Med Micro Block IV – Flashcards

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D)Defenses of alimentary tract
ORAL - contaminated water and food

1. Primarily an infection of the the intestinal mucosa
2. Those which only colonize, produce toxins which can work locally or in some cases at a distance
3. Some invade laterally within the intestines
4. A few may invade deeper to the draining lymph nodes, lymphatics, blood, and systemically
C)1. Chemical barriers to growth and multiplication - acid, bile 2. Competition from normal flora
3. Lots of food, but little or no oxygen in large intestine
D)STOMACH: chemical barrier of gastric acidity, bactericidal
SMALL INTESTINE: low innoculum from stomach, bile and peristalsis prevent colonization
-LARGE INTESTINE: heavily colonized with obligate ANAEROBES and some facultative anaerobes; NORMAL FLORA primary biological defense. Adherence critical

Candida albicans
Herpes Simplex Virus
-Inflammation of the esophagus
-Usually caused by gastroesophageal reflux.
Less frequent causes include infectious agents (largely in immunocompromised patients)

Difficulty and/ or painful swallowing
Acid regurgitation

Barium x-ray
Candida Albicans - Esophagitis
E)Clinical disease:Candidal esophagitis
yellow-white mucosal plaques, firmly adherent, ulceration, luminal narrowing, strictures and necrosis. Dysphagia (difficulty swallowing) and Odynophagia (pain on swallowing).
Perforation is a rare complication
D)Clinical presentation,
A)Yeast producing pseudohyphae
B)Normal flora on mucosal membranes (damp skin)
D)HIV, diabetes, leukemia and lymphoma, use of broad spectrum antibiotics, corticosteroid therapy and organ transplantation.
E)Clinical Disease?
HSV - Esophagitis
E)Clinical Disease: Multiple small superficial ulcers to larger confluent vesicles progressing to ulcers, or diffusely denuded epithelium may occur with progression
-ulcers with raised margins & central crater (some call them "volcanic")
F)Clinical Presentation, serology
A)ds linear DNA,Enveloped
B)Man-latent(trigeminal ganglia & sacral ganglia)
C)Body fluids, close contact, neonatal
D)HIV, hematologic malignancies, chemotherapy, irradiation or other immunosuppressive therapy for malignancies or transplants
E)Clinical Disease???
E)Clinical Disease: Symptoms indistinguishable from Candida or HSV esophagitis.
-usually indiv. ulcers in esophagus. ulcer margins are distinct & intervening mucosa appears relatively normal
- "punched-out” ulcers
F)Clinical presentation, serology
A)ds DNA virus, enveloped. infects WBCs
B)Man. most have abs(40-100%); virus &endothelial cells)
C)Body fluids, close contact, neonatal
D)patients with AIDS or severe immunosuppression
E)Clinical Disease ??????????
GI intoxications and infections
-Signs and Symptoms (one or more may be present)
+diarrhea - watery feces (3 or more in a day)
+dysentery (gut pain, diarrhea, often bloody, containing inflammmatory cells)
-Time frame relative to consumption : hours to days
+epidemiology (other cases?)
+type of foods eaten
+drugs (antibiotics, etc.)
GENERAL relationship of damage to symptoms (method of classifying diseases)
B)Noninflammatory Diarrhea
C)Inflammatory diarrhea/dysentery
A)rapid onset, usually toxin
B)large volume
-usually without blood or pus
-usually small intestinal effects (secretory bowel)
-usually from toxin
-Public health definition: 3 or more loose stools in a 24 hr period
C)smaller volume, pus (white cells), can be bloody, fever, abdominal pain, tenesmus
- usually from large intestine (inflammatory bowel)
-usually from invasive organisms
Transmission & Prevention for GI intoxications and infections
A)Diarrheal infections are highly contagious
A)person to person spread
-contaminated food or water
-some pets
***Contagious as long as a person has diarrhea, or even longer
B)wash hands frequently
cook foods thoroughly, wash raw fruits/vegetables well
avoid eating undercooked meat
refrigerate leftovers quickly
clean kitchen counters and cooking utensils
never drink from streams, springs, lakes
use bottled water in developing countries or treat water
Tx of GI intoxications and infections
Viral infections will go away without treatment
-Most GI infections caused by viruses and many bacterial infections do not need tx
+Immunocompromised individuals w/ a bacterial intestinal infection may need abxs to prevent infection from spreading systemically
-Most common tx is replacement of fluid & electrolytes
+ may be oral or intravenous if dehydration is severe. *esp. impt. in infants
-Parasitic infection will probably be treated with antiparasitic medicine
-Stool sample may be needed to determine cause
+useful in parasitic infections, outbreak situations, or when there are complications; in most cases specific cause is not det.
Staph Aureus
F)Normally a clinical diagnosis.
-Stool, vomitus and food can be tested for toxin and cultured if indicated.
-ELISA for enterotoxins in food, can detect 1 ng of toxin/g of food.
G)Self Limiting; Rehydration
H)Proper cooking and storage of foods; education of food handlers:
food handlers with opens wounds felt to be Staphylococcal infections should either cover them completely or be excused from food preparation – anyone with upper respiratory infections should be excused from food preparation/handling
A)Gram positive, catalase positive cocci, ?-hemolytic
-Virulence factors: Produce 7 distinct enterotoxins; staphylococcal enterotoxin B (SEB) is most important
+Staphylococcal toxins stimulate vagus nerve endings in the stomach lining that control vomiting response.
+Staphylococcal toxins are also superantigens and stimulate T cell proliferation; release TNF? and IFN? from T cells in the blood stream results in nausea, vomiting, malaise.
+Highly stable to boiling, acid, and enzymes
C)consumption of contaminated foods
-Primary foods: custards, creamy dishes, mayonnaise
D)warmer months where people consume foods not kept refrigerated or improperly prepared foods.
Staph Aureus
Clincal Disease: Staphylococcal Intoxication Dose: as little as 1 microgram of toxin in contaminated food.
Clinical Disease:
1)Acute disease is an intoxication not an infection.
- Due to ingestion of pre-formed heat stable enterotoxins.
- Sudden onset of severe nausea and vomiting.
- Abdominal cramps, diarrhea, headache in some
- Rapid onset is a key feature (<1 - up to 6 hr)
3. Duration of illness: Self resolving within 24-48 hrs
4. Antibiotic therapy not indicated
F)Normally a clinical diagnosis. Stool/ vomitus and food can be tested for toxin and cultured if indicated. See following slides.
G)Self Limiting; Rehydration
H)Proper cooking and storage of foods; education of food handlers

Bacillus cereus
A)Gram positive rod, spore former; beta hemolytic - Aerobe
- VIRULENCE FACTORS: heat labile and heat stable enterotoxins
B)Ubiquitous - Widely disseminated in nature; may be present in stools of healthy individuals
C)Consumption of contaminated food; improper handling/cleaning (vegetables/grains)
D)Usually occurs because heat-resistant endospores survive cooking or pasteurization and then germinate and multiply when the food is inadequately refrigerated.
B. Cereus
Clinical Disease: Emetic syndrome
Clinical Disease:
Intoxication - Rapid-onset
toxin is Cereulide (a circular peptide) -stimulates vagus nerve leading to emetic response; produced only by some strains
Caused by ingestion of pre-formed heat stable toxin (survives 90 min at 126?C)
1-6 hrs incubation period; symptoms last ~24 hours
Profuse vomiting, nausea, and abdominal cramps; Diarrhea usually absent
Boiled rice held for prolonged periods at ambient temperature, fried rice, pasta
Diagnosed by the isolation of >105 B. cereus organisms from the incriminated food.
B. cereus
Clinical Disease: Diarrheal syndrome
Infection - Slow-onset
Ingestion of organisms and subsequent production of heat-labile toxin that stimulates adenylate cyclase causing intestinal fluid secretion
Diarrheal enterotoxin (activates adenylate cyclase – cAMP)
Heat labile at 5 min 56?C (132oF) or 30 min 45?C (113oF)
>6 -16 hrs incubation period; symptoms last 24-48 hrs
Watery diarrhea, nausea, abdominal cramps; Vomiting generally absent
Associated with stews with vegetables, vegetable dishes; spices may harbor spores which may introduce the organism into other foods
The long-incubation or diarrheal form is diagnosed by isolation of the organism from stool and food.
F)confirmed by detecting toxin in feces of patients
-egg yolk agar-lecithinase prod.
-double zone of hemolysis
G)Supportive care, antibiotics not indicated.
H)Refrigeration to prevent production of enterotoxin OR adequate reheating to kill heat labile enterotoxin

Clostridium perfringens
A)Gram positive, spore forming rod; anaerobic (to aerotolerant)
+ heat labile enterotoxin associated with spore coat; released on lysis;
+ CPE enterotoxin, which breaks down tight junctions between endothelial cells in the gut
B)Ubiquitous in nature; humans
C)Ingestion of contaminated foods
+High risk foods - Meats, poultry, meat products (protein rich)
D)young and elderly in institutions
Clostridium perfringes
Clinical Disease: Toxico-infection
Clinical Disease:
Incubation - 6-16 hours (could be longer); Duration - generally lasts 24 hours or less. In the elderly or infirm, symptoms may last 1-2 weeks.
Symptoms - Abdominal cramps, watery diarrhea, nausea - usually no fever or vomiting
High infective dose required: 108 to 109 – ingestion of spore/microbes (toxin associated with spore coat)
Clostridium perfringes: Clinical Disease
-Another more serious but rare disease: Clostridial necrotizing entercolitis (pig-bel)
Clinical Disease:
Rare and often fatal enterotoxemia of humans caused by the ?-toxin of ....... type C.
Clinical - acute abdominal pain, bloody diarrhea, vomiting, ulceration of the small intestine (jejunum and ileum), perforation of the intestinal wall and acute toxemia.
F)Vomit/Stool/serum/food can be tested for toxin or either may be cultured
-Toxin neutralization assay in mice
G)Supportive care, ventilatory support; antibiotics
-Trivalent botulinum antitoxin (Types A,B,E) (horse-derived)
-Baby BIg (human-derived botulism Ig) - treatment for infant botulism (Types A and B)
H)vaccine under investigation
Adequate washing to remove spores from root vegetables
Adequate cooking (80oC for 20 minutes), maintain acid pH, or refrigeration to prevent growth
Every case of food-borne botulism is treated as a public health emergency because the responsible food might still be available for consumption.

Clostridium Botulinum
A)G+ spore forming bacilli (rod); obligate anaerobes
VIRULENCE FACTOR – Botulinum toxin(s)
B)Ubiquitous in soil (neutral and alkaline soils), water, sewage, and as part of the normal flora in GI tracts of humans and animals
C)Foods contaminated with spores
D)High risk foods: Home-canned foods with low acid content; Improperly canned commercial foods; Home-canned or fermented fish; Herb-infused oils; Baked potatoes (with skins) in aluminum foil; Cheese sauce; Bottled garlic
Clostridium botulinum
-Virulence Factors
Virulence Factors
Variety of invasive enzymes: lipase, caseinase, gelatinase, lecithinase

Botulinum toxin (heat labile 121?C 15 min)
Produces eight serologically distinct botulinum toxins, four associated with human disease
A-B type toxin: receptor mediated endocytosis
Targets cholinergic nerves; blocks neurotransmission by preventing release of acetylcholine (excitatory)
Flaccid paralysis – descending, bilateral
Clostridium botulinum
Clinical Disease: Botulism
Clinical Disease:
1. Foodborne Botulism in healthy children and adults
Food intoxication – preformed toxin
12 - 72 hrs incubation period; Duration – days to months: Complete recovery may take months to years
Bilateral descending paralysis, respiratory impairment
Blurred vision, ptosis (drooping eyelids), dilated pupils, diplopia, loss of co-ordination
Loss of throat and mouth function, dysphagia, dry mouth, throat and tongue
Abdominal pain and constipation (may have diarrhea, nausea/vomiting)
Supportive treatment for respiratory distress; Death from respiratory failure. (5%)
Clostridium botulinum
Clinical Disease:
Infant Botulism (most common in US)

3. Wound Botulism (infection)
Toxin production after spores contaminate wound
1-4 day incubation period
-14-year-old boy fractured his right ulna and radius and subsequently developed wound botulism.
Clinical Disease:
2.Food infection – 3 to 30 days incubation
Spores become vegetative cells in gut; out-competed by normal flora found in adults but NOT in infants < 1yr
Common food source: honey, home canned vegetables and fruits, corn syrup
Lethargy, weakness, constipation, poor feeding and sucking reflex, lack of facial expression - Floppiness, “Floppy baby” syndrome
Diarrheal Disease
Signs and Symptoms of GI Infections:
Usually abdominal cramping followed by diarrhea.
loss of appetite
weight loss
mucus or blood in the stool

