D IARRHEAL SYNDROME IN CLINIC OF INFECTIOUS DISEASES. CHOLERA

1. DIARRHEALSYNDROME INCLINIC OF INFECTIOUS DISEASES. CHOLERA

2. Diarrhea - more frequent bowel movement and stool dilution when during the day singleor repeated emptying of intestine from the liquid feces more than 300 ml happened

3. Actuality of diarrhea High incidence of diarrheal disease, which yield only the spread of ARI.The structure of infant mortality exceeds 30-50%.According to WHO, the world annually from 68.4 to 275 million diarrheal diseases.Expanding the palette of micro-organisms that cause diarrhea.Increasing the number of persons with immunodeficiency conditions, from which diarrhea is happened.Significant increasing of the population in different regions and poor water supply.

4. Actuality of diarrhea Diarrhea often occurs in travelers - in almost one third of people.   The spectrum of pathogens as follows: enterotoxin-UGI E. coli  40-60%, enteropatogenic E. coli  15%, enteroinvasive E. coli  5%  Shigella, Salmonella, Campylobacter, rotavirus, lamblia, amoeba - 5% unknown etiology - up to 40% of cases.

5. According to the WHO classification, all diarrheal diseases are divided into: 1. Infectious 2. Noninfectious

7. Agents of secretory diarrhea • V. cholerae • Clostridiumperfringens • Еnterotoxin and еnteropathogenic E. coli • B. cereus • S. aureus • occasionally –campylobacter,yersinia, klebsiella • Some simplest - cryptosporydia, microsporidia, balantydia, izospores

8. Enterotoxins stimulative depressors hyalinecyclase adenylcyclase phosphodiasterase ↑c GMP prostaglan- din ↑cAMP ↓ decay cAMP ↓absorption of electrolytes Activation of protein kinase ↑ fluid and electrolytes in the intestine secretion of electrolytes strengthening peristalsis diarrhea Pathogenesis of secretory diarrhoea

9. Secretory diarrhoea Great loss of fluid, which contains little protein, and a large number of K +, Na +, Cl-, HCO3-; Loss of K +, can be up to 1 / 3 of its content in the body, which leads to:          - Dysfunction of myocardium;          - Damage to kidney tubules;          - Paresis intestines;          - Convultions; Development of extracellular isotonic dehydration, hypovolemia with blood coagulation and a violation of microcirculation, tissue hypoxia, metabolic acidosis and respiratory alkalosis, failure of kidney function, liver infarction, trombohemorragic syndrome.

10. Agents of osmotic diarrhea Viruses: rota-, aden-, astro-, crown-, reo-, kalitsy-, Norfolk & Breda viruses and others. The simplest: lyamblia, coxydia. Also appear afterentering of excessive amounts of osmotic active substances that are not absorbed in the intestine (sulfate magnesite, lactulose, sorbitol, etc.), or in the formation of them due to significant malabsorption, as well as bacteria overgrowth.

11. Enterotropic viruses damage of epithelial cells of small bowel ↓activity К+/Nа+-АТphase ↓lactase ↓sucrase ↓transportation of Na, glucose to enterocytes ↓maltase ↑lactose ↑sucrose ↑ мaltose ↑osmotic pressure in intestine ↓absorption of fluids in intestine diarrhea Pathogenesis of osmoticdiarrhoea

12. Agents of invasive diarrhoea Bacteria: Shigella, Salmonella, and enteroinvasive enterohaemoragic escherichia, intestinal yersinia, campylobacter, clostrydia, staphylococci and some other enterobacteria, The simplest: lamblia, amoeba histolytica.

