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A Travel Medicine Case

Thomas Miller MD

Case #1
Jack called from San Francisco at 7:30
pm.
Dad I am leaving for Indonesia in 2
days. Do I need any shots before I
go. What about Malaria prevention?

Topics of Discussion

The travel consultation


Travelers diarrhea
Immunizations
Malaria prophylaxis
Complications

The Travel Consultation

Risk assessment
Risk reduction
Shared decisions
Resources
www.cdc.gov/travel
Travax
Yellow book

Ideally conducted 4 weeks prior to


departure, but 2 weeks will do

Risk assessment
Medical history
Chronic illnesses
Immune status
Vaccination history

Travel itinerary
Destination
Style of travel
Duration
Planned activities

Medical history
Healthy 24 year old
Complete childhood immunizations
Hepatitis A and B vaccines given in
school
Before college
Meningococcus
Updated MMR

Mentawai Islands, Sumatra


Indonesia

Destination: Indonesia
Bali and Mentawai Islands

CDC Travelers Health


Immunizations

Routine
Hepatitis A
Hepatitis B
Typhoid
Rabies
Japanese encephalitis

Malaria prevention

Other than chloroquine

Medicine for diarrhea

Other considerations
Style of travel

Hostel style
Not airconditioned
Not usual tourist destination

Duration 1 month
Planned activities

Travelers Diarrhea

Epidemiology
Most common illness in travelers to resource
poor areas
90% of travelers will make an error in what
they eat or drink within several days
50% of travelers will experience illness over
the course of a 2-3 week vacation

The illness
>2 loose stools over 24 hrs
Fever, nausea, vomiting, cramping
Duration 3-5 days

Cause
Bacteriologic enteropathogens 90%
Enterotoxigenic E. Coli
Others: Camphylobacter, Salmonella, Shigella

Viruses: rotavirus and noravirus


Parasites: giardia, crytosporidium,
cyclospora

Food contamination more common that water

Prevention
Standard food safety measures
Boil it; cook it; peel it or forget it.
Bottled beverages
Restaurant hygiene a bigger factor

Chemoprophylaxis
Peptobismol: 2 tabs qid
Fluoroquinolones Ciprofloxacin 500mg qd
Infection rates reduced from 50% to 5%

Not routinely recommended


Mild disease that responds to treatment

Last for 24-36 hours with improvement


within 6-12hr

Usual side effects


C dif
Promotion of resistant bacteria

Special Populations
VIPs
Vulnerable hosts

Immune incompetent
HIV, transplant, chemotherapy

Inflammatory bowel disease


Renal insufficiency
Diabetes

Treatment
Loperamide (imodium): antisecretory
Fluoroquinolones
Ciprofloxacin 500bid x 1 day
Can be extended for 3 days if needed
Shortens the course of illness by 1.5 days
Improvement noted with 6-12hr

Oral rehydration
Sodas and broth
Oral rehydration therapy

Rifaximin
New nonabsorbable antibiotic
A rifamycin
Broad spectrum of activity against gram
pos. and neg. organisms
Approved for the treatment of
uncomplicated travelers diarrhea
Little effect on gut flora

Tested in Central America,


Caribbean, Kenya
Dose: 200mg tid
Comparable to fluoroquinolones in effect
TLUS cut from 60hr to 30hr
Side effects similar to placebo

Prophylactic use
Dose: 200mg qd
75% effective

Disadvantages
Not effective for invasive disease dysentery
Fever
Systemic toxicity
Bloody diarrhea

Cost $3.80/pill

A Vaccine for TD?

Background
Enterotoxigenic E coli causes most TD
Heat-labile enterotoxin (LT) is found in 2/3 of
ETEC
Natural immunity to LT occurs and provides
protection
Oral cholera vaccine cross reacts with LT and
protects against TD
LT is strongly antigenic

Too toxic for oral, nasal and parenteral routes

Transdermal immunization (Patch)


Tested in a small feasibility study
No difference in occurrence of TD
Reduced the incidence of severe
diarrhea
Vaccine recipients experienced a milder
illness
Skin reactions occurred at the site of
application

My patient
Standard precautions
Not a VIP
No chronic diseases
Loperamide
Ciprofloxacin 500 bid x 3 days max

Immunizations

Routine
Hepatitis A
Hepatitis B
Typhoid
Rabies
Japanese encephalitis

Typhoid Vaccine

Typhoid fever
Caused by Salmonella enterica
Source: contaminated food or water
Risk in South Asia highest
Fever, headache, malaise, not diarrhea
400 cases per year in US travelers
Second most common cause of fever in
return travelers

