Measles virus (Morbilli virus)

Measles (Latin morbilli) is an acute viral disease of mainly childhood, characterized by general intoxication, fever, catarrh of the mucous membranes of the respiratory tract and maculopapular rash.

The causative agent of measles was isolated in 1954 by J. Enders and T. Pibles. Morphologically, it is similar to other paramyxoviruses: virion diameter 150-250 nm, virus genome is a single-stranded unfragmented negative RNA 15,900 nucleotides long included in the spiral nucleocapsid. The genome carries 6 genes in the following order: N, P, M, F. H, L. They encode proteins: nucleoprotein (N), phosphoprotein (P), matrix (M), fusion protein (F), hemagglutinin (H) and polymerase (L). A feature of the viral genome is the presence in its M-F-intergenic region of a large non-coding region of about 1000 nucleotides in size. Like other paramyxoviruses, the measles virus has haemagglutinating, hemolytic and symplast-forming activity, but it lacks neuraminidase.

Hemagglutinin, hemolysin (F), nucleoprotein (NP) and matrix protein differ in antigenic specificity and degree of immunogenicity. Hemagglutinin is the most immunogenic. With the help of monoclonal antibodies, several serovariants of the human measles virus were detected. It also has common antigenic determinants with the viruses of dog plague and rinderpest.

Laboratory animals to the measles virus are unresponsive. Only in monkeys does the virus cause disease with characteristic clinical symptoms, and in the wild, monkeys can get infected from humans.

In chicken embryos, the measles virus breeds poorly. For its isolation, primary-trypsinized kidney cultures of monkey kidneys or human embryos are used, in which the virus during reproduction multiplies the characteristic cytopathic effect (formation of giant multinucleated cells - symplasts and syncytia - and granular inclusions in the cytoplasm and nucleus). However, the measles virus can also be adapted to cell cultures from the kidney of dogs, calves or human amnion cells, as well as to various transplantable lines. The virus can have a mutagenic effect on the chromosomes of cells.

The virus is unstable, rapidly inactivated in acidic medium, reduces its activity at a temperature of 37 ° С, at 56 ° С perishes in 30 minutes, easily destroyed by fat solvents, detergents, very sensitive to sunlight and quickly dies in the external environment. Resistant to low temperature (-70 ° C). These circumstances should be considered when transporting and storing live measles vaccine.

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Pathogenesis and symptoms of measles

Infection occurs by airborne droplets. The virus multiplies in the epithelial cells of the mucous membrane of the nasopharynx, trachea and bronchi. Penetrating into the blood, causes damage to the endothelial cells of the vessels, resulting in a rash. The most characteristic symptom is the formation on the mucous membrane of the cheeks of Koplik-Filatov stains. The incubation period is about 10 days. The picture of the disease is so characteristic that the diagnosis is easily put clinically. In the prodromal period - the phenomenon of acute respiratory disease (rhinitis, pharyngitis, conjunctivitis). Differential diagnostic significance is the appearance of Koplik-Filatov stains. A papular rash usually appears on the fourth day after the temperature rises, first on the head (forehead, behind the ears), and then spreads throughout the body. The body temperature is normalized to the 7th-8th day.

The most common complication is pneumonia, and in the early period of the disease - edema of the larynx, croup. Very rarely measles proceeds in unusual, severe form - in the form of acute measles encephalitis, more often in children older than 8-10 years of age. In children who received with the preventive purpose of measles immunoglobulin, the disease proceeds in a mild form (mitigated measles). Post-infectious immunity is strong, lifelong, caused by viral neutralizing antibodies, T-cytotoxic lymphocytes and immune memory cells.

Epidemiology of measles

The source of infection is only a sick person. It becomes contagious from the last day of the incubation period and until the 4th-5th day after the appearance of the rash.

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Subacute sclerosing panencephalitis

The measles virus causes not only an acute productive infection, which is measles, but, very rarely, a severe slow infection - subacute sclerosing panencephalitis (PSPE). It was first described in 1933 by J. Dawson and represents a progressive disease of the central nervous system in children and adolescents. Sick children become irritable, crying, they get frustrated with speech, vision is disturbed, they cease to recognize surrounding objects; in patients, the intellect decreases rapidly, coma and death occur.

The cause of this disease remained unclear for a long time. In the 60's. XX century. In sick children, anticorporeal antibodies were found in huge titers (up to 1:16 000), and in the brain cells - inclusions characteristic of measles containing nucleocapsids like paramyxoviruses. Finally, strains similar to the measles virus were isolated from the brain tissue and lymph nodes of the dead people.

The disease develops when the measles virus is introduced into the cells of the central nervous system. Propagation of the virus in these cells is disturbed at the stage of morphogenesis, apparently due to the absence of M-protein (in such patients antibodies to the M-antigen are not detected). As a result, a large number of defective virions, deprived of supercapsid and M-protein, accumulate in cells. Molecular mechanisms of disruption of the synthesis of viral proteins can be different. One of them is related to the existence of a gradient in the level of transcription, which manifests itself in the fact that genes distant from the 3'-end of genomic RNA are transcribed to a lesser degree than genes located closer to it. If, in acute measles infection, transcription levels of near and far from the 3'-end of the genes differ by no more than 5-fold, then at PSPE these differences reach 200-fold level. This leads to a decrease in the synthesis of proteins M, F and H below the level necessary for the assembly and budding of the virion, i.e., the formation and accumulation of defective interfering particles (DIC). Perhaps because the pathogenesis of PSPE lies in the violation of not only immune, but also some genetic mechanisms.

Diagnosis of measles

Laboratory diagnosis of measles is carried out if necessary. A test system for the identification of the measles virus genome based on a single-tube reverse transcription reaction in combination with PCR (using a modified polymerase) is proposed. To isolate the virus with the test material (mucus from the nasopharynx, blood for the day before the onset of the rash), cell cultures are infected. The virus is identified using RIF, RTGA, and RN in cell cultures. To monitor the state of immunity apply RTGA, IFM and RSK.

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Specific measles prevention

The only radical way to fight measles is vaccine prevention. For this purpose, highly effective live vaccines from attenuated measles strains (from strain L-16 and clone M-5) are used. Elimination of measles from the European Region should be achieved by 2007, and by 2010 its elimination should be certified in all countries of the world.

Read also: Vaccination against measles, mumps and rubella

For this, it is necessary to achieve the vaccination of 98-100% of newly born children aged 9-12 months. In addition, every 5-7 years must be additionally revaccinated for all children aged 9-10 months. Up to 14-16 years to reduce the number of persons susceptible to measles.