GI

Question 1

Bacteroides fragilis
Structure, Path, and Virulence

Answer 1

The prototypical endogenous anaerobic pathogen that is a minor member of the GI flora

Pleomorphic in size and shape, so it resembles a population of organisms on Gram stain. They are Gram negative rods and have a polysaccharide capsule (anti-phagocytic, as are short chian fatty acids produced during anaerobic metabolism). Its LPS has little endotoxin activity

Anaerobes that can produce disease can normally tolerate oxygen. They often have catalase and superoxide dismutase

Produces a heatl-labile zinc metalloprotease toxin (BFT) that leads to F-actin rearrangement and chloride secretion with fluid loss.

Can adhere to the peritoneal surfaces via fimbriae

Growth is stimulated by 20% bile

Question 2

Bacteroides fragilis

Disease, Diagnosis, and Treatment

Answer 2

Most common organism isolated from intraabdominal infections, and can cause gastroenteritis if it produces enterotoxin (watery diarrhea)

Can form gynecologic abscesses, and is the most common anaerobe isolated in blood cultures (bacteremia)

Can lead to myonecrosis following soft-tissue infection (normally through inoculation, as it is not part of the normal skin flora)

Culture on media containing bile (which stimulates growth), gentamicin (which it is resistant to, as well as kanamycin, vancomycin, and colistin), and esculin (which it hydrolyzes to produce a black precipitate)

Most produce B-lactams, so they are resistant to penicillins and cephalosporins

Treat with metronidazole, carbapenems, and B-lactam-B-lactamase inhibitors

In adults, B. fragilis is primarily associated with infections of the peritoneal cavity where it induces abscess formation following bowel perforation

Question 3

Campylobacter sp.

Answer 3

Small, comma-shaped, microaerophilic (grows in reduced oxygen and increased CO2), gram-negative rods that are motile via a polar flagellum. Found in stool

It (and Helicobacter) are characterized by 1) low GC content in DNA, 2) inability to ferment/oxidize carbs, 3)microaerophilic growth requirements

Conditions that increase gastric pH favor disease, as it would normally be killed by the acid. They are zoonotic infections associated with contaminated poultry, milk, water. It is uncommon for the disease to be transmitted by food handlers even though fecal-oral transmission can happen.

More of these infections per year than salmonella and shigella combined. It is most common in young children and 20-40 year old adults, especially in developing nations. Most common causes of bacterial gastroenteritis in US

Disease: diarrhea, fever, and abdominal pain (acute enteritis) with bloody stools that can be mistaken for acute appendicitis b/c of abdominal pain. Chronic infections can occur in immunocompromised. Normally the diseases are self-limited

• C. jejuni* is the most common cause of bacterial gastroenteritis in the US. It hits the jejunum, and is also associated with Guillain-Barre and reactive arthritis. A commercial antigen test that is fairly accurate is available for C. jejuni and C. coli.
• C.coli* is more common in developing countries, and is unique in that it grows at 42 C.
• C. fetus* causes systemic (intravascular and extraintestinal) infections including septic abortion, meningitis, bacteremia, arthritis. It is covered with a heat stabile “S protein” that inhibits C3b binding (main virulence factor). Normally hits immunocompromised elderly people.
• C. upsaliensis* is also associated with Guillain-barre, and is transmitted through contact with domestic dogs.

Microscopically, thin and not easily seen with gram stain; however, obserbation of S-shaped organism in stool is very specific.

Culture is finicky: slow growing at 42C, use charcoal to absorb toxins, has to be microaerophilic, and has to contain antibiotics to kill other bacteria

Jejuni main organism in humans (99%)

Treat: Erythromycin or Azithromycin. Proper pasteurization and food handling

Question 4

Helicobacter

Answer 4

Spiral, gram-negative rods characterized by sequence analysis of their 16S rRNA genes, cellular fatty acids, urease production (which can be used in diagnosis), and presence of highly motile polar flagella (has corkscrew motility). Stain with Warthin-Starry silver stain (100% specific)

Catalase and oxidase positive. They do not use carbs, but can frement amino acids. Its LPS does not have high endotoxin activity, but the O side chain is similar to Blood group antigens (immune protection)

Associated with gastritis (feeling of fullness, nausea, vomiting, and hypochlorhydria), peptic ulcers, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue (MALT) B-cell lymphomas.

It survives in the stomach by 1) initially blocking acid production via an acid-inihbitory protein and 2) using urease to generate ammonia to neutralize the acid. It then passes through the gastric mucus and adheres to cells via surface-adhesion proteins.

Induces tissue damage via: mucinase, phospholipases, vacuolating cytotoxin A (VacA: causes damaging vaculole formation upon endocytosis), cytotoxin-associated gene (cagA: type IV secretion system that interferes with cytoskeletal structure of epithelial cells), and IL-8 induction (brings damaging neutrophils). cagA strains and higher IL-1 production have higher risk of causing cancer.

Humans are primary reservoirs; we transmit via the fecal-oral route. Can actually be protective against GERD and adenocarcinomas of the lower esophagus.

