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Flashcards in Round 2 Deck (245):
1

Initial upper GI bleed management

Remember ABC’s
Airway?
CPR?

IV access
At least 2 large bore IVs

Infusion
Crystalloid
Blood products

2

Varices

Presentation: Dramatic bleeding, usually hematemesis
Causes: Portal hypertension
Associated with: Liver disease/cirrhosis

Treatment:
Octreotide or Vasopressin
Proton Pump inhibitor
Non-selective Beta-blocker
Variceal band ligation

3

Responsible for tolerance

Treg cells

4

NSAIDs and Peptic Ulcer Disease

Direct injury effects
Systemic effects
COX inhibition and  prostaglandin production
Prostaglandins in the gut regulate mucus secretion and basal bicarbonate secretion
Prostaglandins are trophic for gastric epithelia and play role in feedback inhibition of gastric acid secretion
COX-2 selective inhibitors still pose risk for PUD

5

Intraepithelial Barrier

Intraepithelial Lymphocytes (IEL) promote barrier repair and are rapidly recruited
Majority of IELs express CD8 (recognize MHC class I Ag)
Two types of TCR
αβ, thymus derived
γδ, non-thymic derived
15% of small intestine IEL
40% of colonic IEL
Produce keratinocyte growth factor

6

Lamina Propria

Reservoir to 70-80% total lymphocytes
Predominate T cells are CD4, recognize MHC class II Ag

7

M Cells

Some bacteria and viruses cross the epithelial barrier via M Cells

8

α-Defensin

Neutrophils, NK cells, Paneth cells

9

β-Defensin

Leukocytes and Epithelial cells

10

Paneth Cells

Small intestine is lined with villi interspersed with Crypts.
Paneth cells harbor pro-defensin 5
Degranulation occurs following bacteria penetration

11

Type 1 Interferons

(IFN-α/β)
Induces MHC Class I expression
Kill Infected Host Cell

12

Natural resistance-associated macrophage proteins

remove mn to starve bacteria

13

Calprotectin

Broad spectrum scavenger of divalent cations is Calprotectin, S100 protein that sequesters Ca, Fe, Zn and Mn

14

Lipocalin

remove lipids to starve bacteria

15

indoleamine 2,3-dioxygenase

Tryptophan removal to starve bacteria

16

anti-inflammatory mediators

IL-10, IL-1ra

17

pro-inflammatory mediators

IFN-gamma, TNF-alpha, IL-12

18

TH1 Lymphocytes

Acute Inflammation

19

IFN-γ

Acute Inflammation

20

M-1 Macrophage

Acute Inflammation

21

IgG

Acute Inflammation

22

sIgA

Acute Inflammation

23

CTL cells

Acute Inflammation

24

NK cells

Acute Inflammation

25

TH2

Chronic Inflammation

26

TH17 Lymphocytes

Chronic Inflammation

27

IL-4

Chronic Inflammation

28

IL-17

Chronic Inflammation

29

M-2 Macrophage

Chronic Inflammation

30

IgE

Chronic Inflammation

31

Eosinophils

Chronic Inflammation

32

Basophils

Chronic Inflammation

33

secretory diarrhea

characterized as an infection of the proximal small bowel marked by watery diarrhea that does NOT contain fecal leukocytes. Viruses that cause gastroenteritis do not infect the colon

34

Rotavirus Clinical presentation:

gastroenteritis

35

Norwalk Virus (Norovirus) Clinical presentation:

gastroenteritis

36

Adenovirus Clinical presentation:

gastroenteritis (do not confuse with other serotypes of adenoviruses that cause respiratory tract infections)

37

Rotavirus Pathology:

transmitted via the fecal to oral route. After ingestion of the virus it travels in the GI tract (the virus particle is stable within the low pH of the gastrointestinal system) to eventually infect the villus cells of the proximal small intestine. Here the virus replicates within these cells eventually lysing these cells which leads to the impaired adsorption of carbohydrates and other nutrients. This can lead to vomiting followed by watery diarrhea.

38

Norwalk Virus (Norovirus) Pathology:

fecal to oral transmission usually through direct contact or through contaminated food and water. Causes a local infection and inflammation in the proximal small intestine.

39

Adenovirus Pathology:

fecal to oral transmission. Causes a local infection and inflammation in the proximal small intestine. If inhaled into the lungs some respiratory symptoms can be present.

40

Rotavirus Diagnosis:

stool specimen, serology for the virus. Electron microscopy and RT-PCR also possible.

41

Norwalk Virus (Norovirus) Diagnosis:

not typically done. When done it is through visualization of the virus in stool specimens or PCR/serology of stool and/or vomit specimens.

42

Adenovirus Diagnosis:

PCR detection of the viral genome within a stool sample

43

Rotavirus Treatment:

rehydration (supportive). There is a rotavirus vaccine (live oral attenuated).

44

Norwalk Virus (Norovirus) Treatment:

usually not required because it is self-limited. When done, treatment consists of rehydration (supportive) if there is severe fluid loss. Outbreaks can be minimized through proper food handling, clean water supplies, and hand washing.

45

Adenovirus Treatment:

self-limiting infection in immunocompetent individuals. Supportive care only.

46

Rotavirus

because rotaviruses cause no inflammation, diarrhea has no blood. Infection before 6 months of age is uncommon due to passive IgA immunity from the mother’s colostrum. However, by age 3, almost every individual worldwide (~95%) has been infected and develops lifelong immunity. Virus particle contains a double-layered capsid.

47

Norwalk Virus (Norovirus)

this virus is a major cause of group-related or institutional diarrhea.

48

Adenovirus

major cause of acute infantile gastroenteritis. These serotypes of adenoviruses rarely cause fever or respiratory tract symptoms.

49

bifidobacteria

are among the first colonizers in breast-fed infants

50

Staphylococcus aureus

Gram +CocciCatalase +Coagulase +Also a common infectious agent of surgical wounds and cause of scalded skin syndromein food that sits around for a whileno need for antibiotics for a food borne infection

51

Bacillus cereus

Gram +Large Bacilliendospore-formingFacultative anaerobeMostly motileβ hemolytic Box-car shaped Also frequently found on skin and is a threat in hospitals as it produces biofilms that adhere easily to invasive devices. This produces chronic persistent infection, as the biofilm can periodically release B. cereus into the bloodstreamB. Cereus spores are commonly found in the soil and sometimes in plant foods that are grown close to the ground – such legumes, cereals, spices etc..Spores can survive rice cooking processDuration for both only about 24 hrsBecause of its ubiquity, B. cereus often is ignored or dismissed as a contaminant when found in a culture specimen. B. cereus in food and vomitus or feces of same serotype Large numbers of B. cereus of serotype known to produce endotoxinOnly necessary when tracking outbreaks

52

Clostridium botulinum

Gram +BacilliSpore-formingObligate anaerobeMotileSpores or toxin are the important issues for transmission of botulism

53

Staphylococcus aureus Symptoms:

Symptoms:nausea, vomiting, stomach cramps, and diarrhea for 1-3 daysAppear 1-7 hrs following ingestion of foodSelf-limiting, once toxin is gone, illness is gone

54

Staphylococcus aureus diagnosis

Positive diagnosis:Toxin-producing S. aureus can be identified in stool or vomitMost conclusive test is the linking of an illness with a specific food, or in cases in which multiple vehicles exist, detection of pre-formed enterotoxin in food sample(s).Only necessary when tracking outbreaks

55

Bacillus cereus infection

Infection takes two forms:Emetic (vomiting):Diarrheal:Duration for both only about 24 hrs

