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Although fever is nonspecific, it raises the suspicion for a serious infection (Table 161-7).4,5 Patients with fever after tropical travel have malaria until proven otherwise. Other common serious infections are listed in Table 161-8.6,7
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The classic clinical triad for all species of malaria is fever, splenomegaly, and thrombocytopenia.8,9 Fever is typically irregular for the first week and later may demonstrate periodicity. Patients usually have continuous symptoms initially followed by episodic pyrexia every 2 to 3 days, depending on the infecting species. Periodicity is unusual with falciparum malaria. Serious malaria infections occur primarily in young children, pregnant women, the elderly, individuals never previously infected, and patients with comorbid medical problems. Because associated symptoms such as headache, cough, and GI problems mimic other conditions, malaria is a consideration in all febrile travelers.
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Diagnosis is based on clinical presentation and confirmed with laboratory evidence of bloodborne protozoa. Patients with fever >38.5°C (101.4°F) of unclear origin and recent or past travel to an endemic area should be screened by blood smears and rapid antigen detection tests when available. Refer to chapter 158 for a detailed discussion of malaria diagnosis and treatment.
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Dengue is the most serious febrile tropical disease after malaria. The World Health Organization reported a 30-fold increase in incidence of dengue in from the 1960s to the 2010s, with up to 50 million cases occurring annually worldwide.10 Suspect dengue fever among travelers with fever developing within 2 weeks of travel. Dengue may be contracted more than once because each of the four strains offers no cross-protective immunity. Many cases are self-limiting, and the illness is not reporTable in the United States.11
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Dengue fever occurs in urban environments in most tropical nations and is transmitted by the peridomestic day-biting Aedes aegypti mosquito. Urban dengue in the Americas, Africa, and the Indian subcontinent is usually classical dengue fever, whereas in Southeast Asia, it manifests as hemorrhagic fever and shock. Classic dengue fever presents after a typically short incubation period of 4 to 7 days with sudden high fever, headache, nausea, vomiting, myalgias, and rash usually lasting several days. Facial flushing, conjunctival injection (although uncommon), and retro-orbital pain can occur. After defervescence, a fine, pale, morbilliform rash develops on the trunk and spreads to the extremities and face. Small children may only present with a mild upper respiratory infection, and classic dengue may be confused with influenza, measles, or rubella. Although other causes of fever can present with a similar clinical picture, such as West Nile fever (transmitted by the Culex mosquito), West Nile fever causes lymphadenopathy, which is usually absent in dengue. Dengue can also cause petechial hemorrhages indistinguishable from meningococcemia.
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Dengue hemorrhagic fever preferentially occurs among infants of immune mothers, children >1 year old, and those with second and subsequent infections. It begins as classical dengue with fever and myalgias. After 2 to 7 days, as pyrexia improves, lassitude, fatigue, and shock develop with an ensuing mortality that is >10%. Clinical features include pleural effusions and bleeding diathesis with epistaxis, purpura, petechia, and marked thrombocytopenia with elevated hematocrit because of vascular permeability. Dengue hemorrhagic fever may rapidly evolve into dengue septic shock, which is often fatal. Dengue septic shock is heralded by abdominal pain, severe emesis, mental status changes, and alternating severe pyrexia and hypothermia.
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Diagnosis of dengue is based on clinical findings; although serology is confirmatory, cross-reactivity often occurs with other flaviviruses. Enzyme-linked immunosorbent assay provides rapid confirmation of infection by day 6 of the illness. Laboratory abnormalities include leukopenia, thrombocytopenia, and hepatic dysfunction. In uncomplicated dengue fever, treatment is supportive and consists of fluids and analgesics. Only acetaminophen is recommended for managing pain and fever because aspirin and other nonsteroidal anti-inflammatory drugs are contraindicated due to anticoagulant properties.
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Enteric fever, or typhoid fever, is a serious infection diagnosed in roughly 400 travelers annually returning to the United States, with an additional 100 cases of paratyphoid. Typhoid and paratyphoid are caused by Salmonella typhi and Salmonella paratyphi, respectively.12 Once malaria is excluded, typhoid fever is commonly the cause of a febrile illness lasting >10 days.13 Imported cases occur in visiting friends and relatives and travelers from Mexico, Indonesia, Peru, and the Indian subcontinent. Vaccination before travel helps thwart acquisition, although protection wanes with time and revaccination is required.
