Illnesses After International Travel
High Altitude Sickness
Update on Diamox for Acute Mountain Sickness
Sunscreens & DEET
Jet Lag 2003
Use of DEET on Children
How to Prepare for Health Care Abroad
Ciprofloxacin Recommended for Travelers' Diarrhea in Children
HIV Increases in Eastern Europe
Counterfeit Anti-Malarial Pills in SE Asia
DEET-Containing Insect Repellents/Toxicity Issues
Acetazolamide and Sulfa Allergy/Dexamethasone for AMS
Malaria in Marines in Liberia
Cipro XR for Travelers' Diarrhea

Of the annual 50 million who travel from the industrialized world to the developing world, 20-70% reports some illness associate with their travel. 1-5% becomes ill enough to seek medical attention. Those staying in local homes (such as with family or friends) are most susceptible to illness as they may have more intense exposure to pathogens and are more likely to forego vaccinations and chemoprophylaxis.

FEVER

Malaria

• The most important cause of fever among persons who have recently traveled
• Malaria caused by Plasmodium falciparum can be rapidly fatal and must be immediately ruled out in all febrile persons who have recently visited an area where malaria is endemic. Approximately 90% of P. falciparum infections are acquired in sub-Saharan Africa, and 90% of travelers who are infected begin to have symptoms within one month after their return.
• In contrast, more than 70% of cases of malaria due to P. vivax infection are acquired in Asia or Latin America, and only 50% of travelers infected with P. vivax begin to have symptoms within 1 month after their return; in approximately 2%, fever develops > 1 one year afterward.
• Malaria remains an important diagnostic consideration in febrile travelers, regardless of any previous use of antimalarial agents as resistance to antimalarial drugs is widespread and increasing.
• Although a history of fever is typically present, 10-40% of persons with malaria may be afebrile when first examined. Patterns of fever are rarely diagnostic, but fevers occurring at regular intervals of 48-72 hours are virtually pathognomonic of P. vivax, P. ovale, and P. malariae infections.
• If initial blood films are negative for malaria, examination should be repeated at least once within 12-24 hours if malaria is still suspected.
• Thrombocytopenia without leukocytosis is a characteristic feature.
• The clinical course of malaria due to P. falciparum is unpredictable, and nonimmune travelers with this type of malaria should generally be admitted to the hospital to facilitate prompt therapy and to allow monitoring for complications (including hypoglycemia). Antimalarial drugs should be administered parenterally if there is evidence of severe malaria (including renal failure, respiratory distress, altered consciousness, seizures, shock, or severe anemia) or if the level of P. falciparum in the blood exceeds 4% of visible erythrocytes in a nonimmune patient.

Dengue

• Mode of transmission, like malaria, is the bite of an infective mosquito. 4-7 day incubation period.
• Has become a major infectious-disease threat in tropical and subtropical areas worldwide, including recent outbreaks in Puerto Rico, and Hawaii.
• After an incubation period of 4-7 days, dengue manifests as an influenza-like illness with fever, headache, and myalgia. In approximately 50%, lymphadenopathy and diffuse erythema or a nonspecific maculopapular or petechial rash develops. Leukopenia and thrombocytopenia are characteristic findings.
• The most serious forms of infection, dengue shock syndrome and dengue hemorrhagic fever, are rare among travelers, occurring primarily in persons previously infected with a different dengue viral serotype.

Rickettsia

• The triad of fever, headache, and myalgia in a person who has recently traveled should also prompt consideration of rickettsial (typhus) infections. Incubation period is about 1 week.
• These infections are transmitted by arthropods, and the detection of a painless eschar at the inoculation site is an important diagnostic clue.
• Persons who have been camping, hiking, or traveling on safari in grassy or scrubby areas are at highest risk for infection.
• Lymphadenopathy, rash, leukopenia, and thrombocytopenia may be present.
• The diagnosis of a rickettsial infection is generally made clinically, prompting treatment (usually with tetracycline) while serologic confirmation is pending.

Leptospirosis

• Acute leptospirosis may also manifest as fever, myalgia, headache, and rash. Incubation period: 7-12 days.
• Conjunctival suffusion (without discharge) is a characteristic diagnostic sign but may occur in only 28-44% of cases.
• A history of exposure to fresh water (rafting or kayaking or wading through flooded streets) in a person with symptoms suggests this diagnosis (exposure to contaminated water or soil is a common mode of transmission).
• The illness may be biphasic and associated with aseptic meningitis, uveitis, elevated liver-function tests, proteinuria, and microscopic hematuria. Penicillin and tetracycline antibiotics are effective.

Typhoid Fever

Typhoid fever may present with fever and headache in a person with otherwise unremarkable findings on physical examination. The majority of cases of typhoid fever in the U.S. are in travelers who have visited family or friends on the Indian subcontinent, in the Philippines, or in Latin America. Incubation period: 7-18 days.
Most affected persons report abdominal discomfort, constipation, or more rarely, diarrhea. Leukopenia, thrombocytopenia, dry cough, and lymphadenopathy may be present. In contrast to dengue and rickettsial infections, typhoid fever may have an insidious onset. The diagnosis is usually made by isolating the causal agent, Salmonella enterica serotype typhi, from blood. If typhoid fever is suspected, empirical therapy with a fluoroquinolone or a 3rd generation cephalosporin may be considered. Vaccines against typhoid fever are only partially protective, and breakthrough infections may occur.

