Pathogenesis and Causes of Salmonellosis

What is Salmonellosis?

Salmonellosis is an acute zoonotic intestinal infection characterized by lesions of the digestive organs with the development of intoxication syndrome and water-electrolyte disorders, less often with typhoid-like or septicopyemic course.

Brief historical information
The first representatives of the genus were found by K. Ebert (1880) in Peyer’s patches, spleen, and lymph nodes of a person who died of typhoid fever; G. Gaffky singled out a pure culture of the causative agent of the disease (1884). Later D.E. Selmon and J. T. Smith (1885) during the outbreak of swine fever and A. Gertner (1888) isolated similar bacteria from the beef and spleen of the deceased person. At the beginning of the 20th century, a separate genus was organized for pathogens in the Enterobacteriaceae family, which was named Salmonella in honor of Salmon. Salmonella are a large group of bacteria, the systematics of which underwent significant changes with the improvement of knowledge about their antigenic structure and biochemical properties. In the early 1930s, F. Kauffmann and P. White proposed to divide salmonella in accordance with their antigenic structure; it is currently used to differentiate Salmonella.

Causes of Salmonellosis

The causative agents are Gram-negative motile sticks of the Salmonella genus of the family Enterobacteriaceae, which unites more than 2,300 serovars, divided by a set of somatic O-antigens into 46 serogroups. According to the structure of the H-antigen, about 2500 serovars are isolated. Despite the abundance of detectable serum variants of Salmonella, the majority of salmonellosis diseases and carrier cases in humans are due to a relatively small number of serovars (10-12). The last classification of Salmonella (1992) identifies two types: S. enterica and S. bongori, which in turn are subdivided into 7 subspecies (subgenera), denoted by numbers or proper names – S. enterica (I), salamae (II), arizonae (III ), diarizonae (IIIb), houtenae (IV), indica (V) and bongori (VI). The main pathogens of salmonellosis are part of the I and II subgenera. The division into subspecies has a certain epidemiological significance, since the natural reservoir of Salmonella I subspecies is warm-blooded animals, and for the other subspecies it is cold-blooded animals and the environment. Bacteria grow on common nutrient media, have a complex antigenic structure: they contain a somatic thermostable O-antigen and a flagellate thermolabile H-antigen. Many representatives identify surface Vi-antigen. Some serotypes are phagotyped. Most salmonella are pathogenic both for humans and for animals and birds, but in epidemiological terms only a few of them are most significant for humans. S. typhimurium, S. enteritidis, S. panama, S. infantis, S. newport, S. agona, S. derby, S. london and some others cause 85-91% of cases of salmonellosis. At the same time, the share of the first two accounts for 75% of all isolates currently isolated from sick people.

Salmonella is long preserved in the environment: in water up to – 5 months, in meat – about 6 months (in bird carcasses more than a year), in milk – up to 20 days, kefir – up to 1 month, in butter – up to 4 months, cheeses – up to 1 year, in egg powder – from 3 to 9 months, on eggshell – from 17 to 24 days, in beer – up to 2 months, in soil – up to 18 months. It was established experimentally that during long-term (over a month) storage of eggs in the refrigerator S. enterica can penetrate into the eggs through the intact shell and multiply in the yolk. At 70 ° C they die for 5-10 minutes, in the thicker piece of meat they withstand boiling for some time, during the process of cooking eggs they remain viable in protein and yolk for 4 minutes. In some products (milk, meat products), salmonella can not only be preserved, but also reproduce, without changing the appearance and taste of products. Salting and smoking have a very weak effect on them, and freezing even increases the time it takes for microorganisms to survive in food. Known so-called resident (hospital) strains of Salmonella, characterized by multiple resistance to antibiotics and disinfectants.

Reservoir and sources of infection – many species of agricultural and wild animals and birds; their disease can occur in the form of pronounced forms, as well as asymptomatic carriage. The most important source of infection in salmonellosis is cattle, as well as pigs, the infection of which can reach 50%. Carrier animals are the most dangerous to humans. In healthy animals, Salmonella does not cause disease, while when the body is weakened, Salmonella penetrate from the intestines into tissues and organs, as a result of which they develop septic diseases. Human infection occurs when caring for animals, their forced slaughter at meat processing plants and the use of intravital or posthumously infected meat, as well as milk and dairy products. Carriage of Salmonella was noted in cats and dogs (10%), as well as among synanthropic rodents (up to 40%). Salmonellosis is widespread among wild birds (pigeons, starlings, sparrows, seagulls, etc.). At the same time, birds can contaminate with droppings and thereby contaminate objects of the external environment and food products. In the last 30 years, in most countries of the world, there has been a sharp increase in the number of positive findings of Salmonella in poultry, primarily chickens.

Humans can be the source of some Salmonella species (S. typhimurium and S. haifa), especially in hospital settings. The greatest danger to a person (sick or carrier) is for children of the first year of life, which are particularly susceptible to salmonella. The duration of the infectious period in patients determines the duration and nature of the disease; it can last for months in animals, and in humans – from several days to 3 weeks. Reconvalescent carriage in humans can sometimes last up to a year.

The mechanism of transmission of salmonellosis is fecal-oral, the main route of transmission is food, mainly through animal products. The most significant are minced meat dishes and meat salads; fish and vegetable products are less important. The waterway of transmission plays a role in the infection of animals in livestock and poultry farms. Contact and household transmission (through contaminated household items, towels, toys, pots, changing tables, playpens, hands of medical personnel and mothers) plays the greatest role in hospitals, especially in maternity, pediatric and geriatric wards. Transmission factors can also be medical instruments, equipment (catheters, endoscopes, etc.) in case of violation of their sterilization regime.

