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Acute Diarrhea Session 20.2 Internal Medicine Pediatrics

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1 Acute Diarrhea Session 20.2 Internal Medicine Pediatrics
Infectious diseases Gastroenterology Pediatrics Family Medicine Pharmacology O&G Radiology Session 20.2

2 Introduction Spectrum of acute infective diarrhea
Mild annoyances to Devastating dehydration Attack rates in children < 5y Developed countries: illnesses per child per year Developing countries: illnesses per child per year

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4 Acute Diarrhea Case 1

5 Case -1 A 26 year old man complains of severe abdominal cramps, nausea, vomiting and diarrhoea for the last 12 hours. He attended a party the night before he became ill. Benadering Geskiedenis Ondersoek Samevatting (Problem list) Hantering

6 What do you want to know from the history?
Suspected food? Time of ingestion Duration and frequency of diarrhoea Presence of blood in stools Abdominal pain Tenesmus Fever Current problem list Acute food poisoning with predominant vomiting Differential diagnosis Staph. Aureus Bacillus cereus Clostridium perfringens

7 Definition Acute diarrhea Abnormally increased
frequency or decreased consistency of stools < 2 weeks (< 3 weeks)

8 Causes of acute diarrhea (Table 1.25; p 37 - Davidson’s)
Infectious agents Non inflammatory (Toxin mediated) Inflammatory Enteroviruses (Rota) Campylobacter Salmonellae Shigella E Coli EIEC, EHEC etc. Cl difficile Parasites Giardiasis Amebiasis Non- Infectious GIT Diverticulitis IBD Metabolic Ketosis VIP Carcinoid syndrome Uremia Generalised illness Sepsis (meninigococ) Pneumonia (atypical) Malaria Drugs

9 Drugs that commonly course diarrhea
GIT Mg++ containing antacids Laxatives Misoprostol CVS Digoxin Quinidine / Procainamid B-blockers ACE Hypolipidemic agents Antibiotics Erythromycin Amox-clav CNS Lithium Valproic acid Fluoxitine Other Theophylline Thyroid hormone Colchicine NSAIDS

10 History Toxin Infectious Incubation period Incubation period
< 12 hours Fever - NO Blood or mucus - NO fecal leukocytes - NO Infectious Incubation period hours Fever - YES Blood or mucus- YES Fecal leucocytes - YES

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12 Examination General Dehydration Weight and BMI
Mild: Thirst, dry mouth, dry axilla, decrease urine output Moderate: Orthostatic hypotension, skin tenting, sunken eyes Severe: Hypotension, tachycardia, confusion, shock Weight and BMI Jaundice, anemia, cyanosis, clubbing, lymph nodes, edema Nutritional status Other signs of underlying disease HIV / AIDS, DM etc.

13 Management - and explanation
What is food poisoning? How did I contract the disease? Is it contagious? Diagnostic investigations Treatment Prognosis General advise - Davidson – Table 1.25

14 Toxin mediated food poisoning
It is NOT an infection DO NOT GIVE ANTIBIOTICS It is a toxemia associated with the ingestion of preformed microbial toxins symptomology occurs rapidly usually within 2-12 hours toxins either affect the intestine (enterotoxin of C. perfringens) or the central nervous system (neurotoxin of C. botulinum) or both (S. aureus and B. cereus)

15 S.aureus toxin exotoxins produced by chromosomal genes
5 distinct antigenic types (A, B, C, D, E) water-soluble, low molecular weight proteins heat stable (resist boiling for 30 minutes) mode of action is unknown enteric effect (diarrhea) + neurologic effect (vomiting)

16 Clinical symptoms S. aureus
Incubation period 1-4 hours after ingestion of contaminated food (generally mayonnaise or dairy products) Vomiting (often projectile) Diarrhea (little or sometimes no ) no fever

17 B. cereus toxin In meat the enterotoxin is formed
stimulate cAMP and cause fluid accumulation in the intestine profuse diarrhea with a little vomiting 10-14 hours after ingestion In rice or pasta the neurotoxin is formed vomiting 2-3 hours after ingestion (?mechanism) little diarrhea no fever

