A Travel Medicine Case

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A Travel Medicine Case

• Thomas Miller MD

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Case 1

• Jack called from San Francisco at 730 pm.
• Dad I am leaving for Indonesia in 2 days. Do I
  need any shots before I go. What about Malaria
  prevention?

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Topics of Discussion

• The travel consultation
• Travelers diarrhea
• Immunizations
• Malaria prophylaxis
• Complications

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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

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Risk assessment

• Medical history
• Chronic illnesses
• Immune status
• Vaccination history
• Travel itinerary
• Destination
• Style of travel
• Duration
• Planned activities

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

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Mentawai Islands, Sumatra Indonesia
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Destination IndonesiaBali and Mentawai Islands

• CDC Travelers Health
• Immunizations
• Routine
• Hepatitis A
• Hepatitis B
• Typhoid
• Rabies
• Japanese encephalitis
• Malaria prevention
• Other than chloroquine
• Medicine for diarrhea

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• Other considerations
• Style of travel
• Hostel style
• Not airconditioned
• Not usual tourist destination
• Duration 1 month
• Planned activities

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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
• gt2 loose stools over 24 hrs
• Fever, nausea, vomiting, cramping
• Duration 3-5 days

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• 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

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• 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

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• 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

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• Special Populations
• VIPs
• Vulnerable hosts
• Immune incompetent
• HIV, transplant, chemotherapy
• Inflammatory bowel disease
• Renal insufficiency
• Diabetes

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• 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

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• 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

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• 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

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• Disadvantages
• Not effective for invasive disease - dysentery
• Fever
• Systemic toxicity
• Bloody diarrhea
• Cost 3.80/pill

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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

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• 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

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

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Immunizations

• Routine
• Hepatitis A
• Hepatitis B
• Typhoid
• Rabies
• Japanese encephalitis

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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

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• 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

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

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• The shared decision
• Oral Typhoid vaccine called to a San Francisco
  pharmacy
• A nice stewardess
• Cold pack

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• Rabies
• Dont pet the dogs
• Time is on our side
• Japanese Encephalitis

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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

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Relative Risk of Malaria among Travelers, 2000
through 2002
Freedman D. N Engl J Med 2008359603-612
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Source of Cases over 10 Years

• Sub-Saharan Africa 60
• Asia 14
• Caribbean, Central and
• South America 13
• Oceana .03

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• 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

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• Prevention
• Avoidance
• Chemoprophylaxis

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• 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

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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

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• 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

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Medical Letter - 2005
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• 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

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

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• 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

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

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How did we do?
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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.

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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

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• 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

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• Outcomes
• 72 hour cure rate
• Azithromycin 1gm 94
• Azithromycin 500mg bid 80
• Levofloxacin 500mg qd 70
• TLUS
• Azithromycin 1gm 39hr
• Azithromycin 500mg bid 43hr
• Levofloxacin 500mg qd 56hr
• Illness longest in patients with resistant
  organisms treated with levofloxacin 76hr

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• Side effects
• Nausea after first dose
• Azithromycin 1gm 14
• One patient vomited
• Azithromycin 500mg bid 6
• Levofloxacin 500mg qd 2
• Nausea for 3 days
• Azithromycin 1gm 17
• Azithromycin 500mg 8
• Levofloxacin 500mg qd 6

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• 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

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• Telephone medicine to Indonesia
• Try to find some azithromycin
• 20-30 of drugs may be counterfeit
• Clear fluids
• Sodas and broth
• Oral rehydration solution

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Happy Campers
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The Second Complication Occurred Several Weeks
Later
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• Doxycycline photosensitivity
• Painful erythematous eruption
• Mechanism poorly understood
• Prevented by sunscreen

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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).

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Clinical Presentations

• Acute mountain sickness (AMS)
• 25 of people at altgt8,000 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 gt14,000 ft.
  Dyspnea with exertion progresses to SOB at rest.
  Supplemental O2 or decent gt 1,000 m is
  lifesaving. May be more rapidly fatal than HACE.

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Tips for reducing risk

• Ascend gradually, if possible. Try not to go
  directly from low altitude to gt9,000 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 gt9,000 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
  

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Treatments

• Acetozolomide Acidifies bloodgt 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

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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