CandidaAlbicans

-Gram Positive, Budding Yeast W/ Pseudohyphae -Opportunistic, part of normal flora (endogenous infections) -Described as a yeast like fungus -Disease:

Oral Thrush (pseudomembrane)/Moniliasis/Candidiasis

-Sites: Tongue, soft palate, cheek, gingivae and pharynx -Clinical Features:

Creamy-White plaques/Cottage Cheese like appearance Candida may spread to the esophagus( sign HIV progressed to AIDs. CD4 count is below 200/micro) Candida esophagitis: Pale plaques with erythematous mucosa It can disseminate via Bloodstream -Predisposing Conditions:

Bottle Feeding (infants), Antibiotics, Steroid, Endocrinal Disorders (Diabetes Mellitus), Smoking, Dentures, Immuno-compromised

-Treatment: Nystatin/ Amphotericin for systemic infection -Identification: Growth on Sabouraud’s Dextrose Agar Germ Tube Test used as identification

Gram stain of lesions: Inflammatory cells with Gram Positive Budding Yeasts and Pseudo hyphae of Candida

Oral Thrush

Esophagitis due to candida

Sabourauds Dextrose Agar Gram Positive Yeast Colonies

Germ Tube Test at 37 degrees

Herpes Simplex Virus-1 -Double Stranded DNA Virus, Icosahedral Symmetry, Enveloped -Virus can infect and spread in axons and ganglia -Remain latent in trigeminal ganglia(can reactivate during stressful conditions) →(HSV2 - in cervical ganglia) -Transmission/Disease: Transmitted through saliva; oral contact Infect and Replicate in Mucoepithelial Cells Fever, Ulcerative lesions on buccal mucosa, tongue, gums and pharynx →Herpes labialis, Cold sores, Gingivostomatitis -Diagnosis: Tzanck Smear: scrapings from base of the lesion stained by Giemsa

- multinucleated giant cells with intranuclear inclusion bodies Cell line culture with demonstration of cytopathic effect EIA and Immunofluorescence for detection of herpes antigen

-Treatment: Acyclovir or Valacyclovir →(prodrugs that need to be activated by Thimidine Kinase)

HerpesLabialis Herpetic pharyngitis

Tzanck smear showing multinucleated giant cells with intra-nuclear inclusion bodies

Coxsackie Virus -Single Stranded, Nonenveloped RNA virus -Picornaviridae Family - Fecal –Oral Spread -Isolate organism from stool samples or from the throat -Coxsackie is resistant to Gastric Acid

-Diagnosis: virus isolation from throat/stool. No specific treatment. Self limited

Hand-Foot-mouth Disease • Agent: CS-A 16 • primarily affects children, but

occasionally adults. • C/F: Oral and pharyngeal

ulcerations, sore throat, vesicular eruptions on the palms/ soleswhich spread to arms and legs.

• Vesicles heal without crusting.

Herpangina • CS-A or CS-B virus. • Vesicles usually at the junction

of the hard and soft palates. • Children and teenagers. • Epidemics during summer. • Lesions aremore vesicular than

herpetic, and consist of multiple small white papules with an erythematous base that appears less inflamed than that with herpetic lesions.

Trench Mouth/ Vincent’s Angina -Fusobacteria are gram negative, anaerobic bacilli

-Borrelia are gram negative spirochetes

-Severe ulcerogingivitis caused by Fusobacteria and Borrelia. Streptococcus and Staphylococcus - Also called Trench Mouth/ Fuso-Spirochetal Disease

Gram stain showing fusiform Fusobacteria and spiral

Borreliavincenti

Streptococcus Virdians: -Gram Positive Cocci in Chains - Alpha Hemolysis ,Optochin Resistant, Bile Insoluable -makedextrain (bioflim, poly saccharides) →biofilms - produce plaques on the teeth, then they produce acid with use of sugar. →Viridans - causes infective endocarditis, affecting the native valve. -Dental Plaques/Caries Usually associated with Strep. Mutans -Strep. Viridians Group ( mutans, sanguis, salivarius and mitis) are the most common cause of infective endocarditis following a dental procedure Production of dextran aids in adherence of S. Mutans to damaged valves

Actinomycosis -Anaerobic, Gram positive -An inflammation of the bone and the muscles around the jawbones. Can

-lead to osteomyelitis

→(staph is MC for osteomyelitis) -Imp bacteria causing infection: Actinomycesisraelii. -Source of infection: usually endogenous

→cannot exist in environment, no spore spread -Cervico facial actinomycosis: Tissue swelling with draining

-abscesses with sulfur granules. (Sinus formation with

discharging of puss with granules) -Radiography shows a “motheaten” appearance of the

bone. (osteolytic lesion) -Gram stain of granule shows sun-ray like appearance of gram-positive branching

filamentous bacteria. -grown on thioglycollate broth medium. Treatment: Ampicillin/ Penicillin G. -Similar:actinomycyes = Nocardia →both are gram positive, branching and filimentous bacilli →Nocardia is partially acid fast aerobic →actinomycyes is acid fast and anaerobic bacteria In actinomycin, when you press on it, yellow (sulphur) granules will come out.

Actinomyces: Gram positive branching filamentous bacilli

Sulfur granule section showing Gram positive branching filamentous bacteria

Epstein Barr Virus -Double Stranded, Enveloped, DNA Virus -Disease: Infectious Mononucleosis -Oral Hairy Leukoplakia Whitish, non-painful plaques on the lateral border of the tongue. Commonly seen in AIDS patients -Diagnosis: Histopathology/ PCR/ Immunohistochemistry -Positive Heterophile Agglutination test( Monospot/Paul Bunnel test) ( if test is negative- think of CMV)

ESOPHAGITIS Candida -most common type of infectious esophagitis. -Candida plaques are friable (detachable) Major predisposing factors include antibiotic use, radiation therapy or chemotherapy, hematologic malignancies, and acquired immunodeficiency syndrome (AIDS).

CMV CMV esophagitis signals a weakened immune system. Symptoms: Difficult and painful swallowing(Odynophagia), - Low-grade fever and mouth sores. -ulcerative lesions Predisposing conditions: HIV/ AIDS, Chemotherapy, Diabetes, Leukemia or lymphoma, Organ transplants →CMV is very common in transplant

(If it were a HSV infection then there would be lesions around the lips or vesicular lesions in the oral cavity→also have small punched out ulcers)

CMV: member of the herpesviridae; owl eye appearance of inclusion body.

GASTRITIS AND PEPTIC ULCER DISEASE

Helicobacter Pylori -Morphological and GrowthCharacteristics: Gram Negative Spiral Bacilli, Oxidase Positive, Urease Positive Demonstrated better by silver staining ( Dietrle/Warthin Starry Stain) Motile with flagella

Grow at 37 deg. Celsius on Campy or Skirrow Agar (Campylobacter grows at 42 deg. )

-VirulenceFactors: Flagella- bacterial mobility and chemo taxis to colonize under mucosa

Urease- neutralize gastric acid and cause gastric mucosal injury( byammonia)

Lipopolysaccharides- Adhere to host cells inflammation Outer proteins- Adhere to host cells

Exotoxins- vacuolating toxin (vacA) causes gastric mucosal injury(punch holes/create vacuoles)

→Cag-PAI (pathogenesis associated island) produces the cagA protein and the Type 4 secretion system Secretory Enzymes: mucinase, protease, lipase(for penetration) Type IV secretion system- pilli like structure, for injection of effectors

Effectors (cagA etc.)- actin remodeling, IL-8 (cytokines) induction, host cell growth and apoptosis inhibition (leading to immortality)

→leading to cancers, gastric adenocarcinoma and MALToma -Pathogenesis:

CagA- Alteration of the signaling pathways, cytoskeleton rearrangement and alteration of tight junctions Urease- Urease breaks down Urea to form ( Urea NH3 + CO2). The ammonia that is produced provides a neutral microenvironment favorable to H. Pylori. VacA- Formation of vacuoles, induction of apoptosis, disruption of epithelial junctions, and blockage of T cell response. PGN/LPS- Induction of inflammatory response in the lamina propria Adhesins- help with attachment to the epithelial cells

1) Bacteria invade mucus and attach to gastric epithelial cells. 2) Helicobacter, its toxins and inflammation cause the layer of mucus to become

thin. 3) Gastric acid destroys epithelial cells and underlying tissue. →long term, cagPIA and changes in signaling pathways and malignant changes Some of the infection is in the fundus or body leading to carcinomas atrophicgastrits, predisposes for gastric carcinoma At the lower part there are duodenal ulcers Gastic ulcer there is pain when eating, patient would be thin Duodenal ulcer patient the pain is better when they eat, fat pt

-Disease/Epidemiology: Chronic active gastritis, gastric ulcer disease, and duodenal ulcer disease are inflammatory diseases that are usually caused by Helicobacter pylori. Most common symptom of PUD is gnawing or burning pain in the epigastrium. Reservoir of infection- Humans Transmission takes place by fecal oral or oral-oral contact In the USA, H pylori is most prevalent among adult older than 60 years of age,African Americans, Hispanics, and lower socioeconomic groups

-There is an association between long-term infection with H pylori and the development of gastric adenocarcinomas or lymphomas. (Classed by WHO as a type 1 carcinogen). -Diagnosis: Invasive Methods( endoscopy and biopsy)

1) Rapid Urease Test(entire broth turns pink bc of urease production)

2) Microscopy: Giemsa or Silver Stain 3) Culture: Campy or Skirrow agar

Non Invasive Methods 1) Breath Test: Radioactive CO2 detected in the breath

after feeding Radioactive urea. 2) Serology: Detection of antibodies against H. pylori.

