WITH the increasing ease and popularity of international travel, ED physicians are seeing greater numbers of patients who present with fever after returning from foreign travels. Most frequently, the fever is caused by common community-acquired illnesses, such as viral upper respiratory tract infections, pneumonias, or urinary tract infections. Nonetheless, fever in returned travelers should always raise concern for a possibly severe or even life-threatening infection of "exotic" origin.
While it is fortunate that these "exotic" diseases are encountered relatively infrequently, it is their very infrequency that can put the patient and the treating physician at a disadvantage. The list of possible diseases is long and diverse and can seem daunting. An organized approach can make diagnosis and treatment much more manageable. In addition to the usual medical history, physicians should obtain a careful travel history, including information about travel dates, geographic locations visited, pretravel immunizations, chemoprophylaxis during travel, and activity-based risk factors, such as insect bites, contact with animals, freshwater exposure, and any history of sexual contact. The evaluation and treatment of the returned traveler with a febrile illness requires an understanding of the common as well as uncommon etiologies, their epidemiology, their modes of presentation, and a systematic approach to diagnosis and treatment.
This issue of Pediatric Emergency Medicine PRACTICE focuses on the identification, evaluation, and treatment of diseases in the returning international child traveler who presents with fever. A review of the most common tropical diseases that affect returning travelers will be provided. Based on a critical evaluation of the pediatric literature and the adult literature as it applies to pediatric patients, we have developed an evidence-based approach to the evaluation of the returning child traveler with fever.
CBC — Complete blood count
CDC — Centers for Disease Control and Prevention
CNS — Central nervous system
DHF — Dengue hemorrhagic fever
DSS — Dengue shock syndrome
DIC — Disseminated intravascular coagulation
EHEC — Enterohemorrhagic Escherichia coli
ELISA — Enzyme-linked immunosorbent assay
EPEC — Enteropathogenic E coli
ETEC — Enterotoxigenic E coli
GPIA — Gelatin particle indirect agglutination
ICU — Intensive care unit
ISTM — International Society for Travel Medicine
MAT — Microscopic agglutination test
NIH — National Institutes of Health
ORS — Oral rehydration salts
PCR — Polymerase chain reaction
RBCs — Red blood cells
RDT — Rapid diagnostic test
RMSF — Rocky Mountain spotted fever
SARS — Severe acute respiratory syndrome
TMP/SMX — Trimethoprim-sulfamethoxazole
VHF — Viral hemorrhagic fever
WBCs — White blood cells
WHO — World Health Organization
Most of the literature on returning travelers with fever pertains to adults. Since the range of diseases is very broad, the topic has been discussed most typically in the format of general review articles.1-3 Historically, there has been little in the medical literature dealing exclusively with the evaluation of returning child travelers. The few publications there are have typically been either retrospective4 or focused on a single infection (eg, malaria).5 A general review article in 1999 from Yale University provided information on the epidemiology of travel-related morbidity and mortality in children, with a focus primarily on prevention, but also with some discussion of treatment of infectious diseases that may be acquired abroad.6 One of the first prospective studies of children hospitalized for fever after traveling showed that 45% had nonspecific fever as a final diagnosis.7 This study was limited in that it included only those children who had returned within the previous 4 weeks. This short window may have resulted in a considerable number of missed cases, due to varied incubation periods.8 A small number of prospective observational studies of hospitalized returning child travelers with fever come from the United Kingdom.7,9,10 These studies demonstrate that nonspecific viral illnesses, malaria, diarrhea, hepatitis, typhoid fever, and dengue fever are the most common imported diseases in children. In a Swiss retrospective survey of infants and children, 40% of pediatric travelers to the tropics experienced travelers' diarrhea, and close to 20% became bedridden.11 Although the array of diseases travelers contact in various parts of the world are similar, the prevalence with which they are diagnosed in different regions of the world varies considerably, depending upon the location of the reporting hospital and the geographic locations through which a person has traveled. Examples of these differences are reflected in the literature from Australia (higher incidence of dengue fever, with a greater percentage of patients having traveled through Southeast Asia) and the United Kingdom (higher incidence of malaria, with a greater percentage of patients having returned from the Indian subcontinent).3,4
