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CHAPTER 162: Global Travelers 1079 PROTOZOA Cats are the host of the intracellular protozoan Toxoplasma gondii, which causes toxoplasmosis. Human toxoplasmosis can occur in three ways: by ingestion of uncooked or raw meat, especially pork or mutton containing the Toxoplasma cysts; by ingestion of the oocysts from cat and wild-animal feces; and transplacentally. 38 Transplacental trans mission can result in fetal abnormalities including retinochoroiditis, hydrocephalus, hepatosplenomegaly, and thrombocytopenia. Pregnant women should limit their contact to only indoor cats, avoid chang ing cat litter, and wear gloves when gardening or in contact with soil or sand that could be contaminated with toxoplasma. The encysted trophozoite can become reactivated in a previously infected host if the host becomes immunocompromised. Treatment of acute chorioretinitis, of severely symptomatic patients, or in certain pregnancy conditions is with pyrimethamine (25 to 100 milligrams/d PO for 3 to 4 weeks) plus sulfadiazine (1.0 to 1.5 grams PO four times a day for 3 to 4 weeks) and folinic acid. 38,41  IMMUNOCOMPROMISED PATIENTS Immunocompromised patients include those with congenital immu nodeficiencies, diabetes mellitus, chronic renal failure, or liver fail ure; splenectomized patients; chronic alcoholics; cancer patients; transplanted patients; and human immunodeficiency virus–positive patients. Of all of these patients, those undergoing chemotherapy and those with acquired immunodeficiency syndrome have the greatest risk of acquiring a zoonotic infection. 41 Salmonella and Campylobacter are the two most common infections acquired by immunocompro mised patients from their pets, but the overall risk of transmission of Salmonella and Campylobacter from contact with pets is low. Other acquired zoonotic infections in immunocompromised patients are listed in Table 161-8. TABLE 161-8 Zoonotic Infections in Immunocompromised Patients Infection Source Clinical Findings Antibiotic Treatment Cat-scratch disease, Bartonella henselae Cats Pyogenic granulomas, regional lymphadenopathy, and fever Azithromycin Add rifampin for severe disease Bordetella bronchiseptica Dogs Fever, pharyngitis, and cough TMP-SMX, fluoroquinolones, azithromycin if Bordetella pertussis suspected Campylobacter species Dogs, cats Gastroenteritis and diarrhea See Chapter 160, “Food and Waterborne Illnesses” Cryptococcus neoformans Bird droppings and cats Flulike symptoms early, photophobia, headache, cranial nerve symptoms, and meningeal irritation later Mild disease: fluconazole Severe: amphotericin B + flucytosine followed by fluconazole Cryptosporidium Dogs Diarrhea Immunocompetent host: nitazoxanide HIV positive: HAART only Giardia lamblia Dogs, cats Gastroenteritis and diarrhea See Chapter 160. Listeria monocytogenes Livestock and dairy products Sepsis and meningitis Severe disease: ampicillin + gentamicin Gastroenteritis in at-risk population: amoxicillin or TMP-SMX Mycobacterium M. avium Pet birds Pneumonia and gastroenteritis Clarithromycin or azithromycin + ethambutol + rifampin M.

arrhea See Chapter 160. Listeria monocytogenes Livestock and dairy products Sepsis and meningitis Severe disease: ampicillin + gentamicin Gastroenteritis in at-risk population: amoxicillin or TMP-SMX Mycobacterium M. avium Pet birds Pneumonia and gastroenteritis Clarithromycin or azithromycin + ethambutol + rifampin M. marinum Fish Cutaneous granulomas, skin ulcerations at distal extremities Clarithromycin, minocycline, doxycycline, TMP-SMX, or rifampin + ethambutol Rhodococcus equi Farm animals Pneumonia and cavitating lung lesions Two of the following agents: levofloxacin, rifampin, azithromycin, ciprofloxacin, imipenem, vancomycin Salmonella, Salmonella species Dogs, cats, reptiles, poultry, livestock Gastroenteritis, diarrhea, and sepsis See Chapter 160. Toxoplasmosis, Toxoplasma gondii Cats Pneumonia, brain abscesses, encephalitis, and ocular disease Pyrimethamine + sulfadiazine + folinic acid Abbreviations: HAART = highly active antiretroviral therapy; HIV = human immunodeficiency virus; TMP-SMX = trimethoprim-sulfamethoxazole. REFERENCES The complete reference list is available online at www.TintinalliEM.com. Global Travelers Shawn M. D’Andrea Annelies De Wulf INTRODUCTION Of returning travelers who become ill, many have neither serious nor exotic illnesses. 1 In a study evaluating 82,825 returning travelers seen in global travel clinics between 1996 and 2011, only 4.4% (3655) of the cases involved acute, tropical, potentially life-threatening causes of illness. 2 The initial task is to separate the more common causes of symptoms, such as upper respiratory infections, diarrheal illnesses, reactions to stress, fatigue, or new medications, from more ominous causes of illness in travelers. Key points for the initial ED care are as follows: 1. Isolate and use personal protective precautions early when evaluating patients with suspected travel-related infections. 2. Identify red flag symptoms such as hemorrhage and altered men tal status and initiate isolation and treatment prior to diagnostic confirmation. 3. Consider malaria in the febrile patient returning from travel, even in the presence of prophylaxis, and initiate treatment promptly. 4. Report suspected reportable illnesses. CHAPTER Tintinalli_Sec13_p0997-1100.indd 1079 8/2/19 8:12 PM

tal status and initiate isolation and treatment prior to diagnostic confirmation. 3. Consider malaria in the febrile patient returning from travel, even in the presence of prophylaxis, and initiate treatment promptly. 4. Report suspected reportable illnesses. CHAPTER Tintinalli_Sec13_p0997-1100.indd 1079 8/2/19 8:12 PM 1080 SECTION 13: Infectious Diseases PHYSICAL EXAMINATION AND DIAGNOSTIC TESTING Evaluate the abdomen for hepatosplenomegaly or focal abdominal dis comfort. Examine for lymphadenopathy and inspect the skin for rashes, lesions, or pallor. Ophthalmologic examination should look for scleral icterus, conjunctival injection, and petechiae. Remain alert for subtle neurologic signs and altered mental status. Suspect an imported disease in the presence of high fever, signs of hemorrhage, diarrhea, shortness of breath, skin lesions, and neurologic disturbances. Table 162-6 lists other signs of tropical illness. Usually one or more hallmark symptoms or signs are associated with specific infections, guiding diagnostic testing and categorization. These include fever, CNS complaints, abdominal pain, diarrhea, skin and eye complaints, and respiratory symptoms. Initial studies include a CBC with differential, hepatic function tests, and urinalysis; thick and thin blood smears for malaria with rapid antigen detection test if available; blood cultures, urine cultures, stool cultures, and stool analysis for WBCs, ova, and parasites; and chest radiograph. TABLE 162-1 Risk of Infectious Exposure •   High risk (1 in 10 travelers): diarrhea, upper respiratory illness, and noninfectious illnesses such as injuries and exacerbation of preexisting chronic diseases •   Moderate risk (1 in 200 travelers): dengue fever, chikungunya, enteroviral infection, gastroenteritis, giardiasis, hepatitis A, malaria, salmonellosis, sexually transmitted diseases, shigellosis •   Low risk (1 in 1000 travelers): amebiasis, ascariasis, measles, mumps, enterobiasis, scabies, tuberculosis, typhoid, hepatitis B •   Very low risk (1 in >1000 travelers): human immunodeficiency virus, anthrax, Chagas’ disease, hemorrhagic fevers, pertussis, plague, typhus, hookworm TABLE 162-2 Typical Incubation Periods for Selected Tropical Infections Incubation Period Infections Likely <10 d (short incubation) Traveler’s diarrhea Dengue fever and arboviral infections Chikungunya Yellow fever Anthrax Diphtheria Malaria Typhoid fever Meningococcal infections Plague Tularemia Typhus (louse- and flea-borne) <21 d (intermediate incubation) Leptospirosis Viral hemorrhagic fevers Malaria Enteric fevers (typhoid, paratyphoid) Typhus African trypanosomiasis Rabies Zika >21 d Viral hepatitis (A, B, C, D, E) Malaria Acute HIV infection Amebic liver abscess Schistosomiasis (Katayama fever) Visceral leishmaniasis Filariasis >Months Tuberculosis Malaria Filariasis Viral hepatitis B, C HIV Visceral leishmaniasis Rabies Syphilis African and American (Chagas’ disease) trypanosomiasis Abbreviation: HIV = human immunodeficiency virus.  INITIAL EVALUATION OF THE RETURNING TRAVELER Illness before and after travel is common 3 (Table 162-1). Start by evaluating the travel destination. Diseases such as malaria are uncom mon in the United States, but are leading causes of mortality overseas. Other parasitic agents, such as helminths and rickettsia, also occur with increased frequency and severity in the tropics (see Chapters 159 and 161, “Malaria” and “Zoonotic Infections”). Although both tuberculosis and human immunodeficiency virus are endemic to the United States, consider these in patients presenting from areas with a higher disease burden. HISTORY Once imported disease in recent travelers is suspected, direct the history (Tables 162-2, 162-3, and 162-4.).

