Approach to illness associated with travel to Latin America and the Caribbean

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].

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 [4]. The World Health Organization website also has regularly updated information about outbreaks.

The approach to evaluation of illness associated with travel to Latin America and the Caribbean will be reviewed here.

Issues related to travel to other regions are discussed separately:

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

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

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

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 Central America include Belize, Costa Rica, El Salvador, Guatemala, Honduras, Nicaragua, and Panama. Climates are mostly tropical with abundant rain forests; rainy seasons generally last from April through November. Costa Rica contains mountainous regions as well as high-altitude plains.

The countries within the Caribbean include Anguilla, Antigua, Aruba, the Bahamas, Barbados, British Virgin Islands, Cayman Islands, Cuba, Curaçao, Dominica, Dominican Republic, Grenada, Guadeloupe, Haiti, Jamaica, Martinique, Montserrat, Puerto Rico, Saint Barthélemy, Saint Kitts and Nevis, Saint Lucia, Saint Martin (French), Saint Vincent and the Grenadines, Sint Maarten (Dutch), Trinidad and Tobago, and Turks and Caicos Islands. The region includes hundreds of islands. The tropical climate has variable rainfall dependent on elevation, and the topography ranges from flat terrain of non-volcanic origin to mountainous terrain.

The tropical zone of South America includes the countries of Bolivia, Brazil, Colombia, Ecuador, French Guiana, Guyana (previously known as British Guiana), Paraguay, Peru, Suriname, and Venezuela.

The temperate zone of South America includes the countries of Argentina, Chile, Falkland Islands, and Uruguay. Travelers to temperate regions are less likely to encounter infections found in the tropics. Visitors to high-altitude regions in the Andes may develop altitude sickness.

SURVEILLANCE DATA — The largest contemporary experience in travel-related disease in resource-limited countries comes from GeoSentinel, the global surveillance network of the International Society of Travel Medicine and the United States Centers for Disease Control and Prevention [5-9]. The GeoSentinel report was updated in 2013, spanning 1997 to 2011; this report encompasses data on more than 140,000 patients with confirmed or suspected travel-related illness [8]. Among the approximately 8000 ill travelers who returned from Central or South America:

●Most patients presented within one month after returning from travel (61 percent)

●The manifestations of travelers who returned from Latin America and the Caribbean were grouped into six major syndromic categories:

•Gastrointestinal diagnoses (acute and chronic diarrhea)

•Systemic febrile illnesses

•Dermatologic conditions

•Respiratory or pharyngeal diagnoses

•Neurologic diagnoses

•Genitourinary, sexually transmitted infection, and gynecologic diagnoses

●Among the patients with gastrointestinal infections (20 percent), infection due to Giardia was predominant, followed by Strongyloides, Campylobacter, Dientamoeba fragilis, and Entamoeba histolytica.

●Among the patients with a systemic febrile illness (14 percent), the most common etiology was dengue, followed by malaria (Plasmodium vivax was more common than P. falciparum) and enteric fever due to Salmonella enterica serotype Typhi or Salmonella enterica serotype Paratyphi.

●Among patients with dermatologic conditions, the most common were cutaneous larva migrans (15 percent), myiasis, and scabies.

●Among patients with a nondiarrheal gastrointestinal disorder, 26 percent had intestinal nematode infection with Strongyloides or Ascaris, and 10 percent had acute hepatitis. The remaining patients had gastritis or peptic ulcer disease, hemorrhoids, or constipation.

In a subset of patients in this cohort with acute and potentially life-threatening diseases, among 166 returned travelers to the United States from Central and South America between 1996 and 2011, the etiologies of acute illness included typhoid or paratyphoid fever (35 percent), malaria (39 percent), leptospirosis (16 percent), spotted fever group rickettsiosis (5 percent), murine typhus (1 percent), and melioidosis (1 percent) [9].

Diseases associated with travel to Latin America and the Caribbean are summarized in the table (table 2).

INITIAL EVALUATION — The focus of the initial evaluation should be on diagnosis of infections that are treatable, transmissible, and/or have serious sequelae (table 3).

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 4) [5,6,10]:

●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 5 and figure 1).

●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 2) 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 6).

●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 'Evaluate for malaria' 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 should include complete blood count and differential, liver enzymes, blood cultures and blood smears and rapid diagnostic test for malaria (if there was exposure to an area with malaria transmission), and/or rapid diagnostic testing for respiratory viruses. Additional studies depend upon exposures and other factors (table 7).