(Limitation—does not differentiate past from current infection) -Treatment: →Triple drug therapy →(proton pump inhibitor (PPI) and atleast 2 Ab and Bismuthsubsalicylate) →Omeprazole (PPI) +amoxicillin + Clarithromycin.Treat for 10-14 days. →Omeprasole/Bismuth subsalicylate + Amoxilillin/Tetracycline = Metronidazole/ Clarithromycin

Definitions: GASTROENTERITIS: Syndrome characterized by gastrointestinal symptoms including nausea, vomiting, diarrhea and abdominal discomfort (seen with food poisoning) ENTEROCOLITIS: Inflammation involving the mucosa of both the small and large intestine COLITIS: Inflammation involving the large intestine. Presents as dysentery, more lower abd DIARRHEA: Abnormal fecal discharge characterized by frequent and or fluid stool; usually resulting from disease of the small intestine and involving increased fluid and electrolyte loss DYSENTERY: An inflammatory disorder of the GIT often associated with blood and pus in the feces and symptoms of pain, fever, abdominal cramps; usually resulting from disease of the large intestine. Organisms usually invade via mucosa

DIARRHEA

Type Symptoms Stool findings

1 Diarrheas due to intoxication

Abd. cramps, vomiting, watery diarrhea, No fever.

Watery. No blood. No fecal leukocytes

2 Non-inflammatory or Secretory diarrhea

Watery diarrhea, Abd cramps, vomiting. Usually no fever.

Watery, Mucus+ No RBC. No fecal leukocytes

3 Inflammatory or Bloody diarrhea

Watery to bloody diarrhea, abdominal cramps,Tenesmus, Fever +/-

Mucus+ Blood+ Leukocytes ++

4 Hemorrhagic colitis

Watery, bloody diarrhea. Usually no fever

Blood+ No leukocytes

Penetrating Infections: Enteric Fever: Salmonella Typhi, Yersinia Enterocolitica

Diarrhea: inflammatory, bloody: 1)Bacterial Causes:

Campylobacter jejuni Salmonella enterocolitis/ GE Yersinia enterocolitica. Vibrio parahemolyticus. Shigella EnteroinvasiveE.coli

2) Parasitic Causes: EntamebaHistolytica Balantidum Coli

3) Toxin Mediated Colitis Hemorrhagic Colitis: EHEC Pseudomembranous Colitis: Clostridium Difficile

Diarrhea: non-inflammatory secretory: 1) Bacterial intoxications/ Toxin mediated food poisoning

S.aureus Bacillus cereus C.perfringens C.botulinum (no diarrhea)

2) Viruses Rotavirus ( most common cause in children) Noro/Norwalk Virus- ( most common among adults) 3) Bacteria ETEC**, EPEC, EAEC, Vibrio Cholerae 4) Parasites Giardia lamblia

Cryptosporidium Isospora belli. Cyclospora

Comparative Features of food Intoxications:

→short incubation periods means that the toxins have been pre formed.

Staphylococci -Gram positivecocci in clusters -Staphylocci is classified based on the presence of Coagulase Coagulase Positive: S. Aureus Coagulase Negative: S Epidermidis/S. Saprophyticus - major component of normal flora -20%-50% of healthy people are nasal carriers of Staph -Staph is a leading cause of nosocomial infections Staphylococcus Aureus -Gram positive cocciin grape like clustersNon-motile, Non-sporing -Aerobic, Facultative anaerobe -Catalase Positivebreak down H2O2 into water and oxygen -Coagulase PositiveEnzyme which converts fibrinogen to fibrin -Nutrient agar: small, opaque colonies with golden yellow pigment -Blood Agar: Beta hemolysis with clear zone around colonies -Grow in media containing high salt concentration (6.5%)*** -Ferments Mannitol

Etiology Incubation period

Common foods

Patho- genesis

Clinical findings

Staphylococcus aureus

1-6 hrs. Ham, potato salad, cream pastries, mayonnaise

Production of enterotoxin.

Vomiting, diarrhea

Bacillus cereus ( emetic type)

1-6 hrs. Rice. Heat stable toxin Vomiting and diarrhea

Bacillus cereus ( diarrheal type)

> 6 hrs Meat and vegetables.

Heat labile toxin Diarrhea

Clostridium perfringens

8-24 hrs Meat , poultry, gravies.

Enterotoxin Watery diarrhea

Clostridium botulinum

12-72 hrs Food botulism: Canned foods, Infant botulism: honey fed to infants.

A-B neurotoxin which acts on neuromuscular junctions and inhibits the release of acetylcholine.

Neuromuscular paralysis. CONSTIPATION NO DIARRHEA, Floppy Baby Syndrome.

-Virulence Factors/Disease: -Toxin Related Disease: Staphyloccal scalded skin syndrome Staphyloccal food poisoning

Toxic Shock Syndrome -Food Poisoning:

Foods :Processed meat, salty ham and salted pork, potato salad, macaroni salad, ice cream, cream or custard- filled pastry Short incubation period: 2-6 hrs, usually 4 hrs Source: Food Handler Virulence Factor: Enterotoxins A B C D E G -Toxins are preformed and are heat stable →Antibiotics wont work on preformed toxins -Can act as superantigens Mode of Action:

Stimulate release of inflammatory mediators in mast cells, increasing intestinal peristalsis and fluid loss, as well as nausea and vomiting. Stimulate reflexes in the abdominal viscera, which are transmitted to vomiting centers in the brain stem via the vagus nerve

-Pathogenesis of food poisoning: 1) Food containing protein is cooked (bacteria usually killed).

2) Then the food is contaminated by staphylococci on hands (competing bacteria have been eliminated. 3) Food is left out. Organisms incubate in food long enough to form/release toxins. Reheating will eliminate staphylococci but not the toxin 4) Food containing toxins is eaten and within 1-6 hours intoxication occurs.

-Symptoms: Severe nausea, vomiting, abdominal pain and diarrhea. NO FEVER. This is a self limiting condition. -Management and Prevention:

Sample: Food, Vomitus, Feces Microscopy: Not very useful Culture: Mannitol Salt Agar selective medium and identify by catalase and coagulase test. Toxin detection in the food

Self limiting, does not require antibiotics Prevention: Hand hygiene during food prep/screening of food handlers

Gram Positive Cocci in Clusters

Golden yellow pigment of S. aureus

Beta hemolysis of S. aureus

Mannitol salt agar showing yellow colonies of S.aureus.

Bacillus Cereus - Aerobic, Spore-bearing, Gram Positive Bacilli -Spore is within the bacillary body w/ a strepto bacillary appearance (chain) -Spores survive in soil / Nonfastidious in nature -Associated with two types of food poisoning which are toxin mediate. -Spores contaminate foods; germinate into vegetative forms and elaborate toxins -Types of food poisoning associated with Bacillus Cereus: Emetic Form: -Associated with fired rice, is heat stable -Emetic toxin which has action similar to Staphylococcal Toxin →reflex on neural receptors vaivagus to vomiting center -Abdominal cramps and vomiting , fever is uncommon -Incubation time of 1-5 hours and resolves within 9 hours Diarrheal Form: -Associated with meat, poultry and soups

-Diarrheal toxin stimulates adenylcyclase-cAMP resulting in outpouring of fluids - More diarrhea than vomiting, fever is uncommon -Incubation period of 8 to 16 hours, resolves within 24 hours

-Lab Diagnosis and Treatment: Detection of toxin, Self limiting condition, no antibiotics required →Grows on blood or nutrient Agar

Clostridium rod shaped, spore forming, anaerobe (quickly decolorize = pink) →anaerobic so NO superoxide dismutase = NO catalyze -Which forms of Clostridia are associated with food poisoning? C. Perfringens and C. Botulinum (sausage) -Main difference between C. Perfringensvs. C Botulinum? C. Perfringens causes diarrhea and Botulism causes constipation.

Clostridium species Disease

Clostridium perfringens Food poisoning ; Gas Gangrene

Clostridium botulinum Botulism and SIDS

Clostridium difficile Antibiotic associated diarrhea and Pseudomembranous colitis

Clostridium tetani Tetanus

Clostridium Perfringens -Morphology: -Gram positive bacilli, sub terminal spores →Non-motile, Anaerobic -Spores don’t take up the stain. When found in wound scab, causes by gas gangrene, →with Gas gangrene there will NOT be any spores only bacilli -Box car or toy car, is used to describe the morphology -Identification Tests: growth needs anaerobic media and anaerobic conditions Robertson Cooked Meat Medium

Toxins Produced by C. Perfringens: 12 differnent types of toxins Important toxins: Alpha toxin/ Phosolipase C ( lecithinase) Collagenase ( tissue destruction seen in gas gangrene) Toxins responsible for food poisoning: Enterotoxin( heat labile) produced by C PerfringensType A -Results in SecretoryDiarrhea. Associated with meat pies, gravy etc. -contaminated with spores Beta toxin produced by Type C. Results in bloody diarrhea →Pig Bel (also known as Darmbrands disease)rupture of theintestine →results in necrotizing enteritis. →Consumption of Pork when ingested with certain trypsin inhibitors ( sweet potatoes) ,allows the organism to survive →Seen in australia

Target/Double zone of hemolysis on blood agar Stormy fermentation in milk media:

Acid and gas formation in Litmus dsfasdfaadsaf dsfsadfamilk medium

NAGLER’S REACTION- demonstrated on Egg Yolk Agar. This neutralization test is used for C. Perfringens. It detects the alpha toxin, (lecithinase or phospholysin.) →Zone of opacity = Lecithinase breaking egg yolk

