Travelers’ Diarrhea Paul Hladon, MD, DTM&H ----Surgical Urgent Care & Emergency Services Southern California Permanente Medical Group Kaiser Permanente Medical Center Panorama City, CA Travelers’ Diarrhea Paul Hladon, MD, DTM&H ----Surgical Urgent Care & Emergency Services Southern California Permanente Medical Group Kaiser Permanente Medical Center Panorama City, CA DTM&H www.astmh.or g www.istm.org Leisure Reading Objectives Common etiologies of travelers’ diarrhea (TD) Basic pathophysiology of TD Treatment for TD Prophylaxis against TD Prevention of food & waterborne illness in travelers Diarrhea Familiar to most travelers, esp. tropics Most common travel-related health problem – 25-50% of travelers Bacteria (≥ 60%) most common cause GI syndromes in tropics: Watery diarrhea & gastroenteritis Inflammatory diarrhea / dysentery Persistent diarrhea > 2 weeks Travelers’ diarrhea (TD) What is TD? Normal ecology of GI tract upset by exposure to new foods & microorg. Precise definition elusive Three or more loose stools in 24hr plus at least one sx of enteric disease: Nausea, vomiting, cramps, fever, urgency, tenesmus, bloody / mucoid stools Mean duration of sx = 3-5 days w/o tx Variable clinical course & severity What is TD? Majority of cases are self-limited & uncomplicated 5-15% of TD cases Æ dysentery, IV tx These same 5-15% of pts tend to seek medical consultation Falciparum malaria? Fever + diarrhea (14%) Fever in returning travelers… TD Risk http://www.salix.com/assets/images/xifaxan/travelers-diarrhea-risk-areas.gif TD Risk Regional differences in risk & etiology Attack rates (median) same for Latin America, Asia & Africa (54%) Four- or five-star hotels NOT protective against TD Adventure travelers at higher risk than hotel population in general TD Risk Travelers at risk: Immunocompromised, children under 6 Low gastric acidity Young adults, adventurers, “extreme” travelers High socioeconomic status No travel to tropics in 6 months Travel from developed to underdeveloped area Length of stay & “native” itinerary Elderly, pregnancy, very young, immunocompromised, GI disease Æ complications from TD TD Etiology ETEC = enterotoxigenic E. coli Single most important pathogen worldwide ETEC, Campylobacter jejuni & Shigella spp. Æ 45% of identifiable pathogens EAEC, Salmonella, Aeromonas, Plesiomonas, V.cholerae, V. parahaemolyticus, V. vulnificus, Yersinia, [Giardia & Cryptosporidium (3%)] Norovirus, Norwalk virus (5-15%) NO identifiable cause over ½ of cases TD Etiology ETEC Especially in Latin America, South Asia & Africa E. coli ETEC Æ 108 organisms required for clinical illness – large inoculum Poor sanitation, humans main reservoir EAEC – emerging TD pathogen, 2nd only to ETEC in some studies – LA EIEC – dysentery sx, rare TD EHEC – shiga-like toxin, HUS, TTP, hemorrhagic colitis, O157:H7, rare TD EPEC – infants in dev. world, rare TD E. coli ETEC – plasmids code for enterotoxins Heat Stabile (ST) & Heat Labile (LT) Pathogenic ETEC strains – one or both ST – alters fluid transport in distal small bowel, ↑ cGMP LT – similar to cholera toxin, ↑ cAMP Secretion of isotonic fluid, ↑ Clsecretion, ↓ Na+ absorption Campylobacter Campylobacter infections – worldwide, hyperendemic in tropics Exposure to animals / food products Developing countries – children, yearround, non-inflammatory, watery Developed countries – age 15-29, summer / fall, inflammatory, bloody Adhere & invade epithelial cells Æ cellular injury Æ diarrhea Shigellosis Diarrhea, dysentery, death 100-200 organisms for dz. Fly-borne, person-to-person Human reservoir – epidemics Cell invasion, lysis, ulceration in terminal ileum & colon Grossly bloody / mucoid stools, tenesmus, painful straining, crampy abdominal pain Shigellosis Inflammation & ulceration of colonic mucosa & intense proctitis Rectal prolapse, toxic megacolon HUS – hemolytic anemia, oliguric renal failure & thrombocytopenia Children & adults with dysentery in tropics Æ Shigella infection most likely aapredbook.aappublications.org TD Etiology Salmonella spp. – non-typhi infections Vibrio spp. – seafood buffets Cholera possible in travelers but rare Viruses – adeno, astro, rota, calici – cruise ship & hotel outbreaks Protozoa – protracted diarrhea, longer duration of stay Giardia, Entamoeba, Cryptosporidium, Cyclospora TD Pathophysiology SMALL bowel Large volume Secretory Watery Enterotoxin Adherence Enteritis Leukocytes (-) Diarrhea ETEC, EAEC V.cholerae Salmonella vs. vs. vs. vs. vs. vs. vs. vs. vs. LARGE bowel Small volume Invasive Bloody Cytotoxin Invasion Colitis Leukocytes (+) Dysentery