Transcript Travel Medicine - Duke University

Duke Internal Medicine Residency Curriculum
Travel Medicine
Melissa Huang
Kevin Coleman
Shannon Dunlay
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Learning Objectives
• Identify the most common causes of morbidity/ mortality in
the international traveler
• Discuss epidemiology, diagnosis, and treatment of common
travel illnesses
– Traveler’s diarrhea
– Malaria
– Hepatitis A
• Discuss appropriate pre-travel clinical evaluation
• Discuss appropriate evaluation of fever in the returning
traveler
• Identify useful resources for patients & physicians
• Quiz questions
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Common Diseases Vary by Region
• Central & South America
– Arthropod borne: Malaria,
Dengue, Leshmania, Chagas,
RMSF
– Food/water borne: Traveler’s
diarrhea, Leptospirosis, Hep A,
Cholera, Typhoid
• East Asia
– Arthropod borne: Malaria,
Japanese encephalitis, Dengue,
yellow fever, typhoid
– Food/ water borne: Diarrhea,
Cholera, Typhoid, Hep A&E,
poliomyelitis, schistosomiasis
(avoid swimming in fresh
water)
• Southeast Asia
– Similar to East Asia but
chloroquine-resistant P.
falciparum is more
widespread
• Sub-Saharan Africa
– Malaria, dengue, yellow fever,
African trypanosomiasis,
Leishmaniasis,
Onochocercosis, Typhus,
hemorrhagic fever (Lassa
fever, Rift Valley fever, Ebola,
Marburg
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The leading causes of morbidity
and mortality in international
travelers include:
•
•
•
•
•
•
Motor vehicle accidents
Traveler’s diarrhea
Malaria
Upper respiratory infections
Hepatitis A
Sexually transmitted diseases
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Motor Vehicle Accidents
• Leading cause of morbidity/ mortality in
travelers
• Prevention is the key:
– Importance of wearing seat belts
– Following driving safety precautions
• Risks associated with blood transfusions
from potentially unsafe blood products
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Traveler’s Diarrhea
Definitions: 3 classifications used to define
traveler’s diarrhea1:
• Classic: Passage of 3 or more unformed
stools in 24 hrs + at least one of the
following symptoms: nausea, vomiting,
abdominal pain/ cramping, fever, blood in
stools
• Mild: Passage of 1-2 unformed stools in 24
hrs without additional symptoms
• Moderate: Passage of 1-2 unformed stools
in 24 hrs + at least one of the following
symptoms: nausea, vomiting, abdominal
pain/ cramping, fevers, blood in stools OR
passage of >2 unformed stools in 24 hrs
without other symptoms
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Traveler’s Diarrhea: Epidemiology
• 40-60% of traveler’s to developing nations
develop traveler’s diarrhea2
• Transmission is primarily via food and water
• Epidemiology and risk depends on geographic
locations, seasons, exposures
• Risk factors:
– Burden of ingested organisms
– Patient profile, i.e., patients with altered GI
anatomy, abnormal motility, suppressed
gastric acid secretion (on PPI or H2 blockers)
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Traveler’s diarrhea
Diagnosis: clinical- distinguish between: watery
diarrhea vs. dysentery (bloody) vs. chronic diarrhea
Watery
Diarrhea
Dysentery
(15% of cases)
Chronic
diarrhea (rare)
Acute; watery;
self-limited
Bloody; often with
fevers
Non-bloody;
afebrile; persists
over a few weeks
Causes:
•Often no etiologic agent identified; usually self-limited
•When symptoms are severe or persist >48-72hrs, medical
intervention and work-up may be warranted (stool cultures, O&P)
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Etiologies of Traveler’s Diarrhea
Bacterial
(>90% of all
traveler’s
diarrhea)
Viral
Parasites
Polymicrobial
Enterotoxigenic E. coli, Salmonella spp.,
Campylobacter jejuni, Shigella spp.,
Enteroaggregative E. coli, Vibrio spp., C. diff,
Aeromona hydrophilia, Plesiomonas shigelloides,
Yersenia enterocolitica
Rotavirus (most common, up to 9%), enteric
adenovirus3
Cryptosporidium parvum, Microsporidia,
Isospora belli, Giardia lamblia, Entamoeba
histolytica (uncommon pathogens)
Up to 20% of travelers in the U.S. had diarrheal
infections w/ >1 organism4
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Traveler’s diarrhea: prevention is key
• Food and water precautions:
– Eat only foods that are thoroughly cleaned and recently
cooked
– Wash all fruits and vegetables with clean water
– Peel all raw fruits and vegetables
– Avoid raw meat, fish, vegetables, salads, unpasteurized
dairy; particularly when dining out
– Avoid drinking tap water or using ice- even bottled water
isn’t always safe!