Symptoms typically last a few days
Chronic diarrhea - symptoms >2 weeks
Call doctor if chronic diarrhea or see blood in stool
Non-Inflammatory Diarrhea
Vibrio cholera
Listeria monocytogenes
Giardia lamblia
Cryptosporidium parvum
Cyclospora cayetanensis
Isospora belli
Norwalk virus
Characterized by:
Mucosal hypersecretion or decreased absorption
without mucosal destruction; generally involves the
small intestine.
Abrupt onset, brief duration, fever and systemic symptoms usually are absent (except for symptoms related directly to intestinal fluid loss)
Viral gastroenteritis
-noroviruses, rotavirus, adenovirus(group , serotypes 40&41), astroviruses
GI tract infection caused by viruses
Transmission - by ingestion of contaminated food and water [fecal-oral route] and, in the case of some viruses, by aerosols
Clinical signs and symptoms
Mainly watery diarrhea and vomiting
May include headache, fever, and abdominal cramps
Course of disease
1-8 day incubation period [many <1 – 2 days]
Acute disease lasts 1 – 10 days
Treatment – replacement of fluid and electrolytes
ex of viruses????? (4)
Noroviruses (formerly Norwalk Viruses)
Family: Caliciviridae
-described as round w/ ragged surface
A)Infectious agent

Other notes:
A)(+)ssRNA, No envelope, Small
B)human GI tract
C)fecal contamination of food, water, and fomites; also spread by aerosols

other notes:Infectious dose – very low (<102 virus particles)
Causes large common source outbreaks, usually from infected food handler, or outbreaks among people confined in close quarters
Pathogenesis of ??????????Interfere with function of intestinal brush border
Prevents absorption of water and nutrients
Gastric emptying may be delayed
Histologic changes of brush border
Blunted villi
Cytoplasmic vacuolation
Infiltration with mononuclear cells
Noroviruses: Clinical Disease
-Norovirus disease
Clinical Disease:????????Acute onset
Diarrhea with nausea (adults) and vomiting (children)
Abdominal cramps
No bloody stools
1/3 patients may have fever
<1-2 day incubation period
Resolution in 1 – 2.5 days
-Most common cause of gastroenteritis in U.S.; estimated 23 million cases per year
-Epidemics among people in close quarters
F)Laboratory diagnosis for large outbreaks done at CDC or at state labs; virus not grown in culture
+ELISA on stool or emesis sample
+RT-PCR can also be used
G)No specific treatment; replacement of fluid and electrolytes
H)No vaccine
-Care in food preparation and personal hygiene – viruses are very resistant to heat, acid, detergent, and chlorine in drinking water
Family: Reoviridae
-virus has wheel like appearance
A)Infectious agent
D)Risk factors/High risk pops.
A)ds RNA with 11 segments; no envelope
+Five major serotypes (most common is Type A for serious infant diarrhea
+Infective dose 10-100 infectious viral particles
B)Human GI tract
C)Fecal-oral including aerosols
D)Infants/children; most common cause of diarrhea in infants <2 y.o.
-Clinical Disease
Clinical Disease:
-Fever, vomiting, watery diarrhea
-Frequent coryza (runny nose) and cough
-Dehydration is leading complication; very serious in undernourished or already dehydrated infant
-Leading cause of severe diarrhea in children (6 - 24 months of age); not so common in U.S. since introduction to vaccine
-Re-infection common throughout life; mild in adults
Rotavirus Pathogenesis
Pathogenesis of ??????????-Partial proteolysis to give ISVP that is infective (virion is not infective)
-Pathogenesis: loss of electrolytes and fluid
+Malabsorption diarrhea due to infection of & damage to enterocytes; osmotic effect of unabsorbed nutrients
++Shortening and blunting of microvilli
++Mononuclear infiltrate (cytokine component??)
+NSP4, a viral enterotoxin, contributes a secretory component to the diarrhea
++promotes intracellular Ca2+ ,
++disrupts tight junctions between cell
++stimulates the enteric nervous system
1)RotaTeq - new oral vaccine from Merck in Feb 2006.
-Pentavalent against serotypes G1, G2, G3, G4 and P1
-Recombination between human major outer capsid proteins and bovine strain WC3
-Given at 2, 4, and 6 months
2)Rotarix – oral vaccine from GlaxcoSmithKline in 2008
-Effective against serotypes G1, G3, G4, and G9; recombination between bovine and human viruses
-Only requires two doses at 2 and 4 months
F)***direct detection of viral Ags in the stool (ELISA)
G)replacement of fluid and electrolytes
-Children with immunodeficiency
disorders may be treated with .......-specific immunoglobulin preparation, administered orally to
decrease shedding and ameliorate disease
H)Vaccine now recommended
-Hospitalized patients should be isolated to prevent hospital outbreak
***2 FDA approved vaccines
-what are they & describe them.
Adenovirus 40/41 are enteroviruses
Family: Adenoviridae
A)Infectious agent
D)Risk factors/High risk pops.
A)ds DNA; no envelope
C)person-to-person, fecal-oral, fomites
E)Clinical Disease
E)Infantile diarrhea - watery diarrhea, fever;
-Incubation period of 8-10 days and disease period of 7-8 days
-Asymptomatic to mild illness in older children and adults
F)EIA for adenovirus 40/41 in stool specimens
G)supportive and symptomatic treatment
E)Clinical Disease:
watery diarrhea and low grade fever predominate
Incubation period of 1 – 5 days and disease lasts 1 – 5 days
Milder than Rotavirus in all; many adults who are infected are asymptomatic
H)Food safety; hygiene
A)Positive ss RNA, non-enveloped; 8 serotypes; serotype 1 causes 65% of infections
B)Worldwide; infantile diarrhea
C)fecal-oral water/food and aerosols
D)elderly & institutionalized patients; more serious in immunocompromised children and adults
-Single-celled eukaryotic organisms
+Most are motile except Apicomplexa
+Many have life cycles that alternate between trophozoite (metabolically active form ) and cyst (metabolically inactive form and resistant to many environmental conditions)
+Sexual or asexual reproduction (fission) or both
-Important: cysts not killed by chlorine levels used in most water purification systems; removal requires filtration
F)Trophozoites (occasionally cysts) in stool
-Fecal specimens often negative as organisms tend to be shed in “showers”(transiently released in groups) so Need a minimun of three stool specimens
-ELISA, IFA for antigen
G)Drug resistant cyst; susceptible trophozoite
H)Cysts are resistant to standard chlorine concentrations; but boiling or filtering water helps remove trophozoites

A)flagellated protozoan; two nuclei: trophozoite has sucking disc for attachment
B)Zoonotic - Worldwide, wilderness disease
+Found in beavers, cattle, dogs, cats
+Low level of human asymptomatic carriers
C)Oral-fecal/contaminated food and water
D)Daycare, prisons, homeless
+IgA deficient patients – particular risk; campers
Giardia lamblia
Clinical Disease: Giardiasis
Clinical Disease:????????~1-2 Weeks
Foul smelling, watery diarrhea with a greasy/oily appearance
Flatulence, abdominal cramps
F)Tiny oocysts in fresh stool specimens, acid fast stain; EIA for antigen
G)Self limiting in healthy
No totally effective treatment
H)Food safety; Resistant to chlorination Rx

A)Intracellular parasite in epithelial cells of intestinal villi (TINY <6 µm )
B)Worldwide :Water, domestic & wild animals; Reptiles, fish; humans
C)Oral-fecal/contaminated food and water; farm run-off often implicated in outbreaks
D)farmers and farm workers!!!
-Immunocompromised for serious disease
Cryptosporidium parvum.
Clinical Disease: Cryptosporidiosis (Similar to Isospora spp. Inf.)

-(a)Following ingestion, excystation occurs

(b)sporozoites are released and parasitize intestinal epithelial cells

(c) Upon fertilization, oocysts develop that sporulate in the infected host. Oocysts are infective upon excretion
Clinical Disease:

Asymptomatic to mild diarrhea
AIDS-associated severe diarrhea
F)Small oocysts, modified acid-fast stain or by UV fluorescence microscopy (auto-fluorescent)
Morphology similar to Cryptosporidium parvum with some IMPORTANT DIFFERENCES (Cysts larger; autofluorescent); EIA for antigen
G)Self-limiting (days to months) for most but may use SXT in immunocompromised individuals
Can be re-infected

A)Cyclospora oocysts - intracellular sporozoite
SMALL (5-10 µm)
C)Fecal-oral; Primarily – contaminated water, food
Peru, Brazil, Haiti are primary sites of outbreaks
Guatemalan raspberries brought it to the US 1990

Clinical Disease: Cyclosporiasis – median onset 7 days
Mild watery diarrhea, bloating, stomach cramps, nausea, vomiting, muscle aches, low-grade fever, and fatigue
Associated with villus atrophy and crypt hyperplasia – malabsorbtion syndrome
Cyclospora cayetanesis
Clinical Disease: Cyclosporiasis

Oocysts excyst in the gastrointestinal tract, freeing the sporozoites which invade the epithelial cells of the small intestine . Inside the cells they undergo asexual multiplication and sexual development to mature into oocysts, which will be shed in stools
Clinical Disease:
median onset 7 days
Mild watery diarrhea, bloating, stomach cramps, nausea, vomiting, muscle aches, low-grade fever, and fatigue
Associated with villus atrophy and crypt hyperplasia – malabsorbtion syndrome

When freshly passed in stools, the oocyst is not infective; it needs days or weeks after being passed in a bowel movement to become infectious.
F)Stool acid fast stain
Ultraviolet autofluorescence microscopy
duodenal aspirate
-fluorescent blue-violet w/ 365 nm filter
G)Trimethoprim-sulfamethoxazole - Relapse in 50% of patients
H)food safety

A)Sporozoan protozoan; large OVAL oocyst
B)Humans, no known animal reservoir
Endemic in Africa, Australia, the Caribbean Islands, Latin America, and Southeast Asia
C)Ingestion of mature oocysts contaminated food, water
D)primarily in AIDs patients
Isospora belli
Clinical Disease: Isosporiasis

Isospora belli oocyst containing two sporoblasts: the sporoblasts stain red and ?the cyst wall appears as a dark-red outline. ?(Acid-fast stain).
-Must remain in environment 2-3 days before it becomes infective
Clinical Disease:???????-diffuse watery diarrhea, abdominal cramps
AIDS-associated malabsorption syndrome(life-threatening)
Affects distal duodenum, proximal jejunum epithelial cells
E)Clinical Disease: based on type of E.coli: ETEC, EPEC, EAEC
F)Clinical presentation; isolation and biotyping
G)Self limiting in general
H)Food safety

Traveler’s diarrhea
ETEC – Enterotoxigenic

Childhood diarrhea
II. EPEC - Enteropathogenic
III. EAEC - Enteroaggregative
A)gram negative, lactose fermenting, indole positive, bacillus (rod)
Broad range of genus specific virulence factors
Adhesins CFA, Bfp, AAF
Exotoxins Sta, East-1, LT
B)Most common aerobic, gram negative bacilli in GI tract
C)Fecal-oral; autoinnoculation
E)Clinical Disease: based on ....: ETEC, EPEC, EAEC
ETEC – Enterotoxigenic E. coli
Common cause of “traveler’s diarrhea” -Incubation 1-3 days
Disease - Watery diarrhea, abdominal cramps, nausea, low-grade fever - Duration 3 to >7 days
Toxins cause hypersecretion of fluids and electrolytes
Large numbers of E. coli are ingested (food or water), survive in the stomach and produce toxins.

