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Travel Health in the Developing World. Christopher Sanford, MD, MPH, DTM&H Clinical Asst. Professor, Dept. of Family Med. Co-Director, Travel Clinic, Hall Care Center University of Washington Seattle, Washington, USA September, 2009. Amazon River, Peru. Overview of pre-travel encounter:.

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Travel health in the developing world l.jpg

Travel Health in the Developing World

Christopher Sanford, MD, MPH, DTM&H

Clinical Asst. Professor, Dept. of Family Med.

Co-Director, Travel Clinic, Hall Care Center

University of Washington Seattle, Washington, USA

September, 2009

Amazon River,

Peru


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Overview of pre-travel encounter:

  • 1) Intake questions: Itinerary, activities.

    Past medical history incl. immunizations.

  • 2) Advised immunizations.

  • 3) Malaria: PPMs, medication.

  • 4) Travelers’ diarrhea: diet, carry along med.

  • 5) Urban medicine: cars, smog, etc.

  • 6) Resources.


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Intake questions

  • Where to

  • For how long

  • For what purpose

  • Staying in what kind of place

  • Guided or not

  • Previous developing world travel or not


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Intake questions

  • Past medical history—

    • Allergies

      • History of antimalarial use if any

    • Medications

    • Medical problems

      • History of depression, anxiety

    • LMP, birth control

      • None of antimalarials proven safe in pregnancy


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Immunizations

  • Review of past immunizations

  • Advised recommendations:

    • Routine

    • Required

    • Recommended


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Immunizations (cont.)

  • 1. Routine:

    • Td (tetanus + diphtheria)—or Tdap within 10 years

    • MMR

    • Influenza

    • Hepatitis B

    • Polio


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Tdap

  • Give Tdap if it’s been over 10 years since Td.

  • Then in 10 years pt gets usual Td

  • Tdap is a once/life vaccine

  • CDC site: “Adults aged 19-64 years who have not previously received Tdap should receive a single dose of Tdap if their last dose of tetanus toxoid-containing vaccine was administered more than 10 years prior”


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MMR

  • 2 doses, at least 4 weeks apart


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Influenza

  • Important

  • International travelers develop influenza more often than do folks who stay at home.

  • Transmission is year-round at the equator.


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Hepatitis B

  • 3 doses: at time 0, 1, and 6 months.

  • A large proportion of travelers have risks.


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Polio

  • One dose as an adult on top of the usual pediatric series.

  • If going to area with polio:

    • Now in about 25 countries in Africa

    • And the Indian subcontinent: India, Pakistan, Bangladesh


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Immunizations (cont.)

  • 2. Required: a short list.

  • Yellow fever:

    • tropical Africa

    • tropical South America

    • [none in Asia]


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Yellow fever

Distribution

[None in Asia]


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Yellow fever

  • Required for entry into

  • In South America:

    • Bolivia, and French Guiana


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Yellow fever

  • Required for entry into:

  • Africa:

    • Angola, Benin, Burkina Faso, Burundi, Cameroon, Central African Republic, Chad, Congo, Cote de I’voire, Democratic Republic of Congo, Gabon, Ghana, Liberia, Mali, Mauritania (for stay over 2 weeks), Niger, Rwanda, Sao Tome and Principe, Sierra Leone, and Togo.

  • Not required for return to U.S. regardless of previous destination.


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Meningococcal:

  • Required for Hajj (Muslim pilgrimage to Mecca)

  • Recommended for high risk travelers

    • Meningitis belt of sub-Saharan Africa

    • Crowded living conditions, e.g. dorm


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Immunizations (cont.)

  • 3. Recommended

    • Everyone: Hepatitis A

    • Typhoid fever

    • Consider: rabies

    • Consider: Japanese encephalitis

    • Cholera: No.

Rabies avoidance: never hold hands with a gorilla.


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Hepatitis A

  • Appropriate for every nation in the developing world.

  • “The most frequent vaccine-preventable disease in international travelers.”

  • 2 doses, at least 6 months apart.

  • Don’t give Ig to immunocompetent travelers over the age of one year.

  • Lifetime protection.


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Typhoid fever

  • Present throughout developing world.

