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Gastrointestinal (GI) Infections - Overview

Diarrheal Diseases
GI infections are among the most common infective syndromes in humans.
Epidemiology:
They can affect any part of the GI tract and are caused by bacteria, viruses, or parasites.
● Leading cause of illness worldwide
● Major morbidity & mortality, esp. in developing countries
Table 39.1 – GI Infective Syndromes ● Young children often get diarrhea ~3x/year
Diarrheal Diseases Definition (WHO):
● Diarrhea: ≥3 loose/liquid stools/day ● ≥3 loose/liquid stools/day, more than usual for that person
● Dysentery: Diarrhea with blood & mucus + fever, pain, tenesmus Types by Duration:
● Traveler’s diarrhea: Watery diarrhea in travelers
● Acute diarrhea: <14 days (usually viral)
● Persistent diarrhea: Lasts >14 days
● Persistent/chronic diarrhea: >14 days
● Gastroenteritis: Inflammation of stomach & intestines
● Food poisoning: Toxin-mediated illness (often rapid onset)
Dysentery
Other GI Syndromes
● Definition: Diarrhea with blood & mucus
● Acute vomiting
● Symptoms: Fever, abdominal pain, tenesmus (urge to pass stool despite empty colon)
● Necrotizing enterocolitis
● Often bacterial (e.g., Shigella)
● Necrotizing enteritis
● Pseudomembranous enterocolitis: Often C. difficile related
● Peptic ulcer disease Traveler’s Diarrhea
● Infections of GI structures: e.g., Appendicitis Epidemiology:
● Affects 20–50% of travelers from temperate → tropical regions
Resident Microbial Flora of GIT (Asia, Africa, Latin America)
Upper GIT: Common Pathogens (Table 39.3):
● Sparse flora 1. Enterotoxigenic E. coli (ETEC) – most common
○ Oral cavity: Streptococci 2. Enteroaggregative E. coli (EAEC)
○ Stomach: Lactobacilli 3. Campylobacter
Lower GIT: 4. Shigella

● Microbial load increases distally Symptoms:

○ Distal ileum: 10¹¹–10¹²/g ● Onset: 3–5 days after travel
○ Large intestine: Anaerobes > aerobes (1000:1 ratio) ● Sudden abdominal cramps, anorexia, watery diarrhea
◆ Most common anaerobe: Bacteroides fragilis ● Self-limited: usually resolves in 1–5 days
◆ Common aerobes: E. coli, Klebsiella (Enterobacteriaceae)
◆ Also present: Yeasts (Candida), Parasites (Entamoeba coli) Persistent & Chronic Diarrhea
Functions of Normal Flora: ● Persistent diarrhea: Lasts ≥14 days (usually 2–4 weeks)
● Prevent colonization by pathogens ● Chronic diarrhea: Lasts >4 weeks
 ● Common settings: Cruise ships, children, immunocompromised ○ Bacteria: EPEC, EHEC
Etiological Agents ○ Parasites: Cryptosporidium, Cyclospora
○ Viruses: Rotavirus, Norovirus
Type Organisms
Parasites Giardia lamblia, Cryptosporidium, 3. Toxin Production

Entamoeba histolytica, Cyclospora Toxin Type Effect

Bacteria Campylobacter, Clostridioides Enterotoxins Watery diarrhea via increased
difficile secretion
Viruses Cytomegalovirus (esp. in Cytotoxins Mucosal damage → inflammatory
immunocompromised) diarrhea
Fungi Microsporidia (esp. in Neurotoxins Vomiting via CNS stimulation
immunocompromised) 4. Invasion of Mucosa
● Causes cell destruction → dysentery
Gastroenteritis (Infectious Diarrhea)
● Invasive agents:
● Inflammation of stomach & intestine
○ Bacteria: Shigella, EIEC, C. jejuni, Y. enterocolitica
● Symptoms: Diarrhea + vomiting + abdominal pain, ± mucus/blood, fever, or dehydration
○ Parasites: Entamoeba histolytica, Balantidium coli

Food Poisoning
Predisposing Factors to Diarrheal Diseases
● Illness from contaminated food/drink
● Caused by microorganisms or their toxins Factor Effect
Suppression of normal flora Loss of protective barrier
Pathogenesis of Diarrhea
1. Infective Dose (Inoculum Size)
Reduced gastric acidity Increases risk of acid-labile
organisms (e.g. V. cholerae)
Pathogen Infective Dose
Impaired intestinal motility Delayed clearance of pathogens
Shigella, Giardia, Entamoeba 10–100 organisms
histolytica Age Children <5 yrs: more vulnerable
(e.g. rotavirus, weaning diarrhea)
Salmonella 10³–10⁵ bacilli
Breastfeeding Protective via maternal antibodies
Vibrio cholerae 10⁵–10⁸ bacilli
2. Adherence to Mucosa Immunocompromised state Higher risk of Salmonella,
● Helps colonization and outcompetes normal flora Cryptosporidium, Microsporidia,
● Key agents:
 ○ Coronavirus → Cup-like depressions
etc.
Antibiotic use Risk of C. difficile infection Bacterial Culture
Closed communities Outbreaks common in schools, ● Enrichment media:
○ Selenite F broth, alkaline peptone water (for enrichment)
day-cares, cruise ships ● Selective media:
Blood group O More susceptible to V. cholerae, ○ MacConkey agar, DCA, XLD, TCBS (Vibrio)
● Identification:
Shigella, E. coli O157, Norovirus ○ Biochemical tests / Automated systems
Laboratory Diagnosis of Diarrhea ○ Serotyping with group/type-specific antisera
● ● Antibiotic Sensitivity Testing: Essential for treatment planning
Specimen: Fresh fecal sample with mucus/blood
● Container: Sterile, screw-capped, wide-mouthed
● Transport: Tissue Culture
○ Within 1 hour preferred ● Used for enteric viruses and some E. coli strains
○ If delayed, use: ○ ETEC → Penetrates HeLa/HEp-2 cells
◆ Cary-Blair medium ○ EHEC → Cytotoxic effect on Vero cells
◆ Alkaline peptone water (if cholera suspected)
● Alternate: Rectal swab (in carriers)
Antigen Detection
● ELISA → Rotavirus antigen
Laboratory Diagnosis of Diarrheal Diseases ● Immunochromatographic tests → E. histolytica, Giardia, Cryptosporidium
Macroscopic Examination ● Rapid tests for C. difficile (glutamate dehydrogenase, toxin A/B)
● Color & Consistency: Formed, semi-formed, liquid
● Blood → Suggests dysentery Molecular Methods
● Mucus/Pus → Suggests inflammatory diarrhea ● PCR Assays: Detect specific genes of enteric pathogens
● Visible Parasites: Enterobius, Ascaris, Taenia segments ● BioFire FilmArray GI Panel: Fully automated multiplex PCR for:
○ Bacteria, viruses, parasites causing diarrhea
Microscopy
● Wet Mount (saline/iodine): Detects: Treatment of Diarrheal Diseases
○ Pus cells, RBCs
General Management:
○ Cysts, trophozoites, eggs, larvae (for parasites)
● Mainstay: Fluid therapy (to prevent/treat dehydration)
● Hanging Drop Prep: Shows darting motility of Vibrio cholerae
● Adjuncts: Anti-motility agents, adsorbents (for moderate-severe cases)
● Gram Stain: Not routinely done (due to normal flora)
● Modified Acid-Fast Stain (0.5–1% H₂SO₄): Detects:
Antibiotics (Only for severe or specific infections):
○ Cryptosporidium, Cyclospora, Cystoisospora oocysts Drug Indication
● Electron Microscopy:
○ Rotavirus → Wheel-like Ciprofloxacin / Levofloxacin General bacterial diarrhea (3–5
○ Astrovirus → Star-like
days)
 ○ Papua New Guinea (Pigbel)
Azithromycin Campylobacter
○ Germany (Darmbrand)
Metronidazole / Vancomycin C. difficile infection
Other GI Infective Syndromes 3. Pseudomembranous Enterocolitis
1. Acute Nausea & Vomiting ● Caused by: Clostridioides difficile
● Seen after: Prolonged broad-spectrum antibiotic use
● Can occur as part of diarrheal illnesses
● Pathology:
● Main agents:
○ Pseudomembranes on colonic mucosa (1–2 mm whitish-yellow plaques)
○ Food poisoning (toxin-mediated, <6h onset):
● Chapter: 43 (more details there)
◆ S. aureus, B. cereus (emetic type)
○ Winter vomiting disease (gastric flu):
◆ Occurs in winter, temperate regions 4. Esophagitis
◆ Caused by Caliciviruses: Norovirus, Sapovirus ● Common in: Immunocompromised hosts (e.g. HIV, malignancy)
● Symptoms: Odynophagia, dysphagia, foreign body sensation
2. Necrotizing Enterocolitis (NEC) ● Common agents:
○ Candida albicans
● Fulminant disease, affects premature infants
○ Herpes Simplex Virus (HSV)
● (Details continue in the next chapter...)
○ Cytomegalovirus (CMV)

Other Infective Syndromes of the GIT 5. Gastritis

● Inflammation of gastric mucosa
1. Necrotizing Enterocolitis (NEC) ● Symptoms: Nausea, epigastric pain, vomiting, fever, burping
● Major cause of mortality in low-birth-weight infants ● Cause: Helicobacter pylori (recovered from gastric biopsy)
● Most common site: Terminal ileum ● Related conditions:
● Features: ○ Peptic Ulcer Disease (gastric or duodenal ulcers)
○ Mucosal sloughing ○ Gastric carcinoma
○ Necrosis of bowel wall ● Peptic ulcer pain:
○ May lead to perforation, peritonitis, bacteremia ○ Gastric ulcer: Empty stomach
● Common pathogens: ○ Duodenal ulcer: 2–3 hours after food
○ Pseudomonas
○ Klebsiella 6. Appendicitis
○ E. coli (EPEC, O111:B4)
● Acute inflammation of the vermiform appendix
○ Salmonella
● Complications: Obstruction, perforation, peritonitis, abscesses
○ Clostridium perfringens & C. butyricum
● Age group: Adolescents & young adults
● Polymicrobial:
2. Necrotizing Enteritis (Enteritis Necroticans / Pigbel) ○ Aerobic + anaerobic gram-negative bacilli
● Location: Jejunum (ischemic necrosis + gas in tissue planes)
● Caused by: Clostridium perfringens type C (produces β-toxin) 7. Proctitis
● Seen in:
 ● Inflammation of the rectum 8–16 hours Bacillus cereus (diarrheal),
● Symptoms:
○ Rectal itching, mucus discharge → ulcers/abscesses Clostridium perfringens
● Cause: Sexually transmitted (via anal intercourse)
> 16 hours Salmonella spp., Listeria
● Agents:
○ Chlamydia trachomatis monocytogenes, Campylobacter
○ Herpes Simplex Virus (HSV) (See Table 40.1 for complete list in textbooks)
○ Treponema pallidum Non-Microbial Causes
○ Neisseria gonorrhoeae ● Capsaicin (hot peppers)
● Toxins in fish/shellfish
8. Whipple’s Disease ● Chemical poisons
● Rare; affects small intestine, CNS, and endocardium
● Agent: Tropheryma whipplei (gram-positive actinomycete) FOOD POISONING WITH ONSET WITHIN 1–6 HOURS
● Pathogenesis: Caused by preformed toxins already present in food. Rapid onset.
○ Malabsorption of fats and carbs
● Symptoms: Fever, abdominal pain, diarrhea
1. Staphylococcal Food Poisoning
● Diagnosis:
● Source: Contamination by human carriers (S. aureus), especially food handlers
○ PAS-positive macrophages in intestinal biopsy
● Food involved: Ham, poultry, salads, mayonnaise, pastries, dairy products
○ PCR targeting 16S rRNA
● Incubation: 1–6 hours
● Treatment:
● Toxin: Preformed enterotoxin (heat-stable, resistant to gastric juice)
○ Doxycycline + Hydroxychloroquine (1 year)
● Mechanism: Stimulates vagus nerve and vomiting center, increases intestinal motility
○ Then lifelong doxycycline
● Symptoms:
○ Nausea
FOOD POISONING ○ Vomiting
Definition: ○ Sometimes diarrhea
Food poisoning refers to illness caused by consumption of food or drink contaminated with ○ Hypotension
microorganisms or their toxins. It commonly leads to outbreaks of diarrhea (common-source ○ Dehydration
outbreaks). ○ No fever
○ Duration: Resolves in 8–10 hours
● Serotypes:
ETIOLOGY
○ 15 types (A–E, G–P)
Food poisoning may be caused by microbial or non-microbial agents.
○ Type A – Most common cause of food poisoning
Microbial Causes
○ Type F – Causes toxic shock syndrome (not food poisoning)
Grouped based on incubation time:
● Diagnosis:
Incubation Time Examples ○ ELISA
○ Latex agglutination
< 6 hours Staphylococcus aureus, Bacillus ○ Multiplex PCR (detect toxin gene)
cereus (emetic) ● Treatment:
 ○ Supportive only: correct fluid and electrolyte imbalance Laboratory Diagnosis
○ No antibiotics needed ● Stool culture using MYPA medium
● Important Note: ○ Contains mannitol, egg yolk, polymyxin B, phenol red, agar
○ No secondary spread ● Microscopy: Gram-positive, spore-forming, motile bacillus
○ Heat does not destroy the toxin
Treatment of B. cereus Infections
2. Bacillus cereus Infections ● Susceptible to:
● Habitat: Soil, food (vegetables, milk, cereals, spices, meat, poultry) ○ Clindamycin
● Toxins: ○ Erythromycin
○ Emetic toxin – Preformed, heat-stable ○ Vancomycin
○ Diarrheal toxin – Produced after ingestion ○ Tetracycline
● Resistant to:
A. Emetic Type ○ Penicillin (due to β-lactamase production)
● Incubation: ~1 hour ○ Trimethoprim
● Toxin: Preformed, heat-stable (similar to S. aureus toxin)
● Food: Contaminated fried rice FOOD POISONING (Onset within 8–16 Hours)
● Mechanism: These organisms produce toxins in the intestine after ingestion (not preformed), so the
○ Spores survive boiling incubation period is longer.
○ If cooked rice is not refrigerated, spores germinate
○ Frying before serving does not destroy toxin
1. Bacillus cereus – Diarrheal Type
● Symptoms:
● Toxin: Diarrheal toxin (resembles E. coli heat-labile enterotoxin)
○ Nausea, vomiting
● Incubation: 8–16 hours
○ Similar to S. aureus food poisoning
● Symptoms:
● Duration: Short, self-limiting
○ Watery diarrhea
○ Abdominal cramps
B. Diarrheal Type
○ Vomiting uncommon
● Incubation: 8–16 hours ● Food sources: Meat, vegetables, milk, cereals
● Toxin: Produced after ingestion, not preformed ● Lab: Detected in stool via selective media (e.g. MYPA)
● Symptoms: Watery diarrhea, abdominal cramps

2. Clostridium perfringens Food Poisoning

Other Manifestations of Bacillus cereus
● Toxin: Enterotoxin produced after ingestion
● Ocular Disease: ● Incubation: 6–24 hours
○ Keratitis and panophthalmitis post-trauma ● Symptoms:
○ Can lead to vision loss ○ Moderate to severe abdominal cramps
● Systemic Infections: (Rare) ○ Watery diarrhea
○ Endocarditis, meningitis, osteomyelitis, pneumonia ○ Vomiting and fever uncommon
○ Risk ↑ with medical devices or IV drug use ○ Self-limited, resolves in <24 hours
● Food sources: Inadequately cooked beef, poultry, legumes
 Undercooked
diarrhea, fever, poultry, raw
● Other diseases: Skin/soft tissue infections (e.g., gas gangrene – see Chapter 53) cramps milk, water

FOOD POISONING (Onset >16 Hours) Vibrio 1–3 days

Dysentery-like
Contaminated
These organisms have longer incubation periods; symptoms start ≥16 hours after food parahaemolyti- seafood,
illness esp.
consumption.
cus oysters
Organism Incubation Key Features Food Source
Listeria 1–4 weeks
Flu-like
Soft cheeses,
illness in
Vibrio cholerae 1–4 days Profuse watery Seafood, raw
monocyto- pregnancy,
raw sprouts,
diarrhea, fruits/
genes meningitis
meat, seafood,
in
nausea, vegetables,
elderly
raw milk
vomiting, fever, contaminated
Norovirus 12–48 hours Diarrhea, Contaminated
chills water
vomiting, salad, fruits,
ETEC Watery
3–4 days
Contaminated
nausea, cramps shellfish, water
(Enterotoxi- diarrhea
meat, cheese,
Cyclospora ~1 week Watery diarrhea, Raw fruits/
genic E. coli) salads, water
fatigue, weight vegetables,
EHEC Bloody
3–4 days
Ground beef,
loss herbs
(Enterohemor- diarrhea,
raw milk/ ± HUS
Clostridium 12–36 h Neurotoxic: Improperly
rhagic E. coli) vegetables,
(5–10%)
botulinum diplopia, canned/
apple juice
dysphagia, fermented
Salmonella 6 h – 6 days Inflammatory Eggs, poultry,
paralysis foods, honey
(non-typhoidal) diarrhea, fever, meat,
(infants)
cramps unpasteurized
Fungal Variable Rare, specific Contaminated
milk, juice
(Mycotic) toxins (e.g., grains, nuts,
Shigella 1–2 days Dysentery Potato salad,
toxins aflatoxins) moldy foods
(bloody/mucoid eggs, raw LABORATORY DIAGNOSIS (Food Poisoning)
stools), fever vegetables Clinical History is Key
● Inquire about:
Campylobacter 2–5 days Bloody Undercooked ○ Type of food consumed
diarrhea, fever, poultry, raw ○ Time of onset
○ Symptoms pattern
cramps
Specimens: ciprofloxacin)
● Vomitus
● Stool Cholera Azithromycin
● Suspected food samples
Listeria (pregnancy) Ampicillin
Laboratory Methods: Traveler’s diarrhea (severe Azithromycin or ciprofloxacin
1. Viable Plate Count (Standard)
ETEC)
● Homogenize food in sterile diluent (e.g., Ringer’s solution)
● Plate onto appropriate media
2. Pre-enrichment & Selective Enrichment
● Recover damaged pathogens → Selective media for specific bacteria BOTULISM
3. Toxin Detection Definition
● ELISA – Detects enterotoxins in stool Botulism is a rare, neuroparalytic disease caused by the botulinum toxin produced by
● PCR – Detects genes encoding toxins (e.g., S. aureus, B. cereus, C. perfringens) Clostridium botulinum — a gram-positive, spore-forming, obligate anaerobic bacillus.
● The name "botulism" is derived from Latin botulus = sausage (historically linked to food
TREATMENT OF FOOD POISONING poisoning from sausages).
1. Supportive Therapy (Mainstay)
● Rehydration: Epidemiology & Source
○ Oral Rehydration Solution (ORS)
● Ubiquitous in nature — found in:
○ IV fluids if severe dehydration
○ Soil
● Electrolyte replacement
○ Animal manure
○ Vegetables
2. Symptomatic Treatment
○ Sea mud
● Absorbents: Aluminum hydroxide
● Antisecretory agents: Bismuth subsalicylate
Pathogenesis

3. Antitoxins Botulinum Toxin (BT)

● Botulism: Administer heptavalent botulinum equine antitoxin (if suspected) ● Most potent neurotoxin known to mankind
● Produced only after bacterial autolysis, not secreted
4. Dietary Advice ● Initially synthesized as inactive protoxin, activated by proteolytic enzymes
● Spore → Germination → Toxin Production (requires anaerobic conditions)
● Avoid dairy/lactose during acute diarrhea due to temporary disaccharidase deficiency
Mechanism of Action
5. Antibiotics ● Toxin enters via ingestion, inhalation, or wounds
Not routinely recommended unless indicated ● Transported in blood → Peripheral cholinergic nerve terminals
● Blocks acetylcholine release at neuromuscular junction
Indication Antibiotic ● Flaccid paralysis (no CNS involvement)

Shigellosis Fluoroquinolone (e.g.,

Toxin Serotypes
 Toxin Serotypes
● Features: GI symptoms + neurologic signs
Serotype Details ● Mostly sporadic, rare outbreaks
A, B, E Cause most human cases
2. Wound Botulism
A Most severe
● Spores contaminate wounds
C1, C2, D, F, G Rare ● No GI symptoms
● Seen in IV drug users (e.g. black tar heroin)
C2 Enterotoxin (not neurotoxin) ● Similar neurologic picture to food-borne

C&D Phage-encoded toxins

3. Infant Botulism
Therapeutic Use of BT
● Most common form (75% cases)
● Controlled use for neuromuscular conditions:
● Age: ≤ 1 year
○ Strabismus
● Source: Honey (contains spores)
○ Blepharospasm
● Spores germinate in infant’s gut (due to immature flora)
○ Myoclonus
Symptoms:
○ Also in cosmetic medicine (e.g., Botox)
● Poor suck/swallow
● Weak cry
Recovery ● Ptosis
● Acetylcholine blockade is permanent, but reversible: ● Floppy baby syndrome (extreme hypotonia)
○ 2–4 months recovery via axon sprouting ● Self-limited; may require assisted feeding
● Spores do not produce toxins directly ● Rarely: respiratory failure, death

Clinical Manifestations 4. Adult Intestinal Botulism

● Incubation: 18–36 hours ● Rare
● Caused by ↓ acetylcholine at cranial & parasympathetic nerve terminals ● Seen in adults with altered gut flora
Symptoms ● Pathogenesis same as infant botulism
● Diplopia, dysphagia, dysarthria
● Descending, symmetrical, flaccid paralysis 5. Iatrogenic Botulism
● ↓ Deep tendon reflexes ● Caused by overdose of botulinum toxin during therapeutic or cosmetic use
● Constipation
● No sensory or cognitive impairment
6. Inhalational Botulism
● Severe: Respiratory muscle paralysis → may cause death
● Bioterrorism risk
● Inhalation of aerosolized toxin/spores
Types of Botulism
1. Food-borne Botulism
LABORATORY DIAGNOSIS OF BOTULISM
● Due to ingestion of preformed toxin
1. Isolation of Bacilli
● Sources: Homemade/improperly canned/fermented food/beverages
 ● Specimens: Suspected food or feces Types of Mycotic Poisoning
● Techniques:
○ Gram stain: Type Details
◆ Gram-positive
1. Mycotoxicosis From ingestion of food
◆ Non-capsulated bacilli
◆ With subterminal, oval, bulging spores contaminated with fungal toxins
○ Culture:
2. Aflatoxin Aspergillus flavus, Penicillium
◆ Robertson’s Cooked Meat (RCM) broth
○ Confirmation: puberulum Causes: Hepatoma,
◆ Gram stain
cirrhosis
◆ Biochemical tests
◆ MALDI-TOF (automated ID) 3. Fumonisins Fusarium moniliforme
○ Serotyping with type-specific antisera
Causes: Esophageal carcinoma
2. Toxin Demonstration (Mouse Bioassay) 4. Ochratoxin Aspergillus ochraceus, A.
● More significant than isolating bacilli niger, Penicillium verrucosum
● Toxin is injected into mouse
● Observe for paralysis = diagnostic
Causes: Nephropathy
● Still considered gold standard
5. Mycetism Toxicity from eating poisonous

TREATMENT OF BOTULISM
mushrooms
CHEMICAL CAUSES OF FOOD POISONING
1. Intensive Supportive Care
● ICU management Non-microbial Causes
● Mechanical ventilation for respiratory paralysis Includes:
2. Botulinum Antitoxin ● Capsaicin (hot peppers)
● ● Marine toxins from fish/shellfish
Administer immediately on clinical suspicion
● ● Heavy metals (e.g. arsenic, mercury)
Do NOT wait for lab confirmation
● ● Other chemical agents
Neutralizes only unbound toxin (no effect after binding to nerve endings)
3. Wound Botulism
●
SCOMBROID FOOD POISONING
Prompt debridement and drainage
● Antibiotics: Feature Details
○ Penicillin
○ Metronidazole Organism Morganella morganii
(Enterobacteriaceae family)
MYCOTOXICOSES
Source Sea fish
Definition
Food poisoning caused by fungal toxins (mycotoxins) Pathogenesis Converts histidine → histamine in
 fish Serratia, Pantoea
Symptoms Resemble histamine toxicity VI – Proteeae Proteus, Morganella, Providencia
Prevention Store fish at <16°C (prevents VII – Yersinieae Yersinia
histamine formation) VIII – Erwinieae Erwinia
Gram stain Gram-negative bacillus 3. Modern Molecular Taxonomy (Post-2016)
● Introduced order: Enterobacterales
● New families proposed
FAMILY ENTEROBACTERIACEAE ● Ewing’s classification still widely used in labs
General Properties
All members share the following: ESCHERICHIA COLI (E. coli)
● Gram-negative bacilli Overview
● Aerobes & facultative anaerobes
● First described by Escherich (1885)
● Nonfastidious: Grow on simple media (e.g., nutrient agar)
● Most common aerobic gut flora
● Glucose fermenters: Produce acid ± gas
● Indicator of fecal contamination (especially thermotolerant E. coli, survives at 44°C)
● Nitrate reducers → nitrite
● Catalase positive (except Shigella dysenteriae type 1)
● Oxidase negative Virulence Factors of E. coli
● Motile with peritrichous flagella, except: A. Surface Antigens (Basis for serotyping)
→ Shigella and Klebsiella (non-motile) ● E. coli serotype: O:K:H (e.g., O121:K37:H8)

Antigen Details
Classification Methods
1. Based on Lactose Fermentation (on MacConkey Agar)
O (somatic) On LPS; induces antibody
● Practical and widely used in labs response
● Differentiates lactose fermenters vs non-lactose fermenters
2. Ewing’s Classification (Tribal System)
H (flagellar) Motility; contributes to virulence
Based on common properties; widely used. K (capsular) May inhibit phagocytosis;
Tribe Genera inagglutinable by O antiserum
I – Escherichieae Escherichia, Shigella Fimbrial (pilus) Adhesion & colonization
II – Edwardsielleae Edwardsiella Notable Fimbrial Types:
● CFA: Enterotoxigenic E. coli (ETEC)
III – Salmonelleae Salmonella ● Mannose-resistant fimbriae: Uropathogenic E. coli
● P fimbriae: Binds P blood group antigens (urinary tract infections)
IV – Citrobactereae Citrobacter
V – Klebsielleae Klebsiella, Enterobacter, Hafnia, B. Toxins (Exotoxins)
Toxin Function Associated Condition Peritonitis Primary and secondary (after gut
Heat-labile toxin (LT) ↑ cAMP → watery ETEC perforation); most common
diarrhea causative agent

Heat-stable toxin ↑ cGMP → watery ETEC Visceral abscesses e.g., hepatic abscess
(ST) diarrhea Pneumonia Especially ventilator-associated
Verotoxin (Shiga-like Inhibits 60S ribosome EHEC (e.g., O157:H7) pneumonia in hospitalized
toxin) patients

CNF-1 (Cytotoxic Cytotoxic to bladder/ UTI Neonatal meningitis Especially strains with K1 capsule
Necrotizing Factor-1) kidney cells Wound/soft tissue infections Especially diabetic foot ulcers
SAT (Secreted Urotoxic UTI Prostatitis Most common cause of bacterial
Autotransporter prostatitis
Toxin) Osteomyelitis Seen in trauma or
Other Escherichia Species (Rarely Pathogenic) immunocompromised settings
● E. fergusonii
● E. hermannii
Endovascular infections Can lead to bacteremia, sepsis
● E. vulneris Laboratory Diagnosis

Step Details
E. coli in Public Health
● Indicator organism for recent fecal contamination in water Sample collection Based on infection site: urine,
● Thermotolerant strains especially important in water testing
stool, pus, CSF, blood, wound

Clinical Manifestations of E. coli

swab, etc.

System/Infection Details Direct smear Gram-negative bacilli, often with

pus cells
UTI (most common cause) 70–75% cases due to
uropathogenic E. coli (UPEC); Culture - Blood agar: Moist, gray colonies

uses P fimbriae, CFA - MacConkey: Pink, flat LF

colonies
Diarrhea Caused by 6 pathotypes of
diarrheagenic E. coli (see below) Motility E. coli is motile (except EIEC)
 O157:H7 most Sorbitol
Biochemical tests Conventional or automated (Stx1, Stx2) common; MacConkey,
(MALDI-TOF, VITEK) bloody diarrhea ELISA, PCR,
Antimicrobial testing Essential for management (due to without fever; Vero cell
rising resistance) HUS risk cytotoxicity
Diarrheagenic E. coli (children); low
WHO: >300 million cases & ~200,000 deaths annually infective dose
Pathotype Mechanism Key Features Diagnosis EAEC Aggregative Persistent/acute PCR (aggR,
EPEC Adherence, A/E Infantile Detection of A/E adherence diarrhea aatA), HEp-2
lesions diarrhea; lesion genes (infants, test
outbreaks; travelers); brick-
person-to- like stacking on
person; cup-like HEp-2 cells
pedestals DAEC Diffuse Diarrhea in 2–6 HEp-2
ETEC Toxins (LT, ST) Traveler’s Detection of LT, adherence yr old children; adherence test,
+ CFA adhesion diarrhea, ST toxins expresses PCR
watery stool; (ELISA) diffuse
infants & adults; adherence
non-invasive fimbriae
EIEC Invasion of Bacillary ELISA for VMA, Special Notes on Key Pathotypes:
Enteropathogenic E. coli (EPEC)
epithelium dysentery HeLa invasion
● No toxins
(VMA gene) (blood + assay ● A/E lesions: Disrupt brush border
mucus); ● Common in infants
Enterotoxigenic E. coli (ETEC)
resembles ● Produces:
Shigella; ○ LT toxin → ↑cAMP
○ ST toxin → ↑cGMP
nonmotile, NLF
● Major cause of traveler's diarrhea
EHEC/STEC Shiga toxin O157:H7 most Sorbitol Enteroinvasive E. coli (EIEC)
● Invasive, like Shigella
(Stx1, Stx2) common;
bloody diarrhea
without fever;
 ● Nonmotile, NLF (non-lactose fermenter) subcontinent
● Causes dysentery-like illness
Enterohemorrhagic E. coli (EHEC/STEC) S. sonnei 1 Most common in
● Shiga toxin (Stx1, Stx2) → microangiopathy developed countries;
● Diseases:
○ Hemorrhagic colitis colicin typing (26
○ Hemolytic uremic syndrome (HUS) → renal failure, CNS damage types)
● O157:H7: Doesn’t ferment sorbitol
● • All species are non-motile, non-sporing, and non-capsulated.
● Low infectious dose (100 bacilli)
Enteroaggregative E. coli (EAEC)
●
Pathogenesis
Forms stacked-brick biofilm
● Chronic diarrhea in developing countries Factor Details
● Gene: aggR, aatA
Diffusely Adherent E. coli (DAEC) Transmission Fecal-oral: contaminated fingers
● Diffuse adherence to HEp-2 cells (most common), food, water, flies,
● Affects children 2–6 years
sexual (MSM)
SHIGELLA INFECTIONS (Shigellosis) Infective dose Extremely low: 10–100 bacilli
Entry point M cells of intestinal epithelium
Introduction
●
Invasion mechanism Via large virulence plasmid
Named after Kiyoshi Shiga, who isolated S. dysenteriae type 1 in 1896.
● Causes bacillary dysentery — a disease characterized by bloody, mucopurulent stools. encoding Ipa proteins, Type III
secretion system
Classification
Intracellular spread IcsA protein mediates actin
Species Serotypes Notes
polymerization, cell-to-cell
S. dysenteriae 15 Most severe form;
spread
produces Shiga toxin
Toxins - ShET (enterotoxin): in S. flexneri
(type 1); non-
2a - Shiga toxin: in S. dysenteriae
mannitol fermenter
type 1 (resembles EHEC Stx) -
S. flexneri 8 Most common in
Endotoxin: causes ulceration/
developing countries
inflammation
S. boydii 19 Least common; Clinical Manifestations
restricted to Indian Shigellosis progresses through 5 phases:
Phase Features XLD agar Red colonies without black
1. Incubation 1–4 days center
Motility Test
2. Initial (Watery) Watery diarrhea, fever, vomiting,
● Shigella is nonmotile
malaise Biochemical Reactions

3. Dysentery phase Bloody mucopurulent stools, Test Result

tenesmus, cramps; self-limiting Catalase Positive (except S. dysenteriae
4. Complications Mostly in <5 yrs: • Toxic type 1)
megacolon • Rectal prolapse • Oxidase Negative
Ekiri syndrome (toxic Indole, Citrate, Urease All negative (ICU–)
encephalopathy: seizures, TSI (Triple Sugar Iron) Alkaline/Acid, no gas, no H₂S
cerebral edema) • Rare:
Mannitol fermentation Positive for all except S.
meningitis, pneumonia
dysenteriae
5. Post-infectious Reactive arthritis, uveitis, Identification

urethritis (HLA-B27 positive), esp. ● Automated systems (e.g. VITEK, MALDI-TOF) may not reliably differentiate from E. coli.
● Final ID by slide agglutination with:
S. flexneri ○ Polyvalent antisera (genus level)
Laboratory Diagnosis ○ Group-specific antisera (species)
○ Type-specific antisera (serotype)
Sample
● Colicin typing: For S. sonnei
● Fresh stool (preferred over rectal swabs)
Antimicrobial Susceptibility
● Transport in Sach’s buffered glycerol saline if delay
● Done on Mueller-Hinton agar using disk diffusion.
Microscopy (wet mount)
● Shows pus cells, RBCs, macrophages
Culture Key Differentiating Features: Shigella vs E. coli

Media Findings Feature Shigella E. coli

Enrichment Selenite F broth, GN broth Motility Nonmotile Motile
MacConkey agar Pale, non-lactose fermenting Lactose fermentation Mostly NLF Mostly LF
(NLF) colonies Mannitol fermentation Negative (S. Positive
DCA agar Colorless colonies dysenteriae only)
 ●

H₂S production Absent Some strains: present negative bacilli:

○ Quinolones
Indole Negative Variable ○ Cephalosporins

Shiga toxin Yes (S. dysenteriae) Also seen in EHEC

SALMONELLA INFECTIONS (SALMONELLOSIS)
(STEC)
Classification
EDWARDSIELLA INFECTIONS ● Genus Salmonella has 6 species, classified by surface antigens (O, H, Vi).
● Human pathogens belong to S. enterica subsp. enterica.
General Characteristics
● Edwardsiella is a commensal in the gut of reptiles and fishes. Two Major Clinical Groups
● Human infection is rare, usually associated with:
○
Group Includes Notes
Ingestion of undercooked aquatic animals
○ Snake-related injuries Typhoidal S. Typhi, S. Paratyphi Strictly human
salmonellae A, B, C pathogens → Enteric
Clinically Significant Species
● Edwardsiella tarda is the most frequently isolated species from humans.
fever(typhoid/
paratyphoid)
Clinical Presentations
Non-typhoidal S. Typhimurium, S. Zoonotic →
1. Gastroenteritis – most common presentation
2. Extraintestinal infections: salmonellae (NTS) Enteritidis, etc. Gastroenteritis,
○ Septic shock sometimes
○ Liver abscess
○ Wound infections following trauma involving aquatic environments bacteremia
Important NTS Serotypes
Identification ● S. Typhimurium
● Done via: ● S. Enteritidis
○ MALDI-TOF ● S. Newport
○ VITEK ● S. Javiana
○ Biochemical tests: ● S. Heidelberg
◆ Ferments only glucose and maltose ● S. Choleraesuis (source: pigs)
◆ Non-lactose fermenter ● S. Dublin (source: cattle)
◆ H₂S production positive
NTS vs Typhoidal Salmonellae
Treatment
Feature Non-Typhoidal Typhoidal
● Unlike E. coli, E. tarda is usually susceptible to antimicrobials effective against gram-
Salmonellae (NTS)
 Typhoidal
Salmonellae (NTS) Salmonellae
2. Bacteremia (Up to 8%)
Reservoir Animals (zoonotic) Humans only
● Can lead to:
Transmission Foodborne: Eggs, Waterborne ○ Endovascular infections: Endocarditis, arteritis
○ Metastatic seeding to organs
poultry, meat, dairy ● Risk factors:
Prevalence Worldwide Mostly in developing ○ NTS serotypes: S. Choleraesuis, S. Dublin
○ Age extremes (infants, elderly)
countries ○ Immunocompromised (esp. HIV)

Seasonality Peaks in rainy season Not specifically

3. Metastatic Localized Infections
(tropics), warm seasonal
● Intra-abdominal: Liver/splenic abscess, cholecystitis
months (temperate) ● Meningitis: Common in infants and HIV+ adults
● Pulmonary: Lobar pneumonia, lung abscess
Outbreaks Common in hospitals Community-based
● UTI: Pyelonephritis, cystitis (esp. with stones/anatomic defects)
outbreaks ● Genital: Ovarian/testicular abscess, prostatitis, epididymitis
● Osteomyelitis: Common in sickle cell disease, bone disorders
Pathology Neutrophilic Mononuclear ● Reactive arthritis (Reiter’s syndrome):
infiltration in intestinal infiltration ○ In persons with HLA-B27
○ Involves arthritis, urethritis, conjunctivitis
mucosa
Carrier State Rare (<1%) become Carrier state more Treatment of NTS Infections
chronic carriers common
Uncomplicated Gastroenteritis
Pathogenesis
● Conservative management
● Similar to typhoidal salmonellae, except:
○ Fluid and electrolyte replacement
○ In NTS, there is massive neutrophil infiltration of intestinal mucosa (vs.
● Antibiotics are not used routinely:
mononuclear in typhoid).
○ Can increase carrier rate and relapse

Clinical Manifestations of NTS

Antibiotics Indicated In:
1. Invasive NTS infection
1. Gastroenteritis (Most common)
2. Severe gastroenteritis at risk of becoming invasive
● Incubation: 6–48 hours after ingestion 3. High-risk groups (e.g., infants, elderly, immunocompromised)
● Symptoms: Nausea, vomiting, watery diarrhea, fever, abdominal cramps
● Duration: Self-limiting, resolves in 3–7 days
Drugs of Choice
● Post-infection shedding: Can last 4–5 weeks
● Ciprofloxacin: For severe cases or preemptive treatment
● Chronic carriers: Rare (<1%)
● Ceftriaxone: For bacteremia, invasive NTS
 ● Zoonotic infection
Drug Resistance ● Reservoirs: Pigs, wild/domestic animals
● Transmission: Ingestion of contaminated food, especially raw pork, milk, etc.
● NTS are more drug-resistant than typhoidal Salmonellae.
● Common in children
● MDR-NTS:
● More prevalent in colder climates
○ Resistant to ≥5 drugs:
◆ Ampicillin
◆ Chloramphenicol Clinical Features
◆ Streptomycin
Manifestation Notes
◆ Sulfonamides
◆ Tetracyclines Gastroenteritis - Self-limited diarrhea (with/
○ Known as the ACSSuT resistance pattern
without blood)- Common in young
Emerging Resistance children
● Ceftriaxone resistance: Intestinal complications - Terminal ileitis (esp. Y.
○ Due to AmpC β-lactamases
● Ciprofloxacin resistance:
enterocolitica)- Mesenteric
○ Due to point mutations in DNA gyrase genes adenitis- Mimics
appendicitis(pseudoappendicitis)
YERSINIA INFECTIONS
Septicemia - Seen in adults with: • Diabetes•
Overview Liver disease• Iron overload-
● The tribe Yersinieae includes the genus Yersinia, comprising three human pathogens:
Features: Fever, leukocytosis
• Species • Disease
Post-infective phenomena - Especially in Y. enterocolitica -
• Yersinia pestis • Plague – fulminant systemic Autoimmune reaction to non-
zoonosis viable bacterial components-
• Y. enterocolitica • Yersiniosis (gastrointestinal) Seen in adults
• Y. pseudotuberculosis • Yersiniosis Manifestations include: • Reactive arthritis (in HLA-B27
● • Y. pestis was first isolated in 1894 by Alexandre Yersin in Hong Kong.
individuals)• Erythema nodosum•
● Vector: Transmitted from rodents via rat fleas (arthropod vector).
● Plague is discussed separately in Chapter 81. Graves’ disease
Superantigen-related illness - Y. pseudotuberculosis strains
YERSINIOSIS (Due to Y. enterocolitica and Y. pseudotuberculosis)
produce superantigen mitogen-
Epidemiology Causes scarlet-like fever
 ○ Agglutination test
(Russia), Izumi fever (Japan)-
○ ELISA
Implicated in Kawasaki disease ● Uses O-antigen type–specific sera
pathogenesis
TREATMENT
LABORATORY DIAGNOSIS

Most cases
Culture Isolation
● Self-limiting → No treatment required
Sample Source Media/Notes Treatment required in:
Blood Inoculate into blood culture ● Systemic infections (e.g., septicemia)
Drugs of choice:
bottles
● Fluoroquinolones: Ciprofloxacin
Lymph node aspirate Inoculated on blood agar, ● Third-generation cephalosporins: Cefotaxime

nutrient agar, MacConkey agar

PLESIOMONAS
Feces/food/soil Use selective media like
Deoxycholate Citrate Agar (DCA) Classification
● • Incubation temperature: ● Plesiomonas is a:
• At 25°C and 37°C → differentiates from most pathogens (which grow only at 37°C) ○ Oxidase-positive
• Cold enrichment: Incubate in phosphate-buffered saline at 4°C for 3 weeks ○ Motile
○ Fermenting
Identification ○ Gram-negative bacillus
● Reclassified: Now under Enterobacteriaceae (previously under Vibrionaceae)
Test/Property Y. enterocolitica / Y. ● Based on DNA hybridization studies
pseudotuberculosis
Species
Motility Motile at 22°C, non-motile at
● Only species: Plesiomonas shigelloides
37°C ● Named so because it is antigenically related to Shigella sonnei

Cold enrichment Growth improves with

Habitat
refrigeration (4°C) ● Found as saprophyte in:
Automated ID Done via MALDI-TOF or other ○ Water
○ Soil
systems ● Also exists as:
Serology ○ Commensal in animals
● Antibodies detected by: ○ Rarely in human intestines
 □
like E. coli)
Human Infections ◇ K. pneumoniae subsp. ozaenae
◇ K. pneumoniae subsp. rhinoscleromatis
● Rare
■ Infections of nasal cavity
● Mainly causes gastroenteritis
■ Discussed in Chapter 78
○ Can be severe in immunocompromised patients
2. K. oxytoca
● Extraintestinal infections (rare):
◆ Causes similar infections to K. pneumoniae subsp. pneumoniae
○ Meningitis
3. Klebsiella granulomatis
○ Septicemia
◆ Causes granuloma inguinale (donovanosis)—a sexually transmitted
○ Cellulitis
infection
○ Septic arthritis
◆ Discussed in Chapter 77

INFECTIONS DUE TO NON-GI PATHOGENS

Citrobacter species
(Enterobacteriaceae members primarily causing extra-intestinal infections)
● Mostly environmental contaminants
● Can cause:
Uropathogenic E. coli (UPEC) ○ UTIs
● Most common cause of UTI ○ Gallbladder infections
● Discussed in Chapter 76 ○ Middle ear infections
○ Neonatal meningitis (Chapter 76)
Typhoidal Salmonellae
● Include: Serratia species
○ S. Typhi ● S. marcescens is most significant
○ S. Paratyphi A, B, and C ● Found in environment
● Cause enteric (typhoid/paratyphoid) fever ● Increasingly reported in nosocomial infections:
● Discussed under bloodstream infections (Chapter 30) ○ Meningitis
○ Endocarditis
Klebsiella species ○ Septicemia
○ UTIs
● Commensals in intestines; also found in soil
○ Respiratory and wound infections
● Includes:
● Covered in Chapter 61
1. K. pneumoniae
◆ 3 subspecies:
◇ K. pneumoniae subsp. pneumoniae Tribe Proteeae
■ Most pathogenic Includes three genera:
■ Causes: 1. Proteus
□ Severe lobar pneumonia (Chapter 61) 2. Morganella
□ UTIs 3. Providencia
□ Pyogenic infections ● Part of normal intestinal flora
□ Rarely causes diarrhea (due to heat-stable enterotoxin, ● Cause nosocomial outbreaks:
 ○ UTIs vulnificus
○ Wound infections
● Covered in Chapter 76
Serogrouping (Based on O Antigen – Sakazaki typing)
● >200 serogroups
● O1:
Morganella morganii
○ Causes all pandemics & most epidemics
● Also found in sea fish
○ Agglutinated by O1 antisera
● Causes scombroid food poisoning after seafood intake ● O139:
(Chapter 40)
○ Identified in 1992
○ Caused epidemics in coastal India & Bangladesh
Yersinia pestis ● Non-O1/O139:
● Agent of plague ○ Occasionally cause sporadic diarrhea or extraintestinal infections
● Systemic zoonosis transmitted from rodents by rat flea ● Old terms (obsolete):
● Discussed in Chapter 81 ○ NAG vibrios / NCV (Non-cholera vibrios) – previously for non-O1 strains

Cholera and Vibrio Infections Biotyping of O1 Serogroup

● Two Biotypes:
General Features of Vibrio 1. Classical
2. El Tor
● Shape: Curved, comma-shaped, Gram-negative bacilli
● Table: Classical vs El Tor Biotype
● Motility: Actively motile with single polar flagellum
● Name origin: "Vibrio" due to vibratory motility Feature Classical El Tor
● Discovery: Isolated by Robert Koch in 1886 (called Komma bacillus)
β-hemolysis on sheep Negative Positive
Habitat blood agar
● Ubiquitous in marine environments: seawater, seafood, rivers, surface waters, sewage Chick erythrocyte Negative Positive
● Salt-loving (halophilic)
agglutination
Classification of Vibrios Polymyxin B (50 IU) Susceptible Resistant
Based on Salt Requirement:
Group IV phage Susceptible Resistant
Type Salt Requirement Examples susceptibility
Nonhalophilic Grow without salt V. cholerae, V. El Tor Phage V Resistant Susceptible
(optimum 1%) mimicus susceptibility
Halophilic Require salt to grow V. parahaemolyticus, VP test Negative Positive
(up to 7–10%) V. alginolyticus, V.
Cholera toxin gene CTX-1 CTX-2
● • History: ○ Highly motile
○ Classical: Caused first 6 pandemics, highly virulent ○ Secretes:
○ El Tor: ◆ Mucinase
◆ Caused 7th pandemic (from 1961) ◆ Proteolytic enzymes
◆ Named after El Tor, Egypt ◆ Hemagglutinin protease (a.k.a. cholera lectin)
◆ Now dominant strain globally 2. Adhesion to intestinal epithelium:
● El Tor Variants/Hybrids: ○ Via Toxin-Coregulated Pilus (TCP)
○ Show traits of both biotypes (e.g., Matlab, Mozambique variants) 3. Toxin production:
○ Cholera toxin (CT) is the main virulence factor
Serotyping (within O1 Serogroup) ○ Structurally/functionally similar to E. coli heat-labile toxin (LT), but more potent

● Based on minor antigenic differences of O antigen

● Serotypes: Cholera Toxin (CT) – Mechanism of Action
1. Ogawa → Most common
Component Function
2. Inaba → Common during epidemics (mutation in rfbT gene from Ogawa)
3. Hikojima → Rare transitional serotype (expresses both Ogawa and Inaba antigens) B subunit Binds to GM1 ganglioside on
epithelial cell surface
Phage Typing
● Classical vs El Tor biotypes can be further differentiated A subunit Enters cell → ADP-ribosylates G
● Basu & Mukherjee typing: Most widely used protein → ↑ adenylate cyclase →
● Updated by:
○ Chattopadhyay (1993) for O1
↑ cAMP
○ Chakrabarti (2000) for O139 strains Result: Massive efflux of chloride ions and water → Profuse watery diarrhea

Pathogenesis of Cholera Cholera: Pathophysiology & Clinical Manifestations

Transmission Effect of Increased cAMP in Small Intestine

● Feco-oral route via contaminated water or food ● In Villus Cells:
Inhibits sodium absorption
Infective Dose ● In Crypt Cells:
Activates chloride secretion
● High: ~10⁸ organisms (due to acid-lability)
Result:
● Increased risk with:
○ ● Accumulation of NaCl in lumen
Hypochlorhydria
○ ● Water follows passively (to maintain osmolality) → leads to:
Antacids
○ ○ Watery diarrhea (loss of isotonic fluid)
Gastrectomy

Steps in Pathogenesis Consequences of Fluid & Electrolyte Loss

● Severe dehydration
1. Mucus layer penetration:
 ● Hypovolemic shock ● Vomiting: May be present
● Metabolic acidosis (due to loss of bicarbonate) ● Fever: Usually absent
● Muscle Cramps: Due to electrolyte loss
Genetic Basis of Cholera Toxin (CTX)
● Phage-encoded: Clinical Progression Based on Fluid Loss
○ CT gene carried by a filamentous bacteriophage (CTXφ)
% Fluid Loss Clinical Features
○ Integrated into V. cholerae genome (prophage)
● Phage also encodes: <5% Increased thirst
○ TCP (toxin-coregulated pilus)
○ Accessory colonization factors
5–10% - Postural hypotension
○ Other regulatory genes - Weakness
- Tachycardia
Additional Virulence Factors - ↓ Skin turgor |

1. Zona Occludens Toxin (Zot): | >10% | - Renal failure (acute tubular necrosis)
○ Disrupts tight junctions between epithelial cells - Oliguria
2. Accessory colonization factors - Weak/absent pulses
3. LPS (Endotoxin): - Sunken eyes, fontanelles
○ Immunogenic; used in killed vaccines - Wrinkled skin (washerwoman hands)
- Somnolence, coma |
Clinical Manifestations of Cholera

Type of Manifestation Percentage Laboratory Diagnosis: Cholera

Asymptomatic 75%
1. Specimens
Mild Diarrhea 20% ● Watery stool (preferred)
Cholera gravis (severe) 5% ● Rectal swab (for asymptomatic carriers)

Incubation Period:
2. Transport Media
24–48 hours
● VR medium
● Cary-Blair medium
Typical Clinical Features
● Watery Diarrhea: 3. Direct Microscopy
○ Sudden onset
● Gram stain:
○ Painless, large volume
○ Short, curved gram-negative rods (comma-shaped)
● Rice Water Stool:
○ "Fish in stream" appearance
○ Cloudy, mucus flakes
● Hanging drop preparation:
○ Non-bilious, no blood, no pus cells
○ Darting motility
○ Fishy, inoffensive odor
 ○ Darting motility
● Multiplex PCR: Detects multiple diarrheal pathogens
4. Culture ● Antimicrobial susceptibility testing: Essential for treatment guidance

Enrichment Broth
● Alkaline peptone water (pH 8.4) Non-O1/O139 V. cholerae
● Monsur’s taurocholate tellurite peptone water
Selective Media Similarities to O1/O139
● TCBS agar:
● Biochemically similar
○ Large yellow colonies
● Same treatment approach:
● Monsur’s GTTT agar
○ Fluid replacement is primary
● Bile salt agar
○ Antibiotics (e.g., tetracycline, ciprofloxacin, 3rd-gen cephalosporins) used in
● MacConkey agar:
severe cases
○ Non-lactose fermenting (translucent) colonies
Culture Smear & Motility Test
Differences
● Short, curved bacilli
● ● Do not agglutinate with O1/O139 antisera
Darting motility
● Do not cause epidemics

5. Identification
Clinical Features
● Biochemical tests (e.g., string test = positive)
● ● Associated with seafood (e.g. raw oysters)
Hemodigestion on blood agar
● ● Watery or partially formed stool, may be bloody or mucoid
Automated systems:
○ ● Abdominal cramps, nausea, vomiting, fever
MALDI-TOF
○ VITEK
Extraintestinal Manifestations
6. Typing Methods ● Otitis media, wound infections, bacteremia (esp. in liver disease patients)
● Usually due to contact with seawater (occupational or recreational)
Method Purpose ● Often require antibiotics

Biotyping Distinguish Classical vs El Tor

HALOPHILIC VIBRIO INFECTIONS
biotypes
Halophilic vibrios grow in high salt concentrations (>6%) and are commonly found in marine
Serogrouping Differentiate O1, O139, non-O1/ environments. Infections rise in late summer and early rainfall.

O139
1. Vibrio parahaemolyticus
Serotyping Differentiate Inaba, Ogawa,
Morphology & Lab Diagnosis
Hikojima (O1 only) ● Capsulated, bipolar staining (fresh cultures)
7. Antigen & Molecular Detection ● Peritrichous flagella (no darting motility)
● TCBS agar: Green colonies (non-sucrose fermenting)
● Cholera dipstick assay (rapid antigen test)
● Wagatsuma agar: Shows β-hemolysis (Kanagawa phenomenon)
 ● Severe cases: respond to tetracycline, drainage
● Swarming on blood agar
● May be urease-positive (some strains) AEROMONAS INFECTIONS
● Grows in up to 8% NaCl
Formerly under Vibrionaceae, now in Aeromonadaceae
● Automated ID: MALDI-TOF, VITEK
Common pathogens: A. hydrophila, A. caviae, A. veronii
Clinical Features
● Food-borne gastroenteritis (raw/undercooked seafood): watery diarrhea, sometimes
dysentery Pathogenic Mechanisms
● Rare extraintestinal infections: otitis, wound infection, sepsis ● Adhesins (S-layer, fimbriae)
Treatment ● Capsule (anti-phagocytic)
● Mostly self-limiting ● Exotoxins: aerolysin, hemolysins, enterotoxins
● Antibiotics (e.g. doxycycline, macrolide) if: ● Endotoxin (LPS)
○ Severe gastroenteritis
○ Underlying disease (e.g. diabetes, liver disease, immunosuppression) Clinical Manifestations
● Bacteremia: Doxycycline + Ceftriaxone ● Gastroenteritis (watery diarrhea, vomiting, sometimes dysentery)
● Peritonitis
2. Vibrio vulnificus ● Musculoskeletal/wound infections
Most virulent Vibrio; “vulnificus” = wound maker ● Bacteremia (esp. in immunocompromised adults/infants)
Clinical Syndromes ● Respiratory infections: epiglottitis, pharyngitis, pneumonia

1. Primary sepsis: In liver disease, iron overload, renal insufficiency, immunosuppressed

2. Primary wound infection: Cellulitis, bullae, necrosis in healthy people exposed to Lab Diagnosis
seawater ● Grows on routine media
Lab Diagnosis ● Oxidase and catalase positive
● Culture from blood or wound ● Species ID by MALDI-TOF, VITEK, or biochemical tests
● Lactose fermenting (unlike most vibrios)
● ID: MALDI-TOF, VITEK Treatment
Treatment
● First-line: Ciprofloxacin, Levofloxacin
● Early antibiotics, wound debridement, supportive care ● Alternatives: Cotrimoxazole, Cefepime
● Sensitive to: tetracycline, fluoroquinolones, 3rd-gen cephalosporins ● Plasmid-mediated resistance (β-lactamase production) reported

3. Vibrio alginolyticus
CAMPYLOBACTERIOSIS
Most salt-tolerant Vibrio (grows at >10% NaCl)
Organism
Clinical Features
● Campylobacter spp.: Curved, Gram-negative, non-sporing, motile rods (darting motility),
● Eye, ear, and wound infections (e.g. otitis externa/media, conjunctivitis)
microaerophilic
● Rare bacteremia (in immunocompromised)
● Major pathogens:
Treatment
○ C. jejuni – most common (80–90%)
● Usually self-limiting
○ C. coli, C. lari, C. upsaliensis – diarrheal disease
● Severe cases: respond to tetracycline, drainage
○ C. fetus – systemic disease (bacteremia, meningitis, etc.)
 Epidemiology Pathogenesis
● Zoonotic: Found in poultry, cattle, sheep, swine, pets Colonization
● Transmission: ● Motility: Reaches mucus layer
○ Ingestion: undercooked poultry, unpasteurized milk, untreated water ● Urease: Converts urea → ammonia → neutralizes acid
○ Contact with infected animals or oral-anal sex ● Other enzymes: amidase, arginase
● Low infective dose: <500 organisms Virulence Factors
Pathogenesis ● Adhesins:
● Flagella: motility + darting movement ○ Blood group antigen-binding adhesin (binds Lewis Ag)
● Adhesion to intestinal cells ○ Adherence-associated lipoprotein
● Toxins: ● VacA (Vacuolating cytotoxin): Forms cytoplasmic vacuoles
○ Enterotoxin (heat-labile, cholera-like) ● CagA:
○ Cytolethal Distending Toxin (CDT) ○ Cytoskeletal rearrangement
● S-layer in C. fetus for immune evasion ○ Oncogene expression
Clinical Manifestations ○ ↑ Proinflammatory cytokines
● Molecular mimicry: LPS mimics Lewis antigen → autoimmunity
● Incubation: 2–4 days
● LPS: Inhibits mucus glycosylation → increases acid damage
● Intestinal:
● Resistance to oxidative stress: Detox enzymes
○ Inflammatory diarrhea (may be bloody)
● Host genetics: IL-1, TLR polymorphisms ↑ risk of cancer
○ Fever, abdominal cramps
○ Self-limiting, but 5–10% may relapse if untreated
Clinical Manifestations
● Complications: ● Gastritis:
○ Guillain–Barré syndrome (esp. serotype O19) ○ Antral → duodenal ulcer
○ Reactive arthritis ○ Pangastritis → gastric cancer
○ Irritable bowel syndrome ● Peptic ulcer disease:
○ Alpha chain disease (intestinal lymphoma) ○ ~70% duodenal ulcers, ~50% gastric ulcers linked to H. pylori
○ Sepsis, meningitis in immunocompromised (esp. C. fetus) ○ Duodenal ulcer: ↑ gastrin → ↑ acid → gastric metaplasia
○ Gastric ulcer: Mechanism less clear (hypochlorhydria)
○ Symptoms: Epigastric burning pain (after meals/empty stomach)
HELICOBACTER INFECTIONS (H. pylori) ● Chronic atrophic gastritis
Characteristics ● Autoimmune gastritis, pernicious anemia
● Curved Gram-negative rod ● Gastric adenocarcinoma, MALT lymphoma
● Highly motile (4–8 unipolar flagella) Protective Role
● Urease positive ● Inverse association with:
● Colonizes stomach mucosa, especially antrum ○ GERD
Epidemiology ○ Barrett’s esophagus
● ○ Esophageal adenocarcinoma
Reservoir: Humans only
● ○ Asthma, allergies
Prevalence: ~50% globally
● Higher in developing countries
● Transmission: Fecal-oral, oral-oral, possibly gastric-oral Laboratory Diagnosis of H. pylori
1. Invasive Tests 1. Etiology and Characteristics
Require endoscopy with gastric biopsies (from antrum and corpus): ● Organism: Clostridioides difficile (formerly Clostridium difficile)
● Histopathology ● Morphology: Obligate anaerobic, gram-positive, spore-forming bacillus
○ Staining: Warthin-Starry silver stain or immunostaining with anti-H. pylori ● Disease: Pseudomembranous colitis, mainly healthcare-associated
antibodies ● Unique: Difficult to isolate (hence “difficile”)
○ Visualizes curved black rods on gastric mucosa
○ Sensitivity improved by combining stains 2. Pathogenesis
● Microbiological Methods ● Risk Factors:
○ Gram stain: Curved, seagull-shaped Gram-negative bacilli ○ Prolonged hospital stay (spore colonization)
○ Culture: Most specific test but less sensitive ○ Prolonged antibiotic use → disrupts normal gut flora
◆ Media: Skirrow’s media, chocolate agar ◆ Common antibiotics implicated: Cephalosporins (ceftriaxone), clindamycin,
◆ Conditions: 37°C, microaerophilic (5% oxygen)
ampicillin, fluoroquinolones
◆ Identification: MALDI-TOF or urease test, biochemical assays ○ Other factors: Advanced age (>65), immunosuppression, chemotherapy, gastric
● Biopsy Urease Test (Rapid Urease Test)
acid suppressants, GI surgeries, electronic rectal thermometer use
○ Detects urease enzyme activity directly in biopsy tissue ● Toxin-Mediated Disease:
○ Uses urea broth with pH indicator → color change if urease present ○ Only toxigenic strains cause disease
○ Rapid, sensitive, inexpensive ○ Produce Toxin A (enterotoxin) and Toxin B (cytotoxin)
○ Toxins glycosylate GTP-binding proteins → disrupt actin cytoskeleton → epithelial
2. Noninvasive Tests damage → diarrhea & pseudomembrane formation
● Urea Breath Test ○ Infants are often asymptomatic carriers (lack toxin receptors)
○ Patient ingests ^13C-labeled urea ○ Host immune response critical: Strong IgG to toxin A → asymptomatic carriage;
○ Urease hydrolyzes urea → releases labeled CO2 weak IgG → disease
○ Detects labeled CO2 in breath by mass spectrometry ● Hypervirulent Strain:
○ Advantages: ○ Ribotype BI/NAP1/027 → produces more toxins → severe disease
◆ Best test for live bacteria detection ○ Drug of choice: Fidaxomicin
◆ Highly sensitive, accurate, quick, simple
◆ Used for treatment monitoring (turns negative after cure) 3. Clinical Manifestations
● Fecal Antigen Test (Coproantigen Assay) ● Main Symptoms:
○ Detects H. pylori antigens in stool (live and dead bacteria) ○ Diarrhea (≥3 unformed stools/day)
○ Sensitivity and specificity: 90–95% ○ Fever, abdominal pain, leukocytosis
○ Used for treatment monitoring and screening in children ○ Blood in stool is rare
● Serology (IgG Antibody ELISA) ● Pseudomembrane:
○ Detects antibodies against H. pylori ○ Composed of necrotic leukocytes, fibrin, mucus, cellular debris
○ Used for screening before endoscopy and in seroepidemiological studies ○ Whitish-yellow plaques on colonic mucosa, size variable
○ Not useful for treatment monitoring (antibodies persist after cure) ○ Causes colonic mucosal damage
○ Relapse common (15–30%)
Clostridioides difficile Infection (CDI)
4. Laboratory Diagnosis
Diagnostic Method Description & Notes Colonoscopy - Visualizes pseudomembranes
Stool Culture - Anaerobic culture on selective (high specificity, low sensitivity)
media (CCFA, CCYA) at 37°C for Histopathology - Biopsy shows
24–48h pseudomembranous colitis on
- Highly sensitive & specific but H&E stain
isolation alone insufficient (due to - Highly specific but low
colonization) sensitivity
Cell Culture Cytotoxin - Detects functional toxin activity
VIRAL GASTROENTERITIS
Neutralization
Common Viral Causes:
- Highly specific but less sensitive ● Rotavirus (most common in children)
and longer turnaround time ● Norovirus, Adenovirus, Astrovirus, Calicivirus, Sapovirus (other notable viruses)
Affects all age groups but most severe in infants and young children.
Antigen Detection - Enzyme immunoassay or rapid
tests detect: ROTAVIRUS DIARRHEA

• Toxin A/B (presence indicates 1. Morphology & Classification

● Family: Reoviridae (only virus family with double-stranded RNA)
toxigenic strain) ● Structure:
• Glutamate Dehydrogenase ○ Size: 60–80 nm
○ Triple-layered, icosahedral capsid (wheel-like appearance → “Rota”)
(GDH) (common antigen, detects ○ Genome: Segmented dsRNA (11 segments)
toxigenic and non-toxigenic ● Important Proteins:
○ VP6: Group-specific
strains) ○ VP7 (G-type): Outer capsid glycoprotein (serotyping)
- GDH positive but toxin negative ○ VP4 (P-type): Spike protein, protease-sensitive (genotyping)
○ NSP4: Non-structural protein, acts as an enterotoxin
suggests non-toxigenic strain 2. Typing
Molecular Methods (PCR, real- - Target genes tcdA (toxin A), ● Group A: Major cause of human disease
● Binary classification:
time PCR) tcdB (toxin B), tpi
○ G-type (VP7) = Serotype (e.g., G1, G2)
- Highly sensitive, specific, and ○ P-type (VP4) = Genotype (e.g., P[8], P[4])
● Most common globally and in India: G1P[8]
fast turnaround
3. Pathogenesis ROTAVAC (India-made)

● Transmission: Fecal–oral route ● Strain: Live attenuated 116E (G9P[11])

● Tropism: Infects small intestinal enterocytes (gastric and colonic mucosa spared) ● Cross-protection: Covers G1P[8] (most common)
● Mechanism: ● Schedule: 3 doses (oral) at 6, 10, and 14 weeks with DPT & OPV
○ Replicates in enterocyte cytoplasm → damages transport → secretory diarrhea ● Efficacy: ~55% in first 2 years of life
○ NSP4 toxin alters permeability and epithelial function ● Side Effects: Crying, irritability, fever, diarrhea (≥5%); no intussusception reported
● Result: Electrolyte and fluid loss → dehydration ● Used in: Indian states (under National Immunization Program since 2020)
ROTARIX
● Strain: Live attenuated G1P[8]
4. Clinical Features
● Cross-protection: G3, G4, G9
● Incubation: 1–3 days
● Schedule: 2 doses (oral): 1st at 6 weeks, 2nd after 4 weeks
● Symptoms:
● Reconstitution required before use
○ Sudden onset vomiting, followed by watery diarrhea, fever, abdominal pain
● Course: Usually self-limiting (~3–8 days)
● Complication: Dehydration (main concern in children)
● Adults: Often asymptomatic but may show seroconversion; outbreaks in closed settings Virus Genome Gastroenteritis
(e.g. geriatric wards)
● Group B rotavirus: Implicated in adult outbreaks (e.g. China) Features
Rotavirus* Segmented dsRNA - Group A: Most
5. Laboratory Diagnosis
common cause of
● Ideal specimen: Early stool sample
severe endemic
Test Description
diarrheal illness in
Immunoelectron Microscopy Characteristic wheel-like virus
children worldwide-
(IEM) seen in stool
Group B: Outbreaks of
ELISA / Latex Agglutination Detects viral antigen in stool
diarrhea in adults
(commonly used)
(notably in China)
RT-PCR Most sensitive method; detects
Norovirus ssRNA - Causes outbreaks
and types RNA segments
of vomiting and
Tissue culture Rarely done; difficult to isolate
diarrheal illness in all
Serology (ELISA) Detect antibody rise; used for age groups,
seroprevalence, not acute especially older
diagnosis children and adults
6. Prevention – Vaccines
Sapovirus ssRNA - Causes sporadic
cases and occasional
outbreaks of diarrheal
illness in infants,
young children, and
the elderly
Astrovirus ssRNA - Second most
common viral agent of
endemic diarrhea in
infants and young
children
Adenovirus* dsDNA - Type 40 & 41:
Cause severe
diarrheal illness in
infants and young
children- Can also
affect
immunocompromised
individuals