Virulence Factors
A. Heat-labile toxin (LT)
A-B type ADP-ribosylating toxin
ADP ribosylates Gs locking Gs in "on" form so cAMP accumulates
Mucosal cells secrete Cl - leads to water loss: diarrhea

B. Heat-stable toxin a (STa)
not inactivated by 100?C, 30 min
acts on guanylate cyclase, yields excess of cGMP (not cAMP)
Blocks ion transport into cells; water moves into the lumen
2. EAEC (EAggEC) Enteroaggregative E. coli
Infantile diarrhea in under-developed countries ( traveler’s diarrhea, HIV patients)
Disease: persistent watery diarrhea with vomiting, dehydration
After infection
Produces EAST 1 – ST-like toxin
Colonization results in shortening of microvilli = decreased absorptive area
Additional Virulence Factors
Aggregative adherence fimbriae AAF
Results in bacterial clumping into small aggregates, noninvasive,
“Stacked Bricks” - bacteria aligning themselves in parallel rows via autoagglutination
3. EPEC Enteropathogenic E. coli
Infantile diarrhea: cause of epidemics in newborn nurseries, less common in developed countries

Disease: Slow in onset, Watery diarrhea, nausea, vomiting, non bloody stools
No LT, ST or other known diarrheal toxin
Colonization via Bfp followed by Tir
insertion and Intimin binding
Attaching-effacing = formation of
pedestal-like structure in cytoplasm
composed of dense mat of actin fibers
Destruction of the absorptive microvilli leading to interruption of absorption/secretion pathways
Dehydration and electrolyte imbalance
Antimicrobial therapy important in “at risk” children
Vibrio spp.
- 3 primary pathogens: Vibrio cholerae , V. parahaemolyticus, V. vulnificus
w/ ... = V. vulnificus

Clinical Disease: Watery diarrhea
F)Clinical presentation; culture
G)Self limiting in general
H)Food safety
A)Gram negative, Comma-shaped (curved) bacilli, oxidase +(200 serotypes)
- 3 primary pathogens
B)contaminated water; (grows in fresh and salty water)
Asymptomatic carriers in endemic areas
C)Fecal-oral: consumption of contaminated or improperly cooked food or seafood and contaminated water
D)anyone; those with liver disease at risk for serious disease with......
A)Vibrio cholerae
Clinical Disease: Cholera
G)1.Restore fluid and electrolyte balance immediately:
- Oral rehydration therapy (ORT) with boiled tap water containing salts (NaCl, KCl, NaHCO3)plus 2% glucose. Glucose = maximum absorption of sodium.
- 25-50% of typical cases are fatal if untreated
2. Administration of antibiotics (tetracycline) only in severe cases
H)1. Improved sanitation - Chlorination of water supplies; sewage treatment.
2. Vaccination: Current approved vaccine is a killed, whole cell suspension. (some live, attenuated vaccines being tried)
Effectiveness ~ 50% for 3-6 months.
Boosters 6 month intervals.
A)O1 and O139 strains produce:
TcpA = Toxin regulated pili for attachment
Cholera toxin (CTX): - increases cellular cAMP [and cGMP] resulting in hypersecretion of electrolytes and water
HAP protein = Hemagglutination protease (mucinase)
Degradation of cell to cell adherence

Clinical Disease: ????????-Incubation period 2-3 days
Profuse watery diarrhea (up to 14-20 liters/day).
Rice water stools (colorless feces, flecks of mucus)
Electrolyte imbalance, massive fluid loss,
Muscle cramps, loss of skin turgor and weak pulse.
Death can occur from: Hypovolemic shock; Metabolic acidosis; Cardiac arrhythmia, renal failure
Vibrio. Parahaemolyticus:
5 – 72 hour incubation period
Clinical Disease:
Secretes a enterotoxin
Self limited diarrhea to mild cholera like illness
Explosive, watery diarrhea, usually no evidence of mucus/blood
abdominal cramps, nausea, vomiting
Treatment, Prevention, Control
Self limited, no antimicrobial; Antibiotics in severe cases
Proper cooking of shellfish
No vaccines
Vibrio vulnificus
16 hrs after ingestion of contaminated food
Clinical Disease: Gastroenteritis (+/- necrotizing fasciitis)
Secretes enterotoxin
Primary septicemia may occur in immunocompromised
Consumption of raw oysters
70% have bulbous skin lesions
Mortality ~ 50% without antimicrobial therapy
G&H)Self limited, no antimicrobial; Antibiotics in severe cases
Proper cooking of shellfish
No vaccines
Clinical Disease: Listeriosis; ~ 20 h incubation period
F)Clinical presentation; isolation and biotyping
-microscopy after cold enrichment(4degrees C), Camp test +, PALCAM agar
G)Self limiting in healthy; treat elderly and immunocompromised
H)Food safety
A)Facultative intracellular Gram + bacillus, non-spore-former (only gram + organism to cause non-inflammatory diarrhea!! Also caused neonatal meningitis…)
B)Isolated from soil, water, effluents, foods, vegetation, mammals, humans/animal feces
C)Fecal-oral; Relatively hi infectious dose (106), Foods: Soft cheeses, undercooked meat and dairy food!!!
D)Infection in anyone; serious disease in High risk populations - Neonates, pregnant women, elderly, AIDS, malignancy, transplant recipients

E)Clinical Disease????????????-virulence factors?????????
Inflammatory diarrhea and dysentery

ex. bugs: Shigella spp.
EIEC, EHEC (+/- inflammatory response)
Salmonella spp.
Campylobacter jejuni
Yersinia enterocolitica
Entamoeba histolytica
Clostridium difficile
A)loose stools smaller in volume (than seen in non-inflammatory) plus PMNs; usually invasive infection of the large intestine
B)usually inflammation of the colon resulting in abdominal pain and cramps, straining at stool (tenesmus), and frequent passage of watery diarrhea or stools containing blood and mucus.

ex. bugs??????????
Inflammatory diarrhea and dysentery
-background of bacteria

-Shigella on Hektoen agar; colonies are NOT black
-Salmonella on Hektoen; black indicates H2S production
Enterobacteriaceae family include Escherichia coli, Shigella species, Salmonella species and other less common bacteria
They are oxidase negative.
How to distinguishMost E. coli strains ferment lactose; Salmonella and Shigella species do not ferment lactose but do ferment glucose.
E. coli is positive for indole production; Salmonella and Shigella are not
Shigella is negative for H2S production and motility; Salmonella is positive for both of these characteristics.
Non Enterobacteriaceae family pathogens include Campylobacter and Helicobacter.
They are curved rods or helical.
They are oxidase positive.
F)Culture and biotyping: Hektoen agar
G)Antibiotics shorten course and should be used in individual cases if warranted by the severity of the disease or to protect contacts
Water and electrolyte therapy.
Avoid use of anti-motility drugs – prolongs illness

H)....... is a reportable disease
Because ....... is a disease that can easily spread to other people, workers at food-related businesses, and institutional workers who have .... or live with someone who has ...... must show that they have no .... germs in their stool.
-No vaccines are presently available for routine use.
A)Gram-negative straight bacillus
Ferments glucose but not lactose
Identical to enteroinvasive E. coli (EIEC); Shigella has retained its own classification as a genus
Four serogroups/species with multiple serotypes:
S. dysenteriae; S. flexneri; S. sonnei; S. boydii
B)Humans; no animal reservoirs
C)Fecal-Oral transmission
-Very low infectious dose (10-100 cfu)
-Organism survives stomach acidity.
D)Primarily a pediatric disease (<15 yrs) - Epidemics in daycare centers, nurseries, custodial institutions; Endemic disease in developing countries
S. flexneri is main cause of endemic .....
S. dysenteriae serotype 1 is main cause of epidemic ......
Shigella-associated sequelae
-Hemolytic uremic syndrome with S. dysenteriae subtype 1 infection
Acute hemolysis
Renal failure and uremia
Disseminated intravascular coagulation (DIC) = thrombocytopenia
Primarily a problem in infants and children under 5 y.o.; can be fatal (15%) or leave permanent kidney or CNS damage
-Reiter’s syndrome (reactive arthritis) with S. flexneri
Occurs 2 – 4 weeks after infection
Occurs most often in men 20 – 40 y.o.; HLA-B7 is a risk factor
Shigella spp
Clinical Disease: Shigellosis (Bacillary dysentery) - Inflammatory

Incubation period 1 – 4 days
Clinical illness 7-10 days
Signs and symptoms:
Diarrhea of frequent small volume stools with blood; may or may not have mucus
Abdominal cramps and tenesmus (unproductive, painful straining) are common. ? entamoeba also causes tenesmus
Fever and anorexia are also common, but are not specific.
Moderate or no dehydration occurs
Serious complications
Metabolic abnormalities
Sepsis with convulsions
Rectal prolapse,
toxic megacolon and/or intestinal perforation
Hemolytic uremic syndrome (HUS also seen in EHEC)
Clinical Disease:
Colonize small intestine within 12 hours: Profuse watery diarrhea due to enterotoxin

Invasion of colonic mucosa: Lower abdominal cramps, tenesmus (crampy rectal pain) with pus, mucus and bloody(red) stools (dysentery), fever, vomiting, dehydration, and convulsions
Bacteria move laterally to new cells by means of actin “propulsion”

Self-limiting in healthy; damage to infected colonic mucosa, no invasion to blood stream.
But may be fatal in infants/young children, HIV
Toxins for Shigella spp.
All species produce enterotoxins which alter electrolyte balance
- ShET1 and ShET2 on chromosome and plasmid

2. S. dysenteriae serotype 1 = Stx gene for Shiga toxin on chromosome
AB type toxin
inhibits protein synthesis by inactivating 60S subunit of ribosome
synergizes with LPS to produce inflammatory cytokines, causing damage to endothelium lining the blood vessels.
Shiga toxin is associated with HUS (hemolytic uremic syndrome) because the toxin also has receptors on the epithelium of the glomeruli
HUS: hemolytic anemia, thrombocytopenia, and renal failure
F) Culture and biotyping
G)Water and electrolyte replacement therapy when patient is dehydrated.
Antibiotics are recommended for EIEC but not for EHEC; some studies have shown that antibiotic increases the risk of developing HUS
H)Hygiene, fully cook meats
A)gram negative rod, lactose fermentation, oxidase negative; indole positive
Invade Large Intestine
1. EIEC - Enteroinvasive
2. EHEC – Enterohemorrhagic (noninflammatory may turn inflammatory due to effects of toxin)
B)humans, domestic animals
E)Clinical Disease: Inflammatory diarrhea
1.Enteroinvasive Escherichia coli (EIEC)
Virulence Factor
Underdeveloped countries
Infective dose - 10 organisms
Fever, cramping, watery diarrhea with leukocytes present (may progress to some blood) Causes bacillary dysentery similar to Shigella spp.
Invasion and destruction of colonic epithelial cells and destruction of epithelial lining
Similar to the invasion by Shigella
Does not produce Shiga-like toxin
Blood and mucus in stools
2. EHEC – Enterohemorrhagic (like Shigella!!)
-virulence factor
Developed countries
Infective dose ~ 10 organisms

Little or no fever, severe abdominal cramps, watery diarrhea followed by bloody diarrhea; HUS possible
Hemorrhagic colitis is disease caused by E. coli O157:H7
0-15% develop HUS (hemolytic uremic syndrome),
Kidney failure, hemolytic anemia, thrombocytopenia
Use of antibiotics felt to contribute to progression to HUS

Destruction of microvillus with decreased absorption (like EPEC)
Shiga-like toxins (Verotoxins) -disrupts protein synthesis
NON SORBITOL FERMENTATION on Sorbitol MacConkey Agar (replaces lactose)
F)Culture and biotyping; Hektoen Agar
G) Antibiotics are contraindicated and do not shorten the duration of illness and tend to increase fecal excretion of the bacteria.
- Antibiotic usage should be reserved for patients whose infections are likely to become systemic.
H)Food safety

A)Infectious Agent: gram negative rod; non-lactose fermentor; produces H2S
-Virulence Factors:
Variety of toxins (several Sop toxins, Sip toxins, etc) which act to:
Alter Cl secretion/transport
Ruffle host cell membrances
Trigger cellular apoptosis
B)Zoonotic -Animal reservoirs (shigella is human reservoir): Poultry, eggs, dairy products, Pet turtles, etc
C)fecal-oral; cross contamination
Low infective dose (105); some sources say 108
D)Anyone, but most cases among young and old; handling pets such as turtles, snakes, chickens; Decreased stomach acid
Clinical Disease: Salmonellosis – inflammatory diarrhea
Clinical Disease:
6-48 hrs after consumption, Course of 2 days to 1 week: Nausea, vomiting, and usually non-bloody diarrhea (will see occult blood) with PMNs, fever, abdominal cramps, myalgias
(rare pseudoappendicitis)
F)Culture and biotyping
Selective media with blood or charcoal to remove oxygen radicals; antibiotics to inhibit growth of normal flora
Microaerophilic and 42oC ; CAMP positive? culture at higher temp!!!!
48-72 hours
G)when deemed necessary, erythromycin and broad spectrum antibiotics.
H)Food safety; Supportive, antibiotics with care

A)Gram negative, comma or S-shaped rod
Virulence Factors:
Production of a cholera toxin-like enterotoxin
hypersecretion of electrolytes and water
Cytolethal distending toxin (CDT) - Invasion of epithelium
B)Poultry, pets, human carriers
C)Zoonotic; acquired from infected animals (poultry products); pets; human carriers
D)young children, and immunocompromised individuals
-Decreased or neutralized stomach acids (antacids, milk, etc) are a risk factor
E)Clinical Disease: Campylobacteriosis -Inflammatory diarrhea with severe abdominal cramping and 10 + stools/day (w/wo blood)
(rare pseudoappendicitis)
F)Culture (low temp enrichment) and biotyping
G)Inflammatory diarrhea alone - self-limiting
Diarrhea with systemic spread - broad spectrum drugs.
H)Proper water purification, pasteurization of milk.
Food-borne disease, washing of the hands and the use of gloves by food providers are very important.