Histological diagnosis is limited b/c of invasive gastric biopsy to get specimen. The most common method of diagnosis involves antigen detection in stool, as they do not require a biopsy or expensive equipment to administer. Antibody detection of IgA/ IgG can’t discriminate acute or chronic infection (they persist for years)

Treat with proton pump inhibitors, macrolides, and becta-lactams.

Other Helicobacters: H. cinnaedi and H. fenneliae: colonize intestines isolated from homosexual men

Question 5

Clostridium difficile

Answer 5

Genus defined by presence of endospores, stricty anaerobic metabolism, inability to reduce sulfate to sulfite, and gram-positive cell wall structure (not all species meet all requirements)

Toxin-producing C. difficile is responsible for antibiotic-associated gastroinestinal disease ranging from self-limited diarrhea to pseudomembranous colitis.

Enterotoxin (Toxin A) is chemotactic for neutrophils, bringing them into the ileum, and disrupts the tight cell-cell junction leading to diarrhea. Cytotoxin (Toxin B) causes actin to depolymerize, disrupting the cytoskeleton. Diagnosis of infection is dependent on finding toxins in stool, not organism itself.

One recent strain had a mutation upregulating toxin production that had a higher mortality rate and was resistant to fluroquinolones (test for binary toxin for this strain).

Surface layer protiens (SLPs) are important for binding to intestinal epithelium

Normal flora in a small number of healthy people

Treat by discontinuing antibiotic, and in severe cases treat with metronidazole or vancomycin

Question 6

E. coli

Answer 6

Gram-negative, fermenting, oxidase negative, facultative anaerobic rods. Most common gram-negative rods isolated from patients with sepsis, cause 80% of all UTIs, and cause gastroenteritis

Most UTIs start in the colon and are more likely to occur with strains possessing adhesions and hemolysin A

Along with group B streptococci, causes the majority of CNS infections in infants younger than 1 month. These strains possess K1 capsular antigen

Often associated with septicemia as an extenstion from a UTI or GI tract infection

E. coli 0157:H7 O antigen on LPS and flagellar H antigen. capsule or fimbrial antigen would be K antigen

Pathogenic E. coli picked up viruelence genes from a plasmid. Bottom line: pathogenic and commensal have same genome i.e. same biochemical properties so no test can really tell the difference. You have to look for antigens and virulence factors

intestinal pathogenic E. coli (iPEC) are the ones we are studying like enterotoxigenic, enteropathogenic

Question 7

Enterotoxigenic E. coli (ETEC)

Answer 7

Seen in young children, particularly in developing countries as well as in travelers to developing countries. High inoculum for disease, spread is through consumption of fecally contaminated food or water. Leads to secretory diarrhea similar to cholera, but less severe.

Produces heat labile toxins, one of which (LT-I) is functionally and structurally similar to cholera toxin (AB toxin that hits GM1 gangliosides and ribosylates Gs leading to increased cAMP).

Produces heat stabile toxins (Sta) that binds to guanylate cyclase leading to increased cGMP and hypersecretion of fluids.

LT-1 and Sta are on a transferable plasmid that also contains colonization factor adhesions (all of which are needed for disease)

Associated with lettuce, fruits and vegetables

Question 8

Enteropathogenic E.coli (EPEC)

Answer 8

First E.coli associated with diarrheal disease and remains a major cause of infant diarrhea (less than 2 yo) in impoverished countries (rare in developed). In developed world associated with outbreak in daycare centers and peds wards

Person to person spread occurs, meaning a low infectuous dose is needed. Leads to watery diarrhea and vomitting

Infection occurs through bacterial attachment followed by destruction of the microvillus (attachment/effacement histopathology). This is mediated by a plasmid encoded bundle forming pili (BFP). Following attachment, secretion of proteins via a type III secretion system occurs. Most of this E. coli’s virulence factors are encoded on a pathogenicity island called the locus of enterocyte effacement (LEE).

Translocated intimin receptor (Tir) is injected into the membrane and serves as a binding site for bacterial adhesin intimin. This eventually leads to cell death.

Question 9

Enteroaggregative E. coli (EAEC)

Answer 9

Cause persistent watery diarrhea with mucus and dehydration in infants in developing countries. One of few bacteria associated with chronic diarrhea and growth retardation.

Characterized by their autoagglutination in a “stacked-brick” arrangement mediated by aggregative adherence frimbriae I which is similar to BFP.

Following adhesion, a biofilm is generated, protecting the bacteria from antibiotics and phagocytes.

Enteroaggregative heat stable toxin (EAST) is related to heat-stable toxin of ETEC

Plasmid encoded toxin also induces fluid secretion

Question 10

Enterohemorrhagic E.coli (EHEC)

Answer 10

Most common disease producing strains in developed countries.

The most common strain (O157:H7) produces bloody diarrheal syndrome known as hemorrhagic colitis evolved from EPEC, has attaching and effacing activity, and has picked up Shiga toxin(an AB toxin carried by bacteriophages that attaches to globotriaosylceramide (GB3) and binds to the 28S subunit of rRNA halting protein synthesis.)

Hits Large Intestine, unable to ferment sorbitol

A/E attaching and effacing lesions: EPEC and EHEC

Disease most common in warm months and in children younger than 5 years who have eaten undercooked ground beef or other meat products, water, unpasteurized milk or fruit juices, uncooked veges.