18 C. perfringens toxin heat-labile protein (34000 mw) profuse diarrhea
inhibits glucose transport in intestinal epithelial cells damages the intestinal epithelium and causes protein loss into GI lumen activity is maximal in the ileum and minimal in the duodenum profuse diarrhea +/- 12 hours after ingestion of meat little or no vomiting no fever

19 C. botulinum toxin 8 antigenic types (A, B, C1, C2, D, E, F, G)
Types A, B, E, F and G are coded by chromosomal genes. C1 and D are coded by phage genes that are lysogenic in C. botulinum. Types A, B and E cause almost all human botulism. All toxins are proteins of 150,000 molecular weight prevent release of acetylcholine at the neuro-muscular junction causing a flaccid paralysis

20 C. botulinum Incubation period symmetric impairment of cranial nerves
6 hours to 8 days after ingestion of green beans, peppers, chili or sausage. a function of the amount and antigenic type of toxin ingested symmetric impairment of cranial nerves followed in a descending pattern by weakness or paralysis of the muscles of the extremities and trunk

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22 physical examination C. botulinum
No fever ophthalmoplegia and ptosis of the eyelids are usually prominent decreased gag reflex facial weakness Mental status and deep tendon reflexes are normal Characteristic EMG findings Nerve conduction studies, blood cell counts, urinalysis, serum electrolytes, cerebrospinal fluid and blood enzymes are normal.

23 Diagnosis C. botulinum Other toxemias Presumptive diagnosis A history
are not severe and symptoms generally disappear within 24 hours Presumptive diagnosis by the presence of a rapidly descending paralysis A history ingestion of home canned food or honey Confirmative diagnosis botulinal toxin in the patients serum or feces or in incriminated food using a mouse toxin-neutralization test

24 Differential diagnosis C. botulinum
Guillain-Barré syndrome ascending paralysis, paresthesias or other sensory abnormalities, elevated CSF protein, a history of an antecedent viral infection Myasthenia gravis descending paralysis, muscle fatigability, response to endrophomium Other food poisonings and gastroenteritis no cranial nerve involvement Chemical (non-microbial) food poisonings symptoms occur within minutes of ingestion

25 Treatment C. botulinum replenishment of fluids and electrolytes
? botulism admit to ICU monitoring of respiratory and cardiac function Airway patency should be guaranteed ET tube or tracheostomy before bulbar or respiratory impairment becomes severe.

26 Treatment C. botulinum Induction of vomiting or gastric lavage
if exposure has occurred within several hours purgation unless there is paralytic ileus even after several days, to facilitate possible elimination of unabsorbed toxin from the gastrointestinal tract alternately, high enemas may be used

27 Treatment C. botulinum Injectable therapeutics sometimes used include:
Trivalent (ABE) equine-origin botulinal antitoxin to neutralize unabsorbed toxin. Guanidine hydrochloride to increase release of acetylcholine from nerve terminals. 4-aminopyridine to increase release of acetylcholine. Several years ago it was recognized the C. botulinum could colonize the gastrointestinal tract of the infant. C. botulinum spores in honey used to sweeten infants milk or water, when ingested, geminate in the infants intestinal tract, colonize it and produce toxin in vivo. Constipation is the first sign of disease; this is followed by the same neurological signs seen in the adult. Antibiotics are generally not effective and may exacerbate the illness by elimination of normal flora. Therapy is the same as for adult botulism except that antitoxin is generally not used because the disease is milder in children.

28 ANTIEMETICS Domperidone Less selective dopamine blockers
is a dopamine blocker selective for the CETZ Less selective dopamine blockers Metoclopramide Promethazine (Aterax® 25 mg 4-6 hourly) Neuroleptics such as prochlorperazine (Stemetil®) initially 20 mg, followed by 10 mg 2 hours later if necessary Avoid in children under 2 years, or weighing less than 10 kg

29 Phosphorated carbohydrate Emetrol® Also: Emex®
solution, sucrose 3.77 g, phosphoric acid g/5 mL Adult dose: Undiluted, mL as required. Paediatric dose: 5-10 mL as required (10-15 minutes before feeds for vomiting and regurgitation in infants).

30 Vomifene® tablets buclizine HCl 25 mg, pyridoxine 50 mg Adult dose: 1-2 tablets 3 times daily

31 Cyclizine Valoid® piperazine-type antihistamine used to prevent and treat motion sickness, vertigo, nausea and vomiting caused by labyrinthine disorders (including Meniere's disease), and by other conditions. less sedative than promethazine, although individual variation in its sedative and anticholinergic effects is common.