56

Bacillus cereus Emetic infection

Emetic (vomiting):1 to 6 hours incubationNausea and vomitingresembles the vomiting illness caused by Staphylococcus aureus enterotoxinsCaused by preformed enterotoxin that forms holes in membranesSelf limiting

57

Bacillus cereus Diarrheal infection

Diarrheal:6-15 hours incubationclinically similar to the symptoms of Clostridium perfringens infectionWatery diarrhea and abdominal crampsMechanism: Caused by large molecular weight enterotoxin that causes intestinal fluid secretion, probably by several mechanismsThis toxin is not likely pre-formed!Ingestion of large amounts of bacteria cause it to generate the toxin in the small intestineVulnerable populations might get sicker and require antibioticsPoor outcomes for systemic infection

58

Bacillus cereus diagnosis

Because of its ubiquity, B. cereus often is ignored or dismissed as a contaminant when found in a culture specimen. B. cereus in food and vomitus or feces of same serotype Large numbers of B. cereus of serotype known to produce endotoxinOnly necessary when tracking outbreaks

59

Botulism

Food borne botulism: ingesting toxinWound botulism: producing toxin Infant botulism: ingested sporesNot really a GI illness, diarrhea not prominent

60

Botulism Diagnosis

Symptoms and history, results of physical exam indicate botulismTests to exclude other causes of the illnessOrganism or toxin in stool sample only indirect evidence

61

Treatment for foodborne botulism

Ventilator if respiratory failure and paralysisAntitoxin if paralysis is not yet completeRemove contaminated food if still likely in gut

62

Botulism toxin

neurotoxinirreversibly blocks the release of acetylcholine from the motoric end plate which results in muscle weakness and paralysisToxin is absorbed from GI tract to bloodstream

63

Symptoms, botulism

Toxin already produced, symptoms can begin when toxin hits GI tractdouble vision, blurred vision, drooping eyelids, slurred speech, difficulty swallowing, dry mouth, and muscle weakness

64

Symptoms, infant botulism

Incubation period, spores have to produce toxin-forming bacterialethargic, feed poorly, are constipated, and have a weak cry and poor muscle toneCan lead to paralysis of respiratory system and other muscles

65

Clostridium perfringens

Gram +BacilliSpore-formingObligate anaerobeNon-motileEnterotoxin binds to receptors in endothelial cell junctions, then generates pores in host mucosa cells.“C. perfringens infection often occurs when foods are prepared in large quantities and kept warm for a long time before serving”

66

Clostridium perfringens Symptoms

Symptoms:Diarrhea and abdominal crampsIncubation 6 to 24 hours (typically 8-12)Symptoms last for less than 24 hoursUsually NO fever or vomitingThe illness is not passed from one person to another

67

Clostridium perfringens Positive diagnosis

Positive diagnosis:Detection of toxin or high amounts of bacteria in fecesC. perfringens normally present in the GI tract, the problem is when you ingest a C. perfringens load high enough to produce enough toxin to generate symptoms

68

Clostridium perfringens Treatment

Treatment:Usually self-limiting, but more serious, longer-lasting cases in immunocompromised individuals should be treated to avoid complications

69

Campylobacter jejuni

Gram -Bacilli (Spirilli)microaerophilicMotileCold sensitive (often leads to false negatives)get it from poultryOne unique feature is that campylobacter cannot usually multiply in food.Symptoms:diarrhea, cramping, abdominal pain, and fever2-5 day incubationSymptoms can last a weekCan have vomiting, diarrhea can be bloodyMechanism: Symptoms are an inflammatory response to cell invasionPositive Diagnosis: stool culturePossible complication: Guillain-Barré syndrome

70

Salmonella enterica

Gram -BacilliNon spore formingH2S positive & lactose negativeMotile, flagellated

71

Salmonellosis

Symptoms:diarrhea, fever, and abdominal cramps 12 hr to 3 day incubationSymptoms typically last 4 to 7 daysMost persons recover without treatmentRemember: reactive arthritis as a possible complicationDiagnosis: we know for sure with a stool cultureTreatment: Hydration. Antibiotics only necessary if infection spreads beyond gut

72

Vibrio parahaemolyticus

Gram (-)Vibrio (curved rod)facultative anaerobesFlagellated, motileOxidase +water lovingDiagnosis: Vibrio may be isolated from cultures of stool, wound, or blood. Form pores in red blood cells but also in epithelial cells, disrupting gut homeostasissushi and shellfish

73

Vibrio parahaemolyticus Symptoms

Fairly mild bloody diarrhea, stomach cramps, fever, nausea, and/or vomiting, Symptoms last less than a week. In the immunocompromised, it can spread to the blood and cause serious or deadly infections in other parts of the body

74

Listeria monocytogenes

Gram positive rod-shaped bacteriaAlthough a rare illness, a leading cause of death by foodborne illnessGram (+)BacillusNon-fastidious!!!Flagellated, motileNon spore formingOxidase -Diagnosis: Stool sample ID inappropriatePositive ID is the bacterium found in a normally sterile siteImmune cells spread Listeria to other organsTrojan horseLiver is a major targetmilk, cheese, seafood, deli

75

Listeriosis

Mild GI infection for mostMore vulnerable are older adults, pregnant women, newborns, and adults with weakened immune systems OPPORTUNISTICFever and muscle aches or stiff neck, or if you develop while pregnant: fever and chillsMeningitis and sepsis in vulnerable populations

76

Shigella

Gram (-)BacillusFacultative anaerobenonmotile (distinguishes from e. coli)Non spore formingMainly lactose negative, H2S (-) (distinguishes from e. coli)Shigella sonnei: most Shigella-caused GI illnessesShigella flexnori: causes bacillary dysenteryShigella dysenteriae: rarest but most severe dysenteryinvade through m cellsSince Shigella is invasive, if not treated it can spread beyond the GI tract and cause complicationsAntibiotics for more severe cases, most usually resolve without antibioticsPossible complication: hemolytic uremic syndrome (HUS)

77

What is dysentery

Frequent, small bowel movements with blood and mucus, accompanied by rectal pain and spasms (tenesmus)

78

Shigella Transmission

Transmission: Mostly bacterium passing from stools or soiled fingers of one person to the mouth of another person.

79

Shigella Symptoms:

Symptoms: diarrhea (often bloody)feverstomach crampsSymptoms start 1-2 days following exposureUsually resolves in 5 to 7 days.

80

E. coli

Gram (-)BacillusFacultative anaerobemotileNon spore formingMainly lactose positiveDiarrheaUrinary tract infectionNeonatal sepsisGram-negative sepsisETECSTECTreatment: antibiotics generally not recommended (decaying bacteria release toxins)Tracking outbreaks: commercial PCR and antibody-based kits.

81

ETEC

Traveler’s Diarrhea, diarrhea in childrenactivates adenylate cyclase, end result water into lumen, NO bacterial penetration.

82

STEC

penetrates like Shigilla toxin. hemorrhagic colitis (HC) and/or HUS can result as a complication; children more vulnerable

83

E. coli Symptoms:

profuse watery diarrhea and abdominal crampingCan progress to bloody diarrhea for STECFever, chillsNausea with or without vomiting, loss of appetiteLess common: headache, muscle aches and bloatingIncubation:1-3 days ETEC, 3-8 for STEC Illness typically lasts 3-4 days, less than 10.

