Evaluation of the Ill Child Returning from Travel in Asia
Authors: Christine E. Waasdorp, MD, FAAP, Major, United States Army, Staff Pediatrician, 121st General Hospital, Seoul, South Korea; Timothy R. Hurtado, DO, FACEP, Major, United States Army, Staff Emergency Physician, 121st General Hospital, Seoul, South Korea; and Ji Yeon Kim, MD, Sincheon-dong Songpa-gu, Seoul, South Korea.
Disclaimer: The views, opinions, and findings contained in this report are those of the authors and should not be construed as official Department of the Army position, policy, or decision unless so designated by other official documentation. Citations of commercial organizations and trade names in reports do not constitute an official Department of the Army endorsement or approval of the products or services of these organizations.
Peer Reviewer: Ronald Perkin, MD, MA, Professor and Chairman, Department of Pediatrics, The Brody School of Medicine at East Carolina University, Greenville, NC.
Editor's Note
Emergency and primary care physicians are increasingly responsible for the evaluation of the recently returned ill traveler. Approximately 1.9 million children travel overseas each year.1 Many of these childrens' families participate in adventure travel in developing countries. During the past decade, Asia has seen a 32% increase in the number of visitors.2 Travel to developing countries is associated with a significant increase in travel-related illness, with two-thirds of long-term travelers reporting a minimum of one illness.3 Fifteen percent to 37% of short-term travelers also will experience one illness, with 11% of those having a febrile illness.4 One percent of ill travelers will die as a result of an infection acquired during travel.5 The longer the duration of travel, the higher the risk of infection. Risk also is associated with the destinations on the itinerary, with less developed countries holding a higher risk. After 1 month of travel without appropriate chemoprophylaxis, the incidence of infection is 1:250 in South Asia and 1:2500 in the more developed Southeast Asia.6 Of the more than 50 million people and 1.9 million children traveling to the developing world annually, approximately 8% seek care for a travel-related illness.1,5,7 Recent travel medicine data suggest that 67% of travel-related illness falls into 4 main categories: febrile illness, acute diarrhea, chronic diarrhea, and dermatologic complaints.7 Providers must be able to include travel-related illness in their differential diagnosis.
—The Editor
Introduction
The evaluation of the ill traveler must include a detailed travel history in addition to the traditional past medical, surgical, and family history. It is paramount to include the extent of travel preparation and review immunizations and compliance with prophylactic medications. The differential diagnosis can be significantly narrowed by recreating the itinerary of where the patient traveled, how long they were in each location, and what activities were completed (e.g., backcountry tours, exposure to livestock, recreational activities such as swimming in fresh water, use of intravenous drugs, tattoos, sexual activity). The list of the traveler's activities and living conditions during travel identifies possible exposures. Adventure travelers and low-budget travelers are more likely to have significant exposures than business travelers. Information about types of food and beverage consumed during travel should be reviewed. History of exposure to insects and known bites assists in determining the risk for arthropod-borne infections (malaria and dengue). Finally, exposures to bodily fluids (during sexual contact, body piercing, tattoos, and blood transfusions) must be investigated as a possible source for infection.8 Extensive travel history—including all of the above elements—will greatly assist the provider in narrowing the differential diagnosis.
Timing of the onset of symptoms often is helpful because the differential diagnosis can be narrowed by calculating an approximate incubation period. Of note, many illnesses (e.g., dengue and malaria) have variable incubation periods, therefore they cannot be excluded based on the duration of symptoms alone. One recent study of more than 17,000 ill returned travelers found that 10% did not seek health care until more than 6 months after travel.7
This paper will review the most likely diagnoses for travelers returning from Asia with fever, rash, diarrhea, jaundice or respiratory symptoms. The likely organisms will be reviewed, along with the appropriate diagnostic and treatment procedures for each illness.