Typhoid vaccine 50-80% effective


Oral live attenuated virus

Every other day for 4 doses


Must be refrigerated
Completed one week before exposure
Headache and fever occur rarely
Boost after 5 years
$30-40

IM: capsular polysaccharide

Single dose
Complete 2 weeks prior to exposure
Local erythema and indration rarely
Boost at 2 years
$30-40

My patient
Leaves in 2 days, but stays for a month
Refrigeration
$$$ and convenience

The shared decision


Oral Typhoid vaccine called to a San
Francisco pharmacy
A nice stewardess
Cold pack

Rabies
Dont pet the dogs
Time is on our side

Japanese Encephalitis

Malaria Prevention

Malaria
Fever, headache, back pain, myalgias
1500 cases per year reported to CDC

Can be fatal

Accounts for 21% of fever in returned travelers


Conveyed by Anopheles mosquito

Feeds from dusk until dawn

No risk in urban areas outside of sub-Saharan


Africa and India business travel
Risk varies significantly from locale to locale

Relative Risk of Malaria among Travelers, 2000 through 2002

Freedman D. N Engl J Med 2008;359:603-612

Source of Cases over 10 Years


Sub-Saharan Africa
Asia
Caribbean, Central and
South America
Oceana

60%
14%
13%
.03%

Visiting Friends and Relatives (VFR


Travelers)
Born in endemic regions and moved away and
subsequent generations
At greatest risk for Malaria

More than 50% of cases

Explanation for risk

High risk conditions living with family


Dont use chemoprophylaxis
Misperceptions about immunity
Peer pressure
Cost

Prevention
Avoidance
Chemoprophylaxis

Avoidance
Limit night time outings
Clothing: long sleeves and pants
Screened or air conditioned rooms
Mosquito netting
Permethrin coated clothes
30% DEET effective for 4-8 hours

NEJM-2002 Comparative Study of


Insect Repellents

15 Volunteers inserted their arms


into a cage with 10 hungry
mosquitoes
Pretested with untreated arm
Tested 16 different products
Time to first bite recorded

Results
DEET superior to all other products
Higher concentrations provided longer
protection
24% solution protected for 300 min
Controlled release formulation was no better

Skin-So-Soft worked for 23 min


Citronella worked for 20 min

Medical Letter - 2005

CONCLUSION The 7% picaridin


formulation currently sold in the US might
be as effective in repelling mosquitoes as
low concentrations of DEET, but no data are
available. Higher strength products sold in
Europe (with 20% picaridin) protect
against mosquitoes for up to 8 hours and
against ticks for a shorter period of time. If
higher concentrations become available in
the US, picaridin could replace DEET due to
its superior tolerability, but its long-term
safety is less well established

20% Picaridin
Now available in US
As effective as Deet
No odor
Not a solvent

Chemoprophylaxis

Chloroquine: first choice for Mexico, much of Central


America and Caribbean
Malarone (atovaquone-proguanil)

Best tolerated
Daily dosing and continued for 1 week after return
Expensive - $300 for 30 day trip

Doxycycline 100mg qd

Cheap and effective


Solar sensitizer and gastrointestinal side effects
Must be continued for 1 month after return

Mefloquine

Associated with psychiatric side effects

Primaquine

G6PD testing required

Our patient
Considers cost and risk of solar
sensitization
Doxycycline and sunscreen

How did we do?

Jacks Second Call


Dad, Robby has had diarrhea for a
week, going over 10 times per day
and getting up at night. The cipro
has not helped at all. He also has
fevers and chills. He wonders
whether he needs to come home and
see a doctor. He is not having blood
in his stool and he is not vomiting. He
is still surfing, but it has been hard.

