Cholera Vaccine in the USA
Published on Dec 12, 2016
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PRESENTATION OUTLINE
Vibrio Cholerae (Latin for quaking and bilious) known to be endemic in the Ganges region as far back as 500 B.C. and spread to naïve populations through early trade routes.
Photo by Leo Reynolds
Long history of pandemics (7 in past 200 years); last one began 1991 in Indonesia, still considered by epidemiologists to be continuing today. Many more frequent, smaller epidemics.
Photo by National Institutes of Health (NIH)
During the1854 epidemic in London, physician John Snow (one of Father's of modern Epidemiology) mapped affected individuals in London; noted a central water pump and suspected the outbreak was likely due to poor sanitation/water/sewage issues.
Photo by Wolfgang Staudt
He ordered the the handle removed off of the Broad Street water pump servicing the central affected Soho community, and the outbreak soon stopped. This led to changes in the city's waste and water systems.
Photo by Frankie Lopez
These clean water efforts spread and soon led to the disappearance of cholera in much of the developed world.
Photo by ell brown
Now acknowledged official discoverer of cholera bacterium was German physician Robert Koch who found cholera bacillus in gut necropsies during an epidemic in Egypt in1883, one year after he discovered the tuberculosis bacillus.
Photo by Sokwanele - Zimbabwe
By 1884 he isolated the cholera bacillus in a pure culture. For these achievements he was awarded Nobel Peace Prize in 1905 for Medicine.
Photo by Martin Jernberg
1885 Spanish physician Jaime Ferrans developed the first live attenuated cholera vaccine, first to immunize humans against a bacterial disease.
Photo by Ian
Vibrio Cholerae bacteria
Oxidase positive, fermentative, Gram negative rod, sometimes appearing comma shaped with single flagella
Some strains cause the disease cholera, notably
Serogroup O1 or O139. Serogroup O1 has two biotypes: El Tor and Classical Further classified into three Serotypes: Ogana, Inaba and Hikojima (unstable and rarely occurs in nature)
There are at least 200 recognized Serogroups known as Non-O1 Non-O139 which are found in aquatic environments and are rarely associated with outbreaks.
Toxigenic Serogroup O1 cause >99% global cases. O139 occurs few areas in Asia.
Photo by Tim Evanson
Cholera grows best at PH 7, and can survive wide range from 18C-37C.
Has a sensory organ which allows it to scan their surroundings, detect needed nutrients, and move toward those food sources using their flagellae.
Non-invasive, colonize the small intestine by penetrating mucus layer, rapidly multiplying.
Photo by El Bingle
Toxigenic strains increased Cl secretion in small intestinal crypt cells, inhibiting absorption of Na and Cl in microvilli.
Cause purging of electrolyte rich fluid into small intestine, which the colon can't absorb.
Subsequent profound loss of Na, Cl, K and Bicarb.
Profuse, watery, milky diarrhea with fishy odor , often pathognomonic and referred to as "Rice Water Stool".
Can lose up to 20L day fluid, or one's body weight.
Photo by ZEISS Microscopy
Spread by fecal contamination to water, shellfish (attaches easily to chitin skeletons), fish, algae, plankton, and fresh grown produce if watered with contaminates. Increased occurrence during warm weather and increased rainfall.
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Mainly found in areas with poor access to safe water/sanitation, especially along rivers and lakes.
Prefers brackish, saline or alkaline (not acidic) environments; but can survive in fresh water.
Can survive low temperatures.
Humans are the primary host.
Photo by austinevan
The most profound epidemics are usually where basic environmental infrastructures have been disrupted or destroyed.
War zones, earthquakes, floods and tsunamis, refugee camps.
Photo by unicefukraine
Currently thought to be endemic in about 69 countries, with most cases unreported.
Estimated internationally 3-5 million cases a year, with average of 100K deaths annually.
In USA almost all cases are contracted abroad; our last outbreak in USA occurred in 1911.
Currently largest epidemic since 2016 has been in Yemen.
Photo by newbeatphoto
Last large
modern epidemic occurred in Haiti (which prior to earthquake was a non endemic region since 1960, so no immunity).
In October 2010 outbreak began 9 months in after earthquake with approximately 812K reported cases and 9K deaths.
United Nations Peacekeeping forces have acknowledged their role in introducing cholera to Haiti. Disease also spread regionally to Puerto Rico and Cuba.
In 2011 42 cases in USA reported were imported from Haiti; since 2012 less than 25 cases annually from Haiti reported.
