Pharmacybrands Final Algorithm for Dukoral Supply May 2012

Algorithm for Dukoral Supply
Has the consumer been advised by a doctor or other relevant
expert to use Dukoral prior to travel?
Is the consumer at risk of cholera infection, e.g. travelling to
epidemic or endemic area for cholera?
No
Yes
Yes
Dukoral can be supplied unless
under 2 years of age. See
training material including
pregnancy advice.
Dosage: Adults and children
over 6 years: Take a total of 2
doses a week apart. Complete
at least 1 week before going to
the affected area. See pack
insert for dosing for 2-6 years.
No
Could the consumer have high exposure
e.g. those staying an extended period,
staying in local villages or working in
communities with known outbreak of
cholera, military personnel?
Is the consumer travelling to a location with medium to high risk
for ETEC, usually developing or tropical countries, e.g. Mexico,
Central America, Latin America, Africa (excluding South Africa),
India, Nepal, The Middle East?
No
Dukoral unlikely to
provide benefit; do
not recommend.
Advise how to
avoid and treat
diarrhoea. See a
doctor for
vaccinations and
antimalarials.
No
No
Yes
Are reasonable benefits of
Dukoral likely? Consider
length of stay, risk factors,
accommodation, importance
to individual of avoiding
travellers’ diarrhoea (e.g.
planned activities, underlying
conditions).
Yes
Yes
Advise:
Avoid food & drink 2 hours
before and 1 hour after
how to avoid and treat
diarrhoea
refrigerate until use
Dukoral does not cover
other conditions. Other
vaccinations and/or malarial
prophylaxis may be needed.
put a reminder on the
calendar for 2 nd dose
Advise on mixing Dukoral:
1. Dissolve the sodium
hydrogen carbonate in a glass
of water (discard half for
children 2-6 years).
2. Shake the vaccine vial (1 vial
= 1 dose, adults and children)
3. Add the vaccine to the
sodium hydrogen carbonate
mixture, mix well and drink all
of mixture immediately.
Prescription exemption if sold
by a pharmacist.
Please see training material. Discuss need for antidiarrhoeals, electrolyte replacements,
hand sanitisers, water purifying tablets, insect repellents, first aid products.
Copyright Pharmacybrands May 2012 Community Pharmacy Dukoral training material.

Training Material, Dukoral
What is Dukoral?
Dukoral is an inactivated oral vaccine, consisting of killed whole-cell Vibrio cholera O1 of several
strains (Inaba and Ogawa serotypes, classical and El Tor biotypes) and purified recombinant cholera
B subunit (WC/rBS).
What is Dukoral used for?
Dukoral is indicated for active immunisation for cholera of adults and children from 2 years of age
with an ongoing or anticipated epidemic or who will be spending an extended period of time in areas
in which cholera infection is a risk.
Dukoral is also indicated for active immunisation of adults and children from 2 years of age who will
be visiting areas posing a great risk of diarrhoeal illness caused by Enterotoxigenic Escherichia coli
(ETEC). The heat-labile toxin of ETEC (which causes diarrhoea) is similar to cholera toxin – that’s why
Dukoral works for prevention of both cholera and ETEC.
The World Health Organisation states “vaccination against cholera and ETEC should be
recommended to at-risk travellers.”[1]
ETEC
ETEC is the most common cause of diarrhoea in visitors to developing and tropical countries.
Countries with higher prevalence include Mexico, Central America, Latin America, Africa (excluding
South Africa), India, Nepal and The Middle East. South East Asia has low prevalence of ETEC. There
are other causes of travellers’ diarrhoea, and Dukoral is not 100% effective, so ensure consumers are
aware of the need for good hygiene practices regardless of whether or not they take Dukoral (see
below).
Travellers’ diarrhoea affects 40-90% of travellers depending on their destination.[2-4] While
generally mild and self-limiting, it is inconvenient and risk is highest in those with chronic conditions,
young children, elderly and those who cannot compensate fluid loss such as travellers to high
altitudes.[4]
Enterotoxigenic E coli (ETEC) is the most common cause of diarrhoea in visitors to developing and
tropical countries,[2, 5] responsible for nearly half of all cases of travellers’ diarrhoea.[6] There is
regional variability in frequency of causes of travellers’ diarrhoea, for example ETEC is thought to be
more common in Latin America than Southeast Asia, but data collection varies between studies and
some information is old, from the 1970s.[7] Transmission of ETEC is usually from contaminated food
and water, and infection occurs 10 hours to 3 days after exposure, typically causing profuse watery
diarrhoea sometimes with low grade fever, abdominal cramping and/or vomiting.[8, 9] While ETEC
diarrhoea commonly lasts 4 to 6 days, one study in Nepal found 19% of travellers and expatriates
suffered for more than 14 days with ETEC diarrhoea.[4] There are variants of ETEC: the more
common heat-labile toxin producing ETEC (which Dukoral protects against)[4] causes an estimated
10 million cases of travellers’ diarrhoea each year;[1] the heat-stable toxin producing ETEC is less
common; and some strains produce both toxins[9].
Copyright Pharmacybrands May 2012 Community Pharmacy Dukoral training material.