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The disease is transmitted in a dose-related fashion after food contamination by feces or urine from actively infected cases or healthy disease carriers. Incubation times and disease severity vary from 1 to 3 weeks. After ingestion, bacteria adhere to the small bowel mucosa, invade lymphoid tissues, and disseminate by lymphatics to the bone marrow, gallbladder, and spleen to reproduce in macrophages. Most pathology occurs in the gut as a consequence of inflammation, necrosis, and ulceration. Typhoid fever classically begins with fever and headache, and then progresses to high fever with chills, headache, cough, abdominal distention, myalgias, constipation, and prostration. The differential diagnosis includes malaria, typhus, viral hepatitis, amebic liver abscess, and other types of infective enteritis. In epidemics, patients can present with acute diarrhea and vomiting, headache, and meningeal signs. Most patients, however, present with constipation rather than diarrhea. Bradycardia relative to fever is classic (but may be absent); after several days of fever, a pale red macular rash may appear on the trunk (rose spots) among fair-skinned individuals. As the disease progresses, splenomegaly develops. Patients may develop leukopenia and elevated liver enzymes, although most cases have nonspecific laboratory values. Complications include small bowel ulceration, anemia, disseminated intravascular coagulopathy, pneumonia, meningitis, myocarditis, cholecystitis, and renal failure. Sequelae include deafness, and neurologic involvement including psychosis, ataxia, and seizures can occur.14
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Diagnosis is clinical and confirmed by culturing blood, urine, or stool (during the second week) or by rapid antigen testing. Although most cultures have a moderate yield, bone marrow culture is most sensitive, and organism identification is possible after antibiotic treatment.
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Current treatment recommendations for typhoid fever include fluoroquinolones (ciprofloxacin), cephalosporins (cefixime and ceftriaxone), or azithromycin, with duration of treatment dependent on severity of illness. Currently, ampicillin, trimethoprim-sulfamethoxazole, and chloramphenicol are unreliable due to resistance. Nalidixic acid–resistant S. typhi strains are also associated with fluoroquinolone resistance; these organisms are found in both India and Southeast Asia. If typhoid meningitis is suspected, administer dexamethasone, 3 milligrams/kg IV loading dose over 30 minutes, followed by 1 milligram/kg IV every 6 hours for eight doses in addition to antibiotics. Supportive treatment includes IV rehydration and blood transfusion (if needed from GI losses). Untreated, mortality is 10% to 15%, mostly in young children.
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RICKETTSIAL SPOTTED FEVERS
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Rickettsial spotted fevers are transmitted by the bite, body fluid, or feces of ixodid arthropod ticks, and the ticks are widely globally distributed. Fleas and mites also transmit rickettsial infections. Among the eight major rickettsial infections, there is great variation in severity. Mortality without treatment approaches 25%, which is lowered to 5% with treatment (see chapter 160). Suspect scrub typhus (Rickettsia orientalis) after rural travel in the Asia-Pacific region and maritime Russia and African tick typhus (Rickettsia conorii var. pijperi) after travel to sub-Saharan Africa or the West Indies.
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Scrub Typhus and African Tick Typhus
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The mite bite, in the case of scrub typhus, or tick bite, with African tick typhus, may go unnoticed. After 3 to 14 days of incubation, patients develop fever, malaise, myalgias, severe headache, rash, nausea, and vomiting. The rash may be absent. Scrub typhus is characterized by a papule at the bite site. The papule later becomes necrotic and forms a crusted black "tache noire" eschar. As organisms disseminate, patients develop fever, malaise, headache, lymphadenopathy, and splenomegaly. African tick typhus presents like scrub typhus, but with much less severe symptoms and localized lymphadenopathy associated with an eschar. Diagnosis is clinical, and serologic tests are confirmatory. Doxycycline, 100 milligrams PO twice daily for 7 to 10 days, is the empirical treatment of choice, and chloramphenicol is an alternative. African tick typhus requires only 3 days of therapy and is often self-limited even without treatment. In severe cases of scrub typhus, death occurs from a multiorgan toxemia within 1 to 2 weeks of illness onset if untreated. Continue treatment for at least 5 days and for 48 hours after defervescence.
