1. Acute infectious diarrhea in children Ievtushenko V. O.O.Bogomolets National Medical University Chair of Children Infectious Diseases

2. Acute infectious diarrhea = acute intestinal infection Acute infectious diarrhea – group of infections of different etiology (viruses, bacteria, fungi, protozoa), with fecal-oral transmission and predominantly impairment of gastrointestinal tract.

3. Infectious diarrhea accounts for more than 2 million deaths annually and is associated with impaired physical and cognitive development in resource- limited countries (WHO) Infectious diarrhea takes third place in mortality structure in children younger 5 years (WHO)

4. Definition Diarrhea – an increased frequency of defecation or stool form changes (mushy or watery stool). Acute diarrhea – an episode that has an acute onset and lasts no longer than 14 days; chronic or persistent diarrhea is defined as an episode that lasts longer than 14 days (WHO).

5. Acute diarrhea 1.Noninfectious 2.Infectious 1)Invasive 2)Secretory

6. Noninfectious diarrhea Pancreatic exocrine function failure Endocrine dysfunctions (thyroid, suprarenal glands diseases) Bile acids insufficiency (cholestasia, postoperative) Intestinal enzymes deficiency (acquired or congenital) Noninfectious inflammation of intestine (allergic diseases, ulcerative colitis, Crohne disease, rheumatic diseases, tumor)

7. Noninfectious diarrhea (continuation) Intestinal motor dysfunction (irritable bowel syndrome, diet disorders) Autoimmune diseases Immunodeficiency (congenital or acquired) Malabsorption Medication intake (laxatives, antibiotics, antihistamines)

8. Infectious diarrhea 1.Secretory – diarrhea predominantly caused by functional disorders of small intestine (syn. watery diarrhea, noninflammatory diarrhea) 2.Invasive – caused by inflammation of small and/or large intestine (syn. bloody diarrhea, inflammatory diarrhea)

9. Diarrhoea Presense of inflammatory impurities in faeces (pus, pus-like mucus, blood) YesNo Invasive doarrhoeaSecretory diarrhoea

10. Etiology Secretory←Diarrhea→Invasive Viruses –Rotavirus –Adenovirus –Norovirus Bacteria –V. cholerae –EPEC –ETEC –EAgEC Protozoa –Cryptosporidium –Isospora –Cyclospora –Giardia lamblia Bacteria –Shigella –Salmonella –EIEC –EHEC –Campylobacter –Y. enterocolitica Protozoa –Entamoeba histolytica

11. Etiology (immunocompromised patients) Cytomegalovirus HSV Mycobacterium avium Criptosporidium Isospora Coccidia Candida

12. Etiologic structure of acute diarrhea in children <5 y.o. (Europa) Rotavirus10-35 % Norovirus2-20 Campylobacter4-13 Adenovirus2-10 Salmonella 5-8 Escherichia coli enteropathogenic (EPEC)1-4,5 Yersinia enterocolitica0,4-3 Lamblia Giardia0,9-3 Cryptosporidium0-3 Shigella 0,3-1,4 Escherichia coli enterotoxigenic (ETEC)0-0,5 Entamoeba histolytica0-4

13. Common causes of infectious diarrhea in children (Europa) < 1 yr1-4 yrs> 5 yrs Rotavirus Campylobacter Norovirus Salmonella Adenovirus Rotavirus Salmonella Campylobacter Yersinia

14. Clinical picture Local symptomatic Gastritis (stomach lining inflammation) Enteritis (small intestinum lining inflammation) Colitis (large intestinum lining inflammation) Symptoms of dehydration Toxic symptoms toxic encephalopathy

15. Local symptomatic Gastritis – nausea, repeated vomiting, pain in upper abdomen Enteritis – nonlocalized pain, flatulence, watery large-volume stool Colitis - urgency, painful defecation, frequent small-volume stool, blood and pus-like mucus in feces

