Approach to illness associated with travel to East Asia

INTRODUCTION — The evaluation of illness in returned travelers should focus on the possible infections given the patient's clinical findings, travel geography, administration (if any) of vaccinations and malaria chemoprophylaxis, the nature and timeframe of potential exposure(s), and the incubation period(s) of the relevant possible infections (table 1) [1,2].

Good resources that provide current information about the infections that occur in various geographic areas are essential [2-4]. The United States Centers for Disease Control and Prevention website includes an online version of Health Information for International Travel under Travelers' Health and updates on travel-related infections [2]. The World Health Organization website also has regularly updated information about outbreaks.

The approach to evaluation of illness associated with travel to East Asia will be reviewed here.

Issues related to travel to other regions are discussed separately:

●(See "Approach to illness associated with travel to South Asia".)

●(See "Approach to illness associated with travel to Southeast Asia".)

●(See "Approach to illness associated with travel to West Africa".)

●(See "Diseases potentially acquired by travel to East Africa".)

●(See "Diseases potentially acquired by travel to Central Africa".)

●(See "Diseases potentially acquired by travel to North Africa".)

●(See "Diseases potentially acquired by travel to Southern Africa".)

●(See "Approach to illness associated with travel to Latin America and the Caribbean".)

Other issues related to travel are discussed separately:

●(See "Evaluation of fever in the returning traveler".)

●(See "Travel advice".)

●(See "Immunizations for travel".)

●(See "Prevention of malaria infection in travelers".)

GEOGRAPHY — The countries within the East Asia region include China, Japan, North Korea (Democratic People's Republic of Korea), South Korea (Republic of Korea), Mongolia, and Taiwan (figure 1).

East Asia an area of diverse geography, from the high mountains, plateau, steppes, and desert of the West to forested regions of the East and tropical rain forests in the South. There are several areas within this region (such as Japan, Hong Kong, South Korea, and Taiwan) where the health risks do not differ appreciably from Western Europe, North America, and Australia.

SURVEILLANCE DATA — The most commonly diagnosed illness in individuals seeking care after travel to East Asia are diarrhea and intestinal infection, enteric fever, arboviruses (including dengue), and tuberculosis. Less common illnesses include malaria and cutaneous leishmaniasis [5,6].

INITIAL EVALUATION — The focus of the initial evaluation should be on diagnosis of infections that are treatable, transmissible, and/or have serious sequelae (table 2).

History and physical examination — The clinical history should establish a number of clinical details and include review of the preceding 12 months prior to presentation (table 3) [7-9]:

●Careful documentation of signs and symptoms and their time of onset – Understanding the clinical timeline is important for establishing the likely incubation period, which is useful for narrowing the differential diagnosis. The causes of travel-associated fever based on the interval since exposure are summarized in the table and figure (table 4 and figure 2).

●The nature of travel (including geographic region, travel dates, type of transportation, and nature of accommodations) – The patient should be asked specifically about travel to areas with malaria transmission (figure 3) and/or areas with ongoing outbreaks (such as viral hemorrhagic fevers or meningitis). In some circumstances, infection control precautions may be warranted based on clinical and exposure history before diagnostic results are available (table 5).

●Relevant activities and exposures (such as consumption of unclean water or undercooked food, insect bites, animal exposure, sexual contact). (See 'Consider the exposure history' below.)

●General medical information (including vaccination history, past medical history, and medications) – If malaria chemoprophylaxis was taken, the clinician should inquire as to the drug, the dose, the intervals between doses, and the duration of therapy prior to arrival and following departure from the transmission area. (See 'Incubation period >10 days' below.)

Physical findings that signal severe illness warranting prompt intervention include hemodynamic instability, respiratory distress, hemorrhagic manifestations, and neurologic findings such as confusion, lethargy, stiff neck, or focal deficits. The physical examination should also include evaluation for skin lesions, lymphadenopathy, retinal or conjunctival changes, enlargement of liver or spleen, genital lesions, and neurologic findings.

Laboratory tests — The initial laboratory evaluation for travelers with fever may include complete blood count and differential, liver enzymes, and blood cultures.

Malaria is not a major risk in this region, with transmission restricted to a few discrete regions (in contrast to neighboring Southeast Asia). Therefore, blood smears and/or rapid diagnostic testing for malaria are indicated only for those who have been to those risk areas.

Additional studies depend upon exposures and other factors (table 6). Diagnostic testing should be targeted to the likeliest possible etiologies based on the epidemiologic exposure and clinical presentation, as discussed below.

SUBSEQUENT CLINICAL APPROACH

Consider the presenting syndrome

Systemic febrile illness

Incubation period ≤10 days — The differential diagnosis of fever with incubation period ≤10 days since exposure in a returning traveler includes:

●Dengue – (See 'Jaundice' below.)

●Chikungunya – (See 'Dermatologic manifestations' below.)

●Zika virus infection – (See 'Dermatologic manifestations' below.)

●Leptospirosis – (See 'Jaundice' below.)

●Typhus – (See 'Dermatologic manifestations' below.)

●Rickettsial infection – (See 'Dermatologic manifestations' below.)

●Coronavirus infections – (See 'Respiratory symptoms' below.)

●Severe fever with thrombocytopenia syndrome - Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral infection transmitted by ticks in central and eastern China, western Japan, and rural areas of South Korea. The illness begins with a nonspecific prodrome, including fever, headache, myalgia, arthralgia, vomiting, and diarrhea, that persists for about a week. Thereafter, patients may develop mucosal hemorrhage, hemorrhagic rash, altered mental status, and multiorgan failure. Laboratory findings include leukopenia, thrombocytopenia, elevated liver enzymes, and disseminated intravascular coagulopathy. Diagnosis is based on serum polymerase chain reaction (PCR) or serology. (See "Severe fever with thrombocytopenia syndrome virus".)

●Enteric fever – (See 'Dermatologic manifestations' below and "Enteric (typhoid and paratyphoid) fever: Epidemiology, clinical manifestations, and diagnosis".)

