M18: Ingestion-Acquired Pathogens Flashcards by Heather Acuff

Introduction to the Establishment of Infectious Diseases:

Pathogen transmission typically (but not always, e.g. endogenous infections are caused by _) plays an important role in the infectious disease cycle.

The initial symptoms of an exogenous infection often reflect its _.

Some pathogens can enter the body by multiple routes. An example is _, which can enter via insect bites, cuts, ingestion and inhalation.

normal flora

transmission

Francisella tularensis

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Pathogens for Transmission Routes:

Inhalation (respiratory) (2)

Ingestion (2)

Blood (1)

Arthropods (2)

STI (2)

Wounds (1)

M. tuberculosis, influenza virus

Salmonella spp., rotavirus

Hepatitis B virus

Borrelia burgdorferi, Plasmodium spp.

HIV virus, N. gonorrhoeae

C. perfringens

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Introduction to the Establishment of Infectious Diseases:

Major routes for pathogen entry (6)

ingestion
inhalation
blood
arthropod bites
STD or urinary
wound/rupture

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Introduction to Ingestion-Acquired Diseases:

Ingestion-acquired illnesses often (but not always) cause _ symptoms, e.g., diarrheal disease of infectious origins is usually acquired by ingestion.

Ingestion-acquired diseases can be _ or _

true infections or intoxications.

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Introduction to Ingestion-Acquired Diseases:

Intoxications: _ is sufficient to obtain disease.

i) Foodborne intoxications often involve _- and _-stable toxins.
ii) Symptoms of these intoxications usually develop (slowly / quickly), since toxin is _.
iii) Symptoms of these intoxications often involve the _: (3).
iv) An exception to (ii) and (iii) is _

ingestion of preformed toxin

i) heat- and pH-
ii) quickly, already present
iii) GI tract: vomiting, diarrhea, cramps
iv) foodborne botulism.

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Introduction to Ingestion-Acquired Diseases:

Infections: ingested pathogen must be _.

i) Invasive pathogens acquired by ingestion: typically cause _ (often evident by the presence of fecal _, which can be diagnostically useful), as well as such _ symptoms as _, _, and _

Invasive pathogens can typically remain _ (e.g., Shigella spp. or nontyphoid Salmonella) or _ (e.g., S. typhi, hepatitis A virus). Symptoms caused by these invasive pathogens typically develop rather (slowly / quickly) (several days).

present in the body

i) inflammation, leucocytes, GI, cramps, diarrhea and (sometimes) fever.

localized in the GI tract
disseminate
slowly

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Introduction to Ingestion-Acquired Diseases:

Infections: ingested pathogen must be _

ii) In vivo _ production by ingestion-acquired pathogens: several _ (e.g., Vibrio cholerae, ETEC, Clostridium perfringens) produce toxins only after they become _.

Usually these toxin-producing bacteria are (invasive / noninvasive) (exception: Shigella dysenteriae).

present in the body.

enterotoxin
bacteria
present in the GI tract

noninvasive

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Introduction to Ingestion-Acquired Diseases:

Toxins produced in the GI tract usually cause mainly GI symptoms (diarrhea, cramps), which is why they are referred to as _.

An exception is EHEC, whose toxin (_) not only affects the _ but can also be absorbed into the circulation and then damage the _.

Symptoms of GI diseases involving pathogens producing toxins in vivo usually develop (slower / quicker) than intoxications (but often a little (slower / faster) than illness caused by invasives).

Other mechanisms: EPEC bind to _ and inject effectors into them to alter _ pathways.

enterotoxins

shiga toxin
colon
kidneys

slower
faster

enterocytes
signal transduction

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Introduction to Ingestion-Acquired Diseases:
Transmission of Ingestion-Acquired Pathogens:

Some pathogens acquired by ingestion are almost exclusively associated with _ or _ infections (e.g., foodborne botulism).

Other pathogens can be ingested in _, _, or by _ (e.g., Shigella spp.).