16. Pathophysiology of Diarrhoea WHY DOES IT OCCUR?

17. Osmotic diarrhoea If excessive amounts of solutes are retained in the intestinal lumen, water will not be absorbed and diarrhoea will result. May be caused by Ingestion of a poorly absorbed substrate (mannitol, sorbitol, MgSO4 and some antacids) Inability to absorb certain substances (malabsorption)

18. Secretory diarrhea Occurs when secretion of water into the intestinal lumen exceeds absorption. Caused by Exposure to toxins from several types of bacteria (e.g. E. coli, Vibrio cholerae) Action of certain substances (some laxatives, some types of asthma medications, antidepressants, cardiac drugs, certain metals, organic toxins, arsenic, insecticides, mushroom toxins, caffeine)

19. Inflammatory diarrhea Occurs when microbial or viral pathogens disrupt the epithelium of the intestine that results in exudation of serum and blood into the intestinal lumen and inefficiency of digestion and absorbtion. Examples of pathogens frequently associated with infectious diarrhea include: Bacteria (Salmonella, E. coli, Campylobacter), Viruses (rotaviruses, coronaviruses, parvoviruses, norovirus), Protozoa (coccidia species, Cryptosporium, Giardia)

20. Dehydration Weight loss Age 5 yo Mild≤5%<3% Moderate6-9%4-6% Severe≥10%>6%

21. Clinical symptoms of dehydration Mild (3-5%) Moderate (5-10%) Severe (>10%) General Alert Restless, Irritable Lethargic Blood PressureNormalNormalNormal/ decreased Quality of PulseNormalNormal, Moderately slightly decreaseddecreased Heart RateNormalIncreasedIncreased Skin TurgorNormalDecreasedDecreased FontanelleNormalSunkenSunken Mucus membranesSlightly dry DryDry EyesNormalSunkenDeeply sunken ExtremitiesWarm, normal DelayedCool, mottled cap refillcap refill Urine OutputSlightly< 1 ml/kg/hr<< 1 ml/kg/hr decreased ThirstSlightly Moderately Increased/ increasedincreaseddecreased

25. Encephalopathy CNS symptoms associated with brain edema and may include: Severe headache Lethargy Meningismus Delirium Convulsions Coma

27. Shigellosis Genus Shigella is grouped into 4 species: Shigella dysenteriae (group A) Shigella flexneri (group B) Shigella boydii (group C) Shigella sonnei (group D)

28. Shigellosis Symptoms include the following: Sudden onset High-grade fever Emesis Anorexia Abdominal pain (commonly left lower quadrant) Tenesmus Seizures (may be an early manifestation) Large-volume watery diarrhea quickly becomes small-volume with purulent mucus and blood (colitis)

29. Salmonellosis Gastrointestinal diseases in humans (Nontyphoidal Salmonella infections) mostly caused by two serotypes: S. Enteritidis (S. enterica serotype Enteritidis) S. Typhimurium (S. enterica serotype Typhimurium)

30. Salmonellosis Common symptoms: Abrupt onset Nausea and vomiting Crampy abdominal pain (primarily in the periumbilical area and right lower quadrant) Liver enlargement Large-volume watery diarrhea (sometimes with blood and dark-green mucus)

31. Yersinia enterocolitica Symptoms Fever Abdominal pain (commonly right lower quadrant) Mesenteric lymphadenitis (may mimic appendicitis) Diarrhea (enterocolitis). Stools may be watery and/or contain leukocytes and sometimes frank blood and mucus Liver enlargement Rash (may be scarlet fever-like), socks and gloves symptom Arthralgia

32. Escherichia coli 5 major groups of diarrheagenic E. coli have been characterized on the basis of clinical, biochemical, and molecular-genetic criteria: 1)enterotoxigenic E. coli (ETEC); 2)enteroinvasive E. coli (EIEC); 3)enteropathogenic E. coli (EPEC); 4)Shiga toxin–producing E. coli (STEC), also known as enterohemorrhagic E. coli (EHEC) or verotoxin producing E. coli (VTEC); 5)enteroaggregative E. coli (EAEC)

