Chapter 161: Global Travelers

Of returning travelers who become ill, many have neither serious nor exotic illnesses.¹ The most likely causes of acute symptoms are common problems such as upper respiratory infections, diarrheal illnesses, or reactions to stress, fatigue, or new medications. The ED physician often does not confirm the final diagnosis, but rather protects the health of the public from potentially communicable diseases, begins diagnostic and therapeutic interventions, and provides appropriate referral. Local or regional international health clinics are good resources for referral of patients who need more advanced evaluation, serologic testing, and long-term follow-up (see http://www.travelersvaccines.com/).

Key points for the initiation of ED care are the following:

1. Isolate and use personal protective precautions early when evaluating patients with suspected travel-related infections.

2. Most travelers do not have exotic diseases; think of common causes.

3. Malaria lurks in the febrile patient returning from travel, even in the presence of prophylaxis.

RISK ASSESSMENT

Of travelers, 64% report one or more illnesses during travel, 26% are ill upon return, and 56% of those ill upon return develop symptoms after arrival in the United States.² Many disease incubation times are longer than the transit times.

Most travelers on vacation or business are abroad for <20 days, and <5% spend extended time overseas. Some travelers originate from disease-endemic nations, as tourists or newly arrived immigrants; these people are at risk of illness due to transit and exposure to areas with high rates of endemic infectious disease. Others at risk include nonvoluntary travelers, such as refugees and displaced persons, as well as landed immigrants returning from visiting their homeland. In all extended-duration travelers, consider endemic illnesses, even if they lived in the area previously. Travelers also have a risk of tropical illness due to increasing adventure-type travel to areas that were previously inaccessible (Table 161-1).

Diseases such as malaria are uncommon in the United States but are leading causes of mortality overseas. Other parasitic agents, such as helminths and rickettsia, also occur with increased frequency and severity in the tropics (see chapters 158 and 160, "Malaria" and "Zoonotic Infections"). Diagnosis of a tropical infection requires a unique set of tests, and therapy is organism specific.

Think of a potential bioterrorist agent as a cause of disease when factors suggest intentional release, such as divergence of the disease presentation from the typical epidemiology of the community and an atypical number of patients presenting with similar clinical syndromes. Examples of diseases that could be weaponized include anthrax, plague, viral hemorrhagic fevers, and tularemia (see chapters 9, "Bioterrorism" and 160).

INCUBATION PERIOD

The approximate incubation period (the time between exposure and signs and symptoms) can be helpful in assessing illness risk. For example, if fever begins >21 days after return or infected patient contact, yellow fever, viral hemorrhagic fevers (including Ebola, covered elsewhere), and other arboviruses (e.g., dengue fever) are unlikely, irrespective of the exposure history (Table 161-2). In comparison, schistosomiasis may cause symptoms 5 weeks after exposure. Many diseases have variable incubation depending on factors such as host immunity and the use of chemoprophylaxis and antipyretics.

HISTORY

Suspect imported disease in recent world travelers, and direct the history appropriately (Table 161-2 and Table 161-3). Note previous medical conditions because immunosuppression, age <5 years, advanced age, pregnancy, and diabetes often render the patient less tolerant of tropical infections.

Ask about the duration of travel (suggesting specific disease incubation periods) and destination or origin (suggesting possible cause), which can focus the differential diagnosis (Table 161-4). Other important considerations are the living conditions and locale of the traveler (rural areas have greater infectious risks of certain diseases), type of accommodation, and travel-related activities (suggesting possible exposure, Table 161-5).

Review any pretravel immunizations and preventive medications, high-risk behaviors, and prior medical conditions. Immunization history is relevant because proper vaccination against hepatitis A, hepatitis B, and yellow fever can effectively rule these out as causes of illness. Adherence to appropriate chemoprophylaxis reduces the risk of acquiring malaria—which is the most important tropical emergency—yet it cannot eliminate the possibility. Because of increasing malaria resistance, assume that the febrile returning traveler has malaria even if chemoprophylaxis was correctly taken.

A history of medications, herbs, and traditional medicines consumed is also useful information, because these may contain antipyretics that can alter disease presentation. If altered mental status exists, suspect cerebral malaria or meningitis and consider early empirical treatment for both until the diagnosis is confirmed.

PHYSICAL EXAMINATION

When assessing vital signs, consider that antipyretics can mask fever. Evaluate the abdomen for hepatosplenomegaly or focal abdominal discomfort. Examine for lymphadenopathy and inspect the skin for rashes, lesions, or pallor. Ophthalmologic examination for scleral icterus, conjunctival injection, or petechiae helps detect causes. Imported diseases should be suspected in the presence of high fever, signs of hemorrhage, diarrhea, shortness of breath, skin lesions, and neurologic disturbances. Table 161-6 lists other signs of tropical illness.³

Usually one or more hallmark symptoms or signs are associated with specific infections, allowing categorization. These include fever, CNS complaints, abdominal pain, diarrhea, skin and eye complaints, and respiratory symptoms. It is important to identify diseases that may be rapidly fatal, easily treatable, and/or potentially contagious.

LABORATORY TESTING

Initial studies include a CBC with differential and platelet count, hepatic function tests, and urinalysis; thick and thin blood smears for malaria (and rapid antigen detection test); blood cultures, urine cultures, stool cultures, and stool analysis for WBCs, ova, and parasites; and a chest radiograph for fever and cough. The absolute eosinophil count is often elevated to >500/mm³ in parasitic diseases caused by worms. In a clinically well-appearing patient in whom malaria treatment is not begun but malaria is suspected, obtain blood for smear every 12 to 24 hours. Specific serologic tests are deployed selectively, such as erythrocyte sedimentation rate, purified protein derivative, syphilis test, human immunodeficiency virus test, and serology for arboviruses or rickettsiae.

Consult an infectious disease specialist early in the evaluation to optimize testing and follow-up. It is also wise to obtain an extra vial of serum in a red-top tube (for serology and immunology) during the initial evaluation. This specimen can be used later for comparison with convalescent-stage specimens.

Although fever is nonspecific, it raises the suspicion for a serious infection (Table 161-7).^4,5 Patients with fever after tropical travel have malaria until proven otherwise. Other common serious infections are listed in Table 161-8.^6,7

MALARIA

The classic clinical triad for all species of malaria is fever, splenomegaly, and thrombocytopenia.^8,9 Fever is typically irregular for the first week and later may demonstrate periodicity. Patients usually have continuous symptoms initially followed by episodic pyrexia every 2 to 3 days, depending on the infecting species. Periodicity is unusual with falciparum malaria. Serious malaria infections occur primarily in young children, pregnant women, the elderly, individuals never previously infected, and patients with comorbid medical problems. Because associated symptoms such as headache, cough, and GI problems mimic other conditions, malaria is a consideration in all febrile travelers.

Diagnosis is based on clinical presentation and confirmed with laboratory evidence of bloodborne protozoa. Patients with fever >38.5°C (101.4°F) of unclear origin and recent or past travel to an endemic area should be screened by blood smears and rapid antigen detection tests when available. Refer to chapter 158 for a detailed discussion of malaria diagnosis and treatment.

DENGUE FEVER

Dengue is the most serious febrile tropical disease after malaria. The World Health Organization reported a 30-fold increase in incidence of dengue in from the 1960s to the 2010s, with up to 50 million cases occurring annually worldwide.¹⁰ Suspect dengue fever among travelers with fever developing within 2 weeks of travel. Dengue may be contracted more than once because each of the four strains offers no cross-protective immunity. Many cases are self-limiting, and the illness is not reporTable in the United States.¹¹

Dengue fever occurs in urban environments in most tropical nations and is transmitted by the peridomestic day-biting Aedes aegypti mosquito. Urban dengue in the Americas, Africa, and the Indian subcontinent is usually classical dengue fever, whereas in Southeast Asia, it manifests as hemorrhagic fever and shock. Classic dengue fever presents after a typically short incubation period of 4 to 7 days with sudden high fever, headache, nausea, vomiting, myalgias, and rash usually lasting several days. Facial flushing, conjunctival injection (although uncommon), and retro-orbital pain can occur. After defervescence, a fine, pale, morbilliform rash develops on the trunk and spreads to the extremities and face. Small children may only present with a mild upper respiratory infection, and classic dengue may be confused with influenza, measles, or rubella. Although other causes of fever can present with a similar clinical picture, such as West Nile fever (transmitted by the Culex mosquito), West Nile fever causes lymphadenopathy, which is usually absent in dengue. Dengue can also cause petechial hemorrhages indistinguishable from meningococcemia.