Pathogenesis of Type AClostridium Perfringens food poisoning: →Organism and spores in animal gut and soil →Contaminate raw meats, Spores survive cooking, germinate and multiply →Reheating insufficient to kill organisms, large numbers ingested →Organisms sporulate and produce toxins in intestines →Toxin alters cell membrane permeability with loss of fluids and intracellular proteins (watery diarrhea) Pathogenesis of Type CClostridium Perfringens food poisoning: →Organisms and spores in animal gut and soil →Contaminate raw meat or Inadequately cooked esp. pork →Large numbers ingested, with low protein diet (inadequate trypsin levels) →Organisms produce beta toxins in small intestine →which do NOT get destroyed due to low trypsin levels →Necrotizing enterocolitis. Severe abdominal pain, bloody diarrhea, risk of intestinal perforation Diagnosis and Treatment: Watery, non inflammatory diarrhea which is self limiting. →No fever/ nausea or vomiting Diagnosis: Usually made on clinical grounds: A. Growth of C. perfringens in food/ feces in very high quantities of ≥ 10^5 →food poisoning toxin usually detected in stool rather than food B. Detection of toxins by immunoassays →No antibiotic treatment required

Clostridium Botulinum -Different types of botulism: Food Botulism, Infant Botulism, Wound Botulism, Iatrogenic Botulism, and Inhalation Botulism. -Botulism transmitted through ingestion of food: Infant Botulism and Food Borne Botulism -Morphology: Large, Spore Forming, Gram Positive Bacilli, Anaerobic Rods 4 different groups producing 7 antigenically distinct Human infections mostly associated with A,B,E,F types

Spores germinate in the contaminated foods when anaerobic conditions are available (occurs in canned foods)

Mode of Action: Botulinum exotoxin is a very potent A-B toxin - NMJ, pre synaptic

Complexed with nontoxic protein that protects it during passage through the digestive tract. Binds to motor neurons pre-synaptically, are endocytosed and inactivates the proteins that regulate the release of acetylcholine (synaptobrevin). This results in flaccid paralysis, which is reversible when the action of the toxin ceases.

How to differentiate classical/foodborne botulism vs. infant botulism? Classical/Foodborne Botulism Infant Botulism

-Lab Diagnosis, Treatment and Prevention of Botulism: -Foodborne Botulism Detection of toxin in food, feces or serum →(it is preformed so the toxin can be seen in food) -Infant Botulism Detection of toxin activity in infant’s feces or serum. Culture of C. Botulinum from feces in large numbers.(there is NO toxic detection in food) -Toxin detected by Mouse Bioassay / Elisa -TreatmentMechanical Ventilator support, trivalent Botulinum antitoxin against A,B and E types. Gastric lavage and Metronidazole/ penicillin therapy -Preventionproper sterilization of canned foods, food storage at 4 deg C and in acidic conditions, avoid honey in children under the age of 1 Causes of non-inflammatory, SECRETORY DIARRHEA Bacteria:E.Coli: ETEC and EPEC, and V.Cholerae (these agents cause toxin mediated food poisoning) Viruses: Rotavirus, Noro/Norwalk Virus Parasites: Giardia Lamblia, Cryptosporidium, Isospora Belli, Cyclospora Bacterial causes of Secretory Diarrhea: E. Coli- Gram Negative Bacilli / Oxidase Negative Vibrio Cholera: Gram Negative curved bacilli / Oxidase Positive

Enterobacteriaceae Gram Negative Bacilli,motile and non-motile Facultative Anaerobic, Ferment Glucose Catalase Positive, Oxidase Negative Reduce nitrates to nitrites Lactose Fermenters: E Coli and Klebsiella Non-Lactose Fermenters: Shigella /Salmonella/ Yersinia/ Proteus

Consumption of preformed toxins present in canned foods contaminated with spores, which have survived the cooking process and produced toxins.

In 1-6 months old infants Weak cry, constipation, inability to

hold the head or feed well, failure to thrive.

Flaccid paralysis: FloppybabySyndrome. Possible cause for SIDS

Infants ingest honey/ milk powder contaminated with spores

Bacilli germinate from the spores Multiply and produce toxin Infectio-toxicosis

Weakness and dizziness after food consumption

Blurred vision with fixed and dilated pupils and dry mouth

CONSTIPATION Flaccid paralysis and

ultimately death due to respiratory paralysis.

Escherichia Coli -Morphology:

Gram negative bacilli, Motile with Peritrichous flagella Posses Fimbriae, Some form capsules →(K1 capsule type is associated with neonatal meningitis)

-Growth Characteristics of E. Coli: Lactose fermenting ( pink ) colonies of E. Coli on MacConkey’s Agar

Green iridescent colonies of E. Coli on eosin methylene blue agar

Antigenic Structure: O Antigen: Somatic antigen; polysaccharide and heat stable. (associated with soma/body of the antigen. H Antigen: (Hauch)Flagella protein antigen, which is heat labile. K Antigen: Capsular polysaccharide antigen associated with virulence. (E. Coli are serotyped on the basis of these antigens) There are 2 serotypes that need to know: O157:H7 this is the specific Ecoli strain EHEC O104:H4this is entero aggregated ecoli both ass. w/heamorrhagic colitis. Plasmids are transmitted via conjugation Diarrhea: 5 major groups of E. Coli cause diarrhea EHEC: Hemorrhagic, hemorrhagic colitis (bloody diarrhea) (H=hamburger) ETEC: Toxigenic, secretory diarrhea(Water and mucus, similar to Cholera) EPEC: Pathogenic, secretory diarrhea associated with pediatric population EIEC: Invasive, causes bloody diarrhea EAEC: Aggregative

Other E.coli EHEC

Sorbitol MacConkey’s agar is a screening medium. Note that EHEC colonies are pale (doesn’t ferment sorbtol) while other E.coli produce pink colonies

Identification tests: Motile

Catalase +, Oxidase –

Indole+, urease -, Citrate –

Sugar fermentation tests

Serotyping into O and H serotypes

EnteroToxigenic E. Coli ( ETEC) -most important cause of traveler’s diarrhea -Pathogenesis: 1) Ingestion of water/food contaminated with ETEC 2) Intestinal Colonization: via colonization factor / pilli 3) Production of labile and stable toxin.

-Labile Toxin:A-b toxin, ADP ribosylation of G protiens, stimulates the adenylatecyclase with Increase in cAMP -Stable Toxin: A-B toxin, stimulates the Guanylatecyclase with Increase in cGMP

4) Resulting in severe watery/secretory diarrhea -Diagnosis/Treatment: Enterotoxin detection by immunoassay, bioassay, DNA probes Treatment: Rehydration therapy for fluid and electrolyte replacement

EnteroPathogenic E. Coli ( EPEC) -most important cause of diarrhea in pediatric age group -Pathogenesis:

Adherence to epithelial cells of Small Intestine; subsequent effacement of the microvilli.(Attachment/Effacement Histopathology) BFP ( Bundle Forming Pili) : lead to initial aggregation and formation of microcolonies→ type 3 secretion acts as molecular syringe Bacterial adhesins called Intim cause polymerization of actin, loss of cell surface integrity and cell death Malabsorption and diarrhea

EnteroHemorrhagic E. Coli( EHEC)/Verocytotoxigenic E. Coli VTEC)/ O157:H7 E. Coli -most important E. Coli causing outbreaks in the USA. (H=Hamburger) -Sources of infection due to EHEC (O157:H7) Contaminated ground beef, lettuce, apple juice etc. -Pathogenesis of Enterohemorrhagic E. Coli: EHEC attaches and effacesthe GIT epithelial cell

Produces Shiga like toxin which inhibits protein synthesis by acting on 60S ribosomal subunit. Toxin can cause Hemolytic Uremic Syndrome: HUS characterized by acute renal failure, thrombocytopenia, and microangiopathic hemolytic anemia

-Clinical Features: Incubation period of 3-4 days mild diarrhea to hemorrhagic colitis watery, bloody diarrhea with abdominal pain, vomiting. -LabratoryHEC forms pale colonies on Sorbitol MacConkeys Agar -TreatmentRehydration therapy, Antibiotics are not indicated

ETEC Vibrio cholerae EPEC

Imp features Travel to developing

countries

Travel to an endemic area such as Latin

america, Asia.

Epidemic/ pandemic

gulf coast/ Louisiana, water, shell fish.

Second most common cause of

infantile diarrhea.

Agent

characteristics

GNB, oxidase neg,

catalase +, LF colonies

on Mac Agar.

GNB (curved), Oxidase positive.

Polar flagella,

Darting/ shooting star motility

Prefers alkaline pH, TCBS-yellow

colonies.

Like other E.coli

Pathogenesis Attachment with fimbrial

adhesins & toxin

production (LT and ST).

Toxins detected by

immunoassay, bioassays,

DNA probes

A-B toxin, attaches to epithelial cells of

microvilli at brush border epithelium via

TCP

catalyses ADP ribosylation , increases

adenylate cyclase, cAMP mechanism

with copious fluid loss.

E.coli produce bundle forming pili

and an adhesin called intimin,

adhere to M cells , cause

rearrangement of actin and

effacement of brush border

microvilli.

C/F Profuse watery diarrhea Intense vomiting and watery diarrhea,

copious fluid loss and dehydration

(Rice water stool)

Profuse watery diarrhea.

Diarrhea with or without ileitis

Treatment Fluid and electrolyte

replacement

Fluid and electrolyte replacement,

Doxycycline/ ciprofloxacin(if needed) Beta lactams/Fluroquinolones

EnteroinvasiveE.Coli( EIEC) -Causes bloody diarrhea -Pathogenesis: Plasmids mediated proteins help invade the colonic mucosa Multiply in the cytoplasm, move into adjacent epithelial cells.