Very low infectuous dose (less than 100 organisms), and person to person spread occurs

Disease ranges from diarrhea to hemorrhagic colitis with severe abdominal pain and bloody diarrhea. Vomitting occurs in half of all patients but high fever is absent.

Hemolytic uremic syndrome, a disorder characterized by acute renal failure, thrombocytopenia, and microangiopathic hemolytic anemia, is often a complication in children (associated more with Stx-2, one of the two shigatoxins)

Question 11

Enteroinvasive E.coli (EIEC)

Answer 11

Rare in the US and uncommon in developing countries. O124, O143, and O164 are pathogenic strains that are closely related to Shigella

Initially causes watery diarrhea, can progress to blood and leukocytes in stool. Does not produce Shigga toxin. ID₅₀ is 10⁶ bacteria (shiella is 10-100)

Hits Large Intestine

They invade and destroy colonic epithelium, leading to watery diarrhea that can progress to dysentery and hemorrhagic colitis with similar mechanism as Shigella: Invasion, phagosomal rupture, intracellular movement and then lateral spread to adjacent cell

Virulence factors are on a plasmid

Invades adjacent epithelial cells by polymerizing actin similar to Listeria

Associated with lettuce, fruits and vegetables

Question 12

Enterococcus

Answer 12

Gram-positive, catalase negative cocci arrranged in pairs and short chains that possess the group D cell wall antigen (similar to streptococci)

Most common species are E. faecalis and E. faecium. Found normally in the GI tract and in poop (Matt Pearce)

E.gallinarum and E.casseliflavus are both resistant to vancomycin

Have relatively few virulence factors, and are easily phagocytozed and killed. They are inherently resistant to many commonly used antibiotics and have gained resistance to many more. tolerant to heat chlorine and some alcohol preps makes it a good nosocomial organism.

Common cause of nosocomial infections of urinary tract, peritoneum, and heart tissue (endocarditis) in pateints who have received broad-spectrum antibiotics

Cannot be differentiated microscopically from S. pneumoniae, but use the optochin test (they are resistant), bile test, and the PYR test. Growth requires B vitamins, nucleic acid bases, and a carbon source. Grows in presence of high concentration of NaCl and bile salts

Treat with a combination of an aminoglycoside and a cell-wall active antibiotic

Question 13

Salmonella

Answer 13

Gram-negative, fermenter, oxidase negative, facultative anaerobic rods.

After ingestion it attaches to mucosa of small intestine and invades M-cells in Peyer patches. It remains in an endocytic vacuole where replication occurs.

Pathogenicity island I (PAI I) encodes salmonella secreted invasion proteins (Ssps) and a type III secretion system. Pathogenicity island II (PAI II) contains genes for host invasion and *another * type III secretion system.

Maintains an animal reservoir in poultry, livestock, rodents, et c. Spread is usually fecal oral and normally occurs in young children and old adults

Salmonella Typhi and Salmonella Paratyphi are highly adapted to humans and don’t cause disease anywhere else. Typhi has a low infectuous dose and allows for person to person spread, unless most other serotypes. Typhi produces typhoid fever, where bacteria reach the liver, spleen, and bone marrow and set up for a recurring infection. Initial signs of sepsis/ bacteremia w/ sustained fever (delirium) for more than a week before abdominal pain and GI symptoms. Typhoid fever shows characteristic leukopenia and mononuclear inflammation.

Gastroenteritis is the most common form of salmonellosis in the US. Symptoms occur 6 to 48 hours following consumption, and cause nausea, vomitting, and bloody or non-bloody diarrhea. Symptoms can last for 2 days to a week before spontaneous resolution.

Septicemia occurs more in pediatric, geriatric, sickle cell, and HIV patients. S. choleraesuis, typhi, paratyphi

Two main diseases: enteric fever (typhoid and paratyphoid) and gastroenteritis (nontyphoidal)

Question 14

Shigella

Answer 14

Gram-negative, fermenter, oxidase negative, facultatively anaerobic rods.

Causes bacillary dysentery

Invades and replicates in cells lining the colon (basal side) by first invading the M cells in Peyer patches. It uses a type III secretion system to inject Ipa(A-D) that induce membrane ruffling leading to engulfment of the bacteria by epithelial cells and macrophages.

It polymerizes actin behind it to propel itself into adjacent cells. They survive phagocytosis by inducing apoptosis of the host cell.

It produces Shiga toxin (see EHEC)

Humans are the only reservoir for Shigella. It is transmitted person to person via the fecal-oral route

Shigellosis is characterized by abdominal cramps, diarrhea, fever, and bloody stools coming 1-3 days following ingestion. Cardinal features include lower abdominal cramps and tenesmus (straining to defecate)

Associated with eggs, lettuce

Evolution: From E.coli to shigella: acquisition of a large plasmid and chromosomal pathogenicity islands as well as loss of genetic loci (like flagella). Most E. coli strains are motiole, lysine decarboxylase positive, use lactose and are indol positive. Shigella is non-motile, LDC negatie and dont use lactose (indol is variable)

Associated with HUS and Reider’s syndrome

Question 15

Vibrio parahaemolyticus

Answer 15

Gram-negative, fermentative, facultatively anaerobic rods

Positive oxidase reaction and polar flagella

Can cause a self-limiting gastroenteritis similar to mild cholera with explosive watery diarrhea. Wound infections can occur on exposure to contaminated seawater.

