Salmonellosis is disease of animals and humans, it is characterized by essential damage of gastrointestinal tract, and more rarely by typhus-like or septicopyemic duration.
Salmonella are non-spore-forming gram negative rods of the family Enterobacteriaceae. Salmonella are motile by peritrichous flagella. Salmonella strains demonstrate sufficient differences in biochemical reactions, antigenic structure, host adaptations, and geographical distribution to be grouped into 10 distinct subgroups, which have been variously designated in proposed taxonomic schemes. Virtually all strains isolated in clinical laboratories and implicated in disease in humans (more than 700 serotypes).
Like other enterobacteria, salmonella has somatic O-antigens, which are lipopolysaccharide components of the cell wall,and flagella H-antigens,which are proteins. There may be detached some serological groups on the basic of the differences in structure of O-antigens. Salmonella preserve viability in external environment for a long time: in water - 11-120 days, in the sea water - 15-27 days, in soil - 1-9 months, in sausage products - 60-130 days, in the eggs, vegetables and fruits till 2,5 months. The optimal temperature for reproduction is 35-37 °Ñ. There are-serological groups A, B, C, D, E and other.
Salmonella can be differentiated from other Enterobacteriaceae on the basis of certain biochemical reactions, including fermentation reactions with specific sugars.
Salmonella organisms grow readily on simple media in aerobic or anaerobic conditions. Cultures of specimens that are normally sterile, such as blood, joint
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fluid, or cerebrospinal fluid, can be done on ordinary media such as blood agar. Excretions or secretions, such as feces or sputum, which have high concentrations of other microorganisms, are usually grown on selective or differential media, such as bismuth sulfate agar or desoxychlorate agar, which contains inhibitors of growth of non-pathogenic organisms of the normal flora.
Animals suffering from primary or secondary salmonellosis, water swimming birds and also human-sick or carries are the main sources of infection in salmonellosis. Mechanism of transmission of infection is fecal-oral. The factors of the transmission of the infection are food-stuffs of animal origin and other products which are polluted by excretions of animals and humans. The promotive factors are violation of the preservation and preparing of the food and also sanitary.
The diseases occur as separate sporadic cases and as outbreaks. Susceptibility of human depends from the premorbidal state of the macroorganism and from the quantity and variety (serotypes) of Salmonella.
Salmonella are primarily pathogens of lower animals. The reservoir of infection in animals constitutes the principal source of nontyphoidal Salmonella organisms that infect man, although infection may be transmitted from person to person, Salmonella have been isolated from almost all animals species, including poultry (chickens, turkeys and ducks), cows, pigs, pets (turtles, cats, dogs, mice, guinea pigs and hamsters), other birds (doves, pigeons, parrots, starlings, sparrows), sheep, seals, donkeys, lizards and snakes.
The most accurate information on sources of human salmonellosis is derived from studies of outbreaks. Poultry (chickens, turkeys, ducks) and poultry products (primarily eggs) are the most important sources of human infection and are estimated to be responsible for about one-half of the common - vehicle epidemic. Salmonella in feces of infected hens may contaminate the surface of egg shells or penetrate into the interior of the egg through hairline cracks. In hens with ovarian infection, organism may gain access to the yolk. Meat,especially beef and pork,are quite often implicated, accounting for about 13 % of the outbreaks, and dairy products, including raw and powdered milk account for about 4 % of the epidemics.
Cross-infection with spread by person to person is responsible for virtually all the outbreaks in neonatal nerseries and in pediatric wards and is important in many outbreaks among hospitalized adults.
The stage is set for cross-infection when Salmonella are introduced into the hospital by admission, or for example, a patient with acute enterocolitis or as asymptomatic carrier with other medical problem or by the introduction of a contaminated common- course vehicle. Hospital personnel then may carry infection on hands or clothing from patient to patient; in some cases fomites (dust, delivery room, furniture), may be implicated in transmission. Hospital personnel who are excreting Salmonella in stools may also occasionally transmit infection to patient.
The development of disease after ingestion of Salmonella is influenced by the number and virulence of the organisms and by multiple host factors.
