Chapter 98. World Travelers

Fever and other symptoms of infection are the most common complaints for returning travelers (see Table 98-1). The evaluation of infectious disease in the returning traveler requires an understanding of the geographical distribution of infections (see Table 98-2), risk factors, incubation periods, clinical manifestations, and appropriate laboratory investigations. See Centers for Disease Control and Prevention (CDC) website for further information: http://wwwnc.cdc.gov/travel/destinations/list.aspx. Traveler's diarrhea, enteroviral infections, gastroenteritis, giardiasis, salmonellosis, shigellosis are discussed in Chapter 96 “Foodborne and Waterborne Diseases” and in Chapter 37 “Diseases Presenting Primarily with Diarrhea”; malaria is discussed in Chapter 95 “Malaria”; upper respiratory infection and pertussis are discussed in Chapter 30 “Pneumonia, Bronchitis, and Upper Respiratory Infections”; STDs are discussed in Chapter 87 “Sexually Transmitted Diseases”; hepatitis A and B are discussed in Chapter 48 “Hepatic Disorders, and Hepatic Failure”; HIV (human immunodeficiency virus). Infections and acquired immune deficiency syndrome are discussed in Chapter 92; anthrax and plague are discussed in Chapter 97 “Zoonotic Diseases.” This chapter covers the most common infectious disease presentations in returning travelers; the reader is referred to the source material, cited at the end of the chapter, for further information, and discussion of less common diseases.

The incubation period for disease is most commonly longer than a traveler's foreign stay, and therefore travelers commonly become febrile/symptomatic upon return. Travel history should include query concerning visits to game parks, farms, caves, health facilities, consumption of exotic foods, activities involving fresh or salt water exposure, insect exposure, sexual activities, epidemics in the area visited, contact with ill people, as well as pretrip immunizations and prophylactic antibiotics taken. A history chronological disease presentation should be taken including height, quality, and duration of fever and chills. Examination findings such as current temperature, rash, eschar, hepatosplenomegaly, lymphadenopathy, jaundice, and other skin findings should be documented.

General laboratory assessment includes malaria smear (and dipstick antigen test if available) should be done for all febrile travelers returning from locations with endemic malaria. Complete blood count: look for lymphopenia (dengue, HIV and typhoid) or eosinophilia (parasites, fungal disease) and thrombocytopenia (malaria, dengue, acute HIV, typhoid). Urinalysis may show proteinuria and hematuria in cases of leptospirosis. Blood cultures should be obtained prior to antibiotics. Liver function tests are indicated if patient is jaundiced. Consider specific testing for diseases suspected by symptoms and risk of exposure. Obtain a chest radiograph for respiratory symptoms, and consider a liver ultrasound if amebic liver abscess is suspected.

Malaria is the most important disease to rule out in returning travelers (discussed in Chapter 95 “Malaria”). The other most common diseases in returning travelers (see also references at the beginning of this chapter) are discussed later in this chapter.

Dengue Fever

Dengue fever is spread by the day-biting Aedes aegypti mosquito. Incubation is 4 to 7 days. Symptoms of classic dengue are high fever, headache, nausea, vomiting, myalgias, and rash (late), lasting several days. Dengue fever acquired in Southeast Asia typically is accompanied by hemorrhagic symptoms and often shock; in this form abdominal pain may be marked. Diagnosis is by PCR (1 to 8 days postsymptom onset) or IgM ELISA, after 4 days of symptoms. Daily blood counts are recommended. Outpatient treatment is recommended in mild cases, with oral hydration as tolerated and close follow-up for blood work. Avoid aspirin and NSAIDs. Inpatient treatment for supportive care is recommended if there is a drop in hematocrit or platelets, or hemorrhagic symptoms, or abnormal vital signs.

Chikungunya

Chikungunya is the second most common arbovirus infection in returning travelers, after dengue fever. Also spread by day-biting mosquitos, chikungunya presents very much like classic dengue fever but additionally with generalized arthralgia. From 5% to 30% of patients with go on to have chronic arthropathy. Diagnosis is by PCR (1 to 4 days postsymptom onset) or IgM, after 5 days of symptoms. Treatment is supportive; chloroquine may reduce long term arthralgias but is not standard therapy. NSAIDs are helpful, but should be avoided until dengue fever has been ruled out.