Epithelial cell destruction with inflammatory infiltration leads to colonic ulceration. (EIEC resembles Shigella in its pathogenesis of enteroinvasion and lateral extension, NO shiga toxin here)

-Clinical Features: Inflammatory diarrheaie.,dysentery with blood and mucus in the stool; fever, vomiting abdominal cramps and tenesmus

→Lateral extension leads to inflammation in the colonic cells →Results in micro abscess and ulcers blood diarrhea Treatment: antibiotics floroquinolones

Secretory Diarrhea by Bacteria

Vibrio Gram Negative curved bacilli Diseases Associated with Vibrio Species Disease

Vibrio Cholerae Cholera: Profuse watery diarrhea

Vibrio Parahemolyticus Food Poisoning, bloody diarrhea Produces hemolysin

Vibrio Vulnificus Diarrhea/Cellulitis/Septicemia (alcoholics). Ingestion of sea food, or enter skin

Vibrio Cholerae -MorphologyGram Negative, Curved Rod Polar Flagella, Darting/Shooting Star motility Grows easily on nutrient and blood agar, alkaline conditions -Laboratory: Selective Medium:

- On TCBSAgar( Thiosulfate-Citrate-BileSalts- Sucrose

Agar)Vibrio Cholerae produces yellow colonies -Identification Tests:

Catalase Positive, Oxidase Positive, Ferments Sucrose Confirmation of identity by serotyping with antiserum (hanging drop test). If antiserum stops movement =Vibrio →emulsion and add antiserum, agglutination =Vibrio

-Epidemiology: Reservoir: Human Colon (no long term carrier) Shellfish/Oysters/Sea Mode of transmission:

A) Fecal-Oral contamination due to food/water (contaminated) B) Ingestion of raw/uncooked fish C) Chances of developing cholera increases multifold when the patient

is on antacid therapy (From 10^7-10^8 to 10^3 -10^5 organisms of cholera after antacid therapy)

-Pathogenesis of Cholera: →Transmission: Fecal Oral Spread, High doses needed for initiating infection

1) Ingestion of food/ water contaminated with V. cholerae 2) Colonization of small intestine with piliand elaboration of toxin(Toxin

regulated co-pilus; trc- pilus) 3) Enterotoxin binds to Gm1 ganglioside receptors This produces a

labiletoxin called cholreagen / cholera toxin 4) Stimulates adenylcyclase and increases cAMPwith massive secretion of ions

and water. 5) Dehydration Hypovolemic Shock. 6) Death Types of Cholera and Strains of V.cholerae -Two types of cholera, O2 and Non O2(which don’t agglutinate by antiserum) -Important Features of Cholera Toxin:

A-B toxin B subunit attaches to GM1 ganglioside receptor and allows internalization of A

subunit A subunit catalyzes ADP-ribosylation which activates adenylatecyclase Increase in cAMP bring forth efflux of ions and water from infected

enterocytes. Massive loss of fluids and electrolytes ( hypokalemia- msucle weakness, cramps,

arrhythmias) Bacteriophage with Ctx( pie) gene is resposnsible for the toxin production -Clinical Features:Rice water stools, hypovolemic shock, death -Diagnosis: Rice watery stool, Microscopy: Darting Motility, Culture on TCBS, confirmation with tests and antiserum -Treatment:

Fluidand Electrolyte replacement Doxycycline/ Ciprofloxacin in severe cases.

-Prevention: Proper sanitation, Vaccination prior to travel to endemic countries →Both vaccines are oral O1 strain with the toxin strain in it, and second is O1 with O139 in it

Viruses Associated With Diarrhea Calicivirus: Rotavirus and Norwalk Virus Calicivirus -Naked, Icosahedral -Positive Sense, ssRNA -Cup shaped depressions on surface of capsid -Cannot be cultivated -Important causes of viral gastroenteritis -Prototype: Norovirus (Norwalk Virus)

Norwalk Virus: -Epidemiology:

Most common cause of Non Bacterial Gastroenteritis in the USA →in adults or children >5 Viral GE/Viral Diarrhea/ Winter vomiting disease Outbreaks-any time of the year, seasonal peaks during winter Common setting for outbreaks: Cruise Ships, schools, resorts, restaurants, hospitals, and nursing homes. This is extremely contagious and causes a delay in gastric emptying which causes vomiting. Outbreaks are associated with: Contaminated water, Salads, Shell Fish →infective dose is 10-100 - very contagious.

-Transmission: Norwalk virus is resistant to heat (60 deg. Celsius), pH-3, detergents and chlorine levels of drinking water Mode of Infection:

1) Feco-oral contamination; through fomites 2) Damage to the intestinal brush border prevents proper absorption of water and nutrients

-Clinical Features: Short Incubation period: 1-2 days Acute onset of watery diarrhea, nausea and vomiting Mild fever may or may not be present No blood or pus in stool. Complication: Dehydration -Diagnosis: Real Time PCR/Elisa -Treatment: Symptomatic: rehydration, bismuth subsalicylate to reduce GI symptoms -Prevention: Safe disposal of stool, effective hand washing, Purification of water

Rotavirus -Most common cause of viral infantile diarrhea -Morphology:

NonenvelopedDS RNA Virus with linear segmented RNA (10-11 segments)- allows for reassortment/recombination

Icosahedral with double shell Outer capsid proteins: VP7 and VP4 Internal structural protein: VP6 6 Non structural proteins: NSP4 acts as an enterotoxin -Pathogenesis:

1. Infection acquired by feco-oral contamination 2. Attach to villi of small intestine and multiply in enterocytes 3. NSP4 (a virally encoded protein) acts as an enterotoxin and triggers

signal transduction and induces secretion 4. Impaired sodium and glucose absorption due to replacement of

damaged cells by non absorbing immature crypt cells.

-Clinical Features: -Infants and children most affected ( 6 months -2 years) -Incubation period: 1-3 days -Watery diarrhea, fever, abdominal pain, vomiting -Self limited illness in most cases ( 3-8 days)

-Predominance during winter months, Infections caused as community outbreaks/ in nosocomial setting -Features of dehydration: Sunken eyes and cheeks, sunken fontanelle, few or no tears, dry mouth/tongue, decreased skin turgor

-Lab diagnosis/ Treatment/ Prevention -Lab Diagnosis-ELISA for antigen in stool, Immune electron microscopy, RTPCR

-Treatment: fluid replacement to correct the loss of electrolytes and water. -Prevention: Waste water treatment, Vaccines: Oral Vaccines -Rota Virus Vaccines: RV5 Rototev(bovine strain, pentavalent) →RV1 Rotarix (GSK) G1P{8} →both vaccines are given in three doses 2, 4, and at 6 months Secretory diarrhea by Viruses

Secretory Diarrhea by Parasites Parasites associated with watery diarrhea: -Giardia -Cryptosporidium -Cyclospora -Isospora( also known as Cystoisospora)

Giardia Lamblia -An intestinal flagellate parasite which is a common cause of travelers diarrhea -Morphology: Trophozite Form:-Half pear shaped organism with tennis racquet appearance/kite shape -Has 8 flagella and 2 axostyles arranged in a bilateral symmetry -Has a large ventral suction disc -The cytoplasm contains two nuclei and two parabasal bodies -Posses ‘Falling Leaf’ motility Cyst Form (infective form) -Ellipsoidal forms with smooth wall, (9-12 micro meters) -The cytoplasm contains four nuclei,axosytle and remnants of flagella -Epidemiology: Giardia has a worldwide distribution

The most frequent protozoan intestinal disease in the US and the most commonly identified cause of water-borne disease Agammaglobulinemia/IgA defiency-predisposes people to a more chronic girardia

Associated with: • breakdown of water purification systems, • drinking from contaminated streams, • travel to endemic areas (Russia, India, Rocky Mountains, etc.) • day care centers.

-Life Cycle: • Primary host: Man. • Other hosts: beavers, pigs and monkeys may serve as reservoirs. • Mode of infection: ingestion of cysts, usually in contaminated water. • Excystation occurs in the duodenum. Trophozoites colonize the upper

small intestine with ventral suction disc. • The free trophozoites are converted into cysts which are passed in the stool.

-Pathogenesis and Clinical Features: Covering of the intestinal epithelium by the trophozoite and flattening of the mucosal surface via the suction disc results in malabsorption of nutrients. Steatorrhea: Flatulence, abdominal distention, nausea and foul smelling bulky, explosive, often watery, diarrhea The stool contains excessive lipids but rarely any blood or necrotic tissue The more chronic stage is associated with malabsorption, disaccharidase deficiency and lactose intolerance

“Gay Bowel Syndrome” -Oral/anal contact with homosexuals can transmit Giardia

-Diagnosis and Treatment: Absence of fever Less of mucus and lack of blood in the stool Presence of cysts or trophozoites in the stool

Enterotest test for demonstration of trophs in the duodenum using a string device that is swallowed Antigen detection test in the stool sample- very sensitive Saline- for the trophozoit forms of the parasites Iodine Mount- used for cyst in stool samples Treatment: Metronidazole is the drug of choice

-Prevention: Filtration of water, chlorination of water sources -Treatment: Metronidazole is DOC

Cryptosporidium Parvum - An intracellular parasite of ilieal epithelial cells -Source: Farm Animals -Common cause of chronic diarrhea in HIV infected patients -Mode of infection: Ingestion of C. Parvum oocysts containing many sporozoites. -Pathogenesis, Clinical features, Lab Diagnosis/Treatment:

Severity of diarrhea depends on load of organisms and immune status of the host Symptoms: Asymptomatic to intractable diarrhea.