A)gram negative rod; two major species cause GI infections/disease: Y. enterocolitica and Y. pseudotuberculosis (Lactose non-fermentor)
B)Animals (Zoonotic)
C)fecal-oral; contaminated food products (milk, meat, water) or blood products, pet feces (It grows at low temperatures)
D)Y. enterocolitica common in children
VFs of Y enterocolitica and the related pathogen Yersinia pseudotuberculosis

-3 invasion proteins which could potentially promote adherence to & invasion of M cells
A)invasin binds to ?1 -chain integrin receptors with high affinity, promoting internalization
Clinical Disease:
1-10 day IP; Fever, inflammatory diarrhea and abdominal period lasting for 1-2 weeks; Chronic form persists for months

Mesenteric Lymphadenitis
In children 5-15 – fever, abdominal pain, and rash and may infect mesenteric lymph nodes - mimicks appendicitis
(Pseudoappendicitis)- rare pseudoappendicitis seen in salmonella and campylobacter

Bacteremia – can occur with progression of disease or transmitted through blood transfusions
Growth at 4oC for 3 weeks sufficient for infective dose (campylobacter grows at high temperature!!)
F)Cysts or motile trophozoites in fecal specimens; ELISA for antigen; Serological assay if fecal specimens negative
G)Antibiotics to reduce intestinal flora
Flagyl (metronidazole), paromomycin
H)Food safety, hygiene, water treatment

A) amoeboid protozoa
B)Human carriers; cysts can survive in soil & water
C)Fecal-oral, mechanical vectors, Contaminated food & water
D)Anyone for disease
-emerging problem in the MSM population (both for transmission and for severe disease)
E)Clinical Disease: Amoebic dysentery (Amoebiasis)
-Bloody diarrhea
-Ulceration of large intestinal wall (flask-shaped lesions)
-Acute - Chronic with Abscess Form, RUQ pain
Clostridium difficile
A)Infectious agent
D)Risk factors/High risk pops.
A)Gram positive spore forming rod; Strict anaerobe (only gram + that causes non-inflammatory diarrhea!!)
Two toxins (both are AB-type toxins!) - act synergistically
enterotoxin (Toxin A)
chemotactic for neutrophils
cytokine production
hypersecretion of fluid
hemorrhagic necrosis
cytotoxin (Toxin B)
Depolymerization of actin
loss of cytoskelton
B)Ubiquitous; colonizes GI tract of 5-10% of healthy individuals
C)via spores
fecal-oral (contaminated clothing, surfaces); aerosols
Pass through stomach, bile acids
Vegetative cells produce toxins
D)hospitalized patients; especially
those on long term antibiotics
Clostridium difficile
Clinical Diseases
(pathonomonic for C. difficile)
Clinical Diseases:
1)Antibiotic Associated Diarrhea
Vomiting, nausea, and diarrhea
Antibiotics disrupt normal flora; Loss of competitive exclusion
most commonly associated with clindamycin use
Uncontrolled proliferation of C. difficile and exotoxin production
Onset 4 - 10 days after start of antibiotic to up to 2 weeks after termination of antibiotic use

2)Pseudomembranous colitis (pathognomonic for.......)
-severe abdominal pain, watery diarrhea with PMNs
Damage to colonic mucosa
Pseudomembrane - Leukocytic infiltrate into lamina propria accompanied by elaboration of a mixture/plaques of fibrin, mucus, and leukocytes, form gray, white, or yellow patches on the mucosa.
F)Culture of blood, bone marrow, urine and tissue biopsy if rose colored spots present
Hallmark histologic finding - typhoid nodules, aggregates of macrophages containing bacteria and erythrocytes
Hektoen agar: produces H2S?black colonies
G)Broad spectrum antibiotics
H)Three vaccines:
Attenuated oral
Parenteral heat killed (no longer used in US)
Parenteral ViCPS (polysaccharide capsular vaccine)

Salmonella Typhi
A)gram negative, lactose nonfermentor
S. typhi and S. paratyphi
B)Humans; NO ANIMAL RESERVOIRS (salmonella non-typhi has an zoonotic reservoir !!)
D)travelers to endemic areas
E)Clinical Disease: Enteric fever/Typhoid fever
-Severe multi-systemic illness
prolonged fever, sustained bacteremia, bacterial invasion of and multiplication within the mononuclear phagocytic cells of the liver, spleen, lymph nodes, and Peyer’s patches.
Constipation common as are rose colored spots on trunk
Potentially fatal if untreated, typhoid fever is most prevalent in underdeveloped countries.
Salmonella Typhi
Clinical Disease: Enteric fever/Typhoid fever

Signs and Symptoms of Typhoid Fever:
-Prolonged low-grade fever that may progress to persistent high-grade fever
-Severe frontal headaches
-Malaise and myalgia
-Anorexia and nausea
-Rose spots in a small %
-Bowel movements may vary from diarrhea to constipation
E)Clinical Disease:
-Severe multi-systemic illness
prolonged fever, sustained bacteremia, bacterial invasion of and multiplication within the mononuclear phagocytic cells of the liver, spleen, lymph nodes, and Peyer’s patches.
Constipation common as are rose colored spots on trunk
Potentially fatal if untreated, typhoid fever is most prevalent in underdeveloped countries.
Parasitic GI infections
Cestodes (Tapeworms)
Diphyllobothrium latum
Taenia saginata/solium
(Echinococcus granulosus) – covered in mass lesions

Trematodes (Flukes)
Clonorchis sinensis
Schistosoma spp.

Nematodes (Roundworms)
Ancylostoma duodenate/ Necator americanus
Enterobius vermicularis
Trichuris trichiura
General structure and information about cestodes (tapeworms)
Body is flat and ribbon-like
Head (scolex) has organs of attachment – suckers and/or hooklets or sucking grooves (bothria)
The body has segments called proglottids; Grow in length by adding proglottids
Hermaphroditic – male and female reproductive organs in each proglottid; at distal end the proglottidds are gravid -> excretion of many eggs
No digestive system; nutrients by absorption from host intestine
Complex life cycles
F)Proglottids & eggs in stool
G)Antiparasitic drugs (praziquantel is one)
H)fully cook fish; care in disposal of human fecal material; good hygiene

A)Fish tapeworm (long)
B)fish, fish eating carnivores worldwide, cool lake regions
C)Consumption of raw or undercooked fish
D)Hunters, fishers
Diphyllobothrium latum
-Clinical Disease:
Clinical Disease:

usually mild, bloating, diarrhea - mechanical presence
Worm load can become so large patients may present with B12 deficiency (megaloblastic anemia)**
Human larval infection
Acquired by drinking pond or ditch water with copepods; also can be acquired from eating tadpoles, frogs, or snakes
Inside intestine larval form penetrates intestinal wall and migrates to various sites
Subcutaneous and eyes frequent sites
Periorbital edema with pain; may develop corneal ulcers
Diagnosis by examination of surgical sections
Treated by surgical removal
E)Clinical Disease: Taeniasis/Tapeworm
Most infections asymptomatic or mild
May cause diarrhea, bloating
F)Detection of proglottids/ova in stool; scolex differences
G)Antiparasitic drugs
H)Cook meats well

A)Taenia solium (pork tapeworm)
Taenia saginata (beef tapeworm)
B)Taenia solium – pigs
Taenia saginata – cattle
C)Ingestion of undercooked meat containing larvae.
General information about trematodes (flukes)
Flat, fleshy, leaf-shaped worms
Most have two suckers, oral and ventral
Incomplete digestive system
Hermaphroditic except schistosomes
Complex life cycles with one or two intermediate hosts
Eggs have lid (operculum)
Many tissue specificities in humans
F)detection of eggs in stool; biopsy
G)Anti-parasitic drugs 
H)Avoid eating raw, pickled, smoked fresh water fish

Clonorchis sinensis
A)Trematode, liver fluke; feeds on bile in humans
B)Fish and animals that eat fish (Dogs, cats, humans)
C)consumption of raw/undercooked freshwater fish
D)eating raw, pickled, smoked fresh water fish
Clonorchis sinensis(Oriental liver fluke)
-Clinical Disease:
Clinical Disease:
Primary site of infection is the biliary tract
Abdominal pain (epigastric), nausea, diarrhea, and eosinophilia
Intermittent obstruction of the biliary ducts -> cholecystitis, cholelithiasis, and impaired liver function; chronic infection (inflammation) can result in fibrosis or hyperplasia
Inflammation results in fibrosis & hyperplasia
Shistosomes cause shistosomiasis
Major parasitic infection of tropical areas (200 million infected)
Three species associated with human disease
Shistosoma mansoni
Shistosoma japonicum
Shistosoma haematobium
Infection through skin-penetrating cercariae released from snails
Adults are not hermaphroditic
Eggs do not have operculum
Coat themselves with host substances so there is little response to organisms in blood vessels
F)Blood test available CDC
S. haematobium - ID of eggs in urine or bladder wall
S. mansoni - ID of eggs in the stool
S. japonicum – ID of eggs in the stool
G)Anti-parasitic drugs
H)Water treatment

A)trematode; Blood fluke
One of the most remarkable immune defenses ever – coat themselves with “self” – so, chronic infections 20 – 30 + years
B)Snails, humans, (water)
C)Cercariae penetrate the skin directly
D)Swimming, bathing in contaminated waters/presence of intermediate host (snail)
Disease of “progress”; irrigation projects in deserts and tropical areas
Schistosoma spp.
-Clinical Disease:
Clinical Disease(s):
Schistosoma haematobium (Nile Valley, elsewhere in Africa, eastern Mediterranean and southern Portugal)
Primary sites of infection - veins of urinary bladder
Organism’s eggs induce fibrosis and granulomas, hematuria, dysuria, urinary frequency, infertility
2. Schistosoma mansoni (most widespread) and Schistosoma japonicum (China, Philippines, Indonesia)
Primary site of infection - small branches of
inferior mesenteric vein
GI bleeding, diarrhea, and liver damage
Hepatosplenomegaly, ascites; “clay pipestem” fibrosis
Damage due to inflammatory response to deposited eggs
3. Non-human pathogens - Cercarial dermatitis;“swimmer’s itch”
Schistosomal organisms which are non-human
pathogens – can penetrate skin – then,
infection aborted
intense pruritis and urticaria
General structure of nematodes
Round, cylindrical unsegmented body
Complete digestive system
Separate sexes in adults
Covered by noncellular, highly resistant cuticle
Divided into intestinal and blood and tissue parasites
F)scotch tape; Adult female and eggs can be recovered (up to 20,000 worms); Anal swabs or “Strube tubes”
G)Anti-parasitic drugs – treat entire family, daycare center, institution
H)good personal hygiene; prompt Rx of infected persons; Keep home free of fomites

B)Humans; no known animal reservoir
C)fecal-oral (eggs)
D)very common in cold climates ; most common helminth infection in US; small children, crowding, cold weather, poor hygiene
Enterobius vermicularis
-Clinical Disease:
Clinical Disease:
-Severity of disease depends on worm burden
+Type IV immune response against female and eggs (kids have itchy butt’s because female worm comes out at night to lay eggs)
+Severe itching, can lead to excoriation
+Eosinophilia and elevated IgE
Trichuris trichiura
C)Ingestion of eggs
E)Infection usually asymptomatic
+May have abdominal pain, diarrhea, flatulence and rectal prolapse in some
F)eggs in stool
G)Antiparasitic drugs
Ancylostoma duodenale/Necator spp.
B)Humans, cats, dogs
C)Direct skin penetration (like Schistoma)
E)ranges from abdominal pain with loss of appetite to severe protein deficiency or iron deficiency anemia to ulcer like symptoms with chronic intestinal blood loss leading to low RBC anemia .
F)eggs in stool
G)Antiparasitic drugs
F)Urease breath test: ingest radioactive urea - CO2
Microscopy: biopsy
Urease: direct specimen analysis or culture
Culture: requires multiple specimens; low sensitivity
Serology: not diagnostic for acute cases
G)Triple, quadruple therapy
2 Antibiotics (metronidazole, and either tetracycline or amoxicillin)
plus proton pump inhibitor (e.g., omeprazole - Prilosec)
plus bismuth subsalicylate(Pepto-Bismol)
H)Vaccine under development

Helicobacter pylori
A) Gram negative curved rod
Primary Virulence Factor:
cag pathogenicity island
~70-90% of populations in developing countries
are colonized (before the age of 10)
~45% in US by adulthood
C)Person to person spread
D)70-100% of patients with gastritis, gastric ulcers, or duodenal ulcers are infected
Clinical Disease: Accepted to be cause of most gastric and duodenal ulcers

A. Gastric ulcer (50-80% have H.pylori)
Pain greater with meals - weight loss
NSAID may exacerbate disease

B. Duodenal ulcer (90% have H.pylori)
Pain decreases with meals - weight gain
H. pylori has been isolated from almost 100% of duodenal ulcers
Virulence Factors
Infection - promotes gastric inflammation, alteration of gastric acid production, and tissue destruction via:

Mucinase – degrades mucous

Urease – neutralizes gastric acid; chemotactic

Heat Shock Protein (HspB) – enhances urease production

+/- Vacuolating cytotoxin – apoptosis of gastric epithelial cells

Infection by this bacterium
Stimulates secretion of IL-8 by host cells
Stimulates secretion of platelet activating factor which results in the hypersecretion of gastric acid

Whats the clinical disease:???????
As the condition worsens, the person may also experience these additional symptoms:
jaundice (yellowed skin, mucous membranes and eye-whites)
dark urine (bilirubinuria)
light colored stools that may contain pus
May have hepatosplenomegaly

It is the course of the hepatitis and the different outcomes after the acute phase that help to distinguish hepatitis due to the various causative agents.
Produces an initial acute phase, often with few if any symptoms.
If there are symptoms, they tend to mimic "flu-like" symptoms such as:
mild fever & fatigue
muscle or joint aches
Nausea, vomiting, diarrhea
loss of appetite
slight abdominal pain

