2Introduction Spectrum of acute infective diarrhea Mild annoyances to Devastating dehydrationAttack rates in children < 5yDeveloped countries: illnesses per child per yearDeveloping countries: illnesses per child per year
5Case -1A 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.BenaderingGeskiedenisOndersoekSamevatting (Problem list)Hantering
6What do you want to know from the history? Suspected food?Time of ingestionDuration and frequency of diarrhoeaPresence of blood in stoolsAbdominal painTenesmusFeverCurrent problem listAcute food poisoning with predominant vomitingDifferential diagnosisStaph. AureusBacillus cereusClostridium perfringens
7Definition Acute diarrhea Abnormally increased frequency ordecreased consistency of stools< 2 weeks (< 3 weeks)
12Examination General Dehydration Weight and BMI Mild: Thirst, dry mouth, dry axilla, decrease urine outputModerate: Orthostatic hypotension, skin tenting, sunken eyesSevere: Hypotension, tachycardia, confusion, shockWeight and BMIJaundice, anemia, cyanosis, clubbing, lymph nodes, edemaNutritional statusOther signs of underlying diseaseHIV / AIDS, DM etc.
13Management - and explanation What is food poisoning?How did I contract the disease?Is it contagious?Diagnostic investigationsTreatmentPrognosisGeneral advise- Davidson – Table 1.25
14Toxin mediated food poisoning It is NOT an infectionDO NOT GIVE ANTIBIOTICSIt is a toxemia associated with the ingestion of preformed microbial toxinssymptomology occurs rapidlyusually within 2-12 hourstoxins either affectthe intestine (enterotoxin of C. perfringens)or the central nervous system (neurotoxin of C. botulinum)or both (S. aureus and B. cereus)
15S.aureus toxin exotoxins produced by chromosomal genes 5 distinct antigenic types (A, B, C, D, E)water-soluble, low molecular weight proteinsheat stable (resist boiling for 30 minutes)mode of action is unknownenteric effect (diarrhea) +neurologic effect (vomiting)
16Clinical symptoms S. aureus Incubation period1-4 hours after ingestion of contaminated food (generally mayonnaise or dairy products)Vomiting (often projectile)Diarrhea (little or sometimes no )no fever
17B. cereus toxin In meat the enterotoxin is formed stimulate cAMP and cause fluid accumulation in the intestineprofuse diarrhea with a little vomiting10-14 hours after ingestionIn rice or pasta the neurotoxin is formedvomiting2-3 hours after ingestion (?mechanism)little diarrheano fever
18C. perfringens toxin heat-labile protein (34000 mw) profuse diarrhea inhibits glucose transport in intestinal epithelial cellsdamages the intestinal epithelium and causes protein loss into GI lumenactivity is maximal in the ileum and minimal in the duodenumprofuse diarrhea+/- 12 hours after ingestion of meatlittle or no vomitingno fever
19C. 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 weightprevent release of acetylcholine at the neuro-muscular junction causing a flaccid paralysis
20C. 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 ingestedsymmetric impairment of cranial nervesfollowed in a descending pattern by weakness or paralysis of the muscles of the extremities and trunk
22physical examination C. botulinum No feverophthalmoplegia and ptosis of the eyelids are usually prominentdecreased gag reflexfacial weaknessMental status and deep tendon reflexes are normalCharacteristic EMG findingsNerve conduction studies, blood cell counts, urinalysis, serum electrolytes, cerebrospinal fluid and blood enzymes are normal.
23Diagnosis C. botulinum Other toxemias Presumptive diagnosis A history are not severe and symptoms generally disappear within 24 hoursPresumptive diagnosisby the presence of a rapidly descending paralysisA historyingestion of home canned food or honeyConfirmative diagnosisbotulinal toxin in the patients serum or feces orin incriminated food using a mouse toxin-neutralization test
24Differential diagnosis C. botulinum Guillain-Barré syndromeascending paralysis, paresthesias or other sensory abnormalities, elevated CSF protein, a history of an antecedent viral infectionMyasthenia gravisdescending paralysis, muscle fatigability, response to endrophomiumOther food poisonings and gastroenteritisno cranial nerve involvementChemical (non-microbial) food poisoningssymptoms occur within minutes of ingestion
25Treatment C. botulinum replenishment of fluids and electrolytes ? botulismadmit to ICUmonitoring of respiratory and cardiac functionAirway patency should be guaranteedET tube or tracheostomybefore bulbar or respiratory impairment becomes severe.
26Treatment C. botulinum Induction of vomiting or gastric lavage if exposure has occurred within several hourspurgationunless there is paralytic ileuseven after several days, to facilitate possible elimination of unabsorbed toxin from the gastrointestinal tractalternately, high enemas may be used
27Treatment 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. botulinumspores in honey used to sweeten infants milk or water, when ingested, geminate in the infants intestinal tract, colonize it andproduce 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 foradult botulism except that antitoxin is generally not used because the disease is milder in children.
28ANTIEMETICS Domperidone Less selective dopamine blockers is a dopamine blocker selective for the CETZLess selective dopamine blockersMetoclopramidePromethazine (Aterax® 25 mg 4-6 hourly)Neurolepticssuch as prochlorperazine (Stemetil®)initially 20 mg, followed by 10 mg 2 hours later if necessaryAvoid in children under 2 years, or weighing less than 10 kg
29Phosphorated 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).
31Cyclizine 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.
