PARAMYXO VIRUSES

Myxo – Mucous/mucin

Myxovirus – RNA Virus infecting mucous membrane

(respiratory) Affinity for certain mucins Causing agglutination of red blood cells

ORTHO (Influenza) & PARA (Others)

MYXO VIRUSES

Orthomyxo Paramyxo

Influenza Virus Parainfluenza Virus

Respiratory Syncytial

Measles Mumps

Parainfluenza Viruses

Important Characters

Spherical/Filamentous/Pleomorphic

Enveloped (150-300nm)

RNA ss – Non segmented

Negative sense genome

5 subtypes – PIV 1/2/3/4a/4b

Viral Proteins

HN – Haemagglutinin neuraminidase F – Fusion M - Matrix (underneath the envelope)

N/NP – Nucleoprotein P – Phosphoprotein L – Large RNA Polymerase

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Transmission, Pathogenesis & Clinical aspects Inhalation – Virus laden droplets

Incubation 2-8 days (nasopharyngeal epithelium) Further 1-3 days – Spread through

tracheobronchial tree

Both upper and lower RTI

Viremia is uncommon in immunocompetent hosts

Infants/children more commonly affected

Respiratory illness

Croup (Laryngotracheobronchitis) Bronchiolitis Pneumonia

Pharyngitis Common cold/rhinitis

Airway inflammation Necrosis/sloughing of epithelium Oedema/excessive mucous production Croup (PIV1,2)

Peaks between 1-2 yrs of age Swelling of vocal cords, larynx, trachea,

bronchi Obstruction of inflow of air (Stridor)

LRTI (PIV3) Alveolar filling Interstitial infiltration

Immunity

Maternal antibodies usually not protective Neutralizing antibodies (protective humoral

immunity) HN & F May not protect against re-infection 21 epitopes in PIV1 HN 20 epitopes in PIV3 F

Repeated infections needed for full protection (implications in vaccine development)

Diagnosis

Specimens: All used successfully Throat swab nasopharyngeal swab nasal wash nasal aspirates

Transport Swab/2-3ml washings VTM (2-3ml) (MEM with 0.5% BSA +

antibacterials/antifungals) 4 °C If delay (Frozen – If delayed >24 hrs)

Serological diagnosis

ELISA/RIA/HI/CFT/WB Drawback – cross reactivity among different PIV types CFT – least cross reactions (max specificity) but least

sensitive ELISA – Most sensitive but least specific 4 fold rise to any PIV type – significant (even if

heterologous antibodies +ve) – can not tell the subtype

Antigen detection Direct immunofluorescence Rapid but less sensitive than viral isolation Highly specific immune reagents (MAbs)required for

serotype identification

Culture/IsolationCell culture

Primary monkey Kidney cells (best) Cynomolgus cell line CPE – 4-7 days – syncytia & roundening Identification & typing –

IF – most rapid & accurate

EGGS - Poor medium - Many repeated blind passages needed

Management

Supportive Prevent secondary bacterial infections

In vitro trials with antivirals Neuraminidase inhibitor – Zanamivir Protein synthesis inhibitor – Puromycin Ascorbic acid Calcium enolate

Novel approach Inhibitors of syncytia formation (synthetic peptides

against F protein) Several immunostimulators tried (no significant

outcome)

Respiratory Syncytial Virus

Respiratory syncytial virus is the most important cause of lower respiratory tract illness in infants and young children, usually outranking all other microbial pathogens as the cause of bronchiolitis and pneumonia in infants under 1 year of age.

Structure RNA ss, unsegmented, negative sense 3 surface proteins

G – Attachment (No HA & NA activity) F – Fusion

2 matrix proteins M, M2

3 Nucleocapsid proteins N, P & L

F & G – Neutralizing Abs – Imp for vaccine development

G protein

F protein

Clinical Presentation

Most common cause of bronchiolitis May also cause –

Pneumonia/croup/pharyngitis/common cold Bronchiolitis

Predominantly in infants Peak age – 2-6 months >80% cases in 1st year of life Often starts with rhinitis After 2-3 days – LRT symptoms appear Wheezing – Hallmark of bronchiolitis Flaring of nostrils, use of accessory muscles. Elevated respiratory rate – 50-80breaths / min.

