Comma-shaped rods Notes

NOTES NOTES COMMA–SHAPED RODS MICROBE OVERVIEW ▪ Gram-negative, facultative anaerobes, motile, non-spore forming CAMPYLOBACTER JEJUNI osms.it/campylobacter-jejuni PATHOLOGY & CAUSES Characteristics ▪ Zoonotic disease ▫ Reservoir in wild, domestic mammals, birds (esp. poultry) ▪ Oxidase +; invasive; microaerophilic; sensitive to heat, desiccation, acidity, irradiation, disinfectants Virulence factors ▪ Fimbriae-like filaments ▫ Promote attachment to intestinal 358 OSMOSIS.ORG epithelial cells ▪ Possesses single, unsheathed flagellum in one end (monotrichous)/two flagella each at both ends (amphitrichous) ▫ Provide motility, chemotaxis (mucin is chemoattractant → tropism for ileum, colon, rectum) ▪ Surface proteins (eg, PEB1, CadF) promote colonization, invasion of intestinal epithelial cells ▪ Lipopolysaccharide (LPS) ▫ Plays role in adherence, evasion of host immune response (undergoes antigenic variation)

Chapter 65 Comma-shaped Rods Culture ▪ Isolation specimen: stool, food ▪ Media: blood/charcoal agar with microaerophilic atmosphere (5–10% O2, 3–5% CO2), thermophilic environment (optimal 42°C/107.6°F) ▪ C. jejuni: one of most common bacterial causes of gastroenteritis with acute diarrhea Transmission ▪ Fecal-oral, contaminated water Pathogenesis ▪ Incubation period 1–7 days; tropism for distal ileum, colon, rectum ▪ Inoculation of bacteria → passage through upper GI tract → colonization, adherence to surface epithelium of distal ileum, colon → non-inflammatory secretory diarrhea (exact mechanism unknown) ▪ Invasion of intestinal epithelium, proliferation → release of cytolethal distending toxin → cell damage, inflammatory response → dysentery with fecal leukocytes ▪ Rare: translocates into lamina propria, spreads to mesenteric lymph nodes (mesenteric adenitis) → extraintestinal infections (e.g. meningitis, cholecystitis, UTI) ▫ Occurs mostly in immunocompromised RISK FACTORS ▪ Consumption of undercooked meat/ unpasteurized milk ▪ Underlying conditions/medications that reduce/buffer gastric acidity (e.g. proton pump inhibitors) ▪ Individuals with HIV/AIDS COMPLICATIONS ▪ Toxic megacolon, massive bleeding, colonic perforation ▪ Reactive arthritis ▪ Associated with Guillain–Barré syndrome ▫ Sialic acid contained bacterial core oligosaccharide can resemble gangliosides → cross-activation of autoreactive T/B cells (molecular mimicry) SIGNS & SYMPTOMS ▪ Vary in severity depending upon inoculum concentrations; range from asymptomatic carriage to systemic illness ▫ Most episodes mild, self-limiting (up to one week); rarely persists up to several weeks ▪ Fever, myalgia, malaise, headache (early symptoms, 1–2 days); severe periumbilical abdominal pain, cramping, secretory, inflammatory diarrhea, vomiting ▫ Abdominal pain may mimic acute appendicitis ▫ Secretory diarrhea: more common in children ▫ Inflammatory diarrhea: tenesmus, bloody stools, fecal leukocytes DIAGNOSIS LAB RESULTS ▪ Stool culture ▪ Rapid diagnosis with carbolfuchsin stain/ phase-contrast/dark-field microscopic examination of fresh stool specimen in case of acute manifestation ▪ PCR-based methods, enzyme immunoassays (EIAs) directly from stool OTHER DIAGNOSTICS ▪ Clinical manifestations ▪ Histology ▫ Acute mucosal inflammation with edema, cellular infiltration of lamina propria, crypt abscess formation TREATMENT MEDICATIONS ▪ Antibiotics for severe cases, immunocompromised individuals ▫ Erythromycin/azithromycin OTHER INTERVENTIONS ▪ Replacement of fluids, electrolytes OSMOSIS.ORG 359

