Y2 2013 Spring Microbiology Block II

What is the primary causative agent of tooth decay?
Streptococcus mutans
What causes cariogenic dental plaques?
Mouth acidity
What is periodontal disease?
Inflammation of the gums in response to plaque bacteria such as in dental calculus or gingivitis
Responsible for tooth loss in the elderly
What causes gingivitis?
Porphyromonas gingivalis
What causes trench mouth?
Synergistic infection of spirochetes (oral spirochete of Treponema genus; T. pallidum is the cause of syphilis) and anaerobic bacteria
What causes watery diarrhea?
Pathogenic mechanisms that attack the proximal small intestine (more than 90% of physiologic net fluid absorption occurs)
What organisms cause the purest form of watery diarrhea?
Enterotoxin-secreting bacteria such as Vibrio cholerae and enterotoxigenic Escherichia coli (ETEC), which cause fluid loss without cellular injury
Which causes of watery diarrhea are uniquely not self limiting to 1-3 days?
V. cholerae, which usually produces a more severe illness

Giardia lamblia, which produces a watery diarrhea that may last for weeks

What is dysentery?
Rapid onset of frequent intestinal evacuations, but the stools are of smaller volume than in watery diarrhea and contain blood and pus
What causes dysentery?
Inflammatory and/or destructive changes in the colonic mucosa either by direct invasion or by production of cytotoxins
What causes enteric fever?
Penetration by the organism of the cells of the distal small bowel with subsequent spread outside the bowel to the biliary tract, liver, mesentery, or reticuloendothelial organs
What is the only infection causing enteric fever that is well studied?
Typhoid fever caused by Salmonella enterica serotype Typhi
What are the most common causes of traveler’s diarrhea?
50% caused by ETEC
10%-20% by Shigella species
Ingestion of uncooked or incompletely cooked foods is the most likely source of infection
What are the most common causes of food poisoning?
Salmonella, Clostridium perfringens, and S. aureus
Most often due to improper storage temperature
What are the most common causes of hospital associated diarrhea?
E. coli (in infants)
C. difficile (patients on antibiotics)
Which hepatitis virus is “silent” and often goes undetected?
Hep C
How is liver cell damage present?
Hepatic cell degeneration and necrosis, cell dropout, ballooning of cells, acidophilic degeneration of hepatocytes forming Councilman or apoptotic bodies
What are the unique features of Hep A?
Single stranded RNA picornavirus
Resists inactivation and is stale at -20C with low pH
Never becomes chronic, has only one serotype, no animal reserve, vaccine existence is leading to eradication of the virus
What kind of abnormal liver cells are characteristic of liver disease?
Kupffer cells
What are the symptoms of Hep A?
Fever, anorexia, nausea, pain in upper right abd, jaundice, dark urine and clay-colored stool, enlarged, tender liver, elevated serum aminotransferase and bilirubin
Will never cause cancer or progress to chronic liver disease
How is Hep A treated?
Almost all are self limiting to a few weeks-months
How is Hep A detected in serology studies?
Fecal HAV detected 4-6 weks
IgM Anti-HAV detected early on but then drops
IgG is inclusive because it increases over time, needs to see the trend
How long in advance must immune serum globulin be given to confer temporary immunity to Hep A?
Protective if given before or during the incubation period of the disease
Not indicated once symptoms have appeared
What are the unique features of Hep B?
Member of hepadnaviridae family
Smallest DNA virus known
All newborns become chronic, 50% of children become chronic
What is present in the nuclei of cells infected with Hep B?
HBcAg, HBeAg, and hepatitis B DNA
What is present in the cytoplasm of cells infected with Hep B?
HBsAg
The HBV S gene codes for what?
The “major” envelope protein HBsAg
What does the HBV P gene code for?
Largest gene, codes for DNA polymerase
What does the HBV C gene code for?
Two nucleocapsid proteins, HBeAg, a soluble, secreted protein and HBcAg, the intracellular core protein
What does the HBV X gene code for?
HBxAg, which can transactivate the transcription of cellular and viral genes; its clinical relevance is not known, but it may contribute to carcinogenesis by binding to p53
How do infants acquire HBV from their mother?
Not vertically, accquired intrauterally via ingestions or abrasions during birth
What are the consequences of chronic HBV infection?
Necrosis of hepatocytes,
Collapse of the reticular framework of liver
Progressive fibrosis
Leads to syndrome of postnecrotic hepatic cirrhosis
What causes extrahepatic manifestations of HBV?
Deposition of HBsAg-anti-HBs circulating immune complexes in tissue blood vessel walls results in prodromal serum sickness-like syndrome, glomerulonephritis, and nephritic syndrome
Polyarteritis nodosa is associated with which Hep virus?
HBV
Develops in considerably fewer than 1% of patients with chronic HBV infection
However, 20 to 30% of patients with PAN have HBsAg in serum
Essential mixed cryoglobulinemia is associated with which Hep virus? What are its features?
HBV, HCV
Precipitates at cold temp
Arthritis
Cutaneous vasculitis (palpable purpura)
Glomerulonephritis (occasional)
Circulating cryoprecipitable immune complexes (more than one immunoglobulin class)
What are the characteristics of HBsAg?
HBV surface antigen formed in excess and seen in serum
What are the characteristics of HBcAg
HBV core antigen found in nucleus of infected hepatocytes by immunofluorescence
What are the characteristics of HBeAg
HBV glycoprotein associated with the core antigen, used as a marker of potential virus activity, only seen when HBsAg is also present
What are the characteristics of Anti-HBs
Ab to HBsAg, correlates with past infection or immunization
What are the characteristics of Anti-HBc
Ab to HBcAg, seen in acute infection and chronic carriers, can be either IgM or IgG (acute vs. chronic)
Anti-HBc IgM indicates what?
Acute HBV infection
Anti-HBc IgG indicates what?
Chronic HBV infection
Presence of Anti-HBe indicates what?
Virus is not actively reacting and is in recession
What is the best diagnostic measure for HBV detection?
IgM antibody to HBcAg along with or without HBsAg in the serum
How is vertical transmission of HBV to newborns prevented?
Use of combined HBIG and HBV vaccine
How do you treat chronic HBV?
Interferon-alpha, Lamivudin, Adefovir
What is the leading cause for liver transplants in the US?
Liver failure due to Hep C
How is HCV contracted?
Commonly transmitted through blood contact (blood transfusion or needle sharing) than through transfer of body fluids; vertical transmission is possible
What is the most common complication of HCV?
Chronic liver disease (80% of cases with a course of intermittent inflammation and normality)
10-20% of chronic patients develop cirrhosis or cancer in the long run
What is the average time from infection to the development of chronic hepatitis in HCV patients?
10-18 years
Often asymptomatic
What are the extra-hepatic manifestations of HCV?
Essential mixed cryoglobulinemia (EMC)
Circulating immune complexes containing HCV RNA
Immune-complex glomerulonephritis
How is HCV diagnosed?
Detection of HCV antibody
May remain negative for 1-3 weeks after clinical onset
May never become positive in up to 20% of patients with acute, resolving disease
How is HCV treated?
Combination treatment with interferon-a and ribavirin
The protein-RNA complex of Hep D is surrounded by what?
HBsAg
How is Hep D diagnosed?
IgM or IgG antibodies or both to the delta antigen in serum
IgM antibodies appear within 3 weeks of infection and persist for several weeks
IgG antibodies persist for years
How is Hep D prevented?
By preventing Hep B
How is Hep D treated?
Interferon alpha
Response to treatment in patients with delta hepatitis (and hepatitis B) is less than in those with hepatitis B alone
The majority of GI pathogenic bacteria grow on what medias?
Majority are gram-neg and grow on MacConkey agar which inhibits gram-pos growth
How is Hektoen agar used to diagnostically distinguish GI pathogenic bacteria?
Inhibits common colon flora
Selective to recover Salmonella and Shigella spp.
Indicators to detect H2S production (black centers to colony)
What does Campylobacter spp. grow on?
Enriched blood agar
What is acute diarrhea and what are its causes?
Diarrhea lasting 7-14 days caused by:
Drugs
Infectious Agents (Virus, Bacteria, Parasite)
Feeding after a long fasting
Fecal Impaction
Which GI bacteria have vaccines?
Most don’t
What makes distinguishing E. coli so difficult?
Many strains are a part of the normal GI flora and basic diagnostics will not discriminate between normal and pathogenic E. coli
What are the most common causes of Enterotoxigenic E. coli (ETEC)?
Ingestion of contaminated water or food
Major cause of travelers diarrhea
What is the most common progression of a GI infection?
Bacteria pass through to intestines
Attachment to mucous layer or intestinal epithelia
Secretion of toxins
Induction of diarrhea and potentially other symptoms
Clearance by host immune system
What are the symptoms of an Enterotoxigenic E. coli (ETEC) infection?
Watery diarrhea, cramps, vomiting, malaise, fever
More severe symptoms if the infecting ETEC strain secretes both types of toxins
What toxins are secreted by Enterotoxigenic E. coli (ETEC)?
Either one or both:
ST (small toxin)
LT (heat labile toxin pierces the membrane of target cell)
How is Enterotoxigenic E. coli (ETEC) diagnosed?
