Paramyxoviridae Virus Family

Paramyxoviridae

• This family includes enveloped, single-stranded negative-sense RNA viruses.
• These viruses replicate in the cytoplasm and range in size from 150 to 300 nm.
• The family has the ability to cause cell fusion leading to giant cells (syncytia).
• Infections caused are present in vertebrates
• Pathogenesis includes the virus’s ability to escape immune detection.
• Infections in humans include parainfluenza virus, respiratory syncytial virus (RSV), measles virus, and mumps virus.

Paramyxoviridae Subfamilies

• Contains two subfamilies relevant to human health: Pneumovirinae and Paramyxovirinae.
• Pneumovirinae gives rise to the genus Pneumovirus, which includes Respiratory syncytial virus.
• Paramyxovirinae gives rise to the Morbillivirus genus, which is measles virus (or Rubeola).
• The Respirovirus genus is also formed, including Para-influenza viruses 1 and 3.
• The Rubulavirus genus is formed, including Mumps virus & Para-influenza viruses 2 and 4.
• Transmission of these viruses occurs via respiratory droplets or direct contact.
• Measles and rubella were targeted for elimination in five different World Health Organization (WHO) regions by 2020.

Parainfluenza Viruses

• Enveloped viruses contain a -ve sense single stranded RNA with four major human serotypes.
• Major cause of croup in children, an infection in upper airways such as larynx and trachea.
• It’s a significant cause of severe lower respiratory tract viral disease in immunocompromised patients.
• The four types of parainfluenza viruses are PIV-1, PIV-2, PIV-3, and PIV-4.
• Parainfluenza viruses preferentially infect ciliated epithelial cells of the upper and lower respiratory tract.
• There is a worldwide distribution
• Infections happen in both children and adults.
• Person-to-person spread is through the exposure to respiratory droplets or contact with contaminated surfaces.
• PIV-1 and PIV-2 cause seasonal outbreaks in the fall, and PIV-3 and PIV-4 cause outbreaks in the spring.
• Parainfluenza virus/croup accounts for at least 1/3 of acute respiratory infections in the pediatric population each year.
• Complications include pneumonia, pulmonary edema, bacterial tracheitis, & death.

Clinical Presentation of Parainfluenza Virus

• Causes mostly limited pediatric infections to the upper respiratory tract with cold symptoms.
• Symptoms develop in about one day after exposure of the virus which can persists for a week or more
• Results in sinuses and middle ear involvement occurs in up to half of children.
• PIV-1 and PIV-2 lead to laryngotracheobronchitis (croup) alongside fever, rhinorrhea, and pharyngitis,.
• this then progresses to a barking cough associated with stridor and difficulty breathing.
• PIV-1 disease is generally more severe than PIV-2 disease.
• PIV-3 disease is more commonly associated with pneumonia and bronchiolitis in children.
• PIV-4 primarily causes mild upper respiratory infections in adults and children.

Parainfluenza Virus Diagnosis and Treatment

• Clinical diagnoses require usage of mainly nucleic acid amplification techniques (NAATs).
• Treatment is supportive, as there is no specific antiviral treatment.
• Croup is managed symptomatically with glucocorticoids and nebulized epinephrine, which relaxes the smooth muscle of the bronchi.
• Treatment includes oxygen, humidified air, and supportive care.
• A vaccine is unavailable.

Respiratory Syncytial Virus RSV

• The respiratory syncytial virus is Enveloped -ve sense single stranded RNA virus.
• Named for ability to form syncytia in respiratory epithelial cells.
• It infects the lower airways (in infants).
• RSV disease is widespread in adults (but can occur in high-risk patients).
• RSV is responsible for the majority of middle ear infections (otitis media) in young children.
• RSV is resposnsible for bronchiolitis in infants which is around half of infant hospitalizations.
• Reinfection frequently occurs due to a lack of long-term immunity in humans.
• RSV accounts for 33 million infections across the world with around 200,000 pediatric deaths.
• 90% of the pediatric population under 2 years of age contract RSV.
• Most common is person-to-person spread (by exposure to respiratory droplets or contact with contaminated surfaces).
• Infections occur annually that begins late fall through early spring, or throughout the year in warmer climates.