84

cholera toxin

Activates adenylate cyclase cAMP →  Na+ absorption,  Cl- excretionWater moves into lumen

85

typhoid fever

Only fecal-oral contaminant, no other host, so water is a big source of contaminatonDrinking water, unwashed fruits/veggiesTravelers are vulnerableVaccine availableLife-threatening illnessIn GI tract and then to bloodstreamHigh fevers (103-104 °F)Weakness and headacheStomach pains, loss of appetite, diarrhea or constipation Sometimes, a rash of flat, rose-colored spotsAfter symptoms clear, person could become a carrierAntibiotic treatment is recommended

86

High inoculum organisms

Tens of thousands or more neededExamples: Vibrio cholerae, C. perfringens

87

Clostridium difficile

Gram +BacilliSpore-formingObligate anaerobeMotileMakes exotoxinsantibiotic diarrhea

88

Giardia lamblia

Also most common intestinal parasite in USGiardiasis (aka Beaver Fever) is the foe of backpackers/hikersSymptoms for 1-2 weeks or more, may seem to resolve and then come backMechanism: presence of parasite causes loss of epithelial absorptive surface area. Trophozoites: Attachment but not penetrationFoul-smelling diarrheaFilter water in areas where Giardia cysts are likely to exist. Water does not need to be contaminated with human sewage. Wildlife can deposit cysts.

89

Cryptosporidium parvum

Often seen when a sanitation system failsPool/waterpark chlorination/UV treatmentStorms or issues with drinking waterDiarrhea symptoms for 1-2 weeks to ~30 days, may seem to resolve and then come backMechanism: Absorption impaired and secretion enhanced when intestinal epithelial cells are infected by Cryptosporidium“Crypto” is opportunisticHIV/Immunocompromised individualsChronic Diarrhea/fluid lossCan be fatalWatery, frequent, non-bloody stoolDisrupts epithelial microvilli, slides into host cells, enveloping itself in the host cell membraneOocysts to sporozoites and backCoccidia subclass

90

Entamoeba histolytica

AmebiasisMore prevalent in tropical/subtropical climatesOnly 10-20% of infected individuals will become ill (CDC)Of US population, male homosexuals most vulnerableBloody, mucus-ey loose stoolRelatively mild symptoms butCan invade the liver and form an abcessX-ray/ultrasound to detect abscess or tissue damageCysts in stool sample. Must differentiate from non-pathogenic entamoeba, takes a specialist.cytotoxic

91

Metronidazole, Tinidazole

Tissue antiparasitic- low concentration in intestine, oral dose almost completely absorbed with high bioavailabilityDespite this, it is the drug of choice to treat symptomatic Giardia infection, even though organism that does not penetrate the epithelium!!Reminder: all about metronidazole/Tinidazole in lectures relating to treatment of H. pyloriDisulfiram reaction, avoid alcoholDisturb normal GI florabreaks down into toxic metabolites, damages DNA

92

Nitazoxanide

Mechanism: Interferes with pyruvate::ferredoxin oxidoreductase enzyme dependent electron transfer, essential to anaerobic energy metabolism protein Selectivity: Species difference in electron transferDistribution: Rapidly metabolized to tizoxanide. Parent compound is not detected in plasma. Moderately absorbed (33%), primarily luminal. For Crypto, used in combination with retroviral therapy for AIDS patients if at all, because of ineffectiveness

93

Iodoquinol

Mechanism: UnknownToxicity: loss of visual acuityUse with caution in patients with thyroid disease – its use interferes with certain thyroid testsDistribution: only 10% of the drug is absorbed so it works locally on the protozoa including cysts in the GI tract, luminal antiparasitic (amebicide)

94

Paromomycin

Mechanism: Aminoglycoside- targets 30S subunit ribosomeToxicity: Diarrhea, other GI effects including issues with intestinal flora because it has activity against some bacteria.Distribution: Luminal antiparasitic- Minimal absorption after oral administrationOtotoxicity, nephrotoxicity

95

TMP-SMX

Spectrum: Broad spectrum, many bacteria, but also effective against apicomplexans including Toxoplasma and Cystoisospora (formerly Isospora), and Cyclosporahits folic acid system

96

Enterobius vermicularis

Staple-sized wormspinwormsWorldwide distribution, most common helminth infection in USPrevalence can reach 50% in children, caregivers of infected children, and institutionalized individuals.Symptom: perianal pruritisAcquired by ingestion of pinworm eggsEggs can remain viable on surfaces for 2-3 weeks

97

Necator americanus/Ancylostoma duodenale

Pruritic Papular Erythematous RashHookworms are bloodsuckers…Major symptom is iron-deficiency anemia¼ ml/day/worm

98

Strongolides stercoralis

Autoinfection possible, especially with Immunosuppressed individualsStomach and GI complaintsRespiratorydry coughthroat irritationSkinan itchy, red rash that occurs where the worm entered the skinrecurrent raised red rash typically along the thighs and buttocks.

99

Trichuris trichiura

Diagnosis:Eggs in feces have a characteristic barrel-shaped appearanceFinger clubbing best indicator ofseverity of infestationBloody diarrhea = iron deficiency anemiaHeavy cases:Frequent, painful stools with mucus, water and blood, tenesmusRectal prolapse

100

Ascaris lumbricoides

Disease: ascariasisDisease: IF symptoms are experienced, abdominal discomfortIf a severe case, intestinal blockagesUltrasonography and radiology to determineHas a lung stage of life cycle, may cause coughDiagnosis: eggs w/thick shells

101

Albendazole and Mebendazole

Broad-spectrum benzimidazole drugsRoundworms and tapewormsDistribution: Limited oral absorption, albendazole is better absorbed if targeting tissue-migrating larvae is importantBroad-spectrum benzimidazole drugsMechanism: Binds to parasite β-tubulin and inhibits the formation of microtubulesDeath can take several days, for some helminths more than one dose may be necessarySpecificity: differences in tubulinToxicity: Systemic toxic affects on liver/bone marrow rareAbdominal pain, nausea, dizziness, headacheEmbryotoxic and teratogenic in pregnant ratsEvidence suggests safe for use in children when warranted

102

Pyrantel pamoate and Levamisole

Mechanism:Levamisole selectively opens a restricted subgroup of nematode acetylcholine receptor (AChR) ion channels in nematode nerve and muscle. depolarization entry of calcium through the opened channels, and an increase in sarcoplasmic calcium, producing spastic muscle contraction the parasite is then unable to maintain its location (often in the intestine) and is then swept away, effecting the cure. Toxicity: Causes nausea, vomiting, diarrheaDistribution: Poorly absorbed

103

Ivermectin

Mechanism: Binds to glutamate-gated chloride channels in invertebrate nerve and muscle cells, causing deactivation of channel: worm paralysis and death by starvationResistance: efflux transportersToxicity:Generally well-tolerated Itching, swollen lymph glands and rarely dizzinessInflammatory reaction due to death of adult wormsSpecificity: This type of channel restricted to phyla Nematoda and Arthropoda. in humans are only in the CNS , Doesn’t cross blood-brain barrierSpectrum: Nematodes- Ascaris, Strongyloides and Onchocerca

104

secretory diarrhea

characterized as an infection of the proximal small bowel marked by watery diarrhea that does NOT contain fecal leukocytes. Viruses that cause gastroenteritis do not infect the colon

105

Rotavirus Clinical presentation:

gastroenteritis

106

Norwalk Virus (Norovirus) Clinical presentation:

gastroenteritis

107

Adenovirus Clinical presentation:

gastroenteritis (do not confuse with other serotypes of adenoviruses that cause respiratory tract infections)

108

Rotavirus Pathology:

transmitted via the fecal to oral route. After ingestion of the virus it travels in the GI tract (the virus particle is stable within the low pH of the gastrointestinal system) to eventually infect the villus cells of the proximal small intestine. Here the virus replicates within these cells eventually lysing these cells which leads to the impaired adsorption of carbohydrates and other nutrients. This can lead to vomiting followed by watery diarrhea.