Characteristic symptoms with ONLY lactose fermenting organisms on differential media
ELISA for toxins
How is Enteropathogenic E. coli (EPEC) contracted?
Lack of good hygienic practices: fecal oral contamination
Most often in infants (1 year old or less usually) with adults as carriers
How is the progression of Enteropathogenic E. coli (EPEC) unique?
Secretes of factors that alter the “host” cells (Type III secretion)
Changes epithelial cell cytoskeleton to create a “pedestal” for the bacterial cell
What are the symptoms of an Enteropathogenic E. coli (EPEC) infection?
Fever, vomiting, watery diarrhea that may contain large amounts of mucus
Associated with clusters in the US such as daycare, hospitals, nursery
How is Enterohemorrhagic E. coli (EHEC) most often contracted?
Lack of good hygienic practices
Ingestion of insufficiently cleaned or cooked foods
Reservoir is usually adult cattle which are asymptomatic
How is the progression of Enterohemorrhagic E. coli (EHEC) unique?
Also involved in Type III secretion and pedestal formation
May result in temporary or permanent systemic damage
What are the signs and symptoms of Enterohemorrhagic E. coli (EHEC)?
Watery diarrhea that progresses to *bloody diarrhea, abdominal cramps, +/- fever, may also develop hemolytic uremic syndrome (HUS)
What causes hemolytic uremic syndrome (HUS)?
o Toxin release into the bloodstream leads to lysis of erythrocytes, thrombocytes, and destruction of glomerular capillary endothelial cells
Children and elderly are more susceptible, can be fatal
Hemolytic uremic syndrome (HUS) is most commonly associated with what?
O157:H7
What toxins are secreted by Enterohemorrhagic E. coli (EHEC)?
Functionally and structurally related to the Shiga toxin
AB type toxins
The A subunit interacts with cellular ribosomes cleaving a single adenine residue from the 28S rRNA* leading to a shut-down of host protein synthesis
What special consideration should be made in the treatment of Enterohemorrhagic E. coli (EHEC)?
Monitoring for renal failure
How is Enterohemorrhagic E. coli (EHEC) diagnosed?
Cultures that fail to ferment sorbitol
MacConkey agar using sorbitol instead of lactose
ELISA for toxins

MUG assay: EHEC typically do not produce b-glucoronidase while 92% of other strains do

How is Enteroinvasive E. coli (EIEC) contracted?
Fecal to oral contamination
Reservoirs involve human sources
What is unique about the progression of Enteroinvasive E. coli (EIEC) infections?
Secretion of factors that induce uptake and transmission by M cells*
Entry into the inferior or lateral sides of intestinal epithelial cells
What are the signs and symptoms of an Enteroinvasive E. coli (EIEC) infection?
Many are asymptomatic or with transient fever
Early: Fever, severe cramps, Watery diarrhea
Late: Reduced fever, increased diarrhea with blood*, urgency, tenesmus
What additional treatment option can be used for Enteroinvasive E. coli (EIEC)?
Antibiotics may be administered for more severe cases and will decrease the length of symptoms
How is Enteroinvasive E. coli (EIEC) diagnosed?
HE (Hektoen enteric) agar, MacConkey
DNA probes are commercially available
What is unique about the progression of Enteroaggregative E. coli (EAEC) infections?
Bacteria replicate and aggregate in a unique “stacked brick” fashion (biofilm)
What is a unique symptom of Enteroaggragative E. coli (EAEC) infection?
May cause a protracted course of diarrhea (>14 days) in adults and children in all parts of the world
What are the toxins secreted by Enteroaggragative E. coli (EAEC)?
ShET1 (Shigella enterotoxin 1) similar to a toxin common in Shigella
EAST1 shows similarity to ETEC toxin ST
Pet: A serine protease that alters the enterocyte cytoskeleton (not in all strains)
Which E. coli strains cause watery diarrhea?
EPEC, ETEC, most Viral, (EAEC)
Which E. coli strains cause bloody diarrhea?
EHEC, Shigella spp./EIEC, (EAEC)
Which E. coli strains cause watery and mucoid diarrhea?
EPEC
Which E. coli strains are associated with recent travels?
ETEC, EAEC, Rotavirus
What is the appearance of Yersinia spp.?
Gram negative bacillus
motile at 25C but not 37C
What does Yersinia culture on?
Most enteric media except Salmonella-Shigella agar
Produces urease
Yersinia is very sensitive to levels of what mineral?
Iron
How is Yersinia contracted?
Ingestion of contaminated food or water
Handling infected animals or carcasses
Very rarely blood transfusion
Swine is the primary reservoir
What is unique about the pathogenesis of Yersinia infections?
Bacteria invade the M cells of the gut and start replicating
Phagocytic cells ingest Yersinia spreading them to the reticuloendothelial system, and are then killed by the bacteria delaying the immune response
What are the signs and symptoms of a Yersinia infection?
Enterocolitis
Mesenteric adenitis and terminal ileitis
Exudative pharyngitis
Tender red nodules on extensor surfaces of limbs
What symptoms does enterocolitis refer to?
Fever lasting 1-3 weeks, diarrhea containing mucous and blood, abdominal cramps, anorexia, nausea and vomiting, Rectal bleeding in severe cases
Potentially severe dehydration
What post-infectious syndrome is common in patients recovering from a Yersinia infection?
Reactive arthritis
What is the general function of toxins secreted by Yersinia?
Most of the virulence factors are regulated in expression by the local environment and are aimed at suppressing the immune system
How is Yersinia diagnosed?
Stool culture on enteric media
What media is used to culture Francisella tularensis?
Requires special media for growth that is enriched in cysteine
How is Francisella tularensis contracted?
Insect bites (no human to human transmission)
What are the signs and symptoms of Francisella tularensis?
Fever (up to 104), chills, headache, myalgias, possible delirium
Inflamed blister that fills with pus and opens to form an ulcer, swollen lymph nodes
Severe sore throat
Chest and abdominal pain, fatigue, weight loss, diarrhea
How is Francisella tularensis diagnosed?
Serology is negative the first week but still the best means for confirmation
Diagnosis is usually based on clinical suspicion
How is Francisella tularensis treated?
Antibiotics (gentamicin or ciprofloxacin)
How is Brucella melitensis contracted?
Direct contact with infected animals or their secretions through skin breaks
Ingestion of unpasteurized dairy products derived from infected animals
Describe the pathogenesis of Brucella melitensis
Transport to regional lymph nodes and growth in lymphoid cells
Spread from the lymph nodes to the reticuloendothelial system
Bursts of bacteremia
What are the signs and symptoms of Brucella melitensis?
Usually 1 of 3 categories:
Febrile illness that resembles typhoid but is less severe
Fever and acute monarthritis, typically of hip or knee, in a young child
Long-lasting fever, misery, and low-back or hip pain in older men
How is Brucella melitensis diagnosed?
Culture from blood, bone marrow, or other tissues
Grows very slowly so allow extra time in cases of suspicion
Serum agglutination test may also be used
Describe the appearance of Brucella melitensis
Small gram-negative rod
Describe the appearance of Bacteroides fragilis
Gram-negative rod
What media is used to culture Bacteroides fragilis?
Forms colonies overnight on blood agar
What are the virulence factors and toxins of Bacteroides fragilis?
Capsule resists phagocytosis and can independently lead to abscess formation
Secretes a heparinase that promotes clotting
Some strains secrete a 20 kDa metalloprotease toxin (BFT) that causes disease without the need for epithelial breaks
How is Bacteroides fragilis contracted?
Can be part of the normal flora and these strains require a break in the anatomic mucosal barriers (unless metalloprotease toxin is present)
How is Bacteroides fragilis treated?
If causing acute diarrhea due to ingestion, is self limiting
If due to epithelial break: Abscess drainage and antibiotics
What is the physical appearance of Helicobacter pylori?
Gram negative curved rod with multiple sheathed flagella for motility
How is H. pylori cultured?
Grows on Skirrow media
Requires a microaerophilic atmosphere and is slow (3-5 days) to grow
How is H. pylori transmitted?
Person to person by fecal-oral route
What is the most common cause of gastritis, gastric ulcer, and duodenal ulcer?
H. pylori
Considered a class I carcinogen
What mediates the virulence factor of H. pylori?
VacA is toxic and directly influences inflammation
CagA stimulates cytokine IL-8 and neutrophil-activating protein (NAP)
Net effect is gastritis, thinning of gastric mucosa, ulcers
How are T and B lymphocytes involved in the creation of gastric ulcers?
H. pylori infection causes lymphocyte infiltration which causes epithelial tissue damage rather than removal of the pathogen
What is the purpose of urease secreted by H. pylori?
Converts urea to ammonia which tends to neutralize the gastric acid
What are the symptoms of H. pylori induced gastritis?
Often symptom free
In symptomatic: belching, nausea, anorexia, vomiting, epigastric pain, bleeding
Possible pyloric stenosis
How is an H. pylori infection diagnosed?
Endoscopic biopsy and culture
Detection of urease activity via urease breath test with 13C- or 14C-labeled urea
Serology for specific antibody
How is H. pylori treated?