Typhoid Fever

Typhoid fever, or enteric fever, is caused by Salmonella typhi and Salmonella paratyphi. Transmission is from contaminated food or water, after contact with the infected urine or feces of symptomatic individuals, or asymptomatic carriers. After malaria is ruled out (by lack of potential exposure or by testing), typhoid fever is the most common febrile disease lasting more than 10 days in returning travelers. Incubation is 1 to 3 weeks. Symptoms include fever with headache initially, then high fever with chills, headache, cough, abdominal distention, myalgias, constipation (most common, but some have diarrhea), and prostration. A classic presentation is bradycardia relative to the height of fever, but is often absent. After several days, a pale red macular rash (“rose spots”) appears on the trunk. Complications include small bowel ulceration, anemia, disseminated intravascular coagulopathy (DIC), pneumonia, meningitis, myocarditis, and renal failure. Remarkable lab findings may include leukopenia and elevated liver enzymes, however not typical. Diagnosis is clinical, confirmation is by stool culture. After initiation of supportive care with fluids and fever control, treatment is ceftriaxone, 2 grams IV. IM for 14 days, or ciprofloxacin 500 to 750 milligrams PO twice daily for 14 days. For severe typhoid fever complicated by delirium, coma, shock, or DIC, administer dexamethasone, 3 milligrams/kilogram IV load. Blood transfusion may be required is severe cases.

Brucellosis

Brucellosis is caused by the bacteria Brucella, most commonly following contact with cattle, goats, camels, dogs, pigs, or after ingestion of unpasteurized milk or cheese. Symptoms include fever, abdominal pain, back pain, fatigue, headache, joint pain, and loss of appetite. Common history is relapsing fever, but can be chronic low grade fever. Examination findings include lymphadenopathy, hepatomegaly, splenomegaly, and may include septic arthritis. Diagnosis is by blood culture, or serology. Consult infectious disease for treatment with doxycycline, rifampicin, and an aminoglycoside, streptomycin or gentamicin for 2 weeks.

Rickettsial Spotted Fevers Including Scrub Typhus

Rickettsial spotted fevers are transmitted by the bite, body fluid, or feces of ixodid arthropod ticks. Mortality without treatment approaches 25%. Scrub typhus (Rickettsia orientalis) and African tick typhus (R conorii) are the most common forms in travelers returning from the Southeast Asia and Africa respectively. Incubation is 3 to 14 days. Symptoms are fever, malaise, myalgias, severe headache, rash (may be absent), nausea, and vomiting followed by lymphadenopathy and splenomegaly. The skin lesion in scrub typhus starts as a papule at the bite site, which becomes necrotic and forms a crusted black eschar. African scrub typhus is in general, less severe. Diagnosis is clinical; serologic tests confirm the diagnosis after empiric treatment with doxycycline 100 milligrams twice daily for 7 to 10 days; chloramphenicol is an alternative.

Typhus Epidemic Louse-Borne Typhus

Epidemic louse-borne typhus, common in Mexico, Guatemala, Ethiopia, and the Himalayas, is caused by R prowazekii and should not be confused with the disease caused by S typhi. Incubation is 8 to 12 days. Patients may or may not be aware of the louse. Symptoms include high fevers, severe headache, and a maculopapular rash between 4 and 7 days. Diagnosis is clinical; serologic tests confirm the diagnosis after empiric treatment with doxycycline 100 milligrams twice daily for 7 to 10 days; chloramphenicol is an alternative.

Leptospirosis (Weil Disease)

Leptospirosis occurs after fresh water exposure to Leptospira interrogans or after exposure to infected dogs. Incubation is 2 to 20 days. Symptoms include high fever, severe headache, chills, myalgias, hepatitis with or without jaundice, and conjunctival injection without purulent discharge. Diagnosis requires serology. Mild disease (within 3 days of symptoms) is treated with amoxicillin 500 milligrams 3 times daily, or doxycycline 100 milligrams twice daily. More severe cases should be treated with penicillin G, 5 million units every 6 hours IV, or ceftriaxone 1 gram IV/IM daily. Treatment duration is 7 to 14 days.