●Malaria – Incubation period ≤10 days is unusual but has been described. (See 'Incubation period >10 days' below.)

The differential diagnosis of acute fever also includes etiologies that may not be specific to international travel, such as urinary tract infection, influenza, or infectious mononucleosis.

Incubation period >10 days — The differential diagnosis of fever with incubation period >10 days since exposure in a returning traveler includes:

●Histoplasmosis – (See 'Respiratory symptoms' below.)

●Acute HIV infection – (See 'Dermatologic manifestations' below.)

●Q fever – (See 'Respiratory symptoms' below.)

●Tuberculosis – (See 'Respiratory symptoms' below.)

●Talaromyces (Penicillium) marneffei (rare)

●Enteric fever – (See 'Dermatologic manifestations' below and "Enteric (typhoid and paratyphoid) fever: Epidemiology, clinical manifestations, and diagnosis".)

●Malaria – In this region, malaria-endemic areas exist in China, North Korea, and South Korea. The transmission risk varies considerably within endemic areas. The risk of malaria in China is restricted to certain rural areas, particularly in the Yunnan Province bordering Myanmar; chloroquine resistance occurs in southern China and provinces bordering Myanmar, Laos, and Vietnam. Plasmodium vivax has re-emerged along the demilitarized zone in the Korean Peninsula, thus far presenting minimal risk to tourists [10-12]. Information regarding areas with malaria is available from the United States Centers for Disease Control and Prevention website.

Malaria is transmitted by Anopheles mosquitoes. Malaria due to Plasmodium falciparum usually manifests within 90 days of exposure (most frequently in the first month after exposure,) but should be considered even if exposure occurred more than 90 days previously. Malaria due to nonfalciparum species may have an incubation period of weeks or months, including up to one to two years after exposure.

Malaria is characterized by fever, malaise, nausea, vomiting, abdominal pain, diarrhea, myalgia, and anemia. Any patient with fever who has spent time in a region where malaria is endemic should be evaluated for malaria, even if afebrile at the time of evaluation (figure 3). Fevers in malaria wax and wane; ≥40 percent of patients may not have fever at the time of the initial evaluation, and physical examination can be normal [13-15].

Use of malaria prophylaxis may delay onset of symptoms. In addition, chemoprophylactic regimens other than primaquine or tafenoquine do not prevent relapse of vivax malaria [16-19]. (See "Prevention of malaria infection in travelers".)

Individuals with fever after travel in a malarious zone should undergo evaluation for malaria, regardless of prophylaxis status. The likelihood of protection against malaria is very high if prophylaxis is taken correctly but the efficacy is not 100 percent. Furthermore, some travelers may fail to take malaria prophylaxis correctly.

The diagnosis of malaria is established by rapid antigen testing or by visualization of parasites on peripheral smear; evaluation of the smear is important for species confirmation and assessment of parasitemia. (See "Malaria: Clinical manifestations and diagnosis in nonpregnant adults and children" and "Laboratory tools for diagnosis of malaria" and "Non-falciparum malaria: P. vivax, P. ovale, and P. malariae".)

The differential diagnosis of prolonged fever also includes etiologies that may be nonspecific to travel, such as endocarditis or occult abscess. Noninfectious etiologies such as malignancy should also be considered.

Gastrointestinal symptoms — Travel-related infections associated with fever and abdominal pain include:

●Enteric fever – Enteric fever (S. enterica serotype Typhi [formerly S. typhi] and S. enterica serovar Paratyphi A, B, and C) is characterized by abdominal pain, fever, chills, and headache. It may be associated with "rose spots" (faint salmon-colored macules on the trunk and abdomen), though these lesions may be sparse or absent. (See 'Incubation period ≤10 days' above.)

●Liver abscess – Liver abscess occurs worldwide and may be pyogenic or amebic; in addition, an invasive liver abscess syndrome due to Klebsiella pneumoniae has been described in East Asia (but also from Sri Lanka) and is often associated with metastatic complications, including endophthalmitis. Liver abscess is characterized by fever and right upper quadrant pain, nausea, vomiting, anorexia, weight loss, and malaise. Some patients with amebic liver abscess report history of dysentery within the previous few months; the incubation period is 8 to 20 weeks (median 12 weeks). The diagnosis of pyogenic liver abscess is made via radiographic imaging, followed by aspiration of the lesion for Gram stain and culture; the diagnosis of amebic liver abscess is made via serology or stool evaluation (parasite examination or PCR) (table 7). (See "Pyogenic liver abscess" and "Extraintestinal Entamoeba histolytica amebiasis", section on 'Amebic liver abscess' and "Invasive liver abscess syndrome caused by Klebsiella pneumoniae".)

●Fluke infections:

•Schistosomiasis (rare) - Schistosomiasis due to Schistosoma japonicum is endemic in parts of rural China. Transmission occurs via contact with fresh water where snails are intermediate hosts. Human skin is penetrated by cercariae released from the snail; these become schistosomulae and migrate to the liver where they mature into adult worms, which then migrate (against portal blood flow) to the mesenteric venules of the intestine. Clinical manifestations include intestinal symptoms (abdominal pain, anorexia, diarrhea) and hepatosplenic disease due to inflammation around trapped eggs in the presinusoidal periportal spaces of the liver; chronic infection leads to portal vein occlusion and portal hypertension with splenomegaly. Among returned travelers, serology is the most sensitive and useful test for screening. Among individuals living in endemic areas, stool should be obtained for egg microscopy and antigen detection. (See "Schistosomiasis: Epidemiology and clinical manifestations" and "Schistosomiasis: Diagnosis".)

•Liver flukes (rare) – Fascioliasis is endemic in sheep-rearing areas of temperate climates, including Central and South America, Europe, Asia, Africa, and the Middle East. Fascioliasis is transmitted by ingestion of watercress; the incubation period is 6 to 12 weeks. Clinical manifestations include fever, right upper quadrant pain, and eosinophilia. The diagnosis of liver fluke infection is established by identifying eggs in stool, duodenal aspirates, or bile specimens. (See "Liver flukes: Fascioliasis".)