Dukoral provides protection against the heat-labile toxin-producing ETEC through anti-toxin
immunity rather than through antibodies against bacterial cells; this protection starts 7 days after
the second dose.[4] Dukoral provides short-term protection against ETEC diarrhoea of around 50%
regardless of what toxin is produced, and this efficacy rate increases if only heat-labile toxin
producing strains are included.[4]
The Committee to Advise on Tropical Medicine and Travel in Canada suggests the following points
for appropriate usage.[10] Because 25-50% of travellers’ diarrhoea is caused by ETEC bacteria, the
protection by the vaccine is approximately 50%, and using the vaccine has the potential to give a
false sense of security (and possibly be less strict on food and water hygiene), using this vaccine for
travellers’ diarrhoea cannot be routinely recommended for most travellers. Therefore the decision
as to whether or not to use Dukoral depends on the individual circumstances. Those at higher risk
are:
People with increased risk of serious consequences from travellers’ diarrhoea because of
their chronic illness, such as chronic renal failure, congestive heart failure, insulin-dependent
diabetes mellitus, inflammatory bowel disease
People with increased risk of getting travellers’ diarrhoea, such as young children (over age
of 2 years), or those with low gastric acid (e.g. on proton pump inhibitors)
People who are immunosuppressed
People with a history of repeated severe travellers’ diarrhoea
People for whom travellers’ diarrhoea will be particularly difficult to manage, e.g. business
travellers, elite athletes. Although not specifically mentioned by the Canadians, trampers in
remote areas of developing countries are another logical at-risk group,
For these people travellers’ diarrhoea in a developing country is likely to cause considerable
discomfort and difficulty in adhering to their travel plans; 30% of Western travellers with travellers’
diarrhoea are confined to their room and 40% have to change their scheduled activities.[4]
Travellers’ diarrhoea is a risk factor for irritable bowel syndrome,[5, 11] and can lead to chronic
reactive arthritis.[5]
Treatment of travellers’ diarrhoea is usually rehydration with an antidiarrhoeal if necessary; in some
cases antimicrobial treatment is recommended.[12] Antimicrobial treatment of ETEC is becoming
more difficult due to resistance; resistance to tetracyclines, cotrimoxazole and ampicillin is high and
resistance is occurring even with the quinolones which are currently the preferred antimicrobial
treatment for travellers’ diarrhoea.[8] In diarrhoea with frequent watery stools oral antibiotics (and
other medication) may be poorly absorbed due to rapid intestinal transit.[2]
Important points to reiterate with the consumer:
Dukoral only reduces the risk of diarrhoea from ETEC and cholera. Good hygiene (see below)
remains vital.
Refer to the doctor 4-6 weeks before travel to ensure routine vaccinations are up-to-date and
travel vaccinations and/or malarial prophylaxis are covered. See www.who.int/ith/en/ or
http://wwwnc.cdc.gov/travel/page/vaccinations.htm for latest travel vaccination requirements.
Copyright Pharmacybrands May 2012 Community Pharmacy Dukoral training material.