1/3rd may be afebrile – fever does not indicate the severity

Diagnosis

Cell culture Nasal swab, throat swab, tracheal aspirates

nasopharyngeal aspirates – All tested for efficiency Nasal washes/aspirates – better than swabs Cell lines

Human epithelial (HEp-2) – 8-10 days Human lung fibroblast (WI-38 or MRC 5) – 14 days Rhesus monkey kidney – 7 days

CPE - Distinct syncytia formation - Balled up syncytia become detached & float freely Identification by – IFA (most common)

Antigen detection

ELISA/IF assays Several kits available commercially IF -Best results with pool of antibodies to Fusion & Nucleoproteins - 91 % sensitivity ELISA - 79% sensitivity

Antibody detection CFT/ELISA Poor sensitivity in infants

Management

Bacterial superinfections infrequent – routine antibiotics not warranted

Supportive care – fluids/electrolyte monitoring Bronchodilators- Conflicting reports, no beneficial

role. Antivirals – Ribavirin - initial reports showed benefit - findings not confirmed - considered primarily in severe cases RSV-IGIV (RespiGam) - Passive transfer of specific antibodies - Prophylactic (premature, congenital heart disease)

Measles

100-150 nm

RNA ss, negative sense

Outer envelope proteins H –Attachment (CD46, CD150) F – Fusion M - Matrix

Pathogenesis & Clinical aspects

Natural infection only in humans Age : 6 months to 5 years old (maternal

antibodies are protective) Air-borne transmission Highly contagious (90% attack rate in

susceptible individuals) Permanent immunity acquired after disease –

single serotype

Virus gains access via respiratory tract

It multiplies locally

Spreads to regional lymphoid tissue

Further multiplication occurs

Primary viremia disseminates the virus

Then replicates in the reticuloendothelial system.

A secondary viremia seeds the epithelial surfaces of the body where focal replication occurs

skin respiratory tract conjunctiva.

Multinucleated giant cells with intranuclear inclusions are seen in lymphoid tissues throughout the body

Characterized by

Fever

URT catarrhal

koplik’s spots

Maculopapular rash Seuence:behind the ear→along thehairline→face→neck→chest→back→abdomen→ limbs→hand and feet(palm,sole)

Complications Bronchopneumonia (most fatal complication) Otitis media Myocarditis Laryngitis Neurologic complications:

Post Infectious Encephalomyelitis (PIE)1:1000 After1-3 weeks Immunological reaction

Subacute Sclerosing Panencephalitis (SSPE).1:300,000After 5-15 years (dormant/persistant infection)Defective viral replicationHigh antibody titres in CSF

Laboratory Diagnosis

Antigen Detection Directly in epithelial cells in respiratory

secretions and urine Nucleoprotein detection- The most abundant

viral protein in infected cellsSerological Diagnosis fourfold rise in antibody titer between acute-

phase and convalescent-phase sera Specific IgM antibody in a single serum

specimen drawn between 1 and 2 weeks after the onset of rash

ELISA, HI, and Nt tests all may be used

Isolation and Identification of Virus Samples

Nasopharyngeal and conjunctival swabs Blood Respiratory secretions Urine

Cell lines Monkey or human kidney cells Lymphoblastoid cell line (B95-a)

Detection Cytopathic effects (multinucleated giant cells

containing both intranuclear and intracytoplasmic inclusion bodies) take 7–10 days to develop

Fluorescent antibody staining to detect measles antigens in the inoculated cultures.

Management & Prevention

General therapy: rest, nursing and diet

Symptomatic therapy: fever and cough

Support therapy : Vitamin A

Treatment of complications

Active immunization Lived attenuated measles vaccine.

MUMPs

Pathogenesis & Clinical aspects Humans are the only natural hosts Acute contagious disease More than one-third of all mumps

infections are asymptomatic. Primary replication occurs in nasal or

upper respiratory tract epithelial cells. Viremia then disseminates the virus to

the salivary glands and other major organ systems.

Mumps is a systemic viral disease with a propensity to replicate in epithelial cells in various visceral organs.

The incubation period -2 weeks to 4 weeks A prodromal period of malaise and anorexia Rapid enlargement of parotid glands as well as

other salivary glands. Hallmark - Nonsuppurative enlargement salivary

glands. Virus is shed in the saliva from about 3 days

before to 9 days after the onset of salivary gland swelling.

Infected individuals who do not exhibit obvious symptoms (inapparent infections) are equally capable of transmitting infection.

Mostly causes a mild childhood disease, but in adults complications including meningitis and orchitis are fairly common.

Complications

Central nervous system involvement – Aseptic meningitis (10-30% cases)

Testes and ovaries may be affected, especially after puberty.

Pancreatitis is reported in about 4% of cases

Immunity

Immunity is permanent after a single infection.

There is only one antigenic type of mumps virus

It does not exhibit significant antigenic variation

Antibodies against the HN antigen correlate well with immunity.(Protective )

Laboratory Diagnosis

Serology Fourfold or greater rise in antibody titer is

evidence of mumps infection.

Specific IgM in serum drawn early in illness strongly suggests recent infection

The ELISA or HI test is commonly used

Isolation and Identification of Virus Samples

Saliva Cerebrospinal fluid Urine

Cell line – Monkey Kidney cell line Detection

Cytopathic effects typical of mumps virus consist of cell rounding and giant cell formation

Immunofluorescence

Management

There is no specific therapy Supportive/symptomatic treatment Immunization with attenuated live

mumps virus vaccine is the best approach

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