  • Risk in increased in long-stay travelers, and those off the beaten path.

  • Either oral (good for 5 years).

    • Minimum age 6 years. 4 pills. One pill every other day.

  • Or via injection (good for 2 years).

    • Minimum age 2 years. One dose.


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Rabies

  • Three doses, over 28 days.

  • Expensive.

  • Rabies rare in travelers.

  • Consider for prolonged stay, backpackers, spelunkers, others with significant risk.

  • Pre-exposure series does not remove need for immediate post-exposure treatment.


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Japanese encephalitis

  • Spread by mosquitoes, present throughout South and Southeast Asia.

  • Expensive

  • Rare--rural only. Associated with rice and pig farming.

  • Vaccine: 3 doses over 30 d.

  • Adverse effects: can be delayed. Finish series at least ten days prior to departure.


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Malaria

  • Personal protection measures are more important than medications.

    • DEET to skin (20-35% not 100%)

    • Permethrin to clothes, every 2 weeks.

    • Bednet, preferably impregnated with permethrin

    • Long sleeves/pants

    • Also benefit for diseases other than malaria, (e.g. dengue.)


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DEET

permethrin


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Malaria: medications

  • There are approx. 100 countries with malaria. Chloroquine still effective in only a handful.

    • Mexico, and Central America to west of Panama Canal

    • Island of Hispaniola (Dominican Republic and Haiti)

    • North Africa (prophylaxis not recommended)


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chloroquine-sensitive areas

  • chloroquine or Plaquenil once/week

    • Schedule: start one week before entry, take once/week while in malaria country, take for four weeks after exit.

    • In US, Plaquenil is one-fifth cost of chloroquine

    • Dose

      • chloroquine: 300 mg base = 500 mg salt once/week

      • Plaquenil: 310 mg base = 400 mg salt once/week


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Chloroquine-resistant countries

  • 3 options:

  • doxycycline

  • mefloquine (Larium)

  • atovaquone/proguanil (Malarone)


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doxycycline

Dose: 100 mg once/day.

Start one day prior to entry to malaria area, take once/day while, continue for 28 days after leaving malaria area.

Cheap. Approx. 16 cents/pill.

Side effects:

photosensitivity. Less than one percent.

esophageal erosion. Don’t swallow tablet “dry”


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Mefloquine (Larium)

  • 250 mg (salt) once/week. Start one week prior to entry into malaria area, continue once/week while there, continue once/week for four weeks after leaving malaria area.

  • Price: intermediate.

  • Contraindications: people with any type of psychiatric history ever (e.g., depression, anxiety) should not take this.


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Mefloquine (Larium) (cont.)

  • Side effects (cont.)

    • No one should take this who:

      • Has had cardiac conduction defects

      • Seizures (aside from uncomplicated febrile seizures in childhood)

      • Doesn’t want to take it.


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Malarone (atovaquone and proguanil)

  • Expensive.

  • Once/day: begin one day prior to entry into malaria area; take one/day while there, continue once/day for 7 days after exiting malaria area.

  • Only one adult strength: Each tablet: 250 mg atovaquone + 100 mg proguanil

  • Side effects: lowest rate of the 3 drugs for chloroquine-resistant malaria.

  • Rash, GI upset, mood changes.


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What about carry-along standby self-treatment, instead of prophylaxis?

My vote: no.

You can’t diagnosis malaria clinically. Diagnosis is only possible via laboratory exam (thick and thin smears of blood).

Card diagnostic test is not yet ready for prime time.

May be an option in the future.


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An exception prophylaxis?

  • Consider carry along/standby medication for geographically remote traveler.

  • E.g. Malarone if not taking it for prophylaxis.


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Travelers’ diarrhea prophylaxis?

  • A self-limited illness in most international travelers.

  • Duration can be shortened by antibiotics.

  • Very common. Up to 50% over 2-4 weeks.


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Sign with unknown prophylaxis?

significance, Korea


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Synonyms prophylaxis?

  • Aztec two-step

  • Delhi belly

  • Hong Kong dog

  • Montezuma’s revenge

  • Rangoon runs

  • Turista

  • etc., etc., etc. (DuPont & Steffen [see bibliography] lists 32 synonyms)


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Cause of travelers’ diarrhea prophylaxis?