-Aids Patients: chronic, voluminous, protracted watery diarrhea, cramping abdominal pain and weight loss

Lab Test: Acid fast stain of stool sample shows acid fast ooscysts (3-5 micro metes in size)

Identification based on Size is very important: Cryptosporidium : (3-5 micro meters) Cyclospora: (7-10 micro meters) Isospora: (15-25 micro meters) Other test: Direct Immunofluorescent testing, biopsy studies, Polyermase chain reaction for detection of oocysts in stool samples and environment Treatment: Nitrazoxanide, puromycin/azithromycin/paramomycin

(acid fast stain of cryptosporidium of stool shows acid fast oocysts (3-5um in size))

CyclosporaCayetanensis -Fecal-Oral route -Direct transmission from person to person UNLIKELY -Food or waterborne USUALLY -Associated with contaminated raspberries, basil and lettucecontaminated with oocysts -Symptoms of Cylosporiasis:

Diarrhea protracted approx. 6 weeks; esp. in HIV positive patients, cramps, dehydration

South America and Nepal are common places where this is endemic

-Lab Diagnosis: Autofluorescent -Demonstration of acid fast oocysts in stool sample →( 7-10um in size) -Treatment:Trimethoprim-sulfamethozaxole (Bactrim)

Isospora Belli -Increasing incidence in AIDS patients. -The infection occurs via the oro-fecal route. -The infective stage of the organism is an elliptical oocyst. -Cause severe watery diarrhea. -Diagnosis by demonstration of acid fast elliptical oocysts. -Mild infections resolve themselves with rest and mild diet. -Sheathers Sucrose Technique- used to concentrate the parasites to view under the microscope -Heavier infections can be treated with TMP-SMZ.

Acid fast oocysts of Cryptosporidium (3-5um) and Cyclospora (7-10um).

Acid fast and elliptical oocysts of I.belli.

Diarrhea by Parasites

Invasive Bloody Diarrhea: Causes Campylobacter, Shigella, EIEC, Salmonella(gastroenteritis), Yersinia, EntamebaHistolytica Invasive in nature, Inflammatory Response, Patient may have fever, Abdominal Pain, Tenesmus Stool: contains a lot of mucus ( due to irradiation of gastric mucosa) and leukocytes and usually has blood Toxin Mediated Bloody Diarrhea: Causes Hemorrhagic Colitis: EHEC Pseudomembranous colitis: Clostridium Difficile

Campylobacter: -Morphology: Comma shaped, thin, gram negative rods which are motile w/ polar flagella →non fermenter Visible as ‘S’ shaped forms ( GULL wing forms) in a stool specimen Microaerophilic, Grown on special media under reduced conditions Grows well at 42 degrees C**. Catalase positive, Oxidase Positive -Reservoirs of Infection: Infections are zoonotic. ( Animal gut harbors the organism and under stress can shed large amounts of organisms in its feces) Common sources of infection: Contaminated eggs, chicken, milk Handling puppies and kitten (puppy butt) Uncommon to be transmitted through food handlers. -Epidemiology: Most common cause of invasive bacterial gastroenteritis in the United States Epidemics are most common in the spring and fall months Peak incidence; infants and children/20-40 years -Pathogenesis: Conditions which decrease gastric acid secretions favor the disease** Agammaglobinenemia- predisposed to the disease Low infectious dose( 500 organisms) Invasion of the intestinal mucosa with ulceration and abscess formation and infiltration of lamina propria with neutrophils, mononuclear cells. Inflammatory diarrhea with blood and inflammatory cells in the feces Campylobacter Fetus- has an “S” Antigen on its surface which can block the attachment of C3b, preventing compliment mediated cell lysis, when c3b attachment is inhibited the organism can enter the bloodstream and causes septicemia -Complications: Cross reactivity between surface lipopolysaccharide of C.jejuni and peripheral nerve glycosphingolipids →Immune related: →Symmetric weakness over days, recovery over months(GB syndrome O19) →Painful joint swellings that lasts for weeks to years.(Reactive arthritis) -Diagnosis: Microscopic picture: curved rods, “Gull Wings” appearance Growth on CAMPY blood agar at 42 deg. C Skirrows medium/ Butzlers medium Oxidase Positive, Gram Negative curved bacilli, microaerophilic -Treatment/Prevention: Self limited usually wont require antibiotics, fluid and electrolyte replacement Antibiotic of choice: Macrolides/Fluoroquinolones Prevention: Safe handing and proper cooking of foods. →Prevent contamination of water and cross contamination.

Salmonella -Diseases caused by Salmonella: Septicemia/food poisoning/osteomyelitis , Enteric Fever (Typhoid) -Salmonella Food Poisoning/Gastroenteritis Non-Typhoidal Salmonellae -S. Enteritidis -S. Typhimurium Source: Eggs, Chicken, Reptiles, Turtles Diarrhea: Watery/occasionally bloody/ abdominal cramps/ fever/myalgia -Enteric Fever Typhoidal Salmonellae

-Salmonella Typhi -Salmonella Paratyphi A

Source: Human Carrier Clinical: High fever, diarrhea/constipation, Rose Spots, hepatospleenomegaly* -Salmonella: Morphology Gram negative rods.Motile with peritrichate flagella.Sensitive to Acid Posses Somatic O, Flagellar H and Capsular Vi Antigen -Growth/Identification: Grow on MacConkey’s Agar: NLF or pale colonies Selective medium: Salmonella Shigella Agar/ Hektoen Enteric Agar Catalase Positive, Oxidase Negative. Produces H2S* → Further Identification by sugar fermentation and agglutination with antisera -Antigenic Structure: 1) Somatic Antigen (O) -O antigen is LPS complex of the cell wall. It is heat stable and less immunogenic. 2) Flagellar Antigen (H) -H Antigen: Heat labile protein of flagella which is strongly immunogenic 3) Surface Antigen (Vi) -Associated with outer coat of salmonella which provides a weak slime capsule to help induce phagocytosis and promotes uptake by macrophages in which salmonella will grow -Detection of Anti O and Anti H antibodies by WIDAL test which is an agglutination test (evoke the production of antibodies against the O antigen, knows as anti O ,

some against H known as anti H and others against Vi)is used for the diagnosis of Enteric Fever. (Note: you cannot use the WIDAL test for food poisoning, only used with Typhoidal Salmonella) -Virulence Factors: Vi Antigen: withstands complement mediated killing Antigenic Phase Variation: Help to evade the action of antibodies Intracellular Existence: Resist killing within macrophages by inhibiting fusion of phagosomes with lysosomes, withstands oxygen dependent and independent killing and tolerate acids within phagocytic vesicles Endotoxins

Salmonella Gastroenteritis -Sources of infection: Exotic Pets: Turtles, SnakesPoultry: Meat and Eggs -Pathogenesis: Ingestion of organisms (infectious dose-10^5), people on antacids/proton pump inhibitors/achlorhidric/gastrectomy are more susceptible to infection- requires less of an infectious dose Invasion of Mucosa in the ileo-cecal junction. Penetration of the intestinal epithelial cells ( peyers patches), inflammation and shallow ulcerations. Release of prostaglandins, Increased cyclic AMP, Loose Diarrhea -Clinical Findings: Fever, Nausea, Vomiting, Diarrhea which is occasionally bloody, abd pain, myalgia, headache Incubation period: 8-48 hours (long) -Complications: Important cause of Osteomyelitis in those with sickle cell disease Septicemia in HIV/Immunodefiency Patients Endocarditis/Arthritis -Lab Diagnosis: Sample: Feces Culture: on selective media: MacConkeys Agar, Hektoen Enteric Agar Growth of NLF colonies: motile. H2S producer -Treatment/Prevention: Antibiotics not recommended for enteritis For septicemia: Ampicillin/Fluoroquinolones/3rd gen. cephalosporin/TMP-SX Proper cooking of poultry and avoidance of cross contamination

Enteric Fever ( Typhoid) Human carrier harbors Salmonella in the gall bladder/urinary tract -Pathogenesis:

a. Ingestion of food/ water contaminated with S.typhi from a carrier b. Incubation period: 7-14 days c. Bacteria attach to and invade M (microfold) cells of Peyer’s patches

and enterocytes in ileocaecal region d. Bacteria phagocytosed and mutiply intracellularly, reach the basolateral

side of M cells e. FEVER: Bacteria in Peyer’s Patches, mesenteric duct and blood stream:

Primary Bacteremia f. Hepatosplenomegaly-Organs like Liver, Spleen, bone marrow are

seeded g. Step Ladder Pyrexia: Secondary wave of bacteremia with onset of

disease. h. Salmonella multiply in bile in the gall bladder i. Peyer’s patches and lymphoid follicles of intestine involved. Hyperplasia

and necrosis of Peyer’s patches. -Clinical Findings:

Symptoms: Fever, Headache, Anorexia, Loss of appetite, Myalgia, Diarrhea/Constipation Signs: Step Ladder Pyrexia, Hepatosplenomegaly, Skin Rash: Rose Spots( develop 2nd-3rd week of illness), Leucopenia ( due to destruction of bone marrow), Bradycardia

-Complications: Major complications: GI hemorrhage and perforation of bowels with peritonitis. After recovery few may become carriers. Sites: Gall bladder, biliary passages

-Laboratory Diagnosis of Enteric Fever: 1.Blood/ Bone marrow culture for S.typhi Antigen detection test. 2.Demonstration of antibodies: 2nd week onwards:WIDAL test: High titers of antibodies against O and H antigens 3.By week 3, stool cultures will be positive 4.Urine cultures are positive

Enteric Fever Treatment/Prevention: Treatment: Fluoroquinolones/ 3rd generation cephalosporins.

Prevention: Hygienic measures, Treat carriers Vaccines: 1. Attenuated oral vaccine of S.typhi strain 21(Ty21a). 2. Killed vaccine-given parenterally. 3. ViCPS- capsular polysaccharide vaccine.

Shigella -The bacteria causing BACILLARY DYSENTRY -Morphology : Gram negative bacilli of Enterobacteriacae Family Facultative anaerobic, Nonmotile Non Lactose Fermenter, Oxidase Negative Resistant to acid( very few organisms can cause infection-10) H2S-nonproducer -Different Species:

1. Shigellasonneimost comon in USA 2. Shigellaflexneri developing countries 3. Shigellaboydii 4. Shigelladysenteriae produces shiga like toxin, produces a STX gene, clips

out 60sRNA and inhibits protein synthesis -Epidemiology: Source: another human being; NO animal source

Mode of Infection: Feco-Oral contamination through finger, fomite, feces, flies, gay bowel syndrome Low infectious dose Setting: Day care centers, old age homes, armybarracks, public toilets, including flush handles and doorknobs.