Most strains produces a thermostable direct hemolysin (TDH, Kanagawa hemolysin). This is important for marking virulent strains. It lyses human blood but not sheep blood

Most common gastroenteritis associated with contaminated seafood (especially in Japan/Asia)

Question 16

Vibrio vulnificus

Answer 16

Gram-negative, fermentative, facultatively anaerobic rods

Positive oxidase reaction and polar flagella, contain two circular chromosomes

Require salt for growth

Causes a life-threatening bacteremia that must be treated promptly with minocycline combined with a fluroquinolone or cefotaxime.

Associated with infection after exposure to seawater or eating improperly cooked shellfish

High mortality rate, particularly in patients with underlying hepatic, hematopoietic, or renal disease or those who are immunosuppressed.

Capsule production is important for widespread bacteremia

Question 17

Yersenia enterocolitica

Answer 17

Gram-negative, oxidase positive, fermentative, facultatively anaerobic rods

Can grow at cold temperatures on food in the refrigerator (especially unpasteurized dairy, pork)

Has a type III secretion system that injects Yop proteins to inhibit phagocytosis na induce apoptosis in macrophages.

All are zoonotic; pigs, rodents, livestock and rabbits are the natural reservoirs

Common cause of enterocolitis in Scandinavian and other European countries and in the colder areas of North America. Associated with eating contaminated meat or drinking water, milk. Infections are more common during cold months.

Disease occurs after 1-10 days, leads to diarrhea, fever, and abdominal pain that can last for 1-2 weeks, and can lead to a chronic infection. Disease involves the terminal ileum and can mimic acute appendicitis (pseudoappendicitis). In a small proportion of cases, skin rash, joint pains, bacteremia can occur. Is also associated with infection spread via contaminated blood donations.

Question 18

Cryptosporidium sp.

Answer 18

Sporozoa

Oranisms are found just within the brush border of the intestinal epithelium. They attach and replicate via merogony, gametogony, and sporgony, leading to infectious oocyst (double cell wall) formation. Sporogny is the one that can be excreted from digestive tract to spread infection

Infection in reptiles, mammals and fish. Water is an important mode of transmission, as they are resistant to ozone and chlorination. Fecal-oral route is also important means of transmission

Infections can lead to asymptomatic carriage, self-limiting entercolitis characterized by watery diarrhea without blood (this is worse for AIDS patients)

Epicellular location: forms circular membrane that wraps around parasite fusing to enclose the parasite. Provides protection to organism. Does not invade so non-bloody diarrhea

Diagnose by concentrating oocytes via modified zinc sulfate centrifugal floation technique or by Sheather sugar flotation procedure and acid-fast staining or immunofluorescence

Hard to treat in AIDS patients, spiramycin may help control diarrhea

Question 19

Entamoeba histolytica

Answer 19

Amoebae

Cyst and trophozoite forms are detected in fecal specimens (cysts are infectious). In fresh stools, the actively motile trophozoites are seen.

Gastric acid stimulates release of the trophozoite from ingested cyst in the duodenum. Local tissue destruction occurs leading to flask shaped uclerations, thought to be due to a cytotoxin.

Amoebae are killed by ambient oxygen concentrations

It is found in cold areas, but infections occur more often in tropical and subtropical regions with shitty water (pun intended). It can be vectored by cockroaches and flies, and is associated with oral-anal sexual practices.

Can cause asymptomatic carriage, intestinal amebiasis (abdominal pain, cramping, and diarrhea with more severe cases being bloody) and extraintestinal infection (usually hits the liver, abscess formation is common)

Identify via microscopy. Trophozoite has a big nucleus with a central dot (karyosome) and you may see ingested erythrocytes in the cytoplasm

Treat acute, fulminating amebiasis is treated with metronidazole followed by iodoquinol. Avoid things that could have poop on them or in them like the plague.

Question 20

Giardia lamblia

Answer 20

Flagellate with cyst and trophozoite stages that moves by their flagella. Diseases produced by flagellates are mainly due to mechanical irritation and inflammation.

Infection initiated by cyst ingestion (10-25 cysts needed). Gastric acid stimulates excystation and release of trophozoites in the duodenum and jejunum, where they multiply by binary fission. They attach to tips of villi by an “ventral sucking disk.” Frank necrosis does not occur, and organism rarely ever spreads outside GI tract.

Has a sylvatic distribution in many streams, lakes, and mountain resorts worldwide. Maintained in reservoirs like beavers and muskrats. Resistant to chlorination. Associated with poor sanitation.

Can lead to asymptomatic carriage, mild diarrhea (sudden onset, foul -smelling, watery diarrhea, abdominal cramps, flatulence, and steatorrhea), or a severe malabsorption syndrome

Finding them in stool is hit or miss, as they come in spurts or “showers.” There is a fecal antigen test that is fairl specific

Treat with metronidazole or nitazoxanide with furazolidone, tinidazole, paramomycin, or quinacrine. Boil your water, avoid high risk sexual behavior

Question 21

Enterobius vermicularis

Answer 21

AKA the pinworm: a small white worm that is often found in the perianal or vagina of infected children. This is the most common helminthic infection in North America.