The Internet offers some of the most helpful and timely information on travel-related diseases. Current updates on regional outbreaks and information about specific diseases and treatment approaches — even "live chat" with experts — are all now available online. (Table 1) Knowledge of current disease outbreaks in specific locations around the world can be helpful in determining potential causative agents of febrile illnesses in the returning traveler. Epidemics of meningococcal disease,12 hepatitis A,13 severe acute respiratory syndrome (SARS),14 poliomyelitis,15 and measles16 have recently been reported. Region-specific information can be obtained from a variety of sources. The Red Book and Health Information for International Travel publish general information on worldwide exposure risk. The CDC Division of Quarantine publishes a biweekly summary of Health Information for International Travel (the Blue Sheet, available on request from the CDC). The summary lists where cholera and yellow fever are currently being reported. The CDC can also provide more than information — for instance, some diseases are so unusual that specific medications are not readily available in all locations. To treat African trypanosomiasis in the United States, for example, the appropriate therapeutic agents are available only through the Centers for Disease Control and Prevention. This agency also has specialists available at all times to help clinicians in the diagnosis and management of other uncommon infections. The Parasitology Division of the National Institutes of Health offers special expertise in the evaluation of eosinophilia. A review of offlinedatabases and Internet resources with information about 65 Web sites was published by Keystone, Kozarsky, and Freedman in 2001.17
Approximately 1 billion passengers travel by air every year. Of these, more than 50 million visit a developing country.18,19 Studies from the past 2 decades suggest that, for every 100,000 travelers to the developing countries, 50,000 will have a health problem during or after the trip. Of these, 16% will seek medical care, 10% will be bedridden, 2.2% will be incapacitated in their work, 0.6% will be admitted to a hospital, 0.1% will require air evacuation, and 1 will die.20,21 An estimated 1.9 million children travel internationally every year.22 In addition, many adults who have jobs in foreign countries now wish to have their children and other family members reside with them. As it is with nontravelers of the same ages, accidents (automobile accidents with failure to use seat belts, motorcycle accidents, and concurrent use of alcohol) are the leading cause of mortality in young adult, adolescent, and pediatric travelers.6,23,24
Infectious diseases are a major cause of morbidity among international travelers.18,21 Though one would think that experienced travelers would be the most aware, families who travel back home to visit relatives in their countries of origin have the greatest likelihood of returning home ill compared to any other category of traveler. 5,25,26 People who visit friends and relatives account for a disproportionate burden of imported illnesses compared with tourists.27 A British study showed that international travelers under age 15 years who were visiting friends or relatives as their primary reason for travel were 8 times more likely to acquire hepatitis A than like-aged tourists to the same destination.28 Although children account for only 4% of travelers, 25% of travel-related hospitalizations in the United Kingdom are for children.18 Diarrhea illnesses are the most common infirmities acquired while traveling abroad. Approximately 40% of persons traveling from industrialized to developing countries will succumb to travelers' diarrhea.18,21,29,30 Malaria is a less frequent but more life-threatening concern for travelers. An estimated 30,000 North American and European travelers contract malaria annually.31 A study from Toronto in 1998 revealed the worrisome finding that, in nonendemic centers, there is a 7.6-day delay in the onset of treatment of Plasmodium falciparum, due to a combination of factors: the failure of physicians to recognize malaria, slow and inaccurate laboratory diagnosis, and failure to initiate prompt and appropriate therapy.32 This means that physicians and other medical personnel who do not routinely deal with travel-related illnesses are often slow to make the diagnosis (or even miss it completely) and slow to begin treating diseases that are potentially life-threatening.
Although the list of all possible tropical diseases in children is quite lengthy, the list of diseases that are likely to present to the ED or office is much shorter. Nonspecific viral illness is the most common final diagnosis in pediatric patients admitted to the hospital with febrile illnessesafter traveling. "Exotic" diseases are less common. The differential diagnosis for prolonged fevers after travel in includes malaria, dengue fever, schistosomiasis, brucellosis, tularemia, leptospirosis, tuberculosis, rickettsial disease, viral hepatitis, mononucleosis, human immunodeficiency virus, and cytomegalovirus infections.33 A comparison of 3 prospective observational studies that looked at the diseases brought back by pediatric travelers returning to the United Kingdom showed that malaria was the diagnosis in 13-41% of cases, diarrhea illnesses occurred in 10-27%, hepatitis A in 3-10%, pneumonia in 3-8%, typhoid fever in 0-6%, and dengue fever in 0-6% of cases.7-9
Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report. To help the reader judge the strength of each reference, pertinent information about the study, such as the type of study and the number of patients in the study, will be included in bold type following the reference, where available. In addition, the most informative references cited in the paper, as determined by the authors, will be noted by an asterisk (*) next to the number of the reference.