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Introduction into the course of infectious diseases. General description of group of intestinal infections. Typhoid fever. Paratyphoids A and B. Salmonellosis. Food poisoning.

http://intranet.tdmu.edu.ua/data/books/And-INF.pdf

Typhoid fever, paratyphoid A and B are an acute illnesses from the group of intestinal infections. They are characterized by cyclic course, bacteremia, intoxication, rash on the skin, lesions of the lymphatic apparatus of the small intestine. Besides that, typhoid  fever  is characterized by high fever of different duration, development of so-called status typhosus, hepatosplenomegaly, lesions of organs of the gastrointestinal tract, relapses and various complications.

http://www.cdc.gov/nczved/divisions/dfbmd/diseases/typhoid_fever/

History and geographical distribution

Typhoid fever is well known for a long time as an illness of mankind.

The  causative  agent  of  typhoid  fever  was  described  by  Ebert  in  1880. Pure  culture  of  the  agent  was  isolated  by  Gafki  in  1884.

Typhoid  fever  was  one  of  the  most  widespread  and  serious  infectious  disease  in  19^th  century  and  in  the  beginning  of  20-th  century  in  all  countries  of  the  world, especially  in  the  large  towns  due  to  groupment  of  the  people  and  building  of  waterpipe  and  canalization  allowed  to  decrease  morbidity  in  the  large  towns. But  almost  every  calamity (hunger, earthquake)  and  wars  were  accompanied  by  outbreaks  of  typhoid  fever.

Now, the  morbidity  is  sporadic  in  European  countries. However, high  level  of  morbidity  occurs  in  some  countries  due  to  features  of  climate, ecological  conditions  and  social  factors (Mexico, India, Afghanistan, countries  of  Northern  Africa  and  other).

http://www.medicinenet.com/typhoid_fever/article.htm

Etiology

The causative agent of typhoid  is Salmonella typhi of Enterobacteriacea family, genus Salmonella, serological group D.

Salmonella  are  not-spore-forming  rods and motile  by  peretrichous  flagella (Fig.1). Like  other  enterobacteria, Salmonella  have  somatic (O) antigens  which  are  lipopolysaccharide  components  of  the  cell  wall  and  flagellar (H) antigens, which  are  proteins. There  are  approximately  60  O-antigens, which  are  designated  by  numbers  at  letters. The  Kauffmann-White  scheme  categorizes Salmonella  on  the  basis  of  somatic  antigens, each  group  having  a  major  determinant  which  is  a  strongly  reaching  somatic  antigens  and  one  or  more  major  somatic  antigen. Salmonella  typhi  also  has  a  capsular  or  virulence (Vi)  antigen  composed  of  a    homopolymer  of  N-acetyl  galactosaminuronic  acid. The  presence  of  Vi-antigen  on  the  cell  surface  may  block  agglutination  by  anti-O serum.

Fig.1. Salmonella typhi

 

Salmonella  can  be  differentiated  from  other  Enterobacteriaceae  on  basis  of  certain  biochemical  reactions, including  fermentation. Most Salmonella ferment glucose and mannose to produce acid and gas but do not ferment lactose or sucrose; S.typhi does not produce gas. Thus, Salmonella  typhi  has  some  antigenic  and  biochemical  features. That is why typhoid  fever  is  isolated  from  the  other  diseases, caused  by Salmonella. Salmonella  organisms  grow  on  the  media  with  addition  of  bile. The  resistance of agent of typhoid fever and paratyphoid  in the environment is very high. They endure low temperatures  very  well. The  agents of typhoid fever and paratyphoid diseases survive from 1-2 till 25-30 days, in food products.

 

Epidemiology

Typhoid  fever  is  anthroponosis. The  source  of  infection  is  sick  man  or  bacteriocarrier. The  patients  with  typhoid  fever  discharge  the  agent  with  stool, urine,  rarely – with  saliva  and  milk. The  discharge  of  the  agent  is  observed  at  the  and  of  incubation  period, during  all  disease, and  sometimes  in  the  period  of  reconvalescence. In  some  cases  the  discharge  continues  till  three  months (acute  carriers) or  more  than  three  months (chronic  carriers). Chronic  carriers  may  be  from  six  months  till  some  years.

The mechanism of the infection transmission  is fecal-oral. The factors of transmission may be water, milk, various food-stuffs and contaminated feces of the patient or bacterial  carriers. Flies can play the supplementary role.

Susceptibility to agent of typhoid fever and paratyphoid diseases is rather high, however clinical manifestation can be of  different grade. The care rate of typhoid fever and paratyphoid diseases depends on seasonal prevalence. It increases in summer-autumn period, due to consumption of a huge amount of flies, quite often from unknown sources, unwashed fruit and vegetables. The strong immunity develops after disease.

http://www.medicinenet.com/typhoid_fever/page2.htm

Pathogenesis

The   next  phases  are  distinguished  in the  pathogenesis  of  typhoid  fever:

1.     Penetration of the  causative agent into the organism.

2.     Development of lymphadenitis and lymphangitis.

3.     Bacteremia

4.     Intoxication.

5.     Parenchymatous diffusion.

6.     Discharge  of  the  agent from the organism (excretory phase).

7.     Allergic reaction, mainly, of lymphoid tissue of the small intestinum.

8.     Formation of immunity.

The first phase is penetration of the agent in the macroorganism. However, penetration  does not always lead to the development of the pathological process. It depends on the quantity of the agent and the state of barrier functions (stomach in this case). The further path of Salmonella typhi is lymphatic apparatus of  intestine.

The second phase is lymphadenitis, lymphangitis. Salmonellae  achieve  the  small  intestine  and  actively  penetrate  into  solitary  follicules, Peyer’s  patches. There  is  the  reproduction  of  the  agents  and  formation  of  the  focus  of  infection. Microorganisms  penetrate  to  regional  lymphatic  nodes (mesenterial)  along  the  lymphatic  patches. There  is  the  other  focus  of  infection. In the lymphatic apparatus, the typical morphological alterations with  proliferation of  tissue and formation  the large typhoid cells develop.

Bacteria   achieve  the  definite  quantity  and enter  into  the  blood  circulation  through  the  thoracic  duct. It  is  the  next  phase  of  pathogenesis –   bacteremia. In  clinic  bacteremia  means  the  end  of  incubation  period  and  beginning  of  the  clinical  manifestations.  The blood has bactericidal properties. It  leads  to  the  death  of  the  part  of microbes. Intoxicative  syndrome  develops. Intoxication is the fourth phase of pathogenesis. The action of endotoxins causes changes of the state of the central nervous system, adynamia, fever, headaches, violations of dream, appetite.

The fifth phase of a pathogenesis is parenchymatous diffusion of microbes. By the flow of the blood Salmonella of typhoid fever and paratyphoid also are delivered over the organism, enter  into all organs. Microbes  are  fixated especially in liver, spleen, bone marrow, skin. Secondary focuses are formed (typhoid granulomas), from which bacteria likewise from the primary focuses (lymphatic apparatus of the intestine) enter  into the blood, supporting bacteremia. The settling of microbes in the reticuloendothelial system and their destruction in the structures of reticuloendothelial system causes the cleaning of the organism from  infection.