109

Norwalk Virus (Norovirus) Pathology:

fecal to oral transmission usually through direct contact or through contaminated food and water. Causes a local infection and inflammation in the proximal small intestine.

110

Adenovirus Pathology:

fecal to oral transmission. Causes a local infection and inflammation in the proximal small intestine. If inhaled into the lungs some respiratory symptoms can be present.

111

Rotavirus Diagnosis:

stool specimen, serology for the virus. Electron microscopy and RT-PCR also possible.

112

Norwalk Virus (Norovirus) Diagnosis:

not typically done. When done it is through visualization of the virus in stool specimens or PCR/serology of stool and/or vomit specimens.

113

Adenovirus Diagnosis:

PCR detection of the viral genome within a stool sample

114

Rotavirus Treatment:

rehydration (supportive). There is a rotavirus vaccine (live oral attenuated).

115

Norwalk Virus (Norovirus) Treatment:

usually not required because it is self-limited. When done, treatment consists of rehydration (supportive) if there is severe fluid loss. Outbreaks can be minimized through proper food handling, clean water supplies, and hand washing.

116

Adenovirus Treatment:

self-limiting infection in immunocompetent individuals. Supportive care only.

117

Rotavirus

because rotaviruses cause no inflammation, diarrhea has no blood. Infection before 6 months of age is uncommon due to passive IgA immunity from the mother’s colostrum. However, by age 3, almost every individual worldwide (~95%) has been infected and develops lifelong immunity. Virus particle contains a double-layered capsid.

118

Norwalk Virus (Norovirus)

this virus is a major cause of group-related or institutional diarrhea.

119

Adenovirus

major cause of acute infantile gastroenteritis. These serotypes of adenoviruses rarely cause fever or respiratory tract symptoms.

120

bifidobacteria

are among the first colonizers in breast-fed infants

121

Staphylococcus aureus

Gram +CocciCatalase +Coagulase +Also a common infectious agent of surgical wounds and cause of scalded skin syndromein food that sits around for a whileno need for antibiotics for a food borne infection

122

Bacillus cereus

Gram +Large Bacilliendospore-formingFacultative anaerobeMostly motileβ hemolytic Box-car shaped Also frequently found on skin and is a threat in hospitals as it produces biofilms that adhere easily to invasive devices. This produces chronic persistent infection, as the biofilm can periodically release B. cereus into the bloodstreamB. Cereus spores are commonly found in the soil and sometimes in plant foods that are grown close to the ground – such legumes, cereals, spices etc..Spores can survive rice cooking processDuration for both only about 24 hrsBecause of its ubiquity, B. cereus often is ignored or dismissed as a contaminant when found in a culture specimen. B. cereus in food and vomitus or feces of same serotype Large numbers of B. cereus of serotype known to produce endotoxinOnly necessary when tracking outbreaks

123

Clostridium botulinum

Gram +BacilliSpore-formingObligate anaerobeMotileSpores or toxin are the important issues for transmission of botulism

124

Staphylococcus aureus Symptoms:

Symptoms:nausea, vomiting, stomach cramps, and diarrhea for 1-3 daysAppear 1-7 hrs following ingestion of foodSelf-limiting, once toxin is gone, illness is gone

125

Staphylococcus aureus diagnosis

Positive diagnosis:Toxin-producing S. aureus can be identified in stool or vomitMost conclusive test is the linking of an illness with a specific food, or in cases in which multiple vehicles exist, detection of pre-formed enterotoxin in food sample(s).Only necessary when tracking outbreaks

126

Bacillus cereus infection

Infection takes two forms:Emetic (vomiting):Diarrheal:Duration for both only about 24 hrs

127

Bacillus cereus Emetic infection

Emetic (vomiting):1 to 6 hours incubationNausea and vomitingresembles the vomiting illness caused by Staphylococcus aureus enterotoxinsCaused by preformed enterotoxin that forms holes in membranesSelf limiting

128

Bacillus cereus Diarrheal infection

Diarrheal:6-15 hours incubationclinically similar to the symptoms of Clostridium perfringens infectionWatery diarrhea and abdominal crampsMechanism: Caused by large molecular weight enterotoxin that causes intestinal fluid secretion, probably by several mechanismsThis toxin is not likely pre-formed!Ingestion of large amounts of bacteria cause it to generate the toxin in the small intestineVulnerable populations might get sicker and require antibioticsPoor outcomes for systemic infection

129

Bacillus cereus diagnosis

Because of its ubiquity, B. cereus often is ignored or dismissed as a contaminant when found in a culture specimen. B. cereus in food and vomitus or feces of same serotype Large numbers of B. cereus of serotype known to produce endotoxinOnly necessary when tracking outbreaks

130

Botulism

Food borne botulism: ingesting toxinWound botulism: producing toxin Infant botulism: ingested sporesNot really a GI illness, diarrhea not prominent

131

Botulism Diagnosis

Symptoms and history, results of physical exam indicate botulismTests to exclude other causes of the illnessOrganism or toxin in stool sample only indirect evidence

132

Treatment for foodborne botulism

Ventilator if respiratory failure and paralysisAntitoxin if paralysis is not yet completeRemove contaminated food if still likely in gut

133

Botulism toxin

neurotoxinirreversibly blocks the release of acetylcholine from the motoric end plate which results in muscle weakness and paralysisToxin is absorbed from GI tract to bloodstream

134

Symptoms, botulism

Toxin already produced, symptoms can begin when toxin hits GI tractdouble vision, blurred vision, drooping eyelids, slurred speech, difficulty swallowing, dry mouth, and muscle weakness

135

Symptoms, infant botulism

Incubation period, spores have to produce toxin-forming bacterialethargic, feed poorly, are constipated, and have a weak cry and poor muscle toneCan lead to paralysis of respiratory system and other muscles

136

Clostridium perfringens

Gram +BacilliSpore-formingObligate anaerobeNon-motileEnterotoxin binds to receptors in endothelial cell junctions, then generates pores in host mucosa cells.“C. perfringens infection often occurs when foods are prepared in large quantities and kept warm for a long time before serving”

137

Clostridium perfringens Symptoms

Symptoms:Diarrhea and abdominal crampsIncubation 6 to 24 hours (typically 8-12)Symptoms last for less than 24 hoursUsually NO fever or vomitingThe illness is not passed from one person to another

138

Clostridium perfringens Positive diagnosis

Positive diagnosis:Detection of toxin or high amounts of bacteria in fecesC. perfringens normally present in the GI tract, the problem is when you ingest a C. perfringens load high enough to produce enough toxin to generate symptoms

139

Clostridium perfringens Treatment

Treatment:Usually self-limiting, but more serious, longer-lasting cases in immunocompromised individuals should be treated to avoid complications

140

Campylobacter jejuni

Gram -Bacilli (Spirilli)microaerophilicMotileCold sensitive (often leads to false negatives)get it from poultryOne unique feature is that campylobacter cannot usually multiply in food.Symptoms:diarrhea, cramping, abdominal pain, and fever2-5 day incubationSymptoms can last a weekCan have vomiting, diarrhea can be bloodyMechanism: Symptoms are an inflammatory response to cell invasionPositive Diagnosis: stool culturePossible complication: Guillain-Barré syndrome