-Pathogenesis: Reservoir: Only humans.(colon) Transmission: Fecal oral spread. (Resistant to acid) Target: M cell invasion.(colonic mucosa) Bacilli enter the cytoplasm, multiply and polymerize actin jet trails and

spread laterally extending it self Abscess and Ulcers produced. Invasion is rare. (No Bacteremia) Toxin: Shiga toxin: produced by S.dysenteriae, type 1.(has neurotoxic,

cytotoxic and enterotoxic activity). The A-B toxin inhibits protein synthesis by clipping 60S ribosomal

subunit.This toxin has special infinity for the receptors gb3 in the vascular endothelium of the kidneys, causing a destruction of endothelial cells making the surface rough and causing platelets to aggregate and clot resulting in hypo perfusion of the kidney- can cause HUS and hemolytic anemia-don’t give antibiotics for HUS

-Clinical Features: Source of infection: Human case of Shigellosis. 1-10 bacteria can initiate infection. Incubation period: 1-4 days. Fever, lower abdominal pain, tenesmus, watery diarrhea to begin with,

then bloody stools. (dysentery) Complications: arthritis, conjunctivitis, polyneuritis ie. Reiter’s

syndrome( Reiters syndrome is now called reactive arthtritis) “Cant see, Cant pee, Cant Climb a Tree” Hemolytic Uraemic syndrome ( HUS)

-Diagnosis: Stool microscopy:Plenty of inflammatory cells with RBCs and mucus Stool culture:

A) MacConkey’s Agar: NLF Colonies B) Salmonella-Shigella Agar, Transparent colonies with no black center Nonmotile, non H2S producer

-TreatmentFluid and electrolyte replacement -AntibioticsTrimethoprim-Sulfamethoxazole/ Ciprofloxacin -Prevention Proper sewage disposal, potable drinking water ; hand washing. Other Causes of Toxin Mediated Bloody Diarrhea: ClostridumDifficile and Enterhemorrhagic E. Coli ClostridumDifficile -Morphology: Gram-positive anaerobic bacilli, produces spores Surface layer proteins bind to cell surface and C. Difficile elaborates two toxins:-Toxin A:Enterotoxin MOA: Attracts neutrophils and stimulates their release of cytokines; Cytopathic effect with disruption of cell to cell junction and increased permeability of intestinal wall causing diarrhea -Toxin B:Cytotoxin MOA: Depolymerization of actin with destruction of cellular cytoskeleton Pathogenesis:Consume broad spectrum Ab. Expansion of Toxin A and Toxin B -Antibiotic associated diarrhea - benign self limited diarrhea -Pseudomembranous Colitis:Life threat condition with severe bloody diarrhea -Diagnosis:

1. Demonstration of enterotoxin/ cytotoxin in stool samples. 2. Immunoassays, tissue culture assays. 3. Recent techniques: detection of C.difficiletoxin genes in stool sample by

Nucleic acid amplification 4. Gene detection via PCR quick detection

-Treatment: Discontinue implicated antibiotics, →Therapy with Metronidazole/Vancomycin

Yersinia Enterocolitica -Associated with gastroenteritis and pseudo-appendicitis -Yersinia Species: association w/ human diseases -Yersinia Pestis Plague

-Yersinia Enterocolitica Gastroenteritis, Mesenteric Lymphadenitis(intense abdominal pain), Reactive Arthritis(it is immune mediatedAg Ab complexes form and are deposited in the joints attract complements inc inflammation and pain in the joints) -Yersinia Pseudo-tuberculosisGastroenteritis, Septicemia, Osteomyelitis

-Features/Transmission: -Gram negative, fermenter, oxidase negative, has LPS

-Ability to grow in cold temperatures at 4 deg. C: used for cold enrichment of the organism. -Exposure to contaminated food products (meat, milk, water- these are foods you store in the refrigerator) -Exposure to contaminatedblood products( parental route), Yersinia is a siderophilic organism hence it loves blood and those with hemochromatosis -Common in Scandinavia, northern Europe, Colder area of N. America (cold) -Increased incidence during the cold temperatures

-Clinical Findings: Involves mainly ileum. Most common in children Patients present with fever, abdominal pain, diarrhea. Chronic cases result in enlargement of mesenteric nodes, which are

painful and mimic Appendicitis. May be associated with Blood transfusion associated bacteremia.

-Treatment: Usually self limited. Antibiotics needed in severe condition. Susceptible to Cephalosporins, TMP-SMZ, Tetracycline.

DIARRHEA: inflammatory, bloody Dysentery

TROPHOZOITE ( VEG. FORM)- Notice the ingested RBC

Bacterial causes: Campylobacter jejuni Salmonella enterocolitis/ GE Shigella Yersinia enterocolitica. Vibrio parahemolyticus. EnteroinvasiveE.coli Clostridium difficile.

Parasitic causes: Entamebahistolytica Balantidium coli

Clinical Findings of Dysentery Invasive in nature Inflammatory response Stool: contains mucus and leukocytes and usually has blood. Patient may have fever Abdominal pain. Tenesmus.

Parasitic Dysentery: Entamebahistolytica, Balantidium Coli Parasitic dysentery is sometimes caused by Balantidium coli is the only organism that forms cilia on the surface associated with pigs

EntamoebaHistolytica -Geographical Distribution: cosmopolitan -Host: man. -Habitat: Ileo-caecal and sigmoid-rectal regions of the intestine. -Infective stage: Mature Quadrinucleate cyst.** -Mode of infection :Feco-oral Eating contaminated raw vegetables (salads) Drinking contaminated water Flies and food handlers (cyst passers)

-Epidemiological setting: 1. Visit to endemic countries 2. Military and refugee camps 3. Hospitals for mentally ill 4. Prisons 5. Overcrowded day care centers

-Morphological Forms: 1) TROPHOZOITE (VEGETATIVE FORM): Sluggishly motile form with pseudopodia and inclusions like glycogen and

Mature cyst: Quadrinucleated Cyst.

Pre-Cyst

Segment of colon showing Intestinal ulcerations

ingested RBCs from the host. The Trophozoite is for destruction and the cysts are for infection. 2) Precyst: Round or oval with blunt pseudopodia 3) Cyst: Spherical with refractile wall. Immature cyst has glycogen mass & chromatoid bodies (immature cysts) Mature cyst has four nuclei (quadrinucleated cyst)

-Amebiasis: Intestinal Manifestations Intestinal ulcerations: Flask shaped ulcers. Dysentery: stool with blood , mucus and pus. Perforation, secondary bacterial invasion Peritonitis

Tissue destruction due to CYTOLYSIN which lyses colonic epithelial cells and results in tissue destruction. Also inflammatory cells are attracted to the site and undergo lysis which alters cell permeability with increase in intracellular calcium levels

-Extra- Intestinal Manifestations: Brain Abscess Lung Abscess Skin Lesions Liver Abscess (common) Produces Chocolaty/Anchovy Sauce pus from the abscess -Laboratory Diagnosis:

1) Direct stool examination: Saline wet mount: shows

sluggishlymotile trophozoites. Iodine mount: may show cysts. Other stains: iron hematoxylin ortrichrome stain.

2) Concentration techniques for cysts. 3) ELISA: for detection of serum antibodies esp. in extra-intestinal

amebiasis 4) PCR for the serum Antibodies for liver and brain abscess Acute dysentery: 5) Metronidazole followed by Diloxanide 6) Asymptomatic cyst passers: 7) Diloxanide/ iodoquinol

-Treatment: 1) Acute dysentery:

Metronidazole followed by Diloxanide 2) Asymptomatic cyst passers:

Diloxanide/ iodoquinol

HP section of colon showing Flask shaped ulcers.

Shigella spp EIEC E.histolytica

Imp features Humans are the only reservoir. Infective dose: Very low. Commonest sp: S.sonnei

Seen in children in

developing countries, rare

in USA.

Higher incidence in

developing countries,

military camps, refugee

camps.

Agent

characteristics GNB, nonmotile, NLF colonies

on Mac Agar. GNB, LF colonies Parasite with trophozoite

and cyst form.

Pathogenesis Invasive in large intestine and

terminal ileum. Invade M cells,

Rearrange cellular actin to jet

propel into adjacent cells. Shallow ulcers. Shiga toxin: AB toxin—inhibits

protein synthesis, endothelial

damage

By invasion Attaches to mucosa of

large intestine via

adherence proteins, tissue

destruction and ‘ flask

shaped ulcers’,

hemorrhage and necrosis. .

C/F Bloody dysentry with plenty of

leukocytes, abdominal cramps,

tenesmus, fever. Stools are

liquid and scant and mostly

contain pus, mucus and blood.

Same as shigellosis. Dysentry with mucus,

RBCs and leukocytes in

stool Extraintestinal: abscesses

in organs

Treatment S. dysenteriae needs antibiotics. Ampicillin / TMP-SMX/

Fluroquinolones

Same as shigellosis Metronidazole followed

by iodoquinol

Others S.dys, type 1 produces Shiga

toxin which acts as a neurotoxin. Complication—HUS.

Doesnot cause HUS. Complication: Amebic

liver abscess

Amebic Liver Abscess

Chocolaty/ ANCHOVY SAUCE pus from the abscess

Balantidium coli: the parasite causing ciliate dysentery B.coli produces infection which is similar to that seen in amebiasis. Ciliate parasite usually seen in pigs. Trophozoite and Cyst forms have Macro and Micro nuclei. Transmission is due to Feco- Oral contamination with cysts.