Dengue hemorrhagic fever preferentially occurs among infants of immune mothers, children >1 year old, and those with second and subsequent infections. It begins as classical dengue with fever and myalgias. After 2 to 7 days, as pyrexia improves, lassitude, fatigue, and shock develop with an ensuing mortality that is >10%. Clinical features include pleural effusions and bleeding diathesis with epistaxis, purpura, petechia, and marked thrombocytopenia with elevated hematocrit because of vascular permeability. Dengue hemorrhagic fever may rapidly evolve into dengue septic shock, which is often fatal. Dengue septic shock is heralded by abdominal pain, severe emesis, mental status changes, and alternating severe pyrexia and hypothermia.

Diagnosis of dengue is based on clinical findings; although serology is confirmatory, cross-reactivity often occurs with other flaviviruses. Enzyme-linked immunosorbent assay provides rapid confirmation of infection by day 6 of the illness. Laboratory abnormalities include leukopenia, thrombocytopenia, and hepatic dysfunction. In uncomplicated dengue fever, treatment is supportive and consists of fluids and analgesics. Only acetaminophen is recommended for managing pain and fever because aspirin and other nonsteroidal anti-inflammatory drugs are contraindicated due to anticoagulant properties.

TYPHOID FEVER

Enteric fever, or typhoid fever, is a serious infection diagnosed in roughly 400 travelers annually returning to the United States, with an additional 100 cases of paratyphoid. Typhoid and paratyphoid are caused by Salmonella typhi and Salmonella paratyphi, respectively.¹² Once malaria is excluded, typhoid fever is commonly the cause of a febrile illness lasting >10 days.¹³ Imported cases occur in visiting friends and relatives and travelers from Mexico, Indonesia, Peru, and the Indian subcontinent. Vaccination before travel helps thwart acquisition, although protection wanes with time and revaccination is required.

The disease is transmitted in a dose-related fashion after food contamination by feces or urine from actively infected cases or healthy disease carriers. Incubation times and disease severity vary from 1 to 3 weeks. After ingestion, bacteria adhere to the small bowel mucosa, invade lymphoid tissues, and disseminate by lymphatics to the bone marrow, gallbladder, and spleen to reproduce in macrophages. Most pathology occurs in the gut as a consequence of inflammation, necrosis, and ulceration. Typhoid fever classically begins with fever and headache, and then progresses to high fever with chills, headache, cough, abdominal distention, myalgias, constipation, and prostration. The differential diagnosis includes malaria, typhus, viral hepatitis, amebic liver abscess, and other types of infective enteritis. In epidemics, patients can present with acute diarrhea and vomiting, headache, and meningeal signs. Most patients, however, present with constipation rather than diarrhea. Bradycardia relative to fever is classic (but may be absent); after several days of fever, a pale red macular rash may appear on the trunk (rose spots) among fair-skinned individuals. As the disease progresses, splenomegaly develops. Patients may develop leukopenia and elevated liver enzymes, although most cases have nonspecific laboratory values. Complications include small bowel ulceration, anemia, disseminated intravascular coagulopathy, pneumonia, meningitis, myocarditis, cholecystitis, and renal failure. Sequelae include deafness, and neurologic involvement including psychosis, ataxia, and seizures can occur.¹⁴

Diagnosis is clinical and confirmed by culturing blood, urine, or stool (during the second week) or by rapid antigen testing. Although most cultures have a moderate yield, bone marrow culture is most sensitive, and organism identification is possible after antibiotic treatment.

Current treatment recommendations for typhoid fever include fluoroquinolones (ciprofloxacin), cephalosporins (cefixime and ceftriaxone), or azithromycin, with duration of treatment dependent on severity of illness. Currently, ampicillin, trimethoprim-sulfamethoxazole, and chloramphenicol are unreliable due to resistance. Nalidixic acid–resistant S. typhi strains are also associated with fluoroquinolone resistance; these organisms are found in both India and Southeast Asia. If typhoid meningitis is suspected, administer dexamethasone, 3 milligrams/kg IV loading dose over 30 minutes, followed by 1 milligram/kg IV every 6 hours for eight doses in addition to antibiotics. Supportive treatment includes IV rehydration and blood transfusion (if needed from GI losses). Untreated, mortality is 10% to 15%, mostly in young children.

RICKETTSIAL SPOTTED FEVERS

Rickettsial spotted fevers are transmitted by the bite, body fluid, or feces of ixodid arthropod ticks, and the ticks are widely globally distributed. Fleas and mites also transmit rickettsial infections. Among the eight major rickettsial infections, there is great variation in severity. Mortality without treatment approaches 25%, which is lowered to 5% with treatment (see chapter 160). Suspect scrub typhus (Rickettsia orientalis) after rural travel in the Asia-Pacific region and maritime Russia and African tick typhus (Rickettsia conorii var. pijperi) after travel to sub-Saharan Africa or the West Indies.

Scrub Typhus and African Tick Typhus

The mite bite, in the case of scrub typhus, or tick bite, with African tick typhus, may go unnoticed. After 3 to 14 days of incubation, patients develop fever, malaise, myalgias, severe headache, rash, nausea, and vomiting. The rash may be absent. Scrub typhus is characterized by a papule at the bite site. The papule later becomes necrotic and forms a crusted black "tache noire" eschar. As organisms disseminate, patients develop fever, malaise, headache, lymphadenopathy, and splenomegaly. African tick typhus presents like scrub typhus, but with much less severe symptoms and localized lymphadenopathy associated with an eschar. Diagnosis is clinical, and serologic tests are confirmatory. Doxycycline, 100 milligrams PO twice daily for 7 to 10 days, is the empirical treatment of choice, and chloramphenicol is an alternative. African tick typhus requires only 3 days of therapy and is often self-limited even without treatment. In severe cases of scrub typhus, death occurs from a multiorgan toxemia within 1 to 2 weeks of illness onset if untreated. Continue treatment for at least 5 days and for 48 hours after defervescence.

Typhus (Epidemic Louse-Borne Typhus)

Typhus is a rickettsial louse-borne disease caused by Rickettsia prowazekii. Typhus is a different disease from the bacterial disease due to S. typhi, typhoid fever (see above). Epidemic louse-borne typhus is transmitted by the arthropod body louse. Typhus is widespread and found in Central Africa, Asia, and Central, North, and South America. It is also common in cold mountainous regions affected by famine, war, or mass population movement, where adequate clothing exists to harbor the louse or lice. Louse-borne disease occurs after louse body fluids and feces are rubbed into abrasions or after bites. Infection results in high fevers after an 8- to 12-day incubation period. Severe headache is common, and a maculopapular rash appears between days 4 and 7, generally sparing palms and soles. The rash may be hemorrhagic. Diagnosis starts on clinical grounds and is confirmed with serologic testing. Treatment is doxycycline (100 milligrams PO twice daily) or chloramphenicol (50 milligrams/kg/d PO in four divided doses) for 7 days and until 48 hours after defervescence. Untreated, mortality is as high as 60%.