The acute phase and its symptoms is rarely serious or fatal, although occasionally a fulminant or rapidly progressing case will result in death.
F)SEROLOGY - IgM (some cross reactivity with other flaviviridae)
EIA - viral antigen in blood
G)No specific treatment exists for yellow fever however,supportive care is critical for those with severe disease.
Treatment of electrolyte disturbances, shock, arrhythmias, pulmonary edema, hemorrhage, and renal and hepatic dysfunction.
H)The live attenuated virus (17D) vaccine
Booster every 10 years

Yellow Fever Virus
A)ss+RNA, enveloped
B)wild and domestic animals; mosquitoes
C)Mosquitoes as vectors
D)Anyone; travel to endemic areas – Africa and South America
Yellow Fever
-Clinical Disease
Clinical Disease: Two clinical presentations of ..........:
Most common presentation
- Hepatitis like syndrome, self-limiting
Less common – more severe infection
Massive GI hemorrhage “black vomit”, 50% mortality rate
(Worse cases may resemble hemorrhagic diseases)

Pathogenesis: Virus replicates initially in local lymph nodes quickly followed by infection of tissue macrophages, especially in the liver, and then spreads further to lung, kidney, adrenal glands, spleen, and bone marrow.
Will see widespread hemorrhages on mucosal surfaces, in the skin, and within various organs. Numerous petechial hemorrhages and erosion of the gastric mucosa contribute to the hematemesis (vomiting of blood).
F)Microscopy: darkfield
Culture: time-consuming and requires complex media
Serology: titers of 1:100 or greater develop during 2nd week
H)Vector control; vaccination of pets and livestock

Leptospira spp.
A)(Gram neg) spirochete – appears to bend at the ends):
Virulence Factor
Hyaluronidase - mediates invasion
Antigenic variation (>200)

B)Zoonotic: rodents, dogs, farm and wild animals: No human carriage documented
C)exposure to animal urine contaminated water/fomites or handling of infected tissue (abrasions, conjunctiva)
D)rural residents, farmers, veterinarians, hunters and meat handlers; more recently water sports; remodeling old houses
Clinical Disease: Leptospirosis/ Weil’s Disease
-Scleral hemorrhages in a icteric (late stage) patient

-Leptospira spp.
Clinical Disease:
Most infections are clinically inapparent

Clinically apparent disease:
1-2 week incubation period
Flu like symptoms accompany bacteremia
Progressing to:
hepatic and renal dysfunction leading to jaundice and renal failure; possible myocarditis and cardiogenic shock
F)Laboratory Diagnosis
HAV-IgM - acute infection
HAV-IgG – past infection or immunization
G)supportive care
H)Active Vaccination (pre-exposure/post exposure using single antigen vaccine)
Inactivated Hepatitis A virus
Passive immunizationImmune globulin (IG)
Pre and post exposure
Clean water systems; avoidance of food contamination

Hep A
A)ss +sense RNA, no envelope; Single serotype
C)fecal-oral; low infectious dose
Close personal contact(e.g., household contact, sexual contact, day care centers)
Contaminated food, drinking water(e.g., infected food handlers, raw shellfish, raw produce)
Blood exposure (rare)(e.g., injecting drug use, transfusion)
D)Unvaccinated; travelers to HAV-endemic countries; oral-anal sex; illegal drug users
Hep A
Clinical Disease:
-Incubation period: Avg 28 days (range 15-50 days); disease lasts 2 weeks to 3 months

-Signs & Symptoms: diarrhea, dark urine; fatigue, abdominal pain, loss of appetite, intermittent nausea, vomiting and jaundice, elevated liver enzymes (AST/ALT)
Frequency of Jaundice by age group:
<6 yrs(<10%)
6-14 yrs(40%-50%),
>14 yrs(70%-80%)

Chronic sequelae: None

No chronic infection: Protective antibodies develop in response to infection - confers lifelong immunity
E)Clinical Disease: etiologic agent of enteric hepatitis
-Incubation: Avg 40 days, Range 15-60 days
-Signs and Symptoms: malaise, anorexia, abdominal pain, jaundice, and fever
-No chronic infections identified
F)Clinically indistinguishable from Hepatitis A disease
Rule out A and B serologically; or newer serology to identify HEV specifically
H)Avoid drinking water, uncooked shellfish and fruit/vegetables in HEV endemic countries
No vaccine

Hep E
Hepeviridae(old is Calcivirdae)
A)ss +sense RNA virus, non-enveloped, one serotype
B)Unknown; probably human
C)Most outbreaks associated with fecally contaminated drinking water (fecal-oral)
U.S. cases usually have history of travel to HEV-endemic areas
In endemic countries it is responsible ~50% of acute hepatitis cases – sometimes with severe complications (e.g. pregnant women)

Clinical Disease:?????????????
G)1. Interferon ? - for HBeAg +ve carriers with chronic active hepatitis. (also using pegylated Interferon ?)
2. A wide variety of nucleoside analogues including Lamivudine
- Most respond favorably.
- Tendency to relapse on cessation of treatment.
- Rapid drug resistance
H)Active vaccination (subunit vaccine)
Hepatitis B Immunoglobulin post/pre-exposure in appropriate populations
Infant born to Chronic carrier: Ig AND vaccine within 24 hours

Other measures - screening of blood donors, blood and body fluid precautions.

Hep B
A)Enveloped, partially ds circular DNA Uses RNA intermediate
Infected cells produce HBsAg without DNA
Can integrate into host genome
C)Parenteral transmission; sexual; perinatal
D)Unvaccinated; IDUs; neonates of chronic mothers
Endemic regions: China, parts of Africa, Alaska, Pacific Islands – in these areas, most are infected shortly after birth
Hep B
-Clinical Feastures

Pathogeneisis & Immunity:Pathogenesis & Immunity:
TROPISM: liver, pancreas, kidneys
1. Acute Hepatitis
2. Chronic Latent Hepatitis
3. Chronic Active Hepatitis
4. Cirrhosis of Liver
5. Hepatocellular Carcinoma

Cell-mediated response & inflammatory response cause signs & symptoms = lead to resolution.
Ineffective T cell response leads to mild symptoms – but associated with progression to chronic disease state

HBsAg binding to anti-HBs can contribute to vasculitis, arthritis, rash, etc.
Clinical Disease:
Incubation period: Average 60-90 days
Range 45-180 days

Clinical illness: Hepatitis
Frequency of jaundice:
<5 yrs, 5 yrs, 30%-50%
Frequency of chronic infection as
related to age at time of infection : 5 yrs, 2%-10%

Acute case-fatality rate: 0.5%-1%
Premature mortality from
chronic liver disease: 5%-25%
Dx of Hep B
F)A battery/composite of serological tests are used for the diagnosis of acute and chronic hepatitis B infection.

HBsAg - used as a general marker of infection

Anti –HBs (HBsAb) - used to document recovery and/or immunity to HBV infection.

Anti-HBc IgM (HBcAb-IgM)- marker of acute infection.

Anti-HBc IgG (HBcAb-IgG) - past or chronic infection.
HBeAg – measure of active replication
Anti-Hbe - not actively replicating
Patient can still be positive for HBsAg which is made by integrated HBV.
HBV-DNA - Used mainly for monitoring response to therapy.
G)Peginteferon alpha alone or in combination with the nucleoside analogues has been demonstrated to reduce HDV RNA
H)HBV-HDV Coinfection
Pre or postexposure prophylaxis to prevent HBV infection (HBIG and/or Hepatitis B vaccine)
HBV-HDV Superinfection
Education to reduce risk behaviors among persons with chronic HBV infection

Hep D Virus(Delta Virus)
A)ss negative sense RNA genome
-HDAg encoded by HDV RNA
-HDV is a defective virus that acquires an HBsAg coat from HBV and is required for transmission
C)percutaneous/parenteral routes (e.g. needle sharing, acupuncture, ear piercing, tattooing, transfusions, receiving blood products)
D)Associated with the most severe forms of hepatitis in HBsAg positive patients
Hep D Virus
-Clinical Disease
Clinical Disease:
Co-infection with HBV
Severe acute disease may occur
low risk of chronic infection
Super-infection on top of chronic HBV
Results in the most severe acute disease cases
usually develop chronic HBV/HDV infection
high risk of severe chronic liver disease
F)HCV antibody (total Ig)- generally used to diagnose hepatitis C infection. Appear within 7 to 31 weeks of infection
RT-PCR for HCV RNA - confirmation and determination of viral load in monitoring the response to antiviral therapy. May be used to diagnose HCV infection in the acute phase.
Liver Biopsy - confirm chronic active hepatitis
ELISA - screen donor blood products
G)Recombinant interferon ? - may be considered for patients with chronic active hepatitis. The response rate is ~50% but 50% of responders will relapse upon withdrawal of treatment.
-Ribavirin - a combination of interferon and ribavirin is more effective than interferon alone.
-Pegylated interferon/ribavirin – dosage by weight
Most recently – addition of small molecules which inhibit HCV replication
Example: Telaprevir and Boceprevir – a protease inhibitors
H)Screening of blood, organ, tissue donors
High-risk behavior modification
Blood and body fluid precautions
No vaccine which is FDA approved at present time
-Hep C(Flaviviridae)
A)+ ss RNA, Enveloped
-6 genotypes plus subtypes of each of those
C)Same as for HBV however the majority of cases have been linked back to parenteral transmission
D)transfusion or transplant from infected donor; Injecting drug use; Hemodialysis (yrs on treatment); Accidental injuries with needles/sharps; Sexual/household exposure to anti-HCV-positive contact; Multiple sex partners; Birth to HCV-infected mother
Hep C(Flaviviridae)
-Clinical Disease
Clinical Disease:
Most new infections are subclinical
70-90% become chronic
Can Lead to cirrhosis (10-20%) and hepatocellular carcinoma

Acute Clinical illness (jaundice): ~30% (20-30%)
Chronic hepatitis: 70%
Persistent infection: 85-100%
Immunity: No protective antibody response identified yet
Hep G(HGV) & GBV
Flaviviridae, + ss RNA,Envelope
Transmission is the same as for HBV & HCV
Goes on to chronic activity (replication not disease)

Co-infection with HBV or HCV does not change course of those diseases

Is it protective in HIV patients? Not established whether coinfection delays progression of HIV
Infections of the Heart
Infective Endocarditis
-“Viridans” streptococci
-Gram-negative bacilli (HACEK)
-Staphylococcus sp.

Myocarditis/Dilated Cardiomyopathy
-Trypanosoma cruzi

Myocarditis and Pericarditis
-Coxsackie B
Clinical Disease: Endocarditis

Bugs: Staph spp.
-Viridans group
-"HACEK" organisms
Clinical Disease:
Exudative and proliferative inflammatory alterations of the endocardium, (presence of vegetations on surface or within the endocardium and most commonly involving a heart valve)

Should be considered in any patient presenting with a fever of more than several days and a cardiac murmur
The disease has a slow course hallmarked by low-grade fever, night sweats, weight loss and vague systemic complaints.
Usually due to bacteria.