32 Serotonin (5HT3) antagonists
ondansetron, granisetron and tropisetron control of nausea and vomiting induced by chemotherapeutic agents Chemotherapeutic agents and radiotherapy may cause release of 5HT in the small intestine thus activating vagal afferents, which in turn may cause release of 5HT in the area prostrema of the fourth ventricle resulting in vomiting

33 Acute Diarrhea continue Case 2

34 Case– 2 ‘n 40 jarige MIV positiewe dame Benadering Koors
Bloederige diaree Dehidrasie Benadering Geskiedenis Ondersoek Samevatting (Problem list) Hantering

35 History Assess severity Problem list Differential diagnosis
Dehydration Assess severity Infectious diarrhea Fever Bloody stools Immune-compromised ?CD4 Differential diagnosis Enteric viruses Bacteria Campylobacter Shigella Non-typhoid salmonellae Entero-invasive E. coli Enterohaemorrhagic E.coli (EHEC / VTEC) Cl. Difficile Parasites E. Histolytica Cryptosporidium

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39 Treating infective diarrhea
1.) Maintaining or correcting hydration and electrolyte loss: Home made oral hydration fluid 1 litre of clean or boiled water 5 teaspoons of sugar ½ teaspoon of salt Take 1 – 2 cups of this fluid or more, after every diarrhoeal stool

40 Diarrhoeal disease 2.) First line treatment for
uncomplicated diarrhoea: TMP-SMX (BactrimR, SeptranR etc.) 2 tablets 2 X per day for 5 to 7 days + Flagyll mg 3 x per day for 5 to 7 days

41 Diarrhoeal disease 3.) Symptomatic treatment: Codeine phosphate
10mg q 6 – 8 hourly or Loperamide (ImodiumR) 2 tabs stat, then 1 tab after each loose stool to a maximum of 4 tabs per 24 hours only if the patient does not have: fever of > 380C severe abdominal pain or bloody stools

42 Diphenoxylate (2,5mg) + Atropine (0,025mg) Lomotil®
Opiate like constipating effects Drowsiness, Anticholinergic symptoms Avoid Severe liver disease Pseudomembraneous EC Infectious diarrhea (<2y) IBD _ Toxic megacolon

43 Loperamide - Imodium® 2 mg tablets Structurally related to pethidine
4mg stat then 2mg after each loose stool Structurally related to pethidine Binding to opiate receptors CI – same as for lomotil Well tolerated Dry mouth, blurred vision

44 When to refer a patient with diarrhoea to hospital?
Severe dehydration or unable to take oral rehydration fluid (e.g. due to persistent vomiting or unable to swallow because of weakness or to painful to swallow) Fever > 380C Severe abdominal cramps or pain Bloody diarrhoea Diarrhoea not responding to first line therapy within 5 days Persistent diarrhoea or diarrhoea lasting for > 3 weeks

45 Acute Infectious diarrhea in AIDS
Enteric viruses Adenovirus, astrovirus, picornavirus, calcivirus 15 – 30% Most labs cannot detect these virusses Watery diarrhea, acute 1/3 become chronic Any CD4 Supportive treatment

46 Acute Infectious diarrhea in AIDS
Non Typhi- Salmonella 5-15% Watery diarrhea, fever, variable fecal WBCs Any CD4 count Stool + Blood cultures TMP-SMX (1 DS b.d x 14 days) or Ciprofloxacin or 3rd gen Cephalopsporin May need to be extended for > 4 weeks

47 Salmonellae gram- bacilli, facultative anaerobic
members of the enterobacteriaceae may persist within the RES motile with flagellae non-encapsulated except for S typhi and S paratyphi C both of which express the Vi Ag flagellae O Ag Vi Ag

48 Salmonellae H Ag – serotype O Ag = LPS / endotoxin H Ag Group (A-E)
Lipid A = biologically active component Toxic to cells Group (A-E) hypersensitivity reactions fever, leucopenia, hypotension, DIC, death Vi Ag – virulence or invasiveness H Ag O Ag Vi Ag