– Look for carbohydrate beverages and confirm presence of
carbonation upon open
– Purify drinking water by boiling it, treating with chlorine or
iodine or filtering it when clean water is not available
– CDC sound byte: “Boil it, cook it, peel it, or forget it.”
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Prevention
• Prevention
– A recent study found that travelers to Mexico who
were given rifaximin had a significant reduction in the
development of travelers diarrhea compared with
placebo (14.74% vs. 53.7%, risk ratio 0.27)5
– The primary cause of traveler’s diarrhea in Mexico is
ETEC and there are no studies in countries where
invasive pathogens are more common
– Previously prophylactic antibiotics were discouraged
due to side effects, drug reactions, false sense of
security leading to lapse in precautionary measures,
and antibiotic resistance
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Traveler’s Diarrhea: Treatment
• Fluid replacement/ oral rehydration:
– Most important!!!
– Oral rehydration therapy (ORT) contains both carbohydrate
and salt as glucose facilitates water reabsorption & Na/ glc
absorption are coupled
• Antimotility agents: addition of loperamide may reduce
duration to <1day, but avoid if diarrhea bloody or w/ fevers
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Treatment
• Treatment once diarrhea develops
– Shortens disease duration to about 1 day after
initiation
– Abx options (2-3 day course): fluoroquinolone,
azithromycin
– Rifaximin does not work to treat invasive pathogens
(bloody)
– Physicians should provide a prescription for antibiotics
for travelers to take & fill if diarrhea develops during
travel
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Malaria: Epidemiology and Diagnosis
• 4 species of Plasmodia cause human malaria:
falciparum (most dangerous), malariae, ovale, vivax
• While traveling, several hundred U.S. citizens contract
malaria annually5
• Diagnosis: requires heightened clinical suspicion when
a febrile illness occurs in a patient that recently traveled
to an endemic area
– Made by ID of parasites on Giemsa stained thick and
thin blood smear microscopy
– Clinical presentation: fevers,
chills, headache, myalgias,
arthralgias, nausea, vomiting,
diarrhea
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Malaria Epidemiology
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Malaria: Treatment
Treatment based on Plasmodia Species, Parasitemia & Resistance
P.
falcip
arum
Mild to moderate Quinine sulfate 650mg PO TID x3D +
ChloroquineDoxycycline 100mg PO BID x7D (can substitute
Resistant
pyrimethamine in non-resistant areas
Severe
ChloroquineResistant
Quinidine 10mg/kg IV over 1-2hrs, then
0.02mg/kg/min + Doxycycline 100mg PO/IV
Q12hrs **Consider exchange transfusion when
parasitemia >10%
Non-chloroquine Chloroquine 600mg POx1 then 300mg PO x3D
resistant
P. Vivax, P. ovale, P.
malariae
Chloroquine PO **for vivax & ovale,
+Primaquine 15mg PO QD x14D to eradicate
dormant hepatic form (G6PD deficiency test 1st)
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Malaria: Prevention
• Physicians should provide travelers with advice
• Antimicrobial prophylaxis based on resistance patterns, risk of
malaria in travel region, side effects/ contraindications
– Initiate chemoprophylaxis prior to arrival and continue after
departure
– It is still possible to acquire malaria on chemoprophylaxis
• Mosquito avoidance techniques
–
–
–
–
Mosquitoes that transmit malaria usually feed at night
Remain in screened areas as much as possible
Use mosquito netting treated with Permethrin
Cover exposed skin w/ Permethrin treated clothing **should repel
mosquitoes for >1wk even with washing6
– Apply DEET containing insect repellant (30-50% concentration)
• No effective malaria vaccines are currently available
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Malaria: Chemoprophylaxis Agents
• Chloroquine
– 1st line agent effective against all 4 malaria species
– 500mg Qwk 1-2 wks prior to arrival and for 4 wks after departure
– SE: GI, dizziness, H/A, blurred vision, RARE ocular toxicity
• Mefloquine
– Primary choice in areas w/ Chloroquine-Res P. falciparum
– Dosing: 250mg PO QDx3D, then 250mg PO Qwk
– SE: Neuropsychiatric (nightmares, seizures, psychosis)7, nausea,
dizziness, vertigo
• Alternative agents in chloroquine-resistant areas:
– Atovaquone-proguanil: fewer side effects than mefloquine
– Doxycycline: requires daily administration and has
photosensitivity8
– Primaquine: hemolysis if G6PD deficient, eradicates hepatic
stages of P. vivax and ovale9
– Pyrimethamine/ sulfa: can cause severe mucocutaneous rxns.