Haitian cholera outbreak was found to be related to Asiatic strains; it possessed increased virulence, more drug resistance, and more robust environmental persistence than many strains.
During the height of the outbreak timing from initial symptom development to death occasionally was only 12 hours.
UNICEF/WHO announced Haitian epidemic over 2/2019, with likely elimination.
Photo by benwatts
"Blue Death"-victims sometimes have a blue tint to their skin once affected.
The overwhelming fluid and subsequent electrolyte loss if not treated can lead to-
Dehydration, vomiting, leg cramps, postural hypotension, tachycardia, weakness, oliguria, acute tubular necrosis, renal failure, coma, and death can occur (50-60% of patients).
Photo by Ian Espinosa
Overall, casual contact with an infected person is low risk. Surveillance of close contacts for 5 days after last exposure.
Incubation time 12 hrs to 5 days.
Usually infection is asymptomatic or mild, but occasionally severe (5-10%).
Illness can last 1 week, with contagious period lasting 7-14 days.
No lasting antibody protection, possible to become infected again if re-exposed.
Photo by Trey Ratcliff
Definitive diagnosis is with stool or rectal swab culture gold standard (TCBS agar); there are also rapid test kits during epidemics that don't yield an isolate for further testing. However, in urgent situations/epidemics symptomatic treatment starts immediately.
It is a notifiable disease.
Photo by Jaron Nix
Relatively simple treatment if started quickly:
Replacing oral fluids and electrolytes ORS- 80% management.
Homemade equivalent is 6 tsp of sugar and one 1/2 tsp salt in 1 L H20. Often stool amounts measured and that can determine replacement amount needed (cholera cot)
Sometimes IV's (LR or NS) needed- 20%.
Managing nausea/vomiting helps, usually subsides once electrolyte balance better.
In some cases if no improvement antibiotics are started after rehydration underway and nausea/vomiting controlled.
Doxycycline in single dose 7 mg/kg, not to exceed 300 mg/dose.
Erythromycin or azithromycin for those pregnant and children.
Decreases duration of symptoms and
decreases vibrio carriage time.
First line doxycyline; azithromycin for pregnant and children.
Cures 94% adults, 60% kids. Adding zinc treatment for children decreases severity and duration.
Photo by ColaLife
Conditions with high risk for poor clinical outcomes from cholera:
Pregnant
Immunocompromised
CVD/Renal disease
Chronic antacid therapy/partial gastrectomy (since cholera thrives in low acid environment)
Photo by groundreporter
Outside of the USA, four killed oral cholera vaccines available. Two WHO approved, two non approved.
WHO approved:
Dukoral-2001(Netherlands), licensed in 60 countries.
Shanchol-2011 (India),licensed in India, Philippines, Nepal, Malaysia, Cote d'Ivoire
Photo by redcharlie
Non-WHO qualified: ORAVACS (Shanghai) only licensed in China and Philippines. M ORC-Vax (Vietnam) only licensed in Vietnam
Photo by Doan Tuan
For some time now cholera vaccine not needed for international travel/country entrance; no longer space for documentation on the International Certificate of Vaccination.
Photo by CDC Global Health
Vaxchora (Vax-cora)
PaxVax recently purchased by Emergent Biosolutions
FDA approved in 6/20/2016 as the only currently licensed cholera vaccine in USA.
First cholera vaccine available in USA since 2000, last one taken off the market when deemed ineffective.
Single dose oral live attenuated vaccine, indicated for active immunization against vibrio cholerae serogroup O1.
Photo by frankieleon
The attenuated live bacteria replicate in the GI tract, with a rise in vibriocidal antibody noted in an average of 10 days. Peak effectiveness for 3 months at 90%, decreasing to 80% after 3 months.
Photo by Gregory Culmer
Vaxchora needs to be given at least 10 days before arrival in cholera region.
Vaccine potentially may shed (~10% patients) in stool for at least 7 days potentially to close contacts.
Needs to be taken at least 10 days prior to chloroquine, or may lessen vaccine efficacy.
Wait 14 days after oral or parenteral antibiotic use, as they may blunt antibody response.
Photo by chunghow33
Currently length of protection unknown, no recommendation for booster at this time.
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Only approved for ages 18-64.
If self pay, cost roughly $230-300 with online coupons available.Currently no company patient assistance program.
Photo by Fabian Blank
On 6/22/16 the Advisory Committee on Immunization Practices (ACIP) unanimously voted to recommend Vaxchora for high risk people traveling to active toxigenic O1 cholera regions.