Causes dysentery Treatment: Metronidazole

Helminth Parasites associated with GIT Infections

Trophozoite and Cyst forms of B.coli

Enumeration of important helminths infecting the GIT

Enterobius vermicularis pin/seat worm (most common in USA) Ascaris lumbricoides round worms (most common world wide) Ancylostoma and Necator round worm Trichuris trichiurawhip worm Diphyllobothrium latum fist tail worm Echinococcus granulosus Dog tail or hydatid worm Fasciola hepatica common liver fluke Clonorchis sinensis Chinese liver fluke NEMATODES AscarisLumbricoides/ Round worm Commonest Helminth found world wide. Largest Nematode infecting man. Adult worms are cylindrical and have an earth worm like appearance Eggs are bile stained (yellowish), oval or elliptical with a knobby appearance Produce eggs or ova which are shed in the stool unfertilized is much bigger then fertilized

Adult AscarisLumbricoides (Round Worm)

-Morphology -MODE OF INFECTION: ingestion of mature eggs. -HABITAT: small intestine. ( jejunum/illium) -SYMPTOMS AND COMPLICATIONS: Vague abdominal pain, abdominal distension,

intermittent loose stool. Loeffler’s syndrome/ pneumonia: Cough,

wheezing due to movement of the larvae. Intestinal complications: bolus of worms

can lead to intestinal / bile duct obstruction.***

-DIAGNOSIS : Stool saline mount: fertilized or

unfertilized ova in stool. -TREATMENT:

Mebendazole/ Albendazole

Hookworms: Ancylostomaduodenaleand NecatorAmericanus important causes of iron deficiency anemia ( microcytic hypochromic anemia)

A.d N.a sucks blood AncylostomaCaninum and Brasiliense are animal hookworms which can affect human beings and cause cutaneous larva migrans

-Adult worms reside in the small intestine and have sharp mouth parts. -Eggs are non bile stained, oval and have blastomeres within. -Larvae hatch out of the eggs and are infectious

Unfertilized and fertilized ova ( lumpy/bumpy/bile stained yellow)

Form eggs bastomeres entire eggs are passed out in the stool There are two forms of larva Rhabditi form and filariform →falari is the infective form (right, thin and long) -Mode of infection

Penetration of skin by filariform larva Larvae migrate through bloodstream, lungs and then are localized in the jejunum. Adult forms suck blood and cause iron deficiency anemia.

-Diagnosis: Demonstration of Ova in stool -Treatment: Mebendazole and iron therapy

EnterobiusVermicularis Synonyms: pinworm, seatworm Live in the caecum and vermiform appendix.

MODE OF INFECTION: Autoinfection by anus-hand-mouth route or from soiled bed clothes/

pyjamas. Exposure to viable eggs in the environment

Symptoms: perianal or perineal itchingsevere at night, caused by the migration of

female pinworms to the anus to lay eggs. Nocturnal enuresis. May cause appendicitis.

Lab Diagnosis/Treatment: NIH (National Institute of Health swab) for perianal swabbing. Stool examination: for ova. Scotch Tape Method Treatment: Mebendazole.

Adult HookWorms in the Mucosa

Sharp teeth in the oral cavity.( hook on and suck blood causing anemia)

Egg of Hookworm/ 4 blastomeres

Larva of Hookworm

Eggs of Enterobiusvermicularis: non bile stained, planoconvex (asymmetrical) , and have a transparent shell and a coiled larva

TrichurisTrichiura: Whip worm Mode of infectioningestion of

eggs. Adult worm is whip shaped and

localizes in caecum. Eggs arebile stained, barrel shaped and have bipolar mucus

plugs. Complications:

Causes appendicitis. Inflammatory effect: large intestinal mucosal inflammation,

edematous rectum, rectal prolapse. Rectal bleeding may lead to anemia

Treatment: Albendazole. "Tricks you then whips you"

Cestodes: Tapeworms -General Features:

Parasites with flat, ribbon like bodies and long segmented bodies. No body cavity. Morphology: Adult parasite has 3 basic parts: Head/ Scolex with suckers and hooks: used for attachment to the mucosa of small intestine Neck/ Strobila : attaches the head to the body Body: consists of segments/ proglottids—used for diagnosis Hermaphrodites and donot have separate sexes.

Prolapsed rectum: a complication of T. Trichiura

Diagnosis: demonstration of eggs in stool. Eggs are smooth like a barrel and has 2 mucus plugs

Fish

tap

ew

orm

: ad

ults fo

rm fo

un

d in

fish

Tape Worms, which can infect man:

Fish tapeworm/ Diphyllobothriumlatum/Broad Tapeworm General Features: One of the largest tape worms Definitive host: Man (no one eats man) 2 Intermediate hosts: Crustacean (Cyclops)

and Fish Larvalform found in the flesh of fish is called

Sparaganum( also known as Plerocercoid Larva)

Mode of infection: Ingestion of raw or undercookedfish, ‘gefilte fish’ having the larval form( sporangium/ pleroceroid) . Abdominal pain, nausea, weight loss. Complications: Causes Vitamin B12 deficiency and MegaloblasticAnemia due to competition for dietary vitamins Life Cycle:

1. Unembryonate eggs passes in feces 2. Eggs embryonate in water 3. Coracidia hatch from eggs and are ingested by crustaceans 4. Procercoid larvae in body cavity of crustaceans 5. Infected crustacean ingested by small freshwater fish.

Procercoid larva released from crustacean, develops into pierocercoid larva.

6. Predator Fish eats small fish 7. Humans ingest raw uncooked infected fish. 8. Once in small intestine, larvae breaks open and

develops into adult form 9. Proglottids release immature eggs 10. Unembryonated eggs passed in feces.

Diagnoses:By demonstration of bile stained, operculated eggs in stool Treatment: Praziquantel

Operculated eggs of D.latum

EchinococcusGranulosus/ Dog Tape Worm -Features: The dog tapeworm is common in Asia, Australia, southern parts of South

America and northern parts of North America. Smallest of all tapeworms (3 to 9 mm long) with only 3 proglottids. (head,

neck and there is immature, mature Gravid proglottid = Which contains the eggs)

Definitive host: Dog. Intermediate host: Sheep / MAN

In the liver the cyst leads to jaundice In the lungs Resp dystress In the brain ICSOL (intracranial space occupying lesion) -Mode of Infection:

Ingestion of ova/ egg of E.granulosus( these are bilestained ova) Produces Hydatid cyst in the liver, lungs, brain etc Hydatid cyst is the larval form of the parasite It is a slow growing, tumor-like space occupying structure. Has several layers and inner layer develops brood capsules where tapeworm heads develop. Common sites: liver, lungs, bones, brain. Symptoms are due to pressure effects: pain/ biliary rupture/ cough or dyspnea/Can result in an anaphylactic shock – if during surgery the fluid of the cyst leaks out

-Diagnosis:

Biopsy, Imaging, Casoni’s Test ( this is a skin test looking for Type 1 Hypersensitivity reaction against hydatid)

Treatment: Albendazole

Adult worm

Hydatid cyst; Aspiration is contraindicated as the hydatid fluid may lead to anaphylaxis

Trematodes / Flukes Common Features: Flat fleshy leaf shaped worms Have muscular oral and ventral suckers Most flukes are hermaphrodites Adult produces eggs which are operculated. Common liver fluke: Fasciola hepatica Chinese liver fluke: Ophisthorchis (Clonorchis) sinensis

Fasciola Hepatica: Common Liver fluke -Geography:

Found in sheep raising areas like Australia, japan, Soviet Union, Egypt, Latin America

-Definitive host: Sheep/ Man -Intermediate host Snail and Water Vegetation. -Mode of infection:

Ingestion of metacercariae in water plants.( infective form) Passage of the larva through the liver produces tenderness, hepatitis, biliary obstruction, portal cirrhosis and liver rot. Fasciola Hepatica- once the metacercariae are in the intestine, it goes through the gutwall/ peritoeinal cavity right into the liver Ophisthorchis/ Clonorchissinensis/ Chinese liver fluke infection is acquired by ingestion of fish. Complication: adenocarcinoma of bile duct. Chinese liver fluke- attach to duodenum and have a retrograde migration through the pancreatic duct and go into the bile duct to the liverthis is why you get adenocarcinoma of bile duct/gall bladder (which is not seen in Fasciola Hepatica)

-Diagnosis: Demonstration of operculated eggs in stool -Treatment: Praziquantel / preferred drug is bithional

Viral Hepatitis

Hepatitis B Virus HBV is associated with Serum hepatitis Acute/ Chronic hepatitis and hepatocellular carcinoma Almost 1/3 of population in infected with Hep B virus First detected in an Australian aborigine: HBsAg is also called Australian antigen

-Morphological features of Hepatitis B Virus: Hepadna virus Icosahedral symmetry Enveloped virus with circular partially Double

Stranded DNA Enzymes: Has reverse transcriptase enzyme

RNA directed DNA polymerase activity. -Important antigens:

• Hepatitis B surface antigen: HBsAg (Envelope) ,seen in serum

• Hepatitis B core antigen (Core):HBcAg- remains only in liver and never seen in serum

• Hepatitis B e Antigen( core associated antigen ) which is secreted in serum

• Hepatitis B x Ag: Transactivator of replication Types of HBV particles encountered in the serum

Transmission Electron Microscopic view of the particles seen in the serum of patients with HBV infection

Dane particle(42nm)

tubular forms (22 nm diameter)

Spherical forms(22 nm)

Steps in HBV Replication

Epidemiology of Hepatitis B:

High rates of sero-positivity are observed in Italy, Greece, Africa, and Southeast Asia

Transmission:

Virion binds to cell surface receptors with cell surface glycoproteins . Ligand: transferrin receptor /Annexin V on hepatocytes

Transcription of the genome : RNA strands transcribed from viral DNA by a

Cellular RNA polymerase.* mRNA used for protein synthesis and as a

template for DNA synthesis.