Many (but not all) ingestion-acquired pathogens are transmitted via direct or indirect _.

food- or water-borne

food, water, or by direct fecal-oral contact

fecal-oral contamination

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Introduction to Ingestion-Acquired Diseases:
Transmission of Ingestion-Acquired Pathogens:

Food poisoning: there are ~30-70 million cases of food poisoning in the USA each year, resulting in 5-9 thousand deaths. In _ countries, these illnesses cause even more deaths (in the millions/year), particularly in _ (this is also true of waterborne infections).

i) >75% of all foodborne disease has a _ origin (once thought this was mostly bacterial, but increasing evidence for viral cause also).
ii) _, _, and _ are most common symptoms, but sometimes also include _.
iii) Typically result from a combination of _, _, and/or _

underdeveloped
young children

i) microbial
ii) Diarrhea, cramping and vomiting, fever
iii) incomplete cooking, poor sanitation during handling and/or poor food storage conditions.

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Bacterial Intoxications:
Staph aureus:

Mechanism

Symptoms

heat-stable enterotoxin

vomiting

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Bacterial Intoxications:
Bacillus cereus (emetic form):

Mechanism

Symptoms

heat-stable enterotoxin

vomiting

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Bacterial Intoxications:
Clostridium botulinum:

Mechanism

Symptoms

heat-labile neurotoxin

flaccid paralysis

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Bacteria Producing Enterotoxins in vivo:
Clostridium perfringens:

Mechanism

Symptoms

heat-labile enterotoxin

diarrhea, cramps

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Bacteria Producing Enterotoxins in vivo:
B. cereus:

Mechanism

Symptoms

heat-labile enterotoxin

diarrhea, cramps

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Bacteria Producing Enterotoxins in vivo:
EHEC:

Mechanism

Symptoms

shiga toxin

diarrhea, cramps

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Bacteria Producing Enterotoxins in vivo:
ETEC:

Mechanism

Symptoms

heat-labile and heat-stable enterotoxins

diarrhea

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Bacteria that Invade the Intestinal Epithelium:
Nontyphoid Salmonella:

Mechanism

Symptoms

Invasion and Inflammation

fever and diarrhea

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Bacteria that Invade the Intestinal Epithelium:
Shigella spp.:

Mechanism

Symptoms

Invasion and Inflammation

dysentery/diarrhea and fever

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Bacteria that Invade the Intestinal Epithelium:
Campylobacter jejuni:

Mechanism

Symptoms

Invasion and Inflammation

fever and diarrhea

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Bacteria that Invade the Intestinal Epithelium:
Yersinia enterocolitica:

Mechanism

Symptoms

Invasion and Inflammation

fever and diarrhea

Bacteria that Invade the Intestinal Epithelium:
Listeria monocytogenes:

Mechanism

Symptoms

Invasion and Inflammation

influenza-like

Viruses:
Hepatitis A:

Mechanism

Symptoms

necrosis

fever and malaise, then hepatitis

Viruses:
Noroviruses:

Mechanism

Symptoms

necrosis

vomiting and diarrhea

Parasites: Trichinella spp.: Mechanism Symptoms

invasion fever

The Six Most Common Food Poisoning Bacteria in the USA (6)

``` Nontyphoid Salmonella Clostridium perfringens Shigella spp. Campylobacter jejuni E. coli Staphylococcus aureus ```

Waterborne infections: in 1993 there was a massive outbreak of cryptosporidiosis in Milwaukee, causing many deaths. i) In the USA, waterborne infections often result from _ or from _. Many waterborne pathogens are highly resistant to _. ii) Waterborne outbreaks are considered to be (more / less) of a potential public health threat than food poisoning since nearly everyone ingests water for drinking, brushing teeth, etc. iii) These illnesses usually produce morbidity in the _ but can be fatal in _ individuals.

aging water treatment plants equipment breakdowns at those plants chlorination more healthy compromised

``` Common Disease(s) caused by Waterborne Microbial Pathogens: Bacteria: ``` Vibrio cholerae Other gram-negatives, e.g., E. coli, Shigella

cholera fever and diarrhea

``` Common Disease(s) caused by Waterborne Microbial Pathogens: Parasites: ``` Giardia spp. Entamoeba histolytica Cryptosporidium spp.

chronic diarrhea, cramps, weight loss, fatigue varies from mild diarrhea to severe dysentery (more serious in immuno-compromised) varies from mild diarrhea to severe dysentery (in immunocompromised)