Infection is initiated by eating embryonated eggs that hatch in the small intestine and migrate to the large intestine. Males and females mate and lay eggs in the perianal folds (up to 20,000).

Occurs worldwide, more prevalent in temperature regions where person-to-person contact is high.

No animal reservoir is known.

Autoinfection is when they hatch in the perianal folds then crawl back into the anus. Terrifying.

May produce inflammation, itching, loss of sleep, and allergic reactions to eggs as well as granuloma formation around the eggs in the intestines.

Diagnose by symptoms and detection of eggs. Treat with albendazole or mebendazole. Treat the entire family to prevent reinfection. Eggs can be found in dust and can be inhaled.

Question 22

Trichuris trichiura

Answer 22

Commonly called a whipworm because it resembles the handle and lash of a whip.

Ingested eggs hatch into a larval worm in the small intestine then migrate to the cecum where they penetrate the mucosa and mature to adults. After 3 months, females start laying 3000 to 10,000 eggs a day and can live up to 8 years. Eggs need around 3 weeks to become infectious.

Eggs are dark bile staining, barrel shaped, and have polar plugs in the egg shell

Associated with poor sanitation and using human feces as fertilizer.

Symptoms are dependent on worm burden. With few worms, asymptomatic infection occurs. More worms lead to abdominal pain and distension, bloody diarrhea, weakness, and weight loss. Appendicitis may occur as worms fill the lumen of the appendix. Prolapse of the rectum, anemia, eosinophilia are possible.

Treat with albendazole or mebendazole

Question 23

Ascaris lumbricoides

Answer 23

Large (20-35 cm) pink worms that affect the world’s population more than any other parasite.

Complex life cycle: first the eggs are ingested, the worm penetrates the wall of the duodenum and makes its way to the liver and heart. It then goes to the pulmonary circulation, where the larvae grow and molt in alveoli. They are then coughed up and swallowed to return to the small intestine (jejunum mostly). They mate and can lay 200,000 eggs a day for as long as a year.

Prevalent with poor sanitation and human feces as fertilizer. Humans are only reservoirs, but a similar species that can infect humans is present in pigs.

Worms can migrate to bile duct and cause liver damage, peforate the intestines leading to secondary bacterial infections. If enough are present, they can block the bowel. Migration to lungs can mimic an asthma attack

They do not attach to the intestines but must constantly be wiggling around to stay in. Terrifying.

Exam stool for knobby-coated, bile-stained, fertilized and unfertilized eggs. Adult worms can occasionally be passed with the feces.

Treat with albendazole or mebendazole

Question 24

Necator americanus

Answer 24

New World hookworm

Life cycle: filariform larva penetrates intact skin normally through feet, enters circulation, is carried to the lungs, is coughed up, swallowed, and develops in the small intestine. On contact with soil, the rhabditiform (noninfective) form is hatched and takes 2 weeks to develop to the filariform (infectious) larvae. Both have mouth parts for sucking blood from tissue

Found in warm, humid conditions (southern US)

Can produce allergic reactions and rash at site of entry. Can cause a microcytic hypchromic anemia due to blood loss. In severe, chronic infections, emaciation and physical/mental retardation may occur

Stool exam shows non-bile-stained segmented eggs with a thin shell surrounding a brown larva

Treat with albendazole or mebendazole, iron therapy is recommended

Question 25

Ancylostoma duodenale

Answer 25

The exact same as N americanus, except this is found in a different geographic distribution and has chitinous teeth, where as N. americanus has shearing chitinous plates.

It also steals a little more blood (.15 to .25 ml Vs. .03 ml per day)

Question 26

Strongyloides stercoralis

Answer 26

Similar to hookworms except 1) eggs hatch into larvae in the intestine and before they are passed in feces, 2)larva can mature into filariforms in the intestine and can autoinfect, and 3) a free-living, nonparasitic cycle can be established outside the host

Similar life cycle to hookworms, except both forms of larva can be released and mature in intestines.

Low prevalence by broader geographic distribution in northern US and Canada. Sexual transmission and animal reservoirs (pigs)

Strongyloidiasis can lead to pneumonitis as well as inflammation and ulceration of the biliary and pancreatic ducts, colon, small bowel. This can lead to epigastric pain, tenderness, vomiting, diarrhea, and malabsorption. Symptoms can mimic peptic ulcer disease; peripheral eosinophilia should cause suspicion of strongyloides.

Hyperinfection can occur due to autoinfection; it has a mortality rate of 86%. Extrainestinal infection most commonly involves the lung. Widespread dissemination is common.

Eggs are generally not seen in stool samples. Can occur in “showers” similar to Giardia, so collect multiple stools. Can use the Baermann funnel gauze method of detection

Treat with ivermectin. Watch out for any secretions from patients, as they are infectious

Question 27

Toxocara canis

Answer 27

Ascarid worms that are naturally parasitic in the intestines of dogs.

