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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

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a travel medicine case

A Travel Medicine Case

Thomas Miller MD

case 1
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
Topics of Discussion
  • The travel consultation
  • Travelers’ diarrhea
  • Immunizations
  • Malaria prophylaxis
  • Complications
the travel consultation
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

Risk assessment
slide9
Medical history
    • Healthy 24 year old
    • Complete childhood immunizations
    • Hepatitis A and B vaccines given in school
    • Before college
      • Meningococcus
      • Updated MMR
destination indonesia bali and mentawai islands
Destination: IndonesiaBali and Mentawai Islands
  • CDC Traveler’s Health
    • Immunizations
      • Routine
      • Hepatitis A
      • Hepatitis B
      • Typhoid
      • Rabies
      • Japanese encephalitis
    • Malaria prevention
      • Other than chloroquine
    • Medicine for diarrhea
slide14
Other considerations
    • Style of travel
      • Hostel style
        • Not airconditioned
        • Not usual tourist destination
    • Duration – 1 month
    • Planned activities
travelers diarrhea
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
slide16
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

slide17
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%
slide18
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
slide19
Special Populations
    • VIP’s
    • Vulnerable hosts
      • Immune incompetent
        • HIV, transplant, chemotherapy
      • Inflammatory bowel disease
      • Renal insufficiency
      • Diabetes
slide20
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
slide21
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
slide22
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
slide23
Disadvantages
    • Not effective for invasive disease - dysentery
      • Fever
      • Systemic toxicity
      • Bloody diarrhea
    • Cost – $3.80/pill
a vaccine for td
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
slide25
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
slide26
My patient
    • Standard precautions
    • Not a VIP
    • No chronic diseases
    • Loperamide
    • Ciprofloxacin 500 bid x 3 days max
immunizations
Immunizations
  • Routine
  • Hepatitis A
  • Hepatitis B
  • Typhoid
  • Rabies
  • Japanese encephalitis
typhoid vaccine
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
slide29
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
slide30
My patient
    • Leaves in 2 days, but stays for a month
    • Refrigeration
    • $$$ and convenience
slide31
The shared decision
    • Oral Typhoid vaccine called to a San Francisco pharmacy
    • A nice stewardess
    • Cold pack
slide32
Rabies
    • Don’t pet the dogs
    • Time is on our side
  • Japanese Encephalitis
malaria prevention
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
slide34

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
Source of Cases over 10 Years

Sub-Saharan Africa 60%

Asia 14%

Caribbean, Central and

South America 13%

Oceana .03%

slide36
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
      • Don’t use chemoprophylaxis
        • Misperceptions about immunity
        • Peer pressure
        • Cost
slide37
Prevention
    • Avoidance
    • Chemoprophylaxis
slide38
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
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
slide40
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
slide42
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
slide43
20% Picaridin
    • Now available in US
    • As effective as Deet
    • No odor
    • Not a solvent
slide44
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
slide45
Our patient
    • Considers cost and risk of solar sensitization
    • Doxycycline and sunscreen
jack s second call
Jack’s 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
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
slide50
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%
slide51
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
slide52
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%
slide53
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

slide54
Telephone medicine to Indonesia
    • Try to find some azithromycin
      • 20-30% of drugs may be counterfeit
    • Clear fluids
      • Sodas and broth
      • Oral rehydration solution
slide60
Doxycycline photosensitivity
    • Painful erythematous eruption
    • Mechanism poorly understood
    • Prevented by sunscreen
altitude sickness
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 3–5 days; Rec: acclimatizing for a few days at 8,000–9,000 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
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
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
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
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