” and “Zoonotic Infections”). Although both tuberculosis and human immunodeficiency virus are endemic to the United States, consider these in patients presenting from areas with a higher disease burden. HISTORY Once imported disease in recent travelers is suspected, direct the history (Tables 162-2, 162-3, and 162-4.). Immunosuppression, age <5 years, advanced age, pregnancy, and diabetes often render the patient less tolerant of tropical infections. Ask about the duration of travel and timing of return ( Table 162-2). For example, if fever begins >21 days after return from travel, yellow fever, viral hemorrhagic fevers (including Ebola, covered elsewhere), and other arboviruses (e.g., dengue fever) are unlikely, irrespective of the exposure history (Table 162-2). In comparison, schistosomiasis may cause symptoms 4 to 8 weeks after exposure. Incubation periods may vary somewhat depending on host factors such as immune status and the use of chemoprophylaxis. Other important considerations are the specific locales of the traveler, as rural versus urban areas have different infectious disease risks, types of accommodation (e.g., tents or beds without bed nets), and travel-related activities (e.g., exposure to jungles, farm animals), and high-risk behaviors (e.g., eating jungle meat, drinking untreated water) (Table 162-5). Review any pretravel immunizations and preventive medications. Proper vaccination against hepatitis A, hepatitis B, and yellow fever can effectively rule these out as causes of illness. Although chemoprophy laxis reduces the risk of acquiring malaria, it does not eliminate the possibility. Because of increasing malaria resistance and variable adherence to chemoprophylaxis regimens, consider malaria in the febrile returning traveler even with reported chemoprophylaxis. A history of medications, herbs, and traditional medicines is also useful. These may contain antipyretics and other components that can alter disease presentation. If altered mental status and the appropriate travel history exist, sus pect cerebral malaria or meningitis and provide prompt empiric treat ment. In the context of fever and hemorrhagic symptoms with travel to affected areas, initiate infection control practices until Ebola and other hemorrhagic viruses are excluded. In the case of suspected bioterrorism, initiate infection control and decontamination immediately. It is important to identify diseases that may be rapidly fatal, easily treatable, and/ or potentially contagious. Do not await confirmatory testing to initiate decontamination, isolation, and treatment. Tintinalli_Sec13_p0997-1100.indd 1080 8/2/19 8:12 PM

ism, initiate infection control and decontamination immediately. It is important to identify diseases that may be rapidly fatal, easily treatable, and/ or potentially contagious. Do not await confirmatory testing to initiate decontamination, isolation, and treatment. Tintinalli_Sec13_p0997-1100.indd 1080 8/2/19 8:12 PM CHAPTER 162: Global Travelers 1081 TABLE 162-3 Travel-Specific Aspects of the Medical History Pretravel information •   Previous medical condition •   Pediatric patient, diabetes, pregnancy, immunosuppression (especially human immunodeficiency virus [HIV]/acquired immunodeficiency syndrome or steroid use) •   Pretravel consultation and preparation (self-treatment medications, vaccination history, prophylaxis, etc.) •   Type and compliance with chemoprophylaxis, particularly malaria •   History of routine childhood immunization (DPT, polio, MMR, HiB, etc.) •   Nation of birth and citizenship Travel information •   Exact itinerary of departure and arrival (within the last 3–5 y may be relevant) •   Season of travel (monsoon, dry season) •   Destinations visited (including locations of transit or stopovers) •   Urban or rural, altitude •   Purpose of travel and activities in country •   General purpose of visit or travel (e.g., “adventure travel” with high exposure to remote, natural elements) •   Contacts and their health •   Habitat and location of lodging (bed nets, window screens, thatched roof, mud walls) •   Crowded living or sleeping conditions •   High-risk activities (e.g., medical care of displaced populations, spelunking in caves) •   Opioid use or injection drug use •   Sexual intercourse with high-risk sexual contacts (unprotected with anyone; with highrisk populations, e.g., commercial sex workers, in areas with high prevalence of HIV); dates and nature of sexual contact •   Exposure to environment (swimming in freshwater or saltwater, hiking, trekking, digging, or soil contact, e.g., open-toed shoes or bare feet) •   Consumption of high-risk foods (wild game or bush meat, raw or undercooked meats or fish, unpasteurized milk products, food from street vendors, natural sources of water, salads) •   Exposure to dogs, birds, or rodents •   Adverse incidents •   Insect or animal bites •   Saliva from animals to open wounds •   Assault or trauma •   Status and health of fellow travelers •   Possible ill contacts •   In-country medical consultations sought, remedies used, and procedures (injections, acupuncture, transfusions, dental procedures, body piercing, or tattooing) Abbreviations: DPT = diphtheria, pertussis, and tetanus; HiB = Haemophilus influenzae type b; MMR = measles, mumps, and rubella. TABLE 162-4 Regional Tropical Illnesses •   Africa: malaria, human immunodeficiency virus, TB, hookworm, tapeworm, roundworm, brucellosis, yellow fever (and other hemorrhagic fevers such as Lassa fever or Ebola), relapsing fever, schistosomiasis, tick typhus, filariasis, strongyloidiasis, Zika, chikungunya •   Central and South America: malaria, relapsing fever, dengue fever, filariasis, TB, schistosomiasis, Chagas’ disease, typhus, Zika, chikungunya •   Mexico and the Caribbean: dengue fever, hookworm, malaria, cysticercosis, amebiasis, Zika •   Australia, New Zealand: dengue fever, Q fever, Murray Valley encephalitis, Japanese encephalitis •   Middle East: hookworm, malaria, anthrax, brucellosis, middle eastern respiratory virus •   Europe: giardiasis, Lyme disease, tick-borne encephalitis, babesiosis, chikungunya (southern Europe) •   China and East Asia: dengue fever, hookworm, malaria, strongyloidiasis, hemorrhagic fever, Japanese encephalitis, Zika, chikungunya Abbreviation: TB = tuberculosis. In a clinically well-appearing patient in whom malaria treatment is suspected, obtain blood for smear every 12 to 24 hours.

ikungunya (southern Europe) •   China and East Asia: dengue fever, hookworm, malaria, strongyloidiasis, hemorrhagic fever, Japanese encephalitis, Zika, chikungunya Abbreviation: TB = tuberculosis. In a clinically well-appearing patient in whom malaria treatment is suspected, obtain blood for smear every 12 to 24 hours. Use other spe cific serologic tests selectively, such as erythrocyte sedimentation rate, purified protein derivative, syphilis testing, human immunodeficiency virus testing, and serology for arboviruses or rickettsiae. Infectious disease consultation early in the evaluation can optimize testing and follow-up. Obtain an extra vial of serum in a red-top tube (for serology and immunology) during the initial evaluation for followup testing.  DISEASES COMMONLY ASSOCIATED WITH FEVER Although fever is nonspecific, it raises the suspicion for a serious infection and is present in up to about 90% of serious travel-related illnesses (Table 162-7). 2,5-7 Treat patients with fever after tropical travel as if they have malaria until proven otherwise. Other common serious infections are listed in Table 162-8.8,9 MALARIA The classic clinical triad for all species of malaria is fever, spleno megaly, and thrombocytopenia. 10,11 Fever is typically irregular for the first week and later may be periodic. 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 who are immuno logically naive or who have lost their acquired immunity through pro longed absence from an endemic country, and patients with comorbid medical problems. Because associated symptoms such as headache, cough, and GI problems mimic other conditions, malaria should be a consideration in all febrile travelers. If a patient has the appropriate travel history and altered mental status, suspect cerebral malaria and initiate treatment promptly. Diagnosis is based on clinical presentation then 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 159, “Malaria, ” for a detailed discussion of malaria diagnosis and treatment. DENGUE FEVER The World Health Organization reports a 30-fold increase in incidence of dengue in the past 30 years, becoming a leading cause of morbidity and mortality in the tropics. 12 Suspect dengue fever among travelers with fever developing within 2 weeks of travel. Dengue may be contracted more than once, and subsequent infections may be progressively more severe. Dengue is transmitted by the day-biting Aedes aegypti mosquito. Dengue fever presents after a typically short incubation period of 4 to 7 days with sudden high fever, headache, nausea, vomiting, severe myalgias (hence the term “break bone fever”), and rash usually lasting several days. Facial flushing, conjunctival injection (although uncommon), and retro-orbital pain can occur. After defervescence, a fine, pale, morbilli form rash develops on the trunk and spreads to the extremities and face. Small children may only present with a mild upper respiratory infection. Dengue may be confused with influenza, measles, or rubella. West Nile fever can also present similarly, but also causes lymphadenopathy, which is usually absent in dengue. Dengue can cause petechial hemorrhages indistinguishable from meningococcemia.

