The Traveler in the ED: Common Presentations
The Traveler in the ED: Common Presentations
Authors: Gary D. Hals MD, PhD, Attending Physician, Department of Emergency Medicine, Palmetto Richland Memorial Hospital, Columbia, SC; and Danielle Davis, MD, Resident Physician, Department of Emergency Medicine, Palmetto Richland Memorial Hospital, Columbia, SC.
Peer Reviewer: Fredrick M. Abrahamian, DO, FACEP, Associate Professor of Medicine, David Geffen School of Medicine at University of California–Los Angeles; Director of Education, Department of Emergency Medicine, Olive View–UCLA Medical Center, Sylmar, CA.
Regardless of where we practice, increasingly we are confronted with patients who have been exposed to unusual diseases through travel. In a previous series of articles, we reviewed the diseases associated with travel, largely based on the geography. This article reviews infectious disease associated with travel by symptoms. This is a good review both for the traveler as well as the general patient in the emergency department.
Sandra M. Schneider, MD, FACEP, Editor
About 3% of travelers report a fever during or soon after their trip. Fever is the presenting complaint in 20-28% of post-travel medical visits.1 In one British study of 1084 admitted patients, 50% of travelers had a chief complaint of fever.1 A larger study of 24,920 ill travelers found 26% of patients with fever were admitted compared to only 3% of those without fever.2 More than 17% of those admitted had a disease preventable by vaccine (e.g., Salmonella typhi, hepatitis A, influenza) or chemoprophylaxis (falciparum malaria).2
The majority of patients presenting with fever after travel will ultimately have common, non-travel related diseases, such as upper respiratory infections or urinary tract infections.3 Up to 25% of all travel-related febrile illnesses are self-limited viruses that resolve spontaneously within 48-72 hours.4 The emergency physician must identify and treat the subset of patients who present with potentially serious diseases.
Diseases that Kill Quickly.
Table 1 summarizes diseases that can be rapidly fatal. Of these, malaria is both common in returning travelers and potentially deadly when not diagnosed early. Malaria is the most common travel-related disease in febrile ill travelers.2,4,5 Overall, an estimated 10,000 cases of malaria per year are reported in travelers from industrialized countries.6 Malaria is also the most common diagnosis in travel-related admissions, and accounted for 27% of admission in one study.3 Travel to sub-Saharan Africa and Central South America is particularly risky. Accurate diagnosis of acute malaria can be notoriously difficult but should be considered in any febrile patient with history of travel to an endemic area,7 especially Africa. About 10-40% of patients with malaria do not present with fever, but have gastrointestinal (GI) symptoms, respiratory symptoms, or headache.2,8 Prophylaxis is only 80-90% effective even when taken correctly.9 Ultimately, though, malaria should be considered for any febrile traveler, and should be ruled out in any febrile traveler who requires admission. It is not unheard of for travelers to be diagnosed with malaria even though they have not been to areas where malaria is thought to exist (e.g. "runway malaria").6
After malaria, the most common diagnosis is an "unspecified febrile illness."10 These cases are presumed to be from unspecified viral illnesses.
Dengue fever is potentially deadly and is the second most common identified cause of fever in travelers in most studies.2,5,7 Dengue fever is seen more commonly in those returning from Southeast Asia and Central/South America.2 Dengue was more common than malaria in Southeast Asia by a factor of 2.5. The next most common diseases were enteric fever (typhoid, paratyphoid) and rickettsial diseases. More than 70% of the enteric fever cases were from Southeast Asia.2 Other more common diseases to consider in febrile travelers include: acute schistosomiasis, leptospirosis, viral hepatitis, and legioinelleosis.11
General Approach. A good travel-related history is essential. (See Table 2.) Incubation times can be very helpful. The history of any pre-travel vaccinations is also important. Specific exposures and the type of travel (rural, urban, business, etc.) can identify elevated risks for certain diseases.
Fever Pattern. Although they are not diagnostic alone, fever patterns can provide helpful clues to suggest specific diseases. Most physicians are familiar with the classic fever patterns of the different malarial parasites: tertian fever (fever every other day) with P. malariae and quartan fever (fever every 3 days) with P. falciparum, P.ovale, and P. vivax. These patterns are uncommon in ill travelers with malaria infection, seen in about 33% of cases.12,13
Fever patterns can be helpful with dengue fever, where the classic pattern is termed "saddleback fever." In contrast to malaria, this fever pattern is common in dengue patients with early infection.14 It refers to a fever where a brief (1-2 day) afebrile period occurs between two longer periods of fever. Saddleback fevers are also seen with leptospirosis, chikungunya fever, and brucellosis.15
When looking for fever patterns, do not forget there is normally a diurnal fever pattern, with temperatures higher in the afternoon/early evening and lower in the morning. This is an expected fever pattern and does not insinuate presence of exotic disease. With this in mind, the presence of morning fever spikes suggests typhoid fever.15
Physical Signs. The presence of lymphadenopathy or maculopapular rashes is not consistent with the diagnosis of malaria.1 Generalized lymphadenopathy can be seen with acute HIV infection, acute schistosomiasis, rickettsial diseases (spotted fevers, African tick-bite fever), and trypanosomiasis. Localized lymphadenopathy in the inguinal region suggests an STD (chancroid, herpes, syphilis, or LGV). Otherwise the presence of localized lymphadenopathy should prompt a search for skin lesions. The inoculation eschar(s) associated with rickettsial diseases (spotted fevers, typhus, African tick bite fever) develop at the site of the insect bite. A chancre at the tsetse fly bite site is seen in African trypanosomiasis. Other skin findings associated with specific diseases include the rose spots with typhoid fever, urticaria with acute schistosomiasis, and unilateral orbital edema with Chagas' disease. Maculopapular rashes can be seen in dengue fever, typhus, leptospirosis, secondary syphilis, viral hemorrhagic fevers, and African trypanosomiasis. Petechiae and purpura are findings in viral hemorrhagic fevers, meningococcal disease, and typhus.