13. Agent Invasion of intestinal wall Inflammation ↑kinin ↑pg ↑ histamin ↑serotonin ↑cytokinin Violation of microcirculation ↑ Adenocyclase Increased peristalsis Damage of membranes Exudates with mucous and blood Diarrhea Pathogenesis of invasivediarrhoea

14. Secretory diarrhea. Clinical manifestations Acute beginingfrom the imperative (order) call for a bowel movement; liquid stool, watery, abundant (0,5-1 liters for defecation), without pathological impurities often turbidly with floating white flakes, like rice-water, have a weak smell of fresh fish or friction potatoes;

15. Secretory diarrhea. Clinical manifestations abdominal pain is not typical, may be slightly unpleasant aching sensation around the navel, which intensifies during defecation; abundant vomiting, repeated, often suddenly, without nausea, like a fountain; initially contains the remains of food, then - like rice broth; body temperature is often normal or subfebril, in significant dehydration - subnormal; diarrhea and vomiting lead to dehydration, which can reach the III-IV degree.

16. Degrees of Dehydration I - fluid loss 1-3%; II - 4-6%; III - 7-9%; IV - 10% of body weight and more

17. DEHYDRATIONAL SHOCK Develops with bacterial diarrhea, the clinical syndrome of gastroenteritis, caused by: cholera; salmonellosis (gastrointestinal form); escherichiosis caused by Enterotoxic and Enteropathogenic species;food poisoning caused by semipathogenic flora; staphylococcal toxicosis; intestinal yersiniosis.

18. Gastroenterocolitis Vomit,diarrhea Loss of isotonic fluids, electrolytes and alkali Decrease of Blood vol Disorders of systemic haemodynamics Metabolic acidosis Hypoxia Deficit of mackroergs Polysat lipids Electrolytic violations Polyorgan insufficiency Pathogenesis of hypovolemic shock

19. Dehydrational shock Diarrhea (watery or rice-water stool), without abdominal pain without fever Fountain vomiting without nausea Thirst Dehydration Forensic cyanosis. Wrinkled skin, gray and cold to the touch, a sharp decline in tissue elasticity and turgor pressure, "washerwoman hands”, symptom of glasses Voice hoarse, often aphonia Generalized convulsions Body temperature decreased Pulse filamentary 100-120 and> for 1 min. AT <80 and 50 mm Hg. Heart tones very weak activity often arrhythmic, Hyperventilation Anuria

20. Dehydrational shock Cholera, IV degree of dehydration. Skin easily taken in the fold, which is not elastic Dehydrational face of the patient

21. A child with IV degree dehydration Suffering from cholera, dehydration IV degree

22. Dehydrational shockLaboratory test Thickening of blood - pseudoerythrocytosis leukocytosis, increased hematocrit (0.55 l / l and more), blood viscosity, relative density plasma (1030 and older), protein, globulin Renal impairment - creatinine level in blood higher than 150 micromole / l A significant deficiency of electrolytes - (K +, Na +, Cl-, HCO3-) Uncompensated metabolic acidosis and respiratory hYpocapnia - (capillary blood pH 7,1-7,3 and often lower - rate 7,36-7,44, lack of buffer bases reaches 10-20 mmol / l - in normal 0,5 ± 2, 5)

23. Osmotic diarrhea Acute begining, more often - with vomiting and watery diarrhea; moderate general signs of intoxication; emptying abundant, watery, yellow or yellow-greenish color, frothy, with a sharp odor, undigested remnants of food (stearrhea, kreatoreya, amiloreya) without mucous and blood; short-term increase in body temperature; possible rhinitis, swelling of the tongue, mucous membrane hyperemia fauces and its granularity weak pain in epigastric and periumbilical areas, gross burburogmi at palpation in caecum ; blood count at the beginning without changes later - with relative leukopenia and limfotsytozom monotsytozom; incoprogramundigested food, starch grains, unaltered muscle fibers.

