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Acute Diarrhea Session 20.2 Internal Medicine – Infectious diseases – Gastroenterology Pediatrics Family Medicine Pharmacology O&G Radiology Introduction Spectrum of acute infective diarrhea Mild annoyances to Devastating dehydration Attack rates in children < 5y Developed countries: 2-3 illnesses per child per year Developing countries: 10-18 illnesses per child per year Acute Diarrhea Case 1 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 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 Definition Acute diarrhea • Abnormally increased – frequency or – decreased consistency of stools • < 2 weeks (< 3 weeks) 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 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 History • Toxin • Infectious – Incubation period – Incubation period • < 12 hours – Fever - NO – Blood or mucus - NO – fecal leukocytes - NO • 24 - 72 hours – Fever - YES – Blood or mucus- YES – Fecal leucocytes - YES Examination • General – Dehydration • 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. Management and explanation • • • • • • • What is food poisoning? How did I contract the disease? Is it contagious? Diagnostic investigations Treatment Prognosis - Davidson – Table 1.25 General advise 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) 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) 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 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 C. perfringens toxin • heat-labile protein (34000 mw) – 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 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 C. botulinum • Incubation period – 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 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. Diagnosis C. botulinum • Other toxemias – 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 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 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. 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 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. ANTIEMETICS • Domperidone – is a dopamine blocker selective for the CETZ • Less selective dopamine blockers – Metoclopramide – Promethazine (Aterax® – Neuroleptics 25 mg 4-6 hourly) • 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 • Phosphorated carbohydrate Emetrol® Also: Emex® • solution, sucrose 3.77 g, phosphoric acid 0.025 g/5 mL Adult dose: Undiluted, 10-20 mL as required. Paediatric dose: 5-10 mL as required (10-15 minutes before feeds for vomiting and regurgitation in infants). • Vomifene® tablets – buclizine HCl 25 mg, pyridoxine 50 mg Adult dose: 1-2 tablets 3 times daily 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. 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 Acute Diarrhea continue Case 2 Case– 2 • ‘n 40 jarige MIV positiewe dame – Koors – Bloederige diaree – Dehidrasie • Benadering – – – – Geskiedenis Ondersoek Samevatting (Problem list) Hantering History • Problem list – 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 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 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 200 - 400mg 3 x per day for 5 to 7 days 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 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 Loperamide - Imodium® • 2 mg tablets – 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 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 Acute Infectious diarrhea in AIDS 1. 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 Acute Infectious diarrhea in AIDS 2. 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 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 Salmonellae • H Ag – serotype H Ag • O Ag = LPS / endotoxin – Lipid A = biologically active component – Toxic to cells – Group (A-E) – hypersensitivity reactions – fever, leucopenia, hypotension, DIC, death O Ag Vi Ag • Vi Ag – virulence or invasiveness Serotype (O + H Ag) • Gastroenteritis – > 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 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 Other host factors • Cell-mediated immunity – glucocorticoids , AIDS , and malignancy • polymorphonuclear leukocytes – sickle cell anemia, malaria , schistosomiasis, and histoplasmosis • humoral immunity Acute Infectious diarrhea in AIDS 3. 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 Acute Infectious diarrhea in AIDS 4. Campylobacter jejuni • • • • • • 4-8% Watery diarrhea or bloody Fever, +/- fecal WBCs Any CD4 Stool culture Erythromycin 500 mg qid x 5 days Acute Infectious diarrhea in AIDS 5. Idiopathic – Variable non infectious causes • • • – – Any CD4 Negative studies • – Rule out medication Dietary IBS Stool + blood culture, O+P, neg C difficili toxin If severe • Ciprofoxacin +/- metronidazole Acute Infectious diarrhea in AIDS 6. Clostridium difficile • • • • • • • 10-15% Watery diarrhea, +/- WBCs, Fever, leucocytosis, Previous AB: Clindamycin, Ampi, cephalosp Any CD4 Stool toxin Endoscopy CT scan • • Metronidazole: 400mg tds x 10 –14 days • • Colitis with thickened mucosa or Vancomycin po Antiperistaltic agents are contraindicated Pseudomembraneous enterocolitis normal mucosa is replaced by pseudomemb ranous plaques of fibrin, cellular debris, and neutrophils If normal intestinal flora is altered, colonization by toxigenic C. difficile can occur 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 Diagnostic approach Fecal WBCs or lactoferin Invasive colitis • Shigella • Campylobacter • C difficile • EHEC Chronic Infectious diarrhea in AIDS • • • • Cryptosporidium Entamoeba Hystolitica Giardia Lamblia CMV Mycobacterium avium complex • Microporidia • Isopora belli • Idiopathic Acute Diarrhea continue Case 3 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) p57 Davidson Typhoid fever Enteric fever or paratyphoid fever = SEPTICAEMIA SYSTEMIC INVASIVE INFECTION