141

Salmonella enterica

Gram -BacilliNon spore formingH2S positive & lactose negativeMotile, flagellated

142

Salmonellosis

Symptoms:diarrhea, fever, and abdominal cramps 12 hr to 3 day incubationSymptoms typically last 4 to 7 daysMost persons recover without treatmentRemember: reactive arthritis as a possible complicationDiagnosis: we know for sure with a stool cultureTreatment: Hydration. Antibiotics only necessary if infection spreads beyond gut

143

Vibrio parahaemolyticus

Gram (-)Vibrio (curved rod)facultative anaerobesFlagellated, motileOxidase +water lovingDiagnosis: Vibrio may be isolated from cultures of stool, wound, or blood. Form pores in red blood cells but also in epithelial cells, disrupting gut homeostasissushi and shellfish

144

Vibrio parahaemolyticus Symptoms

Fairly mild bloody diarrhea, stomach cramps, fever, nausea, and/or vomiting, Symptoms last less than a week. In the immunocompromised, it can spread to the blood and cause serious or deadly infections in other parts of the body

145

Listeria monocytogenes

Gram positive rod-shaped bacteriaAlthough a rare illness, a leading cause of death by foodborne illnessGram (+)BacillusNon-fastidious!!!Flagellated, motileNon spore formingOxidase -Diagnosis: Stool sample ID inappropriatePositive ID is the bacterium found in a normally sterile siteImmune cells spread Listeria to other organsTrojan horseLiver is a major targetmilk, cheese, seafood, deli

146

Listeriosis

Mild GI infection for mostMore vulnerable are older adults, pregnant women, newborns, and adults with weakened immune systems OPPORTUNISTICFever and muscle aches or stiff neck, or if you develop while pregnant: fever and chillsMeningitis and sepsis in vulnerable populations

147

Shigella

Gram (-)BacillusFacultative anaerobenonmotile (distinguishes from e. coli)Non spore formingMainly lactose negative, H2S (-) (distinguishes from e. coli)Shigella sonnei: most Shigella-caused GI illnessesShigella flexnori: causes bacillary dysenteryShigella dysenteriae: rarest but most severe dysenteryinvade through m cellsSince Shigella is invasive, if not treated it can spread beyond the GI tract and cause complicationsAntibiotics for more severe cases, most usually resolve without antibioticsPossible complication: hemolytic uremic syndrome (HUS)

148

What is dysentery

Frequent, small bowel movements with blood and mucus, accompanied by rectal pain and spasms (tenesmus)

149

Shigella Transmission

Transmission: Mostly bacterium passing from stools or soiled fingers of one person to the mouth of another person.

150

Shigella Symptoms:

Symptoms: diarrhea (often bloody)feverstomach crampsSymptoms start 1-2 days following exposureUsually resolves in 5 to 7 days.

151

E. coli

Gram (-)BacillusFacultative anaerobemotileNon spore formingMainly lactose positiveDiarrheaUrinary tract infectionNeonatal sepsisGram-negative sepsisETECSTECTreatment: antibiotics generally not recommended (decaying bacteria release toxins)Tracking outbreaks: commercial PCR and antibody-based kits.

152

ETEC

Traveler’s Diarrhea, diarrhea in childrenactivates adenylate cyclase, end result water into lumen, NO bacterial penetration.

153

STEC

penetrates like Shigilla toxin. hemorrhagic colitis (HC) and/or HUS can result as a complication; children more vulnerable

154

E. coli Symptoms:

profuse watery diarrhea and abdominal crampingCan progress to bloody diarrhea for STECFever, chillsNausea with or without vomiting, loss of appetiteLess common: headache, muscle aches and bloatingIncubation:1-3 days ETEC, 3-8 for STEC Illness typically lasts 3-4 days, less than 10.

155

cholera toxin

Activates adenylate cyclase cAMP →  Na+ absorption,  Cl- excretionWater moves into lumen

156

typhoid fever

Only fecal-oral contaminant, no other host, so water is a big source of contaminatonDrinking water, unwashed fruits/veggiesTravelers are vulnerableVaccine availableLife-threatening illnessIn GI tract and then to bloodstreamHigh fevers (103-104 °F)Weakness and headacheStomach pains, loss of appetite, diarrhea or constipation Sometimes, a rash of flat, rose-colored spotsAfter symptoms clear, person could become a carrierAntibiotic treatment is recommended

157

High inoculum organisms

Tens of thousands or more neededExamples: Vibrio cholerae, C. perfringens

158

Clostridium difficile

Gram +BacilliSpore-formingObligate anaerobeMotileMakes exotoxinsantibiotic diarrhea

159

Giardia lamblia

Also most common intestinal parasite in USGiardiasis (aka Beaver Fever) is the foe of backpackers/hikersSymptoms for 1-2 weeks or more, may seem to resolve and then come backMechanism: presence of parasite causes loss of epithelial absorptive surface area. Trophozoites: Attachment but not penetrationFoul-smelling diarrheaFilter water in areas where Giardia cysts are likely to exist. Water does not need to be contaminated with human sewage. Wildlife can deposit cysts.

160

Cryptosporidium parvum

Often seen when a sanitation system failsPool/waterpark chlorination/UV treatmentStorms or issues with drinking waterDiarrhea symptoms for 1-2 weeks to ~30 days, may seem to resolve and then come backMechanism: Absorption impaired and secretion enhanced when intestinal epithelial cells are infected by Cryptosporidium“Crypto” is opportunisticHIV/Immunocompromised individualsChronic Diarrhea/fluid lossCan be fatalWatery, frequent, non-bloody stoolDisrupts epithelial microvilli, slides into host cells, enveloping itself in the host cell membraneOocysts to sporozoites and backCoccidia subclass

161

Entamoeba histolytica

AmebiasisMore prevalent in tropical/subtropical climatesOnly 10-20% of infected individuals will become ill (CDC)Of US population, male homosexuals most vulnerableBloody, mucus-ey loose stoolRelatively mild symptoms butCan invade the liver and form an abcessX-ray/ultrasound to detect abscess or tissue damageCysts in stool sample. Must differentiate from non-pathogenic entamoeba, takes a specialist.cytotoxic

162

Metronidazole, Tinidazole

Tissue antiparasitic- low concentration in intestine, oral dose almost completely absorbed with high bioavailabilityDespite this, it is the drug of choice to treat symptomatic Giardia infection, even though organism that does not penetrate the epithelium!!Reminder: all about metronidazole/Tinidazole in lectures relating to treatment of H. pyloriDisulfiram reaction, avoid alcoholDisturb normal GI florabreaks down into toxic metabolites, damages DNA

163

Nitazoxanide

Mechanism: Interferes with pyruvate::ferredoxin oxidoreductase enzyme dependent electron transfer, essential to anaerobic energy metabolism protein Selectivity: Species difference in electron transferDistribution: Rapidly metabolized to tizoxanide. Parent compound is not detected in plasma. Moderately absorbed (33%), primarily luminal. For Crypto, used in combination with retroviral therapy for AIDS patients if at all, because of ineffectiveness

164

Iodoquinol

Mechanism: UnknownToxicity: loss of visual acuityUse with caution in patients with thyroid disease – its use interferes with certain thyroid testsDistribution: only 10% of the drug is absorbed so it works locally on the protozoa including cysts in the GI tract, luminal antiparasitic (amebicide)