  • Usually bacterial, usually ETEC (enterotoxigenic E. coli). Relatively recently described EAEC (entero-adherent E. coli) also common

  • More rare causes:

    • Other bacteria: Shigella, Salmonella, Campylobacter

    • Protozoan: Giardia

    • viral


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Dietary strategy to reduce risk of travelers’ diarrhea prophylaxis?

  • Not much evidence that eating practices reduce risk.

  • The (relatively) safe list:→ Dry foods, such as bread.

  • → Packaged foods.

  • → Well-cooked food.

  • → Bottled anything—water, beer, pop (if sealed).

  • → Boiled anything.


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Steffen R, Tornieporth N, Costa Clemens SA, et al. Epidemiology of travelers' diarrhoea: details of a global survey. J Travel Med 2004;11(4):231-238.

  • “This study adds to a growing literature that conventional advice on avoidance of specific food and drink items seems to be ineffective in reducing risk.”

  • “Where one eats may be more important than what one eats.”

  • survey on TD [travelers’ diarrhea] among tourists to Goa (India), Mombasa (Kenya), Montego Bay (Jamaica), and Fortaleza (Brazil).

  • 73,630 travelers (15,631 from Goa, 15,180 from Mombasa, 30,369 from Montego Bay, and 12,449 from Fortaleza)


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  • “there were no differences in [prohibited] food scores between those who did and did not have TD [travelers’ diarrhea]”

  • “Cumulatively, a number of other studies over the past 20 years that were reviewed in a plenary lecture at the ISTM Conference in New York in 2003 have shown similar results.”


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The bad list: things to avoid: between those who did and did not have TD [travelers’ diarrhea]”

  • →Food from street stands (street vendors).

  • →Salads. →Raw food, such as sushi.→Buffets, even at nice hotels or restaurants, in which food sits out for several hours.

  • →Tap water.

  • →Ice. Freezing doesn’t kill most of the germs that can give you the trots.


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Two strategies I don’t recommend: between those who did and did not have TD [travelers’ diarrhea]”

  • Prophylactic antibiotics

    • These can have side effects in

      and of themselves

  • Pepto-Bismol

    • It works: you chew 2 tablets,

      four times/day, for the whole trip.

    • Benefit: 50-65% reduction in travelers’ diarrhea

    • Drawbacks: black tongue, weird black poop


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Stand-by medication between those who did and did not have TD [travelers’ diarrhea]”

  • Taken only if symptoms develop

  • For most of the world: a fluoroquinolone (e.g., ciprofloxacin, levofloxacin)

  • For Southeast Asia*: azithromycin, one dose only.

  • Duration without treatment: 3-5 days.

  • Duration with treatment: 12-24 hours.

    • *Brunei, Burma (Myanmar), Cambodia, East Timor, Indonesia, Laos, Malaysia, Philippines, Singapore, Thailand, Vietnam


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Travelers’ diarrhea caveats: between those who did and did not have TD [travelers’ diarrhea]”

  • Take self-treatment medication only for “normal” diarrhea

    • If blood in stool,

    • Or fever,

    • Or significant abdominal pain,

    • Or if not better 2 days after starting antibiotics—

      See a doc!


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2 between those who did and did not have TD [travelers’ diarrhea]”nd self-treatment drug

  • An antimotility drug: e.g. loperamide (Imodium AD)

  • 2 at onset of symptoms, then 1 after each loose BM not to exceed six/day.


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TD carry-along med algorithm between those who did and did not have TD [travelers’ diarrhea]”

  • Pt feels good Takes nothing

  • Mild diarrhea Imodium-AD only

  • Watery diarrhea Imodium-AD + Cipro

  • Sick See doc

    • Blood in stool

    • Fever

    • Significant abd. pain


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Special oral rehydration solution between those who did and did not have TD [travelers’ diarrhea]”

-Only needed at extremes of age.

-No need to “rest”

the gut during

recovery.


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Should you carry more than one medication for travelers’ diarrhea?