In most febrile patients, pulse rate increases about 10-15 beats/minute for each 1°C (1.8°F) increase in temperature.1 An observed heart rate that is much slower than predicted based on this formula defines relative bradycardia. Diseases known to be associated with relative bradycardia in the presence of high fever include: typhoid fever (with morning fever spikes), early yellow fever, and legionnaires' disease.1
Hepatomegaly is associated with malaria, viral hepatitis, amoebic liver abscess, acute schistosomiasis, and typhoid fever. After acute viral hepatitis, the second most common cause of icterus in travelers is malaria.6 Splenomegaly can be seen with visceral leishmaniasis, acute schistosomiasis, as well as malaria.
Laboratory Studies. CBC with differential, basic chemistry, liver function tests, urinalysis, blood cultures, and chest radiography should be ordered. Thick and thin peripheral blood smears should be ordered to screen for malaria in patients traveling to endemic areas. One negative smear does not rule out the disease.16 The CDC recommends obtaining smears every 12-24 hours for 3 consecutive days before considering malaria ruled out.17 It is best to have the smear evaluated in a laboratory with experience in looking for malaria parasites, as many U.S. hospitals may have no previous experience diagnosing malaria. Rapid detection tests (RDTs) using antibody detection techniques exist, but only one of these tests is approved for use in the United States. Rapid tests primarily detect P. falciparum, do not distinguish between species, and are not designed to replace microscopy.
Low WBC counts can be seen in typhoid fever, rickettsial, and viral infections (e.g., dengue fever, HIV).11 Also, in malaria leukocytes are low or normal in 98% of cases.6 Anemia, thrombocytopenia, LDH, and bilirubin elevation may also be seen with malaria. Thrombocytopenia is also seen in dengue fever, typhoid fever, and viral hemorrhagic fevers.18 Severe malaria is also associated with hypoglycemia. Elevated liver enzymes can be seen in viral hepatitis, but also in dengue fever, typhoid fever, yellow fever, leptospirosis, amoebic abscess, and rickettsial diseases.19 Extremely elevated liver enzymes are most often seen in viral hepatitis and toxin damage.
Eosinophilia is defined as an absolute eosinophil count > 450/µL of peripheral blood,20 and levels are considered very high if > 3000/µL. Eosinophilia can be caused by a variety of conditions, including allergic reactions, neoplasms (leukemia), and diseases that affect various major organ systems, such as end-stage renal disease (ESRD). Patients with corticosteroid use or immunosuppression may not respond to parasites with eosinophilic reactions. On the other hand, HIV-positive patients can develop eosinophilia due to antiretrovirals, especially non-nucleoside reverse transcriptase inhibitors (efavirenz, delavirdine). HIV patients can also have eosinophilia in connection with cytomegalovirus, tuberculosis, or fungal infections.