ll children may only present with a mild upper respiratory infection. Dengue may be confused with influenza, measles, or rubella. West Nile fever can also present similarly, but also causes lymphadenopathy, which is usually absent in dengue. Dengue can cause petechial hemorrhages indistinguishable from meningococcemia. Severe dengue, previously known as dengue hemorrhagic fever, preferentially occurs among infants of immune mothers, children >1 year old, and those with second and subsequent infections. It begins 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 Tintinalli_Sec13_p0997-1100.indd 1081 8/2/19 8:12 PM

ose with second and subsequent infections. It begins 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 Tintinalli_Sec13_p0997-1100.indd 1081 8/2/19 8:12 PM 1082 SECTION 13: Infectious Diseases TABLE 162-5 Specific Exposures and Associated Tropical Infections Contact/Exposure Possible Infections Untreated water, unpasteurized dairy products Salmonellosis, shigellosis, hepatitis, amebiasis, brucellosis, listeriosis, TB Raw or undercooked shellfish Clonorchiasis, paragonimiasis, Vibrio, hepatitis A Raw or undercooked animal flesh Trichinosis (e.g., pig, horse, bear), Salmonella, enterohemorrhagic Escherichia coli Raw vegetables, water plants (e.g., watercress) Fascioliasis Animal contact (and animal products) Rabies, Q fever, tularemia, brucellosis, echinococcosis, anthrax, plague, Nipah virus, toxoplasmosis, herpes B encephalitis Rodent contact Hantavirus, viral hemorrhagic fevers, murine (endemic) typhus, Lassa fever, plague, leptospirosis Arthropod vectors Mosquitoes Malaria, dengue fever, chikungunya, filariasis, yellow fever, Zika, and other arboviral infections Ticks or mites Rickettsioses, tularemia, scrub typhus, Crimean-Congo hemorrhagic fever, African tick bite fever Reduviid (kissing) bugs American trypanosomiasis (Chagas’ disease) Tsetse flies African trypanosomiasis (African sleeping sickness) Fleas Typhus, plague Sandflies Leishmaniasis, sandfly fever Freshwater exposure Schistosomiasis, leptospirosis Barefoot exposure Strongyloidiasis, cutaneous larva migrans, hookworm Sexual contacts Human immunodeficiency virus, hepatitis B, syphilis, gonorrhea, chlamydia, herpes simplex, Zika Infected persons contact Viral hemorrhagic fever, enteric fever, meningococcal infection, TB Abbreviation: TB = tuberculosis. TABLE 162-6 Physical Findings in Selected Tropical Infections Physical Finding Likely Infection or Disease Rash Dengue fever, typhus, syphilis, gonorrhea, Ebola fever, brucellosis, chikungunya, HIV seroconversion Jaundice Hepatitis, malaria, yellow fever, leptospirosis, relapsing fever Lymphadenopathy Rickettsial infections, brucellosis, HIV, Lassa fever, leishmaniasis, Epstein-Barr virus, cytomegalovirus, toxoplasmosis, trypanosomiasis Hepatomegaly Amebiasis, malaria, typhoid, hepatitis, leptospirosis Splenomegaly Malaria, relapsing fever, trypanosomiasis, typhoid, brucellosis, kala-azar, typhus, dengue fever, schistosomiasis Eschar Typhus, borreliosis, Crimean-Congo hemorrhagic fever, anthrax Hemorrhage Lassa, Marburg, or Ebola viruses; Crimean-Congo hemorrhagic fever; meningococcemia, epidemic louse-borne typhus Abbreviation: HIV = human immunodeficiency virus. epistaxis, purpura, petechia, and marked thrombocytopenia with elevated hematocrit because of vascular permeability. Severe dengue may rapidly evolve and is often fatal. Severe dengue exhibits abdominal pain, severe emesis, mental status changes, and alternating severe pyrexia and hypothermia. 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 leu kopenia, thrombocytopenia, and hepatic dysfunction. In uncomplicated dengue fever, treatment is supportive and consists of fluids and anal gesics. Only acetaminophen is recommended for managing pain and fever because aspirin and other NSAIDs are contraindicated due to anticoagulant properties.

abnormalities include leu kopenia, thrombocytopenia, and hepatic dysfunction. In uncomplicated dengue fever, treatment is supportive and consists of fluids and anal gesics. Only acetaminophen is recommended for managing pain and fever because aspirin and other NSAIDs are contraindicated due to anticoagulant properties. TYPHOID FEVER 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. 14 Typhoid and paratyphoid are caused by Salmonella typhi and Salmonella paratyphi, respectively. Once malaria is excluded, typhoid fever is commonly the cause of a febrile illness lasting >10 days. 15 Typhoid fever is endemic in countries with poor sanitation and unsafe drinking water in Africa, the Americas, Southeast Asia, and the Western Pacific regions. 16 Vaccination before travel helps prevent illness, although protection wanes with time and revaccination is required. The disease is transmitted in a dose-related fashion after food con tamination by feces or urine from actively infected cases or healthy disease carriers. Incubation times and disease severity vary from 1 to 3 weeks. Most pathology occurs in the gut because 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. In epidemics, patients can present with acute diarrhea and vomiting, headache, and meningeal signs. However, 30% of patients present with constipation rather than diarrhea. 17 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 indi viduals. 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 perforation, anemia, disseminated intravascular coagulopathy, mycotic aneurism, pneumonia, meningitis, septic arthritis, myocarditis, chole cystitis, and renal failure. Sequelae include deafness, and other neuro logic involvement including psychosis, ataxia, and seizures can occur. Diagnosis is clinical, 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. 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, fluoroquinolone resistance is increasing, especially in travelers returning from South and Southeast Asia, associated with nalidixic acid–resistant S. typhi strains. 19 Ampicillin, trimethoprimsulfamethoxazole, and chloramphenicol are unreliable due to resistance. If the patient is severely ill with suspected typhoid meningitis/encepha litis or shock, administer dexamethasone in addition to antibiotics. Supportive treatment includes IV rehydration and blood transfusion (if needed from GI losses). Relapses can occur after clinical improvement. Untreated, mortality is 10% to 20%, mostly in young children. Tintinalli_Sec13_p0997-1100.indd 1082 8/2/19 8:12 PM

or shock, administer dexamethasone in addition to antibiotics. Supportive treatment includes IV rehydration and blood transfusion (if needed from GI losses). Relapses can occur after clinical improvement. Untreated, mortality is 10% to 20%, mostly in young children. Tintinalli_Sec13_p0997-1100.indd 1082 8/2/19 8:12 PM CHAPTER 162: Global Travelers 1083 TABLE 162-7 Tropical Infectious Diseases Causing Fever Among International Travelers ( Continued) INCUBATION <2 WEEKS Disease Distribution Mode of Transmission Undifferentiated fever Malaria, Zika Most tropical and subtropical areas Infected mosquito bite Dengue Tropics and subtropics, including urban areas Infected mosquito bite Chikungunya Africa, Asia, Latin America, US, southern Europe, and Caribbean Infected mosquito bite Spotted fever Worldwide Infected tick or mite bite Scrub typhus Asia, Australia Infected mite bite Leptospirosis Widespread, mostly tropics Percutaneous contact with animal urine or contaminated soil and water; ingestion Typhoid fever Developing countries, especially Indian subcontinent Contaminated food/water ingestion Acute HIV infection Worldwide Permucosal or percutaneous exposure to infective blood or fluids African trypanosomiasis East African form found in East and South Africa.