Clinical Presentation of RSV

• Infections result in the upper respiratory tract, fever, fatigue, rhinorrhea, nasal congestion, and cough.
• Infection in children and adults presents with symptoms such as fever, fatigue, rhinorrhea, nasal congestion, & cough.
• RSV directly causes acute otitis media in children.
• Secondary bacterial co-infections by S. pneumoniae, or H. influenzae can lead to more severe otitis.
• Infections in infants involve the lower respiratory tract.
• Infants will show the disease after a 2-5 days incubation period.
• Infants develop bronchiolitis and pneumonia with dyspnea or apnea.

RSV Diagnosis and Treatment

• Commonly performed through rapid antigen testing and NAAT (PCR) testing.
• A chest x-ray may show hyperinflation of the lungs and patchy atelectasis.
• Mild infections are treated symptomatically.
• Bronchiolitis is generally managed with supportive care, bronchodilators, and corticosteroids.
• Ribavirin is approved for the treatment of hospitalized infants with lower respiratory tract disease.
• Palivizumab is used for immune prophylaxis.
• A vaccine is not available.

Measles Virus

• Enveloped -ve sense single stranded RNA virus, also known Rubeola.
• A single serotype with H-glycoprotein (H) and fusion protein (F).
• Contains no neuraminidase
• Measles is an acute & febrile exanthematous disease that causes a maculopapular rash.
• Reservoir is present in the human respiratory tract
• Spreads through respiratory route
• Very contagious, present in respiratory secretions for a long time before symptoms appear.
• Symptoms include Fever; 3 Cs (cough, coryza, and conjunctivitis) with photophobia,.
• Koplik spots turns into maculopapular rash

Complications of Measles

• Can lead to encephalitis, giant cell pneumonia (measles pneumonia), subacute sclerosing panencephalitis.

Measles Pathogenesis

• The virus enters via respiratory droplets.
• It first infects alveolar macrophages & dendritic cells.
• The virus multiplies and disseminates in lymph nodes.
• The virus spreads to blood, causing Viremia.
• Virus moves to different body organs (RT, GIT, CNS, UT, conjunctiva, small blood vessels, lymphatics).
• Rash appearance is immune-mediated due to infection of dermal capillary endothelial cells with immune complex formation.
• May end with complete recovery or complications in the CNS.

Clinical Stages of Measles (IP - 10-14 Days)

• Prodrome - flu-like RT symptoms: high fever-cough-headache-coryza-conjunctivitis with photophobia.
• After 2 days - Enanthem manifests as Koplik's spots which are white patches with a red halo in mouth, conjunctiva, and vagina and have a cytopathic effect.
• Koplik's spots manifest 2-3 days before appearance of measles skin rash.
• Eruptive stage - symptoms reappear as Exanthema across the body that starts below the ear.
• The rash is maculopapular and the virus is excreted in urine and RT from 6-7 days to 14 days.

Complications of Measles

• Frequent complications include bronchopneumonia, otitis media, and/or bacterial infection, sinusitis, etc.
• Major complications include encephalitis (rare - 1 per 2000 cases).
• Giant Cell Pneumonia - causes deadly complication of immuno-deficient children.
• Sub-acute sclerosing panecephalitis - rate complication (mean time 6-8 years).
• mutant of measles virus persists in act as a slow virus, chronic progressive CNS degeneration.

Measles Diagnosis and Treatment

• Characteristized by large multinucleated giant cells with cytoplasmic & intranuclear inclution bodies is a major diagnoses.
• Confirmed via isolation, cultivation, and identification.
• Immunofluorescence can detect Abs using viral Ags.
• Isolation, Cultivation, Identification is commonly used for Cell Culture.
• Therapy includes: supportive therapy, antibiotics, and immune globulin doses.