Resistant TD
Reported first in Thailand, but now
spreading throughout SE Asia
Among military personnel in Thailand
Camphylobacter causes 20-60% of TD
85% are resistant to fluoroquinolone

RCT: Azithromycin vs Levofloxacin

156 military personnel with TD enrolled and


randomized (85% using doxycycline for
malaria prophylaxis)

Azithromicin 1gm once


Azithromicin 500mg bid x 3 days
Levofoxacin 500mg qd x 3 days

Pathogens

Bacterial pathogens identified in 81%


Camphylobacter 64%
50% levoquin resistant
93% ciprofloxacin resistant
Salmonella 17%
E coli 10%

Outcomes
72 hour cure rate

Azithromycin 1gm
Azithromycin 500mg bid
Levofloxacin 500mg qd

94%
80%
70%

TLUS

Azithromycin 1gm
Azithromycin 500mg bid
Levofloxacin 500mg qd

39hr
43hr
56hr

Illness longest in patients with resistant


organisms treated with levofloxacin 76hr

Side effects
Nausea after first dose

Azithromycin 1gm

14%

One patient vomited

Azithromycin 500mg bid


Levofloxacin 500mg qd

6%
2%

Nausea for 3 days


Azithromycin 1gm
Azithromycin 500mg
Levofloxacin 500mg qd

17%
8%
6%

Treatment recommendation for


Thailand and other parts of SE Asia
Azithromycin 1gm qd
With a large single dose 46% of active drug
remains in the gut yielding high luminal
levels
Also effective for conventional TD in other
parts of the world

Footnote: Rifaximin is ineffective against


campylobacter

Telephone medicine to Indonesia


Try to find some azithromycin

20-30% of drugs may be counterfeit

Clear fluids
Sodas and broth
Oral rehydration solution

Happy Campers

The Second Complication Occurred


Several Weeks Later

Doxycycline photosensitivity
Painful erythematous eruption
Mechanism poorly understood
Prevented by sunscreen

Altitude Sickness

At 10,000 ft (3,000 m), the inspired PO2 is only 69% of


sea-level value.
Degree of hypoxic stress depends upon altitude, rate of
ascent, and duration of exposure.
Process of acute acclimatization to high altitude takes 35
days; Rec: acclimatizing for a few days at 8,0009,000 ft
before proceeding to higher altitude.
Inadequate acclimatization may lead to altitude illness in
any traveler going to 8,000 ft (2,500 m) or higher.
It is best to average no more than 1,000 ft (300 m) ft per
day in altitude gain above 12,000 ft (3,660 m).

Clinical Presentations

Acute mountain sickness (AMS)

25% of people at alt>8,000 ft. Feels like hangover (HA, nausea). Develops
2-12 hrs after arrival, resolves after 24-72 hrs of acclimatization

High-altitude cerebral edema


(HACE)

Severe progression of AMS (rare), usually involves pulm edema. Sx


include: lethargy, ataxia, confusion. Life threatening: must descend
immmediately, death w/in 24 hrs of sx.

High-altitude pulmonary edema


(HAPE)

May occur in conjunction with AMS or HACE or alone. Incidence is


1/10,000 skiers in Colorado and up to 1 of 100 climbers at >14,000 ft.
Dyspnea with exertion progresses to SOB at rest. Supplemental O2 or
decent > 1,000 m is lifesaving. May be more rapidly fatal than HACE.

Tips for reducing risk

Ascend gradually, if possible. Try not to go directly from low


altitude to >9,000 ft (2,750 m) sleeping altitude in one
day.
Consider using acetazolamide (Diamox) to speed
acclimatization if abrupt ascent is unavoidable.

Avoid alcohol for the first 48 hours.

Participate in only mild exercise for the first 48 hours.

Having a high-altitude exposure at >9,000 ft (2,750 m), for


2 nights or more within 30 days prior to the trip is useful.
Treat an altitude headache with simple analgesics

Treatments

Acetozolomide: Acidifies blood=>


Incr RR

Dose: 125 mg po bid starting one day prior to ascent and continued for 2

days after Usually well tolerated. Sulfa derivative, so test dose


recommended for people w/ hx of anaphylaxis to sulfa.

Dexamethesone:

Very effective in prevention and Tx of HACE, AMS and possibly HAPE


Acetozolamide is recommended for prevention of AMS, Dex for treatment
Dose: 4 mg po Q 6hrs

*HAPE is always associated with pulmonary HTN:


Nifedipine may ameliorate/prevent at a dose of 20 mg ER Q 12 hr

Take Home Points

Know the early symptoms of altitude illness and be willing


to acknowledge when they are present.
Never ascend to sleep at a higher altitude when
experiencing symptoms of altitude illness, no matter how
minor they seem.
Descend if the symptoms become worse while resting at
the same altitude.
Gradual accent is the key! If ascent must be rapid,
acetazolamide may be used prophylactically, and dexamethasone
and pulmonary artery pressure-lowering drugs, such as nifedipine
or sildenafil, may be carried for emergencies