24. Invasive diarrhea Beginning with acute abdominal pain and diarrhea; dominant features of lesions of colon: tenesmus, sensation of incomplete evacuation, false call for defecation; stool scanty, containing only mucous with admixture of blood (rectal split); sigma painful, tight; expressed signs of intoxication; Sigmoidoscopy: catarrhal, catarrhal-hemorrhagic, erosive or ulcerative proctosigmoiditis and sphincteritis; leukocytosis, <eosinophiles count and ESR ↑; coproscopy - remains of undigested food additives and pathological - mucus accumulation of leukocytes with a predominance of neutrophils, many red blood cells and epithelial cells; Dehydration is not typical.

25. Rehydration therapy - restoration of electrolyte and water homeostasis.       - By the time of - the primary and compensatory      - By way of - parenteral and oral Treatment of secretory diarrhea

26. Solutions for parenteral rehydration • Trisault (Philips І) • Quartasault • Acesaultl • Chlosault • Lactosault • Disault (philips- ІІ) – without К+

27. Solutions for oral rehydration therapy (ORS) First generation - oralit (containing 3.5 g sodium chloride, 2.5 g sodium, 1.5 g potassium chloride and 20 g of glucose), glyucosolan, gastrolit and others. Second generation - rehidron, citroglyucosolan and others. - More potassium chloride, citrate instead of soda. Super-ORS (third generation) - ORS-200 (HIPP) - in which glucose-monohydrate replaced it short chain polymers contained in the broth cereals (rice, corn, sago), carrots, reduce the frequency and volume of stool.

28. Hypovolemic shock Intensive therapy «cholera» bed

29. Hypovolemic shockIntensive therapy • Rehydration is performed in the hospital in 2 stages: I(primary) - immediately by the infusions of standard saline solutions 3-4 IV amounting to 10% of body weight during 1 - 1,5 hour, the patient is placed on a "cholera" bed, carefully consider all the fluid loss • II (compensatory) - replenish lost fluids and electrolytes, which continues After stopping vomiting - combined adequate an IV and peroral standard rehydration salt solution - oralit, rehidron Causal treatment - doxacyclin

30. Principles of osmotic diarrhea therapy Rehydration Enzyme preparations Probiotics Enterosorbents In children (severe) - antiviral drugs (human and recombinant interferons)

31. Principles of invasive diarrhea therapy Etiotropic therapy:     - Chemotherapeutic drugs     - Antibiotics Desintoxication Spasmolithics Probiotics ReparantsLocal - adsorbents, anesthetics, reparants

32. Cholera – is a dangerous intestinal infection, that is caused by Vibrio cholerae and characterized by destruction of small intestine with diarrhea, vomiting and dehydration of organism

33. Drawing of Death bringing the cholera, in Le Petit Journal

34. By 12 February 2009, the number of cases of infection by cholera in sub-Saharan Africa had reached 128,548 and the number of fatalities, 4,053.

35. I pandemic – 1816-1826: Began in Bengal and then spread across India by 1820. II – 1829-1851: reached Russia, Hungary and Germany in 1831, London and Paris in 1832. III – 1852-1860: mainly affected Russia, with over a million deaths. IV – 1863-1875: spread mostly in Europe and Africa. V –1881-1896: was the last serious European outbreak. VI – 1899-1923: Russia, Ottoman Empire, Phulippines. VII –began in Indonesia, called El Tor after the strain and reached Bangladesh, India, USSR, North Africa.

36. Recent and ongoing outbreaks • In 2000, some 140,000 cholera cases were officially notified to WHO. • August 2007 – The cholera epidemic started in Orissa, India. Has affected Rayagada, Koraputand Kalahandi districts where more than 2,000 people have been admitted to hospitals. • August 2008 – April 2009: In Zimbabwean cholera outbreak, which is still continuing, an estimated 96,591 people have been infected and 4,201 deaths had been reported.

