Vibrio

Vibrio is a genus of comma-shaped, gram-negative bacilli. It is halophilic, acid labile, and commonly isolated on thiosulfate-citrate-bile-sucrose (TCBS) agar. There are 3 clinically relevant species. Vibrio cholerae (V. cholerae) is found in brackish and marine waters. Vibrio cholerae is associated with cholera, which causes severe, secretory “rice-water” diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea. The other 2 species are Vibrio vulnificus (V. vulnificus) and Vibrio parahaemolyticus (V. parahaemolyticus), which are transmitted through raw or undercooked shellfish and are associated with wound infections, septicemia, and diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea.

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Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

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Classification

Gram negative bacteria classification flowchart

Gram-negative bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview:
Most bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview can be classified according to a lab procedure called Gram staining.
Bacteria with cell walls that have a thin layer of peptidoglycan do not retain the crystal violet stain utilized in Gram staining. These bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview do, however, retain the safranin counterstain and thus appear as pinkish-red on the stain, making them gram negative. These bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview can be further classified according to morphology (diplococci, curved rods, bacilli, and coccobacilli) and their ability to grow in the presence of oxygen (aerobic versus anaerobic). The bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview can be more narrowly identified by growing them on specific media (triple sugar iron (TSI) agar) where their enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body's constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes can be identified (urease, oxidase) and their ability to ferment lactose can be tested.
* Stains poorly on Gram stain
** Pleomorphic rod/coccobacillus
*** Require special transport media

Image by Lecturio.

General Characteristics

Basic features of Vibrio

  • Curved gram-negative bacilli
  • Facultative anaerobes
  • Highly motile: 1–3 polar flagella
  • Non-spore forming
  • Oxidase positive

Major pathogenic species

  • Vibrio cholerae (V. cholerae)
  • V. vulnificus
  • V. parahaemolyticus

Biochemistry and growth characteristics

  • Halophilic: require sodium chloride (NaCl) for growth
  • Acid labile: grows well in alkaline media
  • Thiosulfate-citrate-bile-sucrose (TCBS) agar:
    • V. cholerae ferments sucrose → forms yellow colonies
    • V. parahaemolyticus and V. vulnificus do not ferment sucrose → form green colonies
  • V. parahaemolyticus exhibits the Kanagawa phenomenon:
    • Beta-hemolytic on blood agar if isolated from human host
    • Non-hemolytic if from non-human sources

Reservoirs

  • V. cholerae: found in brackish and marine waters
  • V. vulnificus and V. parahaemolyticus: shellfish

Clinical Relevance of Vibrio cholerae

Epidemiology

  • Primarily occurs in areas with limited access to clean water
  • Endemic in some countries in Africa and Asia
  • Cholera affects only humans.

Transmission

  • Through contaminated food or water
  • Fecal-oral route (person-to-person)

Pathogenesis

  • Not all strains are pathogenic.
  • Pathogenesis is determined by production of cholera toxin (CT):
    • Carried by a lysogenic bacteriophage (CTXΦ)
    • Heat-labile enterotoxin: composed of 1 A subunit (toxic domain) and 5 B subunits (receptor-binding domain)
    • B-subunit binds to the mucosal receptor ganglioside monosialotetrahexosylganglioside (GM1).
    • CT is internalized by endocytosis: The A1 subunit of the toxin activates adenylyl cyclase, which converts adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP).
    • cAMP causes chloride secretion into lumen and inhibition of sodium absorption. 
    • Water follows the osmotic gradient and moves into the lumen, resulting in watery diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea with electrolyte concentrations isotonic to those of plasma.
    • Stool contains large amounts of sodium, chloride, bicarbonate, and potassium with few cells.
  • O lipopolysaccharide antigens: 
    • Confer serologic specificity; > 200 serotypes 
    • Only strains of O1 (classic and El Tor biotypes) and O139 serogroups cause epidemic and pandemic cholera (they are the most virulent).
  • Fimbriae (pili):
    • Aid in attachment to the intestinal mucosa
    • V. cholerae does NOT invade the intestinal mucosa.
    • Co-expressed (co-regulated) with cholera toxin and needed for adherence, biofilm formation, colonization, and as receptors for the bacteriophage that carries the genes for cholera toxin
  • Because V. cholerae are acid labile, a high inoculum is required to overcome the acidity of the gastric mucosa. The infectious dose is reduced:
    • In hypochlorhydric persons
    • In those using antacids
    • When gastric acidity is buffered by a meal
  • The higher the bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview number, the more severe the symptoms.
  • Incubation period: 1–2 days
  • Fluid loss originates in the duodenum and upper jejunum; the ileum is less affected.
  • The colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix is relatively insensitive to the toxin, but the large volume of fluid overwhelms its absorptive capacity.

