Rotavirus infection - Causes and pathogenesis

Causes of rotavirus infection

Rotavirus infection is caused by a member of the Reoviridae family, genus Rotavirus. The name is based on the morphological similarity of rotaviruses to a wheel (from the Latin "rota" - "wheel"). Under an electron microscope, viral particles look like wheels with a wide hub, short spokes and a clearly defined thin rim. The rotavirus virion, 65-75 nm in diameter, consists of an electron-dense center (core) and two peptide shells: an outer and inner capsid. The core, 38-40 nm in diameter, contains internal proteins and genetic material represented by double-stranded RNA. The genome of human and animal rotaviruses consists of 11 fragments, which probably determines the antigenic diversity of rotaviruses. Replication of rotaviruses in the human body occurs exclusively in the epithelial cells of the small intestine.

Rotaviruses contain four main antigens; the main one is the group antigen, a protein of the internal capsid. Taking into account all group-specific antigens, rotaviruses are divided into seven groups: A, B, C, D, E, F, G. Most human and animal rotaviruses belong to group A, within which subgroups (I and II) and serotypes are distinguished. Subgroup II includes up to 70-80% of strains isolated from patients. There is evidence of a possible correlation between certain serotypes and the severity of diarrhea.

Rotaviruses are resistant to environmental factors: they survive for several months in drinking water, open water bodies and wastewater, for 25-30 days on vegetables, and for 15-45 days on cotton and wool. Rotaviruses are not destroyed by repeated freezing, disinfectant solutions, ether, chloroform, ultrasound, but they die when boiled. They are also treated with solutions with a pH greater than 10 or less than 2. Optimal conditions for the existence of viruses are a temperature of 4 °C and high (>90%) or low (<13%) humidity. Infectious activity increases with the addition of proteolytic enzymes (e.g. trypsin, pancreatin).

[ 1 ], [ 2 ], [ 3 ], [ 4 ], [ 5 ], [ 6 ], [ 7 ], [ 8 ], [ 9 ]

Pathogenesis of rotavirus infection

The pathogenesis of rotavirus infection is complex. On the one hand, structural (VP3, VP4, VP6, VP7) and non-structural (NSP1, NSP2, NSP3, NSP4, NSP5) proteins of the virus are of great importance in the development of rotavirus gastroenteritis. In particular, NSP4 peptide is an enterotoxin that causes secretory diarrhea, similar to bacterial toxins; NSP3 affects viral replication, and NSP1 can "prohibit" the production of interferon-regulating factor 3.

On the other hand, already on the first day of the disease, rotavirus is detected in the epithelium of the mucous membrane of the duodenum and upper parts of the jejunum, where it multiplies and accumulates. Penetration of rotavirus into a cell is a multi-stage process. To penetrate into a cell, some serotypes of rotavirus require specific receptors containing sialic acid. An important role of proteins has been established: a2b1-integrin, integrin-aVb3 and hsc70 at the initial stages of interaction between the virus and the cell, while the entire process is controlled by the viral protein VP4. Having penetrated the cell, rotaviruses cause the death of mature epithelial cells of the small intestine and their rejection from the villi. The cells replacing the villous epithelium are functionally inferior and are not able to adequately absorb carbohydrates and simple sugars. The occurrence of disaccharidase (mainly lactase) deficiency leads to the accumulation of undigested disaccharides with high osmotic activity in the intestine, which causes a violation of the reabsorption of water, electrolytes and the development of watery diarrhea, often leading to dehydration. Entering the large intestine, these substances become substrates for fermentation by intestinal microflora with the formation of a large amount of organic acids, carbon dioxide, methane and water. Intracellular metabolism of cyclic adenosine monophosphate and guanosine monophosphate in epithelial cells with this infection remains virtually unchanged.

Thus, at present, two main components are distinguished in the development of diarrheal syndrome: osmotic and secretory.

Epidemiology of rotavirus infection

The main source and reservoir of rotavirus infection is a sick person who excretes a significant amount of viral particles (up to 10 ¹⁰ CFU in 1 g) with feces at the end of the incubation period and in the first days of the disease. After the 4th-5th day of illness, the amount of virus in feces decreases significantly, but the total duration of rotavirus excretion is 2-3 weeks. Patients with impaired immunological reactivity, with chronic concomitant pathology, lactase deficiency excrete viral particles for a long time. The source of the infectious agent can also be healthy virus carriers (children from organized groups and hospitals, adults: first of all, medical personnel of maternity hospitals, somatic and infectious departments), from whose feces rotavirus can be isolated for several months.

The mechanism of transmission of the pathogen is feco-oral. Routes of transmission:

• contact-household (through dirty hands and household items);
• water (when drinking water infected with viruses, including bottled water);
• alimentary (most often when consuming milk and dairy products).

The possibility of airborne transmission of rotavirus infection cannot be ruled out.

Rotavirus infection is highly contagious, as evidenced by the rapid spread of the disease in the environment of patients. During outbreaks, up to 70% of the non-immune population becomes ill. During seroepidemiological testing of blood, 90% of children in older age groups have antibodies to various rotaviruses.

After an infection, in most cases, a short-term type-specific immunity is formed. Repeated diseases are possible, especially in older age groups.

Rotavirus infection is common and is detected in all age groups. In the structure of acute intestinal infections, the share of rotavirus gastroenteritis ranges from 9 to 73% depending on age, region, standard of living and season. Children of the first years of life (mainly from 6 months to 2 years) are especially often ill. Rotaviruses are one of the causes of diarrhea accompanied by severe dehydration in children under 3 years of age; this infection is responsible for up to 30-50% of all cases of diarrhea requiring hospitalization or intensive rehydration. According to WHO, this disease kills 1 to 3 million children worldwide every year. Rotavirus infection accounts for about 25% of cases of so-called traveler's diarrhea. In Russia, the frequency of rotavirus gastroenteritis in the structure of other acute intestinal infections ranges from 7 to 35%. and among children under 3 years of age, it exceeds 60%.

Rotaviruses are one of the most common causes of hospital-acquired infections, especially among premature infants and young children. Rotaviruses account for 9 to 49% of hospital-acquired acute intestinal infections. Hospital-acquired infections are facilitated by a long stay of children in hospital. Medical personnel play a significant role in the transmission of rotaviruses: 20% of employees, even in the absence of intestinal disorders, have IgM antibodies to rotavirus in their blood serum, and rotavirus antigen is detected in coprofiltrates.

In temperate climates, rotavirus infection is seasonal, predominating in the cold winter months, which is associated with better survival of the virus in the environment at low temperatures. In tropical countries, the disease occurs year-round, with some increase in incidence during the cool rainy season.

[ 10 ], [ 11 ], [ 12 ], [ 13 ], [ 14 ], [ 15 ], [ 16 ], [ 17 ], [ 18 ], [ 19 ], [ 20 ]