Paramyxoviruses Dr. Nehal Draz

Myxoviruses Paramyxo viruses Orthomyxo viruses 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 vairus - Measles virus - Respiratory syncytial virus Influenza viruses

Large Spherical envelopped Unsegmented –ve sense RNA The lipid envelope is associated with 2-virus specific glycoptns; Haemaglutinin-Neuraminidase (HN) ptn& fusion (F) ptn

Respiratory Sncytial Virus Commonest cause of bronchitis & pneumonia among infants< 1yr. Causes repeated infections throughout life, usually associated with moderate- to severe cold –like symptoms Severe lower respiratory tract disease may occur at any age, especially elderly & those with compromised cardiac, pulmonary or immune systems

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

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

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, usually upper respiratory tract illness Can also cause severe lower respiratory tract infections ammong immunocompromised patients

Each of the four HPIVs has different clinical & epidemiologic features 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

Laboratory Diagnosis Specimens: nasal secretion-nasopharyngeal aspirate- bronchoalveolar lavage 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

3- Serological tests: Based on Nt, 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

Mumps Viruss 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

Pathogenesis & clinical picture Infects children 5-15years Replicates in the nasopharynx &regional LNs Incubation period: 2-25 d Lasts 3-5 d viremia Salivary Pancreas Testes ovaries glands meninges Long life immunity due to IgG neutralizing Abs

Complications Severe aseptic meningitis in adults Orchitis in adult males which might cause sterility Pancreatitis Oophritis & thyroiditis

Laboratory Diagnosis Specimens: - saliva - CSF - urine 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

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

Prevention Active immunization Mumps vaccine Live attenuated Given by subcutaneous injection Long term immunity Monovalent form or MMR vaccine

Measles virus Causes measles (robeola) 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 repiratory droplet -airborne Most infectious in the early stage Before the rash appears

Pathogenesis & clinical picture Replication initially in the upper & lower respiratory tract Followed by LNs replication 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

Koplick spots: slightly raised white dots, 2-3 mm in diameter are seen on the inside of the cheek shortly before rash onset persist for 1-3 days A characteristic maculopapular rash extending from face 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

Disappear after the rash onset Lasts for 3-7 days 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

The virus invades the body via blood vessels reaches surface epithelium first in the respiratory tract where there are only 1-2 layers of epithelial cells Then in mucosae (Koplik's spots) and finally in the skin (rash).

complications I- Respiratory Otitis media & bacterial pneumonia: common Giant cell pneumonia in patients with impaired CMI ( rare but fatal) II- Neurological Postinfectious encephalitis. Few days after the rash (1:1000) Subacute sclerosing panencephalitis (SSPE) (1:100.000)

Laboratory Diagnosis Specimens: nasal secretions-nasopharyngeal aspirate or swab- urine 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 development of CPE in the form of multinucleated giant cells containing both intranuclear & intracytoplasmic IBs

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

Prevention Passive immunization Measles IGs Active immunization - For immunocompromised patients Intramuscular within 6 days of exposure Prevent measles symptoms in 80% of cases Active immunization Mumps vaccine Live attenuated Given by subcutaneous injection Long term immunity Monovalent form or MMR vaccine

Rubella Virus Causes German measles which is the mildest of common viral exanthems It is a member of rubiviruses but not an arbovirus Envelopped +ve sense ss RNA Posseses hemaglutinating ability

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

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

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

complications Extremely rare (1/6000) Rubella encephalopathy 6 days after the rash appears Complete recovery with no sequalae

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 interference with coxsakie virus

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 titer indicates infection

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.

Congenital rubella is caused by the destructive action of the rubella virus on the fetus at a critical time in development. The most critical time is the first trimester (the first 3 months of a pregnancy). After the fourth month, the mother's rubella infection is less likely to harm the developing fetus. The rate of congenital rubella has decreased dramatically since the introduction of the rubella vaccine.

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) Pregnant women who are not vaccinated and who have not had rubella risk infection to themselves and damage to their unborn baby.

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

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 Live newborn: detection of IgM antirubella Abs in the serum of the baby by ELISA Stillbirth: virus isolation on MKTC During Pregnancy After Birth

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

MMR Contains 3 live attenuated viruses: mumps, measles and rubella Given in 2 doses The first dose: to children 12-15 months of age by subcutaneous injection Why not before that? When is the second dose? Contraindications?

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