Vibrio Cholera Michelle Ross Kristin Roman Risa Siegel

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 E 1 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 p. H

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 • 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

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 n Severest form of cholera – Infection in 2% of infected individuals Patients with blood type O most susceptible n Characterized by voluminous expulsion of electrolyte-rich fluid in patient’s stool n – Amounts greater or equal to patients blood volume n 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 5070% • Risk much higher in children • 10 x greater than adults • As well as pregnant women • 50% risk of fetal death in 3 rd 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 n However, there are no clinical manifestations that can distinguish cholera from other infectious causes of severe diarrhea n – 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 extraintestinal environment or stool samples • Specimens are collected • • Gram Stain show sheets of curved Gram negative rods • Untreated patients have 106 to 108 organisms / m. L • Important to start treatment before the cause of infection is identified: death can occur within hours

Labroratory Diagnosis Cont. n n 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 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 E 1 Tor 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 • 1930 s • “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 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. ”

Risk to New York • Over 8 million people rely on water supply • 1. 3 billion gallons of drinking water daily