Accidental infections of humans occur producing visceral larva migrans (VLM), neural larva migrans (NLM), and ocular larva migrans (OLM). Following egg ingestion, larva hatch, penetrate the intestines and reach the bloodstream, then migrate to various tissues (they can’t carry out the life cycle they normally do in their natural hosts)

Larvae can invade any tissue causing bleding, formation of eosinophilic granulomas, and necrosis. Organs most frequently involved are lungs, heart, kidneys, liver, skeletal muscles, eyes, and CNS. Death may result from respiratory failure, cardiac arrhythmia, or brain damage. Ocular disease can be mistaken for retinoblastoma

ELISA to diagnose, along with clinical presentation and history. Examine fecal material from pets (there won’t be eggs in humans, as there are no egg laying adults present)

Treat symptoms, then potentially use albendazole, mebendazole, diethylcarbamazine, or thiabendazole

Question 28

Taenia saginata

Answer 28

The Beef Tapeworm, can get up to a length of 10 m. Cysticercosis does not occur in humans, and it lacks a crown of hooklets on the scolex

Similar life cycle to T. solium, with infection resulting after cystericerci are ingested from poorly cooked beef. Eggs hatch and larvae mature to adults in the small intestine. Egg production ensues in proglottids.

Patients are generally asymptomatic or may complain of vague abdominal pain, chronic indigestion, and hunger pains

Diagnose based off proglottids and eggs or entire worm

Treat with praziquantel and nicolsamide

Question 29

Taenia solium

Answer 29

Pork tapeworm that uses a scolex with muscular suckers and a crown of hooklets to infect the small intestine. Its proglottids are longer than they are wide

Directly correlated with eating insufficiently cooked pork. Seen infrequently in the U.S.

Seldom causes symptoms other than abdominal discomfort, chronic indigestion, and diarrhea. Most people see the proglottids or a stobila of proglottids in their feces (diagnostic). Eggs have a thick radially striated shell

Treat with nicolsamide

Cysticercosis: infection with larval form of T. solium. Eggs hatch in stomach and release hexacanth embryo or oncosphere. The oncosphere penetrates the intestinal wall and migrates in the circulation where it developes into a cysticercus in muscle, connective tissue, brain, lungs, or eyes. Symptoms are dependent on where the oncosphere ends up.

Diagnose via visualization of cysts

This is associated with fecal oral transmission and autoinfection

Treat with praziquantel or albendazole and steroids to cut down on inflammatory reaction following dead cysts

Question 30

Diphyllobothrium latum

Answer 30

Fish tapeworm that is one of the largest (20-30ft)

Most Complicated Life Cycle Ever: ingestion of a sparganum (ribbon-like larval worm in the flesh of freshwater fish) starts infection. The scolex of the sparganum is lance shaped with lateral grooves (bothria). The proglottids of D. latum are wider than they are long. More than 1 million eggs a day are released in feces. Once in fresh water, the operculate eggs (have a knob at bottom of shell) require a period of 2-4 weeks to develop into a free-swimming larval form called a coracidium. They are then ingested by small crustaceans called copepods, within which the coracidium develops to a procercoid larval form. The crustaceans are eaten by fish, and the infectious plerocercoid (AKA sparganum) develops in the musculature of the fish.

Associated with eating raw or undercooked fish.

Occurs in cool lake regions where raw or pickled fish is popular. Reservoirs include bears, minks, walruses, cats and dogs.

Most cases are asymptomatic, but B12 deficiency is associated with this worm

Treat with niclosamide, give B12 if needed

Question 31

Echinococcus granulosus

Answer 31

Worm with eggs identical in appearance to Taenia. Egg hatches into an oncosphere that penetrates the intestinal wall and migrates to the liver and lungs, as well as the CNS and bone.

An accidental infection with humans serving as dead-end intermediate hosts. The adult forms are found in canines, larval cyst stage is in herbivores (sheep, cattle, et c.)

In humans, the larvae form a unilocular hydatid cyst which looks like a tumor. Brood capsules can form on the surface of this cyst which has tapeworm heads (protoscolices) on it. Cysts can grow on cysts, and if they spill the cystic fluid into body cavities it can cause anaphylactic shock and death. The cysts can also lead to a hydatid sand (?). Cysts may die and calcify

Directly correlated with raising sheep and canine feces

Cysts can also grow in bone and brain. Diagnosis depends on clinical, radiographic, and serologic findings

Treat with surgical resection, educate about canine poop to prevent infection

Question 32

Paragonimus westermani

Answer 32

Lung fluke

Life cycle: egg to snail to infective metacercaria (the infective stage occurs in freshwater crabs and crayfish). Following ingestion, larval worms hatch in the stomach and migrate through the intestinal wall to the abdominal cavity, then through the diaphragm, then to the pleural cavity. Adult worms are in the lungs, and eggs are found in sputum or are swallowed.

Seen in Asia, Africa, India, and Latin America.