Fever Associated With Hemorrhage

Several treatable infections, including meningococcemia, malaria, leptospirosis, and rickettsial infections, can cause fever associated with hemorrhage in travelers.
Viral hemorrhagic fevers (dengue, yellow fever, Lassa fever, Ebola fever, etc.) are rare, but because of their public health implications need to be considered in travelers who present with fever and hemorrhage. Helpful epidemiological clues include a history of visits to rural areas or recent contact with ill persons in areas where viral hemorrhagic fevers are endemic. Most persons note the onset of fever within 3 weeks after exposure. If a viral hemorrhagic fever is suspected, full protective wear and isolation precautions should be used.

Fever Associated with Involvement of the Central Nervous System

• Special considerations in travelers include malaria, tuberculosis, typhoid fever, rickettsial infections, poliomyelitis, rabies, and viral encephalitides.
• Meningococcal meningitis has been associated with the annual hajj pilgrimage to Mecca, in Saudi Arabia.
• Aseptic meningitis may occur in association with leptospirosis.
• Eosinophilic meningitis should prompt consideration of coccidioidomycosis and angiostrongyliasis; the latter is caused by invasion of the meningeal space by the rat lungworm
• A number of tourists to game parks in northern Tanzania recently acquired trypanosomiasis, which is transmitted through the bite of the tsetse fly. This illness manifests as an erythematous swelling or chancre at the site of the fly bite, fever, headache, and myalgia, before it progresses to encephalitis. During the acute phase of the disease, trypanosomes (microscopic unicellular protozoa) are often detectable on smears of peripheral blood.

Fever Associated with Respiratory Findings

In addition to the usual respiratory pathogens, consider the following in travelers:
•Travelers in spas on cruise ships and in hotels have acquired L. pneumophila infection.
• International travelers are at increased risk for tuberculosis, which may become evident months or years after travel.
• Recent outbreaks of histoplasmosis and coccidioidomycosis among travelers to Mexico have been reported.
• The presence of fever, pneumonia, and hepatitis should prompt consideration of Q fever (which is caused by Coxiella burnetii and is associated with animal exposure)
• Cough, nonspecific pulmonary infiltrates, and peripheral eosinophilia should prompt consideration of Löffler's syndrome, which results from transient migration of larval helminthes (ascaris, hookworm, or strongyloides) through the alveolar spaces.

Fever Associated with Eosinophilia

Peripheral eosinophilia is characteristically associated with helminthic infections in which the worms dwell in or migrate through tissues. Diagnoses to be considered in febrile travelers with eosinophilia include hookworm, ascaris, or strongyloides infection; schistosomiasis; visceral larva migrans (toxocariasis); lymphatic filariasis; and acute trichinosis. The initial workup of travelers with fever and eosinophilia should include examination of a stool specimen for ova and parasites, serologic tests for strongyloidiasis, schistosomiasis, or other helminthic infections, and examination of blood smears or skin snips to detect microfilariae, depending on the geographic areas of travel and the clinical findings.

Diarrhea

• Diarrhea lasting 2 weeks or longer is reported by 5-10% of travelers and in 1-3% it lasts 4 weeks or longer. Causative bacterial or viral agents may be identified in 50-75% of travelers with diarrhea that lasts less than 2 weeks. As the duration of diarrhea increases, the likelihood of identifying a specific infectious cause decreases, although the likelihood of diagnosing a parasitic infection increases.
• Giardia, Cryptosporidium, Entamoeba, and Cyclospora are the most frequently identified parasites, although they are detected in fewer than 1/3 of travelers with chronic diarrhea and in only 1-5% of travelers with acute diarrhea.
• Invasive or inflammatory enteropathy (e.g., dysentery): should be suspected in persons with diarrhea if the stool is bloody, if fever is present, or if leukocytes are detected in the stool; often has a fairly abrupt onset (over a period of hours); may be complicated by metastatic infections, reactive arthropathy, or Campylobacter jejuni–associated Guillain–Barré syndrome.
• Fluoroquinolone-resistant C. jejuni is being recognized with increasing frequency, especially among travelers to Southeast Asia.
• Amebic dysentery, which is caused by E. histolytica, often presents insidiously (over a period of days) and may be complicated by hepatic abscess formation.
• Prolonged traveler’s diarrhea with malabsorption should prompt consideration of protozoal infection of the small bowel (especially infection with G. lamblia) and tropical sprue (pathologically indistinguishable from nontropical sprue – gluten sensitive enteropathy – but does not respond to the removal of gluten from the diet; prolonged tetracycline and folate are effective).
• Diarrhea that begins more than one month after travel is probably not due to exposure during travel.
• Persons with acute, noninflammatory diarrhea may be treated empirically with fluids, an antimicrobial agent such as a fluoroquinolone or a macrolide, and an antimotility agent. Those with an invasive enteropathy (heralded by bloody diarrhea and fever) should also be treated with a fluoroquinolone or a macrolide, but antimotility agents should generally not be used.
• The occurrence of bloody stools without fever or with only low-grade fever should prompt consideration of enterohemorrhagic E. coli infection. Antimicrobial use by persons with enterohemorrhagic E. coli–associated diarrhea appears to be associated with an increased risk of the hemolytic–uremic syndrome.
• The sensitivity of examination of a single stool specimen for the detection of ova and parasites generally exceeds 80%. Indications for microscopic examination of the stool for O&P: evidence of an invasive enteropathy; the diarrhea is persistent or unresponsive to empirical therapy; or if the infected person is immunocompromised.
• In many cases of persistent diarrhea, no known causative agent is identified. In these cases, some experts recommend an empirical course of an antibiotic for suspected bacterial diarrhea or metronidazole for presumed giardiasis, since G. lamblia is the most commonly identified intestinal parasite in travelers.