Clonorchiasis due to Clonorchis sinensis (also known as Chinese liver fluke), is endemic in China, Japan, Taiwan, Vietnam, and Korea. When acute symptoms manifest, they usually begin 10 to 26 days after consumption of heavily infected undercooked fish and last for two to four weeks. The illness is characterized by fever, anorexia, abdominal pain, myalgia, arthralgia, malaise, and urticaria. Late in the course of infection, symptoms can occur due to chronic mechanical injury and bile duct obstruction by adult flukes; these include fatigue, abdominal discomfort, anorexia, weight loss, dyspepsia, and diarrhea. Severe disease can result in obstructive jaundice, pancreatitis, recurrent cholangitis, and pyogenic liver abscesses. The diagnosis can be established by identifying eggs in stool, duodenal aspirates, or bile specimens. (See "Liver flukes: Clonorchis, Opisthorchis, and Metorchis".)

•Fasciolopsiasis (rare) - Fasciolopsiasis (giant intestinal fluke) infection is common in Southeast Asia and the Far East. Transmission to humans is typically associated with ingestion of contaminated water or plants, particularly bamboo shoots, watercress, or water chestnuts. Fasciolopsiasis is usually asymptomatic. When symptoms do occur, it is usually in the setting of heavy infection and the onset is typically 30 to 60 days after exposure. Symptoms are due to inflammation, ulceration, and microabscesses that can develop where the flukes attach to the intestine. Anorexia, vomiting, diarrhea, abdominal pain, and signs of malabsorption can occur. The diagnosis is established by demonstrating either adult worms or eggs in the stool or other fluids.

●Echinococcosis (rare) – Clinical manifestations of Echinococcus multilocularis infection include right upper quadrant discomfort, malaise, and weight loss. The infection is transmitted via ingestion of a tapeworm whose life cycle includes a definitive host (usually dogs) and an intermediate host (such as sheep). In this region, the main risk areas are restricted to western China and Mongolia. Onset of clinical manifestations typically occurs decades following infection. The diagnosis is typically established by ultrasound imaging in combination with serologic testing.

The differential diagnosis of fever with abdominal pain also includes cosmopolitan etiologies unrelated to travel such as appendicitis, diverticulitis, cholecystitis, pancreatitis, or cholangitis due to stones.

Travel-related infections associated with fever and diarrhea include:

●Invasive enteropathies

•Campylobacter infection – Campylobacter infection is characterized by acute onset of watery or bloody diarrhea, abdominal pain and cramping, and nausea and vomiting. Fever frequently precedes onset of diarrhea and may be high grade. Campylobacter is a zoonotic bacterial infection acquired by ingesting contaminated food or water. Incubation is usually 2 to 5 days (range 1 to 10 days). Diagnosis is made by stool culture or PCR. (See "Campylobacter infection: Clinical manifestations, diagnosis, and treatment".)

•Vibrio parahaemolyticus infection – V. parahaemolyticus causes diarrheal illness; it thrives in warmer water and areas of diminished salinity. Infection is particularly associated with consumption of raw or undercooked seafood, especially shellfish. The median incubation period is 17 hours. The diagnosis is established by stool culture. (See "Vibrio parahaemolyticus infections".)

•Shigellosis – Shigellosis is a bacterial infection of the distal small intestine and colon characterized by fever, diarrhea (sometimes bloody), nausea, and sometimes cramps and vomiting. Infection occurs worldwide and is acquired by ingestion of food or water that has been contaminated by an infected person, or via fecal-oral transmission. The incubation period is usually one to three days (up to a week). The diagnosis is established via stool culture or PCR. (See "Shigella infection: Epidemiology, clinical manifestations, and diagnosis".)

•Nontyphoidal salmonellosis – Nontyphoidal salmonellosis infection is characterized by diarrhea, nausea, vomiting, fever, and abdominal cramping. Infection occurs worldwide; transmission is fecal-oral. The incubation period is 6 to 72 hours, and diagnosis is established via culture or PCR of stool or blood culture. (See "Nontyphoidal Salmonella: Gastrointestinal infection and asymptomatic carriage".)

●Cyclosporiasis – Cyclosporiasis is characterized by anorexia, nausea, flatulence, fatigue, abdominal cramping, diarrhea, low-grade fever, and weight loss. Transmission is via ingestion of contaminated food or water. The infection is most frequently reported in Latin America, the Indian subcontinent, and Southeast Asia. The incubation period is approximately one week. The diagnosis is established via stool microscopy or PCR. (See "Cyclospora infection".)

●Cryptosporidiosis – Cryptosporidiosis is characterized by voluminous watery diarrhea and low-grade fever. Fever may precedes onset of diarrhea. Infection occurs worldwide, and transmission occurs via waterborne, foodborne, or fecal-oral routes. The incubation period is 3 to 28 days, and the diagnosis is established via stool microscopy, PCR, or enzyme immunoassay. (See "Cryptosporidiosis: Epidemiology, clinical manifestations, and diagnosis".)

●Intestinal amebiasis – Intestinal amebiasis is characterized by loose stools that may be bloody; fever occurs in less than half of patients. Infection occurs worldwide, and transmission is fecal-oral. The incubation period is variable (one to three weeks) and the diagnosis is established via serology or antigen testing together with detection of the parasite in stool or extraintestinal sites (such as necrotic debris from liver abscess). (See "Intestinal Entamoeba histolytica amebiasis".)

●Strongyloidiasis – Most patients with Strongyloides infection do not experience prominent symptoms. When manifestations do occur, they may include abdominal pain with diarrhea, cough, or rash. Some patients have eosinophilia in the absence of symptoms. The disease is transmitted via penetration of larvae into the skin followed by eventual migration to the intestines, and it is endemic in rural areas of tropical and subtropical regions. The incubation period is weeks to decades; the diagnosis is usually made by detecting rhabditiform larvae in concentrated stool or via serology. (See 'Respiratory symptoms' below and "Strongyloidiasis".)

