Micro - GIT Flashcards

Question

Vibrio cholerae

Answer 1

• Family Vibrionaceae. Curved Gram-ve rods, (May be linked end to end) forming S shapes. Motile (single polar flagellum) – Non-spore forming. Oxidase +ve. Halotolerant – O & H antigens. Serogroup: O1 & O139 – Ferment sucrose & mannose NOT arabinose – Acid sensitive - think about intake. CHOLERA TOXIN. Bacteriophage encoded. AB toxin. Receptor: Ganglioside GM1 Sx: hypovolemic shock, acidosis, vomiting, rice water stool, mm cramping (d/t dehydration) Tx: Replace ionic loss. Oral and/or IV admin glucose. Prevention: Parentally administered vaccine. (killed Vibrio cells) Lasts 3-6 months. Only effective O1 serotype Not Recommended by FDA. Sanitation & Hygiene. Dx: Clinical presentation, screening of stool samples -> oxidase activity. Sucrose +! vs other Vibrio. Cholera Ags: Serotypes: Inaba, Ogawa, and Hikojima. Biotypes: "classic" and El Tor

Answer 2

2 different dz's 1) Necrotic enteritis (Darmbrand & Pig-Bel) RARE (Papua New Guinea) C. perfringens strain type C 2) Type A food-borne infection Major cause food-borne infection in U.S C. perfringens strain type A * Sources of C.perfringens type A. Ubiquitous: soil/dust. 50% raw/frozen meat contain C. perfringens. Intestinal tract Humans & Domestic animals * If nml flora of animals, sporulate during cooking, germinate when food is cooling. When in GIT, make C. perfringens enterotoxin (CPE) -> alters SI permeability * Sx's: watery diarrhoea & severe abdominal pain. NO FEVER, NAUSEA, AND VOMITING. * Mortality rate = 0. Elderly & Immunocompromised patients (monitored) Dx • Case hx and sx's • Large # (>10^6/g) C. perfringens spores in faeces • Large # vegetative cells (same serotype) in incriminated food (>10^6/g) • Presence of enterotoxin in feces

Answer 3

Diarrheal -> Resembles C. perfringens. Characterization: diarrhoea & abdominal pain. Incubation: 8-16hrs. Duration: 12-24 hr. (Foods: meat & vegetable dishes, sauces, pasta, desserts & dairy products) LT Enterotoxin(s) prodn vegetative growth (late exponential phase) (in SI) adenyl acyclase-cAMP Vs. food poisoning, infxn has: longer incubation, ENTEROTOXIN, water diarrhea (instead of vomiting), LT protein (vs ST neurotoxin)

Answer 4

Family Reoviridae. Wheel-shape, non-enveloped • 10 human rotavirus serotypes (G1-G4 important) Group A(1): Worldwide distribution. Non-group A (B(2),C(3)): Limited distribution (B - China) • 80% of children have had it by age 4 or 5 • Factors for High Incidence & Mort: Unsafe water, inadeq sanitation Age: 5 years ASX. Protection against diarrhoeal infection • Temperate, Developed countries: “Winter Gastro” Tropical, Developing countries: Year long (Summer) • Transmission: vary Faecal-oral route, water-borne, or air-borne • Incubation period:<48hrs(1-3days) • Replication: epi cells of SI • Shedding MAY persist for 10 days or more. Peak within 8 days

Answer 5

• Histopath studies: shortening & blunting of villi patchy, irregular intact mucosa, mononuclear cell infilt of LP • Diarrhea d/t loss of absorptive area and flux of H2O/fluid across dmged surface * Illness: Sudden onset waterydiarrhoea +/- vomiting. Up to 6 days (longer: immunocompromised) * Complications: Dehydration, severe & LIFE-THREATENING Detection • Virus in stool (peak at day 3/4 of diarrhea) • Latex agglutination • ELISA/EIA (for characterisation) • Electron Microscopy (labour intensive, insensitive) • Electrophoresis of RNA segments

Answer 6

1st Rotavirus Vaccine (Rotashield®) • 1998: FDA approved Live Oral Tetravalent Vaccine: 3 x 2.5ml doses @ 2, 4 & 6 months of age • Prelicensure Studies: Prevent 50% rotavirus cases, 70% severe cases; 100% associated dehydration • Adverse rxns: Intussusception 15 cases • July 1999: CDC recommended discontinuing use. FDA notified manufacturer & doctors • Merck: RotaTeq® – Live, oral, pentavalent (G1, G2, G3, (G4), P7 and P1 – 1st dose between 6-12 weeks of age • 3 doses: 6-32 weeks of age – 3rd dose NOT given after 32 weeks of age • FDA Approved: Feb 2006 • Glaxo_Smith_Kline:Rotarix® • Live, attenuated oral, GP1 • 2doses – 1st 2 months of age – 2nd 4 months of age • FDA approved License April 2008 Suspended in March 2010 for about 1 mo d/t – Porcine Circovirus 1 & 2 (PCV1; PCV2) DNA found

