Fever and Diarrhea in the Returned Traveler Dr. Chris Greenaway Division of Infectious Diseases, SMBD- Jewish General Hospital Consultant, McGill Center for Tropical Diseases

46 year old Kenyan female presents to your office with a 4 day history of high fever 40C and cough 13 year old son has had a similar illness for 6 days Physical exam is normal What do you want to know? What investigations do you want to do? Case #1

Seen in a walk-in clinic CXR- normal Given 2 nd gen cephlosporin Sent home

What do you want to know? 1.Travel history and itinerary 2.Exposure history 3.Pre-travel preparation

1. Travel itinerary countries duration urban vs. rural accommodation exact arrival/departure dates

Incubation periods for selected tropical diseases Short: < 10 days bacterial enteritis typhoid dengue Marburg/Ebola SARS Other viral Rickettsia- typhus, other

Incubation periods (Cont’d.) Intermediate ( days) malaria brucellosis typhus leptospirosis Q fever trypanosomiasis typhoid fever Lassa fever

Incubation periods (Cont’d.) Long: > 21 days viral hepatitis Malaria tuberculosis schistosomiasis HIV Amoebic Liver Abscess African trypanosomiasis Visceral leishmaniasis

2. Exposure history Activity: Raw,undercooked food Untreated water/milk Fresh water exposure Disease risk: hepatitis, enteritis Enteritis, brucellosis schistosomiasis, leptospirosis

Exposure history (Cont’d.) Activity: sexual contact Sexual contact tattooing, piercing Disease risk: syphilis, GC, chlamydia HIV, hepatitis B, Hepatitis C

3. Pre-Travel Preparation i. Immunizations: efficacy: yellow fever > 95% hepatitis A > 95% hepatitis B 80-95% typhoid fever 70% meningococcal meningitis > 90% Japanese encephalitis > 90%

Pre-Travel Preparation (Cont’d) ii. malaria chemoprophylaxis: drug dose compliance duration iii. other medications

Case #1 3 days later she is brought to ER at the JGH with confusion and high fever. Has been ill for 7 days Initial Lab results ABG: pH: 7.0, pCO2:32, HCO3: 8, pO2: 539 WBC: 6.3, Hb: 152, Plts: 17 (59% PMNs, 9% Immature, 22% lymphs) Cr: 681, BUN: 51, Lactate: 11 Bili 211/131, ALT:54, Alk Phos: 51, GGT: 24, LDH: 931 What is your diagnosis?

Case #1 Lab did a malaria smear because of severe thrombocytopenia P. falciparum: 15% parasitemia Fever began, 1 week after returning from trip to Kenya, South Africa and Uganda.

Case #1 Died 3 hours later from severe falciparium malaria just as IV Quinine was started

Case #1 EBI KIMANANI Born in a small village in Kenya, 1 of 11 children PhD Biostatistician Active advocate in the fight against diseases that ravaged Africa. Travelled extensively to Africa setting up research protocols for new drugs to treat Malaria and HIV. Married with 3 sons (10, 13, 15 yrs)

T ravelers Immigrants malaria, malaria, malaria prolonged fever TB, TB, TB

Fever from the Tropics (percent) MacLean (N=587) Doherty (N=195) O’Brien (N=232) Malaria Resp Tract Diarrhea Hepatitis 633 Dengue 268 UTI Enteric Fever 223 TB Unknown

Spectrum of Disease by Region of Origin in Ill Travellers- GeoSentinel CaribbeanCentral America South America Sub-Saharan Africa South AsiaSE Asia Diarrhea Acute/chronic Diarrhea Acute/chronic Parasitic Diarrhea Acute/chronic Parasitic MalariaDiarrhea Larva migrans LeishmaniaDiarrhea Acute, chronic, parasitic Dengue MyiasisLarva migransSchistosomiasisEnteric FeverLarva migrans DengueMyiasisFilariaMalaria DengueRickettsia Freedman NEJM 2006;354:

Fever from the tropics is often not tropical...but is still malaria until proven otherwise

Investigations of the Returned Traveller with Fever ON ALL PATIENTS MALARIA smear If suspect rpt Q12 X3 CBC Cr, BUN LFTs Blood C&S U/A Urine C&S OTHER Depends on focal symptoms ie CXR Serology Stool C&S Other imaging Etc

Case #2 38 year old male with a 4 day history of fever and chills beginning 1 week after returning from a 1 month trip visiting family in India The physical exam shows a moderately toxic male with a temperature of 39, Pulse of 90 and LLQ tenderness on palpation, spleen tip palpable No rash, no lymphadenopathy

Case #2 Labs Hb 115, WBC 6.0, Plts 110 LFTs Bili normal, ALT- 302, AST-336, Normal Alk Phos, LDH 997 Cr/BUN- normal

Case #2 Differential Diagnosis Malaria, malaria, malaria Typhoid Fever Leptospirosis Endocarditis Pyelonephritis Hepatititis- A, E, C, B Blood cultures – positive for Salmonella typhi Malaria Smear - Negative

Typhoid Fever- Epidemiology Highest Risk Countries (0.3/1000 travelers/month) Indian Subcontinent SE Asia Central America- Mexico Western South America – Peru Parts of North and West Africa Middle East

Typhoid fever: Clinical IP: 3-60 days (7-14 d) Prolonged fever (99), anorexia (85), headache (85), abdominal pain (50) constipation (40), diarrhea (45), cough (35), sore throat (20) apathy (70), hepatomegaly (50), splenomegaly (35), rose spots (0-50), relative bradycardia (15)

Typhoid fever: Complications Clinical: intestinal perforation 3% intestinal hemorrhage 15% neuropsychiatric: delirium, stupor, coma myocarditis 1-5% Relapse: <5% (2-4 wks); fatality <1% Chronic carriage: 30% x 1 mo; 10% x 3 mo; 3% x 1 yr

Typhoid fever: Diagnosis general: anemia, N WBC,  platelets, relative lymphocytosis,  AST, ALT blood culture: 40-80% bone marrow culture 80-95% internal secretions: 60-80% (aspiration) stool culture (wk.2) 50%, urine culture 5- 10% rose spots: 60%

Case #3 28 year old female with a 3 day history of fever, headache and photophobia and a 1 day history of arthritis of her knees, wrists and hands and a truncal rash. She had just return 2 days prior from a 3 week trip to Mauritius. What else do you want to know? What tests do you want to do?

Case #3 Labs WBC 2.8, lymphopenia, monocytosis, Hb- 115, Platelets- 100 PT/PTT- normal Cr/BUN- normal LFTs- normal Malaria smear- Negative Blood cultures- Negative

Differential Dx Fever Short incubation period Arthritis Rash Negative malaria smear Chickungunya Dengue Parvovirus Rubella Leptospirosis Rickettsia- typhus

Chikungunya Outbreak in 2005 in Islands of the Indian Ocean (Reunion, Mauritius) and India, Sri Lanka Arbovirus transmitted by mosquitos Arthralgias (100%), myalgias (97%), headache (84%), diffuse MP rash (77%), lymphadenopathy (41). 1/3 may have arthralgias up to 1 month (occas months) Fever duration ~4 days Incubation 4-7 days Lymphopenia (67%), thrombocytopenia (50%), increase ALT/AST (67%) Dx with serology

Dengue Fever: Clinical short incubation period: 2-7 d. (max. 10) classical dengue: -fever -retroorbital pain -rash -headache -myalgia/bone pain (45%) saddle back fever (2-7 d, afeb 1-2 d, recurrence) rash day 3-5; maculopapular, diffuse erythema atypical presentation common short duration: < 1 week

Dengue: diagnosis leukopenia, thrombocytopenia Mild to mod increase LFTs, LDH dengue IgM positive 4 fold rise in dengue IgG antibodies

Case #4 35 year old female with a 2 day history of diarrhea tinged with blood, 1 day history of chills and fever She had just return 1 days prior from a 2 week trip to Mexico What tests would you like to do? What is the most likely diagnosis?