LEPTOSPIROSIS (WEIL'S DISEASE)

Leptospirosis, or Weil's disease, follows mucous membrane or percutaneous exposure to freshwater contaminated by Leptospira interrogans. Infected animals excrete the spirochete in their urine. Infected patients typically have had contact with dogs; swam, rafted, or waded in contaminated surface water; or farmed or gardened in contaminated areas. Outbreaks commonly occur after flooding. Although the risk to most routine travelers is low, recent ecotourists and adventure travelers have become infected after intense water exposure.

The clinical course can be asymptomatic, but often symptoms illustrate a biphasic pattern. After an incubation of 2 to 20 days, high fever, severe headache, chills, myalgias, hepatitis (with or without jaundice), and nonspecific influenza-like symptoms develop. NoTable is conjunctival injection without purulent discharge. Symptoms resolve in 4 to 7 days, followed several days later by the severe, icteric Weil's disease caused by circulating antibodies. The second phase lasts for up to 4 weeks and can include aseptic meningitis, renal failure, uveitis, rash, and, rarely, circulatory collapse. Isolation of leptospires from blood, urine, or cerebrospinal fluid is diagnostic, although sensitivity varies with duration of symptoms. Serology is most often used to confirm the diagnosis. Treatment reduces the severity and duration of symptoms and may prevent the second disease phase. Mild disease can be treated within the first 3 days of illness with PO amoxicillin, 500 milligrams four times daily, or doxycycline, 100 milligrams twice daily, whereas more severe cases require IV penicillin (1.5 million units every 6 hours), ceftriaxone (1 gram daily), or ampicillin (1 gram every 6 hours). Treatment duration is 7 to 14 days total. Consider empiric therapy with PO doxycycline or IV penicillin (or ampicillin) if leptospirosis is suspected.

RELAPSING FEVER

Relapsing fever is a bacterial infection caused by the spiral-shaped Borrelia species (Borrelia recurrentis) transmitted by lice or tick bites. It is rare among travelers, yet should be suspected in those who have contact with refugee and displaced populations. After being introduced by a louse or tick bite, Borrelia reproduce in body fluids and produce endotoxins affecting the liver, spleen, and capillaries. After incubation of 3 to 10 days, patients develop fever, chills, headache, myalgias, abdominal pain, and jaundice. In severe cases, mental status changes, meningoencephalitis, myocarditis, hepatic failure, and disseminated intravascular coagulopathy occur. After 5 to 7 days, fever may spontaneously abate, accompanied by hypotension, and, near day 14, fever may recur. The number of relapses varies, with 1 to 2 relapses in louse-borne fever, 3 to 6 relapses in tickborne fever, and up to 11 relapses in African varieties. Diagnosis is made by clinical suspicion and confirmed by identifying spirochetes blood peripheral smear, cerebrospinal fluid, or bone marrow. Spirochetes are best observed in blood when taken during the febrile period. Louse-borne and tickborne relapsing fever is treated with tetracycline, 500 milligrams PO every 6 hours for 10 days; doxycycline, 100 milligrams PO every 12 hours for 7 to 10 days; or erythromycin, 500 milligrams PO every 6 hours for 10 days. When CNS involvement is suspected, ceftriaxone, 2 grams IV, should be given every 24 hours.

Among the most feared tropical diseases are viral hemorrhagic fevers. However, viral hemorrhagic fevers are rare when compared with other febrile hemorrhagic infections such as malaria, dengue fever, meningococcemia, leptospirosis, plague, bacterial sepsis, and rickettsial fevers. Neisseria meningitidis is the most common cause of acute hemorrhagic fever in temperate climates. Among travelers, several treaTable infections, including Lassa fever, meningococcemia, leptospirosis, and rickettsial infection, can cause fever associated with hemorrhage. Most people with viral hemorrhagic fevers, such as dengue, hantavirus (see chapter 160), Lassa, Ebola, Marburg, and Rift Valley, develop fever within 3 weeks after exposure. Establish a precise travel itinerary to estimate the incubation time. Viral hemorrhagic fever usually follows the bite of infected mosquitoes and ticks, close contact with rodent/bat excreta, or direct contact with infected, symptomatic individuals (the latter notably for Ebola).

In the event of a suspected viral hemorrhagic fever of tropical origin, institute control measures, including isolation in a negative-pressure room, the use of high-efficiency particulate-arresting respirators, and the use of gloves and gowns. Immediately notify local public health officials for suspected contagious viral hemorrhagic fevers such as Marburg, Lassa, Ebola, or Crimean-Congo hemorrhagic fever. If intentional bioterrorism is suspected, notify local law enforcement officials, the Federal Bureau of Investigation, and the Centers for Disease Control and Prevention (1-770-488-7100).

CRIMEAN-CONGO HEMORRHAGIC FEVER

This tickborne viral disease is common in Africa, eastern Europe, Asia, and the Middle East, especially in Turkey.¹⁵ Agriculture workers are at greatest risk, but healthcare workers are the second most affected group. Mortality ranges from 3% to 30%.¹⁵ The prehemorrhagic period is characterized by the sudden onset of fever, headache, myalgia, dizziness, and, possibly, mental confusion. The hemorrhagic period is short (2 to 3 days), develops rapidly, usually begins between the third to fifth day of disease, and may be accompanied by tender hepatomegaly. The most common bleeding sites are the nose, GI system (hematemesis, melena, and intra-abdominal), uterus (menometrorrhagia) and urinary tract (hematuria), and the respiratory tract (hemoptysis). Thrombocytopenia is common. Patients may have leukopenia and elevated liver enzymes, lactate dehydrogenase, and creatinine. Prothrombin time and activated PTT can be prolonged.

Diagnosis is clinical and confirmed with serology. Treatment is primarily supportive, including treatment of coagulopathy and respiratory support in severe cases.¹⁵ Oral or IV forms of ribavirin are available and used in more severe cases; treat for 10 days (30 milligrams/kg as an initial loading dose, then 15 milligrams/kg every 6 hours for 4 days, and then 7.5 milligrams/kg every 8 hours for 6 days).¹⁵

YELLOW FEVER

Yellow fever, an acute zoonotic flavivirus, has a jungle monkey reservoir, and its equatorial belt lies in South/Central America and Africa. Recent outbreaks in Bolivia, Kenya, and Nigeria indicate that it could reappear in the southern United States, where the day-biting mosquito vector A. aegypti (also transmitting dengue) is endemic. Yellow fever vaccination is mandatory in endemic areas. Outbreaks are common near tourist areas and may occur among nonimmunized adventure travelers who travel to endemic areas.

Yellow fever ranges in severity from an undifferentiated self-limited flulike illness to a hemorrhagic fever that is fatal in 20% of cases. After an incubation of 3 to 6 days, patients develop fever, headache, myalgias, conjunctival injection, abdominal pain, prostration, facial flushing, and relative bradycardia. In most cases, patients recover, but in others, fever remission lasts a few hours to several days, followed by renewed high fever, vomiting, headache, back pain, shock, multiorgan failure, and bleeding diathesis. The classic presentation is a triad of jaundice, black emesis, and albuminuria. In severe cases, hypotension, shock, and metabolic acidosis develop, complicated by myocardial dysfunction and arrhythmias. Confusion, seizures, and coma are common in the late stages of the illness, and death can occur within 7 to 10 days after onset. The diagnosis is primarily clinical, although confirmation is possible through virus identification or rising antibody titers in recovering patients. Leukopenia and albuminuria are typical, direct bilirubin levels rise, and liver enzymes are elevated for several days during which time azotemia and oliguria ensue. Treatment is supportive, with fluid replacement and management of hematologic complications.

LASSA FEVER

Lassa fever, an arenavirus, was first detected in Lassa, Nigeria, and is spread by contact with bush rat excreta. Epidemics were noted with civil unrest and forced migration of populations. The likelihood of travelers becoming infected is low because it is primarily a disease of rural communities where bush rats thrive. Although Lassa fever is mostly found in rural West Africa, it has been exported to Europe and North America by infected patients. The disease is highly contagious through close contact with blood and body fluids.