Crimean-Congo Hemorrhagic Fever

Crimean-congo hemorrhagic fever is a tick-borne viral disease that is rising in frequency in Africa, Asia, eastern Europe and the Middle East. Agricultural workers are at the greatest risk, but it can be acquired from contact with the blood of patients. Symptoms include sudden onset of fever, headache, myalgia, dizziness, and possibly mental confusion. The hemorrhagic period is short (2 to 3 days), starts the third to fifth day of illness, and may manifest with epistaxis, hemoptysis, GI bleeding, vaginal bleeding, or hematuria. Patients may have thrombocytopenia, elevated liver enzymes and creatinine; prothrombin time and activated partial thromboplastin time may be prolonged. Diagnosis is clinical with confirmation by serology. Treatment is supportive, and may require transfusions and or respiratory support. Ribavirin is used in moderate to severe cases, 30 milligrams/kilogram load, then 15 milligrams/kilogram every 6 hours for 4 days, then 7.5 milligrams/kilogram for 6 days.

Yellow Fever

Yellow fever is caused by a flavivirus, transmitted by a day-biting mosquito, occurring along a broad equatorial belt in South and Central America and Africa. Symptoms range from a mild flulike illness to hemorrhagic fever with 20% mortality. After an incubation period of 3 to 6 days, typical early symptoms include fever, headache, myalgias, conjunctival injection, abdominal pain, prostration, facial flushing, and relative bradycardia, subsequently the classic jaundice, black emesis, and albuminuria is found. Symptoms may progress to shock, multiorgan failure, and bleeding diathesis. Treatment is supportive including transfusion as needed.

Cysticercosis

Cysticercosis is the systemic illness caused by dissemination of the larval form of the pork tapeworm. Humans become infected by ingesting the contaminated food (undercooked pork), or inadvertent contact with contaminated soil. Involvement of almost any tissue can occur. CNS infection is known as neurocysticercosis, and is the most important cause of seizures worldwide. Additional symptoms of neurocysticercosis include headache, visual or mental status changes, stroke, meningoencephalitis, and obstructive hydrocephalus. Noncontrast CT is shows calcifications of inactive disease, and may reveal hydrocephalus. Therapy is praziquantel, 17 milligrams/kilogram/dose 3 times daily (albendazole also used). Steroids are recommended for those with encephalitis, hydrocephalus, or vasculitis.

African Trypanosomiasis (African Sleeping Sickness)

Sleeping sickness is transmitted by the aggressive tsetse fly. After a bite, a localized inflammatory reaction occurs followed in 2 to 3 days by a painless chancre that increases in size for 2 to 3 weeks, and then gradually regresses. Intermittent fevers follow, with malaise, rash, and eventual CNS involvement occurs, causing behavioral and neurologic changes, encephalitis, coma, and death. Other complications include hemolysis, anemia, pancarditis, and meningoencephalitis. Diagnosis is made by rapid evaluation of blood smears for the mobile parasite. Consult infectious disease expert for diagnosis and treatment with suramin and other agents.

Chagas Disease (American Trypanosomiasis)

The protozoan T cruzi is endemic in regions of Latin America and is reported as far north as Texas. It is spread by the reduviid “kissing bug” or “assassin” bug. The bug typically bites nocturnally after emerging from rural adobe walls or thatched roofs. Symptoms of the acute phase are unilateral periorbital edema (Romaña sign) or painful cutaneous edema at the site of skin penetration (chagoma), and is followed by a toxemic phase with parasitemia causing lymphadenopathy and hepatosplenomegaly. The acute phase diagnosis is made by examination of peripheral blood smears demonstrating motile parasites, or by blood culture. In the chronic phase, serologic tests or tissue biopsy are useful. Recommended treatment is nifurtimox (consult infections disease).

Leishmaniasis (Visceral)

Leishmania is an intracellular protozoan transmitted by Lutzomyia or Phlebotomus sandflies. Leishmaniasis should be suspected in the military and their families living proximal to jungles, adventure travelers, field biologists, and emigrants from endemic zones. The disease has a variety of syndromic presentations, the most important of which is visceral leishmaniasis, or Kala-azar, or Black Fever. It is typified by a pentad of fever, weight loss, hepatosplenomegaly, pancytopenia, and hypergammaglobulinemia. Treat visceral disease with pentavalent antimonials, either sodium stibogluconate (available through the CDC) or meglumine antimonate, available in some European countries.