Onset of disease coincides with larval migration and is associated with fever, chills, and high eosinophilia. Adult flukes in lungs produce fever, cough, and increased sputum. Cavitation occurs, and sputum becomes dark with eggs and blood (rusty sputum); severe chest pain occurs. Can also migrate to CNS causing cerebral paragonimiasis

Exam sputum and feces for golden brown, operculated eggs. Chest X-rays often show nodular cysts

Treat with triclabendazole. Avoid uncooked crabs/crayfish

Question 33

Opisthorchis sinesis

Answer 33

Chinese Liver Fluke

Eggs are eaten by snails, then fish (where infective metacercariae develop). When uncooked meat is eaten, flukes develop and head to the bile ducts where they mature. The worms are self-fertile

Found in China, Japan, Korea, Vietnam and is tied to eating uncooked, pickled, smoked, or dried freshwater fish. Dogs, cats, and fish-eating mammals are reservoir hosts.

Usually mild symptoms, but can cause fever, diarrhea, epigastric pain, hpatomegaly, anorexia, and occasionally jaundice. Biliary obstruction may occur, and chronic infection can lead to adenocarcinoma. Invasion of gall bladder can lead to cholecystitis, cholelithiasis, and impaired liver function as well as liver abscesses

Eggs are diagnostic (they have a distinct operculum with prominent shoulders and a tiny knob at the posterior pole).

Treat with praziquantel, avoid undercooked fish

Question 34

Hepatitis Viruses (General)

Answer 34

A family of six viruses (A -E, G) whose target is the liver. They differ greatly in structure, mode of replication, and mode of transmission

HepA (HAV) and HepB (HBV) are classical hepatitis viruses. The rest are called non-A, non-B hepatitis (NANBH) viruses

Each virus damages the liver to cause symptoms of jaundice and release of liver enzymes.

Question 35

Hepatitis A

Answer 35

Known as infectious hepatitis

Caused by a naked, icosahedral capsid encolosed, positive single stranded RNA (resembles mRNA) picornavirus. Only one serotype

Interacts with receptor expressed on hepatocytes and Kupffer cells and is not cytolytic (released by exocytosis). It is released in bile and spread in stool.

CD4s and NK cells are needed to rid infection. Antibody protection is lifelong. Damage to liver is probably immunologically mediated.

Spread by fecal oral route via contaminated water, shellfish, or other food; associated with poor hygiene or overcrowding

Has an incubation of 1 month, the beginning of which is asymptomatic but still capable of spreading disease. Symptoms occur abruptly 15 to 50 days after exposure and include fever, fatigue, nausea, loss of appetite, abdominal pain, dark urine, pale stool and jaundice (less jaundice in children). Fulminant hepatitis occurs rarely but has an 80% mortality rate

Find IgMs via ELISA to diagnose

Does not cause chronic disease.

Rarely is fatal

Treat by preventitive measures, passive immunization, and killed HAV vaccines

Question 36

Hepatitis B (structure and replication)

Answer 36

Known as serum hepatitis

Caused by an unusually stable enveloped hepadnavirus with a small, circular, partly double stranded DNA genome. Although it is a DNA virus, it encodes a reverse transcriptase and replicates via an RNA intermediate. Virion is also known as the Dane particle. Has an icosahedral capsid fromed by the hepatitis B core antigen (HBcAg)

Has an envelope containing three forms of the glycoprotein hepatitis B surface antigen (HBsAg). HBsAg containing particles are released into the serum and outnumber the actual virons. They are immunogenic. They are different length transcripts of the same gene (S, M, L). L-glycoprotein is responsible for binding to liver cell receptors as well as virion capsid.

Unique replication via an RNA intermediate and release of decoy particles. Capable of integrating entire genome into chromatin.

Question 37

Hepatitis B (Path)

Answer 37

Can cause chronic, symptomatic or asymptomatic disease depending on host immunity. Detection of both the HBsAg and the HBeAg indicates ongoing infection. HBsAg is released into the blood even following an infection.

Found in blood, semen, saliva, milk, vaginal and menstrual secretions and amniotic fluid. Easiest way to get it is injection into blood.

Symptoms not observed for 45 days or longer

Cell-mediated immunity and inflammation are responsible for causing symptoms and effecting resolution of the HBV infection (targets HBcAg). Insufficient T-cell response leads to mild symptoms and development of chronic hepatitis.

Antibodies can be protective by inhibiting virion transport to liver, but can also be blocked by virally secreted HBsAg. Immune complexes between antibodies and HBsAg can lead to hypersensitivity reactions (type III)

Children don’t have as severe of symptoms but are also more likely to become chronic carriers

Question 38

Hepatitis B (Epidemiology and Disease)

Answer 38

Asymptomatic carriers spread the virus via sexual, parenteral, and perinatal routes. Sexual promiscuity and drug abuse are major risk factors

Acute infection: less severe in children, has insiduous onset, same symptoms as HepA; fulminant hepatitis is possible in 1% and is more severe, and complications of type III sensitivities are possible. No treatment is availabe for acute infection, but hepB immune globin can be used for newborns to prevent disease.

Chronic Infection: occurs in 5-10% of people with infections. This can lead to scarring of the liver, cirrhosis, liver failure, or PHC. These people are the main source of the spread of the virus. Chronic HBV can be treated with lamivudine (HIV reverse transcriptase inhibitor) or nucleoside analogs adefovir dipivoxil and famciclovir.