The sixth phase of  pathogenesis is discharge of  the agent from  the organism. The  agents  enter  into  the  intestine  from  the liver  through  the  bile ducts. They are excreted into the external environment with feces of the patient. The  part  of  the  agents  repeatedly penetrates from  the  small  intestine into  lymphatic apparatus of the intestine and  cause  sensibilization  to  microbes.  The  expressive  changes  of  lymphoid  tissue  develop  due  to  repeated  implantation  of  Salmonella  typhi with  development  of  morphological  changes  from  cerebral-like  swelling  to  necrosis  and  formation  of  ulcers.

This process is considered as the seventh phase of pathogenesis – allergic response of lymphoid tissue of the small intestine.

Eighth phase of pathogenesis is formation of immunity and restoration of the physiological equilibrium.

All pathogenic Salmonella species are engulfed by phagocytic cells, which then pass them through the mucosa and present them to the macrophages in the lamina propria. Nontyphoidal salmonellae are phagocytized throughout the distal ileum and colon. With toll-like receptor (TLR)–5 and TLR-4/MD2/CD-14 complex, macrophages recognize pathogen-associated molecular patterns (PAMPs) such as flagella and lipopolysaccharides. Macrophages and intestinal epithelial cells then attract T cells and neutrophils with interleukin 8 (IL-8), causing inflammation and suppressing the infection.

In contrast to the nontyphoidal salmonellae, S typhi enters the host’s system primarily through the distal ileum. S typhi has specialized fimbriae that adhere to the epithelium over clusters of lymphoid tissue in the ileum (Peyer patches), the main relay point for macrophages traveling from the gut into the lymphatic system. S typhi has a Vi capsular antigen that masks PAMPs, avoiding neutrophil-based inflammation. The bacteria then induce their host macrophages to attract more macrophages.

S typhi co-opts the macrophages’ cellular machinery for its own reproduction as it is carried through the mesenteric lymph nodes to the thoracic duct and the lymphatics and then through to the reticuloendothelial tissues of the liver, spleen, bone marrow, and lymph nodes. Once there, the S typhi bacteria pause and continue to multiply until some critical density is reached. Afterward, the bacteria induce macrophage apoptosis, breaking out into the bloodstream to invade the rest of the body.

The bacteria then infect the gallbladder via either bacteremia or direct extension of S typhi –infected bile. The result is that the organism re-enters the gastrointestinal tract in the bile and reinfects Peyer patches. Bacteria that do not reinfect the host are typically shed in the stool and are then available to infect other hosts.

Risk factors

S typhi are able to survive a stomach pH as low as 1.5. Antacids, histamine-2 receptor antagonists (H2 blockers), proton pump inhibitors, gastrectomy, and achlorhydria decrease stomach acidity and facilitate S typhi infection.

HIV/AIDS is clearly associated with an increased risk of nontyphoidal Salmonella infection; however, the data and opinions in the literature as to whether this is true for S typhi infection are conflicting. If an association exists, it is probably minor.

Other risk factors for clinical S typhi infection include various genetic polymorphisms. These risk factors often also predispose to other intracellular pathogens. For instance, PARK2 and PACGR code for a protein aggregate that is essential for breaking down the bacterial signaling molecules that dampen the macrophage response. Polymorphisms in their shared regulatory region are found disproportionately in persons infected with Mycobacterium leprae and S typhi.

On the other hand, protective host mutations also exist. The fimbriae of S typhi bind in vitro to cystic fibrosis transmembrane conductance receptor (CFTR), which is expressed on the gut membrane. Two to 5% of white persons are heterozygous for the CFTR mutation F508del, which is associated with a decreased susceptibility to typhoid fever, as well as to cholera and tuberculosis. The homozygous F508del mutation in CFTR is associated with cystic fibrosis. Thus, typhoid fever may contribute to evolutionary pressure that maintains a steady occurrence of cystic fibrosis, just as malaria maintains sickle cell disease in Africa.

Life cycle of Salmonella typhi.

Environmental and behavioral risk factors that are independently associated with typhoid fever include eating food from street vendors, living in the same household with someone who has new case of typhoid fever, washing the hands inadequately, sharing food from the same plate, drinking unpurified water, and living in a household that does not have a toilet. As the middle class in south Asia grows, some hospitals there are seeing a large number of typhoid fever cases among relatively well-off university students who live in group households with poor hygeine. American clinicians should keep this in mind, as members of this cohort often come to the United States for higher degrees.

 

Pathological anatomy

Sequential changes in tissue in the ileocecal area of the intestinal tract occur during typhoid fever and have been classified into four phases:

1. hyperplasia;

2. necrosis and sloughing;

3. ulceration;

4. healing.

During the first week of clinical symptoms, hyperplastic changes occur in Peyer’s patches in the ileum and in lymphoid follicles in the cecum, causing there tissue to project into the bowel lumen. The hyperplasia regresses after 7-10 days or undergoes necrosis with sloughing of overlying mucosa leading to the formation of characteristic ulcers that parallel the long axis of the ileum (Fig.2). Small punctuate lesions develop in the cecum. Ulcers usually heal completely with little residual scarring, but they may be the sites of hemorrhage or may penetrate to the serosa and lead to bowel perforation.

 

 

Fig.2. Ulcers of ileum

Clinical manifestation

http://www.localhealth.com/article/typhoid-fever-1/symptoms

Typhoid  fever  and  paratyphoid  are  characterized  by  cyclic  course. There  are  such  periods  during  course  of  the  infectious  process: incubation, initial, period  of  climax, early  reconvalescence  and  outcomes.

The incubation period of typhoid fever is usually 10-14 days but it may be  from 7 to 21 days. The incubation period is influenced by the number of organisms ingested. The  duration  of  incubation  period  also depends on virulence  of  microorganism  and  state  of  macroorganism.

Manifestations of enterocolitis occasionally occur within hours after the ingestion of food or drink contaminated with S. typhi if the dose of organisms is large. In these instances symptoms of nausea, vomiting and diarrhea usually resolve completely before the onset  of   symptoms  of  typhoid  fever.

The  onset  of  typhoid  fever  is  insidious  in  contrast  to  sepsis  produced  by  most  other  gram-negative  organisms. The  initial  manifestations  are  nonspecific  and  consist  of  fever, malaise, anorexia, headache  and  myalgias. Remittent  fever  is  prominent  with  gradually  increasing  evening  temperature  elevations  from  less  than 38 °C  to  values  in  the  range  of  40 °C  by  the  end  of  the  first  week  of  illness.

The  disease  turns  into  the  next  stage (climax  of  the  disease)  at  the  end  of  the  first  week. The  appearance   of  the  patients  is  very  typical  in  this  period. The  skin  is  pale.  Patient  is  apathethic. Intoxication  is  increased. Temperature  is  constant and  most  typical  syndrome  of  typhoid  fever  and  paratyphoid. At  first  the  temperature  was  described  by  Vunderlish  in  19  century. Temperature  curve  riminds  trapezium. The  phase  of  increase  of  the  temperature  is  near  one  week. The  phase  of  climax  is  near  two  weeks. The  phase  of  decrease  of  the  temperature  is  near  one  week. Temperature  curve  of     Vunderlish  occurs  rarely. Temperature  curve  has  wave-like  character  more  frequently (temperature  curve  of  Botkin).

Chills   and  diaphoreses  are  seen  in  about  one-third  of  the  patient  even  in the  absence of antimicrobial therapy. Either constipation or diarrhea may occur. Respiratory symptoms, including cough and sore throat may be prominent. Neuropsychiatries manifestations, including confusion, dizziness, seizures, or acute psychotic behavior, may be predominant in an occasional case. Status  typhosus  is  observed  in  serious  course  of  the  disease.