DERMATOLOGIC CONDITIONS

Papules

• Bites from insects (such as bedbugs and fleas) cause pruritic, papular lesions that generally occur in clusters or in a linear distribution.
• Scabies is common in the developing world, and adventurous backpackers and sexually active travelers are those most commonly infected.
• Seabather's eruption is a pruritic, papular rash that is generally confined to the skin that is covered by a bathing suit. It is caused by larval forms of sea anemones and jellyfish that become trapped under bathingsuit fabric after exposure to salt water.
• Cercarial dermatitis usually involves exposed skin and results from penetration of the skin by schistosomal cercariae in fresh water (in cases of swimmer's itch) or coastal water (in cases of clam digger's itch).

Subcutaneous Swellings and Nodules

• Myiasis is caused by invasion of the skin by the larvae of diptera (flies); lesions resemble boils but have a central opening through which serosanguineous material oozes and through which the larvae may emerge. Patients often report intermittent pain and a sensation of movement in the area of the lesion.
• Tungiasis (also known as jiggers), seen in travelers returning from Latin America, Africa, or India, develops after the female sand flea invades the skin, often around the toenails and soles.
• Infection with Loa loa may become evident years after exposure as eye worm or as migratory areas of angioedema (Calabar swellings); thought to be inflammatory reactions to adult worms.

Ulcers

• Ecthyma (pyoderma) is the most frequent cutaneous ulcer among travelers. The shallow, painful, purulent ulcer of ecthyma often results from skin trauma or bites that have become secondarily infected with pyogenic organisms, commonly Staphylococcus aureus or group A streptococci.
• Though less common, ulcers due to cutaneous leishmaniasis are important to recognize. These painless ulcers typically enlarge slowly, with a granulomatous or crusted base and raised margins. Leishmaniasis is occasionally manifested as isolated lymphadenopathy or as lymphocutaneous changes resembling sporotrichosis.

Linear and Migratory Lesions

• Cutaneous larva migrans is the most frequent serpiginous lesion among travelers. It results from the migration of animal hookworms in superficial tissues. It is usually acquired after direct contact of the skin with soil or sand contaminated with dog or cat feces. The lesions, which may initially be papular or vesicular, are pruritic and are commonly found on the foot or buttock.
• Phytophotodermatitis results from exposure of the skin to psoralen-containing compounds, such as those present in limes. Phytophotodermatitis results when the psoralens are exposed to ultraviolet light, resulting in painless, nonpruritic, hyperpigmented streaks that generally do not expand or migrate after presentation.

High-altitude illness = the cerebral and pulmonary syndromes in unacclimatized persons shortly after ascent to high altitude.

Acute mountain sickness and high-altitude cerebral edema = the cerebral abnormalities
High-altitude pulmonary edema = the pulmonary abnormalities

Epidemiological Process and Risk Factors

Whether high-altitude illness occurs is determined by:
• the rate of ascent
• the altitude reached
• the altitude at which an affected person sleeps (referred to as the sleeping altitude)
• individual physiology

Risk factors include:
• a history of high-altitude illness
• residence at an altitude below 900m
• exertion
• certain preexisting cardiopulmonary conditions

Persons > age 50 are a bit less susceptible to acute mountain sickness than younger persons; however, the incidence in children appears to be the same as that in adults.

Physical fitness is not protective against high-altitude illness.

Common conditions such as HTN, CAD, COPD, DM and pregnancy do not appear to affect the susceptibility to high altitude illness.

Acute Mountain Sickness and High-Altitude Cerebral Edema

Clinical Presentation and Diagnosis

Acute mountain sickness consists of nonspecific symptoms and diagnosis is therefore subjective. One proposal defined it as the presence of headache in an unacclimatized person who has recently arrived at an altitude above 2500m plus the presence of one or more of the following: GI symptoms, insomnia, dizziness, and fatigue. The symptoms typically develop within 6-10 hours after ascent, but sometimes as early as 1 hour. There are no diagnostic physical findings except in the few cases that progress to cerebral edema.

High-altitude cerebral edema is the onset of ataxia, altered consciousness, or both in someone with acute mountain sickness or high-altitude pulmonary edema (HAPE). Clinically and pathophysiologically, high-altitude cerebral edema is the end-stage of acute mountain sickness. In those who also have HAPE, severe hypoxemia can lead to rapid progression from acute mountain sickness to high-altitude cerebral edema. Usually, the illness progresses over a period of hours or days. The cause of death is brain herniation.