Primary Hepatocellular Carcinoma: 80% of all PHC can be traced to chronic HBV infections. PHC is usually fatal, and often shows integration of HBV genome into host DNA. HBV X gene may stimulate cell growth, as well as chronic liver repair

Vaccinate with subunit vaccines as a series of three injections. Watch out for any infectious secretions/blood

Question 39

Hepatitis C

Answer 39

Only member of Hepacivirus genus in flaviviridae family. It has a positive sense RNA genome and is enveloped. It shows extensive mutation and antigenic variability, which makes it hard to develop a vaccine

Six major groups/clades

Promotes persistent infection and results in liver disease later in life. Cell-mediated immunity is responsible for resolution and liver damage. Antibody is not protective, and immunity may not be lifelong.

Transmitted via infected blood and sexually. High incidence of asymptomatic infections facilitates spread.

Can cause acute infections, chronic persistent infections, and severe rapid progression to cirrhosis in 15% of patients. Symptoms normally milder than HAV and HBV. Promotes hepatocellular carcinoma in chronically infected patients

Diagnose with ELISA recognition of anti-HCV antibody or detection of RNA genome. Antibody is not always detectable in viremic people, immunocompromised, or patients on hemodialysis.

Treat with interferon alpha alone or with ribavirin

Hepatitis G is pretty much the same thing

Question 40

Hepatitis D

Answer 40

It uses HBV and target cell proteins to replicate and produce its one protein. It is a viral parasite (“even fleas have fleas”)

Very small (1700bp) RNA genome that is circular and forms a rod shape as a result of extensive base pairing. It has its own delta antigen which is surrounded by an HBsAg coat. The RNA is is replicated via the host RNA pol II and functions as a ribozyme to cleave and produce its own mRNA. HBsAg is essential for viral packaging

Source of 40% of fulminant infections. This severe form can cause altered brain function (hepatic encephalopathy), extensive jaundice, and massive hepatic necrosis (80% fatal)

Spread in blood, semen and vaginal secretions, but can only spread in patients with HBV.

Co-infection: when you get HBV and HDV at the same time. HBV has to take hold before HDV can cause infection.

Super infection: when you already had chronic HBV, so HDV can infect immediately. This is worse

No real treatment except to vaccinate for HBV and try to avoid risk factors for HDV if you already have HBV.

Question 41

Hepatitis E

Answer 41

Similar symptoms as HAV disease (only causes acute disease), but has a higher mortality rate (especially in pregnant women)

Problematic in developing countries like India, Pakistan, Nepal, Burma, North Africa, and Mexico

Spread by fecal-oral route in contaminated water

Question 42

Noroviruses

Answer 42

Positive sense RNA viruses that resemble an mRNA similar to picornaviruses (has cap and tail). Genome is in a naked capsid, and they are round with a ragged outline.

Bind to A, B, or O blood group antigens

Only takes ~10 virions to cause disease

Damages the brush border leading to improper absorption of nutrients, watery diarrhea, abdominal cramps, and vomiting. Biopsies show blunted villi, cytoplasmic vacuolation, and infiltration with mononuclear cells

Transmitted with contaminated foods via the fecal oral route. Well-correlated with poor food handling

The prototype is the Norwalk virus, most of them are gastroenteroviruses

Diagnose with RT-PCR to prevent outbreaks. Maintain cleanliness to prevent them to begin with (no real treatment)

Question 43

Reoviruses

Answer 43

Members of reoviridae that contain a double-layered protein capsid containing 10 to 12 segments of double-stranded RNA genomes (reassortment can occur). Stable over a wide pH and temperature range.

Rotavirus causes human infantile gastroenteritis (50% of all cases of diarrhea in children requiring hostpitalization becauase of dehydration)

Looks like a wheel on electron micrographs, causes large cytoplasmic inclusion bodies

Transmitted via fecal oral route. Has a 48 hour incubation

Outer capsid is cleaved in the GI tract to reveal an intermediate/infectious subviral particle. This particle binds to sialic acid-containing glycoproteins and B-adrenergic receptors/integrin

Detect via viral antigen in stool

No antiviral therapy is availabe

Question 44

Mumps

Answer 44

Paramyxovirus that is negative-sense, single stranded RNA in a pleomorphic envelope. RNA polymerase is carried into the cell as part of the nucleocapsid. Replication occurs in the cytoplasm. Has L, N, and NP proteins that associate with M proteins on viral glycoprotein-modified plasma membranes

Cause of acute, benign viral parotitis. Rarely seen in countries that use the live vaccine

Causes a lytic infection of cells.

Hits the upper respiratory tract first then the parotid gland via viremia or the Stensen duct. The viremia can spread the virus to the testes, ovary, pancreas, thyroid, and other organs. Infection of the CNS happens in around 50% of patients

Infects only humans, spreads by respiratory droplets. Released from asymptomatic patients during the initial 7 days of infection. Mumps is often asymptomatic. Biggest presenting symptom is bilateral parotidis accompanied by a fever. Causes swelling in a lot of other organs (testes) as well, and can lead to meningoenceophalitis

Virus can be recovered from saliva, urine, pharynx, CSF; diagnose via serology

Prevent by live attenuated vaccine