Measles Virus: Pathogenesis, Clinical Findings and Lab Diagnosis

MEASLES

-         most common cause of child hood fevers.

-         Spikes carry HA but not an NA function; only one serotype.

-         Disease characterized by fever, respiratory symptoms, and a maculopapular rash.

PATHOGENESIS / PATHOLOGY
- human are the only natural hosts.

-         virus gains access via the respiratory tract, infection then spreads to the regional lymphoid tissues.

-         1⁰ viraemia disseminates the virus ( replicates in the RE- system).

-         2⁰ viremia seeds the epithelial surfaces ( skin, respiratory tract, conjunctiva) where focal replication occurs.

-         Multinucleated giant cells with intranuclear inclusions seen in lymphoid tissues through out the body ( lymph nodes, tonsils, appendix).

-         Incubation period is typically 8-12 days ( may be upto 3 weeks in adults)

-         During prodrome (2-4 days) and the first 2-5 days of rash, virus is present in tears, nasal and throat secretions, urine and blood.

-         Characteristic maculopapular rash appears about day 14; rash develops as a result of interaction of immune T cells with virus infected cells in the small blood vessels; in patients with defective CMI no rash develops.

-         Involvement of CNS is common
 • symptomatic encephalitis in about 1:1000 cases.
 •  progressive measles inclusion body encephalitis in patients with defective CMI, actively replicating virus present in the brain in this usually fatal form.
 • subacute sclerosing panencephalits  ( SSPE) develops years, after initial infection.

CLINICAL FINDINGS
- infection in non- immune hosts almost always symptomatic

-         after an incubation of 8-12 days, measles is typically a 7-11 day illness (2-4 days prodrome) followed by eruptive phase of 5-8 days)

-         prodromal phase characterized by fever, sneezing, coughing, running nose, redness of the eyes, kopliks spots and lymphopenia .

-         koplik’s spot ( pathognomonic for measles) are small, bluish- white ulcerations on buccal mucosa opposite the lower molars; these spots contain giant cells and viral Ag and appear about 2 days before the rash.

-         Rash starts on the head, and spreads progressively to the chest, trunk, drown the limbs, appears as light, pink, discrete maculopapules that coalesce to form blotches, becoming brownish in 5-10 days; fading rash resolves with desquamation over the next 10-14 days.

-         Most common complication is otitis media( 5-9% of cases).

-         Pneumonia is the most common life threatening complication caused by 2⁰- bacterial infections; pulmonary complications account for > 90% of measles – related deaths.

-         Giant cell pneumonia a serious complication in people with CMI deficiency.

-         Complication involving CNS in about 1: 1000 cases.

-         Post infectious encephalomyelitis ( acute disseminated encephalomyelitis) is an autoimmune disease associated with immune response to myelin basic protein.

-         Mortality in measles associated encephalitis is about 10-20% ; majority of survivors have neurologic sequelae.

-         SSPE: - incidence of about 1: 300,000 cases.
- disease begins insidiously 5-15 yrs after a case of measles .
- progressive mental deterioration, involuntary movements, muscular rigidity and coma; fatal with in 1-3 years of onset.
- with in the infected cells is a defective form of measles virus, because it is unable to induce the production of a functional M- protein, is not released as complete virus from the cells.
- oligoclonal antibody to viral proteins appear in the CSF.

-         Virus has been linked with multiple sclerosis, pagets disease of bone and Crohns disease.

-         Induces labour in some- pregnant women, resulting in spontaneous abortion or premature delivery.

-         There occurs a suppression of delayed hypersensitivity after measles infection.

IMMUNITY

-         only one antigenic type; infection confers life long immunity

-         presence of humoral antibody indicates immunity; CMI important in recovery and protection .

-         immune response involved in disease pathogenesis.

-         Local inflammation causes the prodromal symptoms.

-         Specific CMI plays a role in development of rash.

-         Infection causes immune suppression → cause serious 2⁰- infection.

LAB DIAGNOSIS
typical cases reliably diagnosed on clinical grounds; lab diagnosis necessary in modified or atypical cases.

Ag detection
Ag detected directly on exfoliated respiratory cells by IFT using Ab to the viral nucleoprotein.

Isolation and identification of virus

-         nasopharyngeal and conjunctival swabs, blood samples, resp. secretions and urine collected during the febrile period.

-         Monkey or human kidney cells or a lymphoblastoid cell line (B95-a) are optimal; virus grows slowly and typical CPE ( multinucleated giant cells containing both intranuclear and intracytoplasmic inclusion bodies) take 7-10 days to develop. → Warthin- Finkeldey cells.

-         Shell vial culture tests can be done in 2-3 days using fluorescent Ab- staining.

Serology

-         4 fold rise in Ab- titer between acute and convalescent sera or demonstration of specific IgM in single serum specimen drawn between 1 and 2 weeks after onset of rash.

-         ELISA, HI and Nt tests used; ELISA is most practical.

-         High titer Ab in CSF is diagnostic of SSPE

Epidemiology

-         virus is highly contagious; there is a single serotype; inapparent infections are rare; human is only natural host, no animal reservoir.

-         Transmission via the respiratory route; haematogenous transplacental transmission can occur; associated conjunctivitis may also be a source.

-         Patients infectious from 3 days before onset of symptoms until the rash desquamates; infectivity max. at prodrome and diminishes rapidly with onset of rash.

-         Epidemic occur every 2-3 yrs; populations state of immunity is a determining factor, severity of epidemic is a function of the number of susceptible individuals; can cause epidemic in an isolated community where it has not been endemic, in such case mortality rate can be as high as 25%.

-         Rarely causes death in healthy people, but in some malnourished children, it is a leading cause of infant mortality.

Treatment / prevention/ control

-         Vit A treatment in developing countries decreased mortality / morbidity.

-         Virus susceptible in vitro to inhibition by ribavirin.

-         A safe and highly effective live attenuated vaccine is available in either monovalent form or in combination (MR / MMR); given at 12-18 months of age.

-         Due to failure in vaccinating children and infrequent cases of vaccine failure, measles has not been eliminated.

-         Mild clinical reactions (fever or mild rash) will occur in 2-5%  vaccinees

-         Ab- titer lower than after natural infection; but immunity probably life long.

-         Contraindications include pregnancy, allergy to eggs or neomycin, immune comprise and recent administration of Ig.

-         Strain used is Edmonston B or Schwanz, seroconversion rate is >90%.

-         Recommended age for vaccination in developing countries is 9 months; a single subcutaneous injection of vaccine provides protection beginning in about 12 days and lasting for over 20 yrs.

Passive immunization → normal human gamma- globulin with in 6 days of exposure can prevent or modify the disease; valuable in children with immunodeficiency, pregnant women and others at special risk.