Vibrio CholeraVibrio Cholera

Michelle Ross, Kristin Roman, Risa Michelle Ross, Kristin Roman, Risa SiegelSiegel

Clinical Manifestation and Clinical Manifestation and Defenses:Defenses:

CHOLERACHOLERA

Clinical ManifestationsClinical ManifestationsCholera victims are infected when they ingest an Cholera victims are infected when they ingest an

infectiousinfectiousdose of the bacterium – dose of the bacterium – V. choleraeV. cholerae

Most V. Cholera infections are asymptomatic Most V. Cholera infections are asymptomatic (75%)(75%)

- 1 case per 30 to 100 infections in the E1 biotype1 case per 30 to 100 infections in the E1 biotype- 1 case per 2 to 4 infections with the classical 1 case per 2 to 4 infections with the classical

biotypebiotype

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

Incubation PeriodIncubation Period• Ranging from a few hours to 5 daysRanging from a few hours to 5 days

• Most cases presenting within 1-3 daysMost cases presenting within 1-3 days

• As expected for organisms passing As expected for organisms passing through the gastric barrier, the incubation through the gastric barrier, the incubation period is shortest when: period is shortest when: • highest dose of ingested organsimhighest dose of ingested organsim• High gastric pHHigh gastric pH

Infectious DoseInfectious Dose• Infectious dose ranges from 10Infectious dose ranges from 1066 10 101111

colonizing unitscolonizing units• The high level is necessary as the bacteria The high level is necessary as the bacteria

must survive the gastric acid barrier as the must survive the gastric acid barrier as the bacterium is sensitive to acidic conditionsbacterium is sensitive to acidic conditions

• Additionally, Additionally, V. choleraeV. cholerae must penetrate must penetrate the mucus lining the coats the intestinal the mucus lining the coats the intestinal epithelium, the bacterium adheres to and epithelium, the bacterium adheres to and colonizes the epithelial cells of the small colonizes the epithelial cells of the small intestine. intestine.

SymptomsSymptoms• Diarrhea may be Diarrhea may be

sudden or gradualsudden or gradual• Rapid onset of Rapid onset of

water associated water associated with stoolwith stool

• Vomiting, Vomiting, frequently watery, frequently watery, is common and is common and may begin before may begin before or after diarrhea.or after diarrhea.

** Fever is infrequent since cholera is not invasive infection

•Abdominal cramping

Severe DiseaseSevere Disease• Cholera GravisCholera Gravis

• Notable for how quickly healthy person Notable for how quickly healthy person becomes illbecomes ill

• Patients present after a few hours with Patients present after a few hours with massive volume lossmassive volume loss• 500 – 1000 ml per hour, can rapidly lose more 500 – 1000 ml per hour, can rapidly lose more

than 10% of their body weightthan 10% of their body weight• MortalityMortality

• Circulatory collapse from dehydrating effects of Circulatory collapse from dehydrating effects of the pathogenthe pathogen

Cholera GravisCholera Gravis Severest form of choleraSeverest form of cholera

– Infection in 2% of infected individualsInfection in 2% of infected individuals Patients with blood type O most Patients with blood type O most

susceptiblesusceptible Characterized by voluminous expulsion of Characterized by voluminous expulsion of

electrolyte-rich fluid in patient’s stoolelectrolyte-rich fluid in patient’s stool– Amounts greater or equal to patients blood Amounts greater or equal to patients blood

volumevolume Responds well to rehydration therapiesResponds well to rehydration therapies

– In areas where not available, death rates are In areas where not available, death rates are astronomicalastronomical

Complications: Severe DiseaseComplications: Severe Disease• Complications result from massive volume and Complications result from massive volume and

electrolyte loss as the Cholera stool contains high electrolyte loss as the Cholera stool contains high concentrations of sodium, potassium, chloride, concentrations of sodium, potassium, chloride, and bicarbonateand bicarbonate