Causes of diarrhea in travelers that are not typically associated with fever include:

●Travelers' diarrhea – Travelers' diarrhea is classically caused by enterotoxigenic Escherichia coli and other bacterial and viral pathogens; it is characterized by watery diarrhea, malaise, anorexia, and abdominal cramps. Transmission is fecal-oral and most commonly occurs via ingestion of contaminated food or water; risk is highest in South and Southeast Asia, Africa, South and Central America, and Mexico. The incubation period depends on the pathogen and can range from <1 day to several days. Travel-associated diarrhea is usually self-limited. Patients with severe, prolonged, or bloody diarrhea warrant diagnostic evaluation. (See "Travelers' diarrhea: Treatment and prevention".)

●Giardiasis – Giardiasis is characterized by diarrhea, malaise, abdominal cramps, and weight loss. Fever is not prominent. It occurs worldwide and is transmitted by waterborne, foodborne, or fecal-oral routes; the incubation period is typically 7 to 10 days (range 3 to 25 days). The diagnosis may be established by stool microscopy, antigen detection, or PCR. (See "Giardiasis: Epidemiology, clinical manifestations, and diagnosis".)

The differential diagnosis of gastrointestinal symptoms also includes cosmopolitan etiologies unrelated to travel such as appendicitis, cholecystitis, pancreatitis, cholangitis due to stones, or new-onset inflammatory bowel disease.

Jaundice — Travel-related infections associated with jaundice include:

●Severe dengue fever – The cardinal features of dengue hemorrhagic fever include fever, increased vascular permeability, hemorrhagic manifestations, and marked thrombocytopenia (≤100,000 cells/mm³). The virus is transmitted by Aedes aegypti mosquitoes, which have broad epidemiologic distribution (figure 4); the incubation period is 4 to 7 days (range 3 to 10 days). The diagnosis is established via PCR, NS1 antigen, or serologic testing. (See 'Dermatologic manifestations' below and "Dengue virus infection: Clinical manifestations and diagnosis".)

●Acute viral hepatitis

•Hepatitis A and E are acute infections transmitted by the fecal-oral route; the incubation period ranges from 15 to 60 days. Hepatitis A is characterized by nausea, vomiting, anorexia, fever, malaise, and abdominal pain; the infection is usually self-limited and occurs worldwide. The average incubation period is 28 days (range 15 to 50 days). Hepatitis E is usually asymptomatic; symptoms occur in up to 5 percent of cases and resemble those of hepatitis A. Hepatitis E occurs worldwide; the prevalence is highest in Asia and Africa. The infections are diagnosed by serology or PCR. (See "Hepatitis A virus infection in adults: Epidemiology, clinical manifestations, and diagnosis" and "Hepatitis E virus infection".)

•Hepatitis B and C can present acutely or chronically and are transmitted by body fluids. Hepatitis D infection always occurs in association with hepatitis B infection. The incubation periods of hepatitis B and C are 4 to 16 weeks and 2 to 26 weeks, respectively. Hepatitis B and C occur worldwide. The infections are diagnosed by serology or PCR. (See "Hepatitis B virus: Clinical manifestations and natural history" and "Hepatitis B virus: Screening and diagnosis in adults" and "Epidemiology, clinical manifestations and diagnosis of hepatitis D virus infection" and "Clinical manifestations and natural history of chronic hepatitis C virus infection" and "Screening and diagnosis of chronic hepatitis C virus infection".)

●Leptospirosis – Leptospirosis is characterized by fever, rigors, myalgia, conjunctival suffusion, and headache; respiratory involvement can develop as a complication. Less common symptoms and signs include cough, nausea, vomiting, diarrhea, abdominal pain, and jaundice. It is transmitted via exposure to animal urine, contaminated water or soil, or infected animal tissue; outbreaks in endemic areas are associated with increased rainfall or flooding. The incubation is 2 to 29 days. The diagnosis is established via serology or culture of blood or urine. (See "Leptospirosis: Epidemiology, microbiology, clinical manifestations, and diagnosis".)

●Severe malaria – Manifestations of severe malaria are summarized in the table (table 8). (See 'Incubation period >10 days' above and "Malaria: Clinical manifestations and diagnosis in nonpregnant adults and children" and "Laboratory tools for diagnosis of malaria" and "Non-falciparum malaria: P. vivax, P. ovale, and P. malariae".)

●Liver flukes (rare) – (See 'Gastrointestinal symptoms' above.)

The differential diagnosis of fever with jaundice also includes etiologies that may be nonspecific to travel, such as cytomegalovirus infection and Epstein-Barr virus infection. (See "Infectious mononucleosis" and "Epidemiology, clinical manifestations, and treatment of cytomegalovirus infection in immunocompetent adults" and "Overview of diagnostic tests for cytomegalovirus infection".)

Dermatologic manifestations — Localized dermatologic conditions that occur in association with travel to East Asia include cutaneous larva migrans, cutaneous leishmaniasis, myiasis, tungiasis, chiggers, and phytophotodermatitis. These and other issues related to skin lesions in the returning traveler are discussed separately. (See "Skin lesions in the returning traveler" and "Hookworm-related cutaneous larva migrans" and "Cutaneous leishmaniasis: Clinical manifestations and diagnosis" and "Chigger bites" and "Photosensitivity disorders (photodermatoses): Clinical manifestations, diagnosis, and treatment".)

Systemic travel-related infections associated with rash include (table 9):

●Dengue fever – Classic dengue fever is an acute febrile illness accompanied by headache, retro-orbital pain, and marked muscle and bone pains. Fever typically lasts for five to seven days. Hemorrhagic manifestations and thrombocytopenia can also occur. A macular or maculopapular rash occurs in approximately half of cases. The virus is transmitted by Ae. aegypti or Aedes albopictus mosquitoes, which have broad epidemiologic distribution; the incubation period is 4 to 7 days (range 3 to 10 days). The diagnosis is established via serologic testing, NS1 antigen, or PCR. (See 'Jaundice' above and "Dengue virus infection: Clinical manifestations and diagnosis".)