After an incubation period of 3 to 16 days, the disease presents as a viral syndrome with insidious onset of fever, malaise, headache, sore throat, retrosternal chest pain, back pain, abdominal pain, and myalgias. Varied and nonspecific symptoms persist for 4 to 6 days, at which time the patient suddenly deteriorates and becomes gravely ill. Among those infected, 80% have few symptoms and 20% have severe multiorgan disease. The main features are high fever, severe prostration out of proportion to the fever, severe sore throat with dysphagia and yellow-white exudates, abdominal pain, diarrhea, and vomiting. Only one third of patients experience bleeding, which may include oozing from the gums, hematemesis, melena, hematochezia, hemoptysis, hematinuria, or brain hemorrhage. Diagnosis is made by enzyme-linked immunosorbent assay serology, culture, or immunohistochemistry. Strict patient isolation and use of personal protection by healthcare workers are necessary. Treatment is largely supportive, but patients with severe disease may benefit from early treatment with ribavirin IV or PO (see dose for Crimean-Congo hemorrhagic fever above in "Crimean-Congo Hemorrhagic Fever"). Survivors will defervesce within 10 days of disease onset and, except for sensorineural deafness, can make a complete recovery.

EBOLA

Periodic outbreaks of Ebola virus disease have been reported since 1976, when an outbreak occurred in the Democratic Republic of the Congo (Zaire). Since then, outbreaks have occurred in Gabon and Uganda, with the most recent large outbreak in multiple West African countries. Four Ebola species cause disease in humans. Symptoms begin 2 to 21 days after exposure with fever, myalgia, malaise, diarrhea, abdominal pain, and vomiting, and progress to hemorrhage, shock, and end-organ failure. Mortality is high, but those who recover have an antibody response that lasts about 10 years. Disease transmission is by direct contact with infected blood or body fluids, contaminated needles or syringes, or infected bats or primates. The virus is stable, with little mutation in current species compared to that in the epidemic of 1976. Diagnosis is by enzyme-linked immunosorbent assay serology, polymerase chain reaction, culture, or immunochemistry. Treatment is supportive, but vaccines are currently under development. Epidemic containment focuses on avoidance of exposure, and for healthcare workers, use of personal protective equipment. Hospital preparedness consists of the identification of potential exposed contacts by identifying travel and direct exposure history, determining disease signs and symptoms, and then isolating individuals with possible disease.

Fever with acute mental status changes, headache (Table 161-9), nuchal rigidity, and focal neurologic signs is associated with a number of serious infections. CNS involvement with fever in travelers returning from malaria-endemic regions requires emergency presumptive treatment for both malaria and bacterial meningitis (see chapters 158 and 174, "Malaria" and "Central Nervous System and Spinal Infections"). The differential diagnosis for fever with CNS involvement includes malaria, bacterial meningitis, tuberculosis, typhoid fever, rickettsial infections, and rabies. Other causes are viral encephalitides, including Japanese and West Nile encephalitis, which often present similarly.

Patients with altered mental status suspected of tropical illness may demonstrate coma, decreased level of consciousness, meningeal signs, or seizures. Although seizures should arouse suspicion of cerebral malaria, suspect cysticercosis in those with long-term residence in Latin America and a first-time seizure. Meningococcal meningitis occurs with regularity in sub-Saharan Africa along the "meningitis belt" running from Ethiopia in the east to Senegal in the west, and pilgrims attending the Hajj in Saudi Arabia are also at risk of Neisseria meningitis. Aseptic meningitis may be caused by enteroviruses or, less commonly, typhoid fever, leptospirosis, or rickettsiae. Encephalitis may be caused by an arboviral infection, such as Japanese B encephalitis.

JAPANESE ENCEPHALITIS

Japanese encephalitis is a Culex mosquito-borne flavivirus infection that occurs in an epidemic or sporadic pattern over large areas of Asia and the western Pacific. It is rarely transmitted to U.S.-bound travelers because the vector breeds primarily in rural rice fields. Infected patients present with a sudden high fever, headache, nuchal rigidity, vomiting, and seizures (especially infants) after the incubation time of 5 to 15 days. A variety of pyramidal and extrapyramidal signs may develop soon after fever. If the outcome is fatal, it usually occurs in the first 10 days. Diagnosis is based on clinical suspicion, although virus can be isolated from cerebrospinal fluid, and antibody titers can rise. Treatment is supportive with IV fluid and electrolyte management, assisted respiration if necessary, anticonvulsants, and neuropsychiatric consultation during convalescence. Recovery may take months, and varying degrees of residual neurologic damage may persist indefinitely. Immunization is recommended for travelers to rural, endemic regions in Asia.

CYSTICERCOSIS

Cysticercosis is a systemic illness caused by dissemination of the larval form of the pork tapeworm, Taenia solium. The disease affects an estimated 50 million people worldwide. Endemic areas include Mexico, Latin America, sub-Saharan Africa, India, and East Asia. The incidence in the United States is increasing due to increased immigration from endemic areas and increased travel to endemic areas. Humans are definitive T. solium hosts and can carry the intestinal adult tapeworm. An intermediate host, usually a pig, ingests fecally shed egg-containing proglottids or T. solium eggs. Humans develop cysticercosis when they inadvertently ingest eggs from contaminated food or soil or eat undercooked pork.

Infestation can occur in almost any tissue. Involvement of the CNS, neurocysticercosis, is the most clinically important manifestation of the disease. Neurocysticercosis is a leading cause of new adult-onset seizures worldwide. Other symptoms of neurocysticercosis include obstructive hydrocephalus, meningoencephalitis, stroke-like focal deficits, headache, and visual or mental status changes. Noncontrast CT scan shows calcifications of inactive disease and can reveal mass effect or hydrocephalus. Antihelminthic agents are the mainstay of treatment (praziquantel, 50 milligrams/kg/d PO divided three times daily for 15 days). Use steroids in those with encephalitis, hydrocephalus, or vasculitis to avoid inflammation as cysts involute.

Evaluate patients with chronic or relapsing fever lasting beyond 3 weeks after travel initially for non–travel-related infections, inflammatory diseases, and noninfectious disorders. Tropical illnesses that cause chronic fever include protozoal infections (such as trypanosomiasis, leishmaniasis, amebiasis, and malaria), typhoid or paratyphoid fever, and tuberculosis (Table 161-10).

HUMAN AFRICAN TRYPANOSOMIASIS (AFRICAN SLEEPING SICKNESS)

Sleeping sickness is caused by the two identical endemic protozoan subspecies, Trypanosoma brucei gambiense (responsible for most clinical cases) and Trypanosoma brucei rhodesiense, transmitted by the aggressive tsetse fly found in rural Africa. The tsetse fly is indigenous to vegetation near rivers, lakes, forests, and wooded savannah. After a bite, a localized inflammatory reaction occurs, followed in 2 to 3 days by a painless chancre that increases in size for 2 to 3 weeks and then gradually regresses. Trypomastigotes mature and divide in the blood and lymph after the development of the chancre and cause intermittent fever unresponsive to antimalarials. Malaise, rash, wasting, and eventual CNS involvement occur, causing behavioral and neurologic changes, encephalitis, coma, and death. Disease categorization depends on whether the CNS has been invaded or not. Other complications include hemolysis, anemia, pancarditis, and meningoencephalitis.

Diagnosis is made by rapid evaluation of blood smears for the mobile parasite. Organisms can also be identified by aspiration of lymph nodes, chancres, or bone marrow or by CSF examination. The treatment of sleeping sickness varies according to the stage of illness. If the disease has not invaded the CNS, treat with pentamidine or suramin. If the CNS is invaded, treatment requires melarsoprol, eflornithine, or a combination of nifurtimox and eflornithine. Diagnosis and treatment need infectious disease consultation.