In present time patient with typhoid fever usually appears acutely ill. Fever is usually prominent, and in many instances the pulse is slow relative to the temperature.

In  typhoid  fever  symptoms  of  violation  of  cardiovascular  system  are  constant  and  expressive.  The  basis  of  hemodynamic  disorder  is  violation  of  the  tonus  of  the  vessels, damage  of  heart  muscle  due  to  intoxication. Myocardiodystrophy  develops  as  a  result. In  typhoid  fever  relative  bradycardia  is  the  clinical  feature  of  cardiovascular  disorders. The  muffed heart sounds, systolic  murmur  at  the heart  apex, hypotension  are  marked  inrarely. Relative  bradycardia  develops  due  to  endotoxin action  of  the  agent  on X  pair  of  cerebrospinal  nerves.

Rose spots, 2-4 mm erythematous, maculopapular lesions that blanch on pressure, appear on the upper abdomen or on the lateral surface of the body. Roseolas are few (5-15) iumber (Fig. 1). The lesions are transient and resolve in hours to days. Rose spots are observed on the 7-10 day of the disease near in half of patients. Sometimes they dissapears, sometimes exist longer than fever.

Cervical lymphoadenopathy may be present.  Examination of the chest may reveal moist rales. The abdomen is tender, especially in the lower quadrants. Abdominal distention is common, and peristalsis is often hypoactive. The sensation of displacing air – and fluid-filled loops of bowel on palpating of the abdomen is considered to be characteristic. In percussion short sound is marked in ileocaecal area due to enlarged mesenteric lymphatic nodes (Padalka symptom).

Fig.3. Rose spots

Hepatomegaly is noted in about 40-50 % of the patient, and a soft, tender spleen  can be palpated in about 40-60 %. In about 10 % of the patients, changes in consciousness are present and manifest as lethargy, delirium, or coma.

Without antimicrobial therapy, the disease pursues a prolonged course with slow resolution of signs and symptoms 3-4 weeks after onset if there are no complications. Sustained fever is common during the second and third weeks of disease. Fever decreases slowly by lysis, unlike the resolution by crisis seen in the preantibiotic era in many cases of pneumococcal pneumonia. Headache, confusion, respiratory symptoms, and abdominal pain and distention gradually resolve, and the pulse more characteristically reflects degree of fever acute manifestations subsiding. Profound weight loss invariably occurs in untreated patient. Many of the complications of typhoid  fever occur during the period of resolution in the third or fourth week after onset.

Complications

Complications of typhoid fever can be classified as secondary to toxemia (myocarditis, hyperpyrexia, hepatic and bone marrow damage), secondary to local gastrointestinal lesions (haemorrhage and perforation), secondary to prolonged severe illness (suppurative parotitis decubiti, and pneumonia), secondary to growth and persistence of typhoid fever bacilli (relapse, localized infection – meningitis, endocarditis, osteomyelitis or arthritis – and secondary to therapy (bone marrow suppression, hypersensitive reactions and toxic shock).

In the preantimicrobial era, 12-16 % of the patients with typhoid fever died, frequently from complications in the third or fourth week of the disease. Fatalities still occur occasionally, probably in less than one percent of the patients receiving appropriate antimicrobial and pathogenetic  therapy. However, in certain specific geographic areas of Indonesia, India, and Nigeria, fatality rations of 9-32 % have been reported last 10-15 years. It is likely that these results are consequent to suboptimal health and medical care rather that an increase in the clinical severity of typhoid fever.

The complications attributed to “toxemia” might be considered as manifestations of severe disease. Toxic myocarditis occur in severely ill patients, frequently children, and is manifested by tachycardia, weak pulse, muffled heart sounds, and hypotension. The electrocardiogram shows low voltage and T-wave flattening or inversion. Atrial or ventricular arrhythmia may occur.

Major intestinal hemorrhage is usually a late complication that occur during the second or third week of illness. In the preantimicrobial era, gross intestinal hemorrhage occurred in about 5-7 % of the patient with typhoid fever. The incidence of hemorrhage requiring transfusions has been reduced to 1 or 2 %, due to chloramphenicol use. There  is  an  important  sign  of  the  massive  intestinal  hemorrhage  symptom  of  “scissors” (Fig.4). Suddenly  the  temperature  is  decreased  up to  normal  or  subnormal. But  tachycardia   is  observed. The  arterial  pressure  is  reduced. Intestinal perforation usually occurs during third week of illness. Perforation  occurs in  the  terminal  ileum  where  the  number  of  lymphoid  aggregates  is  the largest  and  ulcerations  most  frequent. In  general, perforation  has  reported  in  recent  years  in  one  percent  or  less  of  cases  as  compared  with  2-5 %  in  several  series  collected  in  the  preantibiotic  era.

 

Fig.4. Decreasing of temperature and tachycardia (“scissors” symptom)

Relapse, a recurrence of the manifestation of typhoid fever after initial clinical response, occur in about 8-12 % of the patient who have not received antimicrobial therapy. The relapse rate was found to be doubled in patients receiving chloramphenicol therapy  for 2 weeks. Ampicillin probably does not affect the rate of relapse.

Localization of infection, which may lead to abscess formation, can occur in almost any organ or tissue. Although bacteremia can be assumed to develop in all patient with typhoid fever, localized infections such as meningitis, endocarditis, osteomyelitis, or thyroiditis occur in less then one percent.

The chronic carrier state is detained as documented excretion of S. typhi in stool or urine for a year or more. The chronic carrier state usually follows typhoid fever but as many as one – third of the chronic carriers give no history consistent with this illness. Underlying biliary or urinary tract diseases, especially with stone formation, increase the probability of the chronic enteric or urinary carrier state in   patients with typhoid fever. One to 3 % of the patients with typhoid fever become chronic enteric carriers; however, the incidence is higher in older patients (at the sixth decade) and in women.

http://www.nlm.nih.gov/medlineplus/ency/article/001332.htm

Clinical features of paratyphoids

Epidemiology, pathogens, morphology and clinics of paratyphoid A and B, have, in principal, mutual signs with typhoid fever. However, paratyphoids have some clinical features.

In paratyphoid A incubation period is shorter than in typhoid fever. It’s duration is 8-10 days. The onset of the disease is an acute. Sometimes, the onset of the disease is accompanied by cough, catarrh. Facial hyperemia, blood injection of the sclera’s vessels, herpes on the lips are observed during examination. The temperature is wave-like or remittent. The fever is accompanied by chills and than by diaphoreses. In paratyphoid A the rash appeares in more early periods than in typhoid fever. The rash is polymorphic. Roseolas, petechias and measles-like rash may be observed. The intoxication is temperate. There is no status typhosus. There is normal quantity of leukocytes in peripheral blood. But leukocytosis and lymphocytosis may occur too.

In majority of the patients the disease has a moderate course. But the severe forms may  be observed too, with complications (intestinal hemorrhage, intestinal perforation and other). The relapses are frequently observed in case of   paratyphoid A.

Paratyphoid B incubation period is 5-10 days. The onset of the disease is acute, with expressive chill, myalgia and diaphoreses. At the initial period of the disease the intoxication may be combined with symptoms of acute gastroenteritis. The temperature is not prolonged. Status typhosus is absent in majority of the patients. The symptoms of intoxication disappeares very quickly. The rash is polymorphic, plenty. It  appears at the earlier period. In some cases the course of paratyphoid B may be severe with septic manifestations (purulent meningitis, meningoencephalitis, septicopyemia). In peripheral blood leukocytosis and neutrophylosis are observed.