al urine or contaminated soil and water; ingestion Typhoid fever Developing countries, especially Indian subcontinent Contaminated food/water ingestion Acute HIV infection Worldwide Permucosal or percutaneous exposure to infective blood or fluids African trypanosomiasis East African form found in East and South Africa. West African form found in central and West Africa Infective tsetse fly bite Shigellosis Widespread, most common in developing countries Contaminated food/water ingestion Salmonellosis Widespread, most common in developing countries Contaminated food/water ingestion Campylobacteriosis Widespread, most common in developing countries Contaminated food/water ingestion Fever with hemorrhage Meningococcemia Widespread, highly prevalent in sub-Saharan meningitis belt in dry season from December to June Via respiratory and oral secretions Leptospirosis Widespread, most common in tropical climate Freshwater exposure Crimean-Congo hemorrhagic fever East and West Africa, Eurasia Infected tick bite Viral hemorrhagic fever Worldwide Contact with an infected patient, rodent, bat, tick, or mosquito Other bacterial infection Fever with CNS involvement Meningococcemia See listing above See listing above Rabies Common in Africa, Asia, and Latin America Infected animal saliva exposure Malaria See listing above See listing above Many viral and bacterial forms Arboviral encephalitis (Japanese encephalitis, tick-borne encephalitis, dengue, West Nile, Murray Valley) Worldwide Infected mosquito or tick bite Angiostrongyliasis Widely scattered, most common in East Asia and Southeast Asia Ingestion of contaminated food/water with snail or slug slime Poliomyelitis Primarily Africa and parts of Asia Ingestion of feces-contaminated food/water Fever with respiratory findings Influenza Widespread; outbreaks on cruise ships Direct or airborne droplet transmission Severe acute respiratory syndrome China, Hong Kong, other regions in East Asia Direct or airborne droplet transmission Legionellosis (legionnaires’ disease) Widespread; outbreaks in hotels and cruise ships Inhalation or aspiration of infected droplets Q fever Worldwide Inhalation of infective aerosol from animal source INCUBATION 2–6 WEEKS Malaria See listing above See listing above Typhoid fever See listing above See listing above Hepatitis A and E Widespread; most common in developing countries Contaminated food/water ingestion Acute schistosomiasis Africa, Middle East, Southeast Asia, and Brazil Penetration of skin by larval cercaria during freshwater exposure Amebic liver disease Widespread; developing countries Ingestion of cysts usually in feces-contaminated food/water Leptospirosis See listing above See listing above African trypanosomiasis See listing above See listing above Q fever See listing above See listing above Acute HIV infection Worldwide, increased risk in developing countries Sexual exposure (Continued ) Tintinalli_Sec13_p0997-1100.indd 1083 8/2/19 8:12 PM

ted food/water Leptospirosis See listing above See listing above African trypanosomiasis See listing above See listing above Q fever See listing above See listing above Acute HIV infection Worldwide, increased risk in developing countries Sexual exposure (Continued ) Tintinalli_Sec13_p0997-1100.indd 1083 8/2/19 8:12 PM 1084 SECTION 13: Infectious Diseases TABLE 162-8 Most Common Causes of Fever After Travel to Tropical Regions •   Malaria •   Respiratory tract infections (upper respiratory tract infections, pneumonia, legionnaires’ disease, and influenza) •   Diarrheal disease •   Urinary tract infection •   Dengue fever •   Enteric fever (typhoid, paratyphoid fever) •   Rickettsial infection •   Infectious mononucleosis •   Pharyngitis TABLE 162-7 Tropical Infectious Diseases Causing Fever Among International Travelers ( Continued) INCUBATION >6 WEEKS Malaria See listing above See listing above Tuberculosis Worldwide Inhalation Hepatitis B Widespread Permucosal or percutaneous exposure to infective blood or fluids Visceral leishmaniasis Many parts of Africa, Asia, South America, and Mediterranean basin Infective sand fly bite Lymphatic filariasis Widespread in tropical areas Infected mosquito bite Schistosomiasis See listing above See listing above Amebic liver abscess See listing above See listing above Rabies Worldwide Infected animal saliva exposure African trypanosomiasis See listing above See listing above Abbreviation: HIV = human immunodeficiency virus. RICKETTSIAL SPOTTED FEVERS Rickettsial spotted fevers are transmitted by the bite, body fluid, or feces of ixodid arthropod ticks, which are widely distributed globally. Fleas and mites can also transmit rickettsial infections. Among the eight major rickettsial infections, there is variation in severity. Mortality without treatment approaches 25%, which drops to 5% with treatment (see Chapter 161, “Zoonotic Infections”). Scrub Typhus and African Tick Typhus 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. 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 less severe symptoms and localized lymphade nopathy associated with an eschar. Diagnosis is clinical, and serologic tests are confirmatory. Doxycycline is the empirical treatment of choice; azithromycin and chloramphenicol are alternatives. 22 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. Typhus (Epidemic Louse-Borne Typhus) Typhus is a rickettsial louse-borne disease caused by Rickettsia prowazekii. Typhus is a different disease from typhoid fever, the bacterial disease due to S. typhi (see earlier). 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 rainy seasons and in cold regions affected by famine, war, or mass population move ment, where clothing and blankets harbor the lice.

pidemic 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 rainy seasons and in cold regions affected by famine, war, or mass population move ment, where clothing and blankets harbor the 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 or chloramphenicol until 48 hours after defervescence. 23 Treatment also includes delousing the patient’s clothing. Mortality in severe cases is as high as 24%.24 LEPTOSPIROSIS (WEIL’S DISEASE) Leptospirosis, or Weil’s disease, follows mucous membrane or percutaneous exposure to freshwater contaminated by Leptospira interrogans. Infected animals include many wild and domesticated animals, espe cially rodents, which 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. 25 Although the risk to most routine travelers is low, recent ecotourists and adventure travelers have become infected after intense water exposure. The clinical course can be asymptomatic, but often symptoms illus trate a biphasic pattern. After an incubation of 2 days to 4 weeks, symptoms may include high fever, severe headache, chills, myalgias, hepatitis (with or without jaundice), and nonspecific influenza-like complaints. 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 or doxy cycline, whereas more severe cases require IV penicillin, ceftriaxone, or ampicillin. Treatment duration is 7 to 14 days. Consider empiric therapy with PO doxycycline or IV penicillin (or ampicillin) when suspecting leptospirosis. ZIKA VIRUS Transmitted by the Aedes mosquito, Zika virus (a member of the Flaviviridae family) is transmitted in a wide range of tropical areas in the world. In addition to mosquitos, Zika may be transmitted through sexual intercourse, from mother to fetus in utero and mother to child through breastfeeding, and through blood transfusion. Symptoms may include conjunctivitis, headache, joint pain, fever, and malaise. Although Zika does not commonly pose a serious threat to those infected, it has been associated with Guillain-Barré syndrome. Zika infection of a pregnant woman can cause multiple serious birth defects including severe microcephaly. Offer testing to any pregnant women traveling from Zikaaffected regions exhibiting signs of Zika; counsel men and women with suspected Zika infection or exposure of the risk of sexual transmission. Tintinalli_Sec13_p0997-1100.indd 1084 8/2/19 8:12 PM

