Vibrio Cholera by yadd8eQB

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									          Vibrio Cholera




Michelle Ross, Kristin Roman, Risa Siegel
Clinical Manifestation and
         Defenses:




        CHOLERA
           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
Cholera is not transmissible person-
to-person, but can easily be spread
through contaminated food and water
               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
               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.
                  Symptoms

• Diarrhea may be
  sudden or gradual        •Abdominal cramping
• Rapid onset of water
  associated with stool
                          ** Fever is infrequent since
• Vomiting, frequently
                          cholera is not invasive infection
  watery, is common
  and may begin before
  or after diarrhea.
                 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
                    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 patient’s stool
    – Amounts greater or equal to patients blood volume
   Responds well to rehydration therapies
    – In areas where not available, death rates are
      astronomical
  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
                     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
                       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
                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
             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
         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
       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.
                    Treatment
• The course of treatment is decided by the
  degree of dehydration
• Three options prove most effective:
    • Oral Rehydration
    • Intravenous Rehydration
    • Antimicrobial Therapy
              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
                          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
ORS
        Intravenous Rehydration
• Used in patients who lost more than 10% of
  body weight from dehydration or are unable
  to drink due to vomiting
• Ringer’s Lactate used commercially in
  hospitals with appropriate electrolyte
  concentrations specified to patients needs
      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 =
              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
      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
          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
                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.
 Sari Cloth Filtration:
Preventative Measure




             Using Sari cloth to filter
             Water
           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
                      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 >90% protection against classical biovar
      and 65-80% agaisnt E1Tor biovar.
               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
                 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
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”
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
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
Weaponization: Means to Increase
Virulence
 amplifyand 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.”
Risk to New York

 •   Over 8 million
     people rely on
     water supply

 •   1.3 billion gallons
     of drinking water
     daily

								
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