A large number of Salmonella must be swallowed in most instances to produce disease in healthy human being. However, in the event of infection with unusually virulent organisms or in patients with reduced resistance, symptomatic infection may result from extremely small inocula. Ingested organisms pass from the mouth to the stomach. In the stomach Salmonella are exposed to gastric acid and low pH, which reduce the number of viable organisms. Most Salmonella are perished rapidly at 2.0 pH, which is readily achieved in the normal stomach. Viable bacilli that survive then pass into the small intestine, where the organisms may be further reduced in number or eliminated entirely. The antimicrobial activity observed in the small bowel is related at least in part to the normal microbial flora of the intestine, which elaborate short-chain fatty acids and perhaps other substances capable of killing or inhibiting growth of Salmonella. Studies in animals have shown that the increased susceptibility to Salmonella infection produced by administration of antibiotics rapidly reverts to normal with reestablishment of the normal intestinal flora.
Salmonella that survive the antibacterial mechanisms in the stomach and upper small bowel may multiply in the small intestine. Multiplication of Salmonella in the intestinal tract may be asymptomatic, associated only with transient excretion of organism in stools, or symptomatic, associated with clinical manifestations of either enterocolitis (acute gastroenteritis) enteric fever or bacteremia.
Blood stream invasion, which occurs with variable frequency, may lead to localization of infection and suppuration at almost any site.
Local factors in the stomach and upper intestinal tract are important determinants of the disease. Factors that neutralize the low pH of the stomach or decrease the time the pathogen is exposed to stomach acid diminish local bactericidal action and increase the probability that an infections inoculums will reach the small intestine. The importance of gastric acidity as a defense mechanism is emphasized by the increased incidence of severe Salmonella enterocolitis in persons with achlorhydria, prior gastroectomy, gastroenterostomy, or vagotomy, conditions that reduce acidity or cause faster gastric emptying time.
The oral administration of buffering compounds also increases susceptibility to intestinal infection. It has been suggested that ingestion of organisms in food allows for longer exposure to, gastric acid, thereby necessitating the presence of a relatively larger inoculums to produce disease,whereas water or other liquids,which have a fast gastric transit time, may be less heavily contaminated and still cause disease.
The small intestine provides other protective mechanisms through motility and normal flora. Alteration of the intestinal flora by antibiotics markedly reduces the size of the inoculums required to produce Salmonella infection in animals and humans and prolongs the convalescent carrier state. Prior antimicrobial
therapy also enhances the possibility of infection with antibiotic - resistant Salmonella strains.
Age is an important determinant of disease produced by Salmonella. Salmonella enterocolitis occurs with highest incidence in children less than 5 years old; newborns and infants less one year of age are especially susceptible. The influence of age on incidence may reflect immaturity of humoral and cellular immune mechanisms, diminished antibacterial action of the normal intestinal flora,a high frequently of fecal - oral contamination,or other factors. In some instances, increasing resistance with age is related to immunity consequent to previous exposure to the organism, even though disease has not been produced.
Patient with impaired cellular and humoral immune mechanisms are at increased risk for development of salmonellosis. Impairments of host defenses caused by malnutrition, malignancy, infection with human immunodeficiency virus or therapeutic measures such as corticosteroid or immunosuppressive therapy also predispose to infection and disease.
Salmonella causing enterocolitis are thought to produce diarrhea by a true infection with mucosal invasion and possibly by elaboration of an enterotoxin that acts on upper intestinal transport. Salmonella invasion of intestinal mucosa may lead to local production of inflammatory exudates of mediators that stimulate electrolyte secretion and smooth muscle contraction.
There are two types of toxins: exotoxins and endotoxins. Exotoxins are the toxic products of bacteria which are actively secreted into environment. Endotoxins are toxic substances which are liberated only during the lysis of microbial cells. The principal factor responsible for development of this disease is endotoxical complex of Salmonella, but we should remember that these bacteria produce even exotoxins. Exotoxins and endotoxins have toxical properties.