n cause multiple serious birth defects including severe microcephaly. Offer testing to any pregnant women traveling from Zikaaffected regions exhibiting signs of Zika; counsel men and women with suspected Zika infection or exposure of the risk of sexual transmission. Tintinalli_Sec13_p0997-1100.indd 1084 8/2/19 8:12 PM CHAPTER 162: Global Travelers 1085 The Centers for Disease Control and Prevention currently recommends that men returning from places at risk of Zika virus wait 3 months before having unprotected sex and that women wait 2 months, even if they have not been symptomatic. Treatment is supportive. CHIKUNGUNYA FEVER A self-limited arboviral infection with epidemic potential also spread through the Aedes mosquito species, chikungunya has become a significant cause of illness, especially in the Caribbean and South America. The incubation period is 1 to 12 days (usually 2 to 3 days), and it pres ents with fever, severe myalgias, fatigue, headache, morbilliform rash, and occasional thrombocytopenia. Hemorrhagic complications are rare. Diagnosis is through increases of immunoglobulin M antibodies either in serum or the cerebrospinal fluid. Treatment is supportive, and longterm arthralgia sequelae are not uncommon. RELAPSING FEVER Relapsing fever is a bacterial infection caused by the spiral-shaped Borrelia species (Borrelia species not including Borrelia burgdorferi, the causative organism of Lyme disease) 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 reproduces in body fluids and produces endotoxins affecting the liver, spleen, and capillaries. After incubation of 3 to 10 days, patients develop fever, chills, headache, and myalgias. In rare severe cases, acute respiratory distress syndrome, CNS involvement, and liver failure occur. After spontaneous abatement, fever may relapse several times. Diagnosis is made by clinical suspicion and confirmed by identifying spirochetes in blood peripheral smear, cerebrospinal fluid, or bone marrow. Spirochetes are best seen when blood is sampled during a febrile period. Louse-borne and tick-borne relapsing fever is treated with tetracycline, doxycycline, or erythromycin. Ceftriaxone can also be given with CNS involvement.  DISEASES COMMONLY ASSOCIATED WITH FEVER AND HEMORRHAGE Among the most feared tropical diseases are viral hemorrhagic fevers. However, viral hemorrhagic fevers are rare when compared with other febrile hemorrhagic infections such as malaria, dengue fever, meningo coccemia, leptospirosis, plague, bacterial sepsis, and rickettsial fevers. Neisseria meningitidis is the most common cause of acute hemor rhagic fever in temperate climates. Among travelers, several treatable infections, including Lassa fever, meningococcemia, leptospirosis, and rickettsial infection, can cause fever associated with hemorrhage. Most people with viral hemorrhagic fevers, such as dengue, hantavirus (Chapter 161), Lassa, Ebola, Marburg, and Rift Valley, develop fever within 3 weeks after exposure. Viral hemorrhagic fever usually follows the bite of infected mosquitoes and ticks, close contact with rodent/bat excreta, or direct contact with infected, symptomatic individuals (the latter notably for Ebola). In the event of a suspected viral hemorrhagic fever of tropical origin, institute control measures , including isolation in a negativepressure room, the use of high-efficiency particulate-arresting respira tors, and the use of gloves and gowns. Immediately notify local public health officials for suspected contagious viral hemorrhagic fevers such as Marburg, Lassa, Ebola, or Crimean-Congo hemorrhagic fever.

measures , including isolation in a negativepressure room, the use of high-efficiency particulate-arresting respira tors, and the use of gloves and gowns. Immediately notify local public health officials for suspected contagious viral hemorrhagic fevers such as Marburg, Lassa, Ebola, or Crimean-Congo hemorrhagic fever. If intentional bioterrorism is suspected, notify local law enforce ment officials, the Federal Bureau of Investigation, and the Centers for Disease Control and Prevention. YELLOW FEVER Y ellow fever, an acute zoonotic flavivirus, has a jungle monkey reservoir present in the tropics of South America and Africa, where vaccination is mandatory. Outbreaks are common near tourist areas and may occur among nonimmunized adventure travelers who travel to endemic areas. With the increase in global travel and because the day-biting mosquito vector A. aegypti (which also transmits dengue) is endemic in a wide global distribution, including North and Central America, the Carib bean, as well as parts of Asia, yellow fever outbreaks can appear outside of traditionally endemic areas, as evidenced by a recent outbreak in Brazil. 31,32 Y ellow fever ranges in severity from an undifferentiated self-limited flulike illness to a hemorrhagic fever that is fatal in 20% to 50% of patients who develop severe disease (15% of infected persons). 32,33 After an incubation of 3 to 6 days, patients develop fever, headache, myalgias, conjunctival injection, abdominal pain, prostration, facial flushing, and relative bradycardia. In most cases, patients recover, but in others, fever remission lasts a few hours to several days, followed by renewed high fever, jaundice, vomiting, shock, multiorgan failure, and bleeding diathesis. The classic presentation is a triad of jaundice, black emesis, and albuminuria. Confusion, seizures, and coma are common in the late stages of the illness, and death can occur within 7 to 10 days after onset. The diagnosis is primarily clinical, although confirmation is pos sible through virus identification or rising antibody titers in recovering patients. Leukopenia and albuminuria are typical, direct bilirubin levels rise, and liver enzymes are elevated for several days, during which time azotemia and oliguria ensue. Treatment is supportive, with fluid replacement and management of hematologic complications. EBOLA AND MARBURG VIRUSES Periodic outbreaks of Ebola virus disease have existed since 1976. Transmission is thought to occur via human contact with infected animals, either primates or fruit bats. 34 The most recent large outbreak in mul tiple West African countries had >11,000 associated deaths by 2016. 35,36 Four Ebola species cause disease in humans. Disease transmission is by direct contact with infected blood or body fluids, contaminated needles or syringes, or infected bats or primates. The virus is stable, with little mutation in current species compared to that in the epidemic of 1976. Symptoms begin 2 to 21 days after exposure with fever, myalgia, malaise, diarrhea, abdominal pain, and vomiting, and progress to hem orrhage, shock, and end-organ failure. Mortality is high, but those who recover have an antibody response that lasts about 10 years. Diagnosis is by enzyme-linked immunosorbent assay serology, polymerase chain reaction, culture, or immunochemistry and, in the United States, is performed at the U.S. Centers for Disease Control and Prevention after consultation and acceptance of specimens (770-488-7100). Treatment is supportive with no proven effective antiviral therapy; however, inves tigational therapies including convalescent serum and antibody treat ments have been used.

United States, is performed at the U.S. Centers for Disease Control and Prevention after consultation and acceptance of specimens (770-488-7100). Treatment is supportive with no proven effective antiviral therapy; however, inves tigational therapies including convalescent serum and antibody treat ments have been used. Vaccines remain under development, although at the time of this writing (November 2018), an investigational vaccine is being deployed in the Democratic Republic of Congo, which is combating an ongoing outbreak. Epidemic containment focuses on avoidance of exposure and, for healthcare workers, the use of personal protec tive equipment. Hospital preparedness consists of the identification of potential exposed contacts by identifying travel and direct exposure history, determining disease signs and symptoms, and then isolating individuals with possible disease. Similar to Ebola, episodic outbreaks of Marburg virus infection exist in sub-Saharan Africa, and the virus has been found in African fruit bats. 38 Clinical presentation is similar to Ebola.36 CRIMEAN-CONGO HEMORRHAGIC FEVER This tick-borne viral disease is common in Africa, Eastern Europe, Asia, and the Middle East, especially in Turkey. Mortality ranges from 3% to 30%. The prehemorrhagic period is characterized by the sudden onset of fever, headache, myalgia, dizziness, and, possibly, altered mental status. The hemorrhagic period is short (2 to 3 days), develops rapidly, and usually begins between the third and fifth day of disease. The most common bleeding sites are the nose, GI system (hematemesis, melena, and intra-abdominal), uterus (menometrorrhagia) and urinary tract (hematuria), and the respiratory tract (hemoptysis). Thrombocytopenia is common. Patients may have Tintinalli_Sec13_p0997-1100.indd 1085 8/2/19 8:12 PM