• Therefore in addition to volume depletion, which Therefore in addition to volume depletion, which can cause renal failure, additional complications can cause renal failure, additional complications can occur:can occur:• Hypokalemia: causes arrhythmias, ileus, leg cramps Hypokalemia: causes arrhythmias, ileus, leg cramps • Metabolic Acidosis: due to phosphate moving out of cellsMetabolic Acidosis: due to phosphate moving out of cells• Hypoglycemia: mental status changes and seizuresHypoglycemia: mental status changes and seizures• Hypotension: due to water lossHypotension: due to water loss• Hypofusion of critical organs Hypofusion of critical organs

MortalityMortality• In untreated patients, mortality can reach In untreated patients, mortality can reach

50-70%50-70%• Risk much higher in children Risk much higher in children

• 10x greater than adults 10x greater than adults • As well as pregnant women As well as pregnant women

• 50% risk of fetal death in 350% risk of fetal death in 3rdrd trimester trimester• Patients can die within 2-3 hours of first Patients can die within 2-3 hours of first

sign of illness also seen from 10 hours- sign of illness also seen from 10 hours- several daysseveral days

DiagnosisDiagnosis Cholera should be considered in all cases Cholera should be considered in all cases

with severe watery diarrhea and vomitingwith severe watery diarrhea and vomiting However, there are no clinical However, there are no clinical

manifestations that can distinguish manifestations that can distinguish cholera from other infectious causes of cholera from other infectious causes of severe diarrheasevere diarrhea– Differential Diagnosis include:Differential Diagnosis include:

Enterotoxigenic Enterotoxigenic e. Colie. Coli Bacterial food poisoningBacterial food poisoning Viral gastroenteritisViral gastroenteritis

Visible SymptomsVisible Symptoms• These include:These include:

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

Diagnosis continuedDiagnosis continued• Dehydrating diarrhea may be more Dehydrating diarrhea may be more

common in children but adults should be common in children but adults should be questioned as to recent trips to Africa, Asia questioned as to recent trips to Africa, Asia and central Americaand central America

• Additional questions asked about ingestion Additional questions asked about ingestion of undercooked or raw shellfishof undercooked or raw shellfish

Laboratory DiagnosisLaboratory Diagnosis• Made through isolation of bacteria from extra- Made through isolation of bacteria from extra-

intestinal environment or stool samplesintestinal environment or stool samples• Specimens are collectedSpecimens are collected

• Gram Stain show sheets of curved Gram negative Gram Stain show sheets of curved Gram negative rodsrods

• Untreated patients have 10Untreated patients have 1066 to 10 to 1088 organisms / mL organisms / mL• Important toImportant to start treatment before thestart treatment before the cause cause

of infection is identified: death can occur of infection is identified: death can occur within hourswithin hours

Labroratory Diagnosis Cont.Labroratory Diagnosis Cont. Vibrios often detected by dark field or Vibrios often detected by dark field or

phase contrast microscopy of stoolphase contrast microscopy of stool Organisms are motile, appearing like Organisms are motile, appearing like

“shooting stars”“shooting stars” When plated on sucrose dishes, yellow When plated on sucrose dishes, yellow

colonies appear confirming cholera presentcolonies appear confirming cholera present Additional methods of detection include Additional methods of detection include

PCR and monoclonal antibody-based stool PCR and monoclonal antibody-based stool tests.tests.

TreatmentTreatment• The course of treatment is decided by the The course of treatment is decided by the

degree of dehydrationdegree of dehydration• Three options prove most effective:Three options prove most effective:

• Oral RehydrationOral Rehydration• Intravenous RehydrationIntravenous Rehydration• Antimicrobial TherapyAntimicrobial Therapy

Oral RehydrationOral Rehydration• Oral Rehydration Solutions (ORS) have Oral Rehydration Solutions (ORS) have

reduced mortality from cholera from over reduced mortality from cholera from over 50% to less than 1%.50% to less than 1%.