37. Reasons of danger • Rapid increasing of morbidity to epidemic and pandemic levels • Quarantine infection (according to International convention, 1926) • High lethality

38. Etiology Biovars - Vibrio classical, El-Tor Serovars-Ogava, Inaba, Hikojima,Bengal О-139 Toxic substances - exotoxin (cholerogen), penetration factor, endotoxin Morphology-gramnegative comma-shaped rod, motile, don’t produce capsules and spores

39. Epidemiology Sourse of infection – sick person,reconvalescent and vibrio-carrier(1:100) Mechanism of transmission –fecal- oral Susceptibility – high Seasonal – summer-autumn

40. Types of epidemics • Water (most frequent) • Food • Contact - domestic • Mixed

41. Features of VII pandemics of cholera: • Endemic area – Indonesia • Detection of V. cholerae (El-Tor) from reservoirs (water) before the beginning of epidemia • Obliterated and atypical forms more often • Lethality is low • Prolonged careering

42. Pathogenesis • Penetration into the organism • Adhesion to intestinal wall, multiplication (without destroying of epithelial cells and inflammation) • Exotoxin-cholerogen have activate adenylcyclase • Increasing production of cyclic-3-5-adenosynemonophosphates • Destroying of “natrium pump” • Increasing secretion of electrolytes and water • Dehydratation, demineralization • Hypovolemia, hemodynamics disorders • Tissue hypoxia, metabolic acidosis, respiratory alcalosis

43. Cholera Toxin. The delivery region (blue) binds membrane carbohydrates to get into cells. The toxic part (red) is activated inside the cell

44. Classification • Causative agents: V. cholerae O1 biovar cholerae (A00.0), V. cholerae O1 biovar El-Tor (A00.1), unspecified (A00.9) • Clinical forms: typical and atypical (mildest, gastric, in breast feeding childs and in elderly people) • Degree of severity in typical form:mild, moderate, severe, very severe • Degree of dehydration:without dehydration, with dehydration I, II, III, IV degrees • Complications:choleric algid, collapse, acute kidney insufficiency, pneumonia, abscess, phlegmon

45. Clinic features • Incubation period - from some hours till 5 days (in average 48 hours) • Acute onset • Diarrhea appears suddenly, without pain, often at night or in the morning. Often accompanied by gurgation in the stomach. After 1-2 defecation stool become cloudy, white, fluid, without smell and “rice-water” • Vomiting fountain

46. “Rice-water” character of stool in cholera

47. Clinical-epidemiological features of cholera • Beginning from diarrhea and vomiting • Development of dehydration • Accordance with epidemiologic agents • Colorless watery stool • Absence of abdominal pain and tenesmus • Decreasing of body temperature or normal

48. Cholera hospital in Dhaka

49. Diagnostics • Revealing ofcausative agent in stool, vomiting masses Express-methods(microscopy of “hanging” drop– form, mobility; reaction of immobilization; reaction of agglutinationant cholerae О-serum; reaction immune fluorescence) Inoculation to 1 % peptonic water with furtherreinoculation to Ressler medium • Determination of antibodies titer(retrospective) • Signs of blood thicken (pachyemia): increasing of erythrocyte number, leucocytes, hemoglobin; hematocrite, relative density of plasma; hypokalemia

50. Treatment • Regidration І (primary) - immediately i/vinfusion of salt solutions (Trisol, Acesolum, Lactasol, Quartasol, Hlosol) 10 % of primary patients weight in 1,5-2 hours (under the control of potassium and natrium acidic-alkali balance of blood); It is necessary to punct 3-4 vessels; put patient into“cholera” bed for carefully account of sequel loss of liquor ІІ (compensatory) –correction of sequel loss In case of І and ІІ degrees – adequate per oral regidration with standart salt solutions – оralit, regidron (І – 30 ml/kg, ІІ - 60–70 ml/kg) –in1,5 times higher than loss of liquor with obligatory addition of glucose Antibiotics - cotrimoxazole, erythromycin, doxycycline, chloramphenicol (levomycetin), furazolidone. Fluoroquinolones such as norfloxacin also may be used, but resistance has been reported.