and fifth day of disease. The most common bleeding sites are the nose, GI system (hematemesis, melena, and intra-abdominal), uterus (menometrorrhagia) and urinary tract (hematuria), and the respiratory tract (hemoptysis). Thrombocytopenia is common. Patients may have Tintinalli_Sec13_p0997-1100.indd 1085 8/2/19 8:12 PM 1086 SECTION 13: Infectious Diseases TABLE 162-9 Tropical Infectious Diseases Causing Severe Headache and Fever •   Malaria •   Rickettsial disease •   Dengue fever •   Typhoid fever •   Human African trypanosomiasis leukopenia and elevated liver enzymes, lactate dehydrogenase, and creatinine. Prothrombin time and activated PTT can be prolonged. Diagnosis is clinical and confirmed with serology. Treatment is pri marily supportive, including treatment of coagulopathy and respiratory support in severe cases. Oral or IV forms of ribavirin are available and used in more severe cases; treat for 10 days.39 LASSA FEVER Lassa fever is spread by contact with bush rat excreta or body fluid exposure from an infected person. Although found in rural parts of West Africa, it has been exported to Europe and North America by infected patients, and in endemic areas, impact is high, with up to 16% of admitted patients in hospitals having Lassa fever. After an incubation period of 3 to 16 days, the disease presents as a viral syndrome with insidious onset of fever, malaise, headache, sore throat, retrosternal chest pain, back pain, abdominal pain, and myal gias. Varied and nonspecific symptoms persist for 4 to 6 days, at which time the patient suddenly deteriorates and becomes gravely ill. Among those infected, approximately 80% have mild symptoms and 20% will have severe multiorgan disease. Pregnant women and their fetuses are at elevated risk of severe disease and death. The main features are high fever, prostration, severe sore throat with dysphagia and yellow-white exudates, abdominal pain, diarrhea, and vomiting. Only one third of patients experience bleeding, which may include oozing from the gums, hematemesis, melena, hematochezia, hemoptysis, hematuria, or brain hemorrhage. Diagnosis is made by enzyme-linked immunosorbent assay serology, culture, or immunohistochemistry. Strict patient isola tion and use of personal protection by healthcare workers are necessary. Treatment is largely supportive, but patients with severe disease may benefit from early treatment with ribavirin IV or PO. Survivors will defervesce within 10 days of disease onset and, except for sensorineural deafness, can make a complete recovery.  DISEASES COMMONLY ASSOCIATED WITH FEVER AND CNS INVOLVEMENT Fever with acute mental status changes, headache (Table 162-9), nuchal rigidity, and focal neurologic signs is associated with a number of serious infections. CNS involvement with fever in travelers returning from malaria-endemic regions requires emergency presumptive treat ment for both malaria and bacterial meningitis (see Chapters 159 and 174, “Malaria” and “Central Nervous System and Spinal Infections, ” respectively). The differential diagnosis for fever with CNS involvement includes malaria, meningitis, tuberculosis, typhoid fever, rickettsial infections, and rabies. Other causes are viral encephalitides, including Japanese and West Nile encephalitis, which often present similarly. Patients with altered mental status suspected of tropical illness may demonstrate coma, decreased level of consciousness, meningeal signs, or seizures. Although seizures should arouse suspicion of cerebral malaria, suspect cysticercosis in those with long-term residence in Latin America and a first-time seizure.

larly. Patients with altered mental status suspected of tropical illness may demonstrate coma, decreased level of consciousness, meningeal signs, or seizures. Although seizures should arouse suspicion of cerebral malaria, suspect cysticercosis in those with long-term residence in Latin America and a first-time seizure. Meningococcal meningitis (caused by Neisseria meningitidis) occurs with regularity in sub-Saharan Africa along the “meningitis belt” running from Senegal to Ethiopia, and pilgrims attending the Hajj in Saudi Arabia are also at risk of Neisseria meningitis (Chapter 174). Aseptic meningitis may be caused by enteroviruses or, less commonly, typhoid fever, leptospirosis, or rickettsiae. Encephalitis may be caused by an arboviral infection, such as Japanese encephalitis. JAPANESE ENCEPHALITIS Japanese encephalitis is a vaccine-preventable flavivirus infection that occurs in an epidemic or sporadic pattern over large areas of Asia and the western Pacific. It is rarely transmitted to U.S.-bound travelers because the Culex mosquito vector breeds primarily in rural rice fields. Approximately 25% of infected patients will have severe symptoms, presenting with a sudden high fever, headache, nuchal rigidity, vomiting, and seizures (especially infants) after the incubation time of 5 to 15 days. A variety of pyramidal and extrapyramidal signs may develop soon after fever. If the outcome is fatal, it usually occurs in the first 10 days. Diag nosis is based on clinical suspicion, although virus can be isolated from cerebrospinal fluid, and antibody titers can rise. Treatment is supportive. Recovery may take months, and varying degrees of residual neurologic damage may persist indefinitely. Immunization is recommended for travelers to rural, endemic regions in Asia. CYSTICERCOSIS Cysticercosis is a systemic illness caused by dissemination of the larval form of the pork tapeworm, Taenia solium. The disease affects an esti mated 50 million people worldwide. Endemic areas include Mexico, Latin America, sub-Saharan Africa, India, and East Asia. The incidence in the United States is increasing due to increased immigration from endemic areas and increased travel to endemic areas. Humans are definitive T. solium hosts and can carry the intestinal adult tapeworm. An intermediate host, usually a pig, ingests fecally shed egg-containing proglottids or T. solium eggs. Humans develop cysticercosis when they inadvertently ingest eggs from contaminated food or soil, not from eat ing undercooked pork, which can result in tapeworm infection only. Infestation can occur in almost any tissue. Involvement of the CNS, neurocysticercosis, is the most clinically important manifestation of the disease. Neurocysticercosis is the most common cause of CNS infection globally and the leading cause of adult-onset seizures worldwide. 44 Other symptoms of neurocysticercosis include obstructive hydrocephalus, meningoencephalitis, stroke-like focal deficits, headache, and visual or mental status changes. Noncontrast CT scan shows calcifications of inactive disease and can reveal mass effect or hydrocephalus. Anti helminthic agents (albendazole or praziquantel) are the mainstay of treatment. Use steroids in those with encephalitis, hydrocephalus, or vasculitis to avoid inflammation as cysts involute. In nonendemic areas, check stool studies of household contacts of confirmed cases.  DISEASES COMMONLY ASSOCIATED WITH CHRONIC FEVER Evaluate patients with chronic or relapsing fever lasting beyond 3 weeks after travel initially for non–travel-related infections, inflammatory diseases, and noninfectious disorders.

ute. In nonendemic areas, check stool studies of household contacts of confirmed cases.  DISEASES COMMONLY ASSOCIATED WITH CHRONIC FEVER Evaluate patients with chronic or relapsing fever lasting beyond 3 weeks after travel initially for non–travel-related infections, inflammatory diseases, and noninfectious disorders. Tropical illnesses that cause chronic fever include protozoal infections (e.g., trypanosomiasis, leishmaniasis, amebiasis, and malaria), typhoid or paratyphoid fever, and tuberculosis (Table 162-10). HUMAN AFRICAN TRYPANOSOMIASIS (AFRICAN SLEEPING SICKNESS) Sleeping sickness is caused by the two nearly identical endemic proto zoan subspecies, Trypanosoma brucei gambiense (responsible for most clinical cases) and Trypanosoma brucei rhodesiense , transmitted by the tsetse fly found in rural East and West Africa. Large animal game is the main reservoir. After a bite, a localized inflammatory reaction occurs, followed in 2 to 3 days by a painless chancre (more common in East African than West African sleeping sickness) that increases in size for 2 to 3 weeks and then gradually regresses. Trypomastigotes mature and divide in the blood and lymph and cause intermittent fever unresponsive to antimalarials and occasional rash. In later stages, CNS involvement occurs, causing behavioral and neurologic changes, encephalitis, coma, and death. Disease categorization depends on whether or not the CNS Tintinalli_Sec13_p0997-1100.indd 1086 8/2/19 8:12 PM