  • Cipro for ETEC

  • azithromycin for Campylobacter

  • metronidazole (Flagyl) for Giardia

  • ??

  • No. These can’t be distinguished without laboratory exam.


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Urban medicine I refer you to Ericsson, DuPont, and Steffen’s 315-page

  • Road traffic accidents

  • Air pollution

  • Heat illness

  • Recreational pharmacology

  • Psychological

    illness


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What do U.S. travelers die from in the developing world? I refer you to Ericsson, DuPont, and Steffen’s 315-page

  • About half: heart attacks, strokes (mostly in the elderly).

  • About 25%: road traffic accidents.

  • The rest: drowning, falls from heights, homicide, suicide.

  • Infectious disease: only about 1%.


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Road traffic accidents I refer you to Ericsson, DuPont, and Steffen’s 315-page

  • The rate of fatalities per 100 million miles driven in the US is 1.1; this is similar to Western European rates.

  • The rates in Sri Lanka and Turkey are 23 and 44, respectively.


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  • So does Ghana have the worst roads in the world? I refer you to Ericsson, DuPont, and Steffen’s 315-page

  • No! Ghana has a stable government. In states failed or otherwise harboring complex humanitarian emergencies, deaths/mile traveled are probably much higher.


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Tippling and driving I refer you to Ericsson, DuPont, and Steffen’s 315-page

  • The percentage of drivers with blood alcohol levels higher than 80 mg/dl, indicating impairment, has been found to be 0.4% in Denmark, 3.4% in France—and 21% in Accra, the capital of Ghana. And alarmingly, 4% of bus drivers and 8% of truck drivers in Ghana were found to have blood alcohol levels above this level.

    • Mock CM et al: J Crash Prevent Injury Control 2001; 2(3)pp. 193-202.


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Air pollution even if you’re told the view is wonderful.

  • Mexico City was the worst city in the world in 1992. Now it’s not on the top ten list.

  • Nine of worst ten cities are in China.


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Mexico City even if you’re told the view is wonderful.

Total suspended particulates

(in mcg/cubic meter)

  • Stockholm 9

  • Mexico City 279

  • Lanzhou, China 732

Lanzhou,

China


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Guiyang, China even if you’re told the view is wonderful.

Sulfur dioxide is formed by the burning of fossil fuels, such as oil and gas.

Sulfur dioxide

(in mcg/cubic meter)

  • Los Angeles, California: 9

  • Guiyang, China: 424


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What does this bad air mean to the young, fit, short-term traveler?

  • Usually not much other than irritated eyes and a sore chest.


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Who can get into trouble with heavily polluted air? traveler?

  • Those with pre-existing conditions:

    • Asthma

    • Chronic bronchitis, emphysema

    • Coronary artery disease


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Sex traveler?

No glove, no love


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security traveler?

  • Wallet not in pants pocket, but around neck or waist in a money belt.

  • Have hotel call for taxi

  • Hotel safety boxes are usually safe.

  • Don’t take anything (camera, jewelry) that you would be significantly bummed if you lost


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Security: leave the laptop at home. traveler?

  • Laptop

  • Expensive

  • Needs electricity

  • Needs adaptor plug for most of developing world

  • Can be damaged by humidity or rough handling

  • Useless in bright sunlight

  • High potential for rip-off

  • Clipboard or spiral-bound notebook

  • Cheap

  • No need for electricity

  • No adaptor plug required

  • Relatively indestructible

  • Not hampered by bright sunlight

  • Near-zero potential for rip-off


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photography traveler?

  • If there’s a guy within sight who is carrying a rifle or machine gun: ask permission before you take photographs.


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Recreational pharmacology traveler?

A full one-third of the 2,500 US citizens who are arrested abroad each year are arrested on drug charges. A number of countries, including the Bahamas, the Dominican Republic, Jamaica, Mexico, and the Philippines, have enacted more stringent drug laws which impose mandatory jail sentences for those convicted of possessing even small amounts of marijuana or cocaine for personal use.


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Recreational pharmacology (cont.) traveler?

  • The death penalty remains an option in several countries, including Malaysia, Pakistan, and Turkey, for those caught smuggling illicit drugs.


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Evacuation insurance traveler?