Physical Examination:
The patient presentation is highly variable but ~90% present with fever and new or exacerbated heart murmur
May also include:
Systemic toxicity and leukocytosis.
for Endocarditis
-bugs: Staph spp.
"HACEK" organisms
Median age is 47-60 yrs

~75% patients have predisposing conditions
Highest risk: Artificial heart valves; some complex congenital heart defects and repairs

Moderate risk      Some less complex congenital defect; hypertrophic cardiomyopathy; some cases of rheumatic/other types of valvular heart disease; mitral valve prolapse w/regurgitation

Recommended risk stratification (including evalulation of procedures associated with a high risk of bacteremia)
Clinical Disease: Endocarditis
F)Culture, serology not diagnostic
G)Infections should be quickly identified and drained, appropriate antibiotic therapy started
H)Hand washing an effective prevention strategy; prophylactic antibiotics; Education regarding risk to IDU population
A)Gram positive cocci, clusters
Staphylococcus aureus and Staphylococcus epidermidis (cat +, halophiles)
S.aureus is coagulase + and ferments mannitol
S.epidermidis is coagulase negative and does not ferment mannitol
C)respiratory, via direct contact, fomites, vectors
D)Invasive procedures, underlying cardiac disease,
IDUs – Staph. aureus
Indewelling lines – Staph. epidermidis
E)Clincial Disease: Endocarditis
G)Penicillin w/wo aminoglycosides, Cephalosporins or vancomycins if necessary
H)Good dental hygiene; prophylactic antibiotics in high risk patients

Strep Viridans
A)Gram positive, Catalase negative
Lack group specific surface carbohydrates
Virulence Factors:
Polysaccharide (dextran based) capsule
B)Normal flora of oropharynx, gastrointestinal tact, and genitourinary tract
D)Dental or other invasive procedures; underlying heart disease
The "HACEK" Organisms
Fastidious gram-negatives – meaning they grow best on blood and under increased CO2 levels
Slow growing (48-72 hrs) can take up to 2 weeks for a positive culture so often called “culture negative”
All part of the normal human oropharyngeal or urogenital flora
Cause bacteremia and endocarditis (usually subacute – requirement for pre-existing defect)
Haemophilus aphrophilus/paraphrophilus
Actinobacillus actinomycemcomitans
Cardiobacterium hominis
Which one of these organisms line up on Gram stain as rosette, stick-like forms
Eikenella corrodens
bleach like odor on culture; colonies “erode” agar
Kingella kingae
Clinical Disease: Myocarditis
F)Biopsy - Isolated pockets of inflamed & necrotic myocardial cells
Generally randomly distributed in the heart
Clinical consequences are interdependent on the size, the number, and the location of the lesions
i.e. a small single lesion residing in the conductive tissue may result in a fatal arrhythmia
G)Treat any associated illness
Pain relievers and anti-inflammatory medicines
Drugs may be used to help the heart pump while it heals.
Anti-arrhythmic medicines may be required.
Little damage - medicines and follow-up visits to the doctor
More damage may need to limit some of their activities and take many medicines for the rest of their lives
Severe damage to the heart, a heart transplant may be needed.
H)Early identification and control of infection
Clinical Disease: ?????? Inflammation of the myocardium: the muscular walls of the heart. Inflammation may involve the myocytes, interstitium, vascular elements &/or pericardium (perimyocarditis)

Predominantly affects middle-aged men (average age of onset = 42)
60 % patients have a history of recent viral illness.
Suspected in cases of unexplained heart failure or arrhythmias in the setting of a systemic illness or after symptoms of an upper respiratory tract infection

Physical Examination:
Evidence of rapid heartbeat (tachycardia) and blood tests for recent infection or signs of inflammation)
Electrocardiography (an ECG or EKG); Echocardiography; Endomyocardial biopsy.
Definitive diagnosis requires the demonstration of trypanosomes by microscopy
Antibodies are often detectable by complement fixation or immunofluorescence and provide presumptive diagnosis.
H)Vector control

-Trypanosoma cruzi
A)Flagellated protozoan
B)Reduvid bugs and wild and domestic animals including cattle, pigs, cats, dogs, rats, armadillo, raccoon and (Central/South America)
C)Insect feces contaminating the eye or a break in the skin (Insect – Reduviids); or through consumption of contaminated food (with insect feces); blood transfusion
D)Poor socioeconomic conditions; Mexico, South and Central America; Recent report of bugs in southern US (Texas, California, Georgia, etc)
Clinical Disease: Chagas' disease/Dilated cadiomyopathy (myocarditis with megacolon and megaesophagus)
(dilated cardiomyopathy – enlargement/inflammation of pumping chamber – 1o left ventricle)
3. Chronic stage – abnormal function of the hollow organs, particularly the heart, esophagus and colon (20-30%)
- Cardiac changes include myocardial insufficiency, cardiomegaly, disturbances of atrio-ventricular conduction and the Adams-Stoke syndrome.
- Disturbances of peristalsis lead to megaesophagus and megacolon (difficulties eating and/or passing a stool - constipation)

Trypanosoma cruzi
Clinical Disease:
1. Primary lesion – Chagoma swelling at site of bite; called Romana’s sign if it is on the face, eyelids, conjunctiva

2. Acute stage - appears 7-14 days after infection
- rarely recognized and often resolves with little or no
immediate damage; infected host (usually a child) remains a carrier.
- patient is characterized by restlessness, increasing exhaustion, chills, fever, coughing, wheezing, dypsnea, fluid retention, bone and muscle pains.
- Additionally: lymphadenophaty, hepatomegaly, erythematous rash and acute myocarditis

bugsL Adenovirus & Coxsackie B
-inflammation of the pericardium
Clinical Disease: Pericarditis
F)Rubbing" sounds which indicate there is fluid around the heart.
A chest x-ray will show if heart is enlarged due to increased fluid in the pericardium.
Electrocardiography; Echocardiography; Pericardiocentesis.
Computed tomography (CT) scanning and magnetic resonance imaging (MRI) may be used for a more complete diagnosis.
G)Pain relievers and anti-inflammatory medicines.
If caused by an infection, anti-microbial may be prescribed.
Pericardiocentesis may be needed to remove
Clinical Disease:
pericardium becomes inflamed (damaged from infection or irritation). Inflammatory fluid enters the pericardial region and can increase pressure on the heart; squeezing it and making it harder to pump blood to the body.

Dx: Occurs most often in men between the ages of 20 and 50 years old
Should be considered when a young person develops unexplained heart failure or arrhythmias, or when cardiac abnormalities occur in the course of a recognized systemic infection (like diagnosis of myocarditis)
Fever, chest pains, arrhythmia and even cardiac failure can result.

Physical presentation:
Sharp, piercing chest pain, especially behind the breast bone (retro sternal) spreading to the neck, the left shoulder, and the muscle ridges between the neck and shoulders
Pain comes on suddenly and lasts for days
Pain intensifies when the person takes a deep breath (inspiration) and lying in a flat recumbent position; reliever by anti-inflammatory meds and tends to decrease when sitting up
E)Clinical Disease: Myocarditis and Pericarditis (separately and together)
Mortality rates are high
F)Clinical Expression, serology, PCR, (biopsy variable but the old gold standard)
H)Avoid exposure, water treatment

Coxsackie Virus
A)ss +RNA, Naked Virus
B)Humans; resistant to environmental factors
C)fecal-oral, direct contact with mucosal secretions
E)Clinical Disease: ??????????
Pathogenesis of Coxsackie and Adenovirus
-both use CAR receptor
initially binds to the
CAR receptor on mucosal cells in the gut and spleen and eventually spreads to its target organ, the heart.
Once in the heart, replication of the virus causes damage to the heart cells and induces
migration of white blood cells into the heart tissue.
3. The white blood cells subsequently activate an autoimmune process in which the white blood cells kill the virus infected heart cells and normal heart cells which are not infected. This autoimmune process persists long after viral particles are no longer detected. The destruction and damage to the heart cells results in myocarditis and heart failure.
E)Clinical Disease: Myocarditis and Pericarditis (not at the same time)
F)Clinical presentation; Detection of Antigen; Serology; Virus Isolation
G)There is no specific antiviral therapy

Adeno Virus
A)ds DNA virus, non-enveloped; at least 47 serotypes and 6 subgenera
Like Coxsackie B virus it binds to CAR on host tissue
C)Aerosol, close contact, fecal-oral, direct or indirect to mucosa
E)Clinical Disease: ??????????
Fevers of Unknown Origin
“Fever higher than 38.3oC (101oF) on several occasions (close in time), persisting without diagnosis for at least 3 weeks in spite of at least 1 week’s investigation in hospital.”
F)Atypical lymphocytes/Downey Cells; Heterophile antibodies; Monospot screening test and VCA diagnostic test
Lifelong infections
Asymptomatic shedding cause of contagion

-EBV (Herpesviridae)
A)ds linear DNA, enveloped; infects B cells
B)Man (90-95% infected)
C)Person to person via orapharyngeal route – saliva; kissing, sharing toothbrushes – “Close Contact”
D)Teens, Immunocompromised, some races are at risk for proliferative disease triggered by ....... infection
B)Induced lymphoproliferative disorders

Clinical Disease:
A)Heterophile positive ........
-+/- Exudative pharyngitis
B)1. Burkitt’s lymphoma – jaw and face
(chromosomes 8/14 - c-myc translocation – equatorial Africa)
2. Hairy Oral Leukoplakia – HIV patients; mucosal lesions (unchecked lytic replication of EBV)
3. Nasopharyngeal carcinoma - epithelium of the URT(southern China and Inuit Alaskans)
F)Microscopic examination:
-“Owl’s eye inclusion body
In situ hybridization in tissue
Immunofluorescence/cell culture
Heterophile antibody negative
G)Ganciclovir, cidofovir, foscarnet
H)Screen blood and tissue;
working on vaccine to prevent in utero infection

A)ds linear DNA, enveloped;
infects then goes latent in mononuclear cells
B)Man (90-95% infected)
C)Intimate exposure by mucosal contact
-Chronic shedding - immunocompromised patients
-Transient shedding - asymptomatic healthy individuals
D)Impaired cellular immunity
Clinical Disease:
Clinical Disease: NAME THE BUG!!!!!
Heterophile Negative Mononucleosis (primarily in transfusion patients); no pharyngeal exudate

Cytomegalitic inclusion disease
Most common in utero infection in US
Jaundice, hepatosplenomegaly, purpura (“blueberry”), pneumonitis, CNS damage
F)Blood work; ELISA
G&H)AZT plus interferon ? has been effective in some patients
Prevention as with HIV

HTLV I&II(Retroviridae)
A)Enveloped, diploid, +ssRNA virus; also packages reverse transcriptase and integrase
C)Sexual contact, maternal-neonatal, blood
D)Any one but see geographic map of endemic areas as of the world.
HTLV I & II(Retroviridae)
-Clinical Disease
Clinical Disease:
1. Asymptomatic but associated with progression to Leukemia in 1/20 cases
2. More Recently associated with Tropical Spastic Paraparesis -
Infection of the spinal cord
progressive weakness, stiff muscles, muscle spasms, sensory disturbance and
sphincter dysfunction. Rarely fatal.
Seen in adults living in equatorial areas
F)Detection in blood smears (Thick and thin); DFA
New rapid test for P. falciparum and P. vivax
Indirect Fluorescent Antibody Test
G)choice of drug is based on the infecting species of Plasmodium.
Lots of drug resistance, particularly in P. falciparum is a major so now use combo therapies.
-After beginning treatment, most people improve within 24 to 48 hours, but with falciparum malaria, fever can persist for 5 days.
H)Eradication of infected mosquitos. Vaccines are being developed (Glaxo-Gates – clinical trials); prophylactic antibiotics
Drugs should be taken to prevent malaria during travel in areas where it is prevalent.
The preventive drug is started before travel begins, continued throughout the stay, and extended for a time (which varies for each drug) after the person leaves the high-risk area.
Preventive drugs reduce but do not eliminate the risk of malaria.

Similar drugs to those used to treat
Malarone or Mefloquine commonly used

-Plasmodium vivax and falciparum
A)Sporozoite protozoan – 4 major species
P.vivax – (80% of all infections) - infects only young, immature erythrocytes; forms hypnozoites (primarily in Asia)
P. falciparum – (15% of all infections) – infects erythrocytes of any age; does not form hypnozoites; - most often fatal if untreated due to the greater number of infected erythrocytes (primarily in Africa)
P.malariae - infects old erythrocytes; no hypnozoites; untreated - may last for up to 20 years
P.ovale - infects young erythrocytes; forms hypnozoites; untreated – may last up to a year
B)Man, Mosquitoes
C)Anopheles mosquito, blood transfusions;
D)Anyone who travels to endemic areas, blood transfusions; authochthonous
Infection of Plasmodium vivax and falciparum
Injection of sporozoites into blood, which migrate to liver
Entry into hepatocytes is via Circumsporozoite Protein (CSP)

Intrahepatocellular formation of merozoites (tissue schizont).
Schizogony = nuclear division – Tissue/Erythrogenic Schizont

Merozoites rupture hepatocytes and move into circulation – INFECTIOUS NOW
P. vivax merozoites bind the RBC Duffy antigen on host RBCs
P. falciparum merozoites use PfEMP-1 antigen on the parasite to bind to a large variety of surface antigens on host RBCs

Merozoite differentiates into ring shaped trophozoites within RBC

Trophozoites = erythrogenic schizonts which then replicate using hemoglobin as a nutrient; convert into merozoites for release from RBC

Rupture of RBCs release merozoites to invade other erythrocytes ? cycle is what causes shaking, fever, chcills etc..

Some merozoites become gametocytes (sexual forms); may be picked up by next mosquito (infection of naive mosquitoes)

P. vivax and P. ovale have a latent liver form – hypnozoites
Plasmodium Vivax and falciparum
-Clinical Disease: Malaria (Historic name is Blackwater Fever)(Over 300 million infections per year)
Clinical Disease:
Immune response and rupture of RBCs underlying cause of disease signs and symptoms: Cyclic paroxysms of fever due to release of toxic substances

Prodrome: nonspecific; “flu-like”
Headaches, muscle pains, nausea and vomiting
Clinical disease: Cyclic fevers, chills and “malarial rigors”
Hemolytic anemia
Hypoglycemia (liver dysfunction; parasite; drugs)

In P. falciparum infections -
damage in brain, kidney and liver due to pigments, debris
Orthostatic hypotension [capillary plugging (slugging) by infected cells](specific to P. falciparum)
confusion, coma, neurologic focal signs, severe anemia, respiratory difficulties
Clinical Disease: Cerebral Malaria
-Plasmodium vivax falciparum
*****The histopathology: sequestration of cerebral capillaries and venules with parasitized red blood cells (PRBCs) and non-PRBCs (NPRBCs)
Clinical Disease:
that induce changes in mental status and coma.
Three primary symptoms generally common to both adults and children:
(1) impaired consciousness with non- specific fever;
(2) generalized convulsions and neurological sequelae; and
(3) coma that persists for 24-72 hours, initially rousable and then unrousable.