Patients with exposure to an area with malaria transmission should have diagnostic tests performed promptly (on the day of the encounter). Because parasites may be sequestered in the deep vasculature in patients with falciparum malaria, few parasites may be visible on a peripheral smear even in severe infection. Therefore, if the initial smear is negative, additional smears should be evaluated over the subsequent 24 to 72 hours. Rapid diagnostic tests should be used if available. (See 'Evaluate for malaria' below and "Laboratory tools for diagnosis of malaria".)

SUBSEQUENT CLINICAL APPROACH

Evaluate for malaria — Information regarding areas with malaria is available from the United States Centers for Disease Control and Prevention website.

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 2). 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 [11-13].

Malaria is transmitted by Anopheles mosquitoes. The incubation period of malaria due to P. falciparum is usually 7 to 30 days (but may be longer). The incubation period of non-falciparum malaria is 9 to 14 days. The diagnosis of malaria is established by visualization of parasites on peripheral smear. (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 efficacy of various malaria chemoprophylactic regimens varies by geographic region; even in areas where no resistance has been reported, malaria chemoprophylaxis is not 100 percent effective. Use of chemoprophylaxis may delay the malaria symptom onset, and most chemoprophylactic regimens do not prevent relapse of vivax malaria [14,15]. (See "Prevention of malaria infection in travelers".)

Consider the presenting syndrome — The clinical manifestations should be considered in conjunction with the patient's geographic exposure, the timing of clinical presentation relative to the incubation periods of relevant infections, and the patient's activities while traveling that may represent potential pathogen exposure. Some important syndromic presentations are summarized below with respect to these factors.

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 'Rash' below.)

●Zika virus infection – (See 'Rash' below.)

●Leptospirosis – (See 'Jaundice' below.)

●Rickettsial infection – (See 'Rash' below.)

●Schistosomiasis – (See 'Rash' below.)

●Malaria – Incubation period ≤10 days is unusual but has been described. (See 'Evaluate for malaria' above.)

●Enteric fever – "Enteric fever" refers to both typhoid fever (caused by Salmonella enterica serotype Typhi [formerly S. typhi]) and paratyphoid fever (caused by S. enterica serotype Paratyphi A, B, and C worldwide; predominantly Paratyphi B in South America). Enteric fever is characterized by abdominal pain, fever, and chills. Classic manifestations include relative bradycardia, pulse-temperature dissociation, and "rose spots" (faint salmon-colored macules on the trunk and abdomen). Hepatosplenomegaly, intestinal bleeding, and perforation may occur, leading to secondary bacteremia and peritonitis. The disease occurs worldwide; regions of highest incidence include South Asia, Southeast Asia, and southern Africa. Transmission is fecal-oral; the incubation period is 6 to 30 days. The diagnosis is established via culture. (See 'Rash' below and "Enteric (typhoid and paratyphoid) fever: Epidemiology, clinical manifestations, and diagnosis".)

●Relapsing fever (rare) – Relapsing fever is characterized by recurring febrile episodes that last approximately three days and are separated by afebrile periods. Transmission is via a tick bearing Borrelia spirochetes. Tickborne relapsing fever occurs on every continent except Australia and Antarctica. The incubation period is typically 4 to 14 days; the diagnosis is established via blood smear or serologic testing. (See "Clinical features, diagnosis, and management of relapsing fever".)

The differential diagnosis of acute fever also includes etiologies that may not be specific to international travel, such as urinary tract infection, influenza, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or infectious mononucleosis.

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

●Malaria – (See 'Evaluate for malaria' above.)

●Enteric fever – (See 'Incubation period ≤10 days' above.)

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

●Acute HIV infection – (See 'Rash' below.)

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

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

●Visceral leishmaniasis (rare) – Visceral leishmaniasis is characterized by subacute progression of malaise, fever, weight loss, and splenomegaly (with or without hepatomegaly) over a period of months. Transmission occurs via sand fly bites, and endemic areas include the Mediterranean, the Middle East, Afghanistan, Iran, Pakistan, East Africa, South Asia, and Brazil. The incubation period is usually two to six months; the diagnosis is established by histopathology or culture. (See "Visceral leishmaniasis: Clinical manifestations and diagnosis".)