In salmonellosis the development of infectious process has next stages:
1. Colonization (setting) of pathogenic organism in the place of the inculcation.
2. Invasion and reproduction.
3. Death of the pathogenic bacteria and endotoxins liberation. Infectious process may stop at the stage of colonization due to unknown
reasons. Invasion may be limited by nearest tissues. In majority cases it leads to development of gastrointestinal forms of salmonellosis. For development of the first stage of pathogenesis of salmonellosis the factors violating structural and functional state of gastrointestinal tract play important role (dysbacteriosis, hypovitaminosis and other). These conditions may promote to development of the disease even due to small quantity of bacteria in food-stuffs.
In salmonellosis the principal pathologoanatomical changes develop in the place of inculcation of the agent in the small intestine. Data about changes of small intestine in gastrointestinal forms of salmonellosis may be received only as a result of its biopsy. But biopsy is not used in practice. Investigation of material during biopsy testifies dystrophical changes of epithelium, infiltration of epithelium of mucous membrane by macrophages. Increased quantity of interepithelial leukocytes, polymorphonuclear leukocytes and macrophages is marked.
Principal changes develop in lamina propria of mucous membrane of small intestine in salmonellosis. These changes are accompanied by hyperemia, hemorrhages, edema and intensification of cell infiltration. At the same time the changes of the different parts of gastrointestinal tract develop. There is an acute inflammatory process, dystrophic changes of epithelium, edema, hyperemia and cell infiltration in stomach. There are dystrophy, erosions, hyperemia, edema in mucous of large intestine. Changes in all parts of gastrointestinal tract are transient. They are exposed to reverse development in clinical recovery of the patients.
In half of the patients with salmonellosis nonsharp violations of liver are marked. These changes are considered as compensatory mechanism.
In connection with sufficient efficiency of modern methods of treatment the fatal outcomes are rare. Dystrophic changes of parenchymatous organs were revealed in autopsy of deceaseds from gastrointestinal forms of salmonellosis. These changes were direct cause of death. Inrarely, edema of the lungs and brain, hyperplasia of spleen and mesenteric lymph nodes may develop.
In connection with considerable variability of clinical duration of salmonellosis there are multitude classifications of this disease. The next classification is more comfortable for practice use:
1) Localized (gastrointestinal) forms of salmonellosis:
a) Gastritic variant;
b) Gastroenteritic variant;
c) Gastroenterocolitic variant.
2) Generalized forms:
a) Typhus-like form;
b) Septic form (septicopyemia).
3) Carrier state:
a) Acute carriers;
b) Chronic carriers;
c) Transitory carriers. Clinical symptoms of salmonellosis are studied sufficiently completely.
Gastrointestinal forms of salmonellosis are observed in most of cases of the disease. According data of different authors they occur from 79 to 85 %.
Incubation period is from 4-6 hours up to some days. Onset of the disease is an acute. Prodromal period is not typical or very short. Weakness, malaise, and slight chill characterize it. Then temperature increases to subfebrile in moderate and severe forms accordingly.
After ingestion of contaminated food or water, illness begins in many patients with nausea and vomiting; these symptoms usually resolve within a few hours. Myalgia and headache are common. The cardinal manifestation is diarrhea, which may vary from a few loose stools to fulminate diarrhea. In most cases, stools are loose, of moderate volume, and without blood, swamp-like (Fig. 3). In exceptional
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cases, the stools may be watery and of great volume ("cholera-like"), or, in other instances, of small volume and associated with tenesmus and gross blood ("shigellosis-like"). Temperature elevations to 38-39 °Ñ are common, as are chills; both appear in the majority of patients in whom definitive diagnosis is established. Abdominal cramps occur in about two-thirds of the patient and are often localized to the periumbilical region or lower abdominal quadrants. Bowel sounds are increased and abdominal tenderness is present. At microscopic examination, stool show a moderate number of polymorphonuclear leukocytes and, occasionally, red blood cells. Cross blood is unusual but may be seen in severe cases. Peripheral leukocyte count is usually normal,although neuthrophilia with a shift to younger forms may be present.