In the traveler, the association of eosinophilia with parasitic infections is the prime concern. Helminthic parasites (worms) are most closely tied to eosinophilia. Examples of helminthic parasites include the intestinal parasites, nematodes (roundworms), cestodes (tapeworms), and trematodes (flukes). The most common to be seen in travelers are nematode skin infections causing cutaneous larva migrans. Eosinophilia can also be seen with filariasis and schistosomiasis. Eosinophilia with helminthic parasites is primarily seen during periods of tissue invasion.21 Thus patients with adult tapeworm or roundworm infections may not have any eosinophilia. Levels are at their highest early in infection when tissue invasion and larval migration are at their peak.22 Some parasitic helminthes (hookworms, ascaris, schistosomiasis, and strongyloides) migrate through the lungs during specific life cycle stages and may cause respiratory symptoms along with eosinophilia.4 Pulmonary infiltrates may be noted on chest radiograph during the migration. Eosinophilia is not associated with Giardia lamblia or Entamoeba histolytica infections.22
Traveler's diarrhea is defined as three or more unformed stools over a 24-hour period usually starting during or shortly after a period of foreign travel.23 Along with fever, it is the most common complaint in travelers, prompting the phrase "travel broadens the mind but loosens the bowels."24 The incidence varies with the area visited, but 20-50% of travelers develop symptoms on each trip,24 translating into 20 million cases annually or 50,000 cases a day.25 In 90% of patients, symptoms only last an average of 3.6 days without treatment.26 An estimated 40% of people are ill enough to alter their scheduled activities, another 30% will stay in bed, 10-15% will have symptoms lasting 1 week, and up to 2% will develop symptoms lasting more than one month.27 Ultimately, fewer than 1% are admitted, and deaths are very rare.26
Risk Factors. Where and when one travels, age, type of travel, foods consumed, and comorbid conditions all influence risk. The destination may be the greatest influence for traveler's diarrhea. Low-risk (5-8%) areas include the United States, the United Kingdom, Canada, Japan, north/west Europe, Australia, and New Zealand.28 Moderate risk (10-20%) locations include south/east Europe, Russia (and other former republics of the Soviet Union), China, Israel, Mediterranean countries, Caribbean islands, and South Africa. High-risk (20-60%) areas are Mexico, the Middle East, south/southeast Asia, South/Central America, and Africa. Seasonal impacts are also noted, with highest risk for those traveling from industrialized nations to warm/tropical areas or during the rainy season.29
Small children (< 2 years) and younger adults (15-24 years) are at higher risk.30 Adults older than 55 years have the lowest rate. Staying in rural areas (camping, adventure tours) does carry higher risk, but expensive hotels are no safer than cheaper ones.31 Recent outbreaks of viral diarrhea (norovirus) on cruise ships have been well publicized. Since many cases are due to ingestion of fecally contaminated food/water, higher risk items include raw leafy vegetables, raw or undercooked meat/seafood, unpeeled fruits, unpasteurized dairy products, tap water, and ice.32 Everyone is familiar with the phrase "don't drink the water," but it turns out food is actually much riskier than water.25 Food prepared in private homes is generally the safest, while street vendors pose the highest risk. Immunocompromised patients (ESRD, HIV, chronic steroid use) are at higher risk, and some suggest that other factors such as stress, menstruation, changes in diet, and excessive alcohol consumption also can lead to increased traveler's diarrhea.23 Medications like H2 blockers and proton pump inhibitors have been shown to increase risk for bacterial diarrhea (Salmonella, Campylobacter) by lowering protective gastric acidity.23
Microbiology. Traveler's diarrhea is bacterial in nature in 80% of cases,25 although the pathogen is only identified in about 40-60% of cases.23 Between 15-30% of cases have more than one pathogen identified. The 30% of cases where no pathogen is found are assumed to be bacterial because they respond to antibiotics.33 Of all the possible bacterial causes, enterotoxigenic Escherichia coli (ETEC) is most common and is responsible for nearly 50% of cases in Latin America, Africa, and Asia.34 Other common bacteria species include, in order of decreasing frequency, Shigella, Campylobacter jejuni, Salmonella, Plesiomonas shigelloides, noncholera Vibrio, and Aeromonas.35 Campylobacter is common in Thailand, and resistance to ciprofloxacin has emerged.36 Vibrio parahemolyticus is usually seen with shellfish ingestion and is most commonly seen in Asia.33
Viruses account for about 10% of cases. Noroviruses (Norwalk virus) have been recently associated with cruise ship travel. Rotaviruses have been shown to cause about 10% of traveler's diarrhea in Mexico.37 Viruses typically produce vomiting as well. Parasites (Giardia, Entamoeba histolytica, or Cryptosporidium) are less common than viruses but should be considered when diarrhea lasts longer than one week. Cryptosporidium is more common with travel to Nepal.38
Symptoms and Diagnosis. Bacterial cases tend to begin abruptly with crampy abdominal pain, fever, with nausea and vomiting in 10-20% of cases. ETEC usually produces acute watery diarrhea. Sudden onset of vomiting with shorter incubation times (1-2 hours) suggest disease from pre-formed toxins of S. aureus or B. cereus. Bloody mucoid stools, higher fevers, more severe abdominal pain, and tenesmus are seen more often with Shigella and Campylobacter. While less common, E. coli O157:H7 should be considered if thrombotic thrombocytopenic purpura, anemia, or acute renal failure is present. Patients with typhoid fever (Salmonella typhi) may present with diarrhea, but this is more often seen in children.24 Parasitic diarrhea tends to be more insidious in onset, with symptoms gradually developing over 1-2 weeks without fever or vomiting. Giardia lamblia infection produces symptoms of malabsorption with prolonged diarrhea (pale, foul-smelling, greasy stools), bloating, and gas. Travel to Russia has been associated with Giardia and Cryptosporidium infections.39
In some cases, more serious illness may present as "traveler's diarrhea." Typhoid fever patients may also have headache with confusion, cough, myalgias, and relative bradycardia with the fever. In addition to high fevers, malaria may present with headache, diarrhea, vomiting, and myalgias. STDs (N. gonorrhoeae or C. trachomatis) should be considered in homosexual men who present with diarrhea. Acute schistosomiasis (Katayama's fever) may cause diarrhea along with cough, fever, hepatosplenomegaly, and eosinophilia.