AMERICAN TRYPANOSOMIASIS (CHAGAS' DISEASE)

The protozoan Trypanosoma cruzi is found in up to 5% of emigrants from endemic parts of Latin America and is reported as far north as Texas. It is spread by the reduviid "kissing bug" or "assassin" bug. The bites typically happen nocturnally after the bug emerges from rural adobe walls or thatched roofs. Among travelers, it is rare; it causes an acute illness and, commonly, an asymptomatic infection with complications arising years later in the heart and GI tract. It is transmitted during a blood meal when the bug defecates trypanosome-infected feces around the meal site, causing a local inflammatory reaction and trypanosome inoculation after the host rubs the organism into the bite wound or into adjacent mucous membranes or conjunctiva. Infection can also be acquired by blood transfusion, by laboratory accidents, and congenitally.

Unilateral periorbital edema (Romaña sign) or painful cutaneous edema at the site of skin penetration (chagoma) is followed by a toxemic phase with parasitemia causing lymphadenopathy and hepatosplenomegaly. The acute phase generally lasts 2 to 4 weeks but may last up to 3 months. Next is a long, asymptomatic, latent phase when nerve ganglion cells are gradually destroyed, leading to depressed cardiac and GI function. Cardiac complications include myocarditis, dysrhythmias, cardiomyopathy, and sudden death. Chagas-induced heart disease is the leading form of congestive heart failure in much of Latin America. GI complications are megaesophagus or megacolon.

The acute phase diagnosis is made by examination of peripheral blood smears demonstrating motile parasites or by blood culture or muscle biopsy. In the chronic phase, serologic tests and tissue biopsy are useful. Treatment is available for acute, reactivated, or chronic cases. The two medications used are nifurtimox and benznidazole, which are available in the United States through the Centers for Disease Control and Prevention.

LEISHMANIASIS (VISCERAL)

Leishmania is an intracellular protozoan transmitted by Lutzomyia or Phlebotomus sandflies. The disease occurs sporadically in rural Africa, Asia, the Mediterranean basin, and Central/South America, and outbreaks occasionally occur, such as in Brazil, India, and the Sudan, which places resident expatriates and travelers at risk. The disease is a low risk to most travelers, although European travelers to nonendemic Mediterranean nations occasionally export cases. Suspect Leishmania in the military and their families living proximal to jungles, adventure travelers, field biologists, and emigrants from endemic zones.

The infecting species determines the pathology, ranging from a localized self-healing lesion to widespread, persistent, and potentially destructive disease. Four major clinical syndromes are recognized (Table 161-11).

The most important diagnostic information is patient origin and travel itinerary because endemic areas suggest the infection type. Definitive diagnosis requires reference laboratory expertise to isolate motile extracellular parasites aspirated from bone marrow, spleen, or lymph nodes, or on smears or sections taken from the ulcer edge by punch biopsy.

Treatment of visceral leishmaniasis by infectious disease consultants relies on factors such as the origin of the disease, type of disease, parasite species, and patient comorbidities. Treatment for visceral leishmaniasis is with agents such as amphotericin B, pentavalent antimonials, or miltefosine. Treatment of cutaneous leishmaniasis is either by local therapy, oral systemic therapy, or parenteral systemic therapy.

Illnesses causing abdominal pain and diarrhea are common among world travelers because of infecting bacteria, viruses, soil-transmitted helminths, and other parasites. Most infections are caused by the consumption of undercooked or fecal-contaminated foods and are prevenTable by adequate hygiene, poTable water, and careful food preparation.

SCHISTOSOMIASIS (BILHARZIA OR SNAIL FEVER)

Schistosomiasis, infection with a blood fluke found in Africa, the Middle East, South America, and Asia, infects >200 million people worldwide, with 20 million people suffering severe consequences. Suspect schistosomiasis in travelers with GI symptoms following exposure to freshwater in endemic zones. For most short-term travelers, the risk is low, although significant outbreaks now occur among adventure tourists, Peace Corps workers, and those who swim in infested streams and lakes. The larvae are released into freshwater by snails, which are intermediate hosts. Infection occurs by tiny, free-swimming cercariae that penetrate wet, unbroken skin or are ingested from slow-moving freshwater. Brief or even single exposures like washing or wading can cause infection in previously unexposed asymptomatic individuals. After inoculation, an immediate cercarial allergic and pruritic dermatitis occurs that can last days. In the following 4 to 8 weeks, fever occurs, accompanied by headache, cough, urticaria, diarrhea, hepatosplenomegaly, and hypereosinophilia (Katayama fever). Worms mature into adults in the venous blood and, for the next 30 to 40 years, deposit eggs into selective body tissues (Schistosoma haematobium in the bladder and S. mansoni and S. japonicum in the GI tract). Eggs are deposited throughout the brain, skin, liver, and GI tract. Eggs stimulate a vigorous immune response that results in clinical symptoms.

CNS symptoms include seizures, paralysis, and acute transverse myelitis. S. haematobium infection causes dysuria, frequency, and terminal hematuria, and can cause bladder scarring, calcification, and squamous cell carcinoma. S. japonicum and S. mansoni infections lead to hepatosplenomegaly, hepatic granulomas, and periportal fibrosis. S. japonicum and S. mansoni also can cause diarrhea, abdominal cramps, acute abdominal pain, and, late in the disease course, portal hypertension. S. dermatitis, a non–human-infecting schistosome, has cercariae that only penetrate the superficial skin, causing an irritation known as swimmer's itch.

Diagnosis is by detecting eosinophilia and is made primarily by microscopic identification of ova in mid-day urines or stool or in a biopsy specimen. Serologic antibody detection methods are highly accurate and are usually positive in light infections missed by egg detection. Offer treatment to symptomatic patients and seropositive travelers using praziquantel; some may require a second treatment. For swimmer's itch, no treatment is required.

CLONORCHIASIS (CHINESE OR ORIENTAL LIVER FLUKE)

Clonorchiasis, a trematoidal disease of the bile ducts, is caused by Clonorchis sinensis and follows ingestion of poorly cooked freshwater fish containing encysted larvae. Travelers are at low risk despite the tremendous prevalence among those living in endemic zones such as Southeast Asia. Once ingested, larvae mature into adults, migrate to bile ducts, survive for 30 or more years, and cause fibrosis. The extent of pathology is related to parasite burden, and among the millions infected, only few are symptomatic. Acute symptoms include anorexia and diarrhea and may progress in heavy infections to chronic bile duct obstruction, liver tenderness, and/or jaundice and, in advanced cases, biliary cirrhosis and cholangiocarcinoma. Diagnosis is made by detecting the characteristic embryonated eggs in stool or duodenal aspirate, and eosinophilia is common. Serologic tests using enzyme-linked immunosorbent assay have 70% sensitivity, and CT, abdominal ultrasonography, and upper endoscopy examinations are useful. Treatment is with praziquantel or albendazole.

Diarrhea and gastroenteritis are the most common travel ailments, affecting up to one half of travelers (Table 161-12). Traveler's diarrhea is especially common after travel to Africa, Asia, the Middle East, South and Central America, and Mexico. Diarrhea is typically accompanied by fever, flatulence, nausea, emesis, and abdominal pain, which is usually spasmodic and colicky. Campylobacter jejuni may cause severe and constant pain, and cholera may cause somatic muscle cramps. Nonbloody gastroenteritis and diarrhea are usually caused by bacteria or bacterial toxins, whereas dysentery usually results from toxigenic and invasive bacteria such as Shigella, Salmonella, Campylobacter, Aeromonas, Escherichia coli, or Entamoeba histolytica (Table 161-13). Traveler's diarrhea is not commonly due to viruses.

Acute abdominal pain among travelers should first be considered to be caused by nontravel causes with an expanded travel-based differential diagnosis. Give empiric therapy to those with pain and severe diarrhea using fluoroquinolones (ciprofloxacin or levofloxacin) before stool testing results are available, although regional resistance can occur and should be verified (see chapter 159, "Food and Waterborne Illnesses").