Pathophysiology

The exact process of acute mountain sickness is unknown. Hypoxia-induced cerebral vasodilatation most likely produces the headache. The headache itself can cause other symptoms, such as nausea and malaise, and thereby account for mild acute mountain sickness. An alternative hypothesis is that early acute mountain sickness is due to mild cerebral edema.

In addition, new evidence suggests that on ascent to high altitudes, all people have swelling of the brain. In those with moderate-to-severe acute mountain sickness or high-altitude cerebral edema, neuroimaging demonstrates vasogenic edema. Hypoxia-induced biochemical alteration of the blood–brain barrier may also be important.

Treatment and Prevention

Three axioms are prime:
1. Further ascent should be avoided until the symptoms have resolved.
2. Patients with no response to medical treatment should descend to a lower altitude.
3. At the first sign of high-altitude cerebral edema, patients should descend to a lower altitude.

• Descent and supplementary oxygen are the treatments of choice, and for severe illness, the combination provides optimal therapy. Remarkably, a descent of only 500-1000 m usually leads to resolution of acute mountain sickness; high-altitude cerebral edema may require further descent.
• Simulated descent with portable hyperbaric chambers, now commonly used in remote locations, is also effective.
• When descent is not possible or supplementary oxygen is unavailable, medical therapy becomes crucial with acetazolamide or dexamethasone. Multiple studies have demonstrated that dexamethasone (4-6mg Q6H) is as effective as or superior to acetazolamide and works within 12 hours (acetazolamide causes a bicarbonate diuresis resulting in a metabolic acidosis, triggering a compensatory respiratory stimulation; this improves oxygenation, helps resolve cerebral edema and reduces formation of CSF; the mechanism of dexamethasone is unknown but it may reduce brain-blood volume).
• In 2 studies, a single dose of ibuprofen ameliorated or resolved high-altitude headaches.
• For insomnia requiring treatment, acetazolamide, which reduces periodic breathing and improves nocturnal
oxygenation, is the safest agent. Because of the risk of respiratory depression, sedative hypnotic agents should be avoided in those with acute mountain sickness unless they are combined with acetazolamide.
• After acute mountain sickness has resolved, any further ascent should be made with caution, perhaps with acetazolamide prophylaxis.

Prevention: The best strategy is a gradual ascent to promote acclimatization. Recommended guidelines suggest that once above an altitude of 2500m, the altitude at which one sleeps should not be increased by more than 600m in 24 hours and that an extra day should be added for acclimatization for every increase of 600 to 1200m in this altitude.

Most experts recommend prophylaxis for those who plan an ascent from sea level to over 3000m (sleeping altitude) in one day and for those with a history of acute mountain sickness. Acetazolamide is the preferred drug (125-250mg BID). The combination of acetazolamide and dexamethasone may be more effective than either alone. In 2 trials, Ginkgo biloba prevented acute mountain sickness during gradual ascent to 5000m.

High-Altitude Pulmonary Edema

Clinical Presentation and Diagnosis

HAPE accounts for most deaths from high-altitude illness.

As is the case for acute mountain sickness, the incidence of HAPE is related to the rate of ascent, the altitude reached, individual susceptibility, and exertion; cold, which increases pulmonary-artery pressure by means of sympathetic stimulation, is also a risk factor.

HAPE commonly strikes the second night at a new altitude and rarely occurs after more than 4 days at a given altitude, owing to adaptive cellular and biochemical changes in pulmonary vessels.

Early diagnosis is critical. In the proper setting, decreased performance and a dry cough should raise suspicion of HAPE. Only late in the illness does pink or bloody sputum and respiratory distress develop. Resting tachycardia and tachypnea become more pronounced as high-altitude pulmonary edema progresses.

Cerebral signs and symptoms are common: 50% of those with HAPE have acute mountain sickness, and 14% have high altitude cerebral edema.

Fever is common as are rales, which typically originate in the right axilla and become bilateral as the illness progresses. Upper respiratory tract infection or bronchitis may be precipitating factors, especially in children.

Chest radiography typically reveals a normal-sized heart, full pulmonary arteries, and patchy infiltrates, which are generally confined to the right middle and lower lobes in mild cases and are found in both lungs in more severe cases. ABG typically reveal severe hypoxemia and respiratory alkalosis (but not respiratory acidosis).

Pathophysiology

HAPE is a noncardiogenic pulmonary edema associated with pulmonary hypertension and elevated capillary pressure. The usual pulmonary hypertension on ascent to high altitude is excessive in those with high-altitude pulmonary edema, as a result of exaggerated hypoxic pulmonary vasoconstriction.

Susceptibility: Persons with a prior episode of HAPE may have a risk of recurrence as high as 60% if they abruptly ascend to an altitude of 4559 m. These persons are healthy but have a reduced ventilatory response to hypoxia and an exaggerated pulmonary pressor response to hypoxia and exercise.

Treatment and Prevention

Descent, supplemental oxygen, or both are nearly always successful. Breathing supplemental oxygen reduces pulmonary-artery pressure 30-50% which is sufficient to reverse the effects of the illness rapidly.