●Chikungunya – Chikungunya virus infection is characterized by acute febrile polyarthralgia and arthritis. Skin manifestations (macular or maculopapular rash) occur in 40 to 75 percent of patients. Chikungunya is transmitted by Aedes mosquitoes and occurs in Africa, Asia, Europe, islands in the Indian and Pacific Oceans, and the Americas. The incubation period is 1 to 14 days. The diagnosis is established via serology or reverse-transcriptase PCR. (See "Chikungunya fever: Epidemiology, clinical manifestations, and diagnosis".)

●Zika virus – Zika virus infection is characterized by fever, rash, headache, arthralgia, myalgia, and conjunctivitis [20]. The primary mode of transmission is via Aedes mosquito bites; sexual transmission can also occur. Zika virus infection occurs in Africa, Asia, the Pacific Islands, the Americas, and the Caribbean. The incubation period is 2 to 14 days. The diagnosis of Zika virus infection is established by PCR or serology. (See "Zika virus infection: An overview".)

●Typhus – Scrub typhus (caused by Orientia tsutsugamushi) and murine typhus (caused by Rickettsia typhi) are endemic in regions of East Asia.

•Scrub typhus is transmitted by mites and occurs in rural areas with scrub vegetation but has also been acquired in urban or periurban areas. Scrub typhus may begin insidiously with headache, anorexia, and malaise, or start abruptly with chills and fever. As the illness evolves most patients develop high fever, worsening of headache severity, and myalgias. An eschar or rash may develop in a subset of patients. The diagnosis is established by serology. (See "Scrub typhus", section on 'Diagnosis'.)

•Murine typhus is transmitted to humans by rat or cat fleas and occurs most commonly in urban settings. It is typically a mild illness with an incubation period from 8 to 16 days. The onset of illness is usually abrupt, with nonspecific symptoms followed by fever, a maculopapular rash, and headache. Thrombocytopenia occurs in half of patients. The diagnosis is based on clinical suspicion and may be confirmed serologically. (See "Murine typhus".)

●Acute HIV infection – Acute HIV infection is commonly characterized by fever, lymphadenopathy, sore throat, rash, myalgia/arthralgia, and headache. The infection is transmitted sexually, and infection occurs worldwide. The incubation period is two to four weeks. The diagnosis is established via immunoassay and viral load. (See "Acute and early HIV infection: Clinical manifestations and diagnosis".)

●Measles – Measles is characterized by fever, rash, cough, coryza, and conjunctivitis; pneumonia can develop as a complication of measles. Transmission is human to human, and infection occurs worldwide. The incubation period is 6 to 21 days (median 13 days). The diagnosis is usually established via serologic testing. (See "Measles: Clinical manifestations, diagnosis, treatment, and prevention".)

●Enteric fever – Enteric fever (S. enterica serotype Typhi [formerly S. typhi] and S. enterica serovar Paratyphi A, B, and C) is characterized by abdominal pain, fever, chills, and headache. It may be associated with "rose spots" (faint salmon-colored macules on the trunk and abdomen), though these lesions may be sparse or absent. (See 'Incubation period ≤10 days' above.)

●Meningococcal infection – Meningococcal infection is characterized by acute onset of fever, nausea, vomiting, headache, confusion, and myalgia. Nonblanching purpuric rash may be observed. (See 'Neurologic symptoms' below.)

●Strongyloidiasis (rare) – Strongyloides infection may produce cutaneous reactions when larvae penetrate the skin. These reactions include inflammation, edema, petechiae, serpiginous or urticarial tracts, and pruritus. As larvae migrate, a raised, evanescent pink track develops; these lesions are known as larva currens ("running" larva) and are pathognomonic of strongyloidiasis. (See 'Gastrointestinal symptoms' above and 'Respiratory symptoms' below and "Strongyloidiasis".)

●Anthrax (rare) – Cutaneous anthrax is characterized by a painless papule that enlarges, develops a central vesicle, and subsequently erodes, leaving a necrotic ulcer with a black depressed eschar. Extensive surrounding edema, regional lymphadenopathy, and fever may be present. Anthrax is transmitted by contact with animals or animal materials (eg, skin) contaminated with anthrax spores. In this region, anthrax is largely restricted to rural agricultural regions in western China and Mongolia. The incubation period is one to seven days; the diagnosis is established via culture or by two supportive nonculture methods. (See "Clinical manifestations and diagnosis of anthrax".)

●T. (Penicillium) marneffei (rare) - Talaromycosis infection is an endemic fungal infection that causes disease among immunocompromised patients in Southeast Asia, northern Australia, South Asia (including India), and China. Most patients present with generalized lymphadenopathy, hepatomegaly, and splenomegaly. Skin lesions are relatively common; when present, they are the best clue to diagnosis. Patients may also present with respiratory, gastrointestinal, and neurologic findings. A definitive diagnosis is made by culturing the fungus, most commonly from blood, skin biopsy, bone marrow, or lymph nodes. (See "Epidemiology and clinical manifestations of Talaromyces (Penicillium) marneffei infection" and "Diagnosis and treatment of Talaromyces (Penicillium) marneffei infection".)

Other travel-related hazards with dermatologic manifestations include:

●Snake bites – Venomous snakes are present throughout East Asia. Naja spp (Asian cobras), Bungarus multicinctus (Chinese krait), Trimeresurus flavoviridis (Japanese habu), Trimeresurus mucrosquamatus (Chinese habu), and Agkistrodon blomhoffii (mamushi) are responsible for most deaths and morbidity. Severe envenomation is suggested by confirmation of a bite from a dangerous snake (digital photograph or verified snake specimen), rapidly progressive local effects (swelling, blistering, or bruising), signs of coagulopathy (oozing of blood from the bite site, phlebotomy sites, or gums), and other findings of systemic envenomation including lethargy, nausea, vomiting, headache, epistaxis, weakness, sudden collapse, seizures, or evidence of rhabdomyolysis. (See "Snakebites worldwide: Clinical manifestations and diagnosis" and "Snakebites worldwide: Management".)