HELICOBACTER PYLORI osms.it/helicobacter-pylori PATHOLOGY & CAUSES Characteristics ▪ Urease +, catalase +, oxidase +; noninvasive ▪ Microaerophilic ▫ Requires oxygen, lower concentrations than present in atmosphere Virulence factors ▪ Possesses 2–7 unipolar sheathed flagella (H-antigen) ▫ Provide motility, chemotaxis (sense pH, move bacteria towards beneficial environment) ▪ Lipopolysaccharide (LPS) ▫ Promotes adherence, causes inflammation ▪ Coccoid form ▫ More resistant form; occurs as adaptation to hostile environment outside human body ▪ Urease ▫ Important for survival, colonization ▪ Mucolytic enzymes ▫ Allow passage through mucus layer to gastric epithelium ▪ Adhesive proteins (Hop proteins) ▪ Vacuolating cytotoxin A (VacA) ▫ Damages epithelial cells; disrupts tight junctions, causes apoptosis ▪ Cytotoxin associated gene CagA (CagA) ▫ Triggers inflammation ▪ Type IV secretion system ▫ Pili-like structure for injection of effectors (e.g. CagA) ▪ Proteases, lipases ▪ Biofilm formation Culture ▪ Isolation specimen: vomitus, diarrheal stools ▪ Media: blood agar/selective Skirrow’s media 360 OSMOSIS.ORG incubated at 37ºC/98.6°F in 5% oxygen; small, uniformly sized, translucent bacterial colonies ▪ H. pylori: causative agent of most common chronic infection in humans; common cause of duodenal, gastric ulcers, chronic gastritis Transmission ▪ Unknown; fecal/oral, oral/oral transmission suggested ▪ Reservoir ▫ Human (majority of cases); found in primates in captivity, domestic cats, sheep ▪ Also found in municipal water in endemic areas of infection with polymerase chain reaction (PCR) techniques Pathogenesis ▪ Bacterial urease hydrolyzes gastric luminal urea to form ammonia → ↑ gastric pH → formation of protective layer around bacteria → survival in hostile gastric environment ▪ ↑ pH → mucin liquefies → H. pylori passes through mucous layer to surface epithelium via bacterial flagella, mucolytic enzymes → attaches to specific gastric epithelial cell receptors via surface adhesins (Hop proteins) → release of proteases (VacA, CagA) + host immune response → inflammation, tissue injury ▪ Disruption of mucous layer → susceptibility to acid peptic damage ▪ Chronic inflammation, tissue injury together with acid peptic damage → chronic gastritis, peptic ulcers (10–20% risk) RISK FACTORS ▪ ▪ ▪ ▪ ▪ Low socioeconomic status Increased housing density Lack of running water Genetic susceptibility Swimming in pools, rivers, streams

Chapter 65 Comma-shaped Rods COMPLICATIONS ▪ Gastric carcinoma (1–2% risk): chronic gastritis → atrophic gastritis, intestinal metaplasia, carcinoma ▫ Chronic inflammation, ↑ TNF, ↑ IL-6, ↑ bacterial proteases → excessive tissue damage, cell mutation → intestinal metaplasia → carcinoma ▪ Gastric mucosa-associated lymphomas due to persistent immune stimulation of gastric lymphoid tissue ▫ Omeprazole/pantoprazole + clarithromycin, amoxicillin: in case of penicillin sensitivity, replace amoxicillin with metronidazole SIGNS & SYMPTOMS ▪ Majority of cases asymptomatic ▪ Acute infection ▫ Upper abdominal pain, nausea, loss of appetite ▪ Chronic infection ▫ Chronic gastritis: upper abdominal pain, nausea, bloating, vomiting/melena (black stool) ▫ Peptic ulcers: stomach pain/ache; occurs with empty stomach, between meals, early morning Figure 65.1 Helicobacter organisms in a gastric pit. DIAGNOSIS LAB RESULTS ▪ Blood antibody test ▪ Stool antigen test ▪ Carbon urea breath test ▫ Individual ingests 14C- or 13C-labelled urea, which bacterium metabolizes, yielding labelled carbon dioxide detectable in breath ▪ Urine enzyme-linked immunosorbent assay (ELISA) test TREATMENT MEDICATIONS ▪ One-week “triple therapy”: antacid/acidreducing drugs (H2-receptor antagonists/ proton pump inhibitors) + two antibiotics ▫ Bismuth salicylate + metronidazole + tetracycline ▫ Ranitidine bismuth citrate + tetracycline + clarithromycin/metronidazole OSMOSIS.ORG 361