165

Paromomycin

Mechanism: Aminoglycoside- targets 30S subunit ribosomeToxicity: Diarrhea, other GI effects including issues with intestinal flora because it has activity against some bacteria.Distribution: Luminal antiparasitic- Minimal absorption after oral administrationOtotoxicity, nephrotoxicity

166

TMP-SMX

Spectrum: Broad spectrum, many bacteria, but also effective against apicomplexans including Toxoplasma and Cystoisospora (formerly Isospora), and Cyclosporahits folic acid system

167

Enterobius vermicularis

Staple-sized wormspinwormsWorldwide distribution, most common helminth infection in USPrevalence can reach 50% in children, caregivers of infected children, and institutionalized individuals.Symptom: perianal pruritisAcquired by ingestion of pinworm eggsEggs can remain viable on surfaces for 2-3 weeks

168

Necator americanus/Ancylostoma duodenale

Pruritic Papular Erythematous RashHookworms are bloodsuckers…Major symptom is iron-deficiency anemia¼ ml/day/worm

169

Strongolides stercoralis

Autoinfection possible, especially with Immunosuppressed individualsStomach and GI complaintsRespiratorydry coughthroat irritationSkinan itchy, red rash that occurs where the worm entered the skinrecurrent raised red rash typically along the thighs and buttocks.

170

Trichuris trichiura

Diagnosis:Eggs in feces have a characteristic barrel-shaped appearanceFinger clubbing best indicator ofseverity of infestationBloody diarrhea = iron deficiency anemiaHeavy cases:Frequent, painful stools with mucus, water and blood, tenesmusRectal prolapse

171

Ascaris lumbricoides

Disease: ascariasisDisease: IF symptoms are experienced, abdominal discomfortIf a severe case, intestinal blockagesUltrasonography and radiology to determineHas a lung stage of life cycle, may cause coughDiagnosis: eggs w/thick shells

172

Albendazole and Mebendazole

Broad-spectrum benzimidazole drugsRoundworms and tapewormsDistribution: Limited oral absorption, albendazole is better absorbed if targeting tissue-migrating larvae is importantBroad-spectrum benzimidazole drugsMechanism: Binds to parasite β-tubulin and inhibits the formation of microtubulesDeath can take several days, for some helminths more than one dose may be necessarySpecificity: differences in tubulinToxicity: Systemic toxic affects on liver/bone marrow rareAbdominal pain, nausea, dizziness, headacheEmbryotoxic and teratogenic in pregnant ratsEvidence suggests safe for use in children when warranted

173

Pyrantel pamoate and Levamisole

Mechanism:Levamisole selectively opens a restricted subgroup of nematode acetylcholine receptor (AChR) ion channels in nematode nerve and muscle. depolarization entry of calcium through the opened channels, and an increase in sarcoplasmic calcium, producing spastic muscle contraction the parasite is then unable to maintain its location (often in the intestine) and is then swept away, effecting the cure. Toxicity: Causes nausea, vomiting, diarrheaDistribution: Poorly absorbed

174

Ivermectin

Mechanism: Binds to glutamate-gated chloride channels in invertebrate nerve and muscle cells, causing deactivation of channel: worm paralysis and death by starvationResistance: efflux transportersToxicity:Generally well-tolerated Itching, swollen lymph glands and rarely dizzinessInflammatory reaction due to death of adult wormsSpecificity: This type of channel restricted to phyla Nematoda and Arthropoda. in humans are only in the CNS , Doesn’t cross blood-brain barrierSpectrum: Nematodes- Ascaris, Strongyloides and Onchocerca

175

secretory diarrhea

characterized as an infection of the proximal small bowel marked by watery diarrhea that does NOT contain fecal leukocytes. Viruses that cause gastroenteritis do not infect the colon

176

Rotavirus Clinical presentation:

gastroenteritis

177

Norwalk Virus (Norovirus) Clinical presentation:

gastroenteritis

178

Adenovirus Clinical presentation:

gastroenteritis (do not confuse with other serotypes of adenoviruses that cause respiratory tract infections)

179

Rotavirus Pathology:

transmitted via the fecal to oral route. After ingestion of the virus it travels in the GI tract (the virus particle is stable within the low pH of the gastrointestinal system) to eventually infect the villus cells of the proximal small intestine. Here the virus replicates within these cells eventually lysing these cells which leads to the impaired adsorption of carbohydrates and other nutrients. This can lead to vomiting followed by watery diarrhea.

180

Norwalk Virus (Norovirus) Pathology:

fecal to oral transmission usually through direct contact or through contaminated food and water. Causes a local infection and inflammation in the proximal small intestine.

181

Adenovirus Pathology:

fecal to oral transmission. Causes a local infection and inflammation in the proximal small intestine. If inhaled into the lungs some respiratory symptoms can be present.

182

Rotavirus Diagnosis:

stool specimen, serology for the virus. Electron microscopy and RT-PCR also possible.

183

Norwalk Virus (Norovirus) Diagnosis:

not typically done. When done it is through visualization of the virus in stool specimens or PCR/serology of stool and/or vomit specimens.

184

Adenovirus Diagnosis:

PCR detection of the viral genome within a stool sample

185

Rotavirus Treatment:

rehydration (supportive). There is a rotavirus vaccine (live oral attenuated).

186

Norwalk Virus (Norovirus) Treatment:

usually not required because it is self-limited. When done, treatment consists of rehydration (supportive) if there is severe fluid loss. Outbreaks can be minimized through proper food handling, clean water supplies, and hand washing.

187

Adenovirus Treatment:

self-limiting infection in immunocompetent individuals. Supportive care only.

188

Rotavirus

because rotaviruses cause no inflammation, diarrhea has no blood. Infection before 6 months of age is uncommon due to passive IgA immunity from the mother’s colostrum. However, by age 3, almost every individual worldwide (~95%) has been infected and develops lifelong immunity. Virus particle contains a double-layered capsid.

189

Norwalk Virus (Norovirus)

this virus is a major cause of group-related or institutional diarrhea.

190

Adenovirus

major cause of acute infantile gastroenteritis. These serotypes of adenoviruses rarely cause fever or respiratory tract symptoms.

191

bifidobacteria

are among the first colonizers in breast-fed infants

192

Staphylococcus aureus

Gram +CocciCatalase +Coagulase +Also a common infectious agent of surgical wounds and cause of scalded skin syndromein food that sits around for a whileno need for antibiotics for a food borne infection

193

Bacillus cereus

Gram +Large Bacilliendospore-formingFacultative anaerobeMostly motileβ hemolytic Box-car shaped Also frequently found on skin and is a threat in hospitals as it produces biofilms that adhere easily to invasive devices. This produces chronic persistent infection, as the biofilm can periodically release B. cereus into the bloodstreamB. Cereus spores are commonly found in the soil and sometimes in plant foods that are grown close to the ground – such legumes, cereals, spices etc..Spores can survive rice cooking processDuration for both only about 24 hrsBecause of its ubiquity, B. cereus often is ignored or dismissed as a contaminant when found in a culture specimen. B. cereus in food and vomitus or feces of same serotype Large numbers of B. cereus of serotype known to produce endotoxinOnly necessary when tracking outbreaks

194

Clostridium botulinum

Gram +BacilliSpore-formingObligate anaerobeMotileSpores or toxin are the important issues for transmission of botulism

195

Staphylococcus aureus Symptoms:

Symptoms:nausea, vomiting, stomach cramps, and diarrhea for 1-3 daysAppear 1-7 hrs following ingestion of foodSelf-limiting, once toxin is gone, illness is gone