●Brucellosis (rare) – Brucellosis is characterized by fever, night sweats, anorexia, arthralgia, fatigue, and weight loss. Transmission occurs via contact with fluids from infected animals (sheep, cattle, goats, pigs, or other animals) or derived food products such as unpasteurized milk and cheese. Major endemic areas include the Mediterranean basin, the Persian Gulf, the Indian subcontinent, and parts of Mexico and Central and South America. The incubation is usually one to four weeks but may be several months. The diagnosis is established by culture or serologic testing. (See "Brucellosis: Epidemiology, microbiology, clinical manifestations, and diagnosis".)

●Oroya fever – (See 'Jaundice' below.)

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

●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. Studies of etiology of travelers' diarrhea in travelers to Latin America and the Caribbean have demonstrated that the majority of cases are caused by diarrheagenic E. coli and norovirus [16]. 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 polymerase chain reaction (PCR). (See "Giardiasis: Epidemiology, clinical manifestations, and diagnosis".)

●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".)

•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. 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 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 liver abscess pus). (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, 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".)

●Liver abscess (rare) – Liver abscess occurs worldwide and may be pyogenic or amebic. 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 liver abscess is made via radiographic imaging, followed by aspiration of the lesion for Gram stain, culture, and parasite examination. In addition, E. histolytica infection may be established via serology or stool parasite examination or PCR. (See "Pyogenic liver abscess" and "Extraintestinal Entamoeba histolytica amebiasis", section on 'Amebic liver abscess'.)

●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). Infection occurs in South and Central America, the Middle East and eastern Mediterranean, some sub-Saharan African countries, western China, and the former Soviet Union. Onset of clinical manifestations typically occurs decades following infection. The diagnosis is typically established by ultrasound imaging in combination with serologic testing.

●Cholangitis due to liver fluke infection (rare) – Cholangitis due to liver fluke infection (Fasciola) is characterized by fever and severe right upper quadrant pain in association with eosinophilia (typically 2000 to 5000 eosinophils/microL) and hypodense (migratory) liver lesions on computed tomography. Fasciola is endemic in sheep-rearing areas of temperate climates, including Central and South America, Europe, Asia, Africa, and the Middle East. Infection due to Fasciola is transmitted by ingestion of watercress; the incubation period is 6 to 12 weeks. The diagnosis of liver fluke infection is established by serology and/or identification of eggs in stool, duodenal aspirates, or bile specimens. (See "Liver flukes: Clonorchis, Opisthorchis, and Metorchis" and "Liver flukes: Fascioliasis".)

●Cholera (rare) – Cholera is caused by infection with Vibrio cholerae and is characterized by acute watery diarrhea with potential for rapid loss of fluid leading to hypovolemic shock. Cholera is endemic in over 50 countries worldwide, mostly in Africa and Asia; however, the outbreak in Haiti in 2010 has led to associated outbreaks in neighboring countries in the Caribbean and Central America. It is transmitted by ingestion of contaminated food or water, with a typical incubation period of 1 to 2 (up to 5) days. The mainstay of treatment is volume repletion. Diagnosis is most often made by clinical suspicion in patients with severe acute watery diarrhea with recent travel to epidemic or endemic areas but may be made by stool culture, rapid antigen test, or PCR. (See "Cholera: Epidemiology, clinical features, 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 malaria – Manifestations of severe malaria are summarized in the table (table 8). (See 'Evaluate for malaria' 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".)

●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 3); the incubation period is 4 to 7 days (range 3 to 10 days). The diagnosis is established via PCR, antigen, or serologic testing. (See 'Rash' 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 disease is widespread in South America. The incubation is 2 to 29 days. The diagnosis is established via serology, PCR, or culture of blood or urine. (See "Leptospirosis: Epidemiology, microbiology, clinical manifestations, and diagnosis".)

●Yellow fever (rare) – Yellow fever is characterized by acute infection with nonspecific symptoms, followed by a period of remission and a subsequent episode of illness with hepatic and renal dysfunction. It is transmitted by Ae. aegypti mosquitoes and forest-dwelling mosquitoes in tropical regions of South America and sub-Saharan Africa; the incubation period is three to eight days. The diagnosis is established via serology or PCR. (See "Yellow fever: Epidemiology, clinical manifestations, and diagnosis".)

●Oroya fever (rare) – Oroya fever is characterized by fever, headache, anorexia, and anemia. This acute febrile illness is the initial manifestation of South American bartonellosis, also known as Carrion's disease, and is most commonly caused by Bartonella bacilliformis. It is transmitted by sand fly bite and is endemic to a region in the Andes Mountains of Peru, Colombia, and Ecuador. The incubation period is 10 to 210 days. The diagnosis is established by blood culture or smear. (See "South American bartonellosis: Oroya fever and verruga peruana".)