 

Diagnosis

Definitive diagnosis of typhoid fever and paratyphoid  is made on the basis of pathogen isolation from the patient’s blood. Isolation of the organism from stool, especially in endemic areas, does constitute strong presumptive evidence of typhoid fever in the patient with a typical clinical course. Serologic studies may be helpful, but in many cases of typhoid fever there is no increase in titer of agglutinins during the course of infection, and other illnesses, especially infections with other gram – negative bacilli, may cause nonspecific elevations of agglutinins because of cross – reaching antigens. In untreated disease only about 50 %  of the patient have a fourfold or greater increase in titer of agglutinins (Vidal’s test) against typhoid fever O antigen at any time during the course of disease.

The diagnosis of typhoid fever (enteric fever) is primarily clinical.

Importantly, the reported sensitivities of tests for S typhi vary greatly in the literature, even among the most recent articles and respected journals.

• Culture
• The criterion standard for diagnosis of typhoid fever has long been culture isolation of the organism. Cultures are widely considered 100% specific.
• Culture of bone marrow aspirate is 90% sensitive until at least 5 days after commencement of antibiotics. However, this technique is extremely painful, which may outweigh its benefit.
• Blood, intestinal secretions (vomitus or duodenal aspirate), and stool culture results are positive for S typhi in approximately 85%-90% of patients with typhoid fever who present within the first week of onset. They decline to 20%-30% later in the disease course. In particular, stool culture may be positive for S typhi several days after ingestion of the bacteria secondary to inflammation of the intraluminal dendritic cells. Later in the illness, stool culture results are positive because of bacteria shed through the gallbladder.
• Multiple blood cultures (>3) yield a sensitivity of 73%-97%. Large-volume (10-30 mL) blood culture and clot culture may increase the likelihood of detection.
• Stool culture alone yields a sensitivity of less than 50%, and urine culture alone is even less sensitive. Cultures of punch-biopsy samples of rose spots reportedly yield a sensitivity of 63% and may show positive results even after administration of antibiotics. A single rectal swab culture upon hospital admission can be expected to detect S typhi in 30%-40% of patients. S typhi has also been isolated from the cerebrospinal fluid, peritoneal fluid, mesenteric lymph nodes, resected intestine, pharynx, tonsils, abscess, and bone, among others.
• Bone marrow aspiration and blood are cultured in a selective medium (eg, 10% aqueous oxgall) or a nutritious medium (eg, tryptic soy broth) and are incubated at 37°C for at least 7 days. Subcultures are made daily to one selective medium (eg, MacConkey agar) and one inhibitory medium (eg, Salmonella-Shigella agar). Identification of the organism with these conventional culture techniques usually takes 48-72 hours from acquisition.

Table 2. Sensitivities of Cultures

	Incubation	Week 1	Week 2	Week 3	Week 4
Bone marrow aspirate (0.5-1 mL)		90% (may decrease after 5 d of antibiotics)
Blood (10-30 mL), stool, or duodenal aspirate culture	40%-80%		~20%	Variable (20%-60%)
Urine		25%-30%, timing unpredictable

• Polymerase chain reaction (PCR): PCR has been used for the diagnosis of typhoid fever with varying success. Nested PCR, which involves two rounds of PCR using two primers with different sequences within the H1-d flagellin gene of S typhi, offers the best sensitivity and specificity. Combining assays of blood and urine, this technique has achieved a sensitivity of 82.7% and reported specificity of 100%. However, no type of PCR is widely available for the clinical diagnosis of typhoid fever.
• Specific serologic tests
• Assays that identify Salmonella antibodies or antigens support the diagnosis of typhoid fever, but these results should be confirmed with cultures or DNA evidence.
• The Widal test was the mainstay of typhoid fever diagnosis for decades. It is used to measure agglutinating antibodies against H and O antigens of S typhi. Neither sensitive nor specific, the Widal test is no longer an acceptable clinical method.
• Indirect hemagglutination, indirect fluorescent Vi antibody, and indirect enzyme-linked immunosorbent assay (ELISA) for immunoglobulin M (IgM) and IgG antibodies to S typhi polysaccharide, as well as monoclonal antibodies against S typhi flagellin, are promising, but the success rates of these assays vary greatly in the literature.
• Other nonspecific laboratory studies
• Most patients with typhoid fever are moderately anemic, have an elevated erythrocyte sedimentation rate (ESR), thrombocytopenia, and relative lymphopenia.
• Most also have a slightly elevated prothrombin time (PT) and activated partial thromboplastin time (aPTT) and decreased fibrinogen levels.
• Circulating fibrin degradation products commonly rise to levels seen in subclinical disseminated intravascular coagulation (DIC).
• Liver transaminase and serum bilirubin values usually rise to twice the reference range.
• Mild hyponatremia and hypokalemia are common.
• A serum alanine amino transferase (ALT)–to–lactate dehydrogenase (LDH) ratio of more than 9:1 appears to be helpful in distinguishing typhoid from viral hepatitis. A ratio of greater than 9:1 supports a diagnosis of acute viral hepatitis, while ratio of less than 9:1 supports typhoid hepatitis.

 

Differential diagnosis

The differential diagnosis of typhoid fever requires consideration of many disease processes characterized by fever and abdominal complaints.

Early in the disease the predominance of fever and upper respiratory tract symptoms may suggest influenza or other viral infections. Cough and fever suggest acute bronchitis and, when coupled with rales, raise the question of bacterial pneumonia. Headache, confusion, and fever may prompt consideration of bacterial or aseptic meningitis or meningoencephalitis. Delirium, catatonia, or coma may suggest a diagnosis of psychosis or other neuropsychiatries illness. The abdominal findings may lead to a consideration of acute appendicitis, acute cholecystitis, or intestinal infarction. Bacillary, amebic or ischemic colitis may enter the differential diagnosis if blood diarrhea occurs. As fever continues over a period of weeks, other possibilities might include brucellosis, yersinosis, lymphoma, inflammatory bowel disease, bacterial endocarditis, miliary tuberculosis, malaria, sepsis, epidemic typhus and many other diseases.

Treatment

http://emedicine.medscape.com/article/231135-medication

Antibiotics

Class Summary

Definitive treatment of typhoid fever (enteric fever) is based on susceptibility. As a general principle of antimicrobial treatment, intermediate susceptibility should be regarded as equivalent to resistance. Between 1999 and 2006, 13% of S typhi isolates collected in the United States were multidrug resistant.

Until susceptibilities are determined, antibiotics should be empiric, for which there are various recommendations. The authors of this article consider the 2003 World Health Organization (WHO) guidelines to be outdated. These recommend fluoroquinolone treatment for both complicated and uncomplicated cases of typhoid fever, but 38% of S typhi isolates taken in the United States in 2006 were fluoroquinolone resistant (nalidixic acid–resistant S typhi [NARST]), and the rate of multidrug resistance was 13%. (Multidrug-resistant S typhi is, by definition, resistant to the original first-line agents, ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole.)

The particular sensitivity pattern of the organism in its area of acquisition should be the major basis of empiric antibiotic choice. It may soon become necessary to treat all cases presumptively for multidrug resistance until sensitivities are obtained.

Note that nalidixic acid is a nontherapeutic drug that is used outside of the United States as a stand-in for fluoroquinolones in sensitivity assays. In the United States, it is still used specifically for S typhi infection.