Mortality ratio - 25-50%. (If a person is not treated, CM is fatal in 24-72 hours.)
Disease risk factors include being a child under 10 years of age and living in malaria-endemic area.
Kidney Complication for:
Plasmidium Falciparum & Vivax
Seen in severe falciparum malaria
More common in adults and rarely, if ever, seen in children.
Usually there is a reversible dysfunction, which may progress to acute tubular necrosis and acute renal failure. It carries a high mortality.

Dehydration, increased blood viscosity, hypo-volemia (possible renal hypo-perfusion)
reversible with adequate rehydration.

Intravascular hemolysis and clogging of the tubules by the products of hemolysis
Severe falciparum malaria results in hemolysis of parasitized as well as non-parasitized red cells.

Although hemoglobin itself is not nephrotoxic, other products of hemolysis can cause acute tubular necrosis, particularly in the presence of dehydration and acidosis.
F)Ring structures, “maltese cross” on thin blood smear; Serology = Paired sera
G)Clindamycin plus quinine or atovaquone plus azithromycin are the options
Chloroquine not effective
H)Vector control, Insecticides, Screen blood

-Babesia spp.(Flaviviridae)
B)Wild animals, similar to those where Borrelia burgdorferi is found
C)Ticks as vectors; rare blood transfusions and rarely congenital
D)Tickborne transmission primarily occurs in the Northeast and upper Midwest, especially in parts of New England, New York State, New Jersey, Wisconsin, and Minnesota. Other species seen in Europe, Africa and Asia.
Often co-infection with Borrelia burgdorferi (20%)
-Babesia Species
Clinical Disease: Babesiosis
Clinical Disease: Most infections are probably asymptomatic, as indicated by serologic s
Elderly, immunocompromised, and asplenic at risk for clinical disease .

IP 1-4 wks, lasts several weeks
Malaria like syndrome:
Fever, chills, sweating, myalgias, fatigue, hepatosplenomegaly, hemolytic anemia. and hemoglobineuria (free hemoglobin proteins in urine);
May lead to renal failure

May be fatal in asplenic, elderly or immunocompromised patients who have trouble clearing the infected cells
F)Clinical presentation, Serology (~ 2wks) new test looks for NS1 protein may be seen in first week (from Day 1), PCR
Decreasing WBCs and platelets and rising hematocrit are suggestive of plasma leakage
G)supportive treatment only.
should be given acetaminophen preparations rather than aspirin to avoid aggravation of the bleeding tendency associated with dengue infection.
DHF/DSS require fluid replacement therapy and plasma replacement if necessary: if diagnosis is made early, fatality rates can be kept below 1%.
H)Vector control, mosquito repellant
Mosquito “food” - blocks larval stages
Tetravalent Vaccine in clinical trials (Phase III)

-Dengue Fever Virus(Flaviviridae)
A)Enveloped, ss + sense RNA: four serotypes
Infects monos/macros, B/T cells, causes apoptosis of endothelial cells
B)Monkeys and humans
C)Aedes mosquitoes as vectors
D)Everyone for infection; those with previous exposure are at increased risk of progression to Dengue Hemorrhagic Fever
Dengue Virus(Flaviviridae)
Clinical Disease:
Typical uncomplicated dengue fever (Breakbone Fever)
Clinical Disease:
IP – 1 week
Sudden onset of high-grade fever (up to 105oF)
Retro-orbital pain/frontal headache
Severe joint and muscle pain especially in the lower back pain
Often a maculopapular to petechial rash.
May also see increased bruising and gums may bleed more easily.

The acute phase may last up to one week, with a prolonged convalescence characterized by weakness, malaise, and anorexia. Treatment based on symptoms is recommended.

The illness may be clinically indistinguishable from influenza, measles, or rubella.
Up to 100 million cases/year (most in southeast Asia)
Clinical Disease:
Dengue Hemorrhagic Fever (DHF)

Dengue Shock Syndrome (DSS)
Symptoms of DSS; fluid leaking outside of blood vessels, massive bleeding and shock.
-Early signs: restlessness, cold clammy skin, rapid weak pulse, and narrowing of pulse pressure and/or hypotension
Hypovolemic shock.
Symptoms of this include all of classic form plus severe damage to the blood vessels.
At about the time the fever begins to break, patient becomes restless and lethargic,
Bleeding from the nose, gums or under the skin are common.
Develops hemorrhagic manifestations - petechiae, and purpura or ecchymoses

This form of dengue can be fatal.

Pathogenesis: role of cross reacting antibodies leading to increased infection rates and activation of macrophages leading cytokine storm
F)Serology shows increased titers; Peripheral blood smear show “morulae” vacuole filled with bacteria
Peripheral blood smear (buffy coat preparation) showing intracellular inclusions (arrows) in mononuclear cells of a patient with human monocytotropic ehrlichiosis.
H)Prompt removal of ticks; no vaccine

Ehrlichia chaffeensis
A)Member of the Rickettsia family (intracellular) – appears to have a gram negative cell wall
Infects monocytes
B)white-tailed deer, white-footed mouse, chipmunks, voles, canines
C)Via ticks; seen worldwide ticks but most cases in the US occur in California, Texas and eastern coast, with some cases occurring in the north central states
D)Hunters, campers, veterinarians, park rangers
Ehrlichia chaffeensis
Clinical disease: Human Monocytic Ehrlichiosis
Clinical Disease:
Most cases are asymptomatic so it is rarely diagnosed;
Often classified as a “Fever of Unknown origin (FUO)”

IP - ~ 1 week

Clinical Presentation:
Ranges from mild body aches to severe fever and usually appear within a week or two of a tick bite.
Rash is RARE
If treated quickly with antibiotics, ehrlichiosis generally improves within a few days.

Rarely (5%) disease may progress to leukopenia, pulmonary failure, renal failure, encephalitis; can be fatal (Unknown risk factors)
F)Serology shows increased titers; Peripheral blood smear show “intracellular inclusion = “morulae” filled with bacteria (only way to distinguish from ehrlichia is blood smear showing PMN infected cells)
-Peripheral blood smear showing intracellular inclusion within a neutrophil of a patient with human granulocytic anaplasmosis (arrows). (Wright stain, ?1000.)
H)Prompt removal of ticks; no vaccine

Anaplasma phagocytophilum
A)Member of the Rickettsia family; used to be classed as an Ehrlichia species (gram neg)
Infects granulocytes/PMNs
B)white-tailed deer, white-footed mouse, chipmunks, voles, canines
C)ticks - Common in Atlantic states
D)Hunters, campers, veterinarians, park rangers
Anaplasma phagocytophilum
Clinical disease: Human Granulocytotropic Anaplasmosis
Clinical Disease:
Often missed in diagnosis; Fever of Unknown origin

IP 5-21 days
Infects neutrophils (ehrlichia infects monocytes!)

Clinical presentation:
fever, headache, chills, myalgia, nausea and anorexia; rash may or may not appear.

Symptoms resolve within several weeks or sooner with treatment
Also called Human Granulocytic Ehrlichiosis (due to old classification)
F)Organism in peripheral blood smear - febrile periods; rosettes
-Peripheral blood smear from a patient with tickborne relapsing fever acquired in Idaho. Wright stain.
G)Tetracycline, Penicillin, Erythromycin
H)Avoidance or elimination of arthropod vectors, insecticides, Personal hygiene

Borrelia recurrentis
A)Gram negative, spirochete
- antigenic variation (basis of relapsing disease)
- Extracellular – binds to surface of RBCs causes “rosetting”
B)Humans - louse borne; wild animals -tick borne
C)Tick bite or Infection occurs when lice are crushed, released spirochetes then penetrate skin/mucous membranes
D)Hunters, Low SES (SocioEconomic Status); Louse-borne relapsing fever remains endemic in the highlands of Central and East Africa (Ethiopia, Sudan, Somalia, Chad) and in the South American Andes (Bolivia, Peru).
Borrelia recurrentis
-Clinical Disease: Relapsing fever
Clinical Disease:
most infections not diagnosed; Fever of Unknown Origin
IP – 2-18 days, lasts about 1 week
Clinical presentation:
Fever with shaking chills, myalgias, headache
Later symptoms: nausea & vomiting , weight loss, dry cough and neurological aspects such as meningismus, photophobia, confusion & dizziness (rosettes trigger hemorrhaging, reduced flow in capillary beds)
Neuro components distinguish from dengue as well as Brucella!!!
mild to moderate hepatosplenomegaly & jaundice
nonspecific macular rash and/or scattered petechiae. 
Organisms sequestered in organs after immune response clears from blood which results in relapses
There are usually 3 “relapses” each diminishing in intensity, but there may be up to ten if not treated properly
Assisted by antigenic variation of surface antigens (phase variation and cassette switching)
F)Demonstration of the organism in blood; Blood cultures; ELISAs
G)Treat for 3-6 weeks
H)Drinking/eating only pasteurized cheeses and milk . People who handle meat should wear protective glasses and clothing. Detecting infected animals controls the infection at its source.
Vaccination is available for cattle, but not humans.

Brucella spp.
A)Intracellular, gram negative rod; 4 species
-Infects macrophages and monocytes which carry it to spleen, liver, bone marrow, lymph nodes and kidneys where they become lodged
Virulence Factors: Phase variation of O-antigen!!!
+Phase variation (dissociation of smooth-to-rough transition)
++organisms from smooth colonies have O chains on LPS
++Rough colonies lack O chains on LPS
+Intracellular antiphagocytic (SOD); resistant to serum killing
+prevents phagosome fusion with lysosome
B)Cattle (B. abortus), goats and sheep (B. melitensis), pigs (B. suis), dogs (B. canis). (disease is mild or asymptomatic) (loves the sugar erythritol); have seen some marine infections
C)consumption of contaminated unpasteurized milk, soft cheeses, and other dairy products.
-May also be transmitted via contact with infected meat or the placenta of infected animals,
D)Occupation - jobs requiring frequent contact with animals or meat -- such as slaughterhouse workers,
Brucella spp.
-Clinical Disease: Brucellosis/Undulant Fever
Clinical Disease:
Acute Brucellosis:
Headache, Fever , Chills, Sweats (profuse and malodorous)
Weakness ,Weight loss, Fatigue
Abdominal pain , Back pain , Joint pain
Classically, fever spikes occur every afternoon to levels around 104 degrees Fahrenheit. "Undulant" fever derives its name from this up-and-down fever (daily basis).

NO CNS; NO rash!!!! (to distinguish from Borrellia)

Chronic disease– recurrent fever, joint pain, fatigue and depression often out of proportion to other complaints
May persist for years.
Granulomas formed in the various organs
Infections targeting the Vessels
Infections targeting ..??????/

Rickettsia rickettsii
Ebola Virus
Chikugunya Virus
Wuchereria bancrofti/Brugia malayi
F)Clinical symptoms and history of tick bite, DFA skin lesion biopsy
Silver Stain
-Red structures indicate immunohistological staining of Rickettsia rickettsia in endothelial cells of a blood vessel from a patient with fatal RMSF CDC
G)Early aggressive treatment (empiric)
H) via rodent control, insecticides, and prompt removal of ticks; no vaccine; Doxycycline for post exposure prophylaxis

Rickettsia rickettsia
A)Obligate intracellular bacteria; cell wall similar to gram negative cell wall (similar to Chlamydia)
Infects endothelial lining of small arteries, veins and capillaries
Rearranges Actin!!!
B)Wild rodents, wild and domestic dogs, ticks
C)Hard ticks
Disease rates highest in Spring and Summer
D)Hunters, Hikers, campers
Rickettsia rickettsia
Clinical Disease: Rocky Mountain Spotted Fever
Clinical Disease:
2-14 day incubation period

Rapid onset of headache, fever, malaise, myalgias, vomiting, confusion, GI, periorbital swelling, stiff neck, conjunctivitis and arthralgias
(Triad: Fever, Headache, Rash)

Rash usually develops on 3rd day (up to day 5)
RASH – maculopapular progressing to petechial (Infection results in inflammation and VASCULITIS)
Ankles and wrist first plus swelling**
Trunk, palms, soles, and face
Can become gangrenous (like N. Meningitides)

Without treatment, death 8 -15 days
F)Level 4 for handling; ELISA and RT-PCR to confirm.
G&H)Quarantine infected patients, destroy contaminated animals.
DNA vaccine trials underway.

