Measles virus (Morbilli virus)

Measles (Latin: morbilli) is an acute viral disease, predominantly affecting children, 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. Peebles. Morphologically, it is similar to other paramyxoviruses: the virion diameter is 150-250 nm, the viral genome is represented by a single-stranded non-fragmented negative RNA 15,900 nucleotides long, included in a helical nucleocapsid. The genome carries 6 genes arranged 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. Like other paramyxoviruses, measles virus has hemagglutinating, hemolytic, and symplast-forming activity, but it lacks neuraminidase.

Hemagglutinin, hemolysin (F), nucleoprotein (NP) and matrix protein differ in antigen specificity and degree of immunogenicity. Hemagglutinin has the highest immunogenicity. Several serovariants of the human measles virus have been detected using monoclonal antibodies. It also has common antigen determinants with canine distemper and cattle plague viruses.

Laboratory animals are not very susceptible to the measles virus. Only in monkeys does the virus cause a disease with characteristic clinical symptoms, and in natural conditions monkeys can become infected from people.

The measles virus reproduces poorly in chicken embryos. Primary trypsinized cultures of monkey kidney cells or human embryos are used to isolate it. When reproducing, the virus causes a characteristic cytopathic effect (the 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 kidneys of dogs, calves, or to human amnion cells, as well as to various transplantable lines. The virus can have a mutagenic effect on cell chromosomes.

The virus is unstable, quickly inactivated in an acidic environment, reduces its activity at a temperature of 37 °C, dies after 30 minutes at 56 °C, is easily destroyed by fat solvents, detergents, is very sensitive to sunlight and quickly dies in the external environment. Resistant to low temperatures (-70 °C). These circumstances should be taken into account 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, it causes damage to the vascular endothelial cells, resulting in a rash. The most characteristic symptom is the formation of Koplik-Filatov spots on the mucous membrane of the cheeks. The incubation period is about 10 days. The picture of the disease is so characteristic that the diagnosis is easily made clinically. In the prodromal period - symptoms of acute respiratory infections (rhinitis, pharyngitis, conjunctivitis). The appearance of Koplik-Filatov spots is of differential diagnostic significance. A papular rash usually appears on the fourth day after an increase in temperature, first on the head (forehead, behind the ears), and then spreads throughout the body. Body temperature normalizes by the 7th-8th day.

The most common complication is pneumonia, and in the early period of the disease - laryngeal edema, croup. Very rarely, measles occurs in an unusual, severe form - in the form of acute measles encephalitis, more often in children over 8-10 years of age. In children who received measles immunoglobulin for prophylactic purposes, the disease occurs in a mild form (mitigated measles). Post-infection immunity is strong, lifelong, due to virus-neutralizing antibodies, T-cytotoxic lymphocytes and immune memory cells.

Epidemiology of measles

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

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Subacute sclerosing panencephalitis

The measles virus causes not only an acute productive infection, which is measles, but also, very rarely, a severe slow infection - subacute sclerosing panencephalitis (SSPE). It was first described in 1933 by J. Dawson and is a progressive disease of the central nervous system in children and adolescents. Sick children become irritable, tearful, their speech is impaired, their vision is impaired, they stop recognizing surrounding objects; patients quickly experience a decline in intelligence, a comatose state and death.

The cause of this disease remained unclear for a long time. In the 1960s, measles antibodies were found in huge titers (up to 1:16,000) in sick children, and inclusions characteristic of measles containing nucleocapsids similar to paramyxoviruses were found in brain cells. Finally, strains similar to the measles virus were isolated from the brain tissue and lymph nodes of deceased people.

The disease develops when the measles virus is introduced into the cells of the central nervous system. Virus reproduction in these cells is disrupted at the morphogenesis stage, apparently due to the absence of the M protein (antibodies to the M antigen are not detected in such patients). As a result, a large number of defective virions lacking the supercapsid and M protein accumulate in the cells. The molecular mechanisms of disruption of viral protein synthesis may be different. One of them is associated with the existence of a transcription level gradient, which is manifested in the fact that genes remote from the 3'-end of genomic RNA are transcribed to a lesser extent than genes located closer to it. If in acute measles infection the transcription levels of genes near and far from the 3'-end differ by no more than 5 times, then in PSPE these differences reach a 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. to the formation and accumulation of defective interfering particles (DIP). Perhaps because the pathogenesis of SSPE is based on disorders of not only immune but also some genetic mechanisms.

Diagnosis of measles

Laboratory diagnostics of measles is performed if necessary. A test system for identifying the measles virus genome is proposed based on a single-tube version of the reverse transcription reaction in combination with PCR (using modified polymerase). To isolate the virus, cell cultures are infected with the test material (nasopharyngeal mucus, blood one day before the rash appears). The virus is identified using RIF, RTGA, and RN in cell cultures. RTGA, IFM, and RSC are used to monitor the state of immunity.

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Specific prevention of measles

The only radical way to combat measles is vaccination. For this purpose, highly effective live vaccines from attenuated measles strains (from the L-16 strain and the M-5 clone) 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

To achieve this, it is necessary to achieve vaccination of 98-100% of newborn children aged 9-12 months. In addition, it is necessary to additionally revaccinate all children aged 9-10 months to 14-16 years every 5-7 years to reduce the number of people susceptible to measles.