Death during descent is likely related to the additional exertion involved, which exacerbates HAPE by increasing cardiac output and pulmonary hypertension.

At ski resorts or other such facilities with medical care, mild-to-moderate high-altitude pulmonary edema can be treated with rest and supplemental oxygen for 48 to 72 hours.

Patients with severe HAPE, indicated by the failure of PaO2 to improve to > 90% within 5 minutes after the initiation of high-flow oxygen, and those with concomitant high-altitude cerebral edema must be moved to a lower altitude and possibly hospitalized. If supplemental oxygen is unavailable, then descent, the use of a portable hyperbaric chamber, or both become lifesaving. In clinical studies, nifedipine reduced pulmonary-artery pressure approximately 30% but barely increased the PaO2. Nifedipine is necessary only when supplemental oxygen is unavailable or descent is impossible. Some have suggested use of nifedipine for prophylaxis for HAPE, especially after multiple episodes.

Beta-agonists may have a role in the prevention and treatment of HAPE. Although this requires confirmation, these agents are safe and convenient and should be considered.
Patients who have recurrent HAPE, or HAPE at altitudes below 2500m, may require an evaluation to rule out intracardiac or intrapulmonary shunts, preexisting pulmonary hypertension, mitral valve stenosis, and other conditions that increase pulmonary vascular resistance.

Side Effects

Paresthesias of the fingers and toes, or feet and hands, are ubiquitous with Diamox use. If the patients are warned, it usually doesn't bother them. Paresthesias are most common when circulation has been reduced and then restored to the extremity by sitting cross-legged in a tent, or getting cold and warming back up.

Since Diamox inhibits the breakdown of carbon dioxide, it also adversely affects the taste of carbonated drinks.

Dosage

The current recommended dosage is 125 mg twice daily, which can begin the day of ascent, but might be worth giving the day before. At this lower dosage, paresthesias are significantly less, and diuresis is
Reduced,but the effect on altitude illness appears to be maintained. NOTE: A 125 mg formulation does indeed exist, but not all pharmacies stock it routinely. A dose of 250 mg twice daily is also acceptable if the 125 mg tablet is not available.

According to the University of California, Berkeley Wellness Letter, if you’re using sunscreen and an insect repellent containing DEET, apply extra sunscreen and reapply it often. A concentration of 30% DEET spread on top of a sunscreen with SPF 15 decreases the effectiveness of the screen by about 40%-probably because DEET is a solvent. Combination products, containing DEET and a sunscreen, are available, but the separate products are better because you can keep reapplying sunscreens without having to reapply DEET.

Most travelers have experienced jet lag. The common symptoms—insomnia, fatigue, change in appetite, irritability—are due in part to your body’s cyclical hormone production being temporarily out of synch with your activities. After several days at your destination, your body’s biological clock (circadian rhythm) becomes reset, and the symptoms subside. In general, it takes the body one day to adjust for each time zone crossed.

Like many disorders that have no cure, there are lots of proposed jet lag remedies and preventatives. Numerous travelers have tried jet lag “diets.” More recently, exposure to artificial light sources and melatonin have been touted as being effective in resetting the body’s clock.

NOTE: For short stays of three days or less, adjustment of the body clock is not possible and should not be attempted.

Jet Lag Diets

Despite their apparent popularity, there is no scientific evidence that jet lag diets do any good. Many travelers find these diets too complex and tedious to follow. Any claimed benefits may be purely psychological, due to a placebo effect.

Light Exposure

Light exposure seems to play a role in resetting circadian rhythms. The mechanism involves suppression of the hormone melatonin, which is secreted by the brain’s pineal gland.

The current dogma is that for eastward travel additional morning sunlight (whether cloudy or not) is beneficial, whereas for westward travel, afternoon light is important. Special high intensity lights (>10,000 lux) are available to help accomplish this end. Regardless of travel destination and arrival time, recent studies suggest that exposure to outdoor light at any time of day assists in readjustment of your circadian rhythm.

Melatonin

Ten years of placebo-controlled studies have shown that the hormone melatonin can reset your body’s internal clock. In one study, travelers were given 3 to 5 mg of melatonin at the “destination nighttime” for three days before travel, then for three days after arrival. They experienced much less fatigue, required less time to normalize their sleep patterns, and scored better on a visual analog scale. Some other studies, however, have shown no significant beneficial effect in about 25% of recipients, and up to 10% of travelers taking melatonin have adverse side effects, e.g., headache and excessive drowsiness. In summary, melatonin appears to be somewhat beneficial, but there’s much individual variation in response to this hormone. Although there is little evidence of toxicity, concerns have been raised about melatonin’s safety since the drug’s strength, quality, and purity are not standardized. Also, there are little data on optimal dosing and timing of administration.

Researchers point out that little is known about melatonin’s long-term safety, its effects on reproduction, and its possible dangers to people with autoimmune diseases. Since melatonin is a hormone, it is not recommended for children or during pregnancy. It should also be noted that unidentified chemical impurities have been detected in some melatonin preparations.

Sleeping Pills

Insomnia is one of the most troublesome symptoms of jet lag. While you’re trying to fall asleep, your internal clock is saying “wake up.”