33. Escherichia coli Secretory diarrheaInvasive diarrhea EPECEIEC ETECEHEC EAEC

34. Viral diarrhea Common enteropathogenic viruses: Rotaviruses Noroviruses (Norwalk virus) Adenoviruses Caliciviruses Astroviruses

35. Viral diarrhea Clinical picture Abrupt onset Nausea, repeat vomiting Large-volume watery diarrhea Catarrhal symptoms may be presence

36. Laboratory Studies Stool culture (urine, blood, bile culture if generalized course suspected) Serologic tests (revealing of specific antibody in blood) Antigen detection (used for detection of viral antigen in stool) Blood chemistry (if dehydration or toxic symptoms expressed) Fecal leukocytes and erythrocytes (microscopy)

37. Methods of therapy 1.Rehydration therapy 2.Antibacterial treatment 3.Additional therapy 4.Diet

38. Rehydration therapy Rehydration used in all patients with infectious diarrhea. Rehydration Oral rehydration therapy (ORT) Parenteral (intravenous, IV) rehydration therapy

39. Rehydration therapy Oral rehydration therapy (ORT) is appropriate for patients with mild and moderate dehydration. Compared to IV rehydration, ORT is safer, less costly, and able to be administered in various clinical settings. Oral rehydration solutions (ORS) should contain 45-90 mmol/L of sodium and 74-140 mmol/L of glucose. Acceptable, commercially available ORS include: Rehydron, Naturalyte, Pedialyte, Infalyte, Rehydralyte, WHO Oral Rehydration Salts, and Pediatric Electrolytes.

40. Rehydration therapy Children with severe dehydration should receive fluids IV. Those unable or unwilling to drink or who have repetitive vomiting can receive fluid replacement IV, through an NGT, or sometimes orally through frequently repeated small amounts. For IV therapy used 0.9% or 0.45% Saline, 5% Glucose solutions, Ringer’s solution.

41. Rehydration therapy Volume (daily amount) = Maintenance (base) + Deficit + Ongoing losses

42. Rehydration therapy Maintenance volume Body weightFluid per day 0–10 kg 100 mL/kg 11–20 kg 1,000 mL + 50 mL/kg for each kg > 10 kg >20 kg 1,500 mL + 20 mL/kg for each kg > 20 kg

43. Rehydration therapy Ongoing losses: Diarrhoea – 25-75ml/kg/day Vomiting – 20 ml/kg/day Fever – 10ml/kg Tachipnea – 30 ml/kg/day

44. Rehydration therapy Example: 11-months-old boy (weight – 10 kg) with moderate dehydration. Diarrhea – up to 8 times/day, vomiting – 4 times/day. Deficit: 10kg x 10% = 1kg (1000ml) Base: 100ml/kg x 10kg = 1000ml Ongoing losses: 50ml/kg x 10kg = 500ml 20ml/kg x 10kg = 200ml Volume = 1000ml+1000ml+500ml+200ml=2700ml

45. Antibacterial treatment Indications: Moderate or severe course of invasive diarrhea Moderate or severe course of secretory diarrhea in children under 6 mnth Children under 3 months, immunocompromised children independently of severity of diarrhea Stool with frank blood Bacterial complications

46. Antibacterial treatment Drug of choice for treatment of invasive diarrhea: Azithromycin 10 mg/kg/day (orally) or Ceftriaxone 50-100 mg/kg/day (IV)

47. Additional therapy Zinc (20 mg/day for 14 days) – especially for Shigellosis (not available in Ukraine) Probiotics (lacto-, bifidumbacteria, saccharomyces) Prebiotics (e.g. lactulose) Antidiarrheal drugs (e.g. diosmectite)