196

Staphylococcus aureus diagnosis

Positive diagnosis:Toxin-producing S. aureus can be identified in stool or vomitMost conclusive test is the linking of an illness with a specific food, or in cases in which multiple vehicles exist, detection of pre-formed enterotoxin in food sample(s).Only necessary when tracking outbreaks

197

Bacillus cereus infection

Infection takes two forms:Emetic (vomiting):Diarrheal:Duration for both only about 24 hrs

198

Bacillus cereus Emetic infection

Emetic (vomiting):1 to 6 hours incubationNausea and vomitingresembles the vomiting illness caused by Staphylococcus aureus enterotoxinsCaused by preformed enterotoxin that forms holes in membranesSelf limiting

199

Bacillus cereus Diarrheal infection

Diarrheal:6-15 hours incubationclinically similar to the symptoms of Clostridium perfringens infectionWatery diarrhea and abdominal crampsMechanism: Caused by large molecular weight enterotoxin that causes intestinal fluid secretion, probably by several mechanismsThis toxin is not likely pre-formed!Ingestion of large amounts of bacteria cause it to generate the toxin in the small intestineVulnerable populations might get sicker and require antibioticsPoor outcomes for systemic infection

200

Bacillus cereus diagnosis

Because of its ubiquity, B. cereus often is ignored or dismissed as a contaminant when found in a culture specimen. B. cereus in food and vomitus or feces of same serotype Large numbers of B. cereus of serotype known to produce endotoxinOnly necessary when tracking outbreaks

201

Botulism

Food borne botulism: ingesting toxinWound botulism: producing toxin Infant botulism: ingested sporesNot really a GI illness, diarrhea not prominent

202

Botulism Diagnosis

Symptoms and history, results of physical exam indicate botulismTests to exclude other causes of the illnessOrganism or toxin in stool sample only indirect evidence

203

Treatment for foodborne botulism

Ventilator if respiratory failure and paralysisAntitoxin if paralysis is not yet completeRemove contaminated food if still likely in gut

204

Botulism toxin

neurotoxinirreversibly blocks the release of acetylcholine from the motoric end plate which results in muscle weakness and paralysisToxin is absorbed from GI tract to bloodstream

205

Symptoms, botulism

Toxin already produced, symptoms can begin when toxin hits GI tractdouble vision, blurred vision, drooping eyelids, slurred speech, difficulty swallowing, dry mouth, and muscle weakness

206

Symptoms, infant botulism

Incubation period, spores have to produce toxin-forming bacterialethargic, feed poorly, are constipated, and have a weak cry and poor muscle toneCan lead to paralysis of respiratory system and other muscles

207

Clostridium perfringens

Gram +BacilliSpore-formingObligate anaerobeNon-motileEnterotoxin binds to receptors in endothelial cell junctions, then generates pores in host mucosa cells.“C. perfringens infection often occurs when foods are prepared in large quantities and kept warm for a long time before serving”

208

Clostridium perfringens Symptoms

Symptoms:Diarrhea and abdominal crampsIncubation 6 to 24 hours (typically 8-12)Symptoms last for less than 24 hoursUsually NO fever or vomitingThe illness is not passed from one person to another

209

Clostridium perfringens Positive diagnosis

Positive diagnosis:Detection of toxin or high amounts of bacteria in fecesC. perfringens normally present in the GI tract, the problem is when you ingest a C. perfringens load high enough to produce enough toxin to generate symptoms

210

Clostridium perfringens Treatment

Treatment:Usually self-limiting, but more serious, longer-lasting cases in immunocompromised individuals should be treated to avoid complications

211

Campylobacter jejuni

Gram -Bacilli (Spirilli)microaerophilicMotileCold sensitive (often leads to false negatives)get it from poultryOne unique feature is that campylobacter cannot usually multiply in food.Symptoms:diarrhea, cramping, abdominal pain, and fever2-5 day incubationSymptoms can last a weekCan have vomiting, diarrhea can be bloodyMechanism: Symptoms are an inflammatory response to cell invasionPositive Diagnosis: stool culturePossible complication: Guillain-Barré syndrome

212

Salmonella enterica

Gram -BacilliNon spore formingH2S positive & lactose negativeMotile, flagellated

213

Salmonellosis

Symptoms:diarrhea, fever, and abdominal cramps 12 hr to 3 day incubationSymptoms typically last 4 to 7 daysMost persons recover without treatmentRemember: reactive arthritis as a possible complicationDiagnosis: we know for sure with a stool cultureTreatment: Hydration. Antibiotics only necessary if infection spreads beyond gut

214

Vibrio parahaemolyticus

Gram (-)Vibrio (curved rod)facultative anaerobesFlagellated, motileOxidase +water lovingDiagnosis: Vibrio may be isolated from cultures of stool, wound, or blood. Form pores in red blood cells but also in epithelial cells, disrupting gut homeostasissushi and shellfish

215

Vibrio parahaemolyticus Symptoms

Fairly mild bloody diarrhea, stomach cramps, fever, nausea, and/or vomiting, Symptoms last less than a week. In the immunocompromised, it can spread to the blood and cause serious or deadly infections in other parts of the body

216

Listeria monocytogenes

Gram positive rod-shaped bacteriaAlthough a rare illness, a leading cause of death by foodborne illnessGram (+)BacillusNon-fastidious!!!Flagellated, motileNon spore formingOxidase -Diagnosis: Stool sample ID inappropriatePositive ID is the bacterium found in a normally sterile siteImmune cells spread Listeria to other organsTrojan horseLiver is a major targetmilk, cheese, seafood, deli

217

Listeriosis

Mild GI infection for mostMore vulnerable are older adults, pregnant women, newborns, and adults with weakened immune systems OPPORTUNISTICFever and muscle aches or stiff neck, or if you develop while pregnant: fever and chillsMeningitis and sepsis in vulnerable populations

218

Shigella

Gram (-)BacillusFacultative anaerobenonmotile (distinguishes from e. coli)Non spore formingMainly lactose negative, H2S (-) (distinguishes from e. coli)Shigella sonnei: most Shigella-caused GI illnessesShigella flexnori: causes bacillary dysenteryShigella dysenteriae: rarest but most severe dysenteryinvade through m cellsSince Shigella is invasive, if not treated it can spread beyond the GI tract and cause complicationsAntibiotics for more severe cases, most usually resolve without antibioticsPossible complication: hemolytic uremic syndrome (HUS)

219

What is dysentery

Frequent, small bowel movements with blood and mucus, accompanied by rectal pain and spasms (tenesmus)

220

Shigella Transmission

Transmission: Mostly bacterium passing from stools or soiled fingers of one person to the mouth of another person.

221

Shigella Symptoms:

Symptoms: diarrhea (often bloody)feverstomach crampsSymptoms start 1-2 days following exposureUsually resolves in 5 to 7 days.

222

E. coli

Gram (-)BacillusFacultative anaerobemotileNon spore formingMainly lactose positiveDiarrheaUrinary tract infectionNeonatal sepsisGram-negative sepsisETECSTECTreatment: antibiotics generally not recommended (decaying bacteria release toxins)Tracking outbreaks: commercial PCR and antibody-based kits.

223

ETEC

Traveler’s Diarrhea, diarrhea in childrenactivates adenylate cyclase, end result water into lumen, NO bacterial penetration.