Cholera
Cholera is endemic in many countries, e.g. developing countries in Africa and Asia particularly, and
central and South America to a lesser extent, although uncommon in travellers. Risk is higher where
there is overpopulation and/or displaced people and sanitation and drinking water are poor. Check
destination before travel to see if cholera is a problem (e.g. CDC website
wwwnc.cdc.gov/travel/default.aspx).
Dukoral is an effective prophylaxis for cholera, a potentially severe GI illness caused by Vibrio
cholerae. It is the only vaccine available internationally for cholera and it has WHO
prequalification.[13] The efficacy against cholera is 80-85% for the first 6 months according to the
datasheet,[14] although WHO reports 85-90% efficacy at 6 months in all age groups.[13] While
protection averages 63% at three years,[14] efficacy drops over time,[15] thus some sources cite a 2
year protection[4] and the pack insert recommends a booster dose (if risk remains) at 2 years for
adults, and 6 months for children 2-6 years of age. Given that the vaccine does not provide 100%
coverage, all precautions should be taken to avoid consuming or contact with potentially
contaminated food or water, especially in areas affected by the O139 Bengal strain against which
this vaccine is ineffective.[10]
The WHO reports that the seventh cholera pandemic is ongoing, with cholera considered endemic in
many countries (e.g. developing countries in Africa and Asia particularly, and central and South
America to a lesser extent), and with V cholerae remaining in the environment (particularly estuaries
and brackish water) with risk higher during droughts, floods and the rainy season.[13] Cholera is
highly virulent and incubation is 2 hours to 5 days. While death can occur within hours in healthy
adults and children, most cases are asymptomatic[13] and in healthy travellers, cholera often
presents with mild to moderate severity. Thus, the incidence of diarrhoea due to cholera is thought
to be greatly underestimated.[16] People with O type blood group are more vulnerable to severe
illness. Jong (2008) recommends vaccination in more susceptible people.[2] These may include longterm
travellers, those with underlying severe diseases or gastric hypochlorhydria (including from
medication), those in close contact with the local population (including relief, medical and technical
workers), travellers to high-risk destinations or travellers with insufficient access to medical care.[2,
4] A recent review (2008) noted that vaccination of travellers to endemic cholera areas reduces both
their own risk and risk of importing cholera on their return.[4]
Risk factors for ETEC and Cholera
Risk factors for ETEC and cholera include:[2]
travelling in or prolonged exposure to poor hygiene conditions (e.g. back packers in remote
areas, visitors staying in local villages, aid workers and military personnel)
gastric conditions such as hypochlorhydria (including from gastric acid suppressing
medication such as proton pump inhibitors, H 2 antagonists or frequent antacids) and partial
gastric resection
immune deficiency
poor food handling including poor hygiene in restaurants
drinking unsafe water (including in ice, cleaning teeth)
O type blood group (cholera)
Copyright Pharmacybrands May 2012 Community Pharmacy Dukoral training material.