``` Common Disease(s) caused by Waterborne Microbial Pathogens: Viruses: ``` Hepatitis A virus Noroviruses Rotavirus Enterovirus

fever and vomiting; then hepatitis viral gastroenteritis (vomiting, diarrhea) Diarrhea (rarely dysentery) cramps, dehydration (children) GI illnesses and meningitis or poliomyelitis

GI tract defenses against pathogens (and pathogen countermeasures): Physical and chemical defenses of the GI tract (5)

i) Gastric acid ii) Bile iii) Intestinal proteases iv) Mucus v) Intestinal motility

GI tract defenses against pathogens (and pathogen countermeasures): Pathogen countermeasures against GI tract physical and chemical defenses (6)

i) Ingestion in large numbers ii) Develop acid and/or bile resistance (e.g., O antigen) iii) Being ingested in food (provides physical protection and buffering) iv) Produce urease to raise pH of the microenvironment v) Seek shelter under mucus vi) Adherence

GI tract defenses against pathogens (and pathogen countermeasures): GI tract immune defenses (4)

i) IgA ii) GALT (Peyer's Patches): M cells, B cells, T cells iii) GI tract immune defenses probably have both good and bad effects iv) GI pathogens can develop several countermeasures against GI tract immune defenses

GI tract defenses against pathogens (and pathogen countermeasures): Normal microbial GI flora (2)

i) Help protect against GI pathogens | ii) GI pathogen countermeasures: produce novel pili to adhere to unoccupied sites in the GI tract.

Campylobacter jejuni: Biologic characteristics: (motile / immotile), _ shaped, oxidase-(positive / negative), Gram-(positive / negative) rods. a. _: need rich medium for growth (e.g., Skirrow's or Campy media). b. _. c. Grow best at (high / low) temperatures.

``` motile curved/gull winged positive negative rods ``` a. Fastidious b. Microaerophilic c. high

Campylobacter jejuni: Reservoir and Transmission: C. jejuni has an _ reservoir; typically it is acquired by _. a. There are a million cases/year in USA. b. Can also be transmitted by _ or by _.

animal (zoonotic) ingestion of contaminated food (particularly poultry) b. ingestion of fecally-contaminated water or by handling a sick pet

Campylobacter jejuni: Virulence factors: a. _: for attachment to bowel. b. _: induces intestinal inflammation. c. some strains make an _ with activity like cholera toxin, but many disease isolates don't

a. Adhesins b. LPS c. enterotoxin

Campylobacter jejuni: Pathogenesis: a. After ingestion, C. jejuni attaches to the lower _ / (more commonly) upper _ and then invades. b. Invasion induces _, which is important contributor to symptoms c. Disease symptoms start from (#)-several days after ingestion and usually self-resolve ~(#) days later. d. Symptoms include: (3) e. Sequelae can include _ and _

a. small intestine, large intestine b. inflammation c. 1, 5 d. cramps, diarrhea (sometimes with fecal leucocytes), fever e. arthritis and Guillain-Barre syndrome

Campylobacter jejuni: Diagnosis: a. Lab approaches important: _ and _ tests used. Prevention and Treatment: a. Prevention: _, including complete cooking of foods. Vaccine? b. Treatment: in mild cases, only _ therapy and _ replacement. In severe cases, _ can reduce duration and severity of symptoms.

a. culture and biochemical b. good hygiene, No vaccine available c. symptomatic, fluid, antimicrobials

Giardia spp.: Biologic characteristics: a. Protozoan that grows in two forms: a _ form (_) that multiplies in the duodenum, and a _, which forms in the _. The cysts are (infectious / non-infectious) and are often secreted in large numbers in _. Once ingested and transported to the small intestines, the cysts convert back to the _ form. b. Cysts of Giardia spp. are highly resistant to _ and can persist in the environment.