Clinical presentation

About 50% of infections with classic V. cholerae are asymptomatic and 75% of infections with El Tor biotype of V. cholerae are asymptomatic.

Diarrhea:

  • May be mild, moderate, or severe
  • Clinical presentation of severe, secretory diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea:
    • Typically painless, without tenesmus
    • “Rice-water” stool (non-malodorous, watery stool with flecks of mucus)
    • Stool output can reach as high as 1 L/hour in severe cases (the most of any other infectious diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea).
    • Vomiting: may precede or follow the onset of diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
  • Consequences of severe, secretory diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea:
    • Profound fluid and electrolyte loss → “isotonic dehydration”:
      • A type of dehydration most frequently caused by diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
      • Occurs when the net losses of water and sodium are in the same proportion as normally found in the extracellular fluid
      • Metabolic acidosis Metabolic acidosis The renal system is responsible for eliminating the daily load of non-volatile acids, which is approximately 70 millimoles per day. Metabolic acidosis occurs when there is an increase in the levels of new non-volatile acids (e.g., lactic acid), renal loss of HCO3-, or ingestion of toxic alcohols. Metabolic Acidosis due to loss of bicarbonate
      • Acute kidney injury Acute Kidney Injury Acute kidney injury refers to sudden and often reversible loss of renal function, which develops over days or weeks. Azotemia refers to elevated levels of nitrogen-containing substances in the blood that accompany AKI, which include BUN and creatinine. Acute Kidney Injury (acute renal failure) is a possible complication. 
    • Symptoms and signs depend on volume contraction (severity of hypovolemia):
      • < 5% of normal body weight (NBW): thirst
      • 5%-10% of NBW: postural hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension, weakness, muscle cramps, tachycardia, ↓ skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin turgor, dry oral mucosa 
      • > 10% of NBW: oliguria, weak pulses, sunken eyes (sunken fontanelles in infants), wrinkled skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin, somnolence, coma Coma Coma is defined as a deep state of unarousable unresponsiveness, characterized by a score of 3 points on the GCS. A comatose state can be caused by a multitude of conditions, making the precise epidemiology and prognosis of coma difficult to determine. Coma
    • In severe cases, quick progression to hypovolemic shock Shock Shock is a life-threatening condition associated with impaired circulation that results in tissue hypoxia. The different types of shock are based on the underlying cause: distributive (↑ cardiac output (CO), ↓ systemic vascular resistance (SVR)), cardiogenic (↓ CO, ↑ SVR), hypovolemic (↓ CO, ↑ SVR), obstructive (↓ CO), and mixed. Types of Shock and death if not treated urgently

Pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia:

  • Not uncommon in children
  • Probably from vomitus aspiration
Cholera diarrhea rice water

Typical cholera diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea that looks like “rice water”

Image: “Here, a cup of typical “rice-water” stool from a cholera patient shows flecks of mucus that have settled to the bottom” by CDC. License: Public Domain

Management

Mortality in untreated patients is up to 50%-70% (but < 1% with prompt electrolyte and fluid replacement).

Treatment:

  • Aggressive oral rehydration therapy with electrolytes Electrolytes Electrolytes are mineral salts that dissolve in water and dissociate into charged particles called ions, which can be either be positively (cations) or negatively (anions) charged. Electrolytes are distributed in the extracellular and intracellular compartments in different concentrations. Electrolytes are essential for various basic life-sustaining functions. Electrolytes
  • Antibiotics may be used to shorten duration of diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea, most often doxycycline.

Prevention:

  • Clean water supply and appropriate sanitation are the keys to prevention.
  • General precautions for the prevention of travelers’ diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea:
    • Avoidance of tap water, food from street vendors, raw or undercooked seafood, and raw vegetables
    • Non-bottled water should be treated with chlorine or iodine, filtrated, or boiled. 
  • Vaccines:
    • Killed whole-cell oral vaccines are recommended by the World Health Organization for residents in endemic areas.
    • For U.S. travelers to high-risk areas at high risk for exposure:
      • A live oral vaccine Vaccine A vaccine is usually an antigenic, non-virulent form of a normally virulent microorganism. Vaccinations are a form of primary prevention and are the most effective form due to their safety, efficacy, low cost, and easy access. Vaccination against serotype O1 is available (“Vaxchora”).
      • The vaccine Vaccine A vaccine is usually an antigenic, non-virulent form of a normally virulent microorganism. Vaccinations are a form of primary prevention and are the most effective form due to their safety, efficacy, low cost, and easy access. Vaccination lacks the gene that encodes for the cholera toxin.