Fever
Fever (a temperature of 38.0°C or higher) is a common complaint, affecting 14% to 37% of ill returned travelers, depending on the region of travel.7 Infection remains the most common cause of fever in this population, however other non-infectious diagnoses must be considered and include malignancy, connective tissue disorders, drug fevers, and thromboembolism. Clinicians should consider common causes of fever in their differential (e.g., influenza, pneumonia, gastroenteritis, urinary tract infections, skin infections) in addition to more exotic infectious etiologies.9 Historically, the most common travel-related causes of fever include malaria (27%-42%), respiratory tract infections (14%), dengue fever (8%-15%), and bacterial pneumonia (6%).10-12 However, a recent review of more than 17,000 ill returned travelers who were evaluated in travel clinics found that dengue was the most frequent etiology of fever from all regions visited except for sub-Saharan Africa and Central America.7
Ascertaining the pattern of the fever may be helpful. Classic malarial febrile syndromes include tertian fever (a fever spike every other day with P. vivax) and quartan fever (a fever spike every 3 days with P. malariae). Of note, the initial onset of malarial febrile syndromes typically does not follow a classic pattern.13 Fevers described in a biphasic pattern (a brief absence of fever between febrile periods) may be associated with dengue, yellow fever, and leptospirosis. Fever that recurs in a cyclic fashion after a number of days may be related to relapsing fever from Borrelia. Typhoid fever, yellow fever, and legionellosis may all present with relative bradycardia (less than 15 beats/minute increase for every 1°C increase in temperature).13
The initial task for clinicians evaluating a returned traveler with a fever is to exclude infections that may require immediate intervention. These include P. falciparum malaria, which can progress from minor symptoms to death within 24 hours, bacteremia with septicemia, enteric fever (typhoid and paratyphoid), meningococcemia, leptospirosis, rickettsial infections, and hemorrhagic fevers. Symptoms that should heighten clinicians' index of concern are mental status changes, focal neurological deficits, shortness of breath, hemorrhage, neutropenia, anemia, and thrombocytopenia.6,13
Laboratory tests to consider initially include thick and thin blood smears (especially if patients have traveled to a malaria endemic area), a complete blood count with a differential, a urinalysis, and blood cultures. Stool samples and liver function tests also should be considered. If the patient has respiratory symptoms, a chest radiograph should be ordered. Thick and thin smears are useful not only for detecting malaria but also relapsing fever (Borrelia) and trypanosomiasis. If malaria is high on the differential diagnosis, thick and thin smears should be obtained in a serial fashion in 8-12 hour intervals for 72 hours.14
Malaria. Malaria is classically considered the most common etiology of fever in returned travelers, although new data suggest that this is dependent on the region visited.7 It arises from a bite by a mosquito infected by the protozoan parasite Plasmodium species. It accounts for approximately 1300 to 1400 cases per year in the United States, the vast majority of which are acquired from travel abroad.14,15 Eleven percent of the malaria cases reported in the United States in 2004 were in children younger than 15 years.15 Malaria accounts for 700,000 to 3 million deaths worldwide yearly, the majority of which are children younger than 5 years (in sub-Saharan Africa alone, 90% of deaths from malaria are children younger than 5 years).13,14,16,17 P. vivax malaria should be suspected in any traveler returning from Asia and Latin America where P. falciparum is rare. Travelers who are compliant with their prophylactic antimalarial medication and who maintain vigilance with personal protective measures (e.g., bed nets, insect repellent, and appropriate clothing) have a low risk of contracting the disease.5,17 However, studies report that only 20% to 37% of U.S. citizens who acquired malaria abroad followed an appropriate Centers for Disease Control and Prevention (CDC) recommended prophylactic medicine regimen for their destination.15,18 Travelers who have the highest risk are those who spend extended periods of time in developing countries visiting friends and relatives.5,15,19
The time from infection to presentation varies with the malarial species causing infection. Travelers infected with falciparum malaria typically have symptoms within 1 month of their return (80%-95%).15,17,20 Travelers with vivax malaria often present later. More than 50% were seen more than 1 month after their return, with some patients presenting more than a year later, highlighting the need for vigilance in taking a travel history.15,17,20
Typical malaria symptoms include fever, chills, rigors, sweats, and headache. Other symptoms include flu-like manifestations, such as cough, nausea, vomiting, diarrhea, arthralgias, abdominal pain, and back pain. Children are more prone to gastrointestinal symptoms.6,16 Clinicians should maintain a high index of suspicion, even in the absence of fever, particularly in infants.
One study from Sweden found that children younger than 6 years of age had a significantly higher risk of contracting malaria than other populations (odds ratio of 4.8 with 95% confidence intervals of 1.5-14.8).21 The majority of these children are members of immigrant families who visited friends and relatives.19,21
The mainstay for diagnosing malaria is the thick and thin blood smear. Additional laboratory abnormalities include thrombocytopenia in 70% of patients (either absolute or a significant decrease from 1 day to the next) and anemia, which is seen in 25% of patients.6 Neither result is specific for malaria but should heighten clinician's suspicion in the appropriate clinical and travel setting. Health care providers can find technical support and assistance for the diagnosis of malaria through the CDC's Web site (http://www.dpd.cdc.gov/dpdx).
Treatment depends on the suspected plasmodium species and the drug resistance patterns in the source country. Ill patients should be admitted, particularly if a P. falciparum infection is suspected. These patients may progress from mild disease to severe shock in less than 24 hours. Patients are considered to have severe malaria if they have a parasitemia greater than 5% of red blood cells, end-organ involvement to include the central nervous system, shock, acidosis, or hypoglycemia.14 These patients require admission to an intensive care unit and parenteral therapy until the parasitemia decreases to less than 1% and they are able to tolerate oral fluids and medications. Clinicians should consider exchange transfusions when parasitemia levels exceed 10% or if there is evidence of cerebral malaria, even at lower parasitemia densities. Patients who experience seizures with malaria should be considered to have cerebral malaria until proven otherwise and require aggressive therapy due to fatality rates approaching 40% in untreated patients and as high as 20%-30% in treated patients.16 Appropriate consultation with an infectious disease expert or a physician experienced in treating malaria should be sought. Because of changing guidelines and updates, consultation with the CDC is recommended. The CDC Malarial Hotline can be reached at 770-488-7788 (M-F, 8 a.m.-4:30 p.m.) or after hours at 770-448-7100.
Dengue. Dengue fever is caused by a mosquito-borne arbovirus that is classically thought of as the second most common cause of undifferentiated fever in the returned traveler. There are approximately 100-200 suspected cases diagnosed in the United States each year, with the vast majority from returned travelers.22 Worldwide, dengue causes an estimated 100 million cases each year and approximately 25,000 deaths.23 Children younger than 15 years represent 90% of cases.22 Dengue should be suspected in any traveler who has returned from tropical areas worldwide, including the Caribbean, Central and South America, Asia, Australia, Oceania, and Africa. Travelers to Southeast Asia are at the highest risk.7,24 There are no immunizations or prophylaxis agents available to prevent dengue.