Answer 7

• Originally Family Calciviridae (2002, Noroviridae) • 4 Genera (Norovirus, Sapovirus, Lagovirus & Vesivirus) Non-enveloped Amorphous surface: feathery, ragged outline Virion: ss +ve sense RNA (7.5kb) • CRUISE SHIPS • Estimated 50% outbreaks of acute, nonbacterial gastroenteritis (US) • Older children & adults (Children < 5 yrs) (Camps, schools, nursing homes, etc.) • Winter seasonality? – Winter Vomiting Disease

Answer 8

``` • Location of outbreak Ohio, Hawaii, Snow Mountain, Colorado Taunton & Southampton (UK) Otofuke & Sapporo (Japan) • Considerable genetic homology with Norwalk • Shared virological characteristics ```

Answer 9

• Family Calciviridae • Children & Adults (Elderly) 5 genogroups (GI-GV), Humans I II IV & V 66% gastroenteritis outbreaks in Long term Care facilities (LTCF’s)

Answer 10

• Transmission: 1ary Faecal-oral route Water-borne Food-borne (raw shellfish) • Virus multiplies in small intestine • Produces transient lesions of intestinal mucosa • Spares large intestine (NO faecal leukocytes) • Shed in faeces • Mild & Brief: 24-48 hr following ingestion Lasts 24-60hrs Characterised: abdominal cramps, myalgias, malaise, headache, nausea, low grade fever & 1-2 days diarrhoea • Fatalities are RARE • Diagnosis Criteria (Epidemiological) – 1) Mean (or median) illness duration of 12-60 hrs – 2) Mean (or median) incubation period of 24-48 hrs – 3) > 50% of people with vomiting – 4) No bacterial agent previously found • Disadvantage: NOT SENSITIVE * Virusinstool(peakatday2/5afteronset) • Difficult to culture * RT-qPCR assays * High Sensitivity (10-100 virus copies/reaction) * RT-PCR (for genotyping) • EIA(notsensitive)

Answer 11

• LigoCyte®PharmaceuticalsInc. – norovirus virus like particle (VLP) vaccine (+ chitosan & monophosphoryl lipid A adjuvants) • 2 doses: 3 weeks apart – IM • Clinical trials: 47% efficacy against illness – Illness less severe, shorter duration – No observed side effects

Answer 12

• FamilyAdenoviridae • 2 Genera: Mastadenovirses & Aviadenoviruses Icosahedral protein shell 252 capsomeres Protein core: ds DNA 12 vertices PENTONS each with fibre 2 serotypes associated: 40 & 41 (Group F) • Main Target: Respiratory Tract • Infect: Epithelial cells of Pharynx, Conjunctiva, Small Intestine & occasionally other organ systems • Spread beyond regional lymph nodes NOT usual • Many replicate in intestine & present in stool • Diarrhoea with or without vomiting • 5-15%casesdiarrhoea(2oRotavirus)

Answer 13

* Family Astroviridae * Non-enveloped * Smooth or slightly indented outer shell * Inner 5 or 6 pointed star shaped core • 2-8%sporadiccasesininfants(3oRotavirus) • Infectionthroughyear:Peakinwinter • 7 human serotypes UK: Type 1 prevalent (65% cases) Mexico: 6% cases, Type 2 prevalent (31%) Japan: Type 6

Answer 14

* Emerging GI Pathogen (similar to coronavirus (ssRNA)) | * At risk?: Aged, immunosuppressed & hospitalised

Answer 15

* 27nm icoshedral particle (typical Picornaviridae structure) * Non enveloped symmetrical ss(+) RNA * Spread: Faecal-Oral route, person-to-person Poor sanitation & overcrowding Virus shedding in faeces (10-14d after exposure)

Answer 16

• Icosahedral particle (similar Calciviruses) • Non enveloped symmetrical (+) RNA • Final taxonomic classification? • 1980: Enterically-transmitted non-A, non-B hepatitis Indian subcontinent (Russia, SE Asia, N America, Mexico) • Incubation longer than HAV (mean 6 wks)

Answer 17

- Ingestion of organisms present in food - Colonisation & Invasion of intestines (Except EAEC & EHEC) - Symptomology: Bloody diarrhoea (May begin as watery diarrhoea). Longer incubation due to colonisation. Fever may be present - Toxins Affect: Enterotoxins &/or Cytotoxins

Answer 18

• Shigella sp. Genus: 50 species, into 4 groups “O” antigens GROUP A: Shigella dysenteriae - most severe GROUP B: Shigella flexneri GROUP C: Shigella boydii GROUP D: Shigella sonnei - least severe Closely related to E. coli (antigens & toxin-capabilities)) * Endotoxin(Oantigen) * Exotoxin:Enterotoxin acts as neurotoxin. Causes: meningismus & coma, ulceration * NAD glycohydrolase: Destroys all NAD in human cells. Shuts down metabolism. Cell death - Invade epi cells of LI -> plasmid-encoded endocytosis -> membrane ruffling, production of invasins - Shigella multiply and spread to adjacent epithelial cells

Answer 19

* Shigella dysenteriae type 1 (Shigabacillus) * Shiga toxin (cytotoxin) - inhibits protein synthesis Acts as: Enterotoxin - produces diarrhea Exotoxin - inhibits sugar & Aa absorption in SI Neurotoxin - affects CNS

Answer 20

• Shigella sonnei - children <5 years (day-care) • Shigella flexneri – men who have sex with men • Shigella boydii - rare Readily transmitted faecal-oral route: Sanitation breaks down (4 F’s) • Bloodstream invasion RARE ``` Diagnosis, Isolation & Identification • Isolation from stools, water & food Non-motilem Gram-ve rod NO fermentation lactose NO utilization citric acid NO H2S production (except. S. flexneri) NO gas from glucose ```

Answer 21

SE Asia/S America Similar to Shigellosis less severe (Often mistaken) NO Shiga toxin Infective dose as few as 10 organisms • Pathogenesis Invasion of enterocytes in LARGE INTESTINE Inhibits protein synthesis, killing host cells Causes dead WBC’s (pus), RBC’s and mucosal cells in stool • Management Rehydration therapy

Answer 22

- Enteric Fever - Important morbidity/mortality worldwide - US: ONLY seen in traveller’s to Asia, Mexico, India TYPHOID FEVER • Enteric fever: S.Paratyphi A,B or C - ASYMPTOMATIC CARRIAGE. Carrier state important in transmission ``` Motile, Gram-ve rod NO fermentation lactose H2S production Gas from glucose Serotyping ``` Diagnosis of S. Typhi 1) History of travel to endemic areas 2) Rose coloured spots on abdomen (2-4days) 3) Examination of blood (anaemia, leukopenia, absence of eosinophils) 4) Isolation of S. Typhi on S-S agar 5) Positive Widal reaction (agglutination of O & H antigens)

Answer 23