The duration of fever is less than 2 days in the majority of cases. Diarrhea usually persists less than 7 days, although, rarely, gastrointestinal symptoms may last for several weeks. Prolonged fever and diarrhea suggest a complication or a different diagnosis.
Localization of pain in the right lower quadrant of the abdomen in patients with enterocolitis may lead to a diagnosis of acute appendicitis. At surgery, such patients may have normal appendices or occasionally acute appendicitis rarely with perforation.
Clinic of salmonellosis is characterized by symptoms of damage of cardiovascular system. The basis of these violations is water-electrolytes loss and change of reological properties of the blood.
Changes in organs of respiratory systems are not typical for uncomplicated cases of gastrointestinal forms. But sometimes breathlessness may be observed.
Toxicosis takes place when localized forms of salmonellosis. It is manifested by headache, pain in the muscles, mild ataxia, asymetric reflexes. Development of toxic encephalitis is possible.
Electrolyte and water depletion may be severe during illness, leading to hypovolemic shock. The disease is more severe in children, in seniors, and in patient with achlorhydria, gastroectomy, gastroenterostomy, sickle cell anemia, or other conditions that impair resistance to infection. The frequency of transient bacteremia is less than 5 % in adults. It is increased in children and in persons with severe preceded diseases. Bacteremia has been shown to occur in 8-16 % of infants and children of 3 years age or younger who are hospitalized with Salmonella enterocolitis. Salmonella intestinal infections has tendency to be prolonged in children, who continue to excrete agent in stool for a longer time than adults after subsidence of clinical manifestation of infection.
. Salmonella enterocolitis may develop in hospitalized patients. The illness may be a nosocomial infection or it may result of activation of pre-existing asymptomic intestinal infection by antimicrobial therapy, of surgical diseases of abdomen or from other causes.
In one-two third of children over 5 years and adults positive cultures are observed during second or third week from the onset of the disease. In this time majority of the patients have no symptoms of the disease.
Salmonella can produce an illness characterized by fever and sustained bacteremia without manifestations of enterocolitis. This syndrome may be caused by any Salmonella serotypes. The clinical syndrome of salmonella bacteremia is characterized by a hectic febrile course lasting for days or weeks. The organism is isolated from blood, but stool cultures are often negative. More than 70 % of cases of generalized forms of salmonellosis begin as gastrointestinal form with dyspeptic manifestations. Then, in typhus like variant after subsidence of dyspeptic manifestations the disease acquires signs of typhus infection. The second febrile wave-like or incorrect type continues in most cases during 10-14 days. The principal symptoms of the period of climax of the disease are weakness, adynamia, severe headache, sleeplessness, pains of muscles and joints.
Typical typhus state is not characteristic for this variant of salmonellosis. In majority of the patients enlarged liver and spleen, distantion of abdomen are observed. Approximately, in 25 % of the patients scanty rose sports are observed. Rash appears on 4-10 day,sometimes later. In peripheral blood leukocytosis is observed only in early period of the disease. Then leukopenia is marked, but with neutrophilosis. Sometimes typhus like variant may be without appearances of gastroenteritis. The principal symptoms of beginning period in that cases are fever,chill,headache,weakness. In the period of climax adynamia, pale skin, injections of scleras are observed.
There are single rose spots on the skin of abdomen and chest. In this variant of generalized form of salmonellosis relapses may observed, and rarely, complications, which are typical for typhus fever. Typhus like variant may be with temperate manifestations of intoxication and dyspeptic appearances, with short duration fever. There is marked catarrh, hyperemia of pharynx, laryngotra-cheobronchitis in these patients rarely.
Septic variant (septicopyemia) is sepsis of Salmonella etiology. The development of sepsis is evoked by sharp decrease of the immuneprotective strengths of the organism of the patient. This variant of generalized of Salmonellosis is characterized by acyclic development of the disease, prolonged fever, chills, sweating, hepatosplenomegaly, sometimes development of jaundice, plural purulent metastases in different organs and tissues.