• ORS utilizes the fact that sodium and ORS utilizes the fact that sodium and water absorption in the small intestine is water absorption in the small intestine is facilitated by glucose and occurs in the facilitated by glucose and occurs in the presence of cholera toxinpresence of cholera toxin

• Used when the dehydration is less than Used when the dehydration is less than 10% of body weight 10% of body weight

O.R.S.O.R.S.• The World Health Organization The World Health Organization

recommends a solution containing:recommends a solution containing:• 3.5 g sodium chloride3.5 g sodium chloride• 2.9 g trisodium citrate/ sodium 2.9 g trisodium citrate/ sodium • bicarbonatebicarbonate• 1.5 g potassium chloride1.5 g potassium chloride• 20 g glucose or 40 g sucrose20 g glucose or 40 g sucrose

• Per liter of waterPer liter of water• Min. of 1.5 x the stool volume losses should Min. of 1.5 x the stool volume losses should

be administered be administered • Commercially sold over-the-counter as Commercially sold over-the-counter as

rehydralyterehydralyte

ORSORS

Intravenous RehydrationIntravenous Rehydration• Used in patients who lost more than 10% Used in patients who lost more than 10%

of body weight from dehydration or are of body weight from dehydration or are unable to drink due to vomitingunable to drink due to vomiting

• Ringer’s Lactate used commercially in Ringer’s Lactate used commercially in hospitals with appropriate electrolyte hospitals with appropriate electrolyte concentrations specified to patients needsconcentrations specified to patients needs

Intravenous Rehydration – Intravenous Rehydration – Additional OptionsAdditional Options

• Saline can be used, however, Saline can be used, however, bicarbonate and potassium losses are bicarbonate and potassium losses are not being replacednot being replaced

• Glucose in water; this does not replace Glucose in water; this does not replace the sodium, bicarbonate, or potassium the sodium, bicarbonate, or potassium losseslosses

Dosage =

Antimicrobial TherapyAntimicrobial Therapy• Seen as an adjunct to appropriate Seen as an adjunct to appropriate

rehydrationrehydration• Reduce the volume of diarrhea by a half Reduce the volume of diarrhea by a half

and the duration of excretion to about 1 and the duration of excretion to about 1 day, therefore, they lower the expense of day, therefore, they lower the expense of treatment and play a role in cholera treatment and play a role in cholera control.control.

• Due to short duration of illness, antibiotics Due to short duration of illness, antibiotics not highly recommended:not highly recommended:– High costHigh cost -- Antibiotic Resistance -- Antibiotic Resistance– Limited gain from usageLimited gain from usage

Dosage – Antibiotic AgentsDosage – Antibiotic Agents• Given orally when Given orally when

vomiting stops.vomiting stops.• Tetracycline is the Tetracycline is the

standard treatmentstandard treatment• Administered in single Administered in single

dose dose primarily to prevent primarily to prevent spread spread of secondary infectionof secondary infection

WHO guidelines

Tetracycline ResistanceTetracycline Resistance• Many strains of V. Cholerae now harbor Many strains of V. Cholerae now harbor

plasmids carrying multiple antibiotic plasmids carrying multiple antibiotic resistances.resistances.

• Fluoroquinolones are now an effective Fluoroquinolones are now an effective alternative in regions where tetracycline alternative in regions where tetracycline resistance is commonresistance is common

PreventionPrevention• V. Cholerae is spread through V. Cholerae is spread through

contaminated food and water, contaminated food and water, therefore, prevention depends upon the therefore, prevention depends upon the interruption of fecal-oral transmissioninterruption of fecal-oral transmission

• Anti-biotic prophylaxis, vaccines and Anti-biotic prophylaxis, vaccines and surveillance of new cases are the surveillance of new cases are the answer to preventing the spread of answer to preventing the spread of disease.disease.

Sari Cloth Filtration:Sari Cloth Filtration:Preventative MeasurePreventative Measure

Using Sari cloth to filterWater

Antibiotic prophylaxisAntibiotic prophylaxis• The World Health Organization The World Health Organization

recommends prophylaxis if 1 household recommends prophylaxis if 1 household member in a family becomes ill.member in a family becomes ill.