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Hepatitis A
• Epidemiology
– Occurs worldwide
– Spread via fecal-oral route- more common in areas
with poor sanitation
– Can be spread via contaminated food and water
• Clinical manifestations
– Prodrome of fatigue, malaise, anorexia, fever, RUQ
pain
– Few days later dark urine, jaundice, pruritis
– 2 most common physical findings are jaundice (70%)
and hepatomegaly (80%)10
– Laboratory: AST, ALT (often >1000), bilirubin, alk
phos
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Hepatitis A
• Diagnosis
– Serum IgM Anti-HAV antibodies is gold standard
– Remain positive 4-6 months
• Treatment
– Generally self-limited (full recovery in 3-6 mo)
– Supportive Care
– Rarely develop fulminant hepatic infection, mainly in
patients with concomitant hepatitis C
• Prevention
– Food and water precautions
– Vaccine available: some indications include travel to
specific areas, sexually active gay men, chronic liver
disease, occupational risks, illegal drug users
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Sexually Transmitted Diseases
• Sexual contact with new partners
during travel is common
– Study of 782 travelers, 19%
reported a new sexual partner
and 6% acquire an STD11
• Gonorrhea was diagnosed in 3 per
1000 per month in returning
travelers in a study of >10,000
Swiss citizens traveling to a
developing nation for <3 months12
• Other STDs include: syphilis, HIV,
hepatitis A, B, & C, CMV
• Physicians should counsel patients
about the risks of STDs and
prevention
Secondary syphilis rash
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Pre-travel Evaluation
• All persons traveling to a foreign country should seek
advice from their doctor or a travel medicine provider 4-6
wks in advance of their travel
• Patients should receive counseling, immunizations, and
prophylaxis based on their destination
– Safe food and water
– Insect and arthropod protection
– Immunizations
– Chemoprophylaxis and possible Rx for traveler’s
diarrhea
– Medical help available in the area of travel
• Patients should always ensure that they have a sufficient
supply of their regular prescription medications prior to
travel
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Pre-travel Evaluation: Immunizations
• CDC divides into three categories: routine, recommended, and required
• Routine
– E.g. tetanus-diphtheria, influenza vaccine, pneumococcal vaccine,
hepatitis B, MMR, varicella as appropriate
• Recommended (depends on travel destination- see CDC website at
www.cdc.gov/travel)
– Most common are hepatitis A&B, typhoid, meningococcal (sub-Saharan
Africa May-June), Japanese encephalitis
• Required
– Yellow fever to some sub-Saharan Africa and tropical S. America.
– Meningococcal vaccine for travel to Saudi Arabia during Hajj
• Vaccine contraindications:
– Live virus vaccines (yellow fever, polio, MMR)- pregnant,
immunocompromised
– Yellow fever vaccine contains egg protein- check for allergy
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Pre-travel Consideration: Travel Insurance
• Know your policy- not all major insurers provide coverage
for emergencies while traveling
– Social Security/ Medicare does not provide coverage outside
the U.S.