Dengue typically has an incubation period of 2-7 days (range 2-14 days).6,25 There are 4 distinct serotypes of dengue and infection with 1 conveys no immunity to the other 3. Dengue typically presents with fever, chills, arthralgias, severe myalgias ("break-bone fever"), severe headache, retro-orbital pain, nausea, and vomiting.25 A rash is common, occurring in up to 74% of patients.5,6 The rash typically is biphasic, starting out as a generalized blanching macular erythematous rash which then resolves. After resolution of the fever, a morbilliform, maculopapular rash with sparing of the palms and soles may be seen. Dengue may produce a non-specific febrile illness or be asymptomatic, especially in younger children as they seem to have milder attacks compared to older children and adults.6,22
Dengue fever may progress to dengue hemorrhagic fever. Infants of immune mothers, children older than 1 year, and patients with second and subsequent infections are at the highest risk.23,25 It begins as classic dengue fever; however, as the patient's fever improves (2-7 days into the illness), he develops lassitude, fatigue, and hemorrhaging. Criteria for dengue hemorrhagic fever include fever, any hemorrhage to include epistaxis and gum bleeding, thrombocytopenia (platelets of less than 100 x 109/L), and evidence of increased capillary permeability.25 The extravasation of fluids into the interstitial, pleural, and peritoneal space leads to shock. If left untreated, dengue hemorrhagic fever can develop into dengue shock syndrome. The diagnosis of dengue shock syndrome is primarily clinical, as typical assays do not return in timely fashion. Enzyme-linked immunosorbent assay (ELISA) for IgM may be used by day 6 of the illness, however cross reactivity between other arboviruses can occur. Mortality for untreated dengue shock syndrome can approach 30%, but treated patients can expect good clinical outcomes with a mortality rate of less than 3%.25
The diagnosis of Dengue is made by viral isolation (the gold standard), acute and convalescent titers drawn at 2 and 4 weeks or by polymerase chain reaction studies. These studies are unlikely to be helpful in the emergency department evaluation of the patient. Additional laboratory abnormalities include leukopenia and thrombocytopenia. One study reports that presence of fever, rash, and leukopenia made dengue infection 230 times more likely than malaria, typhoid fever, or a rickettsial infection in travelers who had returned from Asia.26
Treatment is primarily supportive. Mild dengue fever can be treated with oral hydration and pain medications. More severe forms of the disease (dengue shock syndrome) should be treated with parenteral fluids and medications. Children with moderately severe shock (defined as a pulse pressure, or difference of the systolic minus the diastolic pressure, of between 10-20 mmHg) should receive 25 mL/kg of Ringer's lactate over a period of 2 hours. Should this fail to improve their pulse pressure or if the hematocrit continues to rise (indicating worsening vascular permeability), then strong consideration should be given to using a colloid solution such as hetastarch or dextran at 15 mL/kg over 1 hour followed by 10 mL/kg over the next hour. Patients with severe shock (defined as a pulse pressure of less than 10 mmHg) should receive a colloid as their initial resuscitative fluid, then be given Ringer's lactate for maintenance fluids.27 The hematocrit should be monitored closely during the initial resuscitation phase to screen for worsening cardiovascular deterioration. Blood product transfusions (fresh frozen plasma, packed red blood cells, etc.) may be required to correct bleeding diathesis. Careful attention should be paid to intravascular volume status and electrolyte abnormalities.23,25 Overly aggressive fluid resuscitation can lead to respiratory compromise, which is a major contributor to mortality.27 Pain should be treated with acetaminophen and opioids as non-steroidal anti-inflammatory drugs may increase bleeding tendencies.
Typhoid Fever. Salmonella typhi and S. paratyphi, which cause Typhoid fever, are a common cause of febrile illnesses in travelers returning from Asia.7 The CDC receives reports of approximately 400 cases each year in the United States, primarily from ill returned travelers.28 Typhoid fever can be contracted while traveling in India, Africa, Central and South America, the Caribbean, and particularly Asia. S. typhi and S. paratyphi only infect humans and are transmitted by the ingestion of contaminated food or drink in areas with low standards of hygiene. Travelers visiting friends and relatives are at particular risk, similar to other travel-related illnesses.19
Typhoid fever has an incubation period of 1-3 weeks depending on the initial bacterial load ingested.23 Clinically, patients present with high fever, headache, abdominal pain, myalgias, and diarrhea or constipation. Constipation is more common than diarrhea in adults and older children.29 Untreated, the disease progresses to a sustained fever, relative bradycardia, splenomegaly, and in 50% of patients, the classic "Rose spots" rash develops, consisting of faint, blanching, erythematous macules on the trunk. Serious complications include hemorrhage, intestinal perforation, altered mental status, hepatitis, pneumonia, and, rarely, meningitis.6,29 Unique features in children include a higher incidence of diarrhea versus constipation, a high mortality in infants, and high rates of fecal shedding even after clinical recovery.30 Mortality is 10-15% in untreated patients, with children being at the highest risk.23 Typhoid vaccines are available, however their efficacies range from 60-90% depending on the type, so typhoid fever should remain on the differential of the returned travelers, even if they have been vaccinated.31
Diagnosis is based on isolation of the organism from stool, blood, or urine. Aspiration and biopsy from the "rose spots" also may yield Salmonella.23 Typically, laboratory studies are non-specific, however neutropenia, leukopenia, and elevated liver enzymes may be seen.6,23
Since the initial diagnosis is primarily clinical, empirical therapy may be initiated. Patients with mild disease (non-invasive gastroenteritis) should not be treated with antibiotics since therapy does not shorten the duration of disease and can prolong the duration of fecal shedding.30 Patients with significant comorbid illnesses or risk factors (infants younger than 3 months, immunocompromised patients, patients with chronic gastrointestinal disease, etc.) should receive antimicrobial therapy regardless of the severity of their symptoms since they are at risk for invasive disease and complications.30 In patients with severe symptoms (delirium, obtundation, coma, shock) corticosteroids may be beneficial. Regional antibiotic sensitivities should be considered when selecting an initial antibiotic due to increasing resistance. Typically, third-generation cephalosporins and azithromycin are the initial medications of choice.31 Continued treatment should be guided by bacterial sensitivity testing. Approximately 90% of patients can be managed as outpatients, however patients with persistent vomiting and diarrhea or abdominal distention as well as severe disease should be admitted. From 1-5% of all typhoid fever patients will become chronic carriers and continue to excrete organisms for more than one year.6,30 All patients with suspected typhoid fever should be excluded from activities that involve preparing and serving food.