Usually, the disease begins from manifestations of gastroenteritis. Then typical septicopyemia develops with hectic fever. The signs of influence of intoxication on central nervous system are marked from the first days of the disease. They are manifested by irritation, violations of sleep, motive trouble, sometimes delirium. The skin is pale. Rash may appear on the skin (petechias or large hemorrhages).
The secondary purulent focuses may be in any organs and tissues. Localization of infection may be in thyroid, brain membranes, bones, heart, lungs, kidneys, adrenals, pancreas, spleen, liver, pericardium and soft tissues.
Meningitis is a rare complication of Salmonella infection and occur almost exclusively in infants, particularly neonates. Even epidemics of meningitis have
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been reported during outbreaks of Salmonella infection in hospital nurseries. Clinical manifestations are the same as those of any bacterial meningitis in this age group. The clinical course is usually long and marked by relapse. Acute neurologic complications are common and include subdural empyema, cerebral abscesses, and ventriculitis. Acute or chronic hydrocephalus may occur. Mortality is high, despite appropriate antimicrobial therapy.
Pleuropulmonary disease. Pneumonia or empyema, the predominant types of serious respiratory diseases, occur usually in elderly patients or in patients with underlying diseases such as diabetes mellitus, malignancy, cardiovascular disease, or pulmonary disease. Mortality is high.
Arterial infection. Salmonella infection may be with localization in major vessels,including the thoracic and abdominal aortas,coronary arteries,peripheral arteries. Atherosclerotic intrarenal aortic aneurysms are by far the most common vascular sites of localization. The risk of endothelial infection is high in persons over the age of 50 years who have Salmonella bacteremia.
The mechanism of arterial infection is through to be direct implantation at a site of endothelial injury in the bacteremia patient on to extension from an adjacent inflammatory lesion, such as vertebral osteomyelitis. Mortality is high.
Osteomyelitis and arthritis. Osteomyelitis can develop in normal bone but especially likely to occur in patient with sickle - cell hemoglobinopathies, systemic lupus erythematosus, immunosuppressive therapy, bone surgery or trauma. Salmonella, not Staphylococcus, is the most common cause of osteomyelitis in patients with sickle-cell anemia.
Salmonella may cause a metastatic supportive arthritis. Pyogenic arthritis is much less frequent than reactive arthritis.
Splenic abscess and hepatic abscess. Splenic abscess is a rare complication of Salmonella infection. Localization occurs after bacteremia in posttraumatic subcapsular hematomas or splenic cysts. The clinical manifestation is one of left upper quadrant tenderness,fever and leukocytosis.
Salmonella liver abscesses may occur. Usually, the patients have pre- existing
liver disease including amebic abscesses, ecchinococcal cysts, and hematomas.
Association with biliary tract disease exists in occasional cases.
Urogenital tract. Salmonella in stools of carriers or persons with acute illness may gain access to the urinary tract to produce cystitis or pyelonephritis. Localization of Salmonella blood form with abscess formation in kidneys, testicles, or ovaries is also occasionally reported.
Bacteriocarrier of Salmonella is developed after disease. There are acute, chronic and transitory carriers. Acute and chronic carriers are divided depending on duration of excretion of Salmonella. Acute carrier has the duration of excretion of Salmonella from 15 days till 3 months after clinical recovery. The persons, excreting Salmonella over a year, are chronic carriers. The conditions of development of transitory carrier are insignificant dose of the agent and its avirulence.
Complications and outcomes of salmonellosis,as and multiple clinical forms are exposed to wide oscillations. Even gastrointestinal forms of salmonellosis with favorable duration are not finished clinical recovery.
Generalized form of salmonellosis, as rule, is accompanied by complications. Exceeding expression of symptoms of salmonellosis frequently leads to collapse (1.5-6 % of the cases). Collapse may develop at the first day of the disease on the altitude of clinical manifestations before dehydration. Endotoxinemia plays leading role in development of collapse. It is a manifestation of infectious-toxic shock.
Besides expressive hypodynamic disorders acute renal insufficiency, edema of brain, edema of lungs and hemorrhagic syndromes develop. The development of dysbacteriosis is connected with large doses of antibiotics use at any clinical forms of salmonellosis. Dysbacteriosis may be compensated or latent.