• Mass administration of antibiotics to a Mass administration of antibiotics to a whole community is not effective nor whole community is not effective nor recommendedrecommended

VaccinesVaccines

• Two types of cholera vaccines are Two types of cholera vaccines are currently approved for use in humans.currently approved for use in humans.– Killed-whole-cell formulationKilled-whole-cell formulation: killed : killed

bacterial cells from both biovars of serovar 01 bacterial cells from both biovars of serovar 01 and purified B subunit of the cholera toxin.and purified B subunit of the cholera toxin.

Provides immunity to only 50% of adult victims Provides immunity to only 50% of adult victims and to less than 25% of child victims. and to less than 25% of child victims.

– Live-attenuatedLive-attenuated vaccine, genetically vaccine, genetically engineeredengineered

Provides >90% protection against classical Provides >90% protection against classical biovar and 65-80% agaisnt E1Tor biovar.biovar and 65-80% agaisnt E1Tor biovar.

Vaccines: ProblemsVaccines: Problems• The live vaccine is associated with certain The live vaccine is associated with certain

problems:problems:• Side Effects:Side Effects:

• Cause mild diarrhea, abdominal cramping and slight Cause mild diarrhea, abdominal cramping and slight feverfever

• Possible virulence of live strainPossible virulence of live strain• Upon infection of the vaccine strain by cholera toxinUpon infection of the vaccine strain by cholera toxin

SurveillanceSurveillance• In the United States, cases of cholera must In the United States, cases of cholera must

be reported to local and state health be reported to local and state health departmentsdepartments• Bacterial isolates sent to the state health Bacterial isolates sent to the state health

department and Centers for Disease Control department and Centers for Disease Control (CDC) for testing and conformation of Cholera (CDC) for testing and conformation of Cholera toxintoxin

• World wide surveillance is monitored by World wide surveillance is monitored by the World Health Organization (WHO), the World Health Organization (WHO), tracking potential outbreakstracking potential outbreaks

Weaponization: Task Force Weaponization: Task Force on Choleraon Cholera

• 19921992• WHO Global Task Force WHO Global Task Force

on Cholera Controlon Cholera Control• ““aim was to reduce aim was to reduce

mortality and morbidity mortality and morbidity associated with the associated with the disease and to address disease and to address the social and economic the social and economic consequences of cholera”consequences of cholera”

Weaponization: Weaponization: Preventative MeasuresPreventative Measures• Global Water Quality Monitoring Global Water Quality Monitoring

Project (GEMS/WATER) Project (GEMS/WATER) • addresses global issues of water quality addresses global issues of water quality

through a network of monitoring statins in through a network of monitoring statins in rivers, lakes, reservoirs, and groundwater on rivers, lakes, reservoirs, and groundwater on all continentsall continents

Weaponization: Historical Weaponization: Historical PerspectivePerspective• WWIWWI

• allegations that Germany tried to spread cholera allegations that Germany tried to spread cholera in Italyin Italy

• 1930s1930s• ““Japan dropped bombs on Chinese that released Japan dropped bombs on Chinese that released

cholera, among other biological pathogens.”cholera, among other biological pathogens.”• 1980-19931980-1993

• S. Africa Biological Weapons Program S. Africa Biological Weapons Program • included included Bacillus anthracisBacillus anthracis, , Vibrio choleraVibrio cholera, ,

and and Clostridium Clostridium speciesspecies

Weaponization: Means to Weaponization: Means to Increase VirulenceIncrease Virulence amplify and insert virulent portion of amplify and insert virulent portion of

the genome into another pathogen for the genome into another pathogen for either dispersion via aerosolization or either dispersion via aerosolization or water contamination that is contagiouswater contamination that is contagious

““V. cholerae is particularly well adapted V. cholerae is particularly well adapted to its lifestyle in both the aquatic to its lifestyle in both the aquatic environment and as an enteric environment and as an enteric pathogen.”pathogen.”

Risk to New YorkRisk to New York

• Over 8 million Over 8 million people rely on people rely on water supplywater supply

• 1.3 billion 1.3 billion gallons of gallons of drinking water drinking water dailydaily