``` vegetative form (trophozoites) cyst, colon ``` infectious stool trophozoite chlorination

Giardia spp.: Reservoir and transmission: a. Zoonotic reservoir: includes (3) b. Transmission: i) Often acquired by ingestion of _ (campers or communities with aged or broken water systems). ii) Can also be spread from person to person by _, e.g., in day care centers. iii) Less commonly spread by _. Virulence Factors: a. Resistance and persistence of _.

a. wild animals, farm animals and pets. i) contaminated water ii) fecal-oral contact iii) contaminated foods a. cysts

Giardia spp.: Pathogenesis: a. Cysts are very _ (ingestion of ~10 cysts may start an infection). b. After ingestion, cysts develop into _, which multiply in the duodenum. In many (most?) people, no symptoms develop (these people can be _). There is a spectrum of disease: (3). c. When acute disease develops, it starts about 1-3 weeks after ingestion and then resolves 1-4 weeks later (w/o _). Symptoms often persist longer in _ (can result in significant weight loss), but more chronic infection also occurs in some _ (may involve less prominent diarrhea). Relapses are fairly (common / rare) (particularly in the compromised). People with _ deficiency at particular risk for chronic infection or relapse. d. Symptoms: acute form can involve _ involving a foul-smelling, greasy _ devoid of _ or _. e. Symptoms apparently result from _ of fats and carbohydrates in the small intestine. May also involve intestinal _?

a. infectious b. trophozoites, carriers, acute, chronic and relapses (recurrent) c. treatment, children, adults, common, IgA d. explosive, sudden onset diarrhea, stool, blood or mucus e. malabsorption, inflammation

Giardia spp.: Diagnosis: demonstrating the presence of _ or _ in _. Prevention and Treatment: a. Prevention: i) Good municipal _ ii) Good _ iii) Vaccine? b. Treatment: i) _ (Flagyl) is often used (close contacts may be given prophylactic treatment).

trophozoites or cysts in stools i) water treatment ii) personal hygiene iii) No Vaccine is available i) Metronidazole

Cryptosporidium parvum: Biologic characteristics: (small / large) (intracellular / extracellular) _. Multiplies in the _ using both sexual and asexual reproduction. a. _ penetrate enterocytes and then develop into _. b. The trophozoites divide into _, which can multiply sexually or develop into _. c. Oocysts are shed via _. Reservoir and transmission: a. Reservoir: _ b. Typically transmitted by _ c. Can also be spread person to person via _ Virulence factors: a. Poorly understood.

small intracellular protozoan GI tract a. Sporozoites, trophozoites b. merozoites, oocysts c. stool a. zoonotic reservoir (particularly farm animals, but also pets). b. ingestion of contaminated water. c. fecal-oral contact.

Cryptosporidium parvum: Pathogenesis: a. After ingestion, the oocysts develop into _ in the intestines. b. Sporozoites attach (using a ventral sucking disk) to, and then invade _, establishing themselves under the brush border membrane region of _. c. In that cellular region, the sporozoites develop into _, sometimes causing (somehow) diarrhea. May involve an _ component and _. There are also asymptomatic infections. d. _ develops ~ 1 week after ingestion and persists for 1-2 weeks in the immunocompetent. Relapse can occur but only for a limited time-frequency? e. In the immunocompromised, the _ symptoms are more severe and persistent. Infection becomes _. Can be a contributor to death (dehydration).

a. sporozoites b. enterocytes, intestinal epithelial cells c. trophozoites, inflammatory, malabsorption d. Diarrhea e. diarrheal, chronic, dehydration

Cryptosporidium parvum: Diagnosis: a. Demonstrating the presence of oocysts in stool using a modified acid-fast stain. b. Serologic tests can also be used. Prevention and Treatment a. Prevention: i) Good hygiene ii) Adequate water treatment (difficult) since cysts are relatively resistant to chlorine, etc. They are killed by boiling. b. Treatment: i) Not usually necessary for the immunocompetent. Nitazoxanide is FDA-approved for use in these people. ii) Effective therapy lacking for adult immunocompromised (paromomycin?); antiretroviral therapy for AIDS patients helps by restoring immune function. Otherwise, rely on supportive therapy (rehydration, etc.).