●Marine hazards – Marine envenomations are characterized by single or multiple puncture wounds and sudden onset of severe pain. There are many potential marine creatures capable of envenomation; these include jellyfish, sea snakes, blue-ringed octopus, cone shells, stingrays, and stone fish. (See "Jellyfish stings" and "Marine envenomations from corals, sea urchins, fish, or stingrays".)

Respiratory symptoms

Absence of eosinophilia — Travel-related infections associated with fever and respiratory symptoms (in the absence of eosinophilia) include:

●Influenza – Influenza (including seasonal and avian influenza) should be suspected in patients with fever and respiratory symptoms returning from a region where influenza was circulating. The incubation period is two to four days. The diagnosis is established via rapid antigen test or nucleic acid test of nasopharyngeal aspirates, washings, or swabs. (See "Seasonal influenza in adults: Clinical manifestations and diagnosis" and "Avian influenza: Clinical manifestations and diagnosis" and "Avian influenza: Epidemiology and transmission".)

●Coronavirus infections – Coronavirus infections that have emerged from East Asia include Severe acute respiratory syndrome (SARS), caused by SARS-associated coronavirus (SARS-CoV), and coronavirus disease 2019, caused by SARS-CoV-2. (See "Severe acute respiratory syndrome (SARS)" and "Coronaviruses", section on 'Coronavirus disease 2019 (COVID-19) pandemic'.)

●Tuberculosis – Tuberculosis is characterized by cough >2 to 3 weeks' duration, lymphadenopathy, fevers, night sweats, and weight loss. Transmission is human to human, and infection occurs worldwide. The incubation period is at least three months. Diagnostic evaluation begins with chest radiography, followed by sputum acid-fast bacilli smear and nucleic acid amplification testing. (See "Diagnosis of pulmonary tuberculosis in adults".)

The differential diagnosis of fever with respiratory symptoms also includes etiologies nonspecific to travel, such as upper respiratory tract infection and community-acquired pneumonia (due to bacterial or viral pathogens). (See "The common cold in adults: Treatment and prevention" and "Epidemiology, pathogenesis, and microbiology of community-acquired pneumonia in adults" and "Clinical evaluation and diagnostic testing for community-acquired pneumonia in adults".)

Less common travel-related infections with fever and respiratory symptoms include:

●Legionnaires' disease – Legionnaires' disease is characterized by fever, myalgia, headache, and nonproductive cough; abdominal pain and diarrhea may be present. It is transmitted via inhalation of aerosols containing the organism; among travelers, the most common source has been contaminated water in hotels or cruise ships. Infection also occurs in nontravelers. The incubation period is 2 to 10 days (usually 5 to 6 days). Special media is needed to culture the organism; the diagnosis can also be established by specific rapid tests, urine antigen, and serologic testing. (See "Clinical manifestations and diagnosis of Legionella infection".)

●Leptospirosis – Leptospirosis may be complicated by severe pulmonary disease with pulmonary hemorrhage. (See "Leptospirosis: Epidemiology, microbiology, clinical manifestations, and diagnosis".)

●Histoplasmosis – Acute pulmonary histoplasmosis is characterized by fever, headache, nonproductive cough, pleuritic chest pain, and fatigue. The infection is transmitted via inhalation of spores from soil contaminated with bird droppings or bat guano. The infection occurs on all continents except Antarctica, most often in association with river valleys. The incubation period is 3 to 17 days. The diagnosis is established via histopathology, culture, antigen detection, or serology. (See "Pathogenesis and clinical features of pulmonary histoplasmosis" and "Diagnosis and treatment of pulmonary histoplasmosis".)

●Hantavirus – Hantaviruses occur worldwide. New World hantaviruses are associated with hantavirus cardiopulmonary syndrome; Old World hantaviruses are associated with hemorrhagic fever with renal syndrome (HFRS). Hantaviruses are transmitted by aerosolization of rodent urine, feces, or saliva. A severe form of HFRS caused by Hantaan virus occurs in Korea, China, and Japan and is associated with the striped field mouse (Apodemus agrarius). The incubation period is a few days to six weeks; the diagnosis is established via serology. (See "Epidemiology and diagnosis of hantavirus infections" and "Hantavirus cardiopulmonary syndrome" and "Kidney involvement in hantavirus infections".)

●Plague (rare) – Pneumonic plague is characterized by sudden onset of dyspnea, high fever, pleuritic chest pain, and cough that may be accompanied by bloody sputum. Pneumonic plague can be primary (eg, acquired by inhalation of respiratory secretions or aerosolized droplets from infected animals or humans or by laboratory exposure) or secondary (eg, developing in the setting of bubonic or septicemic plague). The disease occurs in the southwestern United States, the former Soviet Union, and foci in Africa, Asia, and South America. The incubation period is two to eight days; the diagnosis is established by isolation of the organism in culture, serologic testing, or rapid testing in some circumstances. (See "Clinical manifestations, diagnosis, and treatment of plague (Yersinia pestis infection)".)

●Psittacosis – Psittacosis is characterized by fever, dry cough, and bird exposure. It is transmitted by exposure to birds, including contact with poultry or visiting aviaries or bird parks. The incubation period is usually 5 to 14 days. The diagnosis is established by serologic testing. (See "Psittacosis".)

●Melioidosis (rare) – Melioidosis is characterized by pneumonia and localized skin infection. Transmission occurs via percutaneous inoculation associated with exposure to wet soil or contaminated water with hematogenous dissemination; less commonly, infection may be transmitted via aspiration of contaminated water. The disease is endemic in South and Southeast Asia and northern Australia, with isolated reports from Africa and South America. The incubation period ranges from 1 to 21 days (but can be months or years). The diagnosis is established via culture. (See "Melioidosis: Epidemiology, clinical manifestations, and diagnosis".)

Travel-associated infections that may include respiratory symptoms but typically present with rash as the prominent feature include measles and anthrax. (See 'Dermatologic manifestations' above.)