• Consider counseling patients to obtain supplemental
health insurance for international travel
• Evacuation insurance
– Less than $50/yr vs. out of pocket costs >$100,000
– Can provide evacuation to major medical areas
• See U.S. Department of State website for list of travel
insurers/ medical evacuation providers:
http://travel.state.gov/travel/index.html
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Primary Care: Fever in a Returning Traveler
• 38% of travelers who sought advice prior to travel
reported illness upon return13
• 53% of hospitalized returning travelers with fever
presented w/in 1 wk of return. Most common diagnoses
were malaria (27%), URI (24%), gastroenteritis (14%),
dengue fever (8%), bacterial pneumonia (6%)14
• Diarrhea and URIs are the most common infections
overall in travelers
• Signs requiring urgent intervention: hemorrhagic
manifestations, respiratory distress, hypotension,
hemodynamic instability, confusion, lethargy,
meningismus, focal neurologic findings
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Fever in Returning Traveler: Evaluation
• Requires a systematic approach:
– Detailed travel history
– Geography, dates of travel, transportation, accommodations
– Exposures: sexual contacts, animals, arthropods, needle/ blood
exposures, food & beverages, soil & water contact
• Clinical Evaluation
– Age, sex, PMH, prior infections, meds, chemoprophylaxis, vaccines
– PE: skin findings, lymphadenopathy, hepatosplenomegaly, genital
lesions, neuro findings, retina/ conjunctiva
– Screening labs: CBC w/ diff, GI panel, bld cultures, malaria
smears, CXR
• Differential diagnosis
– Tailored based on above information
– Include malaria if patient traveled to endemic region
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Resources for Patients & Physicians
• Duke University Medical Center Travel Clinic
– Th & F at Duke South and M&T at Southpoint
– Appointments can be made at 681-6261
• CDC website: http://www.cdc.gov/travel
• Yellow book: a reference for health care providers advising
international travelers on health risks. More info:
http://www2.ncid.cdc.gov/travel/yb/utils/ybBrowseC.asp
• Wilderness Medical Society (WMS) provides courses for
physicians wishing to serve as expedition medical staff
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References
1. Lancet 2000; 356:133
2. UpToDate, “Traveler’s Diarrhea,” October 4, 2005.
3. Arch Virol Suppl 1996; 11:171.
4. Morbidity/ Mortality Weekly Report 1997; 46:536.
5. CDC, Health Information for International Travel. www.cdc.gov
6. J Am Mosq Control Assoc 1989; 5:176.
7. Lancet 1993; 341:1299.
8. Ann Intern Med 1997; 126:963.
9. N Engl J Med 2003; 349:1510.
10. J Infect Dis 1995; 171S1: S15-18.
11. AIDS 1994; 8:247.
12. J Infect Dis 1987; 156:84.
13. J Travel Med 1997; 4:61.
14. Clin Inf Dis 2001; 33: 603
15. Morbidity/ Mortality Weekly Report 2004; 53:21.
16. J R Coll Physicians Lond 1998; 32:235.
17. Emerg Infect Dis 2005; 11:436.
18. J Allergy Clin Immunol 1995; 95:1064
19. JAMA 1994; 272:885.
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Quiz Question #1:
A 26 year old female who recently relocated to the U.S. from
Honduras 6 months ago presents to the emergency department
with a three day history of fever, abdominal pain and vomiting.
She reports that she was treated for malaria 9 months ago with
chloroquine in El Salvador when she presented with similar
symptoms. A thick and thin smear obtained in the ED reveal
plasmodium vivax, 1% parasitemia. What is the most likely
explanation for this patient’s recurrence of malaria?
A. She did not complete her full course of chloroquine in El Salvador
B. She caught malaria from her cousin who is visiting her from El Salvador
C. She had reactivation of liver hypnozoites from the first episode of
malaria
D. She was reinfected by a mosquito carrying malaria here in Durham
E. There is no way she has malaria- the ED is wrong again.
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Quiz Question #2
Referring to the patient in question #1, what is the most
appropriate treatment for her illness?
A. Chloroquine 600mg PO x1, then 300mg PO daily x3 days
B. Chloroquine 600mg PO x1, then 300mg PO daily x3days,
followed by primaquine 15mg PO daily x14 days
C. Quinidine 10mg/kg IV over 1-2 hrs, then 0.02mg/kg/min
IV followed by doxycycline 100mg PO/ IV Q12hrs
D. There is no treatment available that will cure her
recurrent malaria
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Quiz Question #1&2: Explanation
Correct answer #1: C
Correct answer #2: B
Explanation: P. vivax and P. ovale remain dormant in the
liver in hypnozoite form. This form is not eradicated by
treatment with chloroquine alone, so this patient was not
adequately treated during her 1st episode 9 months ago.