Shigella, Yersinia Campylobacter EHEC, EIEC TD Treatment Most cases uncomplicated, self-limited, respond to empiric tx Most tx by travelers themselves Educate travelers how to self-dx & empirically tx TD when it occurs Tx can often limit sx to one day Bacterial diarrhea vs. toxic gastroenteritis (food poisoning) Protozoal diarrhea – long-term traveler TD Treatment Diagnostic work-up not always necessary or cost-effective Timely recognition of severe cases Dysentery, profuse V/D, dehydration Resistance of pathogens, geographic region, invasive vs. non-invasive org. Death in healthy travelers virtually unheard of TD Treatment 1) Rehydration 2) Symptomatic tx 3) Antibiotic tx Oral rehydration solution (ORS) or other fluids of choice Some fluids contain excess sugar & insufficient e-lytes compared to ORS Anti-secretory, anti-motility & antiemetic medications TD Treatment Bismuth subsalicylate: Anti-secretory, anti-inflammatory, anti-bacterial Binds toxins of Vibrio & ETEC Reduces intestinal secretions 524mg (2 tabs or 30mL) Q30 min x 8 doses Reduces stool # & duration of illness by 50% BLACK tongue & stools *Decrease abx absorption – 6 hr window ASA allergy, tinnitus?, warfarin TD Treatment Anti-motility agents: diphenoxylate + atropine (Lomotil), loperamide (Imodium) – maximum 8 tabs / 24 hr Toilets Å medicate? Æ Itinerary OK in cases of invasive diarrhea? Yes Safe to take antibiotic & anti-motility agent for dysentery No adverse effects from one study Recovery time faster with cipro + loperamide TD Treatment Bacterial TD (majority) Æ antibiotics FQ or azithromycin (SE Asia) Thailand: Campylobacter common & resistance to FQ 70-90% Æ azithro Cipro 500 mg bid x 1-3 days – other FQ Azithro 1 gm PO single dose, children 10 mg/kg/day x 3 days TMP/SMX? Only Mexico & Cent. Amer. – high resistance rates worldwide TD Treatment Rifaximin (Xifaxan) – doesn’t cross mucosa – unlikely to be effective in tx dysentery / invasive organisms Rifaximin non-formulary in KPHC Tetracycline or doxycycline possible tx Treatment with abx generally results in recovery in 24-36 hrs TD Treatment Protozoal diarrhea – Central Asia Giardia – tinidazole, metronidazole Entamoeba (rare) – tinidazole, diloxanide or paromomycin Cyclospora – TMP/SMX Dientamoeba fragilis – tetracycline TD Prophylaxis Behavior modification not reliably effective, but prophylactic agents are Risk of side effects & poor judgment – adventurous eaters due to abx px Good choice for travelers whose plans would be ruined by TD – business, honeymoon, short-term etc. TD Prophylaxis Bismuth subsalicylate – 2 tablets qid Anti-microbial & anti-secretory agent, toxin adsorption Protection ranges from 40-65% Lowers bioavailability of doxycycline TD Prophylaxis Prophylactic antimicrobials Neomycin, doxycycline, TMP/SMX have all fallen out of favor Æ resistance FQ – up to 84% protection Rifaximin – 70-80% protection Azithro good for tx of TD (SE Asia), but no guidelines for prophylaxis TD Prophylaxis Bismuth SS Ofloxacin Norfloxacin Ciprofloxacin Levofloxacin *Rifaximin 2 tabs 300 mg 400 mg 500 mg 500 mg 200 mg qid qd qd qd qd qd Exclusive intra-luminal action TD Prevention BOIL it COOK it PEEL it… …or forget it ?????? Despite such measures, rate of TD in travelers has not declined in 50 years In one study, 34% of travelers still contracted TD despite detailed counseling & written instructions TD Prevention Probiotics – safe, but not recommended, modest benefit at best Vaccines – oral cholera & typhoid risk in travelers is low – no good vaccine due to multiple organisms that can cause TD Behavioral modification regarding food & beverages largely unsuccessful TD Prevention SAFE +/- UNSAFE Carbonated drinks Carbonated H2O Boiled H2O Purified H2O Hot, grilled food Processed food Boiled food Peeled fruits Cooked veggies Juices Bottled H2O Packaged ice Dried foods Jam, syrup Washed vegs/fruit Tap water Chipped ice Unpast. milk Salads Sauces, salsa Raw seafood Raw meats Cold desserts Unpeeled fruits Local homes Street vendors Restaurants Keystone, Jay S. et al. Travel Medicine: Expert Consult. Philadelphia, PA. Elsevier, Mosby, 2008, p.193. TD Prevention Food > H2O as contamination source Drink only bottled or purified water, even for brushing teeth or meds Eat foods that are cooked & served “piping” hot Æ 160*F, too hot to eat Only eat fruits peeled by traveler Avoid salads & leafy green vegetables Avoid ice cubes in all beverages TD Prevention Drink only pasteurized milk Avoid raw or undercooked seafood Avoid food from street vendors Dry off canned beverages – soda / beer ? Questions ?