Case #4 Tests Stools C&S Stools C.difficile (if had received prior AB) Malaria smear If toxic Blood cultures, CBC, Cr, LFTs DDx Shigella, Salmonella, Camphylobacter, E.Coli 0157, E. histolytica

DIARRHEA IN THE RETURNED TRAVELLER

Boil it, cook it, peel it, or forget it! Easy to remember…...Impossible to do ! Lawrence Green,1995

Traveller’s Diarrhea Is the most common travel- related health problem Occurs in 25-50% of international travellers

Traveller’s Diarrhea Clinical IP- 1-2 days 1/3 onset in 1st 2 wks. 4-5 loose stools over 4-5 days (85%) fever 10% bloody stool 15% Sequelae 40% modify activities 20% confined to bed 1% hospitalized 8-15% diarrhea > 1 wk 2% persistent diarrhea > 1 mo.

Etiology (Varies by country) Bacteria 50 – 75 % Protozoa 0 – 5 % Viruses 0 – 20 % Unknown 10 – 40 % ETEC20-25% Shigella12-14% Campy 5-9% Salmonella 3-5% Rotavirus 8% Giardia 1-12% E. Histo 5% Crypto 5% Cylospora 11%

Treatment Uncomplicated TD is self-limited and responds well to symptomatic treatment Management determined by Severity of disease Age Underlying conditions Pathogen isolated (eventually)

Treatment – Uncomplicated TD Symptomatic +/- Empiric Antibiotic Treatment Quinolone 3 days Azithromycin 3 days (esp SE Asia/ India Sub-Continent) Rifaximin 3 days

Treatment- Complicated TD Antibiotics High fever >2 days Bloody, Mucoid diarrhea Hydration if: Profuse watery diarrhea Severe vomiting

Case #5 52 year old male RC: Chronic diarrhea x 2 months Travel: Asia 6 months- Sept 7, 2010-March 8, 2011 Australia (7wks), Indonesia (8wks), India (8wks), Australia (1 wk). Arrived in Cdn 1 wk prior Past Hx: Depression, Gastric reflux Meds: Prosac, Trazadone, Losec

Case #5 HPI: 2 month history of non-bloody diarrhea (3- 4 stools/day) that began a fews wks after arrriving in India, associated with cramps and ++flatulence, and 22 lb wt loss -1 wk prior to seen in clinic treated with a 7 day course of Flagyl 500 mg TID without a change in symptoms. Additional Hx : Gay, engaged in oral penile, peri-anal sex, no anal intercourse while in India, HIV – 2 yrs prev

Case #5 CBC- normal LFTs, Cr- normal Stools O & P- pending Stools O & P- Cryptosporidium 1+ DDx: Resistant Giardia, E. Histolytica, Cryptosporidium, Lactose deficiency, post-infectious IBD, Unmasked IBD

Persistent TD Definition: diarrhea > 30 d Swiss 0.9% Peace Corps 1.7% Tour group 2.9% Dupont, Clin Infect Dis 1996;22:124-8 Taylor, Med Clin N Am 1999;83:

Persistent TD Etiology 1. Infection (Giardiasis, C. difficile) 2. Post-infective (IBS, lactose intolerance) 3. Malabsorption (Tropical sprue) 4. Umasking GI (IBD, Coeliac) 5. Idiopathic (Brainerd) 6. Non-tropical (IBD)

Persistent Travellers’ diarrhea Post infectious IBS 70 Lactose intolerance 15 Infectious ( giardiasis, C. diff.) 10 IBD <1 Sprue:tropical or coeliac <1 Keystone JS - personal communication 2001

Approach to persistent T.D. Exclusion of enteric pathogens  Strict lactose-free diet x 5 d.  High fibre (psyllium; metamucil) +/- MOM, lactulose  Cholestyramine (Questran)