Box 5.1 COMPLICATIONS OF FALCIPARUM MALARIA

Diagnosis, Treatment, and Prevention

Malaria should be considered in all persons who develop fever 1 week or longer after travel or residence in an endemic area, and thin and thick Giemsa-stained smears of peripheral blood should be examined by a skilled microscopist. Rapid tests that detect malaria antigens in the blood can be used to screen persons with fever, but microscopic examination of blood is necessary for confirmation of both negative and positive tests. Chloroquine is the drug of choice for infections due to P. malariae, P. ovale, and chloroquine-sensitive strains of P. vivax, and can be used to treat chloroquine-sensitive strains of P. falciparum. After G6PD deficiency has been ruled out, primaquine should also be given to persons with vivax or ovale malaria to prevent relapses. P. falciparum should be considered chloroquine-resistant unless acquired in the Caribbean, Central America, parts of the Middle East, and North Africa. Drugs for treating falciparum malaria are listed in table 5.2. Two artemisinin derivatives have become the drugs of choice: oral artemether-lumefantrine and, for severe cases, intravenous artesunate. Artemether and artesunate are faster acting and better tolerated than other antimalarials. They are always given with a second agent, such as lumefantrine, mefloquine, or atovaquone-proguanil to prevent recrudescences. Monotherapy with artemisinin derivatives has led to drug resistance in parts of Southeast Asia.

    Chemoprophylaxis, as outlined in table 5.3, should be given to all travelers to malarious areas. Travelers should avoid mosquito bites by using repellents, protective clothing, insecticide-impregnated nets, and screens on windows.

BABESIOSIS

Babesiosis, a tick-borne protozoan disease, is rarely reported from tropical areas, but it is a life-threatening problem for residents of or travelers to endemic areas in the northeastern United States, Minnesota, Wisconsin, California, and Washington State. Babesia microti and other species of Babesia cause malaria-like illness with fever, splenomegaly, anemia, and thrombocytopenia. Asplenic persons, the elderly, and persons with debilitating diseases are at risk for high parasitemias, respiratory failure, and death. Mild to moderate illness is treated with atovaquone and azithromycin; the combination of quinine and clindamycin is indicated for severe illnesses. Because the tick vector of Babesia microti may be coinfected with other pathogens, Lyme disease and anaplasmosis (human granulocytic ehrlichiosis) should be considered in persons who remain ill after appropriate treatment of babesiosis.

DENGUE AND CHIKUNGUNYA

Increasing numbers of cases among tourists and other returning travelers have paralleled the global resurgence and rapid spread of dengue. After an incubation period of 3–7 days and occasionally longer, there is an abrupt onset of fever, chills, headache, myalgia, arthralgia, diffuse lymphadenopathy, neutropenia, and thrombocytopenia. An erythematous macular rash occurs in about 50% of cases. Life-threatening dengue hemorrhagic fever and dengue shock syndrome from capillary leak occur among persons who experience a second infection but with a different serotype.

    A clinical diagnosis of dengue is confirmed by serological tests. Viral isolation or PCR-based assays to detect virus are not widely available. Treatment is supportive because no antiviral therapy is available. Currently there is no dengue vaccine, and infection is avoided by prevention of mosquito bites.

    Chikungunya virus, transmitted by Aedes aegypti and Aedes albopictus, the Asian tiger mosquito, has caused outbreaks of a dengue-like illness in Africa, Europe, Southeast Asia, the Indian subcontinent, Indian Ocean islands, and the Caribbean. Chikungunya virus infection frequently causes severe polyarthralgias or arthritis, which may last for weeks, but hemorrhagic fever or shock syndrome does not occur. Serology confirms the diagnosis. No treatment or vaccine is available.

