Avoiding diarrhea: Avoiding diarrhea: epidemiology and epidemiology and

preventionprevention

Patrick KellerPatrick KellerAye OtubuAye OtubuAlex DoyalAlex Doyal

Adam Froyum RoiseAdam Froyum Roise

26 April 200726 April 2007

OutlineOutline

Developing world: CholeraDeveloping world: Cholera Cruise ships: NorovirusCruise ships: Norovirus Hiking: Giardia and CryptosporidiumHiking: Giardia and Cryptosporidium Friends: ShigellaFriends: Shigella

CholeraCholera

An acute diarrheal illness caused by An acute diarrheal illness caused by bacterium bacterium vibrio choleraevibrio cholerae

The most severe diarrheal diseaseThe most severe diarrheal disease

What is it?What is it?

A bacteriaA bacteria El tor subtype of O1 is El tor subtype of O1 is

most common but most common but there have been there have been epidemics caused by epidemics caused by new non- O1 new non- O1 serogroup of V serogroup of V cholerae called O139 cholerae called O139 bengalbengal

Epidemiology Epidemiology 2-4 billion episodes of 2-4 billion episodes of

diarrheal disease occur diarrheal disease occur annually in developing annually in developing countries countries

3-5 million deaths/year3-5 million deaths/year Children under five are Children under five are

the most affectedthe most affected People of blood group O People of blood group O

are at higher riskare at higher risk Infection rates affected by Infection rates affected by

water use patternswater use patterns

How do you get it?How do you get it? Classically a water borne disease Classically a water borne disease

causing bacteria.causing bacteria. Eating or drinking contaminated Eating or drinking contaminated

food or water containing vibrio food or water containing vibrio cholerae bacteriacholerae bacteria

Contaminated food and not water Contaminated food and not water a more likely source in developed a more likely source in developed countries.countries.

Sensitive to climate and grows Sensitive to climate and grows rapidly in warmer environmental rapidly in warmer environmental temps.temps.

Humans are the main reservoir. Humans are the main reservoir. Shell fish and plankton are the Shell fish and plankton are the only animal reservoirs.only animal reservoirs.

The natural habitat is believed to The natural habitat is believed to be the Ganges in Bangladeshbe the Ganges in Bangladesh

What is the mechanismWhat is the mechanism Incubation period:Incubation period: btw 18h and btw 18h and

5 days5 days V.V. cholerae produces the cholerae produces the

cholera toxin (an enterotoxin cholera toxin (an enterotoxin with 2 subunits, A and B)with 2 subunits, A and B)

Toxin interacts with G protein Toxin interacts with G protein and causes release of cyclic and causes release of cyclic AMP and alters ion channel AMP and alters ion channel function to inhibit Nfunction to inhibit Naa++ absorption and increase Cabsorption and increase Cll-- secretionsecretion

Increased ions in lumen pull Increased ions in lumen pull more water more water voluminous voluminous diarrhea. diarrhea.

What are the signs and symptoms?What are the signs and symptoms?

General stomach upsetGeneral stomach upset Massive watery “rice water” Massive watery “rice water”

diarrhea (diarrhea (up to 20liters/dayup to 20liters/day)) Muscle and stomach crampsMuscle and stomach cramps VomitingVomiting Fever (early on)Fever (early on) Can progress from 1st liquid Can progress from 1st liquid

stool to shock within 4-6hrs stool to shock within 4-6hrs without treatment, and death without treatment, and death within 18-24hrs.within 18-24hrs.

((Typical presentation is severe Typical presentation is severe diarrhea but most people with cholera diarrhea but most people with cholera infection have no symptoms or mild infection have no symptoms or mild diarrheadiarrhea))

Signs and symptoms cont’Signs and symptoms cont’

Poor skin turgorPoor skin turgor Wrinkled skinWrinkled skin Sunken eyesSunken eyes Restlessness and Restlessness and

thirstthirst Apathy and LOCApathy and LOC

ComplicationsComplications

Acute renal failureAcute renal failure Electrolyte imbalance (esp. K+)Electrolyte imbalance (esp. K+) Severe hypoglycemiaSevere hypoglycemia Miscarriage of premature delivery in pregnant Miscarriage of premature delivery in pregnant

womenwomen

TreatmentTreatment

Aggressive RehydrationAggressive Rehydration Electrolyte replacementElectrolyte replacement ORT ORT (1tsp salt +8tsp sugar in 1liter (1tsp salt +8tsp sugar in 1liter

of clean/boiled water)of clean/boiled water)

IV therapyIV therapy Tetracycline, Cipro- Tetracycline, Cipro- may may

reduce the duration of symptoms; reduce the duration of symptoms; resistance becoming apparentresistance becoming apparent

Death rate without Death rate without treatment is 50% and treatment is 50% and decreases to less than decreases to less than 1% with tx1% with tx

PreventionPrevention

Clean Water-sterilization, boiling, Clean Water-sterilization, boiling, chlorination, or good municipal water chlorination, or good municipal water treatment treatment