History of antibiotic resistance

Chloramphenicol was used universally to treat typhoid fever from 1948 until the 1970s, when widespread resistance occurred. Ampicillin and trimethoprim-sulfamethoxazole (TMP-SMZ) then became treatments of choice. However, in the late 1980s, some S typhi and S paratyphi strains (multidrug resistant [MDR] S typhi or S paratyphi) developed simultaneous plasmid-mediated resistance to all three of these agents.

Fluoroquinolones are now recommended by most authorities for the treatment of typhoid fever. They are highly effective against susceptible organisms, yielding a better cure rate than cephalosporins. Unfortunately, resistance to first-generation fluoroquinolones is widespread in many parts of Asia.

In recent years, third-generation cephalosporins have been used in regions with high fluoroquinolone resistance rates, particularly in south Asia and Vietnam. Unfortunately, sporadic resistance has been reported, so it is expected that these will become less useful over time.

Mechanisms of antibiotic resistance

The genes for antibiotic resistance in S typhi and S paratyphi are acquired from Escherichia coli and other gram-negative bacteria via plasmids. The plasmids contain cassettes of resistance genes that are incorporated into a region of the Salmonella genome called an integron. Some plasmids carry multiple cassettes and immediately confer resistance to multiple classes of antibiotics. This explains the sudden appearance of MDR strains of S typhi and S paratyphi, often without intermediate strains that have less-extensive resistance.

The initial strains of antibiotic-resistant S typhi and S paratyphi carried chloramphenicol acetyltransferase type I, which encodes an enzyme that inactivates chloramphenicol via acetylation. MDR strains may carry dihydrofolate reductase type VII, which confers resistance to trimethoprim. Interestingly, in areas where these drugs have fallen out of use, S typhi has reverted to wild type, and they are often more effective thaewer agents.

Resistance to fluoroquinolones is evolving in an ominous direction. Fluoroquinolones target DNA gyrase and topoisomerase IV, bacterial enzymes that are part of a complex that uncoils and recoils bacterial DNA for transcription. S typhi most commonly develops fluoroquinolone resistance through specific mutations in gyrA and parC, which code for the binding region of DNA gyrase and topoisomerase IV, respectively.

A single point mutation gyrA confers partial resistance. If a second gyrA point mutation is added, the resistance increases somewhat. However, a mutation in parC added to a single gyrA mutation confers full in vitro resistance to first-generation fluoroquinolones. Clinically, these resistant strains show a 36% failure rate when treated with a first-generation fluoroquinolone such as ciprofloxacin. The risk of relapse after bacterial clearance is higher in both partially and fully resistant strains than in fully susceptible strains.

The third-generation fluoroquinolone gatifloxacin appears to be highly effective against all known clinical strains of S typhi both in vitro and in vivo. due to its unique interface with gyrA. It achieves better results than cephalosporins even among strains that are considered fluoroquinolone resistant. However, gatifloxacin is no longer on the market in the United States, and its use cannot be generalized to any other member of the class.

In any case, as gatifloxacin replaces older fluoroquinolones in high-prevalence resistance is bound to emerge. Any two of a number of gyrA mutations, when added to the parC mutation, confer full in vitro resistance. Although such a combination has yet to be discovered in vivo, all of these mutations exist in various clinic strains, and it seems highly likely that a gatifloxacin-resistant one will be encountered clinically if selective pressure with fluoroquinolones continues to be exerted.

Geography of resistance

Among S typhi isolates obtained in the United States between 1999 and 2006, 43% were resistant to at least one antibiotic.

Nearly half of S typhi isolates found in the United States now come from travelers to the Indian subcontinent, where fluoroquinolone resistance is endemic (see Table 3). The rate of fluoroquinolone resistance in south and Southeast Asia and, to some extent, in East Asia is generally high and rising (see Table 3). Susceptibility to chloramphenicol, TMP-SMZ, and ampicillin in South Asia is rebounding. In Southeast Asia, MDR strains remain predominant, and some acquired resistance to fluoroquinolones by the early 2000s.

The most recent professional guideline for the treatment of typhoid fever in south Asia was issued by the Indian Association of Pediatrics (IAP) in October 2006. Although these guidelines were published for pediatric typhoid fever, the authors feel that they are also applicable to adult cases. For empiric treatment of uncomplicated typhoid fever, the IAP recommends cefixime and, as a second-line agent, azithromycin. For complicated typhoid fever, they recommend ceftriaxone. Aztreonam and imipenem are second-line agents for complicated cases. The authors believe that the IAP recommendations have more validity than the WHO recommendations for empiric treatments of typhoid fever in both adults and children.

In high-prevalence areas outside the areas discussed above, the rate of intermediate sensitivity or resistance to fluoroquinolones is 3.7% in the Americas (P =.132), 4.7% (P =.144) in sub-Saharan Africa, and 10.8% (P =.706) in the Middle East. Therefore, for strains that originate outside of south or Southeast Asia, the WHO recommendations may still be valid—that uncomplicated disease should be treated empirically with oral ciprofloxacin and complicated typhoid fever from these regions should be treated with intravenous ciprofloxacin.

Antibiotic resistance is a moving target. Reports are quickly outdated, and surveys of resistance may have limited geographic scope. Therefore, any recommendation regarding antibiotic treatment must be taken with a grain of salt. In the authors’ opinion, if the origin of the infection is unknown, the combination of a first-generation fluoroquinolone and a third-generation cephalosporin should be used.

Table 3. Antibiotic Recommendations by Origin and Severity

Location	Severity	First-Line Antibiotics	Second-Line Antibiotics
South Asia, East Asia	Uncomplicated	Cefixime PO	Azithromycin PO
	Complicated	Ceftriaxone IV or Cefotaxime IV	Aztreonam IV or Imipenem IV
Eastern Europe, Middle East, sub-Saharan Africa, South America	Uncomplicated	Ciprofloxacin PO or Ofloxacin PO	Cefixime PO or Amoxicillin PO or TMP-SMZ PO or Azithromycin PO
	Complicated	Ciprofloxacin IV or Ofloxacin IV	Ceftriaxone IV or Cefotaxime IV or Ampicillin IV or TMP-SMZ IV
Unknown geographic origin or Southeast Asia	Uncomplicated	Cefixime PO plus Ciprofloxacin PO or Ofloxacin PO	Azithromycin PO*
	Complicated	Ceftriaxone IV or Cefotaxime IV, plus Ciprofloxacin IV or Ofloxacin IV	Aztreonam IV or Imipenem IV, plus Ciprofloxacin IV or Ofloxacin IV
*Note that the combination of azithromycin and fluoroquinolones is not recommended because it may cause QT prolongation and is relatively contraindicated.

Future directions

A meta-analysis found that azithromycin appeared to be superior to fluoroquinolones and ceftriaxone with lower rates of clinical failure and relapse respectively. Although the data did not permit firm conclusions, if further studies confirm the trend, azithromycin could become a first-line treatment.

Chloramphenicol (Chloromycetin)

Binds to 50S bacterial-ribosomal subunits and inhibits bacterial growth by inhibiting protein synthesis. Effective against gram-negative and gram-positive bacteria. Since its introduction in 1948, has proven to be remarkably effective for enteric fever worldwide. For sensitive strains, still most widely used antibiotic to treat typhoid fever. In the 1960s, S typh i strains with plasmid-mediated resistance to chloramphenicol began to appear and later became widespread in many endemic countries of the Americas and Southeast Asia, highlighting need for alternative agents.