Diarrhea and neurologic symptoms can be seen with ciguatera poisoning and paralytic shellfish poisoning. Ciguatera is seen with ingestion of larger reef fish (barracuda, grouper, snapper). GI symptoms are followed by paresthesias and reversal of hot and cold sensation, which can last for years.40 Paralytic shellfish poisoning begins after ingestion of contaminated clams, mussels, oysters, or scallops. A few hours after ingestion, paresthesias of the mouth, face, and fingers develop along with GI symptoms. These are followed by dysarthria, dysphonia, and, in some cases, respiratory compromise.40 Food-borne botulism will present with nausea, vomiting, and diarrhea in about 50% of cases.41 Neurologic symptoms include dysphagia, dysphonia, blurred/double vision, and dry mouth. Besides home canned foods, type E botulism is associated with seafood (salmon eggs, salted fish, or seal or whale meat).42
Treatment. The majority of traveler's diarrhea is self-limiting. Those with only 1-3 days of mild symptoms (no fever, no dehydration) can safely be treated with anti-diarrheal medicines such as loperamide (Imodium). Loperamide has been shown to relieve symptoms even on the first day of use and is more effective than bismuth subsalicylate (Pepto-Bismol).43 Combined loperamide and trimethoprim/sulfamethoxazole is superior to either agent alone.44 However, trimethoprim/sulfamethoxazole along with doxycycline is no longer recommended due to widespread resistance.45 Loperamide is not recommended in children younger than 2 years due to enhanced narcotic effects. Instead, oral rehydration with a glucose- or sucrose-electrolyte preparation should be encouraged. Use of antimotility agents in general is not recommended in cases suggestive of invasive bacterial disease (high fever, bloody diarrhea).
Patients with more than 3 days of symptoms or with signs of more severe disease (fever, dehydration, bloody diarrhea) regardless of duration should be treated with antibiotics.23 Antibiotic use has been shown to reduce abdominal pain and shorten the length of time the patient is incapacitated.46 In most cases, the patient will be empirically treated. Those who do not respond to initial therapy will require further work-up. Choice of antibiotic depends on several factors: resistance, age of patient, pregnancy, and drug-drug interactions. Some authors now recommend 2-3 days of treatment with ciprofloxacin (500 mg BID or 750 mg q day) due to increased treatment failures with a single-dose regimen.25 Presumptive treatment for Giardia may be given to patients with persistent diarrhea (or suggestive symptoms) who do not respond to other antibiotics.33
In the past few years Campylobacter resistance to fluoroquinolones has emerged in Thailand and South Asia, and patients who have traveled to this region should be treated with azithromycin (1000 mg PO or 500 mg PO day one with 250 mg PO days 2-3).29 Fluoroquinolones also have known drug interactions with warfarin and phenytoin; azithromycin should be considered as alterative therapy.23 Fluoroquinolones also are not approved for use in those younger than 18 years of age, although recent studies have suggested they are safe to use in children older than 5 years of age.47 Patients treated with fluoroquinolones should be warned about potential tendon rupture. Azithromycin is also the drug of choice in pregnant patients (Category B).45 Rifaximin (Xifaxan 200 mg PO TID for 3 days) is approved for treatment of traveler's diarrhea. Rifaximin is not absorbed by the intestines. It is not currently approved for use in children (< 12) or pregnant women (Category C). Rifaximin is as effective as ciprofloxacin for non-invasive bacteria, and may be a good alternative for patients without systemic symptoms.48 A recent report describes a transdermal vaccine against E. coli traveler's diarrhea, which in early trials was 75-85% effective and also decreased duration and number of stools.49
Some chronic skin conditions can be exacerbated by travel (i.e., psoriasis). Some are due to exposure to a different climate (i.e., dry skin from very low humidity). Some may be due to phototoxicity caused by medications such as antibiotics (tetracyclines, fluoroquinolones, sulfonamides), NSAIDs (ibuprofen, naprosen), diuretics (furosemide, HCTZ), hypoglycemics (glipizide, glyburide), neuroleptics (phenothiazines), and antifungals (terbinafine, itraconazole). Although not common, photosensitivity to quinine and chloroquine (malaria prophylaxis) has been reported.50,51
Common Diagnoses. Skin problems and rashes are the third most common reason for travelers to seek health care, after diarrhea and fever.33 Table 3 illustrates the most common problems encountered. Simple bacterial skin infections from common bacteria (Staphylococcus, Streptococcus), scabies, and insect-related rashes along with urticaria are common, demonstrating that not every problem the traveler brings back will be an exotic diagnosis.
Cutaneous larva migrans ("creeping eruption") is the most common tropically acquired dermatosis.52 It is found throughout the Caribbean, Central and South America, Africa, and Southeast Asia, and is endemic to the southern and eastern coastal areas of the United States. A review of British travelers found that 32% of infections were acquired in Africa, 30% in the Caribbean, and 25% in Southeast Asia.53 It is caused when nematode (roundworm) parasites develop in moist or sandy soil and enter human skin. Dogs and cats using beaches and sandboxes as litter boxes led to an outbreak in a children's camp in Miami.54 Most often the parasites enter the feet of a barefoot person, and after a few days travel through the nearby skin causing intense itching with erythematous papules or vesicles. In the review of London travelers, 95% had beach exposure, and 39% of lesions were on the feet, 18% on the buttocks, and 16% on the abdomen.53 The skin lesions appear as wandering lines away from the entry point, and can advance 1-2 cm per day. Use of ultrasound has been described as an aid to locate intra-dermal parasites.55 Most cases resolve spontaneously but may take weeks to months for this to occur and can also lead to secondary bacterial infections. Treatment with oral albendazole (Albenza 400 mg PO q D for 3 days) or ivermectin (Stromectol 200 mcg/kg PO once) was effective in 94% of patients in one study.56
Myiasis is the clinical term for infection of the skin with fly larvae or maggots. The majority of infestations are from human botfly (tropical Latin America) or the tumbu fly (sub-Saharan Africa). Botflies can grow as large as 2 cm and lay their larvae on blood-sucking insects that unknowingly transport them to the host where they painlessly burrow through intact skin or into skin defects. They prefer the scalp, face, and extremities. Over the next 5-10 weeks the maggots develop, eventually migrate out of the host, and drop to the ground to pupate into adult flies. Most people develop a painful or itchy nodule with a central small ulcer. Patients can be treated with surgical excision of the larvae. A simpler approach is to apply a suffocating agent (bacon, Vaseline, fingernail polish, adhesive tape) over the central ulcer to force the larvae close to the surface of the skin to breathe. This may take as little as 3 hours or as long as 24 hours.57 Once there, the maggot is grasped with forceps and gently pulled from the skin. A commercial "venom extractor" or suction device can be used to remove persistent larvae when all other methods fail.58 The African tumbu fly is similar, but smaller (< 1 cm). They produce similar symptoms to the botfly and are treated likewise.
Rashes with Systemic Infections. Skin conditions that result from systemic diseases need accurate diagnosis and treatment. In one study, 10% of 269 patients presenting for skin complaints after travel to tropical areas required admission with an average stay of 5 days.59 While malaria is a common cause of disease, rash is not usually caused by malaria.
Bacterial Infections. Bacterial infections in the traveler associated with skin findings include meningitis/sepsis (Neisseria) and rickettsial infections (spotted fevers, African tick-bite fever, typhus). The classic palpable purpura of Neisseria infection is common when the patient presents with sepsis, but the bacteria can cause isolated meningitis without rash. Neisseria is associated with the "meningitis belt" in sub-Saharan Africa (highest risk in dry season of December to June), but outbreaks have been reported in a number of countries (New Zealand, Singapore, China, Norway, Canada, and Saudi Arabia).60-62 All rickettsial infections, except Q fever, are associated with inoculation eschars seen at the site of the vector insect bites. The eschars are areas of necrotic skin surrounded by a red halo and can appear at each tick bite. Between 30-50% of patients with typhoid fever develop characteristic "rose spots," or subtle, salmon-colored, blanching maculopapular lesions about 1-4 cm in size. Symptoms include fever, abdominal pain, diarrhea, headache, dry cough, myalgias, and other physical findings such as enlarged liver and/or spleen and conjunctivitis. Relative bradycardia in the presence of fever also supports the diagnosis.
Viral Infections. Several viruses can produce skin problems in the traveler, including dengue virus, Ebola/Marburg viruses, and HIV. In dengue fever, the fever and rash appear in two phases. The first phase lasts 3-7 days and is associated with high fever, retro-orbital headache, and severe muscle aches. The rash starts 1-2 days after the other symptoms, is maculopapular or scarlatinaform, and begins on the dorsum of the hands and feet. It spreads centrally, sparing the palms, soles, and face, does not itch, and occasionally desquamates. The rash is reported in 50-82% of cases of dengue fever.63 Symptoms abate for 1-2 days, then return sometimes stronger than initially, and last another 2-3 days of rash and fever. Ebola and Marburg fever have associated rashes that begin several days after other symptoms of fever, myalgias, headache, abdominal pain, and diarrhea. The maculopapular rash evolves into petechiae with spontaneous bleeding from all mucosal sites and venipuncture sites. The rash associated with HIV seroconversion (acute retroviral syndrome) is reported in about 66% of known cases, is maculopapular or mobilliform, and is located mostly on the trunk and face.
Protozoan Infections. Protozoan infection with trypanosomes can also have skin findings, both early and late in the course. Nearly all travel-related trypanosomiasis is seen in visitors to East African game parks.64 The initial skin finding is a painless chancre (or tender red nodule) where the patient is bitten about 3-7 days after the bite. The more trypanosomes transmitted by the fly, the more rapid the chancre develops. It typically lasts 1-2 weeks and is more commonly seen in travelers than in natives. Presence of the chancre can help distinguish trypanosomiasis from other travel-related diseases with similar systemic symptoms. After another 1-5 weeks, fever, myalgias, lymphadenopathy, headache, and a generalized rash develop. This rash is pruritic with erythematous papules mostly on the trunk, shoulders, and thighs. This generalized rash is seen in 50% of cases in travelers.64
Systemic Parasites. Systemic parasitic infections causing skin findings include schistosomiasis, leishmaniasis, and filariasis. Two types of skin problems are seen in early schistosomiasis: an early localized reaction and a generalized rash with systemic disease. The first is a localized papular dermatitis similar to "swimmer's itch" and represents a self-limiting inflammatory reaction at the entry site of the free-swimming flukes. It can begin a few hours after swimming, and the association with fresh water exposure can be an important clue. The generalized rash is seen only in the acute phase of schistosomiasis infection (Katayama fever). Katayama fever is thought to be an immune reaction (serum sickness) that occurs in response to the initial release of eggs into the bloodstream. Katayama fever can take 2-12 weeks to appear, and the delay in symptoms often makes the connection to fresh water exposure difficult. Symptoms consist of fever, fatigue, myalgias, urticaria, non-productive cough with patchy infiltrates on chest radiography, and serum eosinophilia.
Cutaneous/Mucocutaneous Leishmaniasis. Leishmaniasis is caused by infection with protozoans of the Leishmania species and can be visceral (most dangerous), cutaneous, or mucocutaneous. Leishmaniasis affects approximately 12 million people in the world with 90% of the cutaneous cases in Iran, Iraq, Saudi Arabia, Syria, Afghanistan, Brazil, and Peru, and 90% of the mucocutaneous cases in Brazil, Bolivia, and Peru.65 Kabul, Afghanistan has a particularly high prevalence in the population (12% overall in 1996),66 and disease is common enough in soldiers returning from Iraq and Afghanistan that it has earned the term "Baghdad boil."67 Cases in travelers to these areas have recently been on the rise, with a 5-fold increase in cutaneous disease noted in travelers returning to the United Kingdom in just 8 years (1995-2003).68 High-risk areas include rural/forested areas of South America, Central America, or Mexico.69
The protozoa are transmitted to humans via bites from sandflies, which are small enough to pass through screens and netting (< 3.5 mm). Incubation varies from two weeks to several months, but can be as long as several years.70 Lesions can be found on any area of the body, but more commonly on exposed areas (face, neck, arms, legs). They begin as a papule or nodules and develop into ulcers with well-defined, elevated margins. Unless secondarily infected by bacteria, they remain painless. Ulcers may heal spontaneously after several months, but will leave flat, depigmented burn-like scars. Spontaneous appearance of new lesions at sites of minor skin damage (abrasions, minor cuts, tattoos), i.e. the Koebner phenomenon, has also been described.72 In 2-3% of cases, untreated cutaneous disease can progress to disseminated mucocutaneous disease, but this seems to be limited to the Americas. Lesions appear in the nasal and oral mucosa and, unless treated, can destroy the lips, entire palate, and nasal septum. Besides obvious disfigurement, secondary bacterial infections can be fatal. Mucocutaneous disease is rare in travelers and only 11 cases have been reported between 2003 and 2005.73
Diagnosis is complicated as the cutaneous disease can mimic tuberculosis, mycotic skin infections, and skin cancers. Cultures are taken via punch biopsy from the border of the lesions. Serologic testing is not helpful for cutaneous disease as antibody titers are too low. Treatment is complicated and consultation with ID specialists is recommended. Only pentavalent antimonial drugs are useful in treatment. They are not widely available and have significant side effects (renal failure, hepatotoxicity, cardiotoxicity – prolonged QT intervals).74 Oral antifungals (ketoconazole, fluconazole) have been used as alternatives.68 Some returning soldiers from Iraq have been treated with localized heating (50°C).75 Fortunately, there is a vaccine in development.76
Cutaneous Filariasis. Dracunculiasis (guinea worm infection) is a problem in tropical Africa. In 2002, 71% of the cases were in Sudan alone.70 People drink contaminated water, and larvae migrate out of the intestine into the retroperitoneum where they mature. After about one year, the female worm migrates to the subcutaneous tissue (usually on the foot) where an ulcer forms. The ulcer first appears as a milky blister containing large numbers of larvae. After the blister bursts, releasing larvae back into the fresh water supply, a portion of the worm (2 mm wide, up to 1 meter long) is usually visible. In some cases, as the worm migrates to the skin, a systemic reaction of urticaria, vomiting, diarrhea, and dyspnea occurs.70 Metronidazole (Flagyl 5 mg/kg BID for 1 week) is used but is only for reducing inflammation at the ulcer site. The worm is removed by progressively winding it onto a stick, which can take a week or more. Unerupted worms are usually removed surgically.
Loiasis caused by Loa loa worms (eye worm) is localized to West and Central Africa. The worms are white and thread-like (up to 7 cm long, 0.3 mm wide), and are transmitted by day-time biting flies. While some patients are asymptomatic, others develop transient localized swellings or subcutaneous edema (Calaber swellings). Although multiple swellings can happen, they tend to occur one at a time. They are not red, may be up to 10-20 cm in diameter, and can last for several weeks. Swelling is most often around joints (wrist or knee). Worms can sometimes be visible in areas of thin skin (conjunctiva, penis, or nipple).70 A single dose of ivermectin (Stromectol 200 mcg/kg) can help decrease parasite levels but has been associated with encephalitis in patients with high parasite loads.77 Albendazole (800 mg PO q day for 3 days) with a repeat course in 2-3 months is also effective with less risk.78
Onchocerciasis (river blindness) is not a common problem for short-term travel, but does pose a risk for travelers staying more than 3 months in central Africa or South/Central America (Brazil, Columbia, Ecuador, Guatemala, Venezuela, and southern Mexico). Estimates are that 20 million people in Africa and 1 million in Central/South America have been infected.70 Onchocerca volvulus is transmitted by black flies usually found near flowing rivers and streams. Worms migrate into connective tissues and can be up to 4 cm long and 0.3 mm wide. Early signs include an itchy erythematous papular rash and if not treated, the worms coalesce into fibrous nodules usually seen over bony prominences. As the name implies, the most severe complication is when the worms enter the cornea, cause corneal fibrosis, and eventual blindness. Treatment is with ivermectin (Stromectol 150 mcg/kg) orally repeated at 3-month intervals until eye symptoms improve, or with 6 weeks of doxycycline.
Acute respiratory illnesses are very common throughout the world. They can vary from simple viral upper respiratory infections to lower tract disease (pneumonias), or in some cases represent the initial symptoms of a more unusual infection (acute schistosomiasis). Surveys of travelers have found that 10-20% of all travelers develop acute respiratory infections; 4% were diagnosed with pneumonia.79 The emergence of SARS in 2003 that originated in China and was later seen in Vietnam, Hong Kong, Singapore, United States, and Canada illustrates how new respiratory diseases can rapidly spread and affect millions of people.
In addition to infection, air pollution can cause reactive airway symptoms in patients who do not normally have these symptoms. In addition, travelers to high altitudes (> 8000 feet) are at risk for high altitude pulmonary edema (HAPE). Scuba divers who dive shortly before air travel may develop decompression illness.
As many as 10% of febrile travelers with respiratory complaints are affected by pneumonia (Streptococcus pneumoniae, Mycoplasma pneumoniae, Chlamydia pneumoniae).80 In tropical areas, influenza is a year-round infection. Further, the vaccine given in the Northern Hemisphere may not be as protective against influenza viruses circulating in tropical regions.6 Of the estimated 18,000 people hospitalized yearly in the United States with legionnaires' disease, nearly 20% are thought to arise due to travel.81 Infection with Leigonella pneumophila has been seen in association with cruise ships, whirlpool spas at resorts and hotels, and contaminated air conditioning as well as hospitals.82,83 Typically patients with legionnaires' disease have a 2-20 day incubation period, and develop fever, myalgias, and cough (dry or productive) with chest radiographic signs of pneumonia. This infection appears to be more common in middle-age or older people with underlying lung disease (COPD, smokers in general) and immunosuppresed patients.6
Less common sources of respiratory symptoms can include malaria, typhoid fever, dengue, typhus, fungal infections, early schistosomiasis, Q fever, plague (presence of buboes), anthrax, and SARS. Both coccidioidomycosis and histoplasmosis outbreaks have recently been documented in travelers to Mexico,84,85 but these infections can be hard to diagnose without bronchoscopy or serologic testing. Certain parasites (hookworms, ascaris, strongyloides) can also migrate through the lungs at a stage of development and produce respiratory symptoms with eosinophilia.
Acute Pulmonary Embolism (PE). A recent study estimated air travel increased the risk of PE 16-fold, while oral contraceptive use increased the risk 14-fold.86 Longer travel has long been associated with an increased risk for PE.87 Air travel longer than 5000 km (3100 miles) carries a risk 150 times higher than for travel < 5000 km.88 Relative venous stasis from immobilization of coach seating, low humidity, relative hypoxia, insufficient fluid intake, and the diuretic effect of alcohol contribute to this increased risk.89 Although no studies directly address obesity and travel-related PE, it is known that obesity itself raises the risk of PE 2- or 3-fold.90
Fever can be produced by PE, and this can be misleading in patients with history of recent travel. In one series, approximately 14% of patients with PE had at least low-grade fever.91 Although fever is typically low, PE is a cause of fever of unknown origin and has been reported to be as high as 40°C.92
Mental Status Changes
Patients with mental status changes can be divided into infectious and non-infectious causes. Most patients will require CT imaging of the brain, CBC, chemistry panels, urine drug screens, and possible lumbar puncture.