If you need to adapt more rapidly to the new time zone, and you have a problem with insomnia, ask your doctor to prescribe a sleeping pill, but not a barbituate such as secobarbital (Seconal) or amobarbital plus secobarbital (Tuinal). These take too long to act, leave you with a hangover, and are potentially fatal in large doses.

The first of the nonbarbituate, short-acting sleeping pills was Halcion (triazolam), a member of the benzodiazepine family (which includes Valium). Although safe and rapidly effective, there were reports (albeit extremely rare) of next-day memory impairment/amnesia associated with this drug.
For travelers who want an alternative to Halcion and similar (benzodiazepine) hypnotics (e.g., Dalmane, Restoril) newer agents are now available, They include the following:

• Ambien (zolpidem): Dose: 5 to 10 mg for adults
• Sonata (zaleplon): Dose: 10 to 20 mg for adults

Ambien and Sonata are chemically unrelated to the benzodiazepines. Sonata (zaleplon) has many attributes of the ideal hypnotic drug, such as rapid absorption, rapid onset, adequate duration of action, and minimum or no residual effect on daytime performance.

Are sleeping pills safe? Generally yes, especially if they are used for only a short time and in the lowest effective dose. According to the Harvard Medical School Health Letter (May 1990), “Taking sleeping pills for a short period—perhaps a few days—can be quite helpful . . . and there is little controversy about prescribing them to help people through a crisis.”

Jet Lag Formulas

These vitamin–amino acid formulas or homeopathic preparations supposedly help reset your biorhythms, but no scientific studies have been done and they
are most likely ineffective. Jet lag formulas previously contained the amino acid L-tryptophan, which has mild sedative qualities, but the purified substance is now banned. Other amino acids have been substituted but may be less effective.

So What to Do?

Before taking medication or using techniques to prevent jet lag, consider the following:

• Is the treatment safe? Are there side effects?
• Is the treatment effective?
• Is the treatment practical and cost-effective?

What Really Causes Jet Lag Anyway?

Feeling tired and irritable after a long trip is not due entirely to changes in your circadian rhythms. The issue is more complex. Consider the typical scenario:

For several days prior to departure, you are frantically taking care of what seems like a thousand and one last minute errands and details • You are probably too keyed up to get enough sleep • Your normal eating and drinking patterns are disrupted • You are somewhat apprehensive about flying • You are anxious about leaving home and/or your family • You fight heavy traffic getting to the airport • You park your car, but wonder if it will be safe • You carry a heavy suitcase half a mile to check in and hope it won’t get lost • You catch a connecting flight • You stand in line again at check-in • You clear security checkpoints • Then you wait in a crowded, smoky airport lounge because your overseas flight is delayed by hours.
It’s no surprise that you’re feeling stressed out even before takeoff. Add to this a lack of sleep enroute, cramped seating, further dehydration—even constipation. Then, after arrival in a foreign country, you face still more hassles simply getting to your hotel. No wonder you’ve got jet lag.

The HealthGuide takes the following view—Jet lag is not a single entity and the symptom complex will probably never be completely alleviated by a single treatment. The symptoms you experience are usually a combination of travel-related physical and emotional stress, sleep deprivation, plus the biological effect of your circadian rhythm being out of synch.

Enroute Strategies to Reduce Jet Lag

• Don’t drink too much alcohol—If you are a drinker, there’s no reason not to have a cocktail or two, but remember that alcohol is a depressant drug, and larger amounts can cause rebound nervous stimulation and restlessness, interfering with your sleep. Contrary to popular belief, a few drinks won’t dehydrate you.
• Don’t drink too much coffee—Excess caffeine may cause nervousness and insomnia. Caffeine also stimulates gastric acid production, which can lead to heartburn. However, if you habitually drink many cups of coffee each day, missing your “caffeine fix” during your flight may not be a good idea—you might get symptoms of caffeine withdrawal and feel even worse (e.g., severe headache)! Coffee-drinker strategy: Reset your watch to destination time when you board the aircraft. Drink your coffee enroute at the destination time that corresponds to your regular “caffeine fix” time at home.
• Do drink water and fruit juices. They are good substitutes for (or complements to) alcoholic drinks and coffee. You may be somewhat dehydrated at the beginning of the flight due to disrupted eating and drinking habits prior to departure. Also, breathing low-humidity cabin air during a long flight will dry the mucous membranes of your throat and make you thirsty. Water and fruit juices are the best drinks to quench your thirst.
• Sleeping enroute—Avoid, unless it coincides with nighttime at your destination.
After Arrival at Your Destination
• The most important principle is to begin all activities, including eating and sleeping, at destination time as soon as possible. If you have an evening arrival, have a light dinner and go to bed late. The next day try to eat and sleep according to the local time.
• If you have a morning arrival, stay active during the day and get as much exposure to natural light as possible, if your schedule and the weather permit. If possible, don’t nap, but overpowering fatigue should not be resisted. If you do nap, keep it under 45 minutes to avoid Stage IV (REM) sleep, which causes grogginess upon awakening. NOTE: For trips less than 3 days, short naps should be taken when you feel most tired.
• Take a sleeping pill if you have troubling insomnia (see below). Discontinue sleeping medication after three to five nights.