Produces rapid improvement in patient’s general condition, followed by defervescence in 3-5 d. Reduced preantibiotic-era case-fatality rates from 10%-15% to 1%-4%. Cures approximately 90% of patients. Administered PO unless patient is nauseous or experiencing diarrhea; in such cases, IV route should be used initially. IM route should be avoided because it may result in unsatisfactory blood levels, delaying defervescence.

Amoxicillin (Trimox, Amoxil, Biomox)

Interferes with synthesis of cell wall mucopeptides during active multiplication, resulting in bactericidal activity against susceptible bacteria. At least as effective as chloramphenicol in rapidity of defervescence and relapse rate. Convalescence carriage occurs less commonly than with other agents when organisms are fully susceptible. Usually given PO with a daily dose of 75-100 mg/kg tid for 14 d.

Trimethoprim and sulfamethoxazole (Bactrim DS, Septra)

Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid. Antibacterial activity of TMP-SMZ includes common urinary tract pathogens, except Pseudomonas aeruginosa. As effective as chloramphenicol in defervescence and relapse rate. Trimethoprim alone has been effective in small groups of patients.

Ciprofloxacin (Cipro)

Fluoroquinolone with activity against pseudomonads, streptococci, MRSA, Staphylococcus epidermidis, and most gram-negative organisms but no activity against anaerobes. Inhibits bacterial DNA synthesis and, consequently, growth. Continue treatment for at least 2 d (7-14 d typical) after signs and symptoms have disappeared. Proven to be highly effective for typhoid and paratyphoid fevers. Defervescence occurs in 3-5 d, and convalescent carriage and relapses are rare. Other quinolones (eg, ofloxacin, norfloxacin, pefloxacin) usually are effective. If vomiting or diarrhea is present, should be given IV. Fluoroquinolones are highly effective against multiresistant strains and have intracellular antibacterial activity.

Not currently recommended for use in children and pregnant women because of observed potential for causing cartilage damage in growing animals. However, arthropathy has not been reported in children following use of nalidixic acid (an earlier quinolone known to produce similar joint damage in young animals) or in children with cystic fibrosis, despite high-dose treatment.

Cefotaxime (Claforan)

Arrests bacterial cell wall synthesis, which inhibits bacterial growth. Third-generation cephalosporin with gram-negative spectrum. Lower efficacy against gram-positive organisms. Excellent in vitro activity against S typhi and other salmonellae and has acceptable efficacy in typhoid fever. Only IV formulations are available. Recently, emergence of domestically acquired ceftriaxone-resistant Salmonella infections has been described.

Azithromycin (Zithromax)

Treats mild to moderate microbial infections. Administered PO at 10 mg/kg/d (not exceeding 500 mg), appears to be effective to treat uncomplicated typhoid fever in children 4-17 y. Confirmation of these results could provide an alternative for treatment of typhoid fever in children in developing countries, where medical resources are scarce.

Ceftriaxone (Rocephin)

Third-generation cephalosporin with broad-spectrum gram-negative activity against gram-positive organisms; Excellent in vitro activity against S typhi and other salmonellae.

Cefoperazone (Cefobid)

Discontinued in the United States. Third-generation cephalosporin with gram-negative spectrum. Lower efficacy against gram-positive organisms.

Ofloxacin (Floxin)

A pyridine carboxylic acid derivative with broad-spectrum bactericidal effect.

Levofloxacin (Levaquin)

For pseudomonal infections and infections due to multidrug-resistant gram-negative organisms.

 

Prophylaxis

http://www.cdc.gov/nczved/divisions/dfbmd/diseases/typhoid_fever/#avoidance

 

Control of Salmonella typhi infection transmitted from person to person depends on high standards of personal hygiene, maintenance of a supply of uncontaminated water, proper sewage dispose and identification, treatment, and follow-up of chronic carriers. Hand washing is of paramount importance in controlling person – to person spread although hands of convalescent carriers are often contaminated after defecation detectable Salmonella are easily removed by washing the hands with soap and water.

Typhoid fever vaccine, a saline suspension of aceton or heat/phenol killed S. typhi enhances the resistance of human beings to infection with S. typhi under experimental and natural conditions. Vaccine efficacy ranges from 51 to 67 %.

There is also renewed interest in testing the capsular polysaccharide of S. typhi (Vi antigen) as a parenteral typhoid fever vaccine.

Typhoid fever vaccine should be considered for persons with intimate continuing exposure to a documented typhoid fever carrier and for persons traveling to areas where there is a recognized appreciable risk to exposure to typhoid fever.

 

Salmonellosis

Salmonellae are widely dispersed in nature, being found in the in the gastrointestinal tracts of domesticated and wild mammals, reptiles, birds, and insects.

May present clinically as gastroenteritis, enteric fever, a bacteremic syndrome, or focal disease. An asymptomatic carrier state may also occur.

http://www.cdc.gov/salmonella/

Historic reference

The  term  “Salmonellosis”  unites  a  large  group  of  diseases, caused  by  multiply  serotypes  of  bacteriums  from genus Salmonellae (more than 2000).

Sallmonellae are named for the pathologist Salmon who first isolated S. cholerae suis from porcine intestine. The antigenic classification or serotyping of Salmonella used today is the result of study of antibody interactions with bacterial surface antigens by Kauffman and White in the 1920s to 1940s. Ames and coworkers in 1973 reported the development of the test that uses S.typhimurium auxotrophic mutants to test the mutagenic activity of chemical compounds.

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.

Etiology

http://www.onlinemedicinetips.com/disease/s/salmonella/Etiology-Of-Salmonella.html

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)(Fig.9).

 

 

Fig.9. Lactose-negative colonies of salmonella growing on MacConkey agar

 

Like other enterobacteria, salmonella has somatic (0) 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 °C. 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 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.

Epidemiology

http://www.safe–poultry.com/salmonellaepidemiology.asp

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 ieonatal 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.

Pathogenesis

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 iumber 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 (Fig.10).

Fig.10. Flask-shaped ulcer with necrosis of epithelium and extrusion of necrotic tissue, fibrin and mucus

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.

Stages of salmonellosis development:

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 inoculation 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.

The transmission of salmonellae to a susceptible host usually occurs via consumption of contaminated foods. The most common sources of salmonellae include beef, poultry, and eggs. In one recent estimate, consumption of egg shell fragments contaminated with S enteritidis was responsible for approximately 182,060 cases of enteritis in the United States in the year 2000. Improperly prepared fruits, vegetables, dairy products, and shellfish have also been implicated as sources of Salmonella.

In the spring of 2008, 1442 persons across 43 states developed infection with S enterica serotype Saintpaul, with the same genetic fingerprint linking contaminated jalapeno and serrano peppers as a source of infection. Almost any type food product could serve a source for infection, including peanut butter, as seen during a recent outbreak of more than 600 cases. Powdered infant formula has been implicated in two consecutive large outbreaks of S enterica serotype Agona among infants in France.

In addition, human-to-human and animal-to-human transmissions can occur. For example, amphibian and reptile exposures are associated with approximately 74,000 Salmonella infections annually in the United States. Salmonellosis outbreaks have also been associated with handling chicks, ducklings, kittens, and hedgehogs. Recently, a study of 28 cases of Styphimurium identified pet rodents as a previously unrecognized source of human Salmonella infection.