Rickettsial Infections. Rickettsial illnesses, including Typhus fevers, spotted fevers, Q fever, cat scratch disease, trench fever, ehrlichiosis, Anaplasmosis, and Sennetsu fever are composed of a diverse group of illnesses from the proteobacteria class. It has been suggested that this class is an under-recognized source of illness and fever in returning travelers.6,23 A large study of more than 17,000 ill returned travelers found that this class of organisms was the fifth leading cause of fever, with particular prevalence in sub-Saharan Africa, South Central Asia, and Southeast Asia.7 Rickettsial illnesses are acute febrile zoonotic diseases transmitted by arthropod bites such as ticks, lice, flies, fleas, and mites.6,23,32,33 As such, ecotourists, backpackers, and adventure travelers are at increased risk of contracting these infections.
The incubation period for rickettsioses is typically around 14 days, however there is variability.6,33 There are four primary groups of rickettsial diseases, and while infection in one group confers partial immunity within the same group, it does not protect the patient from infection by other groups.33 Common symptoms include fever, rash (especially in the spotted fever group), headache, myalgias, and respiratory tract symptoms. A hallmark of the spotted fevers is a local eschar formation at the sight of the arthropod bite which may not be present early in the disease process.6 Regional lymphadenopathy and gastrointestinal manifestations also may be seen.
Most patients manifest only moderate to severe flu-like symptoms; however, a small subset may develop complications to include a vasculitis-like presentation that rapidly can become life-threatening.23,33 Capillary and endothelial damage lead to increased vascular permeability, edema, hypotension, and shock.34 Acute and convalescent antibody testing confirm the diagnosis in most cases. Non-specific laboratory findings include leukopenia, lymphopenia, elevated liver enzymes, and thrombocytopenia.6,34 Since no tests are available for rapid diagnosis in the acute setting, treatment usually is initiated presumptively. Doxycycline or tetracycline are the medications of choice for these infections. Early and prompt therapy will minimize the diseases' sequela. Although doxycycline is associated with dental staining in children younger than 8 years, the American Academy of Pediatrics believes the risk of morbidity from this group of illnesses outweighs the minimal risk of dental staining from a single course of doxycycline and recommends it as the drug of choice.33,34 Outcomes are best when therapy is initiated during the first week of the illness, therefore therapy should not be withheld while waiting for confirmatory tests.33
Rash
Skin lesions and rashes are frequent chief complaints in travelers returning from Asia. The differential diagnosis is large and it is important to identify and treat all significant infections and cutaneous reactions (see Table 1). Supportive care and education should be offered for the more benign conditions. A French study evaluating the frequency of diagnosis associated with travel clinics reported that 26% of the patients were seeking evaluation for a skin condition.6 Twenty-five percent of these patients were diagnosed with cutaneous larva migrans, 18% with pyoderma, 10% with dermatitis or a skin rash due to arthropod exposure, and the remaining 47% had a variety of myiasis, urticaria, cutaneous lesions of unknown etiology, and systemic infections with cutaneous findings.6 A more recent travel medicine study evaluating ill travelers in travel medicine clinics found the most common cause of cutaneous complaint was insect bites.7
| Table 1. Differential Diagnosis of Skin Lesions in Travelers Returning from Asia5 |
|
The differential diagnosis for skin rashes includes many relatively benign conditions that improve with time and minimal treatment. Sunburn is a common skin complaint in travelers resulting from inadequate UV protection and prolonged exposure. Drug eruptions are also common and frequently associated with antibiotic-mediated photosensitivity reactions. Bites and stings from arthropods can cause significant pruritic eruptions. Dermatitis can result from exposure to a large variety of items, including allergens, irritants, plants, and animals.
Elements of the travel history help to identify the likely cause of the skin rash. Exposure to fresh water presents the opportunity for cercarial dermatitis, schistosomiasis, and other parasitic sources of dermatitis. Walking barefoot or exposure to contaminated soil makes cutaneous larva migrans a possible diagnosis. History of contact with other humans requires consideration of sexually transmitted disease (STD) and infestations such as scabies and lice. Finally, insect bites reported during travel require the consideration of Dengue fever and other systemic infections with cutaneous findings.