Correct treatment would entail chloroquine (El Salvador is
not an area with chloroquine-resistant malaria) followed
by primaquine to eradicate liver hypnozoites to prevent
another recurrence. In addition, she should be tested for
G6PD deficiency prior to use of primaquine as this
medication can cause hemolysis in G6PD-deficient
patients.
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Quiz Question #3:
A 30-year HIV positive male recently returned from a trip to
sub-Saharan Africa. He did not take chemoprophylaxis
prior to his trip. His sister notices that he has had a high
fever and is developing altered mental status and rushes
him to the Duke Emergency Department. Upon
presentation, the patient is febrile to 39.5C. He is only
oriented to person and has a generalized seizure shortly
after presentation. Thick & thin smears reveal bananashaped gametocytes within red blood cells. What
plasmodium species is this patient infected with?
A. Plasmodium falciparum
B. Plasmodium vivax
C. Plasmodium ovale
D. Plasmodium malariae
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Question #3 Explanation
Answer: A
Explanation: This patient is having symptoms c/w cerebral
malaria. This can occur in patients infected w/ p.
falciparum. Clinical findings consist of an altered level of
consciousness and seizures. Risk factors include HIV
infection, pregnancy, age (old or young), prior
splenectomy. Patients living in endemic areas are much
less likely to get cerebral malaria even if infected w/ P.
falciparum than non-immune individuals. It is universally
fatal if untreated and is associated with 20% mortality
with treatment.
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Quiz Question #4
A 20-year old female college student presents to the acute
care clinic for evaluation of jaundice. She recently
returned from a Spring Break trip to Cancun, Mexico. On
examination she is grossly jaundiced and has appreciable
hepatomegaly on exam. Laboratory data is significant for
an AST of 1200, ALT 1800, total bilirubin 8.2, INR 1.1.
What laboratory test would help to identify the most
likely diagnosis?
A. Anti-hepatitis C virus antibody
B. Hepatitis B surface antibody
C. Monospot
D. IgM anti-hepatitis A virus antibody
E. IgG anti-hepatitis A virus antibody
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Quiz Question #5:
Referring to the patient in question #4, what is the most
appropriate treatment at this time?
A. Supportive care only
B. Doxycycline 100mg PO BID x7 days
C. Pegylated interferon alone
D. Pegylated interferon plus ribavirin
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Quiz Question #6
Referring to the patient in question #4, what is the most
likely outcome from this illness?
A. Fulminant hepatic failure
B. Chronic infection with resultant cirrhosis over time
C. Resolution without permanent hepatic damage
D. It depends on the treatment used
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Questions #4-6 Explanations
Question #4 Answer: D
Question #5 Answer: A
Question #6 Answer: C
Explanation: This student most likely has acute hepatitis A
virus infection. This is transmitted primarily by fecal-oral
route and is common in areas with poor sanitation. In
patients with appropriate clinical findings, the diagnosis
can be confirmed by an elevated hepatitis A virus IgM
antibody level. The vast majority of cases resolve with
AST/ ALT levels returning to normal within 3 months
(85%) and treatment is supportive.
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Quiz Question #7
A 30-year old male presents to your clinic for evaluation
prior to a trip to Central America. He wants to avoid
getting traveler’s diarrhea during his trip and is
wondering if there is anything he can do to prevent this.
What advice do you offer?
A. Only drink bottled water and you should be fine.
B. Salads are the safest food to eat while dining out.
C. Only eat food that is thoroughly cleaned and recently
cooked and concentrate on drinking carbonated
beverages.
D. There is nothing you can do to prevent traveler’s
diarrhea.
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Quiz Question #7 Explanation
Correct answer: C
Explanation: Prevention is key while traveling to avoid
traveler’s diarrhea. Bottled water is not always safe and
can come from a contaminated source. In addition you
should avoid eating fresh vegetables or salads at
restaurants- only eat those that are cooked or fruits/
vegetables you can peel yourself. Carbonated beverages
are a safe drink if you make sure to verify the presence of
carbonation upon opening.
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