Outcomes of salmonellosis depend on premorbidal state, age, clinical forms, timely diagnostics and treatment.
Diagnostics of salmonellosis is performed on the basis of epidemiological, clinical and laboratory data. Bacteriological and serological methods are used for confirmation of salmonellosis. The main materials for bacteriological investigation are vomiting masses, water after irrigation of stomach, stool, blood, urine.
Serological investigations are used. These are reaction of agglutination (RA) (7-8th day of the disease) and indirect hemagglutination (RIHA). RIHA is more sensitive. It gives positive results on the 5th day of the disease. Diagnostical titer is 1:200. Serological investigation should be done in dynamics of the disease.
Differential diagnosis of salmonellosis is performed with other intestinal diseases - shigellosis, toxic food-borne infections, esherichiasis, cholera; with surgical diseases - appendicitis, pancreatitis, cholecyctitis, thrombosis of mesenterial vessels; gynecological pathology and with therapeutic pathology (myocardial infarction, chronic gastritis aggravation, enterocolitis, ulcerous disease), with acute gastroenteritis of viral origin (enteroviral, rotaviral etiology), poisoning by organic and inorganic poisons, poisoning by mushrooms.
Generalized form of salmonellosis is necessary to differentiate from sepsis of different etiology, pneumonia, malaria, acute pyelonephritis, tuberculosis.
The volume of medical actions depends on the clinical form and a stage of gravity of disease. At gastrointestinal form immediately wash out stomach and intestine with boiled water (isotonic solution of sodii chloridum is the best) then give sorbents per os and give a warm drink. For restoration of hydro-electrolityc balance and normalization of circulatory disorders there should be indicated per os glucosole or rehydroni. Infusion therapy is indicated at expressed dehydration
threesault,quartasault,lactasault. At severe stage of dehydratation one of the specified solutions is infused in vein with rate 80-120 mL/min, 5-10 L of solution is necessary on course of treatment. If hypotension and toxicosis are marked prednisolon and hidrocortizon, polyglucin, reopoliglycin are infused in vein. Pathogenetically 5 % solution of glucose is indicated with desintoxication purpose and restoration of power balance, a solution of sodium hydrocarbonat for acidosis correction, heparin for improvement of reologic properties of blood, preparations of antiallergic action - calcii chloridi, dimedrol, tavegil, indomethacin are prescribed in case of diarrhea (for inhibition of prostaglandines synthesis), calcium gluconate. Antibiotics at gastrointestinal form of salmonellosis are not used.
However at syndrome of hemocolitis and lingering diarrhea furazolidon is indicated in combination with fermental preparations - festal, panzynorm, pancreatin, mezym-forte, pancitrat, vobensim. The broths of herbs has anti-inflammatory, disinfectant and astringent properties, and also properties raising organism reactivity. They are vitamin preparations, pentoxyl, methyluracil, thymalin, enterol-250 also indicated, bificol, colibacterin, bifidumbacterin, linex is used at intestinal dysbacteriosis.
At generalized form simultaneously with pathogenetic therapy there are indicated antibiotics - levomycetin, ampicillin, monomycin, gentamycini sulfas, cefazolin (kefzol), cefotaxim (claforan). At the septic form of disease antibiotics are better to infuse parenteraly. For sanitation of chronic carriers of salmonelas the specified antibiotics use in average therapeutic doses in combination with preparations stimulating nonspecific and immunological reactivity (pentoxyl, methyluracil, splenin, thymalin, T- activin).
The measures of prophylaxis are veterinary-surveillance upon animals and production of meat and dairy industry, laboratory control of food stuffs.
It is necessary to reveal carriers on milk farms, in foods, children's and medical establishments. The maintenance of the rules of personal hygiene and rules of food's cooking plays an important role in prophylaxis of salmonellosis.
1. Etiology, epidemiology and incidence of salmonellosis.
2. Pathogenesis of salmonellosis.
3. Anatomic pathology of disease.
4. Main clinical symptoms and signs of salmonellosis.