Sanitation-proper disposal of wasteSanitation-proper disposal of waste Cook foods properly-esp high risk foodsCook foods properly-esp high risk foods Health education through mass mediaHealth education through mass media Oral Vaccine (Dukoral) licensed and Oral Vaccine (Dukoral) licensed and

available in other countries, but not available in other countries, but not recommeded by CDC to travelersrecommeded by CDC to travelers

Foods to AvoidFoods to Avoid

Raw vegetables Raw vegetables

-Epidemic in Zambia in 2003-Epidemic in Zambia in 2003 ShellfishShellfish

- oysters (concentrate the amount of - oysters (concentrate the amount of vibrios)vibrios)

ReferencesReferences

CDC. Cholera epidemic associated with raw CDC. Cholera epidemic associated with raw vegetables--Lusaka, Zambia, 2003-2004.vegetables--Lusaka, Zambia, 2003-2004.MMWR Morb Mortal Wkly Rep. 2004 Sep MMWR Morb Mortal Wkly Rep. 2004 Sep 3;53(34):783-6. 3;53(34):783-6.

Sack DA, Sack RB, Nair GB, Siddique AK. Sack DA, Sack RB, Nair GB, Siddique AK. Cholera. Lancet 2004; 363:223-33.Cholera. Lancet 2004; 363:223-33.

Morris JG. Clin Infect Dis. 2003 Jul Morris JG. Clin Infect Dis. 2003 Jul 15;37(2):272-80. Cholera and other types of 15;37(2):272-80. Cholera and other types of vibriosis: a story of human pandemics and vibriosis: a story of human pandemics and oysters on the half shelloysters on the half shell

Cruise ship diarrheaCruise ship diarrhea

EpidemiologyEpidemiology

270 acute gastroenteritis (AGE) outbreaks 270 acute gastroenteritis (AGE) outbreaks in US from 2000-2004in US from 2000-2004

81% of 226 eligible outbreaks caused by 81% of 226 eligible outbreaks caused by caliciviruses caliciviruses (>90% of viral AGE)(>90% of viral AGE) Medical facilities: 31%Medical facilities: 31% Restaurants/caterers: 28%Restaurants/caterers: 28% Cruise ships: 16%Cruise ships: 16% Daycare centers: 8%Daycare centers: 8%

Blanton LH, et al. J Infect Dis. 2006 Feb 1;193(3):413-421.

Cruise Ship DiarrheaCruise Ship DiarrheaEpidemiology Epidemiology

YearYear Cases/100,000 Cases/100,000 passenger dayspassenger days

Outbreak Outbreak cases/100,000 cases/100,000 passenger dayspassenger days

19901990 29.229.2 4.2 (<10 outbreaks)4.2 (<10 outbreaks)

20002000 16.316.3 3.5 (<10 outbreaks)3.5 (<10 outbreaks)

2001-42001-4 25.6 25.6 (3.5/cruise)(3.5/cruise)

670 (79 outbreaks)670 (79 outbreaks)

85 cases/cruise85 cases/cruise

Cramer, et al. Am J Prev Med 2006;30(3):252–257.

•In 2002, reports of new variant GII4 strain.

CalicivirusesCaliciviruses

(+)-RNA virus(+)-RNA virus Non-envelopedNon-enveloped Include Norovirus, SapovirusInclude Norovirus, Sapovirus Transmitted by respiration or Transmitted by respiration or

ingestioningestion

Survive in environment: can Survive in environment: can be passed in food, person-to-be passed in food, person-to-person, or on fomitesperson, or on fomites

PresentationPresentation

Incubation period: 1-2 daysIncubation period: 1-2 days 1st sign: abdominal cramps/nausea1st sign: abdominal cramps/nausea Most have vomiting, diarrhea, or bothMost have vomiting, diarrhea, or both 1/5 have systemic symptoms1/5 have systemic symptoms Duration 1-3 days; self-limiting / supporting Duration 1-3 days; self-limiting / supporting

treatment / rehydrationtreatment / rehydration Diarrhea: moderate (4-8 stools per day), Diarrhea: moderate (4-8 stools per day),

non-bloody, no mucus, not non-bloody, no mucus, not inflammatory/no WBCsinflammatory/no WBCs

PreventionPrevention

CDC’s Vessel CDC’s Vessel Sanitation ProgramSanitation Program Started in 1975Started in 1975 Twice annual, unannounced inspections on Twice annual, unannounced inspections on

ships with international itineraries at US portsships with international itineraries at US ports 2001: implemented GISS (electronic 2001: implemented GISS (electronic

gastrointestinal illness surveilance system)gastrointestinal illness surveilance system) B/t 2001-4, 4% of ships failed.B/t 2001-4, 4% of ships failed. http://http://www.cdc.gov/nceh/vsp/default.htmwww.cdc.gov/nceh/vsp/default.htm

PreventionPrevention Things associated w/ outbreaksThings associated w/ outbreaks

Smaller shipSmaller ship Smaller fleetSmaller fleet Older shipsOlder ships

Things not associated with outbreaksThings not associated with outbreaks VSP score/performanceVSP score/performance

Things associated with transmission during an Things associated with transmission during an outbreakoutbreak Having a vomiting cabin mateHaving a vomiting cabin mate Often initially food born, but then multiple routes, Often initially food born, but then multiple routes,

especially person-to personespecially person-to personIsakbaeva, et al., Emerging Infectious Diseases. 2005, 11(1); 154-7.

