Measles Virus (Rubella Virus) Infection

Introduction

Measles is an acute highly infectious disease characterized by fever, respiratory syndrome and maculopopular rash, the introduction of an effective live virus vaccine has dramatically reduced the incidence of this disease but measles is still the leading cause of death of young children in many developing countries.

Measles virus is a member of the genus Morbillivirus and the family paramyxoviridae. This virus is morphologically indistinguishable from parainfluenza and Mumps virus. The virion has the following structure:

• Envelope spikes having hemagglutinin but not neuraminidase function
• Fusion (F) proteins that is a smaller glycoprotein.
• A matrix (M) protein below the envelope lipid bilayer
• The genetic material consists of single stranded negative sense RNA molecule.
• RNA-dependent RNA polymerase.

There is only one serotype of measles and subtypes have not yet been recognized. Humans are the only natural host for measles virus. The virus gains access to the human body through respiratory tract where it multiplies locally. The cellular receptors functions are to bind certain components of complement. Hemagglutinin helps in adsorbing the virus to cells and fusion (F) proteins facilitate uptake of the virion.

Microbiology of Measles virus

Measles virus belongs to the family paramyxoviridae...

Morphology

• The morphology of measles virus is pleomorphic with particles 150nm or more in diameter occasionally ranging up to 700nm. The envelope of measles virus seems to be fragile, making them labile to storage condition and prone to distortion in electron micrographs.
• Spikes on envelope contains Hemagglutinin (HA) but no Neuraminidase (NA). Matrix M protein is located below the envelope lipid bilayer. It also contains F protein which mediates membrane fusion.

Genome

• A viral genome is linear, negative-sense, ssRNA of about 15kb in size. As the genome is not segmented, this negates any opportunity for frequent genetic re- assortment, resulting in the fact that measles virus are antigenically stable.

Pathogenicity

Measles is highly contagious and is transmitted from person to person by respiratory droplets. It is an acute fabric illness; most commonly occurs in children, the incubation period is 9-12 days. A virus infects epithelial cells of respiratory tract and multiplies in lymphoid tissues of the respiratory tract and invades blood stream (primary viremia) and localized in a Reticuloendothelial system, secondary viremia occurs which is flue like with high fever. From blood, viruses localize in the cells of conjunctiva, respiratory tract, urinary tract, lymphoid system, CNS and blood vessels where they replicate.

Clinical disease

1. Prodromal phase

It is prior to the appearance of the rash, the patients suffer from a prodromal phase of 2-4 days with conjunctivitis, swelling of the eyelids, photophobia, high fever to 105F, hacking cough, rhinitis, and malaise. The incubation period is usually 10-21 days. Mostly, it starts with high fever and 3C’s,

• Cory
• Conjunctivitis (associated with photophobia)
• Cough

The prodromal phase lasts for several days and the patients are most infectious at this time.

2. Koplik’s spots

Koplik’s spots are the red spots with a bluish-white center on the buccal mucosa. They appear at the end of a prodromal period and 24-36 hrs before the appearance of a rash.

3. Rash

After 1-3 days, the cute syndrome declines with the widespread appearance of red flat to slightly bumpy maculopapular rash. The rash starts on the forehead to the whole face then spread progressively to the chest, trunk, down the lymph and hit the feet by the third day. Soon after the rash appears, the patients are no longer infectious. Over the next 10-14 days, recovery is usually complete as the rash fades, with considerable desquamation.

4. Exanthematic stage

With the decline of acute symptoms in 1-2 days, a typical widespread maculopapular rash appears, on the skin (Which begins on face and thorax and spread periterally), mucous membrane and conjunctiva. The rashes last for approximately 5 days.

Types of measles

1. Atypical measles

Atypical measles occurs in an individual who receive the older inactivated vaccine and later exposed to wild strains. The wild virus infects permissive cells and undergoes limited replication. The virus is not recovered from the patients and the patients are also not contagious.

2. Modified measles

It is a mild form of measles found in infants receiving mother’s breast milk containing maternal antibodies.

Complications

Viruses may disseminate to many organ systems and can damage those sites. The most common complications of measles are otitis media, pneumonia, eye damage, etc. Acute encephalitis occurs in about 1:1000 cases, but 10% of patients who develops this will die. Measles in pregnant women results in fetal death in 20% of cases. Mostly complication see are described below:

• Measles pneumonia

Pneumonia is a most common life-threatening complication of measles caused by secondary bacterial infection. This occurs in less than 10% of cases in developed countries but is more frequent in developing countries.

• Sub- acute sclerosing panencephalitis (SSPE)

It is a rare late complication of measles infection. It is the chronic degenerative neurological disease that may occur in children or early adolescent who have had measles early in the life. The disorder occurs several years after infective when a defective measles virus persists in the brain and acts as a slow virus. The mutation occurs in the genes for matrix (M) and fusion (F) proteins of measles virus. The children are particularly susceptible, especially those weakened by other disease or malnutrition.

Treatment

Treatment of the measles can be done by ribavirin. Vitamin A treatment in developing countries has also decreased mortality and morbidity. A highly effective and safe attenuated live measles virus vaccine is available. Measles vaccine are available in monovalent from and in combination with live attenuated Rubella Vaccine (MR) vaccine. Live attenuated Rubella and Mumps Vaccine (MR) and live attenuated varicella vaccine (MMRV).

Vaccine schedule

MMR vaccine is given at 15-24 months and at 4-6 years.

Lab diagnosis

Most cases of measles are diagnosed clinically, usually by symptoms.

Specimen:

Nasopharyngeal and conjunctival swabs, blood sample, respiratory secretions etc.

Isolation and identification of virus: Different specimens collected from the patients during the febrile period are an appropriate source for virus isolation. Monkey or human kidney cells are used for culture and isolation. Measles virus grows slowly and typical cytopathic effect develops in 7-10 day.

Nucleic acid detection

Detection of viral RNA by reverse transcriptase PCR (RT-PCR) is a sensitive method that can be applied to a variety of clinical samples for measles diagnosis.

Serological confirmation of measles infection depends on a 4 fold rise in antibody titer between acute phase and convalescent phase on demonstration of measles specific. IgM antibody in a single serum specimen drawn between 1 and 2 weeks after the onset of rash. ELISA, Neutralization test, haemagglutination inhibition test etc are used to detect antibodies in serum.

Epidemiology

Transmission

Transmission occurs predominantly by the respiratory route. Conjunctivitis may also be the source of infection. Infection is transmitted by the patients during few days before and after the rash.

Reservoir

The man is the only natural host of measles and monkey acquired infection from man.

Incidence

The greatest incidence of measles is seen between 1-5 years and by the age of 20 years, 90% individual have had the experience of measles. The disease is endemic throughout the world and epidemics usually occur in late winter and early spring.

The WHO (in 2005), estimated that there were 30-40 million measles cases and 5,30,000 death annually.

REFERENCE

Cheesbrough, M.Medical Laboratory Manual for Tropical Countries. Vol 2. ELBS London, 2007.

Tille, P.Diagnostic Microbiology.13th. Elsevier, 2014.

D Grenwood, Slack RCB, and Peutherer J.Medical Microbiology.Dunclude Livingstone: ELBS, 2001.