49 Serotype (O + H Ag) Gastroenteritis Enteric fever
> 2200 different organisms S. enteritidis + S. typhimurium Distributed throughout the animal kingdom Contaminated food or water poultry, eggs, fast foods may persist for months in cheese, frozen meat, or ice cream Enteric fever S typhi S paratyphi A B - scottmuleri C - hitchfeldi Purely human pathogens

50 symptomatic infection is influenced by
number of organisms >104 to 106 : higher rates of illness + shorter IP even 5 to 100 organisms may cause disease in susceptible hosts Asymptomatic excretion may occur Water supplies are contaminated at lower levels than food serotype intrinsic virulence factors host immune response antibiotic use achlorhydric states, gastric surgery and antacids or H2 blockers or PPI’s ·        Salmonellae that survive passage through the stomach must then compete with the normal intestinal microbial flora (an important but often overlooked barrier to infection) o       mouse studies performed showed that a single injection of streptomycin reduced the oral infectious dose of Salmonella typhimurium by over 100,000-fold. ·        Prophylactic antimicrobial therapy increases the frequency of salmonellosis among travelers

51 Other host factors Cell-mediated immunity polymorphonuclear leukocytes
glucocorticoids , AIDS , and malignancy polymorphonuclear leukocytes sickle cell anemia, malaria , schistosomiasis, and histoplasmosis humoral immunity

52 Acute Infectious diarrhea in AIDS
Shigella 1-3% Watery diarrhea or bloody Fever, fecal WBCs is common Any CD4 count Stool culture TMP-SMX (1 DS x 3 days) ciprofloxacin

53 Acute Infectious diarrhea in AIDS
Campylobacter jejuni 4-8% Watery diarrhea or bloody Fever, +/- fecal WBCs Any CD4 Stool culture Erythromycin 500 mg qid x 5 days

54 Acute Infectious diarrhea in AIDS
Idiopathic Variable non infectious causes Rule out medication Dietary IBS Any CD4 Negative studies Stool + blood culture, O+P, neg C difficili toxin If severe Ciprofoxacin +/- metronidazole

55 Acute Infectious diarrhea in AIDS
Clostridium difficile 10-15% Watery diarrhea, +/- WBCs, Fever, leucocytosis, Previous AB: Clindamycin, Ampi, cephalosp Any CD4 Stool toxin Endoscopy CT scan Colitis with thickened mucosa Metronidazole: 400mg tds x 10 –14 days or Vancomycin po Antiperistaltic agents are contraindicated

56 Pseudomembraneous enterocolitis
normal mucosa is replaced by pseudomembranous plaques of fibrin, cellular debris, and neutrophils If normal intestinal flora is altered, colonization by toxigenic C. difficile can occur

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58 Novel treatment for toxigenic C. difficile
Immunoglobulins "probiotics" nontoxigenic C. difficile Lactobacillus GG "bacteriotherapy" with enemas using normal stool flora or other bacteria Saccharomyces boulardii a nonpathogenic yeast partial to total colectomy sepsis and toxic megacolon or ileus The prevention of C. difficile requires the reduction of antibiotic-associated disease by minimizing high dosage, long-term, or combination antibiotic therapy. Reducing disease transmission depends upon isolation of carriers and symptomatic infected patients and minimization of patient-to-patient transmission. Disinfection of all colonoscopy equipment in 2% alkaline glutaraldehyde for 20 minutes destroys clostridial spores

59 Diagnostic approach

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61 Fecal WBCs or lactoferin
Invasive colitis Shigella Campylobacter C difficile EHEC

62 Chronic Infectious diarrhea in AIDS
Cryptosporidium Entamoeba Hystolitica Giardia Lamblia CMV Mycobacterium avium complex Microporidia Isopora belli Idiopathic

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67 Acute Diarrhea continue Case 3

68 Case 3 50 jarige man Vorige gastrektomie
Terug van ‘n reis na Indië (Suid Afrika) Malaise, anoreksie, delirium Hoe koors, hoofpyn Buikpyn Geringe diaree (hardlywigheid)

69 p57 Davidson Typhoid fever = SEPTICAEMIA Enteric fever
or paratyphoid fever = SEPTICAEMIA SYSTEMIC INVASIVE INFECTION


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