-Ebola Virus
A)enveloped –ssRNA
Infection of the endothelial lining of the vasculature
also may infect neutropils
B)Wild monkeys
C)Contact with infected animals, blood or secretions and accidental needle sticks
D)Living or travel to endemic areas such as Africa. (Laboratory accidents?)
Ebola Virus
Clincial Disase: Ebola/Hemorrhagic fever
Clinical Disease:
flu-like with vomiting and blood diarrhea then
– raised rash becomes petechial, spreads over the body. Viral replication results in breakdown of endothelial cells leading to vascular injury and necrosis in liver, spleen, lymph nodes, and lungs. Bleeding from mucous membranes may occur.
F)Detection of antigens or antibody to the agent in the blood (serology); RT-PCR
G&H)Symptoms are treated, e.g. with analgesics and anticonvulsants.
Chloroquine proposed as prophylactic antiviral agent
Killed by common disinfectants, moist heat and drying. The vector (a mosquito) also needs to be controlled with insecticides
Experimental DNA vaccine

-Chikungunya Virus
Togaviridae family
A)enveloped, +ss RNA
Infects endothelial cells, dendritic cells, macrophages, lymphoid organs, liver, CNS and muscle
More IC related clinical presentation
B)Humans, Monkeys
C)Mosquitoes(Aedes aegypti and Aedes albopictus)
D)Those living in endemic areas: Africa, Asia – esp. India in the last few years
Chikungunya Virus
Clinical Disease: Chikungunya Fever (that which bends up)
-Don't mix up with Dengue fever
Clinical Disease:
patients BEND OVER in pain
IP: 3-12 days

Flu-like symptoms
Severe headache, chills, fever (>40°C,104°F) – may be “saddleback” (remits then returns – similar to relapsing fever)
Joint edema and pain, nausea and vomiting.
A rash may sometimes occur (maculopapular to petechial forms seen – due to leakage of erythrocytes)

Self limiting: 3-5 days.
Some can suffer for joint pain for months.
Children may display neurological symptoms.

Sudden onset of flu-like symptoms including a severe headache, chills, fever (>40°C,104°F), joint edema and pain, nausea and vomiting.
A rash may occur.
Period of prolonged fatigue may last weeks.
F)Blood smears – microfilariae and eosinophilia; clinical presentation later in infection;
NEW – antigen capture ELISA
G&H)Antibiotics show variable effectiveness
Vector control for prevention

Wuchereria bancrofti/Brugia malayi
A)Filarial nematode (found in blood and tissue; reliant on vector to complete life cycle and transmit; larval stage is known as microfilariae
C)Bite (large infective dose required)
D)Living in or travel to tropics and subtropics
Wuchereria bancrofti/Brugia malayi
Clinical Disease: Lymphatic filariasis, Elephantiasis - Bancroftian Filariasis – acute inflammation or chronic lymphatic obstruction = Lymphedema.
Clinical Disease:
Asymptomatic Phase
High microfilaremia infection; Humoral response - Cytokines suppressing the activity of TH1 cells; (elevated EOSINOPHILS)
Can occur for years.- develop into adults.
During the day Microfilaria are present in the deep veins and during the night the migrate to the peripheral circulation (take blood sample at night!!).

2. Inflammatory (Acute) Phase
Antigens from the female adult worms elicit inflammatory responses.
Worms in lymph channels disrupt the flow of the lymph causing lymphedema.
fever, chills, skin infections, painful lymph nodes, and tender skin of the lymphedematous extremity. May include: orchitis and epididymitis
3. Obstructive (Chronic) Phase
Lymph varices, lymph scrotum, chyluria (lymph in urine), and elephantiasis: Microfilariae (in the blood) are not normally present in this phase.
Scar formation in affected tissue areas - thickening of the skin and elephantiasis which develops gradually with the attack of the lymphatic system (permanent lymph blockage)
Elephantiasis affect men mainly on the legs, arms, and scrotum
In women, the legs and arms are affected.
-Global Distribution:
Over 50 million infected with HIV world wide
HIV-1 - world wide
HIV-2 - mainly west Africa (felt to be less transmissible than HIV-1)
3 million deaths per year.
7 million new infections per year,
580,000 new infections in children per year.
Two-thirds of world HIV infections in Sub-Saharan Africa where prevalence is 1 out of 13 people between 15-49
One out of 100 sexually active adults is infected with HIV
-Recombinant forms exist: AE, AG, AB, DF, BC, CD
A)enveloped, diploid, + sense, RNA virus
Encodes and packages within the virion
REVERSE TRANSCRIPTASE (RNA-dependent DNA polymerase)
-integrase&protease: allow integration of the viral genome into the host genome to become a cellular gene
Risk factors for HIV:
-Unprotected sex with HIV+ sex partner
+Insertive anal, vaginal and receptive oral
+Risk probabilities:
female to male: 1 in 700-3000
male to female: 1 in 200-2000
Male to male: 1 in 10-1600

-Presence of other inflammatory STD‘s
-Parenteral exposure:
+Needle stick: 1 in 200 (see notes below)
+IDU sharing “the works” with HIV+

-Mother to infant: 1 in 4 (with treatment: 1 in 25)
+Transplacental – 25-40%
+Intrapartum (at birth) – 60-75%
+Postpartum (1o nursing) – 10-16%
-Transfusion of infected blood: 1 in 450.000 per unit)
.... is present in:
blood (or fluids contaminated by blood and serum)
vaginal fluids
Host related factors are biggest determinate
Enter the body through microabrasions of the mucous membranes
Presence of genital and anorectal ulceration or mucosal disruption increases risk of transmission
Factors that increase infectiousness: primary infection, late stage infection, genital tract infections (source factors)

what are the 5 risk factors?????
Initial Entry of HIV
1)Picked up by Langerhans/Dendritic cells, moved to lymph nodes
2)Direct infection of macrophages (gp120 & CCR5)
3)Direct infection of T cells (gp120 and CXCR4)
4)Infected cells in lymph nodes within 2 days, plasma within 5 days
5)Viremia to other lymphoid organs and CNS = maculopapular rash and flu-like signs and symptoms; evidence for early infection of the CNS - binding and infection of microglial cells
6)Drop in viral concentration to steady state (anti-viral activities) by 3-6 months
-HIV adhesion & penetration:
Viral gp120 binds to CD4 and Co-receptors: CCR5 (macrophages) or CXCR4 (THcells) on T-helper lymphocytes and cells of the macrophage lineage: Macrophages , Dendritic cells, Microglial cells (brain cells)
Many more co-receptors are being implicated: CX3CR1, CCR8, etc.
Clinical Disease/Pathogenesis: HIV/AIDS
Clinical Disease:
HIV infection of CD4 lymphocytes results in cell death by a cytopathology (fusion?syncytia? lose functional T cells) or by triggering apoptosis (programmed cell death)
Antibodies against gp120 may produce antibody dependent cytotoxicity (ADCC)? most important early on with good function B and T cells
CD4s are primarily responsible for delayed type hypersensitivity and cell mediated immunity
As CD4 cells are lost, opportunistic infections and malignancies occur

AIDS develops when any of a number of signs of CD4 depletion occur
opportunistic infections
Kaposi’s sarcoma
AIDS related dementia
wasting syndrome
Stage A: HIV
Clinical Syndrome:
- Initial infection - Seroconversion
Most are asymptomatic but some develop infectious
Symptoms occur within weeks of infection
mononucleosis-like symptoms with a rash not seen with CMV or EBV – affects palms and soles
Highly infectious stage – virus in large concentrations in genital fluids (Remember : Infected cells are found in lymph nodes within 2 days, plasma within 5 days after transmission)
This is a time to educate the patient about maintaining good health,
Diet, exercise, vaccinations, etc

Primary infection may be followed by a long symptom free period during which CD4 cells slowly reduce in number
Stage B: Symptomatic - HIV Disease
-Key descriptors here are: Frequent and Persistent
Clinical Syndrome:
Swollen large lymph nodes (enlarged for > 3 months)
Extreme malaise with weight loss
Recurrent/Frequent fevers and sweats

Beginning of first opportunistic infections
Diarrhea lasting > 1 month
Persistent or frequent yeast infections (oral or vaginal)
Persistent skin rashes or flaky skin
Pelvic inflammatory disease in women that does not respond to treatment
Some people develop frequent and severe herpes infections that cause mouth, genital, or anal sores, or shingles.

May suffer some short-term memory loss
-Infectious conditions associated with early symptomatic phase (stage B):
Bacillary angiomatosus (Bartonella henselae)
Persistent oral thrush or genital candidiasis
Persistent diarrhea (Cryptosporidium)
Hairy leukoplakia (Epstein Barr Virus)
Listeriosis (food borne)
Shingles (Varicella-Zoster reactivation)
TB (Mycobacterium tuberculosis reactivation or possibly primary infection which rapidly progresses)
Stage C - AIDS
-esophageal Candidiasis
-Pneumocisitis jeroveci pneumonia
-Cryptococcal Meningitis
-Mycobacterium avium intracellulare
-CMV retinitis

lymphoma & other malignancies assoc. w/ Stage C:
-Systemic Non-Hodgkins Lymphoma
EBV implicated
-Primary Nervous System Lymphoma
-Anogenital Neoplasia
Clinical Syndrome:

CDC's definition of AIDS:
HIV + with fewer than 200 CD4+ T cells per cubic millimeter of blood and clinical presentation of multiple opportunistic infections.

Wasting syndrome due to HIV (>10% of baseline body weight) – (cachexia)

Continuation of chronic diarrhea, weakness and fever

Neurological problems - encephalopathy
confusion and forgetfulness, Seizures and lack of coordination

Includes 26 clinical conditions - Most are opportunistic
Mycobacterium avium intracellulare
Acid Fast bacilli, facultative intracellular
Found in surface salt and fresh waters, soil, occasionally as a contaminant on fomites; birds, farm animals
Felt to be noncontagious (person to person)
Transmission via inhalation of contaminated water/soil or ingestion
Disease in healthy: none
HIV associated Disease:
Pulmonary – with or without nodules
Disseminated (as with Mycobacterium tuberculosis)
Ethambutol and Rifampicin
Lab aspects of HIV
A)Screening (ELISA) tests for antibodies to a number of viral antigens by enzyme immunoassay
Confirmation using Western blot (eliminates cross-reactive antibodies)
B)Immunologic studies
CD4 counts
C)Viral load testing
(RT-PCR; detect as low as 1- 10 copies of RNA)
D)Resistance genotyping
-Looking at the sequences of the genes in the HIV to see if the sequences have the mutations that cause resistance? to determine which drugs to use
Dx for HIV
HIV Screening: ELISA must be shown to be repeatedly positive (2 out of 3)
HIV Confirmation: Western Blot detects antibodies to:
Important Internal proteins
Polymerase specific proteins
Envelope specific proteins
Negative: no bands
Positive: gp41 + gp120/160 or p24 + gp120/160
Indeterminate: presence of any band pattern that does not meet criteria for positive results
4-20% of WB assays: process of seroconversion, late-stage HIV; Cross-reacting nonspecific antibodies, HIV-2, HIV vaccine recipients, Technical error

P24 detection - measures soluble p24 (not virus); 88.7% sensitivity, 100% specific – used for screening blood donors (early marker of infection – but a negative test does not rule out infection due to the low sensitivity)
Tx for HIV
3)Fusion inhibitors (FI) (Enfuvirtide)
-Enfuvirtide is a 36 amino acid peptide that mimics one section of gp41 – inhibiting fusion of the viral envelope to the host cell cytoplasmic membrane
4)CCR5 co-receptor antagonist (Maraviroc)

5)Inhibitors of HIV Integration (InSTIs) (Raltegravir; Elvitegravir – clinical trials)

****Treatment should be considered if HIV-1 RNA is >100,000 copies/ml or CD4+ cell count is declining
1.Reverse transcriptase inhibitors (RTI) – prevents virus multiplication and spread.
Nucleoside/Nucleotide NRTI (AZT, Lamivudine, Abacavir)
NRTIs were the first group of antiretriviral drug approved for use in HIV/AIDS patients.
Non-Nucleoside: NNRTI ( Delavirdine, Nevirapine)

2.Protease Inhibitors (PI) ( Indinavir, Ritonavir, Nelfinavir) –
inhibits protease cleavage of the viral proteins, inhibiting the production of new virions

**Highly Active AntiRetroviral Treatment (HAART)
combination of drugs (minimum of 2 nucleoside analogs and 1 protease inhibitor)
Today these has been expanded to include a variety of combinations of three or more anti-retroviral drugs

Vaccine – efforts being made at present
Clinical trials with mixed results - Thailand
Late 2009 began HVTN 505 – DNA primed/Ad5 vaccine
-trial: will it significantly reduce viral load in individuals who become infected with HIV***aimed at producing T cell and antibody response to envelope antigens (has done so in monkeys)
Avoid exposure to the virus

Post exposure chemoprophylaxis (risk = 0.3%)
Anti-HIV drugs (following baseline serology)
Pre exposure chemopropylaxis

Protecting children
Anti-HIV drugs to pregnant women and children born from such mothers
Elective Cesarean section delivery done at 38 weeks – infection is lower than normal delivery (1.5% vs 3.5%)
Intrapartum antivirals in some countries
Infected mothers should not breast feed (in US; in developing countries 1.7 million would get HIV but 1.5 million would die if not breastfed)

Microbicides – vaginal and/or rectal
Some increase infection (nonoxynol-9 and cellulose sulfate)
Latest showing laboratory success (Tenofovir – new formulations, Dapivirine, and UC-781 in trials)
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