Schistosomiasis (Snail Fever)

Schistosomiasis should be suspected in travelers presenting with GI symptoms exposed to freshwater. The larvae are released into fresh water by snails. Soon after exposure, “swimmers itch” occurs with a macular-papular pruritic dermatitis over the lower legs, which can last for days. Four to 8 weeks later, fever occurs with headache, cough, urticaria, diarrhea, hepatosplenomegaly, and hypereosinophilia (Katayama fever). Worms mature in the venous blood and (if untreated) deposit eggs in the bladder, GI tract, brain, skin, and liver. Diagnosis is suspected from eosinophilia and microscopic identification of eggs in midday urines or stools. Treatment is with praziquantel, 20 milligrams/kilogram, 2 doses in a single day, except with GI involvement, where 3 doses in a single day are suggested.

Amebiasis

Pathogenic species such as Entamoeba histolytica are endemic to Asia, Africa, and Latin America. Amebiasis is typically spread by asymptomatic carriers whose excrement contains encysted organisms. Incubation is 1 to 3 weeks for colitis, and weeks to months for liver abscess. Symptoms include alternating constipation with diarrhea, over weeks, to abdominal pain, fever, dehydration, and weight loss. Complication such as liver abscess cause fever, right upper quadrant pain, chronic vague abdominal pain, and weight loss. Stool for ova and parasites is diagnostic (specimen should be examined within 30 min of collection). Ultrasound should identify liver abscess. Most common treatment is with metronidazole, 500 to 750 milligrams 3 times daily for 10 days.

Ascariasis

Infection with Ascaris lumbricoides should be suspected following ingestion of street vendor foods or vegetables fertilized by “night soil” (human feces) or animal feces. Symptoms may include a dry cough or pneumonia as young worms are expectorated and migrate from the lungs to the esophagus and gut. A large worm burden can lead to malnutrition and weakness, and a mass of worms may lead to bowel obstruction. Diagnosis is with stool examination and serology. Treatment is with mebendazole, 100 milligrams daily for three days, or albendazole, 400 milligrams twice a day for 3 days or 500 milligrams single dose, or ivermectin, 150 to 200 micrograms/kilogram single dose. The single dose regimens are used, but have lower cure rates.

Enterobiasis (Seatworm or Pinworm)

Infection is typically from fecal-oral contact from contaminated objects. Presentation is intense perianal itching. Diagnosis is with cellophane tape swab of anus to look for worms. Treatment is with mebendazole, 100 milligrams single dose and repeat in 2 weeks, or albendazole, 400 milligrams single dose and repeat in 2 weeks, or pyrantel pamoate, 11 milligrams/kilogram (up to 1 gram) single dose and repeat in 2 weeks.

Ancylostoma Duodenale and Necator Americanus (Hookworm)

Infection follows exposure to contaminated soil; larvae penetrate skin. Worms may migrate to the lungs, may be coughed up, and access the GI tract after being swallowed. Symptoms include abdominal pain; severe anemia; and cutaneous larva migrans, red, wormlike burrows visible underneath the skin. Treatment is with albendazole 400 millligrams single dose (preferred), or mebendazole 100 milligrams twice daily for 3 days, or Pyrantel pamoate, 11 milligrams/kilogram (maximum, 1 gram) daily for 3 days.

Taenia Solium (Pork Tapeworm), Taenia Saginata (Beef Tapeworm), Diphyllobothrium Latum (Fish Tapeworm)

Infection follows ingestion of undercooked pork, beef, or fish. Symptoms include diarrhea, abdominal pain, bowel obstruction, and taenia cysts in eye, heart, and brain (see Cysticercosis above). Diagnosis is by stool examination or serology (may be negative if cysts are calcified). Treatment is with praziquantel, 5 to 10 milligrams/kilogram single dose.

For discussion of other diseases that may be acquired during travel, or other parasites, see the chapter referenced immediately below.