``` # 1 Food-borne bacterial disease in the West From ingested contaminated liquid or solid food, i.e., unpasteurized milk, raw/partially cooked poultry & contaminated water ``` Small, curved-spiral rods, Gram -ve, Non-sporing, Motile (single polar flagellum). Microaerophilic - req. 5% O2, 10% CO2 for growth DO NOT ferment CH2O Catalase +ve No growth at 25C, but at 37C, readily 42 - 43C ``` • Intestinal tract of wide variety of wild & domestic animals (Zoonotic) - Commercially raised poultry - Normal commensal of cows - Long-term commensal of sheep - Pigs (carriers of C. coli) - C. jejuni intestinal commensal - Cats & dogs • Faecal contaminated water ``` ``` • Dose - 104 org (as few as 500 cells) INVASION: • Inflam & Bacteremia suggest invasion TOXIN: – Endotoxin – Enterotoxin: watery diarrhoea – Cytotoxin: Verotoxin similar to Shiga toxin: (Haem colitis) Significance not understood ```

Answer 24

• Symptoms appear 3-5 days after ingestion Vomiting - slight Diarrhea - often profuse (green?) Abdominal pain - often severe Prostration - often severe Pyrexia - often present Other symptoms - bloodstained faeces • Management Usually self-limiting Erythromycin - eradicate C. jejuni from faeces Severe abdominal pain - aminoglycoside, chloramphenicol, doxycycline • Association/Complications – Reactive arthritis (1% cases): Knee joint (6-12 mnths) – Acute Inflammatory Demyelinating Polyneuropathy: Guillain-Barré syndrome (GBS) (30% cases) AKA: Acute Motor Axonal Neuropathy Def dx: oxidase +, catalase +

Answer 25

Yersiniosis - lesser cause Y. pseudotuberculosis * Common in children <7 yrs (1-4 y); adults * Rivals Salmonella - acute gastroenteritis (cooler climates) * -1 - +40C (Psychrotroph – Facultative psychrophile Pathogenesis - poorly understood • Invasive induces inflammatory response Distal ileum (gut-associated lymphoid tissue) Adjacent tissues & mesenteric lymph nodes also infected (mimic appendicitis) • (Chromosomal) ST Enterotoxin •