  • It costs $50-75K to hire a medical jet to evac someone to developed world.

  • Consider evac insurance

    • Medex

    • International SOS

    • DAN (Divers’ Alert Network)


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Resources traveler?

  • cdc.gov

    • Entire “Yellow Book” (Health Information for International Travelers) on line

  • state.gov

    • Crime, terrorism

  • Email of travel clinic


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Post-travel medicine: Chronic travelers’ diarrhea traveler?

  • TD is usually an acute, self-limiting illness; resolves within about 5 days.

  • 3-10% of pts with TD will have symptoms lasting longer than 2 weeks.

  • Up to 3% of travelers have TD lasting over 30 days.


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Work-up of diarrhea in the returned international traveler. traveler?

  • Diarrhea is by far the most common complaint in the returned international traveler.


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TD lab work-up: Step 1 (a.k.a. “the routine”) traveler?

  • A. Stool O&P (ova and parasite) x 3.

    • Not more than one stool sample/day.

  • B. Stool C&S x 1

  • C. Stool Giardia antigen

  • D. Stool C. difficile if history of antibiotic or antimalarial use

  • E. serum wbc with differential

  • F. UA


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Giardia traveler? diagnosis

  • Stool O&P x 3

  • Stool antigen (IFA or ELISA). These tests have a sensitivity of 85-98% and a specificity of 90-100%.

  • Not blood work.

    • ELISA assays for serum antibodies against Giardia are not readily available.

    • Because immunoglobulin G (IgG) levels remain elevated for long periods, they are not beneficial in making the diagnosis of acute giardiasis. Serum anti-Giardia immunoglobulin M (IgM) can be beneficial in distinguishing between acute infections and past infections.

  • Pennardt, Andre: Giardiasis. eMedicine, Last Updated: Feb 4, 2008

    http://www.emedicine.com/EMERG/topic215.htm


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What to do when your lab identifies some protozoan you haven’t heard mentioned since medical school--

  • non-pathogenic:

  • Endolimax nana

  • Entamoeba coli

  • Entamoeba hartmani

  • Entamoeba dispar (looks identical

    to E. histolytica)

  • Iodoamoeba beutschlii

  • Chilomastix mesnili

  • controversial:

  • Blastocystis hominis (common)

  • Dientamoeba fragilis

  • Entamoeba polecki

B.

hominis


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TD lab work-up: Step 2 haven’t heard mentioned since medical school--

  • A. Lactose intolerance test

  • B. d-xylose test

    • If considering celiac disease = sprue, add IgA antibodies: antiendomysial, and antigliadin.

  • C. thyroid function tests

  • D. electrolytes, calcium

  • E. Stool Cryptosporidium, Cyclospora

  • F. Consider: save a tube. (For acute-phase serum.)


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2A) Lactose intolerance test haven’t heard mentioned since medical school--

  • Lactose intolerance is caused by deficiency of the enzyme lactase, which is produced by cells lining the small intestine.

  • Three tests to evaluate this:

    • breath hydrogen test after oral lactose bolus

    • serum glucose after oral lactose bolus

    • stool acidity test (used less often)


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sprue haven’t heard mentioned since medical school--

  • A non-specific term for chronic malabsorption

  • Two types of sprue:

    • sprue = celiac sprue = celiac disease =gluten-sensitive enteropathy

    • Tropical sprue


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2B) D-xylose test haven’t heard mentioned since medical school--

  • Lower than normal range in

    • celiac disease (a.k.a. sprue, a.k.a. celiac sprue, a.k.a. gluten-sensitive enteropathy)


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2B) D-xylose test (cont.) haven’t heard mentioned since medical school--

  • Urine or blood is checked after oral bolus of D-xylose. In sprue, absorption of D-xylose is decreased.

  • Checking both one-hour and three-hour serum levels post oral bolus improves sensitivity (vs. checking one-hour post bolus level only.)

    • Ehrenpreis ED, Salvino M, Craig RM: Improving the serum D-xylose test for identification of patients with small intestinal malabsorption. J Clin Gastroenterol. 2001 Jul:33(1) :36-40.