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

Rash — Localized dermatologic conditions that occur in association with travel to Latin America and the Caribbean 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 Ae. 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, antigen testing, 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 PCR. (See "Chikungunya fever: Epidemiology, clinical manifestations, and diagnosis".)

●Zika virus – Zika virus infection is characterized by fever, rash, headache, arthralgia, myalgia, and conjunctivitis [17]. The primary mode of transmission is via Aedes mosquito bites; sexual transmission can also occur. Zika virus infection occurs in Africa, Southeast 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".)

●Rickettsial infection – Many rickettsial infections present with fever and rash; some are also associated with eschar and/or enlarged nodes (table 10). However, rash may be absent. They are usually transmitted by ticks with an incubation period of 2 to 14 days and span a broad geographic distribution (table 11). The diagnosis may be established via serology or PCR. (See "Other spotted fever group rickettsial infections" and "Human ehrlichiosis and anaplasmosis".)

●Acute schistosomiasis – Acute schistosomiasis is characterized by fever, urticaria and angioedema, chills, myalgias, arthralgias, dry cough, diarrhea, abdominal pain, headache, and accompanied by eosinophilia, resolving over days to weeks. Schistosoma mansoni can be acquired in parts of Brazil, Suriname, Venezuela, and in some Southern Caribbean countries. Transmission occurs through exposure to fresh water (lakes and slow-moving rivers). (See "Schistosomiasis: Epidemiology and clinical manifestations".)

●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 'Gastrointestinal symptoms' above.)

●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".)

●Meningococcal infection – Meningococcal infection is characterized by acute onset of fever, nausea, vomiting, headache, confusion, and myalgia. Non-blanching 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; it occurs in agricultural regions in Central and South America, sub-Saharan Africa, Central and Southwestern Asia, and Southern and Eastern Europe. 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".)

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".)

●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, community-acquired pneumonia (due to bacterial or viral pathogens), and SARS-CoV-2. (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 non-travelers. 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 – (See 'Jaundice' above.) Leptospirosis may be complicated by severe pulmonary disease with pulmonary hemorrhage. (See "Leptospirosis: Epidemiology, microbiology, clinical manifestations, and diagnosis".)

●Q fever – Q fever (Coxiella burnetii infection) may present with a broad spectrum of manifestations. Respiratory infection consists of fever, nonproductive cough, fatigue, headache, and myalgia. Infection may also be associated with hepatitis, endocarditis, and bone and joint disease. The illness occurs worldwide and is most commonly transmitted by contact with infected animals, materials contaminated with animal manure, contaminated aerosols, or ingestion of unpasteurized milk. The incubation period for acute infection is usually 2 to 3 weeks (range few to 30 days). The diagnosis is established via serologic testing.

●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".)

●Blastomycosis – Most patients with blastomycosis present with chronic pneumonia. Infection is transmitted via inhalation in endemic areas. Outside of North America, blastomycosis has been reported most frequently in Africa with occasional cases identified in Mexico, Central and South America, India, and the Middle East. The incubation period from exposure until the onset of pulmonary symptoms is approximately three to six weeks. The diagnosis is established via culture; a presumptive diagnosis of blastomycosis may be made by visualization of the characteristic yeast form in clinical specimens. (See "Clinical manifestations and diagnosis of blastomycosis".)

●Hantavirus (rare) – Hantaviruses occur worldwide. New World hantaviruses are associated with hantavirus cardiopulmonary syndrome; Old World hantaviruses are associated with hemorrhagic fever with renal syndrome. Hantaviruses are transmitted by aerosolization of rodent urine, feces, or saliva. The incubation period is a few days to 6 weeks; the diagnosis is established via serology. (See "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 (rare) – 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 'Rash' 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 disease is transmitted via ingestion of Ascaris eggs (via contaminated food or water); 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 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 'Respiratory symptoms' above and 'Gastrointestinal symptoms' above and "Strongyloidiasis".)

●Dimorphic fungal infection – Fungal infections associated with fever, respiratory symptoms, and eosinophilia include coccidioidomycosis and paracoccidioidomycosis:

•Coccidioidomycosis should be suspected in patients with exposure in endemic areas (southwestern United States, Mexico, Central America, and South America) and a respiratory illness of more than a week's duration. The incubation period is 7 to 21 days. The diagnosis is established via serology or culture. (See "Primary pulmonary coccidioidal infection".)