RICKETTSIAL INFECTIONS

Rickettsia africae, the agent of African tick typhus, has become a common cause of fever among travelers returning from safaris or other outdoor activities in sub-Saharan Africa, especially in southern Africa. Patients present with fever, headache, myalgia, regional lymphadenopathy, leukopenia, thrombocytopenia, and an erythematous lesion with a black necrotic center at the site of the tick bite (Figure 5.1). Rashes are usually absent. The diagnosis is confirmed by serological tests, and the illness responds quickly to doxycycline. Travelers may encounter other tick-borne rickettsial infections in different parts of the world. The spotted fever group includes Rocky Mountain spotted fever due to Rickettsia rickettsii in the Americas and Mediterranean spotted fever (boutonneuse fever) due to Rickettsia conorii in southern Europe, northern Africa, and western Asia. Scrub typhus (tsutsugamushi fever) is caused by Orienta tsutsugamushi, which is transmitted by the bite of larval mites in the Far East, South Pacific, and Australia.

TYPHOID

Salmonella enterica serotype Typhi (S. typhi) and serotype Paratyphi (S. paratyphi) cause enteric fever in persons who ingest fecally contaminated food or water. The risk is highest for travelers to the Indian subcontinent, Southeast Asia, Africa, and Latin America.

Clinical Features

Typhoid fever is characterized by the gradual onset of rising temperatures, rigors, and headache followed by sustained high fevers (often with a comparatively slow pulse), abdominal pain, and hepatosplenomegaly. Constipation is frequent, but up to 50% of patients have diarrhea. Complications include bowel perforation, intestinal bleeding, and shock.

Diagnosis, Treatment, and Prevention

Diagnosis is made by culture of blood, stool, urine, or bone marrow. Ciprofloxacin, other fluoroquinolones, and ceftriaxone are active against most isolates, but increasing resistance to fluoroquinolones and cephalosporins has made azithromycin the drug of choice in some areas of India.

    Prevention of typhoid fever includes avoidance of contaminated food and water and vaccination, either with a single dose of polysaccharide vaccine (Vi) or four doses of oral attenuated live Ty21a vaccine. Neither vaccine is 100% protective, and neither prevents infection with S. paratyphi.

MENINGOCOCCAL INFECTION

Meningococcal meningitis and meningococcemia occur throughout the world, but risk is high in the “meningitis belt” of sub-Saharan Africa, which extends from Senegal to Ethiopia during outbreaks in the dry months of November to June. Outbreaks also have occurred during the Hajj. Prompt diagnosis and treatment with ceftriaxone, cefotaxime, or chloramphenicol, which is still used in developing areas, are essential for preventing fatalities, neurological deficits, and gangrene. Quadrivalent vaccine should be administered to travelers to high-risk destinations.

LEPTOSPIROSIS

Transmission of Leptospira interrogans occurs by contact of skin or mucous membranes with fresh water or moist soil contaminated with the urine of rodents and other mammals. Infection of animals occurs worldwide, and outbreaks have been associated with flooding, military operations, ecotourism, whitewater rafting, and other water sports.

    Leptospirosis presents with fever, headache, myalgia, conjunctival suffusion, and often hepatosplenomegaly or rash. Complications include aseptic meningitis and Weil syndrome with hepatitis, intense jaundice, renal insufficiency, and hemorrhage. The diagnosis is usually made with serological tests, although the organism can be identified by dark field microscopy or culture on special media. Doxycycline, penicillins, or ceftriaxone are equally effective for treatment, and weekly doxycycline can prevent infections in persons with unavoidable exposures.

DIARRHEA

Diarrhea is the most common health problem of travelers to the tropics and developing countries. Bacterial infections are the most frequent cause of travelers’ diarrhea, and most cases present acutely and resolve within a week. The most common pathogens, enterotoxigenic Escherichia coli, Salmonella, Campylobacter, and Shigella respond to short courses of fluoroquinolones or azithromycin; the latter is active against fluoroquinolone-resistant Campylobacter, which is becoming more prevalent in parts of the world. Persistent diarrhea, that is, lasting at least 2–3 weeks, is a common problem that prompts returning travelers to seek health care. Box 5.2 lists the principal causes of persistent diarrhea.

Box 5.2 CAUSES OF PERSISTENT DIARRHEA IN TRAVELERS RETURNING FROM THE TROPICS

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