Reverse transcriptase enzyme is an RNA directed DNA polymerase thatacts on RNA to form neg DNA strand.

Neg strand acts as a template for the positive strand and the RNAse degrades the RNA during the +strand DNA synthesis.

Nucleo-capsid assembled and enveloped in the endoplasmic reticulum and released by exocytosis

Partial ds DNA completed into circular ds DNA and delivered to the nucleus

High Risk groups for HBV Infection

Transmission & Pathogenesis

Spectrum of Conditions/ Diseases by HBV • HBV

• Asymptomatic • Symptomatic:Acute • Symptomatic:Chronic active • Symptomatic:Chronic persistent • Eventually leading to Cirrhosis/Primary Hepatocellular Carcinoma

Clinical outcomes of the HBV disease

Acute hepatitis : Features, Symptoms, Course

1) Exposure 2) Incubation period4 to 20 weeks 3) Pre-Icteric phase: fever, nausea,

myalgia, abd pain 4) Icteric Phase: Jaundice, dark urine,

pale stools, hepatomegaly, increased transaminase levels

5) Chronicity or Resolution

VIREMIA

Spread to infect liver

Multiplies in hepatocytes and integrates into host genome

HBV DNA integrates into the hepatocyte chromatin. Buildup of filamentous forms of HBsAg can produce the ground-glass hepatocyte cytopathology

Course of Illness and Clinical Feature

Clinical Features: Fever, anorexia Nausea/vomiting Increased LFT enzymes Jaundice Immune complex mediated arthritis Few: Fulminant hepatitis

Chronic Hepatitis: Features and progression -Chronic Hepatitis: Chronic active hepatitis : continued destruction of the liver leading to

scarring of the liver, cirrhosis, liver failure, or PHC. Chronic persistent/passive hepatitis : less symptoms. May be detected due

to elevated liver enzyme levels on a routine blood chemistry profile. Chronis Hepatitis Eventually Can lead to Primary Hepatocellular Carcinoma Liver repair and cell growth in response to inflammation and tissue damage. Transactivation of the transcription of cellular proteins and stimulation of cell growth by HBV X gene. Integration into the host chromosome leads to stimulation of genetic rearrangements or juxtaposition of viral promoters next to cellular growth-controlling genes.

Leading to Hepatocellular Carcinoma

Cirrhosis of liver Hepatocellular

carcinoma

Serological Markers and Their Significance 1) HBsAg

Used for early diagnosis of HBV infection Appears before onset of clinical symptoms and is detectable during

prodrome and acute disease. Peaks during acute phase and declines in 3-6 months. Decreases with increase in levels of anti-HBs antibodies.

Presence of HBsAg implies LIVE VIRUS (Acute/ Chronic/Carrier state) Persistence beyond 6 months implies a Chronic carrier state

2) HBeAg 2nd antigen marker to appear Presence indicates high infectivity and active replication. Decreases with

appearance of anti-HBe antibodies. HBV DNA and DNA polymerase are usually seen with HBe Ag soon after

appearance of HBsAg. Presence signifies REPLICATION of the virus Some mutants may not produe HBe antigen HBV DNA and DNA polymerase Appearance of Anti-HBe antibodies implies that acute infection is on the

wane. It is a marker of low infectivity 3) Anti-Hbc Ab

HBc antigen is NEVER detected in theSerum. It is found in hepatocytes.

First antibody to appearshortly before the onset of symptoms, concurrent with the onset of serum aminotransferase levels.It is the marker detectable during the window period. **

Its Detection Signifies: 1) Acute illness-IgM 2) Past acute/Chronic illness- Ig G 3) Window period: Only marker to be detected. 4) Recovery phase: along with other antibodies.

Core window period is the period when the HBsAg is not detectable any more and anti-HBs Ab is not yet detectable

4) Anti HbsAb Appears as the HBsAg declines Its presence signifies immunity and protection Its detection indicates a PAST INFECTION / VACCINATION

Serological Markers in Acute Hepatitis B Infection

Serological markers in Chronic hepatitis B Infection

Interpretation of Serological Markers

LABORATORY DIAGNOSIS OF HEPATITIS B

Serum Transaminase levels for assessing liver function. ELISA for detection of HBs antigen or anti-HBc antibodies. Other assays: Latex agglutination and Immunochromatography

tests PCR: for viral load estimation

Hepatitis B Treatment: Antiviral agents+ Lamivudine- (Reverse Transcriptase inhibitor) Or can prescribe Nucleoside analogues: Famciclovir, Adefovir dipivoxil + Pegylated Alpha Interferon

Hepatits B Prevention: Pre exposure prophylaxis:

Recombinant DNA vaccine containing HBsAg given in scheduled doses followed by booster:

Engerix B (4 doses) (Smithkline) OR Recombivax HB ( 3 doses)(Merck)

Post exposure prophylaxis: Indication: For exposure to HBV infection in a previously non

immunized person/ in a child born to HBV positive mother. Hyper-immune globulin + 3 doses of vaccine

Screening of blood and its products Strict adherence to UNIVERSAL PRECAUTIONS

Universal Precautions:

*HBV is an enveloped virus and not easily destroyed by detergents. Contaminated material can be disinfected with 10% bleach*

Hepatitis C Virus Morphology : Single Standed, PositiveSense, Enveloped

RNA virus Belongs to flaviviridae Replicates in hepatocytes and mononuclear

cells Virusis highly genetically unstable due to

error prone nature of RNA polymerase which lacks a 3’-5’ exonuclease activity

Several mutant strains are present within an infected individual

No effective vaccine to date Does not induce protective immunity after infections.

Epidemiology of HCV: Risk factors/populations at risk

• Blood transfusions • Drug addiction: Shared Drug paraphernalia • Tattooing/ Body piercing • Prisoners • Health care workers (nurses, dentists etc.) • Sex workers • Children born to infected mothers

• Endemic in southern Italy, Spain, central Europe, Japan, Middle east, Egypt, S.E Asia: China, Taiwan, Thailand

Hepatitis C disease: Features Incubation period: 6-12weeks Acute Phase: Jaundice Most Cases AymptomaticLong LatencyChronic fatigue, Joint pains, Cryoglobulins, Skin lesions, DepressionChronic Hepatitis and Hepatocellular Carcinoma Virus enters hepatocytes through CD81(tetraspanin)/ through lipoprotein receptors. CMI(CD8 + T cells are mainly affected); Cytokines are responsible for tissue damage responsible

Lab diagnosis and Treatment Screening for infection ELISA for detection of anti HCV antibodies. Confirmation of infection PCR assay Viral RNA. Monitoring of infectionRT-PCR: for Viral load in serum Assessing likelihood of response to treatment: Genotyping of virus for

looking at prognosis of the case. Pegylated Interferon and Ribavirin

Hepatitis C Infection: Clinical Picture

E-NANBH (Enteric/ Epidemic)

Spread by Fecal- Oral route

Epidemics in India, Pakistan, Nepal, North Africa, Mexico

Similar to HAV Higher incidence of

mortality and morbidity in pregnant women(Expectant mothers)

Lab diagnosis: HEV RNA in stool and IgM detection

No vaccine

Other antiviral agents:Boceprevir, Telaprevir (Protease inhibitors) NO EFFECTIVE VACCINE AVAILABLE

Other NANB hepatitis viruses

HDV HEV

HGV-also called GB virus-C; similar to HCV

Also called Delta agent Depends on HBV for

replicating and producing its envelope

Transmitted thorugh blood, semen and vaginal secretions.

Co-infection: HBV and HDV infections happens together

Super-infection: Chronic HBV carrier gets infected with HDV

Results in fulminant hepatitis, hepatic necrosis and hepatic encephalopathy

Detection of RNA genome/ Delta antigen/ antibodies

Immunization against HBV is protective against HDV as well.

Hepatitis A Virus -MorphologySmall, Nonenveloped, Icosahedral particle, Single Stranded Positive Sense Rna Virus -Nature of the Virus:

Resistant to stomach acid, detergents, ether and chlorform and heat at 56-60 deg C for 30 mins.

Survives for several months in salt water and fresh water Geography/Epidemiology:

Mostly affects children Outbreaks in schools, nurseries Water borne epidemics in places where there is overcrowding Ingestion of food / water contaminated with HAV Associated with consumption of raw/ steamed shellfish

(mussels, clams, oysters) Food handlers

Symptoms: Yellowing of skin and eyes, dark urine, light colored stools, nausea and vomiting, loss of appetite, extreme fatigue

Hepatitis A virus(HAV) Pathogenesis:

1. Enters through ingestion, Incubation period: 2-4 weeks 2. Enters bloodstream through epithelial lining of oropharynx or intestines 3. Enters the liver and replicates in the hepatocytes and Kupffer cells. 4. Receptor for HAV: HAVcr1 or TIM-1 5. Virus released into bile and hence in stool. (10 days prior to jaundice) 6. Hepatocellular damage, increased transaminases and Jaundice 7. Spontaneous resolution in 2-4 weeks; Some infections are inapparent.

Fulminant hepatitis is rare -Resistant to stomach acid, detergents, ether and chlorform and heat at 56 deg C for 30 mins -Virus shed in feces 2-3 weeks before and 1 week after development of jaundice -Most damage due to activity of CD8 + T cells -Doesnot result in chronic infections.

Lab Diagnosis/ Treatment Prophylaxis Cannot be cultured in vitro Presence of HAV-specific IgM indicates acute infection IgG indicates immunity due to infection or vaccine. Post exposure prophylaxis: Hyper Immune serum Vaccine: Inactivated cell culture-derived vaccine At risk population: HCW, child care workers, Homosexuals and travel to

endemic areas Supportive treatment