blood and lymph and cause intermittent fever unresponsive to antimalarials and occasional rash. In later stages, CNS involvement occurs, causing behavioral and neurologic changes, encephalitis, coma, and death. Disease categorization depends on whether or not the CNS Tintinalli_Sec13_p0997-1100.indd 1086 8/2/19 8:12 PM CHAPTER 162: Global Travelers 1087 TABLE 162-10 Selected Causes of Chronic and Relapsing Fevers Etiologic Organism Organism Species Bacterial Bartonellosis Brucellosis Leptospirosis Q fever Relapsing fever Syphilis Tuberculosis Tularemia Typhoid fever Fungal Blastomycosis Coccidioidomycosis Cryptococcosis Histoplasmosis Protozoan Amebic liver disease Visceral leishmaniasis Malaria Human African and human American trypanosomiasis Viral Human immunodeficiency virus Helminthic Angiostrongyliasis Fascioliasis Schistosomiasis Toxocariasis Trichinosis has been invaded. Other complications include hemolysis, anemia, pancarditis, and meningoencephalitis.46,47 Diagnosis is made by rapid evaluation of blood smears for the mobile parasite. Organisms can also be identified by aspiration of lymph nodes, chancres, or bone marrow or by CSF examination. The treatment of sleeping sickness varies according to the stage of illness. If the disease has not invaded the CNS, treat with pentamidine or suramin. If the CNS is invaded, treatment requires eflornithine, a combination of nifurtimox and eflornithine, or melarsoprol. 46,47 A newly approved 10-day regimen of oral fexinidazole (given once daily at a dose of 1800 milligrams on days 1 to 4, and then 1200 milligrams on days 5 to 10) eases the treatment difficulty with similar success to IV regimens that are much more challenging. AMERICAN TRYPANOSOMIASIS (CHAGAS’ DISEASE) The protozoan Trypanosoma cruzi is spread by the reduviid “kissing bug” or “assassin” bug. Among travelers, it is rare; it causes an acute illness and, commonly, an asymptomatic infection with complications arising years later in the heart and GI tract. It is transmitted during a blood meal when the bug defecates trypanosome-infected feces around the meal site, causing a local inflammatory reaction and trypanosome inoculation after the host rubs the organism into the bite wound or into adjacent mucous membranes or conjunctiva. Infection can also be acquired by blood transfusion, by laboratory accidents, congenitally, and by oral transmission. 48,49 Unilateral periorbital edema (Romaña sign) or painful cutaneous edema at the site of skin penetration (chagoma) is followed by a toxemic phase with parasitemia causing lymphadenopathy and hepatospleno megaly. The acute phase generally lasts 2 to 4 weeks but may last up to 3 months. Next is a long, asymptomatic, latent phase when nerve ganglion cells are gradually destroyed, leading to depressed cardiac and GI function. Cardiac complications include myocarditis, dysrhythmias, cardiomyopathy, and sudden death. Chagas-induced heart disease is the leading form of congestive heart failure in much of Latin America. GI complications are also due to the nervous system damage, most com monly in the form of megaesophagus or megacolon. The acute-phase diagnosis occurs by detecting motile parasites on blood smears, by blood culture, or by muscle biopsy. In the chronic phase, serologic tests and tissue biopsy aid. Treatment is available for acute, reactivated, or chronic cases. The two medications used are nifurtimox and benznidazole. LEISHMANIASIS (VISCERAL) Leishmania is an intracellular protozoan transmitted by sandflies. The disease occurs sporadically in rural Africa, Asia, the Mediterranean basin, and Central/South America, and additional global outbreaks occasionally occur.

onic cases. The two medications used are nifurtimox and benznidazole. LEISHMANIASIS (VISCERAL) Leishmania is an intracellular protozoan transmitted by sandflies. The disease occurs sporadically in rural Africa, Asia, the Mediterranean basin, and Central/South America, and additional global outbreaks occasionally occur. Suspect Leishmania in military personnel and their families living proximal to jungles, adventure travelers, field biologists, and emigrants from endemic zones. The infecting species determines the pathology, ranging from a localized self-healing lesion to widespread, persistent, and potentially destructive disease. Four major clinical syndromes exist. The most important diagnostic information is patient origin and travel itinerary because endemic areas suggest the infection type. Definitive diagnosis requires reference laboratory expertise to isolate motile extracellular parasites aspirated from bone marrow, spleen, or lymph nodes, or on smears or sections taken from the ulcer edge by punch biopsy. Treatment is with liposomal amphotericin B.  DISEASES COMMONLY ASSOCIATED WITH ABDOMINAL AND URINARY COMPLAINTS Illnesses causing abdominal pain and diarrhea are common among world travelers because of infecting bacteria, viruses, soil-transmitted helminths, and other parasites. Most infections are caused by the con sumption of undercooked or fecal-contaminated foods and are preventable by adequate hygiene, potable water, and careful food preparation. SCHISTOSOMIASIS (BILHARZIA OR SNAIL FEVER) Schistosomiasis, infection with a blood fluke found in Africa, the Middle East, South America, and Asia, infects >200 million people worldwide, with 20 million people suffering severe consequences. For most shortterm travelers, the risk is low, although significant outbreaks now occur among adventure tourists, longer-term visitors such as missionaries and volunteers, and those who swim in infested streams and lakes. The larvae are released into freshwater by snails, which are intermediate hosts. Infection occurs by tiny, free-swimming cercariae that penetrate wet, unbroken skin or are ingested from slow-moving freshwater. After inoculation, an immediate cercarial allergic and pruritic dermatitis may occur. When Katayama syndrome occurs, fever is accompanied by headache, cough, urticaria, diarrhea, hepatosplenomegaly, and eosinophilia. Worms mature into adults in the venous blood and, for the next 30 to 40 years, deposit eggs into selective body tissues (Schistosoma haematobium in the bladder and Schistosoma mansoni and Schistosoma japonicum in the GI tract). Eggs are deposited throughout the brain, skin, liver, and GI tract. Eggs stimulate a vigorous immune response that results in clinical symptoms. CNS symptoms include seizures, paralysis, and acute transverse myelitis. S. haematobium infection causes dysuria, frequency, and terminal hematuria, and can cause bladder scarring, calcification, and squa mous cell carcinoma. S. japonicum and S. mansoni infections can cause diarrhea, abdominal cramps, and acute abdominal pain and, late in the disease course, can lead to hepatosplenomegaly, hepatic granulomas, periportal fibrosis, and portal hypertension. Diagnosis is suspected by detecting eosinophilia, confirmed by microscopic identification of ova in midday urine or stool samples or in a biopsy specimen. Serologic antibody detection methods are accurate and are usually positive in light infections missed by egg detection. Praziquantel treatment is active against adult worms only; thus, it can not be used for postexposure prophylaxis, and re-treatment may be required. Tintinalli_Sec13_p0997-1100.indd 1087 8/2/19 8:12 PM

Serologic antibody detection methods are accurate and are usually positive in light infections missed by egg detection. Praziquantel treatment is active against adult worms only; thus, it can not be used for postexposure prophylaxis, and re-treatment may be required. Tintinalli_Sec13_p0997-1100.indd 1087 8/2/19 8:12 PM 1088 SECTION 13: Infectious Diseases TABLE 162-11 Common Infectious Diseases Causing Diarrhea in Travelers Cause Organism Comments Acute (duration <2 wk) Viral Norwalk-like virus Rotaviruses Enteroviruses Often not diagnosed; may account for 5%–10% of acute traveler’s diarrhea Bacterial Escherichia coli (enterotoxigenic or enteroaggregative) Campylobacter jejuni Salmonella Shigella Vibrio Clostridium difficile Most common identified cause of acute traveler’s diarrhea; 50%–70% Parasitic Giardia lamblia Cryptosporidium parvum Entamoeba histolytica Cyclospora cayetanensis Isospora belli Balantidium coli Trichinella spiralis Accounts for <1%–5% of acute traveler’s diarrhea Chronic or persistent (duration >2–4 wk) Bacterial See above Rare cause of chronic diarrhea Parasitic Microsporidial Enterocytozoon bieneusi Encephalitozoon intestinalis Almost exclusively in immunocompromised Protozoal G. lamblia E. histolytica Most commonly identified cause Bloody diarrhea with fever; fecal WBCs are rare Helminthic Trichuris trichiura Strongyloides stercoralis Fasciolopsis buski Schistosoma Rarely associated with chronic diarrhea; usually in persons with heavy parasite burdens TABLE 162-12 Causes of Diarrhea With and Without Fever or Blood With Fever Without Fever With blood Bacillary dysentery Campylobacter enterocolitis Salmonella enterocolitis Escherichia coli Amebiasis Balantidium coli Schistosoma Trichuris Without blood Salmonella enteritis Malaria (especially Plasmodium falciparum) Mild shigellosis Campylobacter infections Almost any infections in a child Staphylococcus aureus E. coli (enterotoxigenic) Clostridium perfringens Viral infections of the gut Food toxins AMEBIASIS Pathogenic species such as E. histolytica are found worldwide and disproportionately infect those living in low-income settings. Ame biasis is typically spread by asymptomatic carriers whose excrement contains the encysted organism and is the leading cause of diarrhea globally. Travelers who are traveling for >6 months are at higher risk. Incubation times are typically 1 to 3 weeks for colitis and 2 weeks to several months for liver abscesses. Once cysts are ingested, amebic trophozoites invade the colon wall, lyse tissues, and cause necrotic abscesses. Most infected people are asymptomatic. Symptoms range from alternating constipation and diarrhea over 1 to 3 weeks, to abdominal pain, bloody diarrhea, fever, dehydration, and weight loss. Extraintestinal metastases can infect the liver and, rarely, pericardium, lung, and brain. Colitis can lead to intestinal perforation and peritonitis. Complications such as liver abscesses may cause fever, right upper quadrant pain, or chronic, vague abdominal pain accompanied by weight loss. It can be difficult to differentiate pathogenic organisms (E. histolytica) from benign organisms ( Entamoeba dispar) on stool microscopy with out use of stool antigen detection tests or, preferably, stool polymerase chain reaction. Serology for elevated antibody titers helps identify sys temic disease. Ultrasonography or CT scans may be useful to identify hepatic abscesses. Treatment of asymptomatic cyst passers includes iodoquinol, paro momycin, or diloxanide furoate. For symptomatic disease, choices include metronidazole, or tinidazole followed by either iodoquinol or paromomycin. For liver abscess, severe intestinal disease, or extraintes tinal disease, treat with metronidazole or tinidazole followed by iodo quinol or paromomycin.