VIBRIO CHOLERAE (CHOLERA) osms.it/vibrio-cholerae PATHOLOGY & CAUSES Characteristics ▪ Oxidase +; non-invasive; halophilic; genome consists of two circular chromosomes; sensitive to acid, drying ▪ Reservoir: aquatic environments (saltwater, brackish) ▪ Fermentation: glucose, sucrose Virulence factors ▪ Cholera toxin ▫ Only toxigenic strains; responsible for pathogenesis of massive, watery diarrhea; coded by filamentous bacteriophage (CTXΦ) ▪ Other toxins that increase mucosal permeability ▫ Zona occludens toxin (ZOT), accessory cholera enterotoxin (ACE), WO7 toxin 17 ▪ Lipopolysaccharide (LPS) ▫ > 200 serogroups; O1, O139 associated with cholera epidemics ▪ Motility ▫ Single polar flagellum (H-antigen) ▪ Toxin-coregulated pilus (TCP) ▫ Present only in toxigenic strains; promotes adherence, aggregation of bacteria; coded by genes in Vibrio pathogenicity island (VPI) ▪ Mucinase ▫ Digests mucous layer of gastrointestinal (GI) tract Culture ▪ Isolation specimen: stool, rectal swab ▪ Media: thiosulfate citrate bile salts sucrose (TCBS) agar/taurocholate tellurite gelatin agar (TTGA); large, yellow colonies (2–4mm diameter) with opaque centers, translucent edges 362 OSMOSIS.ORG ▪ V. cholerae: diverse species; pathogenic, toxin-producing (toxigenic) variants cause cholera ▪ Cholera characterized by profound secretory diarrhea → rapid, life-threatening dehydration ▪ Transmitted by fecal-oral route/ contaminated food or water Pathogenesis ▪ Inoculation → passage through upper GI tract → rapid movement of bacteria through mucous via flagellum → colonization of small intestine via TCP → releases cholera toxin ▪ Cholera toxin (AB protein toxin) → B subunit binds to GM1 ganglioside on intestinal epithelial cell, allows entry of A subunit → activates G-protein regulated adenylyl cyclase → ↑ intracellular cyclic adenosine monophosphate (AMP) → secretion of chloride, sodium; inhibition of sodium chloride absorption → massive fluid secretion; loss of sodium, chloride, bicarbonate, potassium TYPES Pathogenic (toxin-producing), nonpathogenic Serological classification: O antigen differences ▪ Serogroup O1 is subdivided into two serotypes (Inaba, Ogawa), two biotypes ▫ El Tor: cause of current global pandemic of cholera ▫ Classical: cause of previous V. cholerae pandemics; now thought extinct ▪ Serogroup O139 ▪ Non-O1/O139 RISK FACTORS ▪ Travel to endemic/epidemic areas ▪ Inadequate access to clean water

Chapter 65 Comma-shaped Rods ▪ Shellfish consumption in areas with sporadic cholera ▪ People with blood group O at higher risk for severe cholera (mechanism unknown) COMPLICATIONS ▪ If untreated ▫ Dehydration, hypovolemic shock in 4–12 hours, death in 18 hours to several days ▪ Renal failure secondary to hypovolemia ▪ Electrolyte imbalances ▫ Hypokalemia, metabolic acidosis ▪ Pneumonia (esp. in children) due to aspiration of vomit SIGNS & SYMPTOMS ▪ Incubation period is 28–48 hours ▪ Asymptomatic to severe depending upon strain, inoculum concentration (≥ 108 → severe form) ▪ Abrupt onset of profound watery diarrhea (grey, cloudy, flecked with mucus; “ricewater stool”); painless, without tenesmus; loss of 1 liter of fluid per hour in severe cases ▪ Moderate to severe vomiting, borborygmus, abdominal discomfort ▪ Dehydration ▫ Thirst, dry mucous membranes, decreased skin turgor, sunken eyes, hypotension, weak/absent radial pulse, tachycardia, tachypnea, hoarse voice, oliguria ▪ Altered mental status ▫ Somnolence, restlessness, lethargy ▫ Culture on TCBS agar ▫ Dark field microscopy/dipstick test of stool specimen for rapid confirmation in non-endemic areas (detectable in stool for 1–2 weeks without antimicrobial therapy) TREATMENT MEDICATIONS ▪ Oral antibiotic treatment reduces duration, severity of disease ▫ Doxycycline for adults ▫ Azithromycin for children, pregnant individuals OTHER INTERVENTIONS ▪ Prophylaxis ▫ WC-rBS (Dukoral) vaccine: monovalent inactivated oral cholera vaccine containing killed whole cells of V. cholerae O1, additional recombinant cholera toxin B subunit ▫ BivWC (Shanchol) vaccine: bivalent inactivated oral vaccine containing killed whole cells of V. cholerae O1, O139 ▫ CVD 103-HgR/Vaxchora vaccine: attenuated oral vaccine derived from serogroup O1 classical Inaba strain ▪ Rapid, aggressive volume replacement (oral/intravenous fluids) ▪ Adequate nutrition to prevent malnutrition ▪ Correction of electrolyte imbalances ▪ Zinc supplementation reduces duration, severity of disease DIAGNOSIS LAB RESULTS ▪ Hypoglycemia/hyperglycemia ▪ Hypercalcemia, hypermagnesemia, hyperphosphatemia ▪ ↑ hematocrit due to volume depletion OTHER DIAGNOSTICS ▪ Clinical presentation ▪ Microbiologic diagnosis OSMOSIS.ORG 363