Combo of antimicrobials and acid reducers
Metronidazole, tetracyclin, clarithromycin*, and amoxycillin*
Proton pump inhibitor
What is the general pathogenic mechanism of bacterial intestinal diseases?
Attachment by pili or other adhesion
Some bacteria transfer substances into host cell that mediate bacterial attachment
Toxin production
Cell division
Loss of microvilli
What is the physical appearance of Vibrio cholera?
Curved gram neg rod commonly found in salt water
Highly motile with single polar flagellum
Cells may be linked end to end forming S shapes and spirals
How is Vibrio cholera cultured?
Oxidase positive and can grow both in aerobic and anaerobic conditions
Grown on Thiosulfate Citrate Bile Salt Sucrose (TCBS) medium which inhibits gram pos
What is the major virulence factor for Vibrio cholera?
Cholera toxin
Colonizing factor known as the toxin-coregulated pilus (TCP)
How is Virbrio cholera detected by serology?
H and O antigens (especially enterobacteriae)
What is the mechanism of action of cholera toxin?
Catalyzes the ADP-ribosylation of the GS (stimulatory) regulatory protein, “locking” it in the active state
Causes persistent activation of adenylate cyclase which causes cAMP accumulation for active secretion of Na+, K+, HCO3-, and water out of the cell
How does Vibrio cholera cause fluid loss?
Increased adenylate cyclase via cholera toxin
What is the osmotic make up of diarrheal fluid?
Can amount to many liters per day, with approximately the same sodium content as plasma but two to five times the potassium and bicarbonate concentrations
What regulates the virulence factors of Vibrio cholera?
Transmembrane protein (ToxR ) that “senses” environmental changes in pH, osmolarity, and temperature which convert it to an active form
What are the symptoms of cholera?
Rapid onset, abd pain, rushes of peristalsis, loose, watery stool containing mucus flecks- the “rice-water stool”
Muscle cramp due to electrolyte imbalance
In severe, hypotension, shock and death may occur within hours if untreated
How is cholera diagnosed?
Isolation of the organism from stool by culture on common bacteriological medium (e.g. blood agar and MacConkey agar) or on a selective medium (thiosulfate-citrate-bile salt-sucrose agar)
Latex agglutination test
How is cholera treated?
Immediate fluid replacement
Antimicrobials: tetracycline or TSX and erythromycin
Usually self-limiting
Less common vibrio species??
Describe the physical appearance of Campylobacter jejuni (dysentery)
Curved motile gram neg rod
Have polar flagella that are often attached to the ends giving an “S” or a “seagull” appearance
How is Campylobacter jejuni cultured?
Microaerohilic (requires low oxygen tension), oxidase positive
Slow growing (2-4 days, sometimes as long as one week) in selective medium (Campy-blood agar or Skirrow agar) at higher temperature (42C)
What is the leading bacterial diarrheal illness in the US?
Campylobacteriosis
How is campylobacter usually contracted?
Domestic animals or consumption of contaminated meat (poultry)
Ingestion of non-pesteurized cow and goat milk as well
How is campylobacter associated with Guillain-Barre syndrome
Antibody elicited by ganglioside-like structures in the C. jejuni LPS core oligosaccharide cross-reacts w/ molecules in the host nerve myelin
These abs are found in the serum of pts w/Guillain-Barre syndrome
Similar to molecular mimicry in rheumatic fever
What are the symptoms of a campylobacter infection (dysentery)?
Fever
Lower abd pain (may be severe enough to mimic acute appendicitis)
Dysenteric stool containing blood and pus
Vomiting (often not present)
Is invasive
Usually self-limiting, recovers within 3-5days
How is campylobacter diagnosed?
Stool isolation and culture via Campy-blood agar or Skirrow agar
Plates are to be incubated in microaerophilic condition
How is campylobacter contraction prevented?
Pesteurization of milk and beverages and chlorination of water is helpful in preventing outbreaks
Proper cooking and handling of poultry products
How is campylobacter treated?
Macrolides (erythromycin is the drug of choice) and fluoroquinolones
Resistant to beta-lactams
What are the relevant species of salmonella that causes diarrhea?
S. enterica and S. typhi
What is the physical appearance of salmonella?
Gram-negative enterobacteria, motile
How is salmonella cultured?
Ferment glucoses with acid and sometimes gas; most of them produce hydrogen sulfide (H2S) not urease
Grows on most common bacteriological media, resistant to chemicals such as bile and dyes
Describe the pathogenesis of S. enterica
Attaches to the enterocytes and M cells in the small and large intestine by pili
Initiates a cytoskeletal change with formation of ruffles (extension of plasma membrane)
Passes through the cells to the lamina propria to produce inflammation
How does S. enterica avoid phagocytosis?
Inducing macrophage apoptosis
What are the symptoms of salmonella infection?
Often described as “food poisoning”
Nausea
Vomiting
Abdominal pain
Loose motion
Fever
What is the classic contaminated food consumed in the contraction of salmonella poisoning?
Potato salad
What causes typhoid fever?
Salmonella typhi
Transmitted by contaminated drinking water, usually associated with travel
Requires a large infecting dose
Describe the pathogenesis of Salmonella typhii
Similar to that of S. enterica
Also kills macrophages by inhibiting phagosome fusion with lysosomes
Capsular Vi antigen inhibits PMN phagocytosis
How does the virulence of Salmonella typhii differ from other strains of salmonella?
Prolonged survival within the macrophages due to its ability to inhibit oxidative burst
Infected macrophages are carried in the lymphatic circulation to mesenteric nodes, spleen, liver and bone marrow
What are the symptoms of typhoid fever?
Involves multiple organs
Incubation 13 days
Fever, headache, faint rash on abd
Diarrhea
Relative bradycardia is characteristic
What are the most important complications of typhoid fever?
Intestinal (terminal ileum or proximal colon) perforation* and cholecsystitis* are the most important complications
Chronic bacteremia and effects of endotoxins may lead to myocarditis, encephalopathy, or IVC
How is Salmonella poisoning diagnosed?
Hektoen enteric agar medium
Bile salts and the indicator dyes inhibit the Gram-pos
Fails to ferment lactose
H2S forms black colonies
How do common GI pathogens present on Hektoen enteric agar cultures?
Fermenters produce yellow-pink colonies (e. g. E. coli)
H2S producers (salmonella) form colonies with black precipitate
Shigella colonies are green or transparent
How is salmonella poisoning treated?
Fluid and electrolyte replacement is the primary therapeutic approach
Chemotherapy includes chloramphenicol (bone marrow depression is an important side effect, dangerous), STX, ampicillin, ceftriaxone, and quinolones
Describe the physical appearance of Shigella
Gram-negative straight rods, nonmotile and non-spore-forming
How is shigella cultured?
Selective Hektoen enteric agar
Does not produce urease or H2S, most do not ferment
How is shigella contracted?
Strictly a human disease with no animal reservoirs
Person to person transmission by fecal-oral route
How does shigella differ in its pathogenesis from other intestinal bacteria?
Invades the cells of the large intestine rather than the small intestine
Describe the pathogenesis of Shigella
Bacteria transcytose through the M cells in large intestine into the underlying phagocytic cells
Infects the adjacent cells directly
The cell by cell extension radially creates focal ulcers in the mucosa
Intense acute inflammation in the lamina propria cause the characteristic dysenteric stool
What is the significance of Shigella toxin?
Not in all strain, increases severity
Has a strong association with the hemolytic uremic syndrome characterized by break up of RBCs in the tiny blood vessels of the body resulting in anemia and kidney failure with occasional nervous system injury
What are the characteristics of dysentery syndrome?
Cramps
Painful straining to pass stools (tenesmus)
A frequent, small-volume, bloody mucoid discharge
Most cases of shigella are due to S. sonnei, which presents with what symptoms?
Fever
Malaise, anorexia
Myalgia (sometimes)
Diarrhea (may become dysenteric)
How is shigella diagnosed?
Culture on selective Hektoen enteric agar
Slide agglutination tests using O group specific antisera (A, B, C, D)
How is shigella treated?
Usually self limiting
Antimicrobials help shortening the period of illness and excretion of the organisms
Antispasmodics are contraindicated
What are the characteristics of Picornaviruses?
Poliovirus (3 serotypes)
Hepatitis A Virus
Coxsackievirus groups A and B
Describe the pathogenesis of picornaviruses
Initial infection is of intestinal epithelia or pharynx, persists throughout disease
Spreads to submucosal lymphoid tissues (Peyer’s patches or tonsils) and regional lymph nodes
Spreads to and replicates in organs of the reticuloendothelial system
What diseases processes/complications are seen with Group A Coxsackievirus infections?
Asceptic Meningitis, Encephalitis, muscle weakness and paralysis (Poliomyelitis-like disease), cerebellar ataxia, exanthems and enanthems
What disease processes/complications are seen with Group B Coxsackievirus infections?
Asceptic Meningitis, Encephalitis, Pericarditis, Myocarditis, Epidemic Mylagia, Orchitis
What disease processes/complications are seen with Echovirus and Enterovirus infections?
Asceptic Meningitis, Encephalitis, muscle weakness and paralysis (Poliomyelitis-like disease), Exanthems and enanthems
What are the disease states of poliovirus?
Abortive poliomyelitis, asceptic meningitis, paralytic poliomyelitis
How are picornavirus infections prevented?
Both Inactivated virus (IPV) and Live-attenuated virus (OV) vaccines exist for poliovirus
IPV is now the standard for use in the US
How are picornaviruses treated?
Most picornavirus infections are mild and resolve on their own
Injection of Ig to the infecting virus is used in severe cases of neonates or those with Ig deficiency
Supportive care for cardiac or CNS
How are picornaviruses contracted?
Fecal-oral route
Describe the pathogenesis of rotaviruses
24-48 hour incubation period
Initial infection is of the mature villis tip cells of the small intestine
Tip cell death leads to cell replacement by cells that cannot absorb nutrients as efficiently leading to osmotic diarrhea
What is the leading cause of severe dehydrating diarrhea in those under 3 years?
Rotavirus
What are the general symptoms of rotavirus?
Vomiting (typically the first symptom)
Abdominal cramps
Watery diarrhea
May frequently occur along with a respiratory tract infection
Lasts 2-8 days, a form of traveler’s diarrhea
How is rotavirus immunity mediated?
VP4 and VP7 (outer shell) are targets for neutralizing antibodies and humoral immunity plays a large role in viral clearance
How is rotavirus infection prevented?
A live-attenuated vaccine is available. The 3 shot course must be completed by 32 months of age due to concerns over a potentially fatal complication
How is rotavirus diagnosed?
Shed in large amounts in the stool (only during an active infection), and a variety of molecular and enzymatic tests can confirm infection
How is rotavirus treated?
Usually self limiting, can be treated with oral fluids
How are Norwalk agent and Noroviruses contracted?
Fecal-oral route, associated with
Foodborne outbreaks associated with unsanitary restaurant workers
Waterborne outbreaks of viral gastroenteritis
Uncooked shellfish
How do Norwalk agent and Norovirus infections progress?
Intestinal villi and microvilli become blunted and shortened
Malabsorption of carbohydrates and fats leads to osmotic diarrhea without involvement of adenylate cyclase
Gastric motor function is delayed and may be the cause of nausea symptoms
Lasts 12 to 60 hours
What are the symptoms of a Norwalk agent or Norovirus infection?
Nausea, vomiting, cramps, and watery diarrhea
Vomiting is more common in children, and diarrhea in adults
Headache, fever, chills, and myalgias
How is immunity to Norwalk agents and Norovirus mediated?
Short term immunity to infection by the same strain (2-3 months)
Lasting immunity is not achieved to any strain
How are Norwalk agent and Norovirus infections treated?
Treatment is usually not necessary as the disease is of short term, self-limiting, and is not severe
What symptoms appear in Picornavirus infections but no in Norovirus infections?
Rashes, lesions, photophobia, tachycardia
Calicivirus infections are more common among what demographic?
Older children and adults and have nausea as a primary symptom
What are the Helminths?
Nematodes (roundworms)
Cestodes (tapeworms)
Trematodes (flukes)
How does the reproduction of helminths correlate with disease severity?
Adult worms do not multiply in human hosts
Symptoms are usually linked with “worm burden” (number of adults present)
What are the nematodes?
Trichuris trichiura (Whipworm)
Enterobius vermicularis (Pinworm)
Ascaris lumbricoides (Roundworm)
Necator americanus and Ancylostoma duodenale (Hookworm)
Strongyloides stercoralis (Threadworm)
How is Trichuris trichiura (Whipworm) contracted?
Ingestion of fecal contaminated soil or foods
What are the symptoms of Trichuris trichiura (Whipworm)?
Light infections are asymptomatic
Heavy infections can have
Epigastric pain, vomiting, distention, flatulence, anorexia and weight loss may occur, severe cases have Trichuris dysentary syndrome, blood and mucous in stools
How is Trichuris trichiura (Whipworm) diagnosed?
Eggs in stool
What kind of complications are seen with Trichuris trichiura (Whipworm)?
Parasites typically induce an IgE response and hypereosinophilia
Mast cell activation may lead to the increase in allergic responses and symptoms coincide with GI complaints
Prolapse of rectum
How is Enterobius vermicularis (Pinworm) contracted/spread?
Fecal-oral route of infection
Person to person transmission is high, especially in children and institutionalized individuals
Female lays eggs in perianal region causes intense itching, leading to scratching, leading to hand and nail contamination, etc.
How do Enterobius vermicularis (Pinworm) infections progress?
Self-infection occurs by scratching perianal area without hand washing
Larvae hatch in the small intestine after ingestion of infective eggs
Adults grow in the colon
Pregnant females migrate nocturnally outside the anus and oviposit while crawling on the skin of the perianal area
What are the symptoms of Enterobius vermicularis (Pinworm)?
Intense nocturnal perianal itching
Insomnia
Can migrate to urogenital tract in females causing a vaginitis and lead to secondary bacterial UTI
Scratching may lead to secondary bacterial skin infections
How is Enterobius vermicularis (Pinworm) diagnosed?
Tape test from perianal region reveals eggs
How is Ascaris lumbricoides (Roundworm) contracted?
Fecal-oral contamination
How does a Ascaris lumbricoides (Roundworm) infection progress?
Adult worms live in the lumen of the small intestine, passes eggs in small intestines
Larva penetrates the intestinal mucosa, carried via the portal vein, then systemic circulation to the lungs
The larvae mature further in the lungs (10 to 14 days), penetrate the alveolar walls, ascend the bronchial tree to the throat, and are swallowed
Egg ingestion to new egg passage takes approximately 9 weeks
What are the symptoms of Ascaris lumbricoides (Roundworm) infection?
Usually asymptomatic
Fever, jaundice, chachexia and mental retardation due to malnutrition, pulmonary symptoms, abdominal tenderness due to obstruction or bowel perforation, Loeffler’s syndrome, Larva migrans
What is Loeffler’s Syndrome?
Originally reported as a benign, acute eosinophilic pneumonia of unknown cause characterized by migrating pulmonary infiltrates and minimal clinical manifestations
What is larva migrans
Dog and cat ascarid larvae (Toxocara spp.) hatched from eggs that are accidentally swallowed
Larvae migrate and encyst as second-stage larvae, terminating development
Produces tracts with hemorrhagic necrosis and eosinophilic and lymphocytic infiltration
Can migrate to the liver causing enlargement and studded nodules
How is Ascaris lumbricoides (Roundworm) diagnosed?
Eggs in stool (negative in early infection)
How is Necator americanus and Ancylostoma duodenale (Hookworm) contracted?
Direct contact (walking barefoot) or ingestion of soil contaminated with human fecal matter
How does a Necator americanus or Ancylostoma duodenale (Hookworm) infection progress?
On contact with the human host, the larvae penetrate the skin and are carried through the veins to the heart and then to the lungs. They penetrate into the pulmonary alveoli, ascend the bronchial tree to the pharynx, and are swallowed
Larvae reach the small intestine, where they reside and mature into adults. Adult worms live in the lumen of the small intestine, where they feed on erythrocytes of the host.
What are the symptoms of Necator americanus and Ancylostoma duodenale (Hookworm)?
Infecting larvae induce pruritic maculopapular dermatitis at site of entry (“ground itch”)
Transient pneumonitis
Epigastric pain, inflammatory diarrhea with eosinophilia
Primary Syndrome: Iron deficiency anemia
Occult blood in stool
Larva migrans
How is Necator americanus and Ancylostoma duodenale (Hookworm) diagnosed?
Eggs in fresh stool, larvae in old stool
How is Strongyloides stercoralis (Threadworm) contracted?
Direct contact of contaminated soil (walking barefoot) or ingestion of contaminated soil
How does a Strongyloides stercoralis (Threadworm) infection progress?
? Colonization of bowel and maturation
? Can spread through lymphatics to blood stream and other organs leading to abscesses, granulomas, or sepsis
Can cause reinfection by maturing in bowel and re-entering through skin in perianal region
What are the symptoms of a Strongyloides stercoralis (Threadworm) infection?
“Ground itch”, cough and Loeffler’s syndrome, chronic watery diarrhea with mucous, may contain blood, urticaria, Larva currens
What is Larva currens?
• Occurs on the trunk or near the anus and is a linear eruption in which the larvae migrate under the skin causing an itchy, non-indurated wheal with a red flare that moves rapidly and disappears in a few hours
What are the cestodes (tapeworm)? What are their features?
Taenia solium (pig tapeworm)
Taenia saginata (beef tapeworm)
Have proglottids and Cystercerci (tissue cysts)
How are Cestodes (tapeworms) and Taenias contracted? How does the infection progress?
Ingestion of cystercerci in meat
Ingestion of eggs
Invasion of tissues and cystercerci formation, most commonly in brain
What are the symptoms of a Cestode (tapeworms) or Taenias infection?
Likely to be asymptomatic
Epigastric discomfort
Nausea
Sensation of hunger
Diarrhea
Cysticercosis if eggs are ingested
How are Cestode (tapeworms) or Taenias diagnosed?
Detection of eggs or proglottids in stool
Cystercerci: plain films reveal calcified “puffed rice” lesions
How are Trematodes (Fluke) contracted?
Biliary infections: Ingestion of poorly cooked, pickled, or smoked fish
Liver infections: Ingestion of metacercariae encysted on aquatic plants (watercress)
How does a trematode (fluke) infection progress in the biliary tract?
Excyst in small intestines, migrate through ampulla of Vater into biliary ducts
Worms lead to adenomatous hyperplasia, inflammation, and duct obstruction
How does a trematode (fluke) infection progress in the liver?
Excyst in duodenum, pass through intestine into peritoneum, invade liver through Glisson’s capsule
Granulomatous reactions, duct obstruction, etc. may occur
How does a biliary trematode (fluke) infection manifest?
Acute infections noted by fever, eosinophilia, and hepatomegaly
Heavy worm burden may lead to constitutional complaints and symptoms associated with cholelithiasis and pancreatitis
How does a liver trematode (fluke) infection manifest?
Fever, hepatomegaly and/or abdominal pain
Nausea, cough, diarrhea, and urticaria are also common
Periods of jaundice
How is a biliary trematode (fluke) infection diagnosed?
Ova can be identified in stools, dilation of ducts by imaging
How is a liver trematode (fluke) infection diagnosed?
Fever, hepatomegaly or liver pain, proper clinical setting
Serology, as ova may not be detected in stool
What are the general characteristics of Staphylococcus aureus?
Ferments mannitol, coagulase-positive, catalase-positive
Gram-positive, cocci in clusters
Non-motile, non-sporeformer
Facultative anaerobe
What causes Staph aureus food poisoning?
Results from bacterial toxin in food, not an infection by the bacteria itself
What foods are commonly contaminated by Staph aureus?
Usually by improper handling of meats
Ham, salted pork (can grow in high salt content
Custard-filled pastries
Potato salad
Ice cream
What are the toxins secreted by Staph aureus?
Enterotoxin A and B
Can lead to severe metabolic alkalosis
What types of media are capable of culturing Staph aureus
?-hemolytic sheep’s blood agar

Selective media:
Mannitol salt agar
Phenylethylalcohol agar (PEA

What are the general characteristics of Clostridium perfringens
Gram-positive, spore-formers
Can be found in the intestinal flora of humans and in the soil
How is Clostridium perfringens food poisoning contracted?
Ingestion of contaminated food via dirt or feces
Often occur in institutions or after large gatherings, can incubate at moderate temps
Most commonly in meat cooked in bulk and then left in warming trays
What increases the likelihood of food poisoning by Clostridium perfringens?
The longer the meat is allowed to sit, more likely of getting sick
What types of media are capable of culturing Clostridium perfringens?
EYA (egg yolk agar) with anti-toxin A in ? of the plate: precipitation forms around colonies to indicate lecithinase activity

Double-zone of hemolysis on blood agar

How does Clostridium perfringens cause food poisoning?
Heat-labile enterotoxin
What are the effects of clostridium enterotoxin?
Maximum effect in the ileum
Minimum effect in the duodenum
Inhibits glucose transport
Damages intestinal epithelium
Causes protein loss into the intestinal lumen
What causes Enteritis necroticans?
Clostridium perfringens, type C
How is enteritis necroticans contracted?
Occurs after large consumption of improperly cooked pork during native feasts
What are the symptoms of Enteritis necroticans?
Severe necrotizing disease of the small intestine
Intense abdominal pain, distension, bloody diarrhea, vomiting & shock
High mortality due to intestinal perforation
How does Clostridium botulinum cause food poisoning?
Ingestion of secreted botulin toxin
What are the effects of botulin toxin?
Small amounts can produce paralysis and death
Attaches to neuromuscular junction of affected nerves
Prevents release of acetylcholine
Approximately 1 microgram of toxin is lethal
What is the most common route of botulin toxin food poisoning?
Home-canned vegetables
What is the progression of botulin intoxication?
Cranial nerve paralysis
Respiratory muscle weakness which can be fatal
Preceding or following onset of paralysis
How is botulin toxin food poisoning diagnosed?
Presence of organism and/or toxin in vomitus, gastric fluid, or stool
How is botulin toxin food poisoning treated?
A-B-E antitoxin
Can slow progression of disease but will not neutralize toxin already bound to neuromuscular junctions
What are the possible pathologies caused by Bacillus cereus food poisoning?
Gastroenteritis
Ocular infections
Intravenous catheter-related sepsis
Diarrhea syndrome
Vomiting syndrome
What are the general characteristics of Bacillus cereus?
Spore-former
?-hemolytic on sheep blood agar
Facultative anaerobe
Motile, gram-positive rod
How does Bacillus cereus food poisoning cause diarrhea syndrome?
Enterotoxin produced, adenylate cyclase is activated in intestinal cells
Similar to action of cholera toxin
What foods are associated with Bacillus cereus induced diarrhea syndrome?
Spaghetti sauces
Dried potatoes, dried milk
Foods are maintained at temperatures between 30-50 degC
What foods are associated with Bacillus cereus induced vomiting syndrome?
Fried rice via a heat stable toxin that does not activate adenylate cyclase
Large amounts can lead to liver failure
What are the toxins secreted by Bacillus cereus?
Heat-stable, proteolysis-resistant enterotoxin: Emetic form
Heat-labile enterotoxin: Diarrheal form
How is Bacillus cereus food poisoning diagnosed?
Samples of contaminated food must be cultured
Identification in stool specimens of symptomatic patients is strong evidence
Grows rapidly on sheep blood aga
Cryptosporidium spp. infections are associated with what mode of contraction?
Contaminated water
What are the general characteristics of Cryptosporidium spp.?
A coccidian, subphylum, Sporozoa (protozoan)
Lives on or just below the epithelial cells of the small intestine
What is significant about the life cycle of Cryptosporidium spp.?
Asexual reproduction allows for continued autoinfection, oocysts are infective when passed
Patients may remain infective after diarrhea ceases
What are the symptoms of a Cryptosporidium infection?
Frequent, watery diarrhea
Nausea, vomiting
Abdominal cramps
Low-grade fever
How does Cryptosporidium cause diarrhea?
Alters osmotic pressure in the gut resulting in in influx of fluid, much like cholera
Epithelial cells are damaged by
Invasion of parasite
T-cell mediated inflammation causing villus atrophy
How is Cryptosporidium infections diagnosed?
Modified Ziehl-Nielsen acid-fast stain
Microscopic observations of small, acid-fast oocysts in smears of fecal specimens
How is Cryptosporidium treated?
Self limiting in most
If immunocompromised, give Paromomycin
What are the general characteristics of Giardia lamblia?
Flagellate
Most commonly identified intestinal parasitic pathogen
Cysts are resistant forms, survive in cold water for several months
How is Giardia lamblia most commonly acquired?
Contaminated water and person contact in institutions or daycare centers
Describe the lifecycle of Giardia lamblia
Trophozoites reproduce by longitudinal, binary fission in the lumen of the proximal small bowel
Encystation occurs as parasites travel to the colon
Cysts are passed out through nondiarrheal feces
What are the symptoms of acute Giardiasis?
Diarrhea, abdominal pain, bloating, nausea, vomiting
How is Giardia lamblia diagnosed?
Microscopic identification of cysts or trophozoites in feces
How is Giardia lamblia treated?
Metronidazole, tinidazole
How is Entamoeba histolytica (a pathogenic amoeba) infection most commonly contracted?
Oral/fecal route, contaminated water, food
Cysts are found in formed stools
Can survive for day-weeks in external environment, trophozoites die in the acidic stomach
What are the characteristics of invasive, intestinal amebiasis via Entamoeba histolytica?
Dysentery, colitis
What are the characteristics of extra-intestinal amebiasis via Entamoeba histolytica?
Liver abscess
Peritonitis
Pleuropulmonary abscess
Cutaneous and genital amebic lesions
What is the mechanism of GI infection by Entamoeba histolytica?
Mediated by an adherence lectin in instestin
Disruption of intestinal barrier by secretion of proteolytic enzymes and invasion of intestinal epithelial cells
What are the characteristic appearance of Entamoeba histolytica GI lesions?
Flask-shaped ulcers
E. histolytica is resistant to what immune mechanisms?
Phagocytosis
Complement-mediated cell lysis
What are the consequences of a heavy infection of Entamoeba histolytica?
Causes vacuoles to coalesce
Sloughing off of the lining causes bloody, mucus-filled stools
How does Entamoeba histolytica cause liver abscesses?
May completely erode the intestinal mucosa
Enters the circulation
Organ most commonly colonized is the liver, causes abscess formation
How does Entamoeba histolytica cause lung abscesses?
Penetration of the diaphragm from hepatic abscesses or from hematogenous spread
How is Entamoeba histolytica diagnosed?
Microscopic evidence of trophozoites in stool specimens via wet mounts or trichrome-stained smears
Sigmoid biopsies
ELISA provides evidence of current infection but is not diagnostic
What are the general characteristics of Cyclospora cayetanensis?
Spore-forming coccidia
Unicellular, coccidian parasite
Oocysts are passed in stools, not infective, distinguishes this organism from Cryptosporidium
Sporulation occurs in the environment at temp. between 22-32 degC
How is Cyclospora cayetanensis most often transmitted?
Fresh produce and water via contamination with sporozoites released asexually into the stool
How is Cylcospora cayetanensis infection prevented?
Can be killed by washing or cooking
Occurs primarily in the tropics and subtropics
How is a Cylcospora cayetanensis infection diagnosed?
Evidence of oocysts in stool specimens by microscopy
Stool specimens should be refrigerated or preserved in 10% formalin
Requires 3 or more specimens collected at 2-3 day intervals due to intermittent release of oocysts
Modified acid-fast stain
What are the symptoms of a Cylcospora cayetanensis infection?
Watery diarrhea which can be severe
Anorexia, nausea, vomiting, abd pain
Low-grade fever, fatigue
Flu-like symptoms
Can persist for several weeks
How are Cylcospora cayetanensis infections treated?
Usually self-limiting in both immunocompetent and immunocompromised individuals, give fluids
Trimethoprim-sulfamethoxazole can reduce symptoms
What is Blepharitis?
Noncontagious inflammation of the lower portion of the eyelids and eyelashes caused by
Poor eyelid hygiene
Excess oil
Staphylococcus aureus
Allergic reaction
What is Dacryocystitis?
Inflammation of the lacrimal sac caused by partial or complete obstruction within the sac or nasolacrimal duct
Bacteria are trapped initiating acute or chronic infection
Older patients are predisposed
What is Conjunctivitis?
Inflammation of the conjunctiva, the outermost layer of the eye covering the sclera
Progressive keratitis can lead to ulceration, scarring, and blindness
What are the three causes of conjunctivitis?
Bacterial (most common) viral, or allergies
What are the characteristics of viral conjunctivitis?
Usually due to an upper respiratory infection
Watery discharge
Red eye
Irritation
Can spread to other eye
What symptoms of bacterial conjunctivitis help differentiate it from viral conjunctivitis?
Stringy discharge
Other symptoms:
Swelling of the conjunctiva
Redness, tearing
Irritation (gritty feeling)
Can spread to other eye
What is the most common cause of bacterial conjunctivitis?
Adults: Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae
Infants: Neisseria gonorrhoeae, Streptococcus pneumonia, Haemophilus influenzae
How do you treat bacterial conjunctivitis?
Antibiotic ointments or eyedrops
Neomycin, polymyxin, bacitracin
Gentamicin, tobramycin against gram-neg microorganisms
What is Ophthalmia neonatorum?
Severe conjunctivitis of newborns, can acquire the infection at birth, typically due to STD pathogens
Neisseria gonorrhoeae, Chlamydia trachomatis, Herpes simplex virus
What is Endophthalmitis? What causes it?
Rare, intraocular infection of the aqueous or vitreous humor caused by normal flora of the eyelids:
Staphylococcus epidermidis
Rarely by pseudomonas (poor prognosis)
What is Uveitis?
Inflammation or swelling of the eye structures responsible for the eye’s blood supply
What are the symptoms of Iritis (anterior uveitis)?
Redness, pain, photophobia due to painful movement of inflamed iris
Blurred vision in severe inflammation
What are the symptoms of Intermediate uveitis (cyclitis)?
Blurring, presence of floaters (black dots or wispy lines which move across the field of vision)
What are the symptoms of posterior uveitis
Blurring, gradual or sudden reduction in vision
Usually painless
What is periorbital cellulitis? what are potential complications?
Acute infection of the tissues surrounding the eye
Can lead to orbital cellulitis and protrusion of the eyeball, meningitis if severe
What causes periorbital cellulitis?
Absence of an effective drainage system, predisposes the parasinuses to invasion
Bacteria, fungi, or parasites can gain access via trauma, surrounding infection, or upper respiratory infection
Haemophilus influenza is grown on what type of media?
Chocolate agar
Requires the 2 erythrocyte growth factors X (hemin)
and V (nicotinamide adenine dinucleotide) for growth
What is the appearance of Haemophilus influenza?
Gram-negative, bacillus (rod)
Non-motile, non-spore forming
Fastidious, facultative anaerobe
What mediates pathogenesis for Haemophilus influenza?
Attachment to respiratory epithelial cells is accomplished using pili
Endotoxin in the cell wall is toxic to ciliated respiratory cells
What is the most virulent strain of H. influenza which is responsible for infections such as bacteremia, meningitis, cellulitis, septic arthritis, and pneumoniae?
Haemophilus influenzae type b (HiB)
Which H. influenza strain causes mucosal infections such as otitis media, conjunctivitis, bronchitis, and pneumoniae?
Nonencapsulated (or non-typeable) strains
80% of individuals are colonized with the non-typeable strains
COPD and cystic fibrosis pts particularly susceptible
What are the general characteristics of Streptococcus pneumonia
Gram-positive, cocci
Usually seen in pairs**(diplo) but not always
Non-spore formers, non-motile
Strep pneumonia is cultured on what media?
Blood agar medium results in alpha-hemolysis (partial hemolysis)
Can grow very quickly under optimal conditions
What determines the virulence of Strep pneumonia?
Capsule interferes phagocytosis by blocking C3b opsonization
What is the Quellung reaction?
Serotyping used to identify a particular capsule type of strep pneumo
Antibody reacts with a particular capsule type, causes capsular swelling
What allows Staph aureus to avoid phagocytosis?
Protein A, a cellular component in the cell wall
What are the virulence factors of Staph aureus?
Cytolytic toxins (alpha and beta hemolysin, staphylococcal leukocidin)
Enzymes (coagulase, hyaluronidase, lipase)
Protein A
How do you differentiate Staph epidermidis from Staph aureus?
Staph epidermidis is coagulase-negative whereas Staph aureus is positive
What type of infections are caused by Staph epidermidis?
Hospital acquired UTIs
Osteomyelitis at prosthetic joints
Native valve endocarditis due to catheters
Bacteremia
Almost ALL cases of infection are hospital acquired
What mediates the antibiotic resistance of Staph epidermidis?
Plasmid-mediated, can also transfer to Staph aureus
What are the general characteristics of Chlamydia trachomatis?
Obligate intracellular parasites
Most common STD in the world, causes blindness and infertility
What is trachoma?
Chlamydia infection of the eye transmitted through eye secretions and eye-seeking flies
Inflammatory reactions results in scarring on the conjunctiva
Eyelid to turns inward where the eyelashes can rub the cornea
What is unique about the life cycle of Chlamydia trachomatis?
Alternates between a non-replicating, infectious elementary body and a replicating, noninfectious reticulate body
How is Chlamydia trachomatis diagnosed?
Immunofluorescence
What is MOTT?
mycobacteria other than tubercle bacilli
Associated with contact lenses, trauma, and wound contamination with soil
Causes Keratitis and Corneal ulcers
What are the most common MOTT pathogens?
Mycobacterium chelonae
Mycobacterium fortuitum
What are the general characteristics of Eikenella corrodens?
Microaerophilic, gram-negative rods
Normal flora of human, mucosal surfaces
Culture requires CO2 environment and hemin in the medium, lab must be notified in advance
Usually a part of a mixed infection with Streptococcus sp.
Gets its name from the fact that it forms pits on the surface of agar medium
How is Francisella tularensis contracted?
Primarily a pathogen of squirrels and rabbits. Humans are infected by the bite of an infected deer fly or tick
or eating undercooked infected meat or handling infected rabbit carcasses
What are the symptoms of tularemia (Francisella tularensis infection)
Highly infectious
Skin ulcers
Swollen, painful lymph nodes
Inflamed eyes, sore throat, mouth sores
How is Francisella tularensis cultured?
Grown on chocolate agar
What causes “cat scratch fever”?
Bartonella henselae: Gram-negative bacillus
What are the characteristics of cat scratch fever (Bartonella henselae infection)?
Parinaud’s Oculoglandular Syndrome, manifests as conjunctivitis, neuroretinitis
Vitritis, posterior uveitis
Discrete foci of retinitis manifested as white retinal or choroidal lesions
What are the characteristics of HSV blepharitis?
Vesicles appear on lid margins and around the eyes
Vesicles can break open forming lesions which can become superinfected by skin flora
What is ocular herpes and what are its characteristics?
HSV infection of the conjunctiva
Swelling of the eyelids
If cornea is involved (Herpes Simplex Keratitis)
Destructive ulceration and perforation of the cornea possible
What is Herpes Simplex Keratitis?
Dendritic keratitis
Secondary herpetic infections
Virus branches out in a dendritic pattern**
Virus deadens the nerves – no pain
What are the characteristics of varicella-zoster blepharitis?
Vesicles may appear on the lid margins
Wartlike lesions can form (molluscum contagiosum) from the pox virus
Can cause keratitis, scleritis, infections of the lacrimal apparatus, endophthalmitis
What ocular infections are caused by adenovirus?
Conjunctivitis and epidemic keratoconjunctivitis
What are the characteristics of CMV retinitis?
Floaters, flashes, and blind spots
Pizza pie retinopathy (CMV infiltrates the vascular endothelium)
More common among immunocompromised or neonates from infected mothers
What are the characteristics of Aspergillus sp?