What you need to knowWhat you need to know

Risk of AGE on a cruise ship: <1%Risk of AGE on a cruise ship: <1% Percent of cruise-ship physician caseload Percent of cruise-ship physician caseload

occupied by diarrhea: <10%.occupied by diarrhea: <10%. But with >10 million passengers a year = But with >10 million passengers a year =

lots of diarrhea. So…lots of diarrhea. So… Wash your hands often.Wash your hands often. Avoid sick people (e.g. cabin mates) and Avoid sick people (e.g. cabin mates) and

“vomit squad”“vomit squad” Look up your cruises inspection score.Look up your cruises inspection score.

Drink the water here:

And you can TROT all the way home!

D. Boulware Medical risks of wilderness hiking. The American Journal of Medicine, Volume 114, Issue 4, Pages 288-293

• In recent surveys 51% of Appalachian trail Hikers experience diarrhea

The happy half use:

• Consistent water treatment

• Frequent hand-washing with soap

• Washing cooking utensils with soap

Occurrence of Cryptosporidium and Giardia was evaluated in 257 water samples from 17 states:

•Cryptosporidium oocysts were detected in 55% of the surface water samples

•Average concentration of 43 oocysts/100 L•Giardia cysts were found in 16% of samples

•Average concentration of 3 cysts/100 L.

J.B. Rose, C.P. Cerba and W. Jablonski, Survey of potable water supplies for cryptosporidium and giardia. Environ Sci Technol 25 (1991), pp. 1393–1400.

Life Cycle

Giardia Cryptosporidium

Prevention

•Cryptosporidium form oocysts between 4 to 7 microns in size.•Giardia cysts are 6 to 10 microns (One micron is one thousandth of a millimetre). •Cryptosporidium is not killed by normal chlorination and is only made harmless by long exposure to concentrated ultra violet light or specialized chemical treatment, Giardia is killed by long contact with chlorine or long exposure to concentrated UV light. •The most successful method of removing oocysts from a water supply is by filtration through microstrainers or cartridge filters.(1 micron absolute)

http://www.drinking-water.co.uk/information%20sheets/cryptosporidium.htm

Treatment

Giardiasis treatment

• Metronidazole

• some other antimicrobials as well

•Treat Giardiasis because chronic infection – also examine close contacts and treat if found.

Cryptosporidiosis treatment

• Supportive unless immunocompromised

www.emedicine.com/emerg/topic215.htm, and med/topic484.htm

ShigellaShigellaMy favourite bloody diarrheaMy favourite bloody diarrhea

EpidemiologyEpidemiology

165 million cases 165 million cases annuallyannually

450,000 in the USA450,000 in the USA 1 million associated 1 million associated

deathsdeaths Spread is by the fecal Spread is by the fecal

oral route of transmissionoral route of transmission Major source is by drinking Major source is by drinking

contaminated food and contaminated food and water sourceswater sources

Highly Infective!Highly Infective! Infective dose is a few as Infective dose is a few as

101011 to 10 to 1022 organisms organisms

PathogenesisPathogenesis

Shigella highly infective b/c Shigella highly infective b/c resistant to natural defensive resistant to natural defensive stomach acidstomach acid

Bugs phagocytosed by Bugs phagocytosed by intestinal epitheliumintestinal epithelium

Once inside of the cell, the Once inside of the cell, the bug spreads directly from bug spreads directly from cell to cellcell to cell

Actin spearActin spear

Clinical ManifestationsClinical Manifestations

Incubation of 1-7daysIncubation of 1-7days

SymptomsSymptoms High feverHigh fever Abdominal crampsAbdominal cramps Bloody diarrheaBloody diarrhea VomitingVomiting

Clinical ManifestationsClinical Manifestations

ComplicationsComplications Rarely bacteremicRarely bacteremic Metabolic disturbancesMetabolic disturbances HUSHUS reactive arthritisreactive arthritis rectal prolapse rectal prolapse neurological neurological

complicationscomplications toxic megacolontoxic megacolon

TreatmentTreatment Break the cycle of the“5-Fs” Break the cycle of the“5-Fs” Best treatment is preventionBest treatment is prevention

Meta analysis showed 59% reduction Meta analysis showed 59% reduction in incidence with handwashingin incidence with handwashing

• Curtis, Cairncross. Lancet Infect Dis 2003 May;3(5):275-81Curtis, Cairncross. Lancet Infect Dis 2003 May;3(5):275-81

No effective treatmentNo effective treatment Self limiting disease, course usually 7 daysSelf limiting disease, course usually 7 days

Cipro and Septra have been shown to decrease Cipro and Septra have been shown to decrease fever by 1-2 daysfever by 1-2 days

No vaccine currently available; in developmentNo vaccine currently available; in development

Questions?Questions?