Although the infectious dose varies among Salmonella strains, a large inoculum is thought to be necessary to overcome stomach acidity and to compete with normal intestinal flora. Large inocula are also associated with higher rates of illness and shorter incubation periods. In general, about 10⁶ bacterial cells are needed to cause infection. Low gastric acidity, which is common in elderly persons and among individuals who use antacids, can decrease the infective dose to 10³ cells, while prior vaccination can increase the number to 10⁹ cells.

After ingestion, infection with salmonellae is characterized by attachment of the bacteria by fimbriae or pili to cells lining the intestinal lumen. Salmonellae selectively attach to specialized epithelial cells (M cells) of the Peyer patches. The bacteria are then internalized by receptor-mediated endocytosis and transported within phagosomes to the lamina propria, where they are released. Once there, salmonellae induce an influx of macrophages (typhoidal strains) or neutrophils (nontyphoidal strains).

The Vi antigen of S typhi is important in preventing antibody-mediated opsonization and complement-mediated lysis. Through the induction of cytokine release and via mononuclear cell migration, S typhi organisms spread through the reticuloendothelial system, mainly to the liver, spleen, and bone marrow. Within 14 days, the bacteria appear in the bloodstream, facilitating secondary metastatic foci (eg, splenic abscess, endocarditis). In some patients, gallbladder infection leads to long-term carriage of S typhi or S paratyphi in bile and secretion to the stool. As a rule, infection with nontyphoidal salmonellae generally precipitates a localized response, while S typhi and other especially virulent strains invade deeper tissues via lymphatics and capillaries and elicit a major immune response.

Virulence factors of salmonellae are complex and encoded both on the organism’s chromosome and on large (34-120 kd) plasmids. Some areas of active investigation include the means by which salmonellae attach to and invade the intestine, survive within phagosomes, effect a massive efflux of electrolytes and water into the intestinal lumen, and develop drug resistance. Several Salmonella pathogenicity islands have been identified that mediate uptake of the bacteria into epithelial cells (type III secretion system [TTSS]), nonphagocytic cell invasion (Salmonella pathogenicity-island 1 [SPI-1]), and survival and replication within macrophages (Salmonella pathogenicity-island 2 [SPI-2], phoP/phoQ).

The severity of illness in individuals with salmonellosis is determined not only by the virulence factors of the infecting strain but also by host properties. In a recent study of 129 nonfecal Salmonella isolates at the Massachusetts General Hospital, the most common risk factors were found to be corticosteroid use, malignancy, diabetes, HIV infection, prior antimicrobial therapy, and immunosuppressive therapy.

Sickle cell disease, malaria, schistosomiasis, bartonellosis, and pernicious anemia have been mentioned in the literature as other comorbidities that predispose to salmonellosis. Infants are at a high risk of developing CNS infection as a result of Salmonella bacteremia. Specific anatomical sites, such as an altered urinary or biliary tract, atherosclerotic aorta, or endovascular devices may facilitate persistent focal Salmonella infection.

Clinical  manifestations

http://www.bettermedicine.com/article/salmonella-infections

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,  without blood, swamp-like and bed smell (Fig.11).

Fig.11. Stool in case of salmonellosis

In exceptional 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 °C 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, laryngotracheobronchitis 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 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.

Arthritis. 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 iormal 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.

Bacteriocarriering 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

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.

Diagnosis

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) (7-8^th day of the disease) and indirect hemagglutination (RIHA). RIHA is more  sensitive. It gives  positive results on the 5^th day of the disease. Diagnostical titer is 1:200. Serological investigation should be done in dynamics of the disease.

Rentgenology investigation shows the increasing of thick intestin (Fig.12).

Fig.12. Tension and swelling of sigmoid colon

Differential diagnosis

Differential diagnosis of salmonellosis is perform 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 forms of salmonellosis is necessary to differentiate from sepsis of different etiology, pneumonia, malaria, acute pyelonephritis, tuberculosis.

• Modern blood culture systems are 80%-100% accurate in detecting bacteremia. As the disease duration increases, the sensitivity of blood cultures decreases, while the sensitivity of stool isolation increases.
• Freshly passed stool is the preferred specimen for isolation of nontyphoidal Salmonella species. Since stool carriage of S typhi may be prolonged, the interpretation of positive results merits caution, and the diagnosis should be established only when accompanied by clinical findings that are typical of infection.
• Bone marrow aspirate and culture is superior to blood culture, since the bacterial concentration in bone marrow is 10 times that of peripheral blood. In patients who received antibiotic therapy prior to hospitalization, bone marrow aspirate may still be positive for Salmonella even if blood culture results are negative.
• In cases of typhoid fever, S typhi or S paratyphi may also be isolated from urine, rose spot biopsy, or gastric or intestinal secretions.
• Grouping of Salmonella isolates is usually performed with polyvalent antisera specific for O and Vi antigen. S typhimurium belongs to group B; S enteritidis and S typhi belong to group D.
• Salmonellosis is a reportable disease in the United States.

Hematology and chemistry

• Although the WBC count is usually within the reference range in patients with salmonellosis, approximately one fourth of patients with typhoid fever are leukopenic, neutropenic, or anemic. Thrombocytopenia is neither universal nor diagnostic.
• The eosinophil count and sedimentation rate are typically low. A high sedimentation rate suggests abscess formation or osteomyelitis. Eosinophilia should prompt a search for concomitant parasitic infection.
• Mild hepatocellular liver function abnormality is common.

Treatment

http://emedicine.medscape.com/article/228174-treatment

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 Sodium 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 – Trisol, Quartasol, Lactasol. 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 proved at severe diarrhea (for downstroke 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).

Prophylaxis

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.

 

Food poisoning

 

Toxic food-borne infections  is  an  acute  transitory  disease, caused  by  conditionally  pathogenic  bacteria. These  bacteria  are  capable  to  produce  exotoxin  (in  food-stuffs). The  disease  is  accompanied  with  symptoms  of  the  damage  of  the  upper  parts  of  the  gastrointestinal  tract (gastritis, gastroenteritis)  and  by  violation  of  the  water-electrolyte  balance.

Etiology

Many  types  of  the  conditionally  pathogenic  bacteria  may be  agents  of  the toxic food-borne infections and  produce  exotoxin  out  of  the  human  organism  on  the  different  food-stuffs.  Enterotoxins (thermoliable and thermostable) increase the secretion of the fluids and salts into  the stomach and intestine. Cytotoxins damage the membranes of the epithelial cells and violate the protein synthetic processes. The agent, producing  enterotoxins  are Clostridium perfringeus, Proteus. vulgaris, Proteus mirabilis, Bacillus cereus. These enterotoxins are also formed by  agents  from  the in families of Klebsiella, Enterobacter, Citrobacter, Serrafia, Pseudomonas, Aeromonas, Edwarsiella. The  majority  of these enterotoxins are thermoliable.

Epidemiology

Pathogenic organisms of the toxic food infections are widely spread in the nature. They may  be everywhere: in the fecal matters of human and animals; in and the soil; in the water; in an air and on the different subjects. The  way  of  the  spread  of  the  infection  is  alimentary. The factors of  the transmission of the disease are solid products (sausages, eggs, meat and fish canned  food) and  liquid products (soup, milk, juices, compotes, jellies, lemonade, beer, cocktails). They  are  the  nutritive  mediums  for  bacteria.

The susceptibility to this group of diseases is very high,  sometimes  till 90-100 %. The  typical  sign  of  the toxic food-borne infections is  not  only  group  but  explosive  character  of illness  due  to  all  participants  of  the  outbreak  become ill during  a  short  period (over  a  few  hours). The diseases toxic food-borne infections are registered during  the  hole   the year, but especially in summer.