The possibility of the air-dust path of the spread of Salmonella in urban conditions with the participation of wild birds contaminating their habitats and feeding places with their droppings has been proven.

The natural susceptibility of people is high, it depends on a combination of many known and unknown factors that determine the outcome of a person’s encounter with the pathogen: the dose of the pathogen, its antigenic structure, and biological properties; individual characteristics of a person, his immune status, etc. The most sensitive to Salmonella are children in the first months of life (especially premature babies), elderly people and persons with an unfavorable premorbid background. Post-infectious immunity lasts less than a year.

Main epidemiological signs. Salmonellosis is classified as a ubiquitous (ubiquitous) infection; in recent years, there has been a trend towards a further increase in morbidity. Unlike most intestinal infections, salmonellosis is most widespread in large comfortable cities, in countries characterized by a high level of economic development, which makes it possible to classify them as “diseases of civilization”. The increase in the spread of salmonellosis on a global scale is associated with a number of reasons, the main of which are the intensification of animal husbandry on an industrial basis, the centralization of food production and the changed methods of their implementation, in particular the increase in the production of semi-finished products. An important role is played by the processes of urbanization, the intensification of migration processes, the expansion of exports and imports of food and feed, intensive environmental pollution, etc. Salmonellosis is recorded in the form of epidemic outbreaks and sporadic cases; quite often, even with a thorough epidemiological investigation, outbreaks remain undeciphered. Their identification is difficult in large cities due to highly developed infrastructure, intensive intracity migration of the population, a wide network of shops and public catering establishments. The manifestations of the epidemic process in salmonellosis are largely determined by the serovar of the causative agent that caused it. In recent years, there has been a significant increase in the incidence of diseases associated with the spread of bacteria (S. enterica) through poultry and eggs, as well as products prepared from them. When bacteria are introduced into large poultry farms, they quickly infect part of the livestock due to their ability to transovarial transmission. Among the sick people, adults predominate (60-70%), although the highest intensive incidence rate was noted among young children. The high sensitivity of young children to small doses of the pathogen predetermines the possibility of transmitting it among them not only by food, but also by the so-called household route. Outbreaks are usually explosive. The incidence of salmonellosis increases in the warm season.

Their anthroponous character has become a peculiar feature of salmonellosis. Most often, the nosocomial spread of Salmonella is associated with contact-household transmission of antibiotic-resistant strains of S. typhimurium or S. haifa. Hospital strains of bacteria are distinguished by multiple resistance to antibiotics and disinfectants. Foci (outbreaks) of nosocomial salmonellosis occur mainly in children’s hospitals (somatic and infectious diseases hospitals, departments for premature infants, newborns, etc.). Outbreaks are often highly fatal in young children and can last for a long time.

Pathogenesis during Salmonellosis

Salmonella, having overcome the factors of nonspecific protection of the oral cavity and stomach, enter the lumen of the small intestine, where they attach to the membranes of enterocytes and release thermostable and / or thermolabile exotoxins. With the help of permeability factors (hyaluronidases), pathogens through the brush border penetrate into the enterocytes. The interaction of bacteria with epithelial cells leads to degenerative changes in microvilli. Interventions of pathogens into the submucous layer of the intestinal wall are counteracted by phagocytes, which is accompanied by the development of an inflammatory reaction.

When bacteria are destroyed, a lipolysaccharide complex (endotoxin) is released, which plays a major role in the development of intoxication syndrome. The lipopolysaccharide complex activates the arachidonic cascade by lipoxygenase and cyclooxygenase pathways. The lipoxygenase pathway leads to the formation of leukotrienes, which stimulate chemotaxis and degranulation reactions, increase vascular permeability, and, indirectly, reduce cardiac output. The cyclooxygenase pathway leads to the formation of prostanoids (thromboxanes, prostaglandin E, PGF2aa, etc.). Enhanced synthesis of prostanoids induces platelet aggregation, leading to thrombus formation in small capillaries. DIC develops with microcirculation disorders. The latter cause changes in metabolism with the accumulation of acidic products in organs and tissues (metabolic acidosis). Prostaglandins stimulate the secretion of electrolytes and fluid into the intestinal lumen, contraction of smooth muscles and increased peristalsis, which ultimately leads to the development of diarrhea and dehydration. In addition, dehydration is facilitated by the action of bacterial enterotoxins, which activate the adenylate cyclase system and the production of cyclic nucleotides. The consequence of dehydration and intoxication is a violation of the activity of the cardiovascular system due to extracardiac mechanisms, which is manifested by tachycardia and a tendency to lower blood pressure. With the maximum severity of exicosis, the development of cellular hyperhydration is possible due to the difference in osmotic potentials between cells and the intercellular space. Clinically, the condition is manifested by acute swelling and cerebral edema. Microcirculation disorders and dehydration lead to degenerative processes in the kidney tubules. Acute renal failure develops, the first clinical sign of which is oliguria with further accumulation of nitrogenous toxins in the blood.

Usually (95-99% of cases) Salmonella does not spread beyond the submucous layer of the intestine, causing the development of the gastrointestinal form of the disease. Only in some cases is it possible for pathogens to enter the bloodstream, while a generalized form of salmonellosis with a typhoid or septic course is observed. The generalization of infection contributes to the lack of cellular and humoral immune responses.

Microscopic examination of the intestinal wall reveals changes in the vessels in the form of hemorrhages in the mucous and submucous layers of the intestinal wall. In the submucosal layer, in addition to microcirculatory disorders, a leukocyte reaction and edema develop.