224

STEC

penetrates like Shigilla toxin. hemorrhagic colitis (HC) and/or HUS can result as a complication; children more vulnerable

225

E. coli Symptoms:

profuse watery diarrhea and abdominal crampingCan progress to bloody diarrhea for STECFever, chillsNausea with or without vomiting, loss of appetiteLess common: headache, muscle aches and bloatingIncubation:1-3 days ETEC, 3-8 for STEC Illness typically lasts 3-4 days, less than 10.

226

cholera toxin

Activates adenylate cyclase cAMP →  Na+ absorption,  Cl- excretionWater moves into lumen

227

typhoid fever

Only fecal-oral contaminant, no other host, so water is a big source of contaminatonDrinking water, unwashed fruits/veggiesTravelers are vulnerableVaccine availableLife-threatening illnessIn GI tract and then to bloodstreamHigh fevers (103-104 °F)Weakness and headacheStomach pains, loss of appetite, diarrhea or constipation Sometimes, a rash of flat, rose-colored spotsAfter symptoms clear, person could become a carrierAntibiotic treatment is recommended

228

High inoculum organisms

Tens of thousands or more neededExamples: Vibrio cholerae, C. perfringens

229

Clostridium difficile

Gram +BacilliSpore-formingObligate anaerobeMotileMakes exotoxinsantibiotic diarrhea

230

Giardia lamblia

Also most common intestinal parasite in USGiardiasis (aka Beaver Fever) is the foe of backpackers/hikersSymptoms for 1-2 weeks or more, may seem to resolve and then come backMechanism: presence of parasite causes loss of epithelial absorptive surface area. Trophozoites: Attachment but not penetrationFoul-smelling diarrheaFilter water in areas where Giardia cysts are likely to exist. Water does not need to be contaminated with human sewage. Wildlife can deposit cysts.

231

Cryptosporidium parvum

Often seen when a sanitation system failsPool/waterpark chlorination/UV treatmentStorms or issues with drinking waterDiarrhea symptoms for 1-2 weeks to ~30 days, may seem to resolve and then come backMechanism: Absorption impaired and secretion enhanced when intestinal epithelial cells are infected by Cryptosporidium“Crypto” is opportunisticHIV/Immunocompromised individualsChronic Diarrhea/fluid lossCan be fatalWatery, frequent, non-bloody stoolDisrupts epithelial microvilli, slides into host cells, enveloping itself in the host cell membraneOocysts to sporozoites and backCoccidia subclass

232

Entamoeba histolytica

AmebiasisMore prevalent in tropical/subtropical climatesOnly 10-20% of infected individuals will become ill (CDC)Of US population, male homosexuals most vulnerableBloody, mucus-ey loose stoolRelatively mild symptoms butCan invade the liver and form an abcessX-ray/ultrasound to detect abscess or tissue damageCysts in stool sample. Must differentiate from non-pathogenic entamoeba, takes a specialist.cytotoxic

233

Metronidazole, Tinidazole

Tissue antiparasitic- low concentration in intestine, oral dose almost completely absorbed with high bioavailabilityDespite this, it is the drug of choice to treat symptomatic Giardia infection, even though organism that does not penetrate the epithelium!!Reminder: all about metronidazole/Tinidazole in lectures relating to treatment of H. pyloriDisulfiram reaction, avoid alcoholDisturb normal GI florabreaks down into toxic metabolites, damages DNA

234

Nitazoxanide

Mechanism: Interferes with pyruvate::ferredoxin oxidoreductase enzyme dependent electron transfer, essential to anaerobic energy metabolism protein Selectivity: Species difference in electron transferDistribution: Rapidly metabolized to tizoxanide. Parent compound is not detected in plasma. Moderately absorbed (33%), primarily luminal. For Crypto, used in combination with retroviral therapy for AIDS patients if at all, because of ineffectiveness

235

Iodoquinol

Mechanism: UnknownToxicity: loss of visual acuityUse with caution in patients with thyroid disease – its use interferes with certain thyroid testsDistribution: only 10% of the drug is absorbed so it works locally on the protozoa including cysts in the GI tract, luminal antiparasitic (amebicide)

236

Paromomycin

Mechanism: Aminoglycoside- targets 30S subunit ribosomeToxicity: Diarrhea, other GI effects including issues with intestinal flora because it has activity against some bacteria.Distribution: Luminal antiparasitic- Minimal absorption after oral administrationOtotoxicity, nephrotoxicity

237

TMP-SMX

Spectrum: Broad spectrum, many bacteria, but also effective against apicomplexans including Toxoplasma and Cystoisospora (formerly Isospora), and Cyclosporahits folic acid system

238

Enterobius vermicularis

Staple-sized wormspinwormsWorldwide distribution, most common helminth infection in USPrevalence can reach 50% in children, caregivers of infected children, and institutionalized individuals.Symptom: perianal pruritisAcquired by ingestion of pinworm eggsEggs can remain viable on surfaces for 2-3 weeks

239

Necator americanus/Ancylostoma duodenale

Pruritic Papular Erythematous RashHookworms are bloodsuckers…Major symptom is iron-deficiency anemia¼ ml/day/worm

240

Strongolides stercoralis

Autoinfection possible, especially with Immunosuppressed individualsStomach and GI complaintsRespiratorydry coughthroat irritationSkinan itchy, red rash that occurs where the worm entered the skinrecurrent raised red rash typically along the thighs and buttocks.

241

Trichuris trichiura

Diagnosis:Eggs in feces have a characteristic barrel-shaped appearanceFinger clubbing best indicator ofseverity of infestationBloody diarrhea = iron deficiency anemiaHeavy cases:Frequent, painful stools with mucus, water and blood, tenesmusRectal prolapse

242

Ascaris lumbricoides

Disease: ascariasisDisease: IF symptoms are experienced, abdominal discomfortIf a severe case, intestinal blockagesUltrasonography and radiology to determineHas a lung stage of life cycle, may cause coughDiagnosis: eggs w/thick shells

243

Albendazole and Mebendazole

Broad-spectrum benzimidazole drugsRoundworms and tapewormsDistribution: Limited oral absorption, albendazole is better absorbed if targeting tissue-migrating larvae is importantBroad-spectrum benzimidazole drugsMechanism: Binds to parasite β-tubulin and inhibits the formation of microtubulesDeath can take several days, for some helminths more than one dose may be necessarySpecificity: differences in tubulinToxicity: Systemic toxic affects on liver/bone marrow rareAbdominal pain, nausea, dizziness, headacheEmbryotoxic and teratogenic in pregnant ratsEvidence suggests safe for use in children when warranted

244

Pyrantel pamoate and Levamisole

Mechanism:Levamisole selectively opens a restricted subgroup of nematode acetylcholine receptor (AChR) ion channels in nematode nerve and muscle. depolarization entry of calcium through the opened channels, and an increase in sarcoplasmic calcium, producing spastic muscle contraction the parasite is then unable to maintain its location (often in the intestine) and is then swept away, effecting the cure. Toxicity: Causes nausea, vomiting, diarrheaDistribution: Poorly absorbed

245

Ivermectin

Mechanism: Binds to glutamate-gated chloride channels in invertebrate nerve and muscle cells, causing deactivation of channel: worm paralysis and death by starvationResistance: efflux transportersToxicity:Generally well-tolerated Itching, swollen lymph glands and rarely dizzinessInflammatory reaction due to death of adult wormsSpecificity: This type of channel restricted to phyla Nematoda and Arthropoda. in humans are only in the CNS , Doesn’t cross blood-brain barrierSpectrum: Nematodes- Ascaris, Strongyloides and Onchocerca