AMEBIASIS

Pathogenic species such as E. histolytica are found worldwide and disproportionately infect those living in low-income settings. Amebiasis is typically spread by asymptomatic carriers whose excrement contains the encysted organism. Short-term travelers are at low risk, but longer-term travelers, such as Peace Corps volunteers, are at higher risk. The disease is most severe among young children, the elderly, and pregnant women. Incubation times are typically 1 to 3 weeks for colitis and 2 weeks to several months for liver abscesses. Once cysts are ingested, amebic trophozoites invade the colon wall, lyse tissues, and cause necrotic abscesses.

Most infected people do not have symptoms. Symptoms range from alternating constipation and diarrhea over 1 to 3 weeks, to abdominal pain, bloody diarrhea, fever, dehydration, and weight loss. Extraintestinal metastases can infect the liver and, rarely, pericardium, lung, and brain. Colitis can lead to intestinal perforation and peritonitis. Complications such as liver abscesses may cause fever, right upper quadrant pain, or chronic, vague abdominal pain accompanied by weight loss. Hepatic abscesses can be fatal if the abscess ruptures.

Stool ova and parasite examination is diagnostic, and organisms are found either as motile trophozoites or cysts. It can be difficult to differentiate pathogenic organisms (E. histolytica) from benign organisms (Entamoeba dispar) without use of stool antigen detection tests. Serology for elevated antibody titers is almost uniformly sensitive for extraintestinal disease and 80% sensitive for invasive colon disease after 1 week of illness. Ultrasonography or CT scans may be useful to identify hepatic abscesses.

Treatment of asymptomatic cyst passers includes iodoquinol, 650 milligrams PO three times a day for 20 days; paromomycin, 500 milligrams PO three times a day for 7 days; or diloxanide furoate, 500 milligrams PO three times a day for 10 days. For symptomatic disease, choices include metronidazole, 500 to 750 milligrams PO three times a day for 5 to 10 days, or tinidazole, 1 gram PO twice a day for 3 days, followed by either iodoquinol or paromomycin in the doses and duration noted earlier. For liver abscess, treat with metronidazole, 750 milligrams PO or IV three times a day for 5 days, followed by iodoquinol or paromomycin as described above.

GIARDIASIS

Giardia lamblia is a flagellated protozoan infecting the small intestine and biliary tree. It is distributed worldwide and is food- or waterborne by fecal contamination with encysted parasites. It is common to rural areas with poor sanitation and impure surface water but has also occurred in day care settings in the United States. In Eastern Europe, it is a common cause of chronic traveler's diarrhea and can be contracted at camping sites and rural swimming areas. Long-term residents of tropical nations are at high risk, but short-term travelers are also at risk. Ingested parasites reside in the duodenum and may lead to malabsorption because of duodenal microvilli obstruction. Symptoms include abdominal cramping, flatulence, and foul-smelling, watery diarrhea without blood or mucus. Chronic infections cause weight loss and anemia, and a common complication is lactose intolerance. Diagnosis is by stool ova and parasites showing either motile trophozoites or cysts. Giardia antigen detection in stool has good sensitivity and specificity. Treatment is with metronidazole (250 milligrams PO three times daily for 5 to 7 days), tinidazole (2 grams PO for one dose), quinacrine (100 milligrams PO three times daily for 7 days), or nitazoxanide (500 milligrams twice daily for 3 days). In children, treat with tinidazole, 50 milligrams/kg up to 2 grams in a single dose, or metronidazole, 35 to 50 milligrams/kg/d PO up to 750 milligrams/dose, three times per day for 10 days. Treatment is not always successful regardless of drug used.

CHOLERA

Cholera is an acute diarrheal disease caused by the bacterium Vibrio cholerae. It is endemic and epidemic to many tropical nations. It is reported in Africa, Asia, Latin America, and most recently Haiti and Mexico. Epidemics occur after flooding or acute population displacement with disruption of the water-sanitation system. Transmission is by fecal contamination of water or food (including raw or poorly cooked seafood and shellfish). Significant bacterial ingestion is required to cause symptoms. The incubation time is 2 to 3 days, and symptoms result from sodium pump inhibition in the GI tract by the cholera toxin. Infection is usually mild but can be life-threatening, particularly among vulnerable populations, such as malnourished children, migrants, and those with chronic illness. Another group at risk are individuals with achlorhydria or those using medications decreasing gastric acidity. There is an asymptomatic carrier state.¹⁶

Severe disease is characterized by profuse, usually painless, watery diarrhea ("rice water stools"), severe dehydration, vomiting, leg cramps, and, occasionally, fever. Rapid fluid loss (up to 15 L/d) leads to extreme dehydration and shock. Without aggressive rehydration, death can occur within hours. With proper fluid resuscitation, almost no patients should die. Diagnosis is clinical, and when suspected, a rectal swab or stool specimen can be sent to a reference laboratory for culture confirmation. Rapid dipstick testing of stool is possible, but should be followed by confirmatory testing.

The cornerstone of treatment is aggressive fluid resuscitation with PO rehydration solution or IV fluids, coupled with correction of metabolic acidosis and hypokalemia. For those with severe illness, antibiotics can shorten the illness course, diminish vomiting, lessen volume resuscitation needs, and ensure that bacteria are eradicated from stool. Doxycycline is the antibiotic of choice, followed by azithromycin or erythromycin for children and pregnant women. Secondary transmission is rare, and close contacts should not be given antibiotics as prophylaxis.

Major infestations are discussed here, and diagnosis and treatment are presented in Table 161-14.

In the patient in whom empirical therapy is chosen due to the appearance of a worm in fecal matter, treatment for nematodes can be considered. By treating the adult patient empirically with albendazole, 400 milligrams twice daily for 3 days (with a single repeat dose in 2 weeks), a number of pathologies can be treated (roundworm, pinworm, whipworm, and hookworm). Send stool samples for laboratory analysis to provide more focused treatment.

ASCARIASIS (ROUNDWORM)

The risk of infection with Ascaris lumbricoides to short-term travelers is low and suspected following ingestion of street vendor foods or vegetables fertilized by "night soil" (human feces) or animal feces. Eggs survive for years in moist soil, and transmission is typically fecal–oral or through poorly cooked food. Symptoms are usually minimal; a dry cough or pneumonia may occur as young worms are expectorated and migrate from the lungs to the esophagus and gut. A large worm burden can lead to malnutrition and weakness, and a mass of worms may lead to bowel obstruction. Wandering Ascaris also traverse internal organs, rarely leading to biliary obstruction, hepatic abscess, acute pancreatitis, acute appendicitis, or hypersensitivity pneumonitis. The diagnosis and treatment are described in Table 161-14.

ENTEROBIASIS (PINWORM, SEATWORM)

Enterobiasis vermicularis is a common tropical disease caused by a small intestinal parasite transmitted by the fecal–oral route and is often acquired from contaminated objects such as toys, utensils, and bedding. It is a common disease among U.S. children and is more likely to be peridomestic rather than after tropical travel. The disease is characterized by intense perianal itching. The diagnosis and treatment are found in Table 161-14.

TRICHURIS (WHIPWORM DISEASE)

Whipworm (Trichuris trichiura) is a nematode parasite of the large intestine distributed globally but most heavily in the tropics. Long-term travelers, former tropical residents, and visitors from the tropics are at high risk. It is obtained by ingesting contaminated soil or vegetables and is not transmissible from person to person. Light infestations are asymptomatic, and heavy infestations cause bloody diarrhea and rectal prolapse. Diagnosis and treatment are found in Table 161-14.

HOOKWORM

Hookworm is a common chronic nematodal infection caused by Ancylostoma duodenale and Necator americanus, which are globally distributed but most heavily in the tropics and subtropics. Because symptoms require large worm burdens, it is a low risk among short-term travelers. Hookworm causes chronic, severe anemia, especially in children. The cutaneous form is called cutaneous larva migrans. Transmission is by direct skin contact with soil contaminated by human feces, often in children with poor footwear exposed to raw sewage. Filariform larvae penetrate the skin. Microscopic examination of stool for eggs is the usual means of diagnosis. Diagnosis and treatment are found in Table 161-14.