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2B) D-xylose test (cont.) haven’t heard mentioned since medical school--

  • Non-specific. Lower than normal value in:

    • Giardia intestinalis, Crohn’s disease, hookworm, lymphatic obstruction, radiation enteropathy, small intestinal bacterial overgrowth, viral gastroenteritis, Whipple’s disease.


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2B) D-xylose/celiac disease (cont.) haven’t heard mentioned since medical school--

  • IgA antibodies: antiendomysial, and antigliadin--more specific for celiac disease (sprue) than D-xylose.

  • Best diagnostic test for celiac disease: small bowel biopsy. Improved symptoms and biopsy after gluten-free diet strongly correlated to celiac disease.


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In long-term ex-pats with GI sx, consider tropical sprue. haven’t heard mentioned since medical school--

  • Tropical sprue: a poorly characterized syndrome of worsening intestinal symptoms with continuing diarrhea and steatorrhea; occurs in ex-pats living long-term (over one year) and residents of tropical and sub-tropical areas. particularly Caribbean, southern India, and SE Asia. (From 30 N. of equator to 30  South.) Rare in short-term travelers.

  • Etiology: unknown


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Tropical sprue: etiology haven’t heard mentioned since medical school--

  • ?? Combination of poor nutrition + infection.

  • Tropical sprue appears to be limited to certain geographic areas, even within the tropics. For example, although it is commonly observed and described in Puerto Rico and the Dominican Republic, it is not reported in Jamaica.


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Tropical sprue (cont.) haven’t heard mentioned since medical school--

  • Sx: light-colored stools, weight loss, chronic diarrhea.

  • Iron, B12 and folic acid deficiency  anemia.

  • Prothrombin deficiencyeasy bruising, prolonged bleeding.

  • Small intestine biopsy: flattened villi.


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Tropical sprue (cont.) haven’t heard mentioned since medical school--

  • Treatment: most patients improve with tetracycline x several months + vitamin B12 and folic acid.

  • Treatment usually results in full recovery.


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Recap: sprue vs. tropical sprue haven’t heard mentioned since medical school--

  • Sprue = celiac disease = celiac sprue = gluten-sensitive enteropathy. Improves with gluten-free diet.

  • Tropical sprue. Unknown cause. Occurs almost exclusively in long-term ex-pats. Improves with antibiotics (TCN) and vitamin supplementation.


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TD lab work-up: step 3 haven’t heard mentioned since medical school--

  • (Consider involving gastroenterologist).

  • Stool hemocults

  • HIV

  • serum gastrin

  • fecal fat


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TD lab work-up: Step 4 haven’t heard mentioned since medical school--

  • (Consider involving gastroenterologist).

  • Endoscopy

    • EGD with duodenal aspirate

    • small bowel biopsy

      • light

      • EM

  • Flex. sig. with biopsy

  • Colonoscopy with biopsy


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Post-infectious malabsorption haven’t heard mentioned since medical school--

  • A.k.a. post-infectious dysmotility syndrome, post-infectious irritable bowel syndrome.

  • A common sequelae of TD.

  • A diagnosis of exclusion.

  • Usually self-limiting.

  • Can evolve into permanent irritable bowel syndrome.


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What to do with that positive haven’t heard mentioned since medical school--Blastocystis identification on stool O&P?

  • If patient is asymptomatic or rapidly improving--nothing.

  • If GI sx are ongoing, and no other pathogen is found--consider treating (with metronidazole). A subset of symptomatic patients will improve.


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Treatment of Giardiasis. haven’t heard mentioned since medical school--

  • Increasing resistance to metronidazole.

  • Consider using tinidazole: 2 g once. You no longer need to go through a compounding pharmacy for this.


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Caveat regarding TD haven’t heard mentioned since medical school--

  • Not all diarrhea that begins during or immediately after international travel is related to that travel.

  • No positive lab findings  “You’re fine.”


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bibliography haven’t heard mentioned since medical school--

  • DuPont HL, Steffen R (eds.): Textbook of Travel Medicine and Health, 2nd Ed. B.C. Decker, 2001.

  • Ericsson, DuPont, and Steffen:Travelers’ Diarrhea. BC Decker, Hamilton, 2003.

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