Presence of eosinophilia — Travel-related infections associated with fever, respiratory symptoms, and eosinophilia are rare; they include:

●Loeffler syndrome – Loeffler syndrome is a condition associated with transpulmonary passage of larvae (Ascaris, hookworm, or Strongyloides); it is characterized by respiratory symptoms (dry cough, dyspnea, fever, wheezing), characteristic radiographic findings (migratory bilateral round infiltrates), and peripheral eosinophilia. The incubation period is a few weeks. The disease occurs in Asia, Africa, and South America. The diagnosis may be definitively established via visualization of Ascaris, hookworm, or Strongyloides larvae in respiratory secretions or gastric aspirates; stool examination is not useful for diagnosis of pulmonary infection. (See "Ascariasis".)

●Strongyloidiasis – Most patients with Strongyloides infection do not experience prominent symptoms. Uncommonly, transpulmonary migration of Strongyloides larvae is associated with dry cough, throat irritation, dyspnea, wheezing, and hemoptysis. Eosinophilia may occur in the presence or the absence of symptoms. (See 'Gastrointestinal symptoms' above and 'Respiratory symptoms' above and "Strongyloidiasis".)

●Paragonimiasis (rare) − Paragonimiasis (lung fluke) can be acquired in most countries of the region. Transmission is via consumption of raw or undercooked crab or crayfish. Between initial infection and first egg production (about two months), fever, malaise, diarrhea, epigastric pain, and/or urticaria may occur. As larvae penetrate the diaphragm and migrate within the pleural cavity, pleuritic chest pain may develop; additional symptoms may include dyspnea, cough, and malaise. During the second phase of infection when mature flukes inhabit the lungs, worms induce inflammation and fibrosis; recurrent hemoptysis is the most common symptom. During late infection the diagnosis can usually be confirmed by identifying Paragonimus eggs in the sputum or bronchoalveolar lavage. (See "Paragonimiasis".)

Issues related to the approach to patients with eosinophilia are discussed further separately. (See "Approach to the patient with unexplained eosinophilia".)

Neurologic symptoms — Travel-related infections associated with fever and neurologic symptoms include:

●Japanese encephalitis – Japanese encephalitis is characterized by acute encephalitis; aseptic meningitis or nonspecific febrile illness with headache also occurs. It is transmitted by mosquitoes and occurs throughout most of Asia and parts of the Western Pacific region. The incubation period is 5 to 15 days. The diagnosis is established via detection of Japanese encephalitis virus-specific immunoglobulin (Ig)M antibody in cerebrospinal fluid (CSF) or serum by an enzyme-linked immunosorbent assay or via PCR. (See "Japanese encephalitis".)

●Meningitis

•Meningococcal infection – Meningococcal infection is characterized by acute onset of fever, nausea, vomiting, headache, confusion, and myalgia. Nonblanching purpuric rash may be observed. The infection is transmitted by person-to-person contact and occurs worldwide; the highest rate of disease is in the meningitis belt of sub-Saharan Africa. The incubation period is 2 to 10 days, and the diagnosis is established via culture of blood or spinal fluid, agglutination tests, or PCR. (See "Clinical manifestations of meningococcal infection" and "Diagnosis of meningococcal infection".)

•Eosinophilic meningitis – Eosinophilic meningitis due to Angiostrongylus cantonensis occurs principally in Southeast Asia; the parasite has also been found outside of this area in regions of Africa, Australia, Cuba, Puerto Rico, and Jamaica. Humans can acquire the infection by eating raw or undercooked snails or slugs infected with the parasite. Clinical manifestations include headache, neck stiffness, nausea, vomiting, and fever. The incubation period of A. cantonensis averages one to three weeks. The diagnosis is based upon the clinical presentation, presence of eosinophilic CSF, pleocytosis, and epidemiologic history of exposure to infective larvae. (See "Eosinophilic meningitis".)

●Cysticercosis – Cysticercosis is characterized by seizures (in the setting of parenchymal involvement); extraparenchymal cysts are associated with symptoms of elevated intracranial pressure (eg, headache, nausea, and vomiting). The disease is transmitted by ingestion of Taenia solium eggs shed in the stool of a human tapeworm carrier; humans become tapeworm carriers by ingesting undercooked pork containing cysticerci in muscle tissue. Cysticercosis is endemic in many regions of Central and South America, sub-Saharan Africa, India, and Asia. The median incubation period for cysticercosis is about 3.5 years. The diagnosis is established via radiography and serology. (See "Cysticercosis: Clinical manifestations and diagnosis".)

●Guillain-Barré syndrome – Guillain-Barré syndrome can be precipitated by infection due to Campylobacter jejuni (within one to two weeks), Zika virus (within one month), and other infections. The cardinal clinical features are progressive, symmetric muscle weakness and diminished deep tendon reflexes. The diagnosis is based upon the clinical presentation. (See "Guillain-Barré syndrome in adults: Pathogenesis, clinical features, and diagnosis".)

●Cerebral malaria – Cerebral malaria is an encephalopathy that presents with impaired consciousness, delirium, and/or seizures. (See "Malaria: Clinical manifestations and diagnosis in nonpregnant adults and children", section on 'Cerebral malaria' and "Laboratory tools for diagnosis of malaria" and 'Incubation period >10 days' above.)

●Rabies (rare) – Rabies is transmitted by animal bite (dogs, bats, and other animals) and is distributed worldwide. The average incubation period is one to three months. Forms of rabies include encephalitic rabies (referred to as "furious rabies" in animals) or paralytic rabies (referred to as "dumb rabies" in animals). Encephalitic rabies is more common (80 percent of cases) and is characterized by fever, hydrophobia, pharyngeal spasms, and hyperactivity, whereas paralytic rabies is characterized by flaccid paralysis. The diagnosis can be made by virus-specific immunofluorescent staining of skin biopsy specimens, isolation of virus from the saliva, or detection of antirabies antibodies in serum or CSF. (See "Clinical manifestations and diagnosis of rabies".)