Diagnosis

  • Stool culture (the gold standard) on selective media (TCBS or taurocholate-tellurite-gelatin agar):
    • V. cholerae produces yellow colonies (due to sucrose fermentation).
    • Non-sucrose fermenting vibriones (e.g., most strains of V. parahaemolyticus and V. vulnificus) produce green colonies.
    • Gram stain and biochemical testing of isolates: All vibriones are oxidase positive.
    • Serotyping with specific antisera
  • Stool microscopic examination: only a few neutrophils because the intestinal wall is not invaded
  • Rapid antigen-detection tests: 
    • Crystal VC: detects O1 and O139 antigens
    • Cholkit: detects O1 antigen
  • Molecular testing (e.g., polymerase chain reaction (PCR): limited to epidemiologic research and surveillance)

Clinical Relevance of V. vulnificus and V. parahaemolyticus

V. vulnificus

  • The leading cause of shellfish-associated deaths in the United States
  • Diarrhea
  • Wound infections:
    • Associated with hand Hand The hand constitutes the distal part of the upper limb and provides the fine, precise movements needed in activities of daily living. It consists of 5 metacarpal bones and 14 phalanges, as well as numerous muscles innervated by the median and ulnar nerves. Hand injuries while opening oysters, or leg Leg The lower leg, or just "leg" in anatomical terms, is the part of the lower limb between the knee and the ankle joint. The bony structure is composed of the tibia and fibula bones, and the muscles of the leg are grouped into the anterior, lateral, and posterior compartments by extensions of fascia. Leg lacerations during boating activities
    • May cause hemorrhagic bullae
    • May range from mild cellulitis Cellulitis Cellulitis is a common infection caused by bacteria that affects the dermis and subcutaneous tissue of the skin. It is frequently caused by Staphylococcus aureus and Streptococcus pyogenes. The skin infection presents as an erythematous and edematous area with warmth and tenderness. Cellulitis to severe necrotizing infections
  • Primary septicemia:
    • Associated with ingestion of raw or undercooked shellfish, most commonly oysters
    • More common in those with chronic, underlying conditions:
      • Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver disease (alcoholics, cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis)
      • Hemochromatosis

V. parahaemolyticus

  • The leading cause of foodborne illness in Japan (especially shellfish)
  • Also associated with diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea, wound infections, and septicemia
  • Same risk factors as V. vulnificus

References

  1. Aryal, S. (2018). Thiosulfate-citrate-bile salts-sucrose (TCBS) Agar. https://microbenotes.com/thiosulfate-citrate-bile-salts-sucrose-tcbs-agar/
  2. Morris J.G. (2020). Vibrio parahaemolyticus infections. UpToDate. Retrieved January 3, 2021, from https://www.uptodate.com/contents/vibrio-parahaemolyticus-infections 
  3. Morris J.G. (2019). Vibrio vulnificus infections. UpToDate. Retrieved January 3, 2021, from https://www.uptodate.com/contents/vibrio-vulnificus-infections
  4. LaRocque R., Harris J.B. (2018). Cholera: Microbiology and pathogenesis. UpToDate. Retrieved January 3, 2021, from https://www.uptodate.com/contents/cholera-microbiology-and-pathogenesis
  5. LaRocque R., Harris J.B. (2020). Clinical features, diagnosis, treatment, and prevention. UpToDate. Retrieved January 3, 2021, from https://www.uptodate.com/contents/cholera-clinical-features-diagnosis-treatment-and-prevention
  6. Walder, M.K., Ryan, E.T. (2018). Cholera and Other Vibrioses. In Jameson, J.L., et al. (Ed.), Harrison’s Principles of Internal Medicine (20th ed. Vol 1, p. 1186–1192).
  7. Riedel, S., Hobden, J.A. (2019). In Riedel, S, Morse, S.A., Mietzner, T., Miller, S. (Eds.), Jawetz, Melnick, & Adelberg’s Medical Microbiology (28th ed, pp. 261–266).
  8. Liu, D. (2015). Toxin-Associated Gastrointestinal Disease. In Molecular Medical Microbiology (2nd ed., Vol. 2, pp. 971–977).
  9. Severin, G. B., et al. (Ed.) (2018). Direct activation of a phospholipase by cyclic gmp-amp in el tor vibrio cholerae. Proceedings of the National Academy of Sciences, 115(26), E6048–E6055. https://doi.org/10.1073/pnas.1801233115

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