32Serotonin (5HT3) antagonists ondansetron, granisetron and tropisetroncontrol of nausea and vomiting induced by chemotherapeutic agentsChemotherapeutic agents and radiotherapy may cause release of 5HT in the small intestinethus activating vagal afferents, which in turn may cause release of 5HT in the area prostrema of the fourth ventricle resulting in vomiting
39Treating infective diarrhea 1.) Maintaining or correcting hydration andelectrolyte loss:Home made oral hydration fluid1 litre of clean or boiled water5 teaspoons of sugar½ teaspoon of saltTake 1 – 2 cups of this fluid or more, after every diarrhoeal stool
40Diarrhoeal disease 2.) First line treatment for uncomplicated diarrhoea:TMP-SMX (BactrimR, SeptranR etc.)2 tablets 2 X per day for 5 to 7 days+Flagyllmg 3 x per day for 5 to 7 days
41Diarrhoeal disease 3.) Symptomatic treatment: Codeine phosphate 10mg q 6 – 8 hourly orLoperamide (ImodiumR)2 tabs stat, then 1 tab after each loose stool to a maximum of 4 tabs per 24 hoursonly if the patient does not have:fever of > 380Csevere abdominal pain orbloody stools
43Loperamide - Imodium® 2 mg tablets Structurally related to pethidine 4mg stat then 2mg after each loose stoolStructurally related to pethidineBinding to opiate receptorsCI – same as for lomotilWell toleratedDry mouth, blurred vision
44When 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 > 380CSevere abdominal cramps or painBloody diarrhoeaDiarrhoea not responding to first line therapy within 5 daysPersistent diarrhoea ordiarrhoea lasting for > 3 weeks
45Acute Infectious diarrhea in AIDS Enteric virusesAdenovirus, astrovirus, picornavirus, calcivirus15 – 30%Most labs cannot detect these virussesWatery diarrhea, acute1/3 become chronicAny CD4Supportive treatment
46Acute Infectious diarrhea in AIDS Non Typhi- Salmonella5-15%Watery diarrhea, fever, variable fecal WBCsAny CD4 countStool + Blood culturesTMP-SMX (1 DS b.d x 14 days)or Ciprofloxacin or 3rd gen CephalopsporinMay need to be extended for > 4 weeks
47Salmonellae gram- bacilli, facultative anaerobic members of the enterobacteriaceaemay persist within the RESmotile with flagellaenon-encapsulatedexcept for S typhi and S paratyphi C both of which express the Vi AgflagellaeO AgVi Ag
48Salmonellae H Ag – serotype O Ag = LPS / endotoxin H Ag Group (A-E) Lipid A = biologically active componentToxic to cellsGroup (A-E)hypersensitivity reactionsfever, leucopenia, hypotension, DIC, deathVi Ag – virulence or invasivenessH AgO AgVi Ag
49Serotype (O + H Ag) Gastroenteritis Enteric fever > 2200 different organismsS. enteritidis + S. typhimuriumDistributed throughout the animal kingdomContaminated food or waterpoultry, eggs, fast foodsmay persist for months in cheese, frozen meat, or ice creamEnteric feverS typhiS paratyphiAB - scottmuleriC - hitchfeldiPurely human pathogens
50symptomatic infection is influenced by number of organisms>104 to 106 : higher rates of illness + shorter IPeven 5 to 100 organisms may cause disease in susceptible hostsAsymptomatic excretion may occurWater supplies are contaminated at lower levels than foodserotypeintrinsic virulence factorshost immune responseantibiotic useachlorhydric 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
51Other host factors Cell-mediated immunity polymorphonuclear leukocytes glucocorticoids , AIDS , and malignancypolymorphonuclear leukocytessickle cell anemia, malaria , schistosomiasis, and histoplasmosishumoral immunity
52Acute Infectious diarrhea in AIDS Shigella1-3%Watery diarrhea or bloodyFever, fecal WBCs is commonAny CD4 countStool cultureTMP-SMX (1 DS x 3 days)ciprofloxacin
53Acute Infectious diarrhea in AIDS Campylobacter jejuni4-8%Watery diarrhea or bloodyFever, +/- fecal WBCsAny CD4Stool cultureErythromycin 500 mg qid x 5 days
54Acute Infectious diarrhea in AIDS IdiopathicVariable non infectious causesRule out medicationDietaryIBSAny CD4Negative studiesStool + blood culture, O+P, neg C difficili toxinIf severeCiprofoxacin +/- metronidazole
55Acute Infectious diarrhea in AIDS Clostridium difficile10-15%Watery diarrhea, +/- WBCs, Fever, leucocytosis,Previous AB: Clindamycin, Ampi, cephalospAny CD4Stool toxinEndoscopyCT scanColitis with thickened mucosaMetronidazole: 400mg tds x 10 –14 daysor Vancomycin poAntiperistaltic agents are contraindicated
56Pseudomembraneous enterocolitis normal mucosa is replaced by pseudomembranous plaques of fibrin, cellular debris, and neutrophilsIf normal intestinal flora is altered, colonization by toxigenic C. difficile can occur
58Novel treatment for toxigenic C. difficile Immunoglobulins"probiotics"nontoxigenic C. difficileLactobacillus GG"bacteriotherapy"with enemas using normal stool flora or other bacteriaSaccharomyces boulardiia nonpathogenic yeastpartial to total colectomysepsis and toxic megacolon or ileusThe 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