Risk from fluid loss is increased in advanced or young age, underlying chronic disease and travelling
at high altitude, thus vaccination and avoidance measures may be particularly important in these
groups (noting minimum age of 2 years for Dukoral). Chronic diseases such as inflammatory bowel
disease and diabetes may be aggravated by travellers’ diarrhoea or cholera.
People taking diuretics need to be especially careful with severe watery diarrhoea and probably
should check with their doctor before travelling as to preferred action (e.g. stopping diuretic during
diarrhoea and seeking medical advice if more than 1-2 days of severe diarrhoea).[2]
Other travel vaccinations and prophylaxis
Other vaccinations and antimalarials are likely to be needed. The vaccinations required depend on
the travel destination/s. Dukoral only provides vaccination for some forms of travellers’ diarrhoea,
and other vaccinations are likely to be necessary and may be more appropriate. Advise consumers to
ensure they are up-to-date on routine immunisations as well, such as tetanus and diphtheria. For upto-date
advice on travel vaccinations see:
World Health Organisation (WHO) International Travel and Health. Available for downloading at:
http://www.who.int/ith/en/
A map of country requirements for yellow fever, rabies and malaria is available at WHO, through
http://www.who.int/ith/en/
Centres for Disease Control and Prevention site (in the United States of America):
http://wwwnc.cdc.gov/travel/page/vaccinations.htm
Other travel supplies
Supplying an electrolyte rehydration product, antidiarrhoeal and water purifying tablets for travel
would be prudent. Alcohol hand wash may be useful; remind the consumer to wait until the hands
are dry after using alcohol for full effect. Insect repellents containing 30% DEET reduce the risk of
mosquito bites, and antimalarial tablets may also be required, depending on area.
Key points for avoiding cholera and travellers’ diarrhoea:
Drink and use safe water, even for cleaning teeth. Avoid ice unless known to be from safe
water. Use bottled water with intact seals or water purification tablets.
Wash your hands often with soap and safe water, especially before eating or food
preparation and after using the toilet. Take alcohol-based hand cleaners for when soap and
water isn’t available (note: let the hands dry before eating or touching food).
Use toilets or bury stools 30 metres away from any body of water.
Cook food well and eat it hot. Particularly avoid undercooked or raw shellfish and fish. Boil
it, cook it, peel it or leave it.
Try to use reputable restaurants. Avoid street vendor food.
Wash yourself, your children, clothes and diapers at least 30 metres away from water
sources used for drinking.
Be prepared in case of diarrhoea, take oral rehydration sachets.
For further information see Safe Food and Water from Centers for Disease Control and Prevention
(CDC), http://wwwnc.cdc.gov/travel/page/safe-food-water.htm.
Copyright Pharmacybrands May 2012 Community Pharmacy Dukoral training material.

Dukoral Dosage
Dosage for ETEC: 2 doses of vaccine in an interval of at least 1 week (no more than 6 weeks).
Complete doses at least 1 week before travelling to the affected area. See pack insert.
Dosage for cholera in adults and children over 6 years: 2 doses.
Dosage for cholera in children aged 2-6 years: 3 doses.
Administer doses at intervals of at least a week (no more than 6 weeks apart).[14]
Don’t forget to advise the consumer to keep the second dose in the fridge.
Avoid food and drink 2 hours before and 1 hour after vaccination (otherwise the vaccination may be
less effective).[14]
See datasheet for further information about boosters.
Precautions
Postpone vaccination in cases of acute illness.[14]
Protection is 80-85% for cholera and up to 67% for ETEC (short-term); clean hygiene practices are
still required.
Dukoral provides protection specific to Vibrio cholerae serogroup O1. Immunisation does not protect
against V. cholerae serogroup O139 or other species of Vibrio.[17]
Limited data is available on immunogenicity and safety of the vaccine in people infected with HIV.
Antibody response may be insufficient in people with immunosuppression.[17]
Trace amounts of formaldehyde used in manufacture may be present; care in known
hypersensitivity to formaldehyde.[17]
Pregnancy
Dukoral is a category B2 drug in pregnancy. According to the NZ datasheet: “The vaccine may be
administered during pregnancy. No specific studies have been conducted to investigate the safety of
Dukoral during pregnancy. However, Dukoral is an inactivated, non-replicating vaccine given orally
and it is not taken up by the blood stream. It is therefore considered to be safe. It has been given to
lactating women in several studies.”[14]
The UK prescribing information is more cautious:[17] “No animal data on reproduction toxicity are
available. Following careful benefit/risk assessment the vaccine may be administered during
pregnancy and to breast-feeding women although no specific clinical studies have been performed
to address this issue.”
Travelling to less developed countries carries other risks for pregnancy – refer to a doctor.
Adverse Events
The NZ datasheet lists only: upset stomach related to the sodium hydrogen carbonate may occur
occasionally.[14]
Copyright Pharmacybrands May 2012 Community Pharmacy Dukoral training material.

The UK prescribing information[17] includes headache (in

17. Crucell Sweden AB. SPC Dukoral Oral Cholera Vaccine. 2011 02/2011 16 March 2012];
Available from: http://www.medicines.org.uk/emc/medicine/14463.
Copyright Pharmacybrands May 2012 Community Pharmacy Dukoral training material.