Fever and Diarrhea in the Returned Traveler

Dr. Chris GreenawayDivision 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

Case #1

• Seen in a walk-in clinic

• CXR- normal

• Given 2nd 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 enteritistyphoiddengueMarburg/EbolaSARSOther viralRickettsia- typhus, other

Incubation periods (Cont’d.)

Intermediate (10 - 21 days)

malaria brucellosistyphus leptospirosisQ fever trypanosomiasistyphoid fever Lassa fever

Incubation periods (Cont’d.)

Long: > 21 days

viral hepatitis Malariatuberculosis schistosomiasis HIVAmoebic Liver AbscessAfrican trypanosomiasisVisceral 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 resultsABG: 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: 11Bili 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)

Travelers 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 32 42 27Resp Tract 11 2.5 24Diarrhea 4.5 6.6 14Hepatitis 6 3 3Dengue 2 6 8UTI 4 2.5 2Enteric Fever 2 2 3TB 1 1 0.4Unknown 25 24.5 9

Spectrum of Disease by Region of Origin in

Ill Travellers- GeoSentinel Caribbean Central

AmericaSouth

America

Sub-Saharan Africa

South Asia SE Asia

Diarrhea

Acute/chronic

Diarrhea

Acute/chronic

Parasitic

Diarrhea

Acute/chronic

Parasitic

Malaria Diarrhea Diarrhea

Larva migrans Larva migrans Leishmania Diarrhea

Acute, chronic, parasitic

Dengue Dengue

Dengue Myiasis Larva migrans Schistosomiasis Enteric Fever Larva migrans

Dengue Myiasis Filaria Malaria Malaria

Malaria Dengue Rickettsia

Freedman NEJM 2006;354:119-130

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 #2Differential 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 %

• ETEC 20-25%• Shigella 12-14%• 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 #5HPI: 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;83:1033-51

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)