Answer 26

CLINICAL FEATURES Self-limiting enterocolitis Incub period 3-7 days. Lasts 14-21 days (Longer) Sx's: abdominal pain & diarrhoea. Mild fever, vomiting rare Post-infective Reactive Arthritis (Autoimmunity Arthritis) • Small proportion patients Pathogenesis poorly understood • MAYBE – Induced polyclonal T-cell stimulation (toxin) – Non-specific immune stimulation of invasin binding to b1 integrins on T lymphocyte – Other bacterial antigens ``` Special investigation • Diagnosis from stool is possible Often considered late: rising antibody titres in paired serum • MacConkey(pinpoint colonies/48hrs) • Specialized Yersinia media ```

Answer 27

``` Not agglutinated by anti O1 sera Halophilic organisms (Common coastal waters) ``` Vibrio parahaemolyticus • Ingestion of raw/poorly cooked seafood Acute abdominal pain, vomiting & watery diarrhea Japan - raw fish (# 1 Food-borne) US - shellfish Vibrio vulnificus - Diarrhoea & infection of cuts (Salt water abrasions) - Virulent strain - Intense skin lesions (gastroenteritis & even severe bacteremia) Dx: • Clinical presentation (Not Cholera) • Screening of stool samples. Oxidase activity Thiosulphate-citrate-bile salts-sucrose (TCBS) agar. Sucrose (differentiating agent) Sucrose -ve V. parahaemolyticus, V. vulnificus

Answer 28

• PATHOGENESIS: Not fully understood NO EAF (Enteric Adherence factor) Possess AAF (Aggregative Adherence factor) Thought: 3 stages 1) Initial adherence to intestinal mucosa and/or mucus layer (fimbriae) 2) Enhanced mucus prodn -> thick mucous biofilm 3) Cytotoxin prodn? -> Dmg to intestinal cells ``` causes: LIFE THREATENING CONDITIONS HAEMORRHAGIC COLITIS HAEMOLYTIC UREMIC SYNDROME (8 -11% cases) Acute renal failure Thrombocytopenia Microangiopathic haemolytic anaemia THROMBOTIC THROMBOCYTOPENIA PURPURA ``` ``` Pathogenesis Attachment (similar to EPEC) Phage encoded: CYTOTOXIN - VEROTOXIN 2 types (VT1 & VT2) both AB toxins Shiga-like toxin (rRNA) blocks protein synthesis ```

Answer 29

1) MacConkey’s agar (Red-Pink colonies) 2) Sorbitol MacConkey’s agar (no fermentation EHEC) 3) (ETEC) Inoculate mouse adrenal cells: stimulation of adenylate cyclase by LT/ST 4) ELISA on toxin bound to antibody 5) DNA probe to detect toxin genes

Answer 30

• 2 toxins Toxin A enterotoxin (fluid accum in bowel) (weak cytotoxin most mammalian cells) Toxin B potent cytotoxin Decreases cellular prot syn & disrupts microfilament system of cells (similar to diphtheria toxin) Clinical Symptoms • Vary: mild diarrhoea -> severe abdominal pain accompanied fever (>101F) & severe wkness • Diarrhoea: watery,usually non-bloody (5-10% bloody), xs mucus & pus (or blood) Hypoalbumineia & Leukocytosis common ``` • Dx: Difficult. Not distinguished from UC & Crohns Colonic examination (presence of pseudomembrane) AND Isolation C. difficile, associated abx therapy ``` ``` Management Discontinue abx - sx's resolve 1-14 days If severe or no response; treat oral abxs: Vancomycin (“gold” standard) or Metronidazole (milder infections) Relapses in 15-20% patients ``` Dificid (fidaxomicin) bid 10 days. Approved by FDA (2011)

Answer 31

``` Biological carcinogen Gram -ve, Non spore-forming, Curved to spiral (1-3 turns). Motile - polar (5-6) flagella Microaerophilic 2-5%O2, 5-10%CO2 Catalase +ve; Urease +ve Coccoidal forms under culture ``` ASSOCIATED CAUSE • Gastritis (stomach atrum) • Duodenal ulcers (& gastric ulcers) • Gastric cancer Pathogenesis Gastric colonisation is common Route of infection UNCLEAR • Mechs UNDER INVESTIGATION Role of cytotoxin, urease, mucinase, flagella • UREASE allow H. pylori survival at pH 2.0 Able to split ammonia from urea = alkaline environment • Virulence Factors: allowing for adhesion & damage to mucosa - cagPAI: VacA cytotoxin; BabA; OipA Jan 28th 2003, FDA approved Helivax Inactivated, whole cell vaccine.

Answer 32

• Oral rehydration (ORT): till normal rehydration restored (determined by: clinical condition/body weight) Sodium: 150-155mmol/l Glucose: 200-220mmol/l Potassium: 4-5mmol/l * Intravenous rehydration: shock, exhaustion precluding oral feeding and oral rehydration failure * Antiemetic drugs: reduce fluid loss

Micro - GIT Flashcards

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