Infectious Causes. Cerebral malaria should always be considered if endemic areas are in the patient's itinerary. Most patients have taken inadequate or no prophylaxis.93 Patients may present with mental status changes/coma, seizures, shock, hypoglycemia. Severe malaria is most often seen with P. falciparum infection in non-immune people (i.e., travelers and children) or primigravida women. Patients will typically have been ill for several days with flu-like symptoms before developing the severe complications. The mortality of this form of malaria is 30% even with ICU care,94 and cerebral malaria is the most common cause of death in severe malaria.95
Meningitis caused by N. meningitidis is well-known in travelers to the "meningitis belt" in sub-Saharan Africa (highest risk in dry seasonDecember to June) and historically to Saudi Arabia in connection with Muslim pilgrimage to Mecca. Young children can have bacteremia, meningitis, or sepsis alone, or some combination of the three. Patients may not always present with the classic fever, headache, stiff neck, photophobia, and petechial rash. Meningitis and sepsis from N. meningitidis can kill in less than 24 hours.
A number of viruses can cause encephalitis-type illness, including Japanese encephalitis, West Nile encephalitis, and rabies. The vast majority of Japanese encephalitis virus infections are asymptomatic, but travelers can develop symptomatic disease, which can be fatal in 25%. Fever, headache, vomiting, along with cranial nerve palsies or ataxia and hyperreflexia are seen. The vaccine currently available in the United States has some side effects that limit its use to people traveling to areas of high risk/known outbreaks.
Although named for Africa, West Nile virus is found in Europe, the Middle East, Asia, the Pacific, and the United States It is related to the Japanese encephalitis virus and is asymptomatic in 60-80% of cases. Only 1% develop encephalitis that begins with a flu-like syndrome. West Nile infection can cause meningitis symptoms as well as a flaccid paralysis that follows 1-2 weeks after the illness. Serum ELISA tests can identify Japanese encephalitis or West Nile infection. Treatment for both is supportive.
Rabies, while uncommon in the United States, is a problem in many areas of the world due to feral dogs or wild animals. In 75% of cases the incubation time may be up to 90 days, and the disease is nearly always fatal. An early symptom may be paresthesia at the bite site. About 80% of cases are "furious" or encephalitic while the other 20% are "dumb" or the paralytic type. Patients with furious rabies have periods of agitation, delirium, hallucinations, and hydrophobia, while the paralytic form appears similar to Guillain-Barré syndrome with ascending symptoms. Patients with history of a dog or wild animal bite outside the United States should be treated with post-exposure prophylaxis (vaccination and immune globulin).
African trypanosomiasis (sleeping sickness) is an infection caused by the tsetse fly found in East African game parks. Patients often develop an ulcer at the bite site, and later develop fevers, myalgias, rash, and lymphadenopathy. The early disease is easily confused with malaria. Persistent headaches with the classic daytime somnolence and nighttime insomnia give the disease its name. The disease is fatal unless treated with surmain, pentamidine, efornithine, or melarsoprol (obtained through the CDC).
Non-Infectious Causes. Besides infection, a large number of problems related to recent travel can cause mental status changes, i.e., hypoglycemia in a diabetic, trauma-related events, and toxicological problems. Patients may have consumed too much alcohol. Drug smugglers (body packers) may suddenly decompensate if a packets ruptures. Anxious travelers may take too many sedatives or combine them with alcohol. Chloroquine (Aralen) and especially a newer drug taken for malaria chemoprophylaxis, mefloquine (Lariam), have been associated with hallucinations and even frank psychosis in patients taking appropriate doses.96-98 Anticholinergic medications taken for motion sickness can cause hallucinations and mental status changes, particularly in the elderly.
Time changes (jet lag) and the stress of travel can be especially hard on the elderly traveler, leading to confusion. In addition, sub-clinical systemic infections in the elderly (UTIs, pneumonia) may not present with fever or any specific complaints. Patients with underlying heart problems (congestive heart failure) may experience exacerbations from the relative hypoxia of airline travel. High-altitude travel (> 8000 feet) can also be associated with high-altitude pulmonary edema and cerebral edema, both of which can produce mental status changes. Typical symptoms are those of increased intracranial pressure (headache, altered mental status, and ataxia). Most patients with central nervous system effects will also have pulmonary symptoms, although case reports exist of patients with isolated symptoms.99 Treatment is first with descent, which usually resolves symptoms, but residual effects can be present for a week.
Frequency of Disease
When evaluating ill travelers in the ED, it is useful to know the incidence of the many possible diseases. In descending order, the most common symptoms in all travelers are diarrhea, fever, and rashes/skin complaints. Of all febrile travelers, malaria is the most common diagnosis followed by unidentified fever. However, dengue fever is a more common diagnosis than malaria in febrile travelers from Asia.
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99. Thomassen O. High-altitude cerebral edema with absence of headache. Wilderness Environ Med 2007;18:45-47.Regardless of where we practice, increasingly we are confronted with patients who have been exposed to unusual diseases through travel. In a previous series of articles, we reviewed the diseases associated with travel, largely based on the geography. This article reviews infectious disease associated with travel by symptoms.
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