What causes leptospirosis?

Causes of Leptospirosis

The genus Leptospira of the family Leptospiraceae is represented by two species: parasitic - L. interrogans and saprophytic - L. biflexa. Both species are divided into numerous serotypes. The latter are the main taxonomic unit that forms serological groups. The classification of leptospira is based on the constancy of their antigen structure. To date, 25 serogroups are known, uniting about 200 pathogenic serotypes of leptospira. The causative agent of leptospirosis in humans and animals belongs to the species L. interrogans. The serogroupsL. interrogans icterohaemorragiae, affecting brown rats, L. interrogans pomona, affecting pigs, L. interrogans canicola - dogs, as well as L. interrogans grippotyphosa, L. interrogans hebdomadis, play the greatest role in the structure of morbidity.

Leptospira are thin, mobile, spiral-shaped microorganisms, ranging in length from a few to 40 nm or more and in diameter from 0.3 to 0.5 nm. Both ends of leptospira are usually bent into hooks, but hookless forms are also found. Leptospira have three main structural elements: an outer membrane, an axial thread, and a cytoplasmic cylinder that is twisted helically around the longitudinal axis. They reproduce by transverse division.

Leptospira are gram-negative. They are strict aerobes; they are grown on nutrient media containing blood serum. The growth optimum is 27-30 °C, but even in such conditions they grow extremely slowly. The pathogenicity factors of leptospira are exotoxin-like substances, endotoxin, enzymes (fibrinolysin, coagulase, lipase, etc.), as well as invasive and adhesive ability. Leptospira are sensitive to high temperatures: boiling kills them instantly, heating to 56-60 °C - for 20 minutes. Leptospira are more resistant to low temperatures. Thus, at -30-70 °C and in frozen organs, they retain viability and virulence for many months. Bile, gastric juice and acidic human urine have a detrimental effect on leptospira, and in the slightly alkaline urine of herbivores they remain viable for several days. In open water bodies with slightly alkaline or neutral reaction, leptospira survive for 1 month, and in damp and waterlogged soil they do not lose pathogenicity for up to 9 months. On food products, leptospira survive for 1-2 days, and under the influence of ultraviolet light and when dried, they die within 2 hours. Leptospira are sensitive to penicillin preparations, chloramphenicol, tetracycline and are extremely sensitive to the action of conventional disinfectants, boiling, salting and marinating. At the same time, low temperatures do not have a detrimental effect on leptospira. This explains their ability to overwinter in open water bodies and damp soil, completely preserving virulence.

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Pathogenesis of leptospirosis

The pathogen penetrates the human body due to its mobility. The entry points are microdamages of the skin and mucous membranes of the oral cavity, esophagus, conjunctiva of the eyes, etc. There are known cases of laboratory infection through damaged skin. With intradermal penetration in an experiment on laboratory animals, leptospires penetrate the blood in 5-60 minutes, apparently bypassing the lymph nodes, which do not perform a barrier function in leptospirosis. At the site of introduction of the pathogen, there is no primary affect. Further spread of leptospires occurs hematogenously, while the lymphatic vessels and regional lymph nodes also remain intact. With the blood flow, leptospires enter various organs and tissues: liver, spleen, kidneys, lungs, central nervous system, where they multiply and accumulate. The first phase of infection develops, lasting from 3 to 8 days, which corresponds to the incubation period.

The second phase of leptospirosis pathogenesis is secondary bacteremia, when the number of leptospires in the blood reaches its maximum and they continue to multiply in the liver and spleen, adrenal glands, causing the clinical onset of the disease. With the blood flow, leptospires are again carried throughout the body, overcoming even the BBB. During this period, along with the reproduction of leptospires, their destruction begins as a consequence of the appearance of antibodies that agglutinate by the fourth day of the disease and lyse leptospires. The accumulation of metabolic products and decay of leptospires in the body is accompanied by fever and intoxication, which increases the sensitization of the body and causes hyperergic reactions. This phase lasts for 1 week, but can be shortened to several days. The maximum concentration of leptospires by the end of the leptospiremia phase is observed in the liver. Leptospira produce hemolysin, which, by affecting the membrane of erythrocytes, causes their hemolysis and the release of free bilirubin. In addition, destructive changes develop in the liver with the formation of inflammation and tissue edema. In severe cases of the disease, the main factor of the pathological process in the liver is damage to the membranes of blood capillaries, which explains the presence of hemorrhages and serous edema. The pathogenesis of jaundice in leptospirosis is dual: on the one hand, the breakdown of erythrocytes due to the toxic effect of hemolysin and hemolytic antigen on membranes, as well as as a result of erythrophagia by cells of the reticuloendothelial system in the spleen, liver and other organs, on the other hand, due to developing parenchymatous inflammation with a violation of the bile-forming and excretory functions of the liver.

