Paramyxo Virus

ParamyxovirusNeeraj Sharma Msc Microbiology PBPC Pokhara Nepal

IntroductionIncludes . 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 RTMeasles & mumps disseminate throughout the body.

Properties Structure and compositionPleomorphic, 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.

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)

The difference between the orthomyxo & paramyxovirusesOrthomyxovirusesParamyxovirusesDiseases caused in humansInfluenza types A, B and CParainfluenza 1-4 infections, RSV diseaes, mumps and measlesgenomessRNA 8 segmented, -ve sensessRNA nonsegmented ve sense Fusion of virus with cellEndosomePlasma membraneTranscription of viral RNAHOST CELL NUCLEUSHost cell cytoplasmGenetic reassortmentfrequentRareRate of antigentic changehighlow

ClassificationParamyxoviridae family has 2 sub families ParamyxovirinaeRespirovirus : Parainfluenza 1,3Rubulavirus: Mumps, Parainfluenza 2, 4a,4bMorbili Virus: measlesHenipavirus: Hendra, Nimph

PneumovirinaePneumo virus: RSVMetapneumovirus: human metapneumovirus

Pneumovirusparamyxoviridae

Parainfluenza (1-4)

Mumps

RSV

Measles

1&2chld&inf3 >2 ysevere4-Mild disease

ParamyxovirusHNMorbillivirus H

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ReplicationTakes place in cytoplasmVirus 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.

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.

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.

Parainfluenzavirus

Para influenza virusPara influenza viruses are ubiquitous and cause common respiratory illness of varying severity in all age groups.

Transmission: dropletTYPE 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

Primary infections in young children usually result inRhinitis 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

Pathogenesis Incubation period 3 to 6 days.In immuno competent host, infection is limited to respiratory epitheliaType 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.

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.

Clinical findingsPrimary 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 doesnt cause serious disease even on first infection.

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 .

In humans it may produce inflammation of conjunctiva. Disease is limited to workers handling the infected birds.Recovery is complete in 10-14 days.

Widely distributed geographically,

Type 3 is most pravalent 1&2 occur at lower rate.

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.

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.

Isolation & Identification:Rapid cell culture technique Slow to produce results.

Serology:Neutralization test, Hemagglutination or ELISA

Treatment and prevention Isolation of the infected patient.Gowning and hand washing by medical personsRibavirin is used in treatment of immuno compromised patient with lower respiratory tract disease No vaccine available.

Respiratory Syncytial Virus

RSV Structure

Most important cause of LRT infection in infants and young childrenMajor 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.

RSV- syncytium formation

PathogenesisLocalised 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

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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

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.

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.

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.

Clinical FeaturesUpper Respiratory InfectionFeverRhinitisPharyngitisLower RespiratoryInfection- Bronchiolitis,PneumoniaCoughPoor feeding, lethargyHypoxemiaRespiratory Distress (tachypnea, retractions)Apnea

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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.

Treatment and preventionTreatment of serious RSV depends primiraly on supportive care Ribavirin is approved for treatment of LRT, administered in aerosoles.No vaccine is available.

Mumps Virus

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IntroductionIt 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.

Time course of Mumps infection

Local replication

Systemic infection

Inoculation EC of URT

Viremia

Virus multiplies in ductal epithelial cells. local inflammation causes Marked swellingParotid gland

pancreas

TestesOvariesPeripheral nervesEyeInner earCNS

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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.

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.

Virus frequently infects kidney and can be detected in urine of most patients.The central nervous system is also commonly infected.

Lab diagnosisNucleic acid detection:By Reverse transcription polymerase chain reaction.Antigen detection:by ELISA or HI testIsolation of the virus from saliva CSF and urineMonkey kidney cells are preferred for viral isolation.

Treatment and preventionImmunization 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.

Measles

Measles

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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.

MeaslesSerious and highly contagiousUsually found in non-immunized or partially-immunized (single vaccine, no booster)Most born before 1957 have had measlesMeasles virus is spread easilyThrough 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

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MeaslesSymptoms start about 10 days after exposureAverage 10 days from exposure to onset of feverAverage 14 days from exposure to onset of rashOther symptoms and complications Ear infectionPneumoniaCNS/ brain infection (as SSPE, subacute sclerosing panencephalitis)Complications may be lethalMore serious in infants and adults, less in children and teensVaccineMeasles (Paramyxoviridae), mumps (Paramyxoviridae), rubella (Togaviridae, + sense) (MMR) vaccine is a live vaccineHas been very effective in limiting spread Links of vaccine to autism have been proposed but not shownManagement 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

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Measles pathogenesis

Lymphatic spread

Wide dissemination

Virus- infected endothelial cells+ immune T cell

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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)

Clinical featuresProdromal stageEruptive stagePost-measles stage

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Prodromal phase starts with high fever and 3CsCoryzaConjunctivitisCough

Eruptive phase Presence of kopliks spot Kopliks spot: Red spot with bluish white centre on the buccal mucosa just above the lower molars.

KOPLIK SPOTSource: http://phil.cdc.gov/PHIL_Images/20040908/4f54ee8f0e5f49f58aaa30c1bc6413ba/6111_lores.jpg

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Measles Koplik Spots

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With decline of acute symptoms in 1 to 2 days typical wide spread maculopapular rashes (morbiliform) rash appear on skinBegins 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.

Lab diagnosis

Same as other paramyxoviruses

Rubella Virus(Germen measles)

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.

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.

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Source of infection Respiratory secretionTransmission droplet, vertical transmissionI.P 2-3 weeks average 18 days

Clinical Symptoms.Eye pain on lateral and upward eye movement (a particularly troublesome complaint)ConjunctivitisSore throatHeadacheGeneral body achesLow-grade feverChillsAnorexiaNauseaTender lymphadenopathy (particularly posterior auricular and suboccipital lymph nodes)

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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)

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.

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Lab diagnosisNucleic acid detection.Isolation and identification of virus.Serology

AgeVaccinesNote9 monthsMeaslesDeep subcutaneous injection into the upper arm.12-15 monthsMMR -1Deep subcutaneous injection into the upper arm.5 yearsMMR -2Deep subcutaneous injection into the upper arm.

Treatment and control

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