The Myth of Dehydration

For many years it has been touted by the travel media that dry cabin air in jet airliners causes dehydration—which presumably could aggravate jet lag. The recommended remedy has always been to drink extra fluids enroute—and avoid certain beverages, such as caffeinated drinks, that would “dehydrate” you. This advice appears to be misleading. According to a new study from the University of Nebraska Medical Center, healthy adults showed the same “hydration status” (as determined from urine analysis and other tests) when they drank caffeinated beverages, such as coffee or caffeinated colas as when they drank only water and/or fruit drinks. Also, the Medical Director of British Airways Aviation Medical Services has stated (in the medical journal Lancet) that low cabin humidity causes, at most, only a 3 oz. water loss during an 8-hour trip. (In fact, the stress of travel may cause your body to retain water.) Therefore, dehydration from dry cabin air, aggravated by certain beverages, appears to be a myth, and compulsively drinking extra water or other fluids enroute is unnecessary.

Keep the Problem of Jet Lag in Perspective

Enjoying your vacation is more important than fighting jet lag. Don’t waste your time following complex jet lag diets and cures that have not been shown to work. Try not to worry too much about jet lag. Less than one-half of travelers report significant symptoms.

Business travelers—If you are traveling on important business, you probably have more need than others to reduce the symptoms of jet lag. Consider the following strategies: (1) reserve a sleeperette (reclining airline seat) to improve the chances of sleeping enroute, (2) budget, if possible, one or two extra days after arrival to rest and recuperate prior to business activities, or (3) break up a long trip (>6 time zones) along the way for a day or two.

In 1998, the American Environmental Protection Agency removed restrictions on the concentration of DEET used on children. The American Academy of Pediatrics has acknowledged that lower concentrations of DEET are not safer than higher concentrations and that higher concentrations of DEET are more effective in repelling insects than are formulations with lower concentrations. Each organization does stress the importance of appropriate use of DEET with care. Follow directions on the product label: 1) Do not apply the repellent on or near the eyes or mouth; 2) apply the repellent only on exposed skin (not skin covered by clothes); and 3) wash remaining DEET off the skin when leaving an area of risk for insect bites. In Canada, where recent safety concerns have limited DEET concentrations, the use of products containing up to 30% DEET is still accepted and advocated.

Be aware that medical care in many parts of the world, excluding Europe and parts of Asia, is sadly deficient compared to health care in the United States and Canada. Beyond the quality issue, there may also be issues of language and communication, social customs, and reimbursement.

Preparation Tips

Bring enough prescription drugs or medications with you to last during your trip, or arrange to have additional medications sent to you. The drugs or medications you require may not be available abroad, may be sold under different names, or may be below the standard of health care in the United States or Canada.

Seek out facilities that have a reputation of caring for foreigners (e.g., the American Hospital in Paris, which is world-famous). In many cities abroad, new facilities are being started that cater specifically to foreign travelers and business clientele (e.g., European Medical Clinics in Moscow, SOS in Beijing).

Clarify payment issues before receiving medical care. Most facilities abroad will want some type of cash payment or guarantee. A travel health policy will make direct payments to the doctor or hospital for emergency treatment. Otherwise, you may have to make the cash payment yourself and then submit the bills later to your insurer, which may present many administrative problems.

Before you depart, purchase a medical evacuation insurance policy that covers air ambulance transport. The insurer should maintain a 24-hour emergency call center that coordinates your medical care in a foreign hospital and arranges transport to another facility, if needed.

Be aware that foreign doctors have the reputation of being less informative than their U.S. counterparts, which may reflect a cultural background where physicians are viewed as authority figures who should be listened to and respected, not questioned or challenged. This attitude could put you in a difficult bind if you were to have questions about diagnosis and treatment. Decide which issues you will try to influence and which you are going to leave alone.

Have "exit strategies" prepared in advance that allow you to bow out gracefully from the medical care (and for the local providers to save face) if you are dissatisfied.

Because of their effectiveness, fluoroquinolone antibiotics (such as Cipro® and Levaquin®) are often recommended for the treatment of travelers' diarrhea (TD) in adults. Many practitioners, however, believe that these drugs are "prohibited" for use in children and adolescents under age 18. The Physicians Desk Reference (PDR) states that fluoroquinolones "have not been proven safe and effective" in the pediatric age group but never states that they should NOT be used. It's really a question of clinical trials in children not having been submitted to the FDA (it's expensive!), not that there is a safety or efficacy issue. In actuality, quinolones are used extensively "off label" to treat children with cystic fibrosis, with no unusual adverse events being reported. Also, studies in children have shown ciprofloxacin to be very effective in the treatment of shigella, salmonella, and campylobacter (Journal of Travel Medicine May/June 2002). Many if not most travel medicine physicians now recommend ciprofloxacin as the drug of choice for the treatment of moderate to severe TD in all infants and children.

HIV infection is spreading rapidly among young eastern Europeans, according to health authorities in Germany. the proportion of young people infected with HIV is twice as high in eastern Europe as it is in the west, and more than 75% of those infected in eastern Europe are younger than 30 years old. Of particular concern is the rise in HIV-infected women, which has increased from 12% to 25% over the past 10 years.

Risk factors that travelers should be aware of include unprotected sex with an HIV-positive partner and the use of contaminated needles and syringes.

Artesunate is the key anti-malaria drug in the treatment of falciparum malaria in SE Asia, and is widely available in the private sector. Now, the medical journal Lancet reports that almost 40% of store-bought artesunate in Burma, Cambodia, Vietnam, and Laos did not contain the active drug. (For images of some of the counterfeit blisterpacks, go to http://www.shoklo-unit.com/fakeas2.pdf)

U.S. and Canadian travelers to SE Asia who may be concerned about exposure to falciparum malaria are advised to take doxycycline of Malarone for prophylaxis. Malarone (atovaquone/proguanil) is also effective as a stand-by treatment.

In spite of lingering consumer myths about the dangers of the insect reppellen DEET, all scientific studies indicate that it is extraordinarily safe and effective (Fradin, Mark MD< lecture, Am Society of Trop Med & Hyg, November 1999, Washington DC; Ann Int Med 1998; 128:931-940.). DEET has been available since 1957, is used each year by 30% of the U.S. population and by more than 200 million people worldwide. Since introduced, there have been more than 8 billion applications.

DEET has the broadest spectrum of activity of any insect repellents available, and is effective against the widest range of insects. There is no evidence that it is a carcinogen, causes birth defects, affects fertility or causes other health problems. Of the more than 20,000 other compounds that have been tested for their ability to repel or kill insects, none has yet been found that is more effective than DEET. Moreover, a study of all known reports of toxicity from DEET strongly suggests that in virtually all cases the DEET-containing product was used in an inappropriate manner.

The concept that acetazolamide (Diamox) rarely causes allergic reactions is based on more than 20 years of observation by Dr. David Shlim, Director of the CIWEC clinic in Kathmandu. Acetazolamide is a widely used drug, especially among trekkers in Nepal, for the prevention of acute mountain sickness (AMS). Because acetazolamide falls in the sulfa drug category, people who are allergic to sulfa drugs (usually a sulfa antibiotic, such as Bactrim) are thought to be at risk if taking any type of sulfa drug. However, Dr. Shlim says he has never observed or treated an allergic reaction to acetazolamide. He has heard about one reaction that could have been related, but never met the patient.

Given that allergic reactions to sulfonamides are fairly common (around 5% overall in sulfa-drug users), it appears that the allergic reaction rate to acetazolamide is very low. Dr. Shlim believes it is reasonable to give one or two test doses at sea level to see if the patient is allergic, and prescribe the drug if no reaction develops.

Dr. Shlim also questions whether the use of dexamethasone (Decadron) for the prevention of AMS can be called "tried and true." Although studies have shown that it could prevent AMS, the studies failed to suggest a mechanism by which it did so. Studies did show that it failed to improve acclimatization, and anecdotal reports have shown that people have gotten severely ill after stopping dexamethasone while at altitude. Dexamethasone is a potent steroid and can have significant side effects, psychologically and physically, and it should not be equated fair to acetazolamide, which improves acclimatization, and has a widely recognized safety profile.

Recently, malaria was reported in 40 U.S. Marines who had landed in Liberia on a peacekeeping mission. This raised the possibility that the drug the marines were taking to prevent malaria (mefloquine, Lariam) had possibly lost its effectiveness against the type of malaria found in West Africa. Recent data, however, suggest it’s not a question of a mefloquine-resistant strain of malaria (in this case, Plasmodium falciparum) having developed. According to health experts, a variety of reasons exist to explain the outbreak, including non-compliance (i.e., not taking the drug), poor absorption of the drug, and a high exposure to malaria parasites. Another possibility is that a loading dose of mefloquine was not given before exposure. This conclusion may have some relevance to travel to West Africa who have been prescribed mefloquine prophylaxis. It is still effective.

Although several fluoroquinolone antibiotics (Cipro, Levaquin) are recommended for the treatment of travelers’ diarrhea, only Bayer’s Cipro (ciprofloxacin) has FDA approval for infectious diarrhea. Brand-name Cipro from Bayer, however, will soon be available only as Cipro XR (500 mg and 1,000 mg strengths). It is indicated for the treatment of urinary tract infections, but can be used “off label” for travelers’ diarrhea. (Bayer did not seek FDA label approval for treating infectious diarrhea for the new Cipro XR formulation.)
Generic ciprofloxacin will continue to be available in the 500 mg strength.
The new Cipro XR is meant to be given once daily, versus 500 mg twice daily for regular Cipro. The clinical efficacy of the 1,000 mg XR formulation with respect to treating travel-related diarrhea is identical to that of regular Cipro, 500 mg, twice daily.

For the treatment of travelers’ diarrhea, Travel Medicine recommends a 1- to 3-day course of ciprofloxacin, either as Cipro XR, 1,000 mg once daily, or generic ciprofloxacin, 500 mg twice daily. Travelers can also treat diarrhea with Levaquin (levofloxacin), 500 mg once daily. No matter which fluoroquinolone is prescribed, a 1- to 3-day course of antibiotic is usually sufficient.