Most commonly encountered genus of fungi in the clinical laboratory
Erects conidiophores from a “foot cell” with a vegetative hyphae
What are the characteristics of Acremonium sp.?
Filamentous fungi isolated from plant debris and soil
Rare cases of keratitis and endophthalmitis
Known to cause opportunisitic infections in immunocompromised
Possess fine, narrow, septate hyphae
What are the characteristics of Penicillium sp.?
Filamentous fungi
Found in soil, decaying vegetation, air
May cause infections in immunocompromised hosts
Has a bottle brush look
Can cause Keratitis and Endophthalmitis
What are the characteristics of Rhizopus sp?
Causative agent for a group of fungal infections classified as zygomycosis, frequently fatal
Causes rhinocerebral infections
Also known as the black bread mold
What predisposes someone to a rhinocerebral infection?
Diabetic ketoacidosis
Immunosuppression
Nosocomial rhinocerebral infections are usually contracted through what means
Contaminated adhesive tape
Contaminated, wooden tongue depressors
What is responsible for approximately 90% of rhinocerebral infections classified as zygomyosis?
Mucormycosis
What causes endophthalmitis due to candida infections?
Exogenously following surgery or trauma (rare)
Endogenoushly due to embolic seeding in the retina (most common cause)
What pathogens can cause corneal ulcers due to improper contact lens use?
Pseudomonas, Bacillus cereus, Acanthamoeba
Keratitis due to Acanthamoeba is associated with what kind of behavior?
Wearing of nondisposable lenses
Use of homemade sodium chloride solutions
Wearing of contacts while swimming
Toxoplasma gondii is most often contracted via what vectors?
Exposure to contaminated water containing tissue cysts
Exposure to oocysts shed by infected cats
Eating meat contaminated with oocysts
Congenital transmission
Congenital infections by Toxoplasma gondii targets what organs?
Retina (chorioretinitis)
Brain
What are the different morphological forms of Toxoplasma gondii?
Oocysts in intestines of members of the cat family (primary host)
Tachyzoite – the invasive form responsible for acute disease
Sporulated and unsporulated oocysts
How is Toxoplasma gondii diagnosed?
Indirect immunofluorescent assay (IFA)
Ring enhancing lesions on imaging is indicative
How is Loa loa (eyeworm) transmitted?
Chrysops fly
Confined to the rain forest and swamp forest areas of West Africa
How is Onchocerca volvulus transmitted?
Spread by the vector, Simulium (the black fly)
What is caused by infection by Onchocerca volvulus?
River Blindness
Microfilaria can migrate into peripheral blood and the eyes during heavy infections, infects the cornea, optic nerve, choroid
Dead microfilaria induce an inflammatory response in the eyes
What causes Myiasis?
Infection of tissues or organs of animals or man by fly larvae
Oestrus ovis (sheep botfly)
Can cause severe conjunctivitis
What are the most common manifestations of a hematological infection?
Anemia
Pancytopenia
Lymphocytosis
Neutrophilia
Eosinophilia
What is Pancytopenia?
A decrease in all blood cell lineages due to toxic effects causing bone marrow necrosis, inflammatory mediators, and hemophagocytic syndrome
What causes Pancytopenia?
Congestive splenomegaly due to infections such as:
Salmonellosis, infectious mono
Tularemia, hepatitis
Syphilis
Toxoplasmosis
Schistosomiasis, malaria
What is Tularemia?
AKA glandular fever, rabbit fever, tick fever, and deer fly fever
Caused by infection by Francisela tularensis acquired from the bite of an infected tick (Ixodes, Dermacentor)
What are the general characteristics of Francisela tularensis?
Gram-negative, non-motile rod
Strict aerobe, fastidious
Intracellular parasite
Acquired from the bite of an infected tick (Ixodes, Dermacentor)
What is the most common clinical manifestation of Tularemia?
Ulceroglandular tularemia
Skin lesion (from a tick bite) is a painful papule which ulcerates having a necrotic center
Leads to lymphadenopathy and bacteremia
How is Tularemia diagnosed?
Direct immunofluorescent staining
What causes Toxoplasmosis?
Toxoplasma gondii, an intracellular blood and tissue parasite
Definitive host is the cat
Infective oocysts are shed in cat feces
Human infection is due to ingestion of improperly cooked meat or oocysts from cat feces
What is the infective form of Toxoplasma gondii?
Trophozoites
Responsible for initial infection and tissue damage
What are some of the more rare causes of Toxoplasmosis?
Transplacental infections
Transfusion infection via contaminated blood
T. gondii has a predilection for infecting which organs?
Heart and lymphoid organs especially
Lung, CNS, and eyes as well
An infant suffering from a congenital case of Toxoplasmosis experiences what symptoms?
Anemia
Jaundice, epilepsy, encephalitis, other neurological disorders
What are the symptoms of Hemophagocytic Syndrome (aka hemophagocytic lymphohistiocytosis (HLH))
Fever, splenomegaly*
Jaundice
Presence of activated macrophages phagocytizing erythrocytes, leukocytes, platelets, and other blood cell precursors
Phagocytosis is detectable in the bone marrow
What is reactive hemophagocytic syndrome?
Hemophagocytic syndromes secondary to an underlying infection
Sporadic and familial cases of HLH are caused by what?
Acute infections
Hemophagocytic Syndrome can interfere with the diagnosis of what treatable infectious disease?
Visceral leishmaniasis
What initial diagnostic tests should be performed if Hemophagocytic syndrome is suspected?
Blood and urine cultures
Chest radiography to screen for tuberculous infections
Serological assays for viral infections
Throat and rectal swabs for viral culture
Fungal antigen testing
Determine if an underlying T-cell lymphoma is present
Hemophagocytic syndrome is associated with HIV patients with what kind of underlying infections?
Pneumococcal disease
Pneumocystosis
Histoplasmosis
What kind of infections associated with animal infections or travel need to be considered in cases of hemophagocytic syndrome?
Leshmaniasis
Brucellosis
Rickettsioses
Malaria
What are the most common symptoms of hemophagocytic syndrome?
Fever*, splenomegaly*
What are the most common lab abnormalities associated with hemophagocytic syndrome?
**Anemia, thrombocytopenia, neutropenia, hypertriglyceridemia, hypofriboginemia
How can the overactivation of macrophages cause hemophagocytic syndrome (HLH)?
High levels of activating cytokines due to viral or nonviral causes
Associated with EBV infection and the presence of episomal EBV genome in T cell lymphocytes
What is Brucellosis?
Infection caused by Brucella sp.
What are the general characteristics of Brucella sp.?
Small, nonmotile, gram-negative rods
Requires complex growth media
Strict aerobe
Slow growth (at least 1 week)
An intracellular parasite of the reticuloendothelial system
What are the two types of colony morphology of Brucella? What is it based off of?
Based on the O antigen of LPS
Smooth (translucent, homogeneous, more virulent)
Rough (opaque, granular, or sticky)
O chain of the smooth strain LPS is a marker for virulence
Describe the pathogenesis of Brucella
An intracellular parasite of the reticuloendothelial system
Microorganisms are phagocytosed by macrophages and monocytes
Acidic environment of the phagolysosome induces virulence genes
Phagocytosed bacteria are carried to the spleen, liver, bone marrow, lymph nodes, and kidneys, forms granulomas
How is Brucellosis contracted?
Consuming contaminated, unpasteurized milk and other dairy products
What is Leishmaniasis? What causes Leishmaniasis?
Infection by Leishmania sp.
Vector-borne disease transmitted by sandflies
What causes the symptoms of a Leishmania infection?
Amastigote forms found in reticulo-endothelial cells of the viscera
Spleen, lymph nodes, liver, intestines
What is distinctive about the incubation period of Leishmaniasis?
Incubation can be as short as 10 days or as long as a year
What are the symptoms of Leishmaniasis?
Anemia, protrusion of abdomen due to splenomegally, and bleeding mucus membranes are most important*
Low grade fever, malaise, wasting, facial edema, diarrhea, breathing difficulties
What causes Rickettsioses?
Rickettsia sp.
Transmitted by tick vectors
What are the general characteristics of Rickettsia?
Obligate intracellular, aerobic, gram-negative rods
How is Rickettsia diagnosed?
Giemsa stain is preferred
Describe the pathogenesis of Rickettsia?
Enters eukaryotic cells by stimulating phagocytosis
Degrades the phagosome membrane using a phospholipase to enter the cytoplasm, necessary for survival
What is the characteristic site of pathologic lesions of Rocky Mountain Spotted Fever?
Small blood vessels
Vessels may be blocked by thrombi causing vasculitis in the heart*, spleen*, skin, liver, kidneys, lungs, or CNS
Severe cases of Rocky Mountain Spotted Fever are in danger of what complication?
Disseminated Intravascular Coagulopathy (DIC)
What is Rocky Mountain Spotted Fever
Rickettsioses due to Rickettsia rickettsii transmitted through the tick
What is Epidemic typhus?
Rickettsioses caused by Rickettsia prowazekii transmitted by exposure to human body louse feces (Pediculus humanus)
What are the symptoms of epidemic typhus?
Splenomegaly*, hypotension*, vascular collapse* if severe
High fever, headache, maculopapular rash
What is Scrub typhus?