Pathogenesis

In  toxic food  infections exotoxin  is  contained  in  food, besides  bacteria. Due to this the incubation period is very short. Time  of  the  of  clinical  manifestations  development  after  influence  of  toxins  to  the  mucous  membrane  is  from  30  minutes  till  2-6 hours.

Pathogenesis  and  clinical  manifestations  of  the  disease  depend  of  the  type  and  dose  exotoxin, and   also  from  other  toxical  substances  microbial  origin, containing  in  the  food-stuff. Enterotoxins (thermoliable and thermostable) are connected  with the epithelial cells of stomach and intestine and act to  the fermental system of the epitheliocytes, but  no cause  morphological changes in these organs. Enterotoxin  activates  ferments  adenylcyclase  and  guanylcyclase increasing  formation  of  the  biological  active  substance (cyclic  adenosinemonophosphates and  cyclic guanidinmonophosphates)  in  the  cells  of  the  mucous  membranes. All these changes lead to the increase rate of secretion of water and salts into  the stomach and intestine and  to  the  development  of  diarrhea and vomiting.

 

Pathological anatomy

Cytotoxins damage the membranes of the epithelial cells and violates synthetic  processes. It  may increase  the  permeability  of  the intestinal  wall  for  different  types  of  the  toxical  substances, and  for  oneself  microorganisms,  development of intoxication and violation of microcirculation and localized inflammatory  alterations  of the  intestinal mucous membrane.

 

Clinical manifestations

The  clinical  manifestations  of  the toxic food-borne infections caused  by  only  enterotoxins  are  less  severe. In   the  majority  of  the  cases  of  the  disease  there  is  no  fever  and  just considerable  inflammatory  changes  of  the  mucous  membrane  of  the  stomach  and  intestine.

The  course  of  the  disease  become  more  severe due to accumulation  of  enterotoxin  and  cytotoxin  in  the  food-stuffs. The  high  fever  and  considerable  change  of  the  mucous  membrane  of  the  gastrointestinal  tract  are  observed.

In toxic food-borne infections there  is  combination  of  the  signs  of  the  damage  of  the  gastrointestinal  tract (gastritis, gastroenteritis  or  gastroenterocolitis) and  signs  of  the  general  intoxication  and  dehydration. The incubation period is from 30 minutes to 24 hours (generally 2-6 hours). The beginning of the disease is an  acute. At  first  the nausea occurs. Frequently  the replated, agonizing  and unrestrained vomiting occurs. Almost  at  the  same  time  with  vomiting  the  diarrhea starts. Stool is watery from 1 to 10-15 times a day. In  considerable  part of patients the  disease is   not accompanied by  severe pain in the stomach and increase of the body temperature of the body. However the disease may be with spasmatic pains in the stomach, with the raise of the body temperature upto 38-39 °C. The raise of the body temperature takes place at the early hours of the disease and through 12-24 hours  the  temperature  is reduced to normal.

During  objective  examination  of  the  patients the  pale  skin, sometimes  cyanosis, cold  extremities  are  observed.  The tongue is coated. Stomach is soft and painful in the epigastrium during palpation. The cardiovascular system also suffers. There is bradycardia (during hyperthermia – tachycardia). The  arterial pressure decrease. In some cases collapse of  short  duration  develops. Due  to  repeated  vomiting  and  plenty  diarrhea  the  signs  of  dehydration  develop. It  may  be  possible  of  the  appearance  of  the  muscle’s  cramps  of  extremities, decrease  of  the  diuresis  and  reduced  turgor  of  the  skin.  The liver and pancreas are not expanded. In hemogram leukocytosis, neutrophylosis and temperate  accelerate ESR are noted.

The duration of the disease in majority of  the cases  is 1-3 days. The  toxical  food  infection  may  be  accompanied  by  severe  complications. Hypovolemic shock and an acute heart insufficiency, connecting  with  violations  of  electrolytic  balance (hypokalemia) are  observed.

Diagnosis

The diagnosis of the toxic food-borne infections is made according the results  of  the  clinical symptoms estimation, epidemiological and laboratory data. The  typical  signs  are  the  impetuous  development  of  the  disease  after  short  incubation  period,  presence  of  symptoms  of  gastritis, gastroenteritis  or  gastroenterocolitis  in  combination  with  intoxication, dehydration, disposition  to  the  vascular  dystonia.

It  is  necessary  to  consider  the  simultaneous  disease  of  the  group  of  the  persons, use  one  itself  food-stuff, the  features  of  this  product, sanitary-hygienic  state  of  commercive  institutions, public  nutrition when  taking epidemiologic  data. It is  necessary  to  reveal  the  sick  men  or  bacteriocarries  among  personnel  of  these  institutions, because  they  may  be  a  source  of  infection  of  the  food.

Materials for bacterial examination are suspicious  food products, vomitory masses, water after irrigation of the stomach, stool  of the patient. Serological methods does not have independent meaning in  the  diagnostics.

Differential diagnosis

Differential diagnosis of toxical food infection is performed with acute intestinal infections (cholera; acute shigellosis; gastrointestinal form of yersiniosis; rotoviral gastroenteritis; campylobacteriosis; dyspeptic variants of  preicteric period of viral hepatitis and others), with surgical diseases (acute appendicitis; cholecystopancreatitis; thrombosis of mysentrical vessels; perforation of ulcers in the stomach  and  duodenum), with gynecological diseases (ectopic pregnancy; toxicosis of the pregnancy), with therapeutic diseases (myocardial infarction; hypertension crisis), with neurological diseases (acute damages of cranial blood circulation, subarachnoidal  hemorrhage), with urological diseases (pyelonephritis; acute renal insufficiency). During the diagnostics it is necessary  to consider the food poisoning; poisoning by mushrooms; salts of hard metals.

 

Treatment

It is necessary to wash out a stomach and intestine to release them from microbes and toxins as soon as possible. For a lavage it is better to use isotonic solution of  Sodium chloridum, boiled water or 1-2 %  solution of sodium  hydrocarbonate. Then give inside the activated microspherical coal (SKN brand). Alternative preparations are Sillard P, Smecta, Enterodes and other enterosorbents. Their early indication promotes the fastest improvement of  health state, preserves intoxication, development of the serious form of bacterial endotoxicosis. In case of development of infection-toxic shock we should immediately infuse in  blood colloid and cristaloid solutions: Polyglucin, Reopoliglycin, donor Albumin, Trisol, Acesol, Quartasol, and also glucocorticoides.

Etiotropic treatment is indicated only at serious forms with development of colitic syndrome: Furazolidon or Enteroseptol. Antibiotics are indicated in case of development of  sepsis – Levomycetin, Gentamicin, Ampicillin, Ofloxacin (Tarivid).

 

Prophylaxis

Prophylaxis  of  the  toxical  food  infection  is  concluded  in  prevention  of infection  of  the  food-stuff, of  the  reproduction  of  the  microorganisms  in  the  food. It  is  necessary  to  keep  the  food-stuffs  and  prepared  food  at  the  temperature  from  2  till  4 ºC.

The  mechanization  and  automatization  of  the  food  objects, the  elaboration  of  the  new  methods  of  the  preserving  and  storage  of  the  food-stuff, the  freezing  at  low  temperature  are  conductive  to  the  successful  prophylaxis  of  the  toxical  food  infection.