Measles & Control

• Live attenuated Measles vaccine (MMR) is an active immunization; administered Subcutaneously.
• Measles Intramuscular Immune Serum Globulin.
• Passive immunization recommended as post-measles exposure prophylaxis.
• Administer within 6 days of initial exposure.

Mumps Virus

• Identified as enveloped -ve sense single-stranded RNA virus.
• Involves single HN glycoprotein, hemagglutinating activity and neuraminidase activity.
• Includes F protein which is Mediates the fusion of virion and host-cell surface membranes.
• The virus shows a single serotype and reservoir is a human respiratory tract,
• Transmits person to person via respiratory droplets.
• Itlytic infection of epithelial cells of the URT and parotid glands

Defining Mumps

• Mumps (Acute benign viral parotitis) causes puffy cheeks and tender jaw from swelling of parotid glands under the ears on one or both sides (bilateral).
• Main symptom of infection also referred to as parotitis.
• Symptoms include fever, headache, muscle aches, tiredness, and appetite loss,.
• In rare cases, mumps can cuase severe complications, cases include complications, pancreatitis, meningoencephalitis, deafness, orchitis (reduced sperm production), oophoritis.

Mumps Symptoms and Pathogenesis

• Clinical symptoms: Acute onset fever, muscle pain & malaise
• Mainly causes parotitis, or painful swelling of the parotid salivary glands, usually bilateral
• It follows complete, uncomplicated recovery + permanent immunity
• Most people with mumps recover completely within two weeks.
• In rare occurances(4-7 days later), people can contract orchitis for males that contract virus post-puberty affecting sperm and sterility, occophoritis on ovaries, nephritis caused by damage to the kidneys, meningitis due to muscle weakness, or deafness.
• Incubation period for mumps is 16-18 days post respiratory droplet saliva.
• It grows within oorpharyx.
• Symptoms appear in parotid gland along and lymphatic tissues

Mumps Diagnosis and Treatment

• Isolates it from from saliva and secretions from parotid glands.
• Grows them on cell cutlure to find the characteristics
• The test results leads to Cytopathic effect creating multinucleated giant cells.
• Testing: ELISA and Complement-fixation test.
• Treatment: Supportive based

Mumps Control

• Best method of defense is Trivalent MMR (Measles-Mumps-Rubella).
• Administer Subcutaneously at 14 months old.
• Provides a life-long immunity

Family Togaviridae Characteristics:

• This family contains lipoprotein enveloped, icosahedral capsid viruses with Positive-sense ssRNA.
• Viruses of Medical Importance include Alphaviruses the arboviruses.
• Arboviruses include Easter/Western equine encephalitis viruses.
• Arboviruses include Chikungunya & Venezuelan equine encephalitis viruses,

Rubella Virus: Disease Characteristics & Transmissions

• Its reservoir is in the human respiratory tract and is transmitted via the respiratory route.
• Rubella is a highly contagious, acute, and febrile exanthematous disease causing a macular rash.
• Maternal Rubella infection is the major contributor for a cause of fetal death & congenital malformation during the first 16 weeks of pregnancy, after pregnancy does not damage the fetus. 2 types of Viruses can be contracted during infection

Impacts to Fetus by Rubella

• Cytolytic: kills virus of embryo, this leads to death in the uterus.
• No-Cytolytic: disrupts normal growth and chromosomal structure.
• Cataracts and deafness.
• Causes Mental retardation (causes mortality in uterus) and heart defects.

Rubella and its Pathogenesis:

• Incubation period is 2 weeks, the virus is shed in RT 2 weeks before & 2 weeks after infection.
• Spreads to local lymph nodes for RES.
• Virus replication goes into viremia to transmit.
• Causes milder macular rash on other tissues .
• In pregnant women will lead to Vertical Transmitted from mother

Rubella Treatment

• Treatment for Postnatal Rubella is benign and requires only symptomatic treatment.
• Get vaccinated by live attennueted rubella vaccine .
• Vaccinate a month before getting pregnancy.
• Vaccine isn't allowed during pregnancy.
• Passive Immunization for pregnant, use immune serum globuin