s iodoquinol, paro momycin, or diloxanide furoate. For symptomatic disease, choices include metronidazole, or tinidazole followed by either iodoquinol or paromomycin. For liver abscess, severe intestinal disease, or extraintes tinal disease, treat with metronidazole or tinidazole followed by iodo quinol or paromomycin. GIARDIASIS Giardia lamblia is a flagellated protozoan infecting the small intestine and biliary tree. It is globally endemic and is food- or waterborne by fecal contamination with encysted parasites and can be transmitted through person-to-person contact. It is a common cause of chronic traveler’s diarrhea and can be contracted at camping sites and rural swimming areas. It can be differentiated from other causes of traveler’s diarrhea by the slow onset of symptoms and incubation period of typi cally longer than 1 week. Ingested parasites reside in the duodenum and may lead to malab sorption because of duodenal microvilli obstruction. Symptoms include abdominal cramping, flatulence, and foul-smelling, watery diarrhea without blood or mucus. Chronic infections cause weight loss and anemia, and a common complication is lactose intolerance. Diagnosis is by duodenal sampling and stool ova and parasites showing either motile trophozoites or cysts. Giardia antigen detection in stool has good sensitivity and specificity. Treatment is with metronidazole, tinidazole, quinacrine, nitazoxanide, paromomycin, or furazolidone. Treatment is not always successful regardless of drug used, and combination therapy may be necessary. 60,61  DISEASES COMMONLY ASSOCIATED WITH ABDOMINAL PAIN AND DIARRHEA Diarrhea and gastroenteritis are the most common travel ailments, affecting up to one half of travelers ( Table 162-11). Traveler’s diarrhea is especially common after travel to Africa, Asia, the Middle East, South and Central America, and Mexico. Diarrhea is typically accompanied by fever, flatulence, nausea, emesis, and abdominal pain, which is usually spasmodic and colicky. Campylobacter jejuni may cause severe and constant pain, and cholera may cause somatic muscle cramps. Nonbloody gastroenteritis and diarrhea are usually caused by bacteria or bacterial toxins, whereas dysentery usually results from toxigenic and invasive bacteria such as Shigella, Salmonella, Campylobacter, Aeromonas, Escherichia coli, or Entamoeba histolytica (Table 162-12). Traveler’s diarrhea is less commonly due to viruses. Acute abdominal pain among travelers is usually caused by nontravel causes with an expanded travel-based differential diagnosis. Mild traveler’s diarrhea can be treated with bismuth or loperamide alone. For moderate to severe traveler’s diarrhea (significant pain or blood in stool), treat empirically with azithromycin or fluoroquinolones (ciprofloxacin or levofloxacin), although resistance to fluoroquinolones is rising. Regional resistance can occur and should be verified (see Chapter 160, “Food and Waterborne Illnesses”). Tintinalli_Sec13_p0997-1100.indd 1088 8/2/19 8:12 PM

in or blood in stool), treat empirically with azithromycin or fluoroquinolones (ciprofloxacin or levofloxacin), although resistance to fluoroquinolones is rising. Regional resistance can occur and should be verified (see Chapter 160, “Food and Waterborne Illnesses”). Tintinalli_Sec13_p0997-1100.indd 1088 8/2/19 8:12 PM CHAPTER 162: Global Travelers 1089 CHOLERA Cholera is an acute diarrheal disease caused by the bacterium Vibrio cholerae. It is endemic and epidemic to many tropical nations. It is reported in Africa, Asia, Latin America, and more recently, Haiti and Mexico. Epidemics occur after flooding or acute population displace ment with disruption of the water-sanitation system. Transmission is by fecal contamination of water or food (including raw or poorly cooked seafood and shellfish). Significant bacterial ingestion is required to cause symptoms. The incubation time is 2 to 3 days, and symptoms result from sodium pump inhibition in the GI tract by the cholera toxin. Infection is usually mild but can be life threatening, particularly among vulnerable populations, such as malnourished children, migrants, and those with chronic illness. Another group at risk are individuals with achlorhydria or those using medications decreasing gastric acidity. There is an asymptomatic carrier state. Severe disease is characterized by profuse, usually painless, watery diarrhea (“rice water stools”), severe dehydration, vomiting, leg cramps, and, occasionally, fever. Rapid fluid loss (up to 15 L/d) leads to extreme dehydration and shock. Aggressive rehydration can prevent death. Without proper fluid resuscitation, death can occur within hours, and mortality rates reach 50% to 75%. 62 Diagnosis is clinical, and when suspected, a rectal swab or stool specimen can be sent to a reference laboratory for culture confirmation. Rapid dipstick testing of stool is possible but should be followed by confirmatory testing. The cornerstone of treatment is aggressive fluid resuscitation with PO rehydration solution or IV fluids, coupled with correction of metabolic acidosis and hypokalemia. For those with severe illness, antibiotics can shorten the illness course, diminish vomiting, lessen volume resuscita tion needs, and ensure that bacteria are eradicated from stool. Doxycy cline is the antibiotic of choice, followed by azithromycin, tetracycline, erythromycin, or ciprofloxacin. Secondary transmission is rare, and close contacts should not be given antibiotics as prophylaxis.  PARASITIC HELMINTH (WORM) INFECTIONS Major infestations are discussed here, and diagnosis and treatment are presented in Table 162-13. In the patient in whom empirical therapy is chosen due to the appearance of a worm in fecal matter, treatment for nematodes can be considered. By treating the adult patient empirically with albendazole for 3 days with a single repeat dose in 2 weeks, a number of pathologies can be treated (roundworm, pinworm, whipworm, and hookworm). Send stool samples for laboratory analysis to provide more focused treatment. Diagnosis and treatment of these worms are provided in Table 162-13. ASCARIASIS (ROUNDWORM) The risk of infection with Ascaris lumbricoides to short-term travelers is low, and infection is suspected following ingestion of street vendor foods or vegetables fertilized by “night soil” (human feces) or animal feces. Eggs survive for years in moist soil, and transmission is typi cally fecal–oral or through poorly cooked food. Symptoms are usually TABLE 162-13 Common Parasitic Helminth (Worm) Infestations Name Source of Contamination Human Symptoms Diagnosis Treatment Ascaris lumbricoides (roundworm) Fecal–oral contamination or poorly cooked food Minimal symptoms; or pneumonia, malnutrition, biliary or bowel obstruction, hepatic abscess, appendicitis, etc.

ually TABLE 162-13 Common Parasitic Helminth (Worm) Infestations Name Source of Contamination Human Symptoms Diagnosis Treatment Ascaris lumbricoides (roundworm) Fecal–oral contamination or poorly cooked food Minimal symptoms; or pneumonia, malnutrition, biliary or bowel obstruction, hepatic abscess, appendicitis, etc. Stool examination, serology. Albendazole, 400 milligrams single dose Mebendazole, 100 milligrams twice a day for 3 d or 500 milligrams single dose Ivermectin, 150–200 micrograms/kg single dose Enterobiasis (pinworm, seatworm) Fecