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TRAVEL MEDICINE PROBLEMS ENCOUNTERED IN EMERGENCY

DEPARTMENTS

Elaine C. Jong, MD, and Russell McMullen, MD

Travelers are likely to seek medical care in the emergency department (ED) before departure on an international trip for evaluation of acute reactions to travel vaccines, and after return from travel for fever, diarrhea, respiratory symptoms, and skin lesions. Returned travelers with symptoms are often anxious because they have been warned about possible fatal consequences of untreated malaria, because they feel ill and weak from diarrhea or respiratory illness acquired during travel and are unable to return to work, or because they have observed individuals with severe advanced stages of exotic tropical diseases during their travels and fear for the worst in them~eJves.'~ This article reviews some of the common illnesses and conditions prompting traveling patients to seek emergency care in the United States.

TRAVEL VACCINE REACTIONS

The receipt of multiple immunizations during the pre-travel time period is not uncommon among persons preparing to depart for foreign travel.*O Multiple vaccine doses may be received by a traveler on a single day to meet scheduling needs. Often, the usual discomfort associated with receipt of each vaccine, plus the standard warnings received during the mandatory informed consent process may prompt the patient to seek emergency care for symptoms occurring in the days to weeks

From the Division of General Jnternal Medicine, Travel and Tropical Medicine Service, University of Washington School of Medicine, Seattle, Washington

EMERGENCY MEDICINE CLINICS OF NORTH AMERICA

VOLUME 15 * NUMBER 1 * FEBRUARY 1997 261

262 JONG & McMULLEN

following immunization. Unexpected and serious reactions can occur after any biological substance has been administered, despite careful review of contraindications to each vaccine based on the traveler’s known allergies to vaccines and other substances, immune status, chronic medical conditions, and current medications.

Anaphylaxis or Serious Hypersensitivity Reactions

There are no specific antidotes for anaphylactic or serious allergic vaccine reactions, so the usual therapy, administration of epinephrine, antihistamines, corticosteroids, or a combination of these in the ED, is used to manage such reactions.

Yellow fever vaccine is a live attenuated virus vaccine prepared from cultures in chicken eggs. Patients without a history of egg allergy are observed for 30 minutes following vaccine administration, and are additionally warned to seek emergency care if they develop swelling, hives, or other acute distress in the hours following receipt of this immunization. The vaccine is contraindicated in persons with a history of anaphylaxis or serious hypersensitivity reaction to eggs and egg products. Desensitization to the yellow fever vaccine can be conducted in the ED according to a protocol described in the package insert.

Allergic reactions occurring within minutes after immunization up to a week following receipt of a dose of Japanese encephalitis vaccine (JEV) have been reported, so patients are usually instructed not depart on their trip for at least 10 days after receipt of a dose of JEV. The serious allergic reactions include generalized urticaria, angioedema, respiratory distress, and anaphylaxis. A possible correlation between allergy to hymenoptera envenomation and JEV hypersensitivity has been postu- lated, and individuals with multiple allergies, especially a history of allergic urticaria or angioedema are thought to be at higher risk for this JEV adverse reaction7

Booster doses of rabies HDCV vaccine are associated with an immune complex-like reaction characterized by urticaria, pruritus, and malaise in up to 6% of persons receiving the booster. If the adverse reactions occur when the rabies HDCV booster doses are being given for continued occupational risk (veterinarians, animal workers, and so forth), the rabies RVA vaccine should be used for the next interval booster. If the rabies HDCV booster doses are being given as postexposure prophylaxis for a high-risk bite or exposure, then the vaccine should not be discontinued because of local or mild systemic reactions?

Gastrointestinal Symptoms

The oral typhoid vaccine, Ty2la vaccine, consists of four capsules, each capsule taken on an empty stomach at 48-hour intervals until the series has been completed. Each vaccine capsule contains 10’ live

TRAVEL MEDICINE PROBLEMS ENCOUNTERED IN EMERGENCY DEPARTMENTS 263

attenuated Salmonella typhi Ty2la strain bacteria, and some patients will experience abdominal discomfort, nausea, and vomiting during the scheduled administration of the vaccine. These symptoms may sometimes be severe enough to require evaluation of the recipient and the administration of fluid and electrolyte therapy in the ED. Fever, headache, and rash occur in less than 5% of vaccine recipientsx

Local Pain and Swelling

Local pain and swelling are common problems following vaccine doses given by subcutaneous or intramuscular injections. They can occur within hours after vaccination and last for 3 to 4 days. The local pain and swelling is due to injection trauma and local inflammation incited by the injected biological. In most cases, local application of ice packs and administration of an oral nonsteroidal anti-inflammatory agent will provide sufficient relief, however, the clinical problem may be pronounced if more than one injection was given in each arm.

Vaccines that are particularly problematic in this regard are tetanus/ diphtheria vaccine, parenteral typhoid vaccine (whole cell inactivated), parenteral cholera vaccine (whole cell inactivated), and plague vaccine. In contrast, hepatitis A vaccine, hepatitis B vaccine, typhoid Vi capsular polysaccharide vaccine, meningococcal vaccine, enchanced inactivated polio vaccine (eIPV), and rabies human diploid cell vaccine (HDCV) or rabies vaccine adsorbed (RVA) doses usually do not cause pronounced local side effect^.^, l9

Several vaccines contain trace amounts of antibiotics and/or other proteins in the final product, and these may contribute to localized hypersensitivity reactions (pain, swelling, erythema, and itching) at the site of injection as well as other adverse reactions.

Large, localized, cutaneous hypersensitivity reactions have been observed following intramuscular injection of immune globulin into the gluteus muscle. This is usually due to an allergic reaction to the thimero- sal preservative used in this relatively large-volume (0.02 mL/kg to 0.06 mL/kg) injection.

Rash, Fever, and Associated Symptoms

Primary vaccination with the live attenuated measles/mumps/rubella virus combination vaccine may be associated with the development of a mild fever and rash 7 to 12 days after vaccination, and the symptoms may last several days. Measles vaccine has been associated with more serious adverse effects such as fever 2 103°F in about 5% to 15% of vaccinees, and central nervous system conditions including encephalitis and encephalopathy at a rate of less than 1 case for every million doses administered?

Rubella vaccine has been associated with development of arthralgia

264 JONC 81 McMULLEN

(up to 25%) and transient arthritis (up to 10%) in adult women vaccine recipient^.^ Also varicella vaccine, a live attenuated viral vaccine, may cause a mild febrile illness accompanied by a rash up to 3 weeks following vaccination. Vaccine recipients are considered potentially infectious for the duration of the rash, and should not be in contact with immunocompromised persons.

MALARIA

Malaria is probably the most important diagnosis to consider in the traveler with fever returning from malarious areas in Africa, Asia, Cen- tral America, and other regions. Malaria in humans is caused by four species, Plasmodium falciparum, P. vivax, P. ovale, and P. malariae. All four species may cause fever (as high as 104 to 105°F in some cases), chills, headache, myalgias, abdominal pain, jaundice, and, occasionally, diarrhea.

The clinical presentation of early malaria can be similar to other illnesses characterized by fever, including viral influenza, dengue fever, meningococcal meningitis, typhoid fever, pneumococcal pneumonia, and viral hepatitis.15, 28, 30 Yet, if the diagnosis of malaria caused by Plasmodium fakiparum is missed, the infected person can become rapidly worse over the course of a day or two as the parasitemia rises in the circulating red blood cells. The parasitized red blood cells tend to sludge in the capillaries, impeding the microcirculation and resulting in symptoms of multiple end-organ failure (coma, renal failure, pulmonary edema, and so forth) and death, if appropriate therapy is not instituted in time.

Diagnosis of Malaria

The biggest challenge in the diagnosis of malaria is to consider it. If the febrile patient has just returned from a trip abroad, the risk of malaria may be obvio~s.~, lo, 13, 30 If the travel occurred several months or even a year or two before the illness, the patient may not relate that travel to the current illness, and may actually answer negatively when asked if there has been any international travel. All febrile patients should therefore be asked specifically if they have traveled outside of the United States or Canada within the past 3 years, if they were born overseas, or if they experienced prolonged residence abroad.

A common fallacy is the belief that if the patient took malaria chemoprophylaxis during travel to a malarious area and for 4 weeks after return, then that person is not at risk of malaria. Unfortunately, because of increasing resistance to antimalarial drugs among P. falciparum and P. vivax strains around the world, even travelers taking the recommended medications as instructed cannot count on 100% protection.28, 29, 30 Chloroquine-resistant P. fakiparum malaria strains are present


Table 1. INTERVAL BETWEEN DATE OF ENTRY AND ONSET OF ILLNESS BY PLASMODIUM SPECIES FOR IMPORTED MALARIA GASES IN THE UNITED STATES (1992)

~~

interval P. vivax P. fakiparum P. malaria P. ovale Total

<1 31.6 88.4 50.0 5.0 51.6 1 -2 18.4 6.6 15.0 30.0 14.4 3-5 23.4 3.5 15.0 10.0 15.5 6-1 2 22.8 1 .o 20.0 40.0 15.5 >12 3.8 0.5 0.0 15.0 2.9 No. of cases 31 6 198 20 20 554

(mo) (”/I (“10) (“/.I (“/.I (“10)

Adapted from Centers for Disease Control and Prevention: Malaria surveillance-United States, 1992. MMWR 4411-17, 1995.

in Asia, Africa, and South America. In some areas, multidrug-resistant P. fakiparum strains resistant to chloroquine and mefloquine have been reported. In Papua New Guinea, Irian Jaya, and areas of Southeast Asia, chloroquine-resistant and primaquine-resistant strains of P. vivax malaria have been reported.’, 23, 26

Another factor contributing to failure of prophylaxis is the unpre- dictable incubation period of malaria, which varies among the four species, and also appears to be influenced by unknown individual host factors. Taking an effective malaria chemoprophylaxis regimen for 4 weeks after leaving a malarious area can be expected to protect against the expression of disease in most cases. However, as illustrated by Table 1, there will still be some cases of malaria with an incubation period extending beyond the recommended 4-week period of medication. The number of later-occurring cases of malaria could theoretically be decreased if the postexposure prophylaxis period were extended to 6 or even 8 weeks after leaving the malarious area. However, prolonging the regimen increases the exposure to potential drug side effects as well as the inconvenience for travelers.

If the diagnosis of malaria is suspected, blood samples should be sent to the clinical laboratory for malaria thick and thin smears, in addition to the standard blood cultures and other blood tests needed to guide diagnosis and patient management. If the patient presents with a fever and headache and/or altered mental status, a lumbar puncture should be performed to get cerebrospinal fluid for culture and diagnostic testing to evaluate for meningitis caused by other agents.

A chest radiograph is indicated if the patient has respiratory symptoms or distress.

Treatment of Malaria

In cases where the febrile patient is very ill and has compelling risk factors for exposure to malaria, it may be necessary to institute

266 JONG & McMULLEN

antimicrobial therapy against serious systemic bacterial infections and antimalarial therapy against P. fulcipavum at the same time even when the diagnosis is not evident from the early work-up. For treatment of malaria in such a case, clinicians are advised to use a combination of quinine sulfate and tetracycline, if the patient can take oral medications, or a combination of quinidine gluconate and doxycycline if the medications must be given par enter all^.^^ The doses of these medications and other recommended therapeutic combinations are given in Tables 2 and 3.

Patients with malaria who are able to tolerate oral medications may be treated as outpatients, if they have social support at home, and are able to call back for advice or assistance. Such patients should return to the ED the day after treatment has been initiated, to get a follow-up malaria smear. This smear will provide assurance that the initial level of parasitemia has improved on the therapy prescribed. Hospitalization is sometimes necessary to initiate therapy for ambulatory patients when there are significant language, cultural, or physical barriers that might interfere with communication, compliance, and return for follow-up. Patients requiring intravenous quinidine gluconate infusion are custom- arily treated as inpatients and placed on a cardiac monitor due to their severe clinical status and to watch for signs of quinidine toxicity (QT interval prolongation).2y

The antimalarial combinations given above have been sufficient to treat the erythrocytic stages of malaria caused by all species, including multidrug-resistant P. fakiparum. However, if the malaria is speciated as P. vivux or P. ovule, then "radical" therapy with primaquine phosphate may be necessary to eradicate latent malaria parasites (hypnozoites) in the liver. The standard adult regimen is 26.3 mg primaquine phosphate

Table 2. MALARIA DRUGS USED FOR ACUTE TREATMENT IN PATIENTS ABLE TO TOLERATE ORAL MEDICATIONS

Drug Adult Dose Pediatric Dose

Plasmodium vivax, P. ovale, and P. malariae: Chloroquine phosphate tablets

sulfate tablets P. fakiparum: Quinine

Plus tetracycline

Or plus doxycycline

Or plus clindamycin

1000-mg initial dose followed by 500 mg at 6, 24, and 48 h later

650 mg 3 times a day for 3 days (continue for 7 days for malaria acquired in Southeast Asia)

250 mg 4 times a day for 7 days

100 mg twice a day orally for 7 days

10 mglkg 3 times a day for 5 days

Chloroquine base 10 mglkg initial dose followed by 5 mglkg at 6, 24, and 48 h later

10 mg quinine sulfatelkg 3 times a day for 3 days (continue for 7 days for malaria acquired in Southeast Asia)

>8 yrs of age: 5 mglkg of body weight orally 4 times a day for 7 days

>8 yrs of age: 2 mglkg of body weight orally twice a day for 7 days

10 mglkg 3 times a day for 5 days


Table 3. TREATMENT OF SEVERE MALARIA IN PATIENTS UNABLE TO TAKE ORAL MEDICATION

Precautions Never give chloroquine, quinine, or quinidine by intravenous bolus injection. If the

patient remains severely ill, the dose of quinine or quinidine should be reduced on the third day of treatment by one third to one half. Oral treatment should replace parenteral treatment as soon as the patient can take oral drugs reliably. Quinine and quinidine may induce hyperinsulinemic hypoglycemia.

Chloroquine-Sensitive Malaria Well-staffed and well-equipped hospital: Chloroquine: 10 mg base/kg by rate-controlled intravenous infusion over 8 hrs,

followed by 15 mg/kg over 24 hrs. Rural health facility: Chloroquine: 3.5 mg base/kg by intramuscular or subcutaneous injection every 6 hrs

until the patient can take oral drugs, or 2.5 mg base/kg IM or SQ every 4 hrs until the patient can take oral drugs.

Chloroquine-Resistant Malaria Well-staffed and well-equipped hospital: Quinine dihydrochloride: Give initial dose of 7 mg quinine dihydrochloride/kg by rate-

controlled intravenous infusion over 30 min followed by 10 mg/kg over 4 hrs, or an initial dose of 20 mg salt/kg over 4 hrs; then give maintenance dose of 10 mg salt/kg infused over 2-8 hrs every 8 hrs (resistant areas) or every 12 hrs (sensitive areas), until the patient can take oral drugs.

States. Note: Quinine dihydrochloride for parenteral use is no longer available in the United

OR Quinidine gluconate: Give initial dose of 10 mg baselkg by rate-controlled intravenous

infusion over 1 hr; followed by maintenance dose of 0.02 mg base/kg/min with cardiac monitoring, until the patient is able to take oral drugs.

Note: This is the regimen recommended by the CDC for treatment of severe malaria in a patient unable to take oral drugs. Quinidine is more cardiotoxic than quinine. The electrocardiogram should be monitored continuously, and the infusion stopped if the QTc interval is prolonged by 225%.

Rural health facility: Quinine dihydrochloride: 20 mg salt/kg by intramuscular injection to the anterior thigh

(split the initial dose between the two thighs) followed by 10 mg/kg every 8 hr (resistant areas) or every 12 hr (sensitive areas), until the patient can take oral drugs.

Note: Quinine dihydrochloride for parenteral use is no longer available in the United States.

Adapted from White NJ, Nosten F: Advances in chemotherapy and prophylaxis of malaria. Current Opinion in Infectious Diseases 6:323-330, 1993.

orally each day for 14 days. However, some of the P. vivax strains (Chesson strains) from the Pacific and Southeast Asia regions may require 52.6 mg primaquine phosphate orally each day for 14 days to eradicate the hepatic hypno~oites .~~ If the radical therapy cannot be administered immediately following completion of treatment for acute P. vivax malaria (because the patient is unable to tolerate oral medications), then it is customary to re-treat the patient with a loading dose of chloroquine at the start of the primaquine therapy.29

268 JONG & McMULLEN

DIARRHEA

Diarrhea and abdominal discomfort are very common complaints among post-travel patients seeking care in the ED. The inconvenience of too frequent loose bowel movements prompts many ambulatory, not seriously ill patients to seek care in the ED, especially if there is a need to return to work shortly after return from the foreign travel.

Travelers' Diarrhea

Returned travelers presenting to the ED with the common complaint of watery or loose nonbloody stools and gastrointestinal upset should be examined for abnormal vital signs and physical findings suggesting significant dehydration, systemic toxicity, or the presence of an acute abdomen. Stool specimens should be obtained voluntarily, by digital examination or by proctoscopy from seriously ill patients. In mildly ill patients with diarrhea and gastrointestinal symptoms, stool specimens may be obtained at the time of the initial visit or brought in from home promptly after the next bowel movement.

The stool specimen should be sent for culture to detect Salrnonella, Shigella, and Carnpylobacter. If the patient gives a history of having taken one or more courses of antibiotics prior to being seen, then Clostridiurn dificile infection also must be considered."rZ1 If the patient gives a history of eating hamburgers that may not have been thoroughly cooked, or other foods implicated in an active outbreaks of E. coli 0157:H7 (unpas- teurized fruit and vegetable juices, alfalfa sprouts, and so forth), then cultures for E. coli 0157:H7 should be ordered.

Giardia, amoebas, and other intestinal parasites are detected by ova and parasite stool examinations. Special procedures on the stool specimens such as the Giardia antigen test and staining for Cyclospora detection may be helpful in diagnosis of persons with a history of prolonged diarrhea. Although both organisms are considered ubiquitous, Giardia and Cyclospora have been associated with ingestion of untreated surface waters in developing areas of the world such as Nepal.4 Special tests to detect Cryptosporidiurn and Microsporidium may be ordered to evaluate prolonged watery diarrhea in patients with compromised immunity.

If the patient has brought in a fresh stool specimen or is able to produce one in the ED, the diagnosis based on morphology can sometimes be made from a wet-mount examination of the stool (Giardia, E. histolytica, Carnpylobacter sp, or Vibrio sp). If an immediate diagnosis is not made, the patient and his/her health care provider can decide based on individual circumstances if an empiric therapeutic trial with one of the oral quinolone antibiotics (ciprofloxacin, ofloxacin, norfloxacin) is warranted (Table 4) while the bacterial cultures and parasite examinations are being performed, or whether the patient should wait for spe-


Table 4. DRUGS FOR EMPlRlC TREATMENT OF TRAVELERS DIARRHEA

Drug Adult Dosage Comments

Bismuth subsalicylate

Loperamide (Imodium)

(Pepto-Bismol)

Trimethoprim/ sulfamethoxazole (Bactrim, Septra, and so forth)

Norfloxacin* (Noroxin)

Ciprofloxacin (Cipro)

Ciprofloxacin* (Cipro)

Ofloxacin* (Floxin)

20 mL (or two tablets) every 30 minutes for 8 doses

Take two caplets (2 mg each) for first dose, then one after each loose stool; do not exceed eight caplets (16 mg) in 24 hours-may take this concurrently with antibiotic therapy

160 mg1800 mg tablet (one double-strength tablet) every 12 hours for 6 doses

400-mg tablet every 12 hours for 6 doses

500-mg tablet every 12 hours for 6 doses

750-mg tablet once at start of diarrhea symptoms

200-mg or 300-mg tablet every 12 hours for 6 dosest

The maximum recommended adult dose is 240 mL (16 tablets) per day

use in dysentery; sold over the counter

Antiperistaltic drug; do not

Antibiotic; do not use in sulfa- allergic patients-useful- ness limited by development of resistance among many enteric bacterial pathogens worldwide

Antibiotic; do not use in pregnancy or in children 1 1 8 years old

pregnancy or in children ~ 1 8 years old

pregnancy or in children < 18 years old

pregnancy or in children (18 years old

Antibiotic; do not use in



*Unlabeled use. tThis drug has been studied for this use at both doses. Adapted from Jong EC, McMullen R: Traveler’s diarrhea: Prevention and self-treatment. In Jong

EC, McMullen R (eds): The Travel and Tropical Medicine Manual, ed 2. Philadelphia, WB Saunders, 1995, pp 67-79.

cific information from the laboratory studies (results of cultures and confirming tests may take as long as 3 to 5 days).11,12,21

If the patient is seriously ill, blood specimens should be sent for a complete blood count, serum electrolytes, and blood cultures, concurrently with placement of an intravenous catheter for parenteral therapy and rehydration. Urine should be obtained for a complete urinalysis, culture, and parasite examination depending on the exposure history.

Lactose Intolerance

Lactose intolerance should be considered in the patient with intermittent diarrhea, bloating, and abdominal cramping, who has negative stool diagnostic studies. Such a patient may give a history of an earlier

270 JONG & McMULLEN

episode of severe diarrhea during travel which seemed to resolve spon- taneously or in response to a course of antimicrobial therapy, and who has now had onset of gastrointestinal symptoms upon return to the United States and a “regular” diet. Restriction of lactose-containing foods, and taking supplemental lactase (the intestinal enzyme that pro- motes the digestion of lactose or milk sugar) at mealtimes may result in remarkable improvement. Commercial preparations of lactase in capsule and liquid form can be purchased without a prescription at many pharmacies and health food stores.

Bloody Diarrhea and Abdominal Pain

Bloody diarrhea and abdominal pain are the hallmarks of amoebic dysentery (Entamoeba histolyfica) or bacterial dysentery (Shigella dysenter- iae, Campylobacfer jejuni, Plesiomonas shigelloides) in the returned traveler. However, if the medical history suggests risk factors in addition to recent international travel, such as recent medication with broad-spec- trum antibiotics, recent ingestion of raw or undercooked hamburger meat, or a familial history of gastrointestinal problems, antibiotic-associated colitis due to Clostridium dificile, hemolytic-uremic syndrome due to infection with E. coli 0157:H7, and primary onset of ulcerative colitis must be included in the differential diagnosis.

Schistosomiasis

If the patient gives a history of wading, swimming or boating in bodies of fresh water, such as rivers, lakes, and streams in areas of Africa, the Middle East, South America, or Asia where the species of the blood fluke schistosomiasis are endemic, this parasitic infection should be added to the differential diagnosis of bloody diarrhea or bloody urine.” 6, l8

The invasive stage of the schistosome parasites, cercariae, penetrate intact wet human skin, sometimes eliciting an itching papular skin rash within hours after exposure that lasts for days. After an incubation period of about 4 to 6 weeks, onset of parasite maturation and egg laying is often manifested by acute abdominal pain and bloody diarrhea in human hosts infected with Schistosoma mansoni, S. japonicum, or S. mekongi. When these symptoms are accompanied by a high fever, headache, cough, urticaria, tender hepatosplenomegaly, and hypereosinophilia of the peripheral blood, the clinical syndrome is known as “Katay- ama fever.”

Infection with the genitourinary species, S. haematobium, can be manifested as lower abdominal pain and bloody urine. The popularity of swimming, snorkeling, and scuba diving in Lake Malawi among visitors to Africa has resulted in an increasing number of reported cases of S. haematobium in returned travelers.


The acute diagnosis of intestinal schistosomiasis ( S . mansoni, S. japonicum, S . mekongi) can be made by finding the characteristic eggs in stool specimens or rectal biopsies. The diagnosis of S. haematobium is best made by collecting the first-morning urine and examining it for the characteristic ova, although random urine samples throughout the day will sometimes contain the eggs. Relatively light infections with schistosomiasis may not be easily detected by stool or urine examinations, and complications of infection have been described in patients whose specimens were negative for ova. Species-specific serologic testing is available from the Parasitic Diseases Branch of the Centers for Disease Control and Prevention (CDC;770-488-4050).

Typhoid Fever

Although typhoid fever is acquired through gastrointestinal infection, diarrhea is not one of the usual presenting symptoms. This serious infection should be considered in travelers with high fever, prostration, abdominal pain, and constipation, who are returning from developing countries, especially India, Indonesia, Mexico, and Peru. The history of having received pretravel immunization with one of the typhoid vaccines does not preclude the diagnosis, as none of the currently available vaccines offers 100% immune protection.*

An evanescent macular rash on the trunk ("rose spots") may be present. Often, stool cultures will not be diagnostic at the time of clinical presentation, although blood cultures, bone marrow cultures, and aspiration of the rose spots may sometimes yield the etiologic agent, Salmonella typhi. Serologic testing is not useful for acute diagnosis, but may help with eventual diagnosis if there is a fourfold rise in antibody titer between acute and convalescent serum specimens.

Acute Abdomen

In addition to the usual differential diagnosis of acute abdomen, the following exotic etiologies should be included in the returned traveler with severe abdominal pain. Spontaneous peritonitis due to Ascaris lumbricoides worms penetrating the intestines with subsequent peritoneal leakage of bowel contents occurs in patients with mature roundworm infections. The eggs are ingested through eating improperly cooked food contaminated with human feces in developing countries (leafy green vegetables are a predictable risk).I7 The worms may get as large as pencils after about a year, and be capable of active migration and penetration through internal organs. Reports of acute appendicitis and acute pancreatitis associated with migration of the worms into small orifices are in the published literature.

Bacterial infection with the pathogen Yersinia enterocolitica, a con- taminant of food and water in areas of poor sanitation, can cause

272 JONG & McMULLEN

infection and inflammation of the lymph nodes surrounding the terminal ileum. The clinical presentation of right lower quadrant pain with re- bound tenderness is often indistinguishable from classic acute appendicitis before surgery, and the diagnosis is often made during laparotomy for appendicitis. The microorganism can be cultured from the lymph nodes, and from the stool, using special culture medium, and prolonged incubation at a lower than usual incubator temperature.

Ciguatera Fish Poisoning

Patients returning from tropical destinations between latitudes + 35 and -35 degrees, who experience onset of acute diarrhea followed by puzzling neurologic symptoms may be afflicted with ciguatera fish poisoning.16 There are 425 species of fish implicated in this poisoning. Common species include barracuda, snapper, grouper, amberjack, sea- bass, surgeonfish, and moray eel.

Small tropical reef-dwelling fish acquire ciguatoxin and maitotoxin synthesized by dinoflagellate Gambierdiscus toxicus through normal feed- ing patterns. The toxin is conserved up the food chain as the smaller fish are eaten by the larger fish. The contaminated fish look, smell, and taste normally. The toxin is not destroyed by cooking or freezing. Two to 6 hours after ingestion of contaminated fish, a person may experience watery diarrhea, abdominal cramps, nausea, and vomiting. The gastrointestinal symptoms may last several days, during which period there is onset of hot-cold sensory reversal, distal paresthesias, and other systemic symptoms.

Ciguatoxin induces partial membrane depolarization by enhancing Na + permeability in voltage-dependent sodium channels in nerve cell membranes; maitotoxin is a calcium channel activator which increases Ca2+ permeability through voltage sensitive cells. Published reports have described complete resolution of symptoms resulting from the acute administration of intravenous mannitol (1 g per kg); amitriptylline; or tocainide (400 mg every 8 hours).Z2, 25 The role of medication in the returned traveler with ciguatera fish poisoning is unclear.

RESPIRATORY TRACT INFECTIONS

Prolonged air travel predisposes travelers to respiratory infections because the low humidity of the ca in air dries out mucous membranes,

The cabin air is recirculated to varying degrees during the flight, thus promoting the spread of infectious diseases transmitted by respiratory droplet spread. At destination, there may be increased exposure to crowds of people with respiratory viruses, other respiratory pathogens, and contaminated fomites. Returned travelers frequently seek care in the ED for persistent cough, congestion, and fever.

thus lowering an important natur hs. 1 respiratory defense mechanism.


The approach to respiratory problems in returned travelers is no different than for community patients in regard to assessing risk factors associated with age, cigarette smoking, presence of chronic disease, and vaccine status (pneumococcal vaccine and influenza vaccine). Travel- associated infections may include entities which occur worldwide, such as viral influenza, pneumococcal pneumonia and legionellosis, as well as infections whose risk is associated with specific geographic areas, such as tuberculosis, lung flukes, parasite-induced bronchospasm, and melioidosis.

Tuberculosis

Tuberculosis infection should be considered in recent travelers who present with cough, fevers, sweats, and malaise. High-risk exposures are more likely to have occurred among travelers who had prolonged exposure to residents, through work or other activities, in areas where tuberculosis is prevalent. Such travelers include teachers, health care workers, volunteer relief workers, and students. A chest radiograph, sputum culture for common respiratory pathogens and Mycobacferiurn tuberculosis, a tuberculin skin test, and respiratory isolation in the ED until a probable diagnosis can be made are recommended initial steps.

If tuberculosis is suspected, treatment recommendations should take into account the most likely geographic source of the infection, due to increased concerns about multidrug-resistant strains of M . tuberculosis throughout the world. If there is a possibility that the tuberculosis infection was acquired in a country with a known high rate of isoniazid resistance, four drug chemotherapy with isoniazid, rifamipin, pyra- zinamide, and either ethambutol or streptomycin may be initiated prior to confirmation of the diagnosis by susceptibility testing. The tuberculosis control officer of the local public health department or the CDC should be consulted as soon as possible.

Lung Fluke Infection

Infection with lung flukes, Paragonimus westerinani and other species, can mimic tuberculosis. The clinical illness consists of a cough which is sometimes productive of bloody sputum, low-grade fever, malaise, and infiltrates or space-occupying lesions seen on the chest radiograph. Para- gonirnus infections can be acquired by eating raw or undercooked crabs and crayfish in Asia, Africa, Latin America, and even in the southern United States. Diagnosis is usually made after obtaining a suggestive exposure history, and examining sputum and stool specimens for the characteristic ova. A quantitative serum antibody test is available from the Parasitic Diseases Branch of the CDC and is helpful for following the course of complicated infections. Treatment with praziquantel, 75

274 JONC & McMULLEN

mg/kg/day given in three divided doses on 2 consecutive days will usually result in a cure.lB

Melioidosis

Infection with a bacterium, Pseudomonas pseudomallei, produces a tuberculosis-like illness called melioidosis. This infection is sometimes accompanied by septicemia and is prevalent in Southeast Asia, especially among people working in rice paddies. Diagnosis of infection is usually made by clinical presentation, history of geographic exposure, location of infiltrates on the chest radiograph, culture of the causative bacterium from pulmonary secretions or blood, and serologic testing.

Parasite-Induced Bronchospasrn

New onset of cough, wheezing, and malaise, with patchy infiltrates on the chest radiograph and hypereosinophilia on the peripheral blood smear are compatible with a hypersensitivity reaction to migrating parasites.

Two to 3 weeks after ingestion of Ascaris ltlmbricoides eggs, the immature larval worms migrate several times through the lungs, and incite a hypersensitivity reaction in susceptible people. The suggestive clinical history would include recent travel and ingestion of local food of uncertain quality. The stool examination may show no characteristic parasite eggs at the time of clinical presentation. This happens when the parasites causing the infection are immature and have not yet started egg laying. However, eggs may be present if older mature worms from previous infections are still present in the intestines. The respiratory symptoms should be managed with standard therapies, and the parasite infection can be cured by a course of mebendazole, one 100-mg tablet by mouth twice a day for 3 days.

Pulmonary migrations of another intestinal worm, Strongyloides stercoralis, in immunocompromised hosts can cause a similar clinical picture to the migrating larval Ascaris infection. Strongyloides infections are transmitted through skin contact with contaminated ground or with other infected individuals. The infection is asymptomatic and usually confined to the gastrointestinal cycle in immunocompetent hosts. How- ever, in immunocompromised hosts, such as patients with cancer or AIDS, or who are taking immunosuppressive drugs, the larval infection can migrate to any internal organ system.

Diagnosis is usually made by finding the larval worms in jejeunal or pulmonary secretions. A commercial serum antibody test is helpful for making the diagnosis in occult infections. Hypereosinophilia of the peripheral blood smear is a common finding during infection, but is not diagnostic. Strongyloides infections are treated with thiabendazole, 25 mg/kg twice a day by mouth for 2 consecutive days. The therapy can


Table 5. STRATEGY FOR TREATMENT OF INTESTINAL NEMATODES IN MIXED INFECTIONS

Group

Ascaris* Hookworm’ Enterobius*

Ascaris* Hookworm* En terobius* Trichuris*

S trongyloides* Ascaris Hookworm Trichuris

Ascaris* Hookworm* En terobius* Trichuris* Strongyloides Taenia

Treatment

Pyrantel pamoate (Antiminth), 50 mg/mL oral suspension. Standard dose: 11 mg/kg in a single oral dose not to exceed a

maximum dose of 1 g. Not recommended for children less than 2 years of age. For Enterobius, repeat the dose after 2 weeks.

Mebendazole (Vermox), 1 00-mg chewable tablet. Standard dose: 100 mg bid x 3 days for adults and children over 2

years of age. Available as a chewable tablet. An infection with Enterobius alone requires only one 100-mg tablet for treatment, with a repeat dose after 2 weeks.

Thiabendazole (Mintezol) 500-mg chewable tablet, or 500 mg/5 mL oral suspension.

Standard dose: 25 mg/kg bid (maximum 3 g/day) x 2 days. For disseminated Strongyloides infection, continue treatment for 5 days or more. Variable activity against Ascaria, hookworm, and Trichuris. Some consultants recommend pyrantel pamoate (as above) 1 week following thiabendazole therapy if the patient is infected concurrently with Ascaris.

Albendazole (Albenza, Zentel), 200-mg tablet; 100 mg/5 mL suspension.

(No FDA indication for use in treatment of these infections) Standard dose: Two 200-mg tablets as a single dose in adults and

children 2 years of age 0; older; 200 mg as a single dose in children 1-2 years old (not studied in children less than 1 year of age; contraindicated in pregnancy). Repeat dose after 2 weeks for Enterobius. Treatment for Strongyloides, Taenia spp, Hymenolepis nana: Two 200-mg tablets as a single dose on 3 consecutive days.

Hymenolepis nana

*The treatment listed for each group is appropriate for any single parasite infection marked with an asterisk within a group, or for multiple parasitism within a given group, provided that one or more parasites is present.

Adapted from Jong EC: Common intestinal roundworms. ln Jong EC, McMullen R (eds): The Travel and Tropical Medicine Manual, ed 2. Philadelphia, WB Saunders, 1995, pp 443-452.

be increased from 2 to 5 days or longer for disseminated infections. Another effective treatment is albendazole, two 200-mg tablets taken as a single dose for 3 consecutive days in individuals older than 2 years of age. Albendazole has recently become commercially available in the United States (Table 5).*’

WORMS AND PARASITES

A ”worm emergency” is likely to occur when a grossly visible worm is recognized by the patient creeping across a body part or emitting from an orifice. Distraught patients have been known to present in the ED in the early hours of the morning with worm specimens in plastic bags, recycled yogurt containers, or wrapped in toilet paper.

276 JONG & McMULLEN

Because most worms need several months to grow to an easily visible size, the travel history may be remote from the clinical presentation, usually by several months to a year or more.

Common Roundworms

Ascavis Zumbricoides is a very common and ubiquitous parasite and may be easily acquired through eating contaminated food during a short trip to an area of poor sanitation. Usually, light to moderate infections are entirely asymptomatic, and the presence of worm(s) may not be recognized until a worm finds internal conditions inhospitable, and decides to exit from the gastrointestinal tract through the anus, or up through the esophagus, exiting from the nose or mouth. Some of the factors that may stimulate roundworms to migrate are fever, decreased intake of food during illness, antibiotics and other medications, and anesthesia.

Although there is no pain and no specific health hazard associated with passing a worm, most people find the spontaneous passage of an earthworm-sized creature disturbing, and seek immediate medical care. The worm specimen can be sent to the laboratory for species confirmation. Pork roundworms, Ascavis suum, may infect humans who eat raw, organically grown root vegetables and leafy green vegetables cultured with unsterilized pig manure. Treatment consists of reassurance and treatment with mebendazole as described in Table 5.17

Tapeworms

Tapeworms are often discovered by patients during defecation or when the tapeworms independently migrate from the rectum and are observed on toilet paper or in undergarments. Many patients describe a funny itching sensation as segments of the tapeworms migrate out. The tapeworm species can be determined by examining the morphology of the proglottids, or tapeworm segments. Beef tapeworms (Taenia saginata) and pork tapeworms (Tuenia solium) are acquired from eating undercooked infected meat. Fish tapeworms (Diphyllobothrium Zatum) are acquired from eating raw or undercooked infected fish, dwarf rodent tapeworms (Hymenolepis nana, H. diminuta) are acquired from accidental ingestion of infected rodent feces, and the dog tapeworm (DipyZZidium caninurn) is acquired by accidental ingestion of an infected flea.

A single 2-gram dose (four tablets) of niclosamide chewed thoroughly will cure beef, pork, fish, and dog tapeworm infections in adults. The dose is adjusted by weight in pediatric infections. One gram is recommended for children 11 to 34 kg, and 1.5 g is recommended for children greater than 34 kg. Praziquantel, given as a single oral dose of 25 mg/kg, is the treatment of choice for dwarf tapeworm infections in adults and children.


Loa Loa

Although not a commonly encountered parasite infection among casual short-term travelers, Lou Ioa infection is a diagnosis that might be considered in returning Peace Corps Volunteers, missionaries, field workers, and recent immigrants from endemic areas in Central and West Africa. The most spectacular presentation is that of a visible worm crawling across the conjunctiva of the eye. Additional clinical findings include "Calaber swellings" large subcutaneous swellings (transient angioedema) over extensor surfaces of extremities, intermittent fevers, and hypereosinophilia on the peripheral blood count.

Diagnosis is dependent on correlating the geographic exposure with the clinical symptoms. Many infected persons are amicrofilaremic, so recovery of parasites from blood filtration is not predictable. Observation of the subconjunctival migration of an adult worm is diagnostic. The recommended emergency response is physical removal of the worm from the eye with fine tweezers after application of topical ophthalmic anesthesia. This therapy relieves patient discomfort and confirms patho- logic diagnosis. The patient should be referred to a tropical medicine or infectious diseases specialist for treatment of the underlying infection with diethylcarbamazine (DEC), available directly from the manufac- turer (Lederle) through a compassionate use protocol. Another drug, ivermectin (Merck) has been used in the treatment of loa loa with variable

SKIN LESIONS

Skin lesions in returning travelers are fairly common and have extensive etiologies. This section focuses on skin lesions associated with several exotic exposures not usually encountered in nontravelers that are unusual enough to prompt the patient to seek medical attention in the ED.

Creeping Eruption

The typical presentation of "creeping eruption" or Cutaneous larva migrans occurs in travelers returning from vacations to tropical beaches who walked barefoot on the beach, or who lay on the sand to sunbathe. The hallmark of this skin condition consists of a serpiginous erythema- tous "track" that advances from a few millimeters to a few centimeters a day, creating an erratic itching track. The lesion commonly occurs on the sole of the foot, but may affect any skin surface that has been in direct contact with damp sandy soil contaminated by dog or cat hookworm larvae (from fecal wastes).

Usually, hookwork larvae are unable to complete a normal life cycle in human hosts, so they migrate in the skin, inciting an inflammatory

278 YONG & McMULLEN

cutaneous hypersensitivity reaction in their pathway. Patients complain of sleeplessness and restlessness due to the intense itching.

The condition may be cured by applying thiabendazole 10% suspension topically four times a day with occlusive dressings for 2 to 7 days, or by systemic treatment with thiabendazole, 25 mg/kg by mouth 2 times a day for 2 days. Left untreated, the larvae usually die within 2 to 8 weeks, and the condition resolves. Surgical excision of the track, or freezing the lesion with liquid nitrogen are not usually successful in curing this problem, and may create unacceptable scarring.

Cutaneous Myiasis

A patient with cutaneous myiasis usually complains of pain and a sensation of "movement" within a papular skin lesion, which has not improved or resolved over the course of several weeks. The skin lesion appears to be a furuncle with a central black hole in the center. Examina- tion of the punctum with a hand lens may reveal moving "bristles" of a live creature that seems to come up to the surface of the skin and then retreats, especially if there is any pressure on the skin. There may be one or more lesions present. This condition is called cutaneous myiasis and is due to the presence of a living fly larva in the subcutaneous tissue. Dermatobium fly larvae are deposited on the skin by biting mosquitoes in Central and South America. In Africa, the Tumbu flies lay their eggs on clothes left out to dry, and the larvae hatch and enter the skin when the clothes are worn.

Removing the larva through the air hole in the skin by grasping it with forceps is likely to be unsuccessful, because the creature will withdraw itself into the lesion. The best way to remove the larva is to put an occlusive dressing over the air hole. Petrolatum jelly held in place by a small plastic cap or bandage over the airhole works well. After several hours, and death by suffocation, the larva can be then removed through a surgical excision over the dome of the lesion. A more dramatic way of coaxing the living larva has been published. The technique consists of placing a slab of raw bacon over the air hole. In time the larva will exit of its own accord, drawn out by the prospect of bacon, and will be found embedded in the bacon.2

Some patients or their referring health care providers may have attempted previous aspiration or manipulation of the lesion, resulting in death of the larvae. Subsequently, a foreign body reaction and secondary bacterial skin infection may develop. Such lesions need to be opened up by surgical incision after local anesthesia, the dead larva carefully removed, and the wound debrided and cleansed thoroughly. A short course of antibiotic therapy may be appropriate to treat any secondary bacterial skin infection present in the tissue around a living or dead larva.


Cutaneous Leishmaniasis

The presence of a relatively painless, shallow skin ulcer with a distinct rolled edge that slowly enlarges over a course of weeks, despite topical or systemic antibiotic therapy is a clue that the lesion might be cutaneous leishmaniasis. The protozoan parasites of the genus Leishmania causing this condition are inoculated into the skin through the bites of small sandflies in tropical and subtropical regions of Latin America, the Mediterranean basin, the Middle East, and Asia.

Following an infected sandfly bite, the lesion begins as a small papule that slowly enlarges, breaks down, and forms an ulcer. A secondary bacterial skin infection in the surrounding tissue may be present. Depending on the species and geographic area, the cutaneous leishmaniasis infections acquired in Latin America may be limited to the skin, or may develop into a more serious condition called mucocutaneous lei~hmaniasis.’~ In the latter condition, the parasite infection results in subsequent destruction of the cartilaginous structures of the nose and oropharynx over months to years.

A combination of diagnostic techniques will help to confirm both the diagnosis and Leishmania species. The best way to make the diagnosis is to isolate the parasite from a punch biopsy specimen taken from the edge of the ulcer. The CDC Parasitic Diseases Branch of the CDC (770- 488-4050) will send out the specialized culture medium and perform the laboratory work if local laboratory resources are not available. In addition to culture, the parasite may be identified by histologic stains of biopsy specimen touch preparations and by standard pathology examination. However, speciation of the parasite is possible only if further specialized testing at certain reference laboratories can be performed on isolates of the parasite cultured from the 1esi0n.I~

Depending on local resources, the ED physician may biopsy the lesion and supervise the treatment in conjunction with advice from the CDC, or may refer the patient with suspected cutaneous leishmaniasis to a tropical medicine, infectious diseases, or dermatology specialist. Treatment of this infection is guided by the clinical presentation, epide- miologic data on Leishmania species transmitted in a given geographic area, and the underlying health of the patient. Physicians caring for returned travelers with this suspected diagnosis are encouraged to contact one of the expert consultants at the CDC to discuss diagnosis and treatment. One of the drugs used for treatment, sodium stibogluconate (Pentostam), is available only under an investigational drug protocol and is supplied directly to the treating physician from the CDC.

SUMMARY

Travelers experiencing adverse side effects from pretravel immunizations and returned travelers who have acquired an illness abroad

280 JONG & McMULLEN

frequently seek care in the ED because they fear unusual, serious, or exotic conditions and they want immediate attention. This article re- viewed several common problems of travelers that are likely to be seen in the emergency department, and presented an approach to initial diagnosis and treatment.

References

1. Baird JK, Basri H, Purnomo: Resistance to chloroquine by Plasmodium vzvax in Irian

2. Brewer TF, Wilson ME, Gonzalez E, et al: Bacon therapy and furuncular myiasis.

3. Centers for Disease Control: Acute schistosomiasis in US travelers returning from Africa. JAMA 2632165-2166, 1990

4. Centers for Disease Control: Outbreaks of diarrhea illness associated with cyanobacte- ria (blue-green algae)-like bodiesxhicago and Nepal, 1989 and 1990. MMWR 40:325- 327, 1991

5. Centers for Disease Control: Rabies prevention-United States, 1991. Recommenda- tions of the Immunization Practices Advisory Committee (ACIP). MMWR 4O:l-19,1991

6. Centers for Disease Control: Schistosomiasis in US. Peace Corps Volunteers-Malawi,

7. Centers for Disease Control and Prevention: Inactivated Japanese encephalitis virus vaccine: Recommendations of the Advisory Committee on Immunization Practices

8. Centers for Disease Control: Typhoid immunization: Recommendations of the Immuni-

9. Centers for Disease Control and Prevention: Health Information for International

10. Centers for Disease Control and Prevention: Malaria surveillance--United States, 1992.

11. DuPont HL, Ericsson CD: Prevention and treatment of traveler’s diarrhea. New Engl J Med 3281821-1827,1993

12. DuPont HL, Ericsson CD, Mathewson JJ, et al: Five versus three days of ofloxacin therapy for traveler’s diarrhea: A placebo-controlled study. Antimicrob Agents Chemo- ther 36237-91, 1992

13. Freedman DO: Imported malaria-here to stay [editorial]. Am J Med 93239-242, 1992 14. Henvaldt BL, Stokes SL, Juranek D D American cutaneous leishmaniasis in U.S. travel-

ers. Ann Intern Med 118:779-784, 1993 15. Hill D: Illness associated with travel to the developing world. In Lobel HO, Steffen R,

Kozarsky P (eds): Travel Medicine 2: Proceedings of the Second Conference on Interna- tional Travel Medicine. Atlanta, International Society of Travel Medicine, 1992, pp

16. Jong EC: Fish and shellfish poisoning: Toxic syndromes. In Jong EC, McMullen R (eds): The Travel and Tropical Medicine Manual, ed 2. Philadelphia, WB Saunders,

17. Jong EC: Common intestinal roundworms. In Jong EC, McMullen R (eds): The Travel and Tropical Medicine Manual, ed 2. Philadelphia, WB Saunders, 1995, pp 443452

18. Jong EC: Blood flukes (schistosomiasis), liver flukes, lung flukes, and intestinal flukes. In Jong EC, McMullen R (eds): The Travel and Tropical Medicine Manual, ed 2. Philadelphia, WB Saunders, 1995, pp 474482

19. Jong EC: Immunizations. In Schlossberg D (ed): Current Therapy of Infectious Disease. St. Louis, Mosby-Year Book, 1996

20. Jong EC, McMullen R Immunization needs of Americans attending a university-based travel medicine clinic from July 1980 to June 1990. In Lobel HO, Steffen R, Kozarsky

Jaya, Indonesia. Am J Trop Med Hyg 44:547-552, 1991

JAMA 270:2087-2088, 1993

1992. MMWR 42~565570, 1993

(ACIP). MMWR 421-15, 1993

zation Practices Committee (ACIP). MMWR 4O:l-7, 1994

Travel, 1995. Washington, DC, US Government Printing Office, 1995

MMWR 44:l-17, 1995

71-73

1995, pp 318-324


P (eds): Travel Medicine 2 Proceedings of the Second Conference on International Travel Medicine. Atlanta, International Society of Travel Medicine, 1992, pp 165-166

21. Jong EC, McMullen R Traveler’s Diarrhea: Prevention and self-treatment. In Jong EC, McMullen R (eds): The Travel and Tropical Medicine Manual, ed 2. Philadelphia, WB Saunders, 1995, pp 67-79

22. Lange WR, Kreider SD Potential benefit of tocainide in the treatment of ciguatera: Report of three cases. Am J Med 84:1087-1088, 1988

23. Luzzi GA, Warrell DA, Barnes AJ, et al: Treatment of primaquine-resistant Plasmodium vivax malaria. Lancet 340310, 1992

24. Nutman TB: Filarial infections. In Jong EC, McMullen R (eds): The Travel and Tropical Medicine Manual, ed 2. Philadelphia, WB Saunders, 1995, pp 460473

25. Palofax NA, Jan LA, Pinano AZ, et al: Successful treatment of ciguatera fish poisoning with intravenous mannitol. JAMA 259:274&2742, 1988

26. Schuurkamp GJ, Spicer PE, Kereu RK, et al: Chloroquine-resistant Plasmodium vivax in Papua, New Guinea. Trans Soc Trop Med Hyg 86321-122, 1992

27. Steffen R, Fuchs E, Schildknecht J: Mefloquine compared with other malaria chemopro- phylactic regimens in tourists visiting East Africa. Lancet 341:1299-1303, 1993

28. Tsai T F Arboviral infections: General considerations for prevention, diagnosis, and treatment in travelers. Seminars in Pediatric Infect Dis 3:62-69, 1992

29. White NJ, Nosten F: Advances in chemotherapy and prophylaxis of malaria: Current Opinion in Infectious Diseases 6:323-330, 1993

30. Winters RA, Muray Hw: Malaria-the mime revisited: Fifteen more years of experience at a New York City teaching hospital. Am J Med 93:243-246, 1992

Address reprint requests to Elaine C. Jong, MD

University of Washington Hall Health Primary Care Center

Box 354410 Seattle, WA 98195

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