Photo by Grupo FAEF
Vaccine has to be administered in facility prepared to deal with potentially infectious medical waste.
Photo by renaissancechambara
Administration of Vaxchora
Advise patients not to eat or drink for 60 minutes before and after taking the vaccine.
Vaxchora vaccine kit kept at -15F to 5F, away from light and moisture. Do not thaw, once removed from freezer must be mixed in 15 minutes.
Pour 100ml of cool purified bottled water into disposable cup, no tap water other fluids.
Photo by justmakeit
Mix buffer packet into water, then add vaccine packet and stir for 30 seconds. it becomes slightly effervescent and needs to be consumed in 15 minutes.
Photo by Boxed Water Is Better
The cup, packets and stirrer must be disposed of in a medical waste container; do not pour down the sink.
Photo by Victor Wong (sfe-co2)
Any spillage must be cleaned up with either 70% isopropyl alcohol or 10% beach solution.
Photo by joelogon
It isn't known how long to wait before you can start antibiotics after administration of Vaxchora (i.e. doxy for antimalarial prophylaxis?)
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The buffer in Vaxchora may interfere with Vivotif absorption, so need to wait at least 8 hours after taking Vaxchora before first dose of Vivotif.
Photo by The Shifted Librarian
Vaccine ingredients/potential allergens:
Active packet contains-
attenuated V. cholerae
sucrose
NaCl
hydrolyzed casein
ascorbic acid
dried lactose
Buffer packet contains-
Na bicarbonate
Na carbonate
ascorbic acid
dried lactose
Photo by eric.delcroix
Adverse Events:
Most common side effects were-
Tiredness-30%
Headache-28%
Abdominal Pain-18%
Nausea/Vomiting-17%
Anorexia-16%
Diarrhea-4%
If given while pregnant, report to PaxVax registry (800-533-5899) since theoretically live bacteria could cross to baby during vaginal birth.
Breastfeeding thought to be OK since locally absorbed only without crossover. No data or recommendation for use at this time.
Photo by bark
High risk groups to consider vaccination:
VFR travelers
Unable or unwilling to follow safe food/water/hygiene measures.
Responders and healthcare workers with direct body fluid contact of cholera patients.
No access to rehydration treatment and medical care.
Photo by Julien Harneis
Blood Type O and cholera risk:
45% USA population
Association noted 1977
Not a greater risk of being infected, but more risk of disease severity.
Lowest world prevalence of type O is in the Ganges Delta, where cholera has been endemic for centuries and has likely genetically imprinted itself.
Most people of course are unaware of their blood type.
Photo by biologycorner
Likewise no data/recommendation for immunocompromised or HIV+ individuals.
In Mali one study showed seroconversion was lower at ~58% 10 days after administration.
Immune response to vaccine likely not as protective.
Several phase 4 clinical studies about use in ages 2-18 yrs, ongoing.
Could not find any studies for those over age 64.
Ideally counsel younger, older, pregnant and immune suppressed individuals to reconsider their travel plans if an option.
Photo by NIAID
Limitations of Vaxchora-Effectiveness not established in persons with pre-existing immunity or known previous exposure to V.Cholerae or any cholera vaccine.
Photo by Ludovic Charlet
Effectiveness not established in people actually living in cholera affected areas.
Photo by www.ricardosantanna.yoga
Not shown to protect against V. Cholerae subgroup O139 or other non-O1 groups.
Photo by SHAN DUTTA
Not for the pregnant or immune deficient. Only approved for age 18-64, can be expensive. Can be shed in stool. Has to be given in special facility.
Photo by Theen ...
CDC notes cholera to be a rare disease in USA travelers who consistently observe safe food,water,sanitation and hand washing measures.
They state virtually no risk of acquiring
the disease.
For the majority of our patients seen, not needed vaccine. Overall risk ratio for travelers is 1 in 500,000.
Photo by Raed Mansour
Summary:
Cholera rare risk for majority of our travelers.
Very preventable with simple food/water/hygiene precautions.
For patients heading into high risk situations, a
vaccine is now an available option in USA with documented peak effectiveness for at least 3 months after administration, but primary protection is to stress preventive measures and self care plan if illness occurs.
Also may wish to have medical evacuation insurance.
Once more longitudinal and retrospective data on length of antibody protection known, we will be able to confidently counsel patients better since no booster dose recommended at this time (Ixiaro).
Photo by Chris Lawton