Rotavirus: Biologic characteristics: a. Member of the _ family ((ss / ds)(DNA / RNA)) genome comprised of 11 segments) b. These viruses have an _ capsid comprised of two layers. c. Envelope? d. Acid-resistant? Reservoir and transmission: a. Reservoir: _ b. Transmission: via _. Usually by _ (by inhalation also?). These viruses (can / cannot) withstand the acidity of the stomach. i) Seasonal: more common in _. Virulence factors: a. Produce a _ protein (i.e., a protein made in infected cells that does not appear in the mature virus) named _; that protein has _-like properties.

a. Reovirus, dsRNA b. icosahedral c. No envelope. d. yes a. humans b. fecal-oral route, ingestion, can c. winter a. nonstructural, NSP4, enterotoxin

Rotavirus: Pathogenesis: a. After ingestion, virus multiples in _. b. Symptoms usually develop within 48 hours in _. Slightly longer incubation time in _. c. Symptoms typically include intense _, often preceded by _. May be _. Symptoms usually continue for several days to a week. d. Rotaviruses have been the most common cause of infectious _ in children 500,000/year) but also occur in the USA (~20-40/year). Rotaviruses can also sicken adults (particularly the elderly), but symptoms are usually _. e. It is possible to be infected without _. f. _ appears to reduce the incidence and severity of disease.

a. intestinal mucosa b. babies/young children, adults c. diarrhea, vomiting, fever d. diarrhea, milder e. showing symptoms f. Previous infection

Rotavirus: Diagnosis: a. Lab tests important: i) _: look for distinct appearance of rotavirus. ii) _ tests now also used. Prevention and treatment: a. Prevention: i) A _ was introduced in 1998 but was then discontinued. New vaccine recently licensed. Now recommended for American infants, given orally at 2, 4 and 6 months. b. Treatment: i) Restore _

i) Electron microscopy ii) Serologic i) live attenuated rotavirus vaccine i) fluid/electrolyte balance

Hepatitis A Virus (HAV): Biologic characteristics: a. _: has ((ss/ds)(DNA/RNA)) genome of (positive / negative) polarity b. Enveloped? c. (#) serotype(s) is/are known. Reservoir and transmission: a. _ only reservoir. b. Usually transmitted via _, often by _. c. Very (common / rare) worldwide, particularly in developing countries.

a. Picornavirus, ssRNA, positive b. Nonenveloped c. Only one a. Humans b. fecal-oral route, ingestion of fecally contaminated food (e.g., raw shellfish) or water c. common

Hepatitis A Virus (HAV): Pathogenesis: a. After ingestion, virus replicates in _. Often no disease develops (_). Somewhat less than 50% of infected people develop a _ after about 2-4 weeks. If sufficient _ are present, the disease does not develop further. b. If insufficient neutralizing antibodies are present, HAV invades the _, spreads to the _, and induces an _ disease. _ usually present at this point. c. Liver damage is probably from an _ response (_). d. Most people with hepatitis A completely recover within 2 months, i.e., this is typically an _. HAV does not cause _. e. Of most concern, a few (~1%) infected people experience a _ that can be fatal. Usually occurs in people with _. f. Infection provides _ (one third of Americans have been infected but

a. gut inapparent infection flu-like illness (low fever, malaise, nausea, diarrhea, etc.) HAV-neutralizing antibodies b. blood, liver, acute inflammatory, Jaundice c. inflammatory, (cytotoxic T cells directed against virus-infected cells) d. acute hepatitis, chronic, long-term infection e. fulminant hepatitis, pre-existing liver disease f. long-term immunity, immune

Hepatitis A Virus (HAV): Diagnosis: a. (Can / Cannot) be distinguished from other types of hepatitis on the basis of clinical signs. b. Definitive diagnosis depends upon demonstrating the presence of anti-HAV _ antibodies (these start to appear shortly before disease and disappear after 6 months). Can't rely upon anti-HAV _ antibodies for diagnosis of active disease because many people have these antibodies from _ (presence of these antibodies _). Prevention and Treatment a. Specific antiviral chemotherapy (available / not available). b. Prevention can be achieved in several ways: i) _ ii) if person recently exposed to HAV, they can be given either HAV _ to obtain passive immunity or (sometimes) HAV _. iii) HAV vaccine: a _ vaccine is recommended for infants at 12 months. Also given to _ and other high-risk people.

a. Cannot b. IgM, IgG, previous inapparent or mild HAV infections, persists forever a. not available i) hygiene ii) immune globulin, vaccine iii) killed virus, travelers