Rickettsioses caused by Rickettsia tsutsugamushi
Transmitted to humans by chigger (mite larva) bites
Occurs in Asiatic-Pacific areas
What are the clinical symptoms of scrub typhus?
*Splenomegaly, *interstitial myocarditis
Fever, headache, macular rash
Delirium, stupor, muscle twitching
What causes increased levels of hepcidin with release of cytokines in cases of anemia due to chronic infection?
Iron is trapped in the reticuloendothelial system
Erythropoietin levels decrease
Cytokines suppress hematopoiesis in the bone marrow
What is the function of Hepcidin?
Key regulator in iron metabolism
Regulates absorption of iron from foods and iron transport across the placenta
Regulates the release of iron from macrophages and the recycling of aged RBCs
How does inflammation affect the actions of Hepcidin and cause anemia?
Production is 100x higher than normal
Results in increased sequestration of iron in macrophages
What are the best known parasitic infections that cause hemolytic anemia?
Malaria (Plasmodium falciparum)
Bartonellosis (Bartonella bacilliformis)
Babesiosis (Babesia microti)
What causes malaria?
Sporozoites of Plasmodium falciparum in the salivary glands of mosquitoes that have ingested blood infected with malarial gametocytes
Describe the pathogenesis of Plasmodium falciparum (malaria)
Sporozoites travel to the liver where they invade and replicate
Merozoites leave the liver through the circulatory system and invade red blood cells
Merozoites continue to replicate, lyse RBCs, and invade other RBCs
Plasmodium falciparum (most severe form of Malaria) feeds on what?
Hemoglobin and other proteins
Ultimately causes destruction of the spleen
Merozoites adhere to glycophorin molecules on the red blood cell surface
Which organisms cause relapsing malaria?
Plasmodium vivax and Plasmodium ovale
After treatment, treatment-resistant parasites reside dormant in the liver
Eventually they invade RBCs and begin a typical erythrocytic cycle
Which organism causes long-lasting malarial infections that are most often asymptomatic?
Plasmodium malariae
RBCs parasitized by Plasmodium vivax display small purplish red granules (with Wright’s stain) called what?
Schuffner’s dots
How is malaria diagnosed?
Giemsa or Wright stains are gold standard
What are other forms of malarial diagnosis?
Malarial RDTs (rapid diagnostic test)
What is Babesiosis?
Zoonosis caused by animal-specific protozoan parasites
Parasites invade RBCs and induce a febrile disease
Hemolytic anemia, hemoglobinuria, shock, death
What Babesia species are responsible for majority of human infections?
Babesia microti
Babesia divergens
What are the most common hosts for Babesia?
White-footed mouse
Deer tick
Humans are accidental hosts, no human to human transfer
How is Babesiosis diagnosed?
Direct blood smears show tetrad formation in RBCs
Indirect fluorescent antibody test
What is Oroya fever (acute)?
Infection by Bartonella bacilliformis (Bartonellosis)
Motile by polar flagellum
Adheres to and invades RBCs
What causes Bartonellosis (Oroya fever)?
Transmitted by the nocturnal sandfly
Limited to a small area in the Andes Mountains
How does intraerythrocytic Bartonella bacilliformis avoid the immune response?
Lacks MHC molecules on the surface of mature erythrocytes
Presentation of Bartonella antigens to the immune system is not possible
How is Bartonellosis diagnosed?
Serologic testing
Microscopic examination of Giemsa-stained blood smears
What alpha toxin is secreted by Clostridium perfringens?
Lecithinase
*What are the actions of the alpha-toxin lecithinase secreted by Clostridium perfringens?
Reacts with red blood cell membrane lipoproteins to produce lysolecithin
Disrupts cell membranes of host cells including Erythrocytes and Leukocytes
Mediates massive hemolysis, increased vascular permeability, and bleeding
Causes myocardial dysfunction
What is the action of Theta-toxin (?-toxin) secreted by Clostridium perfringens?
Is a heat-labile & oxygen-labile hemolysin
Alters capillary permeability
Toxic to heart muscle
Pore-forming (cytolytic)
What is responsible for initial cell destruction in respiratory tract by Clostridium perfringens?
Hydrogen peroxide
Damages erythrocyte membranes*
How does Mycoplasma pneumoniae cause cold autoimmune hemolytic anemia?
Auto-IgM antibodies are directed against the I antigen on red blood cells
Cause agglutination of RBCs* transiently in the fingers, ears, nose
Mycoplasma pneumoniae is inherently immune to what types of antibiotics?
Beta-lactams due to lacking a cell wall
What are the general characteristics of Mycoplasma pneumoniae?
Slow rate of growth
Obligate aerobe
Receptor on Mycoplasma pneumoniae is integral in attachment to eukaryotic host cell membranes in the respiratory tract and RBCs
What are the possible complications of measles vaccination?
Thrombocytopenia*
What are the characteristics of a Rubella infection?
Respiratory transmission
Viruses replicates in the nasopharynx & lymph nodes
Viremia* with spread to other tissues
What are the hemorrhagic manifestations* of a Rubella infection?
Rare, primarily children
Low platelet count, vascular damage
Thromobocytopenic purpura
GI, cerebral, intrarenal hemorrhaging can occur
What are the IgG antibodies that react with RBCs in the cold (below body temperature)
Donath-Landsteiner antibodies cause a rare form of cold-autoimmune hemolytic anemia referred to as Paroxysmal cold hemoglobinuria
Can be idiopathic or associated with Syphilis, Varicella, Mumps, Measles, etc.
What kind of infection can cause Ag/Ab complexes bind to RBC surface and induce hemolysis?
Hemophilus influenzae type b meningitis
What is Polyagglutination?
A rare form of hemolysis caused by metabolites from infectious agents forcing RBCs to exposed normally hidden surface antigens
Example: enteric bacteria can produce neuraminidase
What kinds of infections can cause a disruption of the gastrointestinal or genitourinary mucosa leading to anemia by blood loss?
Helicobacter pylori
Helminthic infections such as nematodes and trematodes
What is the most cause for blood loss anemia in developed countries?
H. pylori
How do Ancylostoma duodenale & Necator americanus (hookworms) cause blood loss?
Due to feeding worms
Microcytic, hypochromic anemia develops
Describe the pathogenesis of Schistosomiasis?
Cercaria penetrate the skin and enter the venous system
Travel to heart, lungs, and portal circulation
What are the symptoms of Acute schistosomiasis (Katayama’s fever)
*Diarrhea (bloody), *Hepatosplenomegaly, *eosinophilia, Cystitis, ureteritis with hematuria* (can lead to bladder cancer)
Fever, cough, abd pain, occasional CNS lesions, pulmonary hypertension
How is Fasciolopsis buski (intestinal fluke) contracted?
Ingestion of encysted larva in aquatic vegetation like water chestnuts
Found only in China, Vietnam, Thailand, parts of Indonesia, Malaysia, India
Attachment of the flukes (Fasciolopsis buski) to the small intestines causes what?
Hemorrhage*
Marked eosinophilia*
Inflammation and ulceration
What parasite causes Megaloblastic Anemia?
Diphyllobothrium latum (Cestode)
(Fish tapeworm)
Common in areas where raw or pickled fish are eaten
What is characteristic of carriers of Cestodes (fish tapeworm) suffering from megaloblastic anemia?
Low serum levels of vitamin B12
What are the characteristics of Trypanosoma?
Flagellated, insect-transmitted protozoa that infects RBCs and tissues
What causes Chagas’ Disease?
Trypanosoma cruzi transmitted by feces of Triatomine (reduviid) bugs, the “kissing bug”
What are the acute symptoms of Chaga’s disease?
Romana’s sign: Eye on one side swells (at location where triatomine bug fecal matter gets rubbed in)
Occur in about 1% of cases
What are prolonged symptoms of Chaga’s disease?
Enlarged liver or spleen*
Fever, fatigue, swollen lymph glands
Brain damage and death in younger
What causes African Sleeping Sickness?
Trypanosoma brucei gambiense (slow progressing)
Trypanosoma brucei rhodesiense (rapidly progressing)
Kinetoplastids (mitochondrial DNA)
What is characteristic of the acute blood stage of infection for African Sleeping Sickness?
Fever, headaches
What causes relapses of African Sleeping Sickness?
Antigenic variation of trypanosomal surface
Life cycle exhibits different morphologies
What are the symptoms of African Sleeping Sickness?
Apathy, fatigue, confusion, motor changes (tics, slurred speech)
Changes in sleep patterns
Extreme fatigue during day, extreme agitation during night
What are potential complications of African Sleeping Sickness?
Trypanosomes cross the blood-brain barrier resulting in meningoencephalitis
Untreated can progress to coma or death
What is Filariasis?
Caused by infections with nematodes (roundworms)
Infective larvae are transmitted by arthropods
How do nematodes (roundworms) cause filariasis?
Female worms produce microfilariae
Microfilariae enter and circulate in the bloodstream
What are the clinical manifestations of lymphatic filariasis?
Eosinophilia is prominent*
Many are asymptomatic though some develop lymphatic dysfunction
How is filariasis diagnosed?
Identify presence of microfilariae in blood
Blood collection must be timed with periodicity of organism

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