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Typhus (Epidemic Louse-Borne Typhus)
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Typhus is a rickettsial louse-borne disease caused by Rickettsia prowazekii. Typhus is a different disease from the bacterial disease due to S. typhi, typhoid fever (see above). Epidemic louse-borne typhus is transmitted by the arthropod body louse. Typhus is widespread and found in Central Africa, Asia, and Central, North, and South America. It is also common in cold mountainous regions affected by famine, war, or mass population movement, where adequate clothing exists to harbor the louse or lice. Louse-borne disease occurs after louse body fluids and feces are rubbed into abrasions or after bites. Infection results in high fevers after an 8- to 12-day incubation period. Severe headache is common, and a maculopapular rash appears between days 4 and 7, generally sparing palms and soles. The rash may be hemorrhagic. Diagnosis starts on clinical grounds and is confirmed with serologic testing. Treatment is doxycycline (100 milligrams PO twice daily) or chloramphenicol (50 milligrams/kg/d PO in four divided doses) for 7 days and until 48 hours after defervescence. Untreated, mortality is as high as 60%.
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LEPTOSPIROSIS (WEIL'S DISEASE)
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Leptospirosis, or Weil's disease, follows mucous membrane or percutaneous exposure to freshwater contaminated by Leptospira interrogans. Infected animals excrete the spirochete in their urine. Infected patients typically have had contact with dogs; swam, rafted, or waded in contaminated surface water; or farmed or gardened in contaminated areas. Outbreaks commonly occur after flooding. Although the risk to most routine travelers is low, recent ecotourists and adventure travelers have become infected after intense water exposure.
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The clinical course can be asymptomatic, but often symptoms illustrate a biphasic pattern. After an incubation of 2 to 20 days, high fever, severe headache, chills, myalgias, hepatitis (with or without jaundice), and nonspecific influenza-like symptoms develop. NoTable is conjunctival injection without purulent discharge. Symptoms resolve in 4 to 7 days, followed several days later by the severe, icteric Weil's disease caused by circulating antibodies. The second phase lasts for up to 4 weeks and can include aseptic meningitis, renal failure, uveitis, rash, and, rarely, circulatory collapse. Isolation of leptospires from blood, urine, or cerebrospinal fluid is diagnostic, although sensitivity varies with duration of symptoms. Serology is most often used to confirm the diagnosis. Treatment reduces the severity and duration of symptoms and may prevent the second disease phase. Mild disease can be treated within the first 3 days of illness with PO amoxicillin, 500 milligrams four times daily, or doxycycline, 100 milligrams twice daily, whereas more severe cases require IV penicillin (1.5 million units every 6 hours), ceftriaxone (1 gram daily), or ampicillin (1 gram every 6 hours). Treatment duration is 7 to 14 days total. Consider empiric therapy with PO doxycycline or IV penicillin (or ampicillin) if leptospirosis is suspected.
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Relapsing fever is a bacterial infection caused by the spiral-shaped Borrelia species (Borrelia recurrentis) transmitted by lice or tick bites. It is rare among travelers, yet should be suspected in those who have contact with refugee and displaced populations. After being introduced by a louse or tick bite, Borrelia reproduce in body fluids and produce endotoxins affecting the liver, spleen, and capillaries. After incubation of 3 to 10 days, patients develop fever, chills, headache, myalgias, abdominal pain, and jaundice. In severe cases, mental status changes, meningoencephalitis, myocarditis, hepatic failure, and disseminated intravascular coagulopathy occur. After 5 to 7 days, fever may spontaneously abate, accompanied by hypotension, and, near day 14, fever may recur. The number of relapses varies, with 1 to 2 relapses in louse-borne fever, 3 to 6 relapses in tickborne fever, and up to 11 relapses in African varieties. Diagnosis is made by clinical suspicion and confirmed by identifying spirochetes blood peripheral smear, cerebrospinal fluid, or bone marrow. Spirochetes are best observed in blood when taken during the febrile period. Louse-borne and tickborne relapsing fever is treated with tetracycline, 500 milligrams PO every 6 hours for 10 days; doxycycline, 100 milligrams PO every 12 hours for 7 to 10 days; or erythromycin, 500 milligrams PO every 6 hours for 10 days. When CNS involvement is suspected, ceftriaxone, 2 grams IV, should be given every 24 hours.