The third phase of leptospirosis pathogenesis is toxic. Leptospires die due to the bactericidal action of blood and accumulation of antibodies, disappear from the blood and accumulate in the convoluted tubules of the kidneys. The toxin accumulated due to the death of leptospires has a toxic effect on various organs and systems. In some patients, leptospires multiply in the convoluted tubules and are excreted from the body with urine. In this case, kidney damage comes to the fore. The most typical kidney damage in leptospirosis is a degenerative process in the epithelium of the tubular apparatus, so it is more correct to consider them as diffuse distal tubular nephrosis. Patients develop signs of acute renal failure with oligoanuria and uremic coma. Severe kidney damage is one of the most common causes of death in leptospirosis.

In the toxemia phase, damage to organs and tissues is caused not only by the toxin and waste products of leptospira, but also by autoantibodies formed as a result of the breakdown of affected tissues and cells of the macroorganism. This period coincides with the second week of the disease, but can be somewhat delayed. The toxin has a damaging effect on the capillary endothelium, which increases their permeability with the formation of thrombi and the development of LVS syndrome.

The central nervous system is affected as a result of leptospira overcoming the blood-brain barrier. Some patients develop serous or purulent meningitis, and less commonly meningoencephalitis.

In some cases, specific leptospirosis myocarditis occurs.

The pathognomonic symptom of leptospirosis is the development of myositis with damage to the skeletal, especially gastrocnemius muscles. The lungs (leptospirosis pneumonia), eyes (iritis, iridocyclitis), and less often other organs are often affected.

Epidemiology of leptospirosis

Leptospirosis is one of the most common natural focal infectious diseases. The source of the infectious agent is wild, farm and domestic animals. The role of individual animal species as a source of leptospirosis infection is far from the same due to their varying degrees of sensitivity to these microorganisms and the nature of the response to infection. Animals that develop a chronic, and in some cases asymptomatic process as a result of infection, accompanied by prolonged excretion of leptospira in the urine, are of the greatest epidemiological and epizootological significance. These animals ensure the preservation of leptospira as a biological species. The greatest significance in natural foci of leptospirosis is given to representatives of the order of rodents, as well as insectivores (hedgehogs, shrews). The carriage of leptospira has been proven in almost 60 species of rodents, of which 53 belong to the family of mouse-like and hamster-like.

The biological plasticity of leptospira makes it possible for them to adapt to agricultural and domestic animals (cattle, pigs, horses, dogs), as well as to synanthropic rodents (gray rats, mice), which form anthropurgic foci of infection that pose a major danger to humans.

From an epidemiological point of view, the incidence of cattle, small cattle, and pigs is important. Animals of any age can get sick, but in adults, leptospirosis often occurs in a latent form, and in young animals - with more pronounced symptoms.

Humans are not important as a source of infection.

The main factor of transmission of the leptospirosis pathogen is water contaminated with excrements (urine) of infected animals. The immediate causes of infection of people are the use of raw water for drinking, washing from open water bodies, swimming in small slow-flowing ponds or wading through them.

Food products contaminated with rodent excrements also play a certain role in the transmission of infection. Transmission of infection most often occurs by contact, but the food route is also possible. Moist soil and pasture grass contaminated with excrements of sick animals can also be transmission factors. Infection can occur during slaughter of cattle, cutting up carcasses, and also when consuming milk and thermally untreated meat. Often, people who have professional contact with sick animals become ill with leptospirosis: veterinarians, exterminators, and agricultural workers.

For leptospirosis to penetrate, the slightest breach in the integrity of the skin is enough.

Epidemic outbreaks of leptospirosis are usually confined to the summer-autumn period. The peak of the disease is in August. There are three main types of outbreaks: waterborne, agricultural and livestock. Leptospirosis is also encountered in the form of sporadic cases, which can be registered throughout the year.

Leptospira are hydrophilic, so leptospirosis is characterized by a high prevalence in areas with many marshy and highly humid lowlands.

The natural susceptibility of people to leptospirosis infection is significant. Post-infection immunity is strong, but type-specific, so repeated diseases caused by other serovars of the pathogen are possible.

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