•Paracoccidioidomycosis should be suspected in patients with endemic exposure (Mexico, Central America, and South America), pulmonary infiltrates, and chronic mucosal ulcers in the upper airways. The incubation period is not well established. The diagnosis is established via microscopic visualization of fungal elements suggestive of Paracoccidioides spp, culture, and/or serologic testing. (See "Clinical manifestations and diagnosis of chronic paracoccidioidomycosis".)

●Tropical pulmonary eosinophilia (rare) – Tropical pulmonary eosinophilia (filariasis) is a clinical manifestation of lymphatic filariasis, which is a parasitic infection caused by nematodes (roundworms). The disease is characterized by gradual onset of nonproductive cough (which is frequently paroxysmal and nocturnal) and blood eosinophilia, usually above 3000/microL. The disease is transmitted by a number of mosquito vectors throughout the Caribbean, South America, Africa, Asia, and the Pacific islands. The incubation period is approximately one month. The diagnosis is established via serology. (See "Tropical pulmonary eosinophilia".)

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

In general, influenza patterns in South America are similar to those of the previous season in North and Central America; influenza season begins in April in South America and in June in Central America.

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

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

●Meningitis

•Meningococcal infection – Meningococcal infection is characterized by acute onset of fever, nausea, vomiting, headache, confusion, and myalgia. Non-blanching 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 cerebrospinal fluid 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 (GBS) 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".)

●West Nile virus – West Nile virus infection is characterized by fever, headache, malaise, back pain, myalgia, and anorexia; neuroinvasive illness can present as encephalitis, meningitis, or an acute asymmetric flaccid paralysis. It is transmitted by mosquitoes and occurs in Africa, the Middle East, parts of Europe and the former Soviet Union, South and Southeast Asia, Australia, and the Americas. The incubation period is 2 to 14 days. The diagnosis is established via serologic testing in serum and spinal fluid. (See "Clinical manifestations and diagnosis of West Nile virus infection".)

●Rabies (rare) – Rabies is characterized by fever, hydrophobia, pharyngeal spasms, and hyperactivity. It is transmitted by animal bite (dogs, bats, and other animals) and is distributed worldwide. The average incubation period is one to three months. The diagnosis can be made by virus-specific immunofluorescent staining of skin biopsy specimens, isolation of virus from the saliva, or detection of anti-rabies antibodies in serum or cerebrospinal fluid. (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".)

Consider the incubation period — The incubation periods for common infections associated with travel are summarized in the table and figure (table 5 and figure 1).

Consider the exposure history — Some important exposures for transmission of infection are summarized below (table 12).

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, yellow fever, West Nile virus infection and filariasis. (See related topics.)

●Flies – Infections transmitted by flies include leishmaniasis (sand fly) and Oroya fever (sand fly). (See "Visceral leishmaniasis: Clinical manifestations and diagnosis" and "Cutaneous leishmaniasis: Clinical manifestations and diagnosis" and "South American bartonellosis: Oroya fever and verruga peruana".)

●Ticks – Infections transmitted by ticks include rickettsial infections, tickborne relapsing fever, anaplasmosis, ehrlichiosis and tularemia. (See related topics.)

●Fleas – Infections transmitted by fleas include murine typhus (Rickettsia 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 – Rickettsialpox (Rickettsia akari) is transmitted by mites. (See "Rickettsialpox".)

●Triatomine bugs – Chagas disease is transmitted by triatomine bugs but is not typically a travel-associated infection. (See "Chagas disease: Epidemiology, screening, and prevention" and "Chagas disease: Acute and congenital Trypanosoma cruzi infection".)

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, Q fever, or tickborne encephalitis.

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 [18,19]. 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 or 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.)

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

SUMMARY

●Important causes of fever among returned travelers from Central and South America include enteric fever (typhoid or paratyphoid fever), malaria, and leptospirosis (table 2). In addition to travel-related infections, cosmopolitan causes of fever should be considered (table 1 and table 3). (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 4). 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 7). (See 'History and physical examination' above.)

●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 2). Malaria is characterized by fever, malaise, nausea, vomiting, abdominal pain, diarrhea, myalgia, and anemia. (See 'Evaluate for malaria' 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 incubation periods for common infections associated with travel are summarized in the table and figure (table 5 and figure 1). (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 12). (See 'Consider the exposure history' above.)

ACKNOWLEDGMENT — The editorial staff at UpToDate acknowledge Aimee Zaas, MD, MHS, and Daniel J Sexton, MD, who contributed to earlier versions of this topic review.