CESTODES (TAPEWORMS)

Among the cestodes, taeniasis and cysticercosis are the most pathologic. Infections occur worldwide, but especially in the tropics, and risk is high among children, the mentally disabled, and immigrants or visitors from endemic nations. Risk to travelers is low but is increased with consumption of undercooked pork, fish, or beef.

Taenia solium and Taenia saginata (Pork and Beef Tapeworm)

T. solium (pork tapeworm) is encountered in the United States in immigrants or visitors to or from Central America and the Middle East. T. saginata (beef tapeworm) is seen more often, especially in those who consume raw beef (e.g., steak tartare), particularly in Latin America, Eastern Europe, Africa, and Russia. Adult worms live in the small intestine. Infected patients can be asymptomatic or present with nausea and vomiting, headache, abdominal pain, pruritus, constipation, diarrhea, and intestinal obstruction. The larval stage of T. solium can cause clinical disease (cysticercosis), which can sometimes be fatal. Taenia cysts may be found in subcutaneous tissue, the eye, brain, and heart, and cause seizures and hydrocephalus. Radiographs of the soft tissues may reveal curvilinear calcifications indicative of cysts, and cysts can be seen in the meninges and brain parenchyma on CT scanning. Diagnosis and treatment are found in Table 161-14. For discussion of neurocysticercosis see the "Cysticercosis" section, above. Dipylidium caninum is discussed in the chapter 160.

Diphyllobothrium latum (Fish Tapeworm)

Diphyllobothrium latum (fish tapeworm) is encountered in those consuming raw fish (e.g., sushi and sashimi) or gefilte fish. Diphyllobothrium can compete with the host for vitamin B₁₂, and patients can develop pernicious anemia. Most patients are asymptomatic, but some develop intestinal or biliary obstruction. Diagnosis and treatment are found in Table 161-14.

STRONGYLOIDES

Strongyloides stercoralis infects the small intestine. Distribution is worldwide, but infection is most common in humid tropics. Infection can develop in overseas military personnel, refugees, or immigrants. The risk is low in short-term travelers. Most infections cause minimal or no symptoms. However, fatalities may occur due to hyperinfection in elderly and immunocompromised patients and those with chronic disease. An upper GI series may reveal a deformed duodenal bulb, and Strongyloides may be confused with ulcer disease. Diagnosis and treatment are found in Table 161-14.

Skin complaints among travelers are common and nonspecific and have many causes. Travel-related skin disease is generally caused by one of the following: (1) exacerbations of previous conditions (e.g., atopic dermatitis, psoriasis); (2) environmental conditions (e.g., photosensitivity, contact allergies); or (3) infective organisms causing infestations or infections.¹⁶ The distribution and timing of the dermatosis may aid diagnosis of rashes associated with systemic illness (Table 161-15).¹⁷ Among rashes reported by travelers, most are minor problems such as sunburn, phototoxic/sensitivity reactions, insect bites, and prickly heat, and are often self-limiting and necessitate symptomatic care. The top 10 tropical travel dermatoses requiring specific therapy are cutaneous larva migrans, pyodermas due to staphylococcal or streptococcal ecthyma, arthropod-reactive dermatoses, myiasis, tungiasis, urticaria, febrile syndromes with rash, cutaneous leishmaniasis, scabies, and fungal infections.¹⁸ The risk of serious conditions tends to increase with the amount of time spent overseas, and thus short-term travelers rarely contract dermatoses such as filariasis, Buruli ulcer, yaws, and leprosy (Hansen's disease). To further aid diagnosis, travelers with dermatoses can fit into five syndromic and morphologic categories (Table 161-16).

Management includes arranging biopsy for patients with chronic ulcerative lesions. Beware of the rare patient presenting with anxiety of parasitosis regardless of travel history. The following are select dermatoses associated with tropical exposures.

ONCHOCERCIASIS (RIVER BLINDNESS)

River blindness is a chronic, nonfatal filarial disease leading to subcutaneous skin changes and blindness. It is caused by Onchocerca volvulus, a nematode transmitted by the female black fly, Simulium species, found near fast-moving rivers in parts of Central/South America and mostly equatorial Africa. Early treatment can prevent blindness and reduce systemic spread, because the incubation period from fly bite to microfilariae appearing in skin is often more than a year. Symptoms include intracTable pruritus, altered skin pigmentation, skin nodules, lymphadenitis, and gradual visual impairment leading to blindness. Adult female worms reside in 2- to 3-cm painless nodules in skin and bones near joints, and release microfilariae that migrate through the skin, causing intense pruritus when they die, leading to chronic dermatitis, edema, and skin atrophy. Skin pigment changes result in "leopard skin," whereas loose pelvic skin is called "hanging groin." Blindness is a result of microfilariae migrating to the eye, invading it, and causing permanent damage when they die. Diagnosis is made by identification of microfilariae from a fresh skin biopsy, nodule biopsies, or in the urine. Slit-lamp examination may reveal microfilariae in the cornea, anterior chamber, or vitreous. Treatment is one dose of ivermectin, 150 micrograms/kg PO, which does not kill the adult worm, but when repeatedly dosed every 6 to 12 months, reduces morbidity by killing microfilariae, suppressing microfilariae release from adults, and preventing spread to eyes and skin. Diethylcarbamazine citrate (DEC) and suramin (which can kill adult worms and microfilariae) have serious side effects and are avoided. Surgical removal of nodules can reduce symptoms, reduce the worm burden, and, if removed from the frontal scalp, help prevent progression of visual impairment and blindness.

LOA LOA (EYE WORM)

Loiasis is caused by a filarial nematode confined to the rain forests of western and central Africa. It is a low risk to short-term travelers but should be suspected among immigrants, refugees, visiting nationals, and expatriates living several months or more in endemic zones. Among travelers, worm burden is usually low, and symptoms are related to hypersensitivity syndromes and not serious disease. The adult worms inhabit subcutaneous tissues, move about freely, and can live for up to 18 years after the patient's last possible exposure. They are spread from the bite of the Chrysops fly and take 1 year to mature. Infections are usually asymptomatic; however, at times, infections cause painful or itchy subcutaneous swellings near the face and extremities known as Calabar swellings. The most dramatic presentation is when a worm passes across the eye under the conjunctiva, thus coining the disease "eye worm."

Patients will complain of "something in their eye," intense irritation, pain, and swelling of the periorbital tissues. The worm usually moves out of the conjunctiva in 30 minutes, but it takes usually several days for symptoms to subside.

Diagnosis is made by clinical presentation and by evaluating daytime-drawn blood for distinctively sheathed microfilariae and high-grade eosinophilia. Treatment for microfilariae and adult worms is diethylcarbamazine citrate, 2 milligrams/kg PO three times daily for 3 weeks. In patients with very high microfilariae counts, diethylcarbamazine citrate may induce a sudden severe hypersensitivity and encephalitic syndrome, so treatment is begun with a very small dose. Alternatives are albendazole or blood filtration to remove large numbers of larvae. Surgical excision is not recommended because multiple worms may not be visible. Subconjunctival worms, however, can be removed from the eye with analgesia and fine tweezers.

CREEPING ERUPTION (CUTANEOUS LARVA MIGRANS)

This erythematous "creeping eruption" commonly occurs among tropical travelers and beach resort vacationers who walk barefoot or sit in beach sand contaminated by dog feces harboring the parasite Ancylostoma braziliense.¹⁹ The lesions are typically slow moving, tracking, and serpiginous, and are a result of an inflammatory reaction from the worm, which is unable to complete its growth cycle in humans (it is only an effective parasite of dogs or cats). Pruritus causes sleeplessness and restlessness, and diagnosis is based on clinical presentation and eosinophilia. Treatment consists of albendazole, 400 milligrams daily for 3 to 7 days, or a single dose of ivermectin, 200 micrograms/kg once. Liquid nitrogen freezing or surgical excision is not recommended because of scarring.