The differential diagnosis of fever with neurologic symptoms also includes etiologies unrelated to travel such as meningitis, encephalitis, brain abscess, and subdural empyema. Travelers with onset of neurologic and/or gastrointestinal symptoms following ingestion of seafood should also be considered for ciguatera fish poisoning and shellfish poisoning. (See "Ciguatera fish poisoning" and "Overview of shellfish, pufferfish, and other marine toxin poisoning".)

Other travel-related illnesses with neurologic manifestations include:

●High-altitude disease – There are large high-altitude areas within the East Asian region, especially in western China (including the Tibetan plateau) and Mongolia. Altitude illness is a high risk for travelers to these regions, especially those who ascend rapidly via motorized transport. High-altitude areas also exist in Japan and Taiwan. Acute mountain sickness (AMS) is diagnosed clinically in a person who lives at low altitude but has recently ascended to high altitude (generally over 2000 m). Symptoms include headache, fatigue, lightheadedness, anorexia, nausea and vomiting, disturbed sleep, and mild shortness of breath with exertion. Onset of AMS is usually delayed for 6 to 12 hours following arrival at high altitude but can occur as rapidly as 1 to 2 hours or as late as 24 hours. (See "High-altitude illness: Physiology, risk factors, and general prevention" and "Acute mountain sickness and high-altitude cerebral edema".).

Consider the incubation period — The clinical suspicion for a given pathogen may be raised or lowered based on the timing of travel/exposure. The incubation periods for common infections associated with travel are summarized in the table and figure (table 4 and figure 2).

Consider the exposure history — Some important exposures for transmission of infection are summarized below (table 10).

Arthropod bites — Insects serve as vectors for a large number of infectious diseases, as follows:

●Mosquitoes – Infections transmitted by mosquitoes include malaria, dengue fever, chikungunya, Zika virus infection, West Nile virus infection, and filariasis. There is no risk for yellow fever in East Asia, although the mosquito vector of yellow fever (Ae. aegypti) is present. (See related topics.)

●Sand flies – Leishmaniasis is transmitted by sand flies. (See "Visceral leishmaniasis: Clinical manifestations and diagnosis" and "Cutaneous leishmaniasis: Clinical manifestations and diagnosis".)

●Ticks – Tick-borne infections include SFTS, spotted fever Rickettsia, and Kyasanur forest disease. (See "Severe fever with thrombocytopenia syndrome virus" and "Other spotted fever group rickettsial infections".)

●Fleas – Infections transmitted by fleas include murine typhus (R. typhi) and plague. (See "Murine typhus", section on 'Diagnosis' and "Clinical manifestations, diagnosis, and treatment of plague (Yersinia pestis infection)".)

●Lice – Infections transmitted by lice include epidemic typhus (Rickettsia prowazekii) and trench fever (Bartonella quintana). (See "Epidemic typhus" and "Bartonella quintana infections: Clinical features, diagnosis, and treatment".)

●Mites – Scrub typhus (O. tsutsugamushi) is transmitted by mites. (See "Scrub typhus".)

Unclean water or undercooked food — Consumption of unclean water or undercooked food may be associated with travelers' diarrhea, giardiasis, enteric fever, salmonellosis, shigellosis, Campylobacter infection, hepatitis A and E, or amebic dysentery.

Consumption of unpasteurized milk and milk products from infected livestock may be associated with listeriosis, brucellosis, or Q fever.

Animal exposures — Animal bites may be associated with transmission of rabies (via dogs, bats, and other mammals), cat-scratch fever (Bartonella henselae), rat-bite fever (Spirillum minus or Streptobacillus moniliformis), and simian herpesvirus B infection (via Old World monkeys, especially macaque family). (See "Zoonoses: Dogs" and "Zoonoses: Cats" and "Zoonoses: Animals other than dogs and cats".)

Contact with animals may be associated with transmission of toxoplasmosis (cats), anthrax (cattle, sheep, goats), Q fever (cattle, sheep, goats), hantavirus infection (rodents), plague (rodents), psittacosis (birds), avian influenza (birds), and rabies (dogs, bats, and other animals).

Sexual contact — Sexual contact with new partners is common among certain subgroups of travelers and visitors to certain locations [21,22]. The clinical history should include a sexual history, including number of partners, types of sexual activities, and whether barrier protection was used. The physical examination should include a careful genital examination in individuals who have had sexual contact while traveling.

Unprotected sex with a new partner, partners, or commercial sex worker may be associated with a number of sexually transmitted infections; these include herpes, syphilis, gonorrhea, chlamydia, HIV, hepatitis (A, B, or C), Zika virus infection, and viral hemorrhagic fevers.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Travel medicine".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Vaccines for travel (The Basics)")

●Beyond the Basics topic (see "Patient education: General travel advice (Beyond the Basics)")

SUMMARY

●The most commonly diagnosed illness in individuals seeking care after travel to East Asia are diarrhea and intestinal infection, arboviruses (including dengue), and tuberculosis (table 1 and table 2). In addition to travel-related infections, cosmopolitan causes of fever should be considered. (See 'Surveillance data' above.)

●The clinical history should include careful documentation of signs and symptoms and their time of onset, the nature of travel, relevant activities and exposures, and general medical information (table 3). The physical examination should include evaluation for skin lesions, lymphadenopathy, retinal or conjunctival changes, enlargement of liver or spleen, genital lesions, and neurologic findings. The approach to the initial laboratory evaluation is summarized in the table (table 6). (See 'History and physical examination' above.)

●The clinician should consider the patient's presenting syndrome in conjunction with the incubation period, relevant epidemiologic exposures, and geographic region of travel. The differential diagnoses for a number of clinical syndromes are summarized above. (See 'Consider the presenting syndrome' above.)

●The clinical suspicion for a given pathogen may be raised or lowered based on the timing of travel/exposure. The incubation periods for common infections associated with travel are summarized in the table and figure (table 4 and figure 2). (See 'Consider the incubation period' above.)

●Relevant exposures for transmission of infection include consumption of unclean water or undercooked food, arthropod bites, animal exposures, and sexual contact (table 10). (See 'Consider the exposure history' above.)