Parasites. Travelers from Asia may be exposed to a large variety of parasites. One of the most common rashes results from exposure to hook worms, particularly those from dog and cat feces (Ancylostoma braziliense and A. caninum). The cutaneous larva migrans begins with a stinging sensation as the larvae burrow through the skin and within hours an erythematous scaly papule develops at the site of entry. A vesicular serpiginous migrating erythematous rash then appears, typically on the hands, feet, or ankles.5,35 Diagnosis is made both clinically and histopathologically with evidence of an oval track. Another common hookworm infection is caused by Necator americanus (Southeast Asia) and Necator duodenale (Northern Asia), which is spread via human feces. This extremely pruritic, erythematous, vesicular rash is found on the hands and feet. A migratory pattern is rare. Diagnosis is typically made with stool ova and parasites (O & P). Associated laboratory abnormalities include anemia and eosinophilia. Both rashes are treated with mebendazole (100 mg BID for 3 days or 500 mg once) or albendazole (400 mg in a single dose).35 Iron supplementation also is recommended to treat the anemia associated with Necatour infections.35
Strongyloides stercoralis is a helminthic infection that results from direct cutaneous exposure to contaminated soil. There is a high risk of infection while traveling in Southeast Asia, as it is endemic in the region.36 Initial signs and symptoms include a rapidly migrating (5-15 cm/hr) urticarial serpiginous rash, often starting on the feet. Patients also may develop pruritic wheals or linear urticaria.36 The rash typically lasts hours to days before subsiding and then recurs in conjunction with additional migration of the larvae.36 The clinical course also may include gastrointestinal (GI) symptoms (anorexia, weight loss, diarrhea, and constipation). If the infection disseminates, the patient may develop respiratory symptoms including cough and wheeze. Diagnosis is made with serology (CDC has capability), multiple stool samples for O & P, biopsy, and IgG levels. Immediate treatment includes symptomatic care with antihistamines for the rash and pruritis and beta-agonist for coughing. Treatment should include ivermectin (200 mcg/kg/day for one to two days) or thiabendazole (50 mg/kg/day every 12 hours for 2 days with a maximum dose of 3 grams per day).36
Gnathostomiasis spinigerum infection occurs after eating raw or undercooked food contaminated with larva. The larva perforates the gastric mucosa and migrates in the peritoneal space to the liver or to the subcutaneous fat, causing right upper quadrant pain or a migrating panniculitis. Skin lesions may occur weeks to years following the initial infection, mainly on the chest and abdomen. Lesions are ill-defined, erythematous, edematous, round, or oval shaped and often are pruritic or painful. Patients also may develop 10-15 cm plaques that occur along the migration pattern. Diagnosis is made by skin biopsy or specific Immunoblot assay looking for the 24 kDa band, which has 100% sensitivity.37,38 Treatment is with albendazole (400 mg twice daily for 21 days).37,38
Bacteria. There are approximately 110 new cases of Hansen's disease or leprosy per year.38 This is caused by Mycobacterium leprae and is transmitted from person to person via respiratory droplets. The slow-growing bacteria affect mainly the skin and peripheral nerves. The incubation period is approximately 5 years, with 1.5% of exposed individuals developing the chronic clinical infection. Presentation has a large spectrum varying from one or more well-defined, hypopigmented patches without definite anesthesia, to large symmetric areas of plaques, nodules, papules of varying sizes or, more severely, complete infiltration of the skin.38 Diagnosis is made by histologic evaluation of the skin including an acid fast stain. The World Health Organization (WHO) recommends a combination of rifampin, ofloxacin, and minocycline for treatment given in a single dose.38
In tropical climates, travelers frequently develop pyoderma and pyomyositis. Pyoderma includes the superficial skin infections folliculitis, impetigo, furunculosis, cellulitis, and erysipelas. The rashes often are the result of increased sweat production, poor hygiene, and frequent insect bites resulting in minor skin trauma. The most common bacteria associated with these infections are Staphylococcus aureus and Group A Streptococcus (GAS). The diagnosis is made clinically and treatment includes topical or oral antibiotics depending on the severity of the infection. More concerning is pyomyositis, an infection starting in the skin and spreading down to the skeletal muscles. The primary symptoms of the infection are myalgias, fluctuant swelling, and erythema. The diagnosis is made by aspirating purulent material from the fluctuant area. Treatment involves incision and drainage of the infected area and antibiotics to cover the likely staphylococcal infection.
Other bacterial infections that present with rash include meningococcemia (palpable purpura and petechiae, classically on the lower extremities), rickettsial infections (eschar develops at the bite site followed by a maculopapular eruption of the distal extremities that subsequently becomes generalized), and other common systemic infections with cutaneous findings.33
Viruses. Many systemic viral infections cause typical findings on the skin exam. Dengue fever presents with a macular or a maculopapular erythematous rash that blanches under light pressure.22 Enteric fever caused by Salmonella typhi or Salmonella paratyphi presents with rose spots, which are evanescent groups of 2-3 mm pink macules on the chest and abdomen seen in 30-74% of infected patients.4,5,6,31 Viral hemorrhagic fever and hemorrhagic dengue can present with petechiae, ecchymosis, and hemorrhage.22 Returning travelers also may present with a benign viral exanthem following exposure to common upper respiratory or enteric viral pathogens (adenovirus, enterovirus, etc.).
Fungus. There are two main patterns of fungal infection to be considered in the returning traveler: superficial cutaneous and deep cutaneous.5 Superficial cutaneous infections frequently follow travel to humid tropical climates. The infections may involve the nail (onychomycosis) and the skin (Tinea capitis, Tinea corporis, Tinea pedis, and Tinea versicolor). Most emergency and primary care providers are familiar with making the diagnosis and selecting treatment with topical or systemic anti-fungals. Travelers to tropical climates with vulvovagnitis are likely to have Candida albicans overgrowth. Women and girls on oral antibiotics for prophylaxis are at high risk for this infection.
Deeper cutaneous fungal infections usually result from the traumatic exposure with broken skin. Presentation often is a painless nodule or papule that may ulcerate. Diagnosis is made by biopsy of the affected area.5 Treatment involves excision of the implanted material followed by oral antifungal agents.5
Infestations. Infestations occur after exposure to infected people or bedding. Scabies, caused by Sarcoptes scabiei, presents with itching, excoriation, and erythematous papules and vesicles. Diagnosis is made by visualization of mites on a skin scraping. Exposure to Pediculosis humanus (lice) results in pruritis and excoriated papules over the affected area. Lice are diagnosed by visualization of the louse and the nits. The treatment of choice for both infections in children is permethrin, as it is less toxic than lindane.39
Diarrhea
Thirty to 50% of travelers to the developing world experience gastrointestinal complaints.40,41 The CDC has ranked Asia as a high- risk area for the development of traveler's diarrhea, with the highest risk being in the months immediately preceding the monsoon season.42 Gastrointestinal infections can be divided into acute infections with a duration of less than 2 weeks and chronic infections with a duration of greater than 2-4 weeks.23
Acute Diarrhea. Diarrhea may result from bacterial, viral, protozoal, or toxin mediated infection of the gastrointestinal tract. Bacteria remain the most common etiology, causing 50-85% of cases, although recent studies show that parasites may be a larger percentage in South Central Asia travelers .7,43 It is important to identify and treat invasive bacterial diarrhea, which presents with sudden onset of diarrhea, cramping, urgency, watery stools, fever, and possibly bloody stools. Invasive bacteria such as Shigella, Salmonella, Campylobacter aeromonas, Escherichia coli, and Clostridium difficile are associated with bloody diarrhea and may require antibiotic treatment.
This is a paradigm shift from the approach to diarrhea in a child who has not been traveling, where antibiotic treatment often is not warranted. In the non-traveler population, viruses account for 60% of acute gastroenteritis, with bacteria as the source in 20% of cases, and parasites in 5%.44 Given the majority of acute gastroenteritis is viral and many bacterial infections become chronic carrier states when treated, treatment rarely is first-line. The travel population is significantly different with a much higher percentage of children infected with bacteria and parasites.
Traveler's diarrhea frequently results from non-invasive bacteria, viruses, or less commonly, parasites. In children, traveler's diarrhea is defined as 3 or more unformed stools daily in addition to symptoms of fever, nausea, vomiting, abdominal pain, or tenesmus. Very young children will demonstrate a two-fold increase in bowel movements with or without the additional symptoms. Oral antibiotics have been shown to shorten the duration of severe diarrhea. Treatment with azithromycin (10 mg/kg/day for 1-3 days) in children younger than 18 years, and ciprofloxacin (500 mg twice daily for 3 days) in those 18 years and older should be con-sidered.41 Diarrhea lasting more than 7-10 days should be evaluated with a stool culture, O & P, and Giardia antigen testing.
Other organisms associated with acute diarrhea are Vibrio cholera, Giardia lamblia, hepatitis A, hepatitis E, Cryptosporidium, Cyclosporiasis, and Entamoeba histolytica. Cholera is caused by the bacterium Vibrio cholerae, with epidemics occurring after flooding or disturbance of water sanitation systems. Severe infection is characterized by painless, profuse watery diarrhea ("rice water stools") resulting in severe dehydration. It also is associated with leg cramps, vomiting, and sometimes fever. Diagnosis is made by stool culture. Treatment requires aggressive hydration and trimethoprim-sulfamethoxazole (TMP-SMX) (5 mg/25 mg/kg orally twice daily for 3 days).22,45 Close contacts should receive prophylaxis with tetracycline.23
Giardia lamblia is another common cause of diarrhea in travelers, especially adventure travelers. Giardiasis presents with abdominal cramping, flatulence, and foul-smelling, watery diarrhea without blood or mucus. Chronic infections may result in weight loss, lactose intolerance, and anemia. Diagnosis is made by stool antigen testing.46 Treatment is with metronidazole (15 mg/kg/24 hrs orally divided 3 times daily for 5 days).46 Historically, parasites account for less than 5% of acute diarrhea associated with travel.23 More recent travel medicine data show parasites are more common than bacteria in travelers returning from South Central Asia, likely a reflection of travelers using antibiotics prior to seeking medical evaluation.7 Possible parasites specific to Asia include: Entamoeba histolytica, Ascariasis lumi, Giardia lamblia, Cryptosporidia parvum, Cyclospora cayetanensis, Trichinella, Schistosoma mekongi, and S. japonica.
Antibiotic-induced diarrhea also must be considered. Ten to 15% of people taking antibiotics will develop diarrhea.47 This often is seen in patients taking doxycycline for malaria prophylaxis with the resultant change in gastrointestinal flora. The diarrhea will resolve with cessation of antibiotics and return of the normal flora. The risk of an invasive bacterial infection including Shigella, Salmonella, Campylobacter, and E. coli is increased when intestinal flora have been altered by antibiotics. Bloody diarrhea or prolonged diarrhea without treatment should alert the provider to this possibility.
Chronic Diarrhea. Diarrhea lasting greater than 2 weeks occurs in 10% of travelers experiencing diarrhea, with 3% having diarrhea for greater than 4 weeks.5 Persistent diarrhea can be the result of a chronic or inadequately treated infection, unrecognized gastrointestinal disease, or a post-infectious process resulting in weeks to months of diarrhea.
Unidentified and untreated bacterial and parasite infections most often are responsible for persistent diarrhea in returned travelers.6 Given that many travelers now are prescribed antibiotics during their pre-travel health assessment to self-medicate for severe diarrhea, bacterial pathogens are less likely and the parasites are increasingly the source of the infection.7
Chronic gastrointestinal disease may manifest at the time of return from travel, complicating the differential diagnosis. Patients with diarrhea containing blood or mucus, or those experiencing abdominal pain, weight loss, and other systemic symptoms may require evaluation for inflammatory bowel diseases and celiac sprue. Additionally, recent studies have shown an increase in the diagnosis of irritable bowel syndrome (IBS) following diarrhea associated with travel.6,48 It has been estimated that 31% of patients will experience IBS in the post-infectious gastroenteritis period.5 Women and patients with significant psychosocial issue are at higher risk.5 Other considerations include lactose intolerance, bacterial overgrowth, and neoplasm.
The evaluation of chronic diarrhea requires multiple fresh stool samples (3-4) to be tested for ova and parasites, microscopic evaluation, stool culture, hemoccult, fecal leukocytes, and serology as appropriate.8 Blood also should be tested to assess for anemia and eosinophilia, associated with chronic helminth infections and bowel inflammation. Serology is the key to the diagnosis of Strongyloides, Amebiasis, cysticercosis, schistosomiasis, and trichinosis. Stool antigen studies should be completed to screen for Giardia lamblia and Amebiasis.
Hepatitis/Jaundice
The most likely cause of acute hepatitis and jaundice in child travelers is viral hepatitis A. This infection is decreasing in occurrence following the recent increase in hepatitis A vaccination, which now is initiated at 12 months of age. The other types of viral hepatitis, including hepatitis B, hepatitis C, and hepatitis E, are seen less frequently. Several other infectious causes have been identified as a potential source of hepatitis in the returning traveler. Malaria infection with high parasite loads can cause hepatitis and jaundice. Typhoid, dengue fever, rickettsial infections, Leptospirosis, and liver flukes also must be considered in the differential diagnosis. Finally, many medication and herbal remedies cause case hepatitis and all medications should be reviewed during the evaluation.
Respiratory Symptoms
When a traveler returning from Asia presents with significant respiratory symptoms, causes such as tuberculosis, avian influenza, SARS, and parasitic infections must be considered in the differential diagnosis. However, common infections caused by viral pathogens S. pneumoniae and mycoplasma should not be discounted. Air pollution is a worldwide problem prevalent in much of Asia, and potentially may lead to post-infectious and allergic bronchospasm in travelers, especially in patients with a history of asthma.5
Bacterial. Tuberculosis. The annual incidence of tuberculosis per 100,000 people is more than 300 in Cambodia; 100-300 in China, Mongolia, and North Korea; and 50-100 in Japan and South Korea. Areas of China demonstrate high rates of multiple drug-resistant tuberculosis.49 Thus, when a traveler returning from Asia presents with cough, fever, diaphoresis, weight loss, and malaise, tuberculosis must be ruled-out.22 Cough associated with tuberculosis initially may be non-productive, but it typically becomes purulent and then blood streaked.50
Travelers who spend significant amounts of time in closed environments (prisons, hospitals, or homeless shelters) are at high risk. Although tuberculosis generally is transmitted through the air, there are documented cases of transmission through unpasteurized milk or milk products from infected cattle.51
Definitive diagnosis is made by the isolation of Mycobacterium tuberculosis via culture from gastric aspirates, sputum, bronchial washings, pleural fluid, CSF, urine, or other body fluids.52 The tuberculin skin test may be helpful in identifying infected individuals, however 10-15% of immunocompetent children with culture-proven disease initially do not have a positive skin test.50,52
Active tuberculosis should be referred to the appropriate specialist to determine the most current multi-drug regimen. The CDC website (http://www.cdc.gov/nchstp/tb/default.htm) maintains the latest guidelines for the treatment of tuberculosis, which is rapidly evolving with the changing resistance patterns worldwide.
Viral. Severe Acute Respiratory Syndrome (SARS). SARS, caused by a coronavirus, manifests as an atypical pneumonia in all age groups.53 It became an international health threat in 2003 with confirmed cases in mainland China, Hong Kong, and Taiwan.54 The disease also has been documented in Vietnam and Singapore.53 During the initial outbreak in 2003, 8 people in the United States had laboratory confirmed SARS, none of whom died. All were ill returned travelers who had visited endemic areas.55
The primary mode of transmission is via direct or indirect contact of mucous membranes (eyes, nose, or mouth) with respiratory droplets from an infected person. The incubation period is 2-7 days and may spread to contacts of affected patients for 10 days. Patients present with fever, cough, shortness of breath, headaches, myalgia, and sore throat. Gastrointestinal complaints are seen in approximately 10-20% of patients. The lung exam may reveal rales and rhonchi. Eighty percent of patients have an oxygen saturation of less than 95%. Because no single symptom or sign is diagnostic or highly suggestive, providers must maintain a high index of suspicion.53
Pulmonary infiltrates are noted on chest radiographs in all patients; however, initial studies may be non-specific. Severe cases typically progress to acute respiratory distress syndrome with extensive bilateral consolidations. Laboratory tests are available to detect the SARS-associated coronavirus (SARS-CoV), including PCR testing, serologic testing, or viral cultures.23 Nonspecific laboratory abnormalities include lymphopenia, modest elevations in alanine aminotransferase, creatine kinase, D-dimers, and activated partial thromboplastin time.
Initial treatment is similar to all community-acquired pneumonia with ventilatory support and broad-spectrum antibiotics until a definitive diagnosis is made.55 SARS-specific therapy is controversial.53
Avian Influenza. Avian influenza (H5N1) is a common organism found in wild birds worldwide. The first cases reported in humans were in 1997 in Hong Kong. Outbreaks of avian influenza (H5N1) in humans have occurred in Thailand, Vietnam, Indonesia, Malaysia, China, and Cambodia.49 Travelers to affected countries who have direct contact with infected poultry, their droppings and secretions, or undercooked poultry products are at risk of infection.56
Avian influenza (H5N1) has an incubation period of approximately 3 days and the illness usually persists for 5-24 days. Symptoms include fever and predominately lower respiratory tract symptoms. Gastrointestinal complaints are more common than in other human influenza illnesses. Conjunctivitis, which has been reported with other avian influenza viruses infecting humans, is uncommon.57
The incidence of minimally symptomatic and mild disease in humans is unknown. Patients with severe infections often develop respiratory distress and require mechanical ventilation.58 Overall the mortality in severe infections is approximately 50%, with children having the highest risk.57
The definitive diagnostic test is a positive viral culture, however cultures are not routinely recommended due to the high risk to laboratory personnel.56 Reverse transcriptase polymerase chain reaction is the preferred test. A four-fold increase in serum neutralizing antibody titer toward the presently circulating genotype of avian viruses also is confirmatory.59
Treatment primarily is supportive with early, aggressive ventilatory assistance. Oseltamivir, an oral neuraminidase inhibitor, is the drug of choice. Zanamivir also may be used, however the older M2 inhibitors amantadine and rimantadine should not be used due to high viral resistance.58,60
Hanta virus. Hantaviruses are rodent-borne RNA bunyaviruses with several known serotypes. There are two major clinical syndromes: hemorrhagic fever and the hantavirus pulmonary syndrome. The hantaviruses known to cause serious hemorrhagic fever associated with a renal syndrome are primarily found in Korea and China. The Seoul viruses (less severe forms) also are found in Korea and China as well.61 These pathogens are transmitted by infected rodents via their contaminated urine, droppings and saliva. Travelers may be infected by contact with infectious aerosols or with direct contact with infectious materials on broken skin or mucous membranes.62 The initial presentation is a flu-like illness of 3 to 4 days duration, which then rapidly progresses to pulmonary edema, hypoxia, hypotension, tachycardia, and metabolic acidosis. Laboratory abnormalities may include thrombocytopenia, azotemia, and proteinuria.23 Diagnosis is made serologically, with the vast majority of patients having both IgM and IgG antibodies by immuno-histochemical staining or by PCR amplification.61 Treatment consists of supportive care measures with careful attention to volume status as a significant contributor to mortality is overaggressive resuscitation.23
Other Etiologies
Additional diagnoses to be considered in the traveler returning from Asia with respiratory symptoms include the common viral upper respiratory infections, human influenza, and the less common Legionella and parasitic pulmonary infections. In tropical climates, influenza is seen year-round. These patients present with the typical influenza symptoms and may respond to amantadine and rimantadine if initiated in the first 48-72 hours of the infection. Legionella should be considered in patients with risk factors of smoking and exposure to aerosolized water sources. Prominent symptoms include a dry cough with fever, and gastrointestinal complaints are common. The chest radiograph classically demonstrates progressive alveolar infiltrates.63 Diagnosis is made by culture or by using the less sensitive urine antigen test. The drug of choice for treatment is erythromycin. Finally, and less likely, are the parasites that migrate from the gastrointestinal tract to the pulmonary airways. These infections often present with hemoptysis or rusty sputum.64 Chest radiographs demonstrates patchy infiltrates or radiolucencies in the mid-lung fields.64 Diagnosis is made by visualization of the trematode or eggs on fecal smears, ELISA, or by antigen detection. Treatment is with praziquantel (25 mg/kg/day divided three times days for three days).23
Conclusion
The emergency and primary care physician will be increasingly required to evaluate the ill returning traveler from Asia and other areas of the world. During this evaluation the provider must identify life-threatening and serious infections and conditions that require immediate treatment, stabilization, and hospitalization. Referral for expert consultations also should be made for those patients who require additional evaluation, but are stable for release following the initial evaluation. Providers must be able to include travel-related illness in their differential diagnosis and should understand the initial evaluation and treatment options.
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The evaluation of the ill traveler must include a detailed travel history in addition to the traditional past medical, surgical, and family history. It is paramount to include the extent of travel preparation and review immunizations and compliance with prophylactic medications.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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