Vibrio Cholera

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Vibrio Cholera
Michelle Ross, Kristin Roman, Risa Siegel
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Clinical Manifestation and DefensesCHOLERA
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Clinical Manifestations

• Cholera victims are infected when they ingest an
  infectious
• dose of the bacterium V. cholerae
• Most V. Cholera infections are asymptomatic (75)
• 1 case per 30 to 100 infections in the E1 biotype
• 1 case per 2 to 4 infections with the classical
  biotype

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Cholera is not transmissible person-to-person,
but can easily be spread through contaminated
food and water
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Incubation Period

• Ranging from a few hours to 5 days
• Most cases presenting within 1-3 days
• As expected for organisms passing through the
  gastric barrier, the incubation period is
  shortest when
• highest dose of ingested organsim
• High gastric pH

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Infectious Dose

• Infectious dose ranges from 106 1011 colonizing
  units
• The high level is necessary as the bacteria must
  survive the gastric acid barrier as the bacterium
  is sensitive to acidic conditions
• Additionally, V. cholerae must penetrate the
  mucus lining the coats the intestinal epithelium,
  the bacterium adheres to and colonizes the
  epithelial cells of the small intestine.

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Symptoms

• Diarrhea may be sudden or gradual
• Rapid onset of water associated with stool
• Vomiting, frequently watery, is common and may
  begin before or after diarrhea.

• Abdominal cramping

Fever is infrequent since cholera is not
invasive infection
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Severe Disease

• Cholera Gravis
• Notable for how quickly healthy person becomes
  ill
• Patients present after a few hours with massive
  volume loss
• 500 1000 ml per hour, can rapidly lose more
  than 10 of their body weight
• Mortality
• Circulatory collapse from dehydrating effects of
  the pathogen

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Cholera Gravis

• Severest form of cholera
• Infection in 2 of infected individuals
• Patients with blood type O most susceptible
• Characterized by voluminous expulsion of
  electrolyte-rich fluid in patients stool
• Amounts greater or equal to patients blood volume
• Responds well to rehydration therapies
• In areas where not available, death rates are
  astronomical

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Complications Severe Disease

• Complications result from massive volume and
  electrolyte loss as the Cholera stool contains
  high concentrations of sodium, potassium,
  chloride, and bicarbonate
• Therefore in addition to volume depletion, which
  can cause renal failure, additional complications
  can occur
• Hypokalemia causes arrhythmias, ileus, leg
  cramps
• Metabolic Acidosis due to phosphate moving out
  of cells
• Hypoglycemia mental status changes and seizures
• Hypotension due to water loss
• Hypofusion of critical organs

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Mortality

• In untreated patients, mortality can reach 50-70
• Risk much higher in children
• 10x greater than adults
• As well as pregnant women
• 50 risk of fetal death in 3rd trimester
• Patients can die within 2-3 hours of first sign
  of illness also seen from 10 hours- several days

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Diagnosis

• Cholera should be considered in all cases with
  severe watery diarrhea and vomiting
• However, there are no clinical manifestations
  that can distinguish cholera from other
  infectious causes of severe diarrhea
• Differential Diagnosis include
• Enterotoxigenic e. Coli
• Bacterial food poisoning
• Viral gastroenteritis

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Visible Symptoms

• These include
• Sunken eyes and cheeks
• Decreased skin suppleness
• Dry mucous membranes
• Urine production is sharply
• decreased or stopped altogether
• Renal failure is the most common
• complication seen in recent outbreaks

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Diagnosis continued

• Dehydrating diarrhea may be more common in
  children but adults should be questioned as to
  recent trips to Africa, Asia and central America
• Additional questions asked about ingestion of
  undercooked or raw shellfish

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Laboratory Diagnosis

• Made through isolation of bacteria from extra-
  intestinal environment or stool samples
• Specimens are collected
• Gram Stain show sheets of curved Gram negative
  rods
• Untreated patients have 106 to 108 organisms / mL
• Important to start treatment before the cause of
  infection is identified death can occur within
  hours

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Labroratory Diagnosis Cont.

• Vibrios often detected by dark field or phase
  contrast microscopy of stool
• Organisms are motile, appearing like shooting
  stars
• When plated on sucrose dishes, yellow colonies
  appear confirming cholera present
• Additional methods of detection include PCR and
  monoclonal antibody-based stool tests.

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Treatment

• The course of treatment is decided by the degree
  of dehydration
• Three options prove most effective
• Oral Rehydration
• Intravenous Rehydration
• Antimicrobial Therapy

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Oral Rehydration

• Oral Rehydration Solutions (ORS) have reduced
  mortality from cholera from over 50 to less than
  1.
• ORS utilizes the fact that sodium and water
  absorption in the small intestine is facilitated
  by glucose and occurs in the presence of cholera
  toxin
• Used when the dehydration is less than 10 of
  body weight

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O.R.S.

• The World Health Organization recommends a
  solution containing
• 3.5 g sodium chloride
• 2.9 g trisodium citrate/ sodium
• bicarbonate
• 1.5 g potassium chloride
• 20 g glucose or 40 g sucrose
• Per liter of water
• Min. of 1.5 x the stool volume losses should be
  administered
• Commercially sold over-the-counter as
• rehydralyte

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ORS
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Intravenous Rehydration

• Used in patients who lost more than 10 of body
  weight from dehydration or are unable to drink
  due to vomiting
• Ringers Lactate used commercially in hospitals
  with appropriate electrolyte concentrations
  specified to patients needs

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Intravenous Rehydration Additional Options

• Saline can be used, however, bicarbonate and
  potassium losses are not being replaced
• Glucose in water this does not replace the
  sodium, bicarbonate, or potassium losses

Dosage
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Antimicrobial Therapy

• Seen as an adjunct to appropriate rehydration
• Reduce the volume of diarrhea by a half and the
  duration of excretion to about 1 day, therefore,
  they lower the expense of treatment and play a
  role in cholera control.
• Due to short duration of illness, antibiotics not
  highly recommended
• High cost -- Antibiotic Resistance
• Limited gain from usage

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Dosage Antibiotic Agents

• Given orally when vomiting stops.
• Tetracycline is the standard treatment
• Administered in single dose
• primarily to prevent spread
• of secondary infection

WHO guidelines
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Tetracycline Resistance

• Many strains of V. Cholerae now harbor plasmids
  carrying multiple antibiotic resistances.
• Fluoroquinolones are now an effective alternative
  in regions where tetracycline resistance is common

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Prevention

• V. Cholerae is spread through contaminated food
  and water, therefore, prevention depends upon the
  interruption of fecal-oral transmission
• Anti-biotic prophylaxis, vaccines and
  surveillance of new cases are the answer to
  preventing the spread of disease.

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Sari Cloth FiltrationPreventative Measure
Using Sari cloth to filter Water
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Antibiotic prophylaxis

• The World Health Organization recommends
  prophylaxis if 1 household member in a family
  becomes ill.
• Mass administration of antibiotics to a whole
  community is not effective nor recommended

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Vaccines

• Two types of cholera vaccines are currently
  approved for use in humans.
• Killed-whole-cell formulation killed bacterial
  cells from both biovars of serovar 01 and
  purified B subunit of the cholera toxin.
• Provides immunity to only 50 of adult victims
  and to less than 25 of child victims.
• Live-attenuated vaccine, genetically engineered
• Provides gt90 protection against classical biovar
  and 65-80 agaisnt E1Tor biovar.

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Vaccines Problems

• The live vaccine is associated with certain
  problems
• Side Effects
• Cause mild diarrhea, abdominal cramping and
  slight fever
• Possible virulence of live strain
• Upon infection of the vaccine strain by cholera
  toxin

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Surveillance

• In the United States, cases of cholera must be
  reported to local and state health departments
• Bacterial isolates sent to the state health
  department and Centers for Disease Control (CDC)
  for testing and conformation of Cholera toxin
• World wide surveillance is monitored by the World
  Health Organization (WHO), tracking potential
  outbreaks

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Weaponization Task Force on Cholera

• 1992
• WHO Global Task Force on Cholera Control
• aim was to reduce mortality and morbidity
  associated with the disease and to address the
  social and economic consequences of cholera

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Weaponization Preventative Measures

• Global Water Quality Monitoring Project
  (GEMS/WATER)
• addresses global issues of water quality through
  a network of monitoring statins in rivers, lakes,
  reservoirs, and groundwater on all continents

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Weaponization Historical Perspective

• WWI
• allegations that Germany tried to spread cholera
  in Italy
• 1930s
• Japan dropped bombs on Chinese that released
  cholera, among other biological pathogens.
• 1980-1993
• S. Africa Biological Weapons Program
• included Bacillus anthracis, Vibrio cholera, and
  Clostridium species

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Weaponization Means to Increase Virulence

• amplify and insert virulent portion of the genome
  into another pathogen for either dispersion via
  aerosolization or water contamination that is
  contagious
• V. cholerae is particularly well adapted to its
  lifestyle in both the aquatic environment and as
  an enteric pathogen.

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Risk to New York

• Over 8 million people rely on water supply
• 1.3 billion gallons of drinking water daily