
- 69. Image in a 4-year-old girl with a 4-day history of low-grade fever, symptoms of an upper respiratory tract infection, and rash. Courtesy of Pamela L. Dyne, MD.
- 70. Lab diagnosis Nucleic acid detection. Isolation and identification of virus. Serology
- 71. Age Vaccines Note 9 months Measles Deep subcutaneous injection into the upper arm. 12-15 months MMR -1 Deep subcutaneous injection into the upper arm. 5 years MMR -2 Deep subcutaneous injection into the upper arm. Treatment and control