CUTANEOUS LEISHMANIASIS

Cutaneous leishmaniasis is the most important cause of chronic skin ulceration in the world and is spread by sandflies in tropical and subtropical regions of Latin America, Africa, the Middle East, and Asia. This should be suspected among travelers such as military personnel, biologists, ecotourists, and adventure travelers, and should be part of the differential diagnosis of cutaneous ulcers among travelers, foreign visitors, and immigrants from endemic areas. Although there are a variety of subtypes causing varying infections, the common presentation is of a small papule slowly enlarging and forming a painless shallow skin ulcer with a noticeable rolled edge like a volcano, with a raised edge and central crater, often with a scab. Diagnosis is made by tissue biopsy of the indurated ulcer margin or scraping of the base with material placed on a slide followed by Giemsa stain. Many forms are self-limiting; treat based on clinical presentation and in concert with infectious disease consultants or the Centers for Disease Control and Prevention Parasitic Diseases Branch.

BANCROFTIAN FILARIASIS (WUCHERERIA BANCROFTI)

Bancroftian filariasis, a filarial disease, is caused by nematodes residing in the subcutaneous tissues and lymphatics for up to 10 years. It is common to South America, Africa, and Asia and the risk to short-term travelers is low, although cases are imported by long-term travelers. It is transmitted by flies or mosquitoes permitting larvae to enter the puncture wound during their blood meal. Adult filariae then reside in lymphatics and produce microfilariae that migrate to the bloodstream at night. Because the incubation period is long, first symptoms usually develop after 6 months or later (up to 5 years). The most common symptom is recurrent bouts of "filarial fevers" lasting 2 to 3 weeks, associated with warmth and tenderness overlying a lymphatic vessel, followed by retrograde lymphangitis. The most frequently affected sites are extremities, breasts, and spermatic cord. As more attacks occur, lymphatics are chronically damaged, and the most important consequence is the disfiguring and ostracizing condition elephantiasis. Diagnosis depends on finding the sheathed microfilariae in a nocturnal peripheral blood smear. Serology is often useful in mild infections. Treatment is diethylcarbamazine citrate, 2 milligrams/kg three times daily for 3 weeks. This drug is well tolerated but can cause hypersensitivity reactions because of early antigen liberation, resulting in fever, headache, nausea, and urticaria. Symptoms can be reduced by starting with a small dose. Repeated treatment may be necessary.

Returning travelers frequently develop respiratory complaints such as persistent cough, sinus congestion, and fever, and such nonspecific symptoms may be due to travel-related causes such as malaria, typhoid fever, typhus, and dengue. Common local respiratory pathogens, such as viral causes like influenza, and bacterial infections are the most common triggers. Risk factors for pulmonary disease include prolonged air travel with recirculation of dry cabin air and exposure to fellow travelers with infectious agents. Long-term travelers are at increased risk for tuberculosis that may manifest many years after travel. In the ED, isolate the patient because contagious infections such as tuberculosis, influenza, or coronaviruses, such as severe acute respiratory syndrome or Middle East respiratory syndrome, are possible. Also, have healthcare workers use personal protective devices.

Once public health threats are reasonably excluded, the evaluation is similar as for any nontravel patients. Additionally, ask about travel-related risk factors because a variety of pathogens such as viruses (viral hemorrhagic fevers), helminths (Strongyloides, Schistosoma, Paragonimus, Ascaris), and protozoa (E. histolytica, Trypanosoma, Leishmania) produce pulmonary symptoms or radiographic infiltrates.

MIDDLE EAST RESPIRATORY SYNDROME, SEVERE ACUTE RESPIRATORY SYNDROME, AND EMERGING INFECTIONS

Between September 2012 and February 2014, the World Health Organization reported a total of 182 cases of the Middle East respiratory syndrome coronavirus infection with 79 deaths²⁰; cases now exist in the United States. Like the 2003 to 2004 outbreak of severe acute respiratory syndrome, Middle East respiratory syndrome is caused by a coronavirus. The Centers for Disease Control and Prevention defines clinical criteria for a suspected case of Middle East respiratory syndrome as follows:

• Fever (≥38°C, 100.4°F) and pneumonia or acute respiratory distress syndrome (based on clinical or radiological evidence);

  AND

• history of travel from countries in or near the Arabian Peninsula within 14 days before symptom onset;

  OR

• close contact with a symptomatic traveler who developed fever and acute respiratory illness (not necessarily pneumonia) within 14 days after traveling from countries in or near the Arabian Peninsula;

  OR

• is a member of a cluster of patients with severe acute respiratory illness (e.g., fever and pneumonia requiring hospitalization) of unknown etiology in which MERS-CoV [Middle East respiratory syndrome coronavirus] is being evaluated, in consultation with state and local health departments.²¹

Although not certain, Middle East respiratory syndrome is likely to be spread by "droplet infection," through exposure to respiratory droplets spread by a cough or sneeze from an infected person. Polymerase chain reaction can be used to detect Middle East respiratory syndrome coronavirus.

Preventative measures are aimed at reducing close contact with infected persons and nosocomial transmission. Hospitalized patients should be placed on airborne precautions, and healthcare providers should use gowns, gloves, eye protection, and respiratory protection with a minimum of an N95 mask.²² Medical personnel treating patients suspected of infection with Middle East respiratory syndrome coronavirus should promptly notify local and state health departments of the case.

Treatment of Middle East respiratory syndrome is supportive care.

TUBERCULOSIS

Refugees and immigrants or expatriate workers (especially healthcare workers) returning from endemic areas are at higher risk of clinical tuberculosis (e.g., Eastern Europe, Africa, Asia). The risk of tuberculosis in travelers is approximately 3% per year of stay in endemic areas. High-risk sites for multidrug-resistant mycobacteria are Russia, Eastern Europe, Southeast Asia, China, southern Africa and South America. The initial ED management of suspected tuberculosis after respiratory isolation is discussed elsewhere (see chapter 67, "Tuberculosis").

PARAGONIMUS (LUNG FLUKE DISEASE)

Paragonimus westermani is a trematoidal infection primarily affecting the lungs. It is widely distributed, but is mostly found in the Far East and Southeast Asia (China is the major endemic site). It is uncommon in short-term travelers but should be considered among immigrants or long-term residents of Asia who are also at risk for tuberculosis and among travelers indulging in local exotic foods. Humans are infected by swallowing larvae contaminating raw or pickled crustaceans. Incubation lasts 6 to 12 weeks, as larvae migrate from the duodenum to the lungs, where they cause cough (sometimes with rusty sputum), pleuritic chest pain, and hemoptysis. Chest pain is often present, and fever with night sweats may occur during early infections, causing tuberculosis to be incorrectly diagnosed.

Chest radiographs demonstrate diffuse segmental infiltrates, nodules, ring cysts, or pleural effusions. Suspect paragonimiasis when no sputum smear acid-fast bacilli are found. If parasites do not reach the lung, diverse symptoms develop depending on fluke location. Symptoms include abdominal pain, diarrhea, migrating subcutaneous swelling, blindness, epididymis, testicular inflammation, and a variety of cerebral symptoms. Seizures can occur from intracranial encysted adults. Diagnosis is made by finding the characteristic eggs in sputum, urine, or stool, or by serologic tests. The treatment of choice is praziquantel or bithionol.

PARASITE-INDUCED BRONCHOSPASM

The most common helminths causing pulmonary symptoms are Ascaris and Strongyloides. A suggestive clinical history includes recent travel and ingestion of local food of uncertain quality. Suspicion should be raised by any new pulmonary symptoms such as cough or wheezing associated with patchy infiltrates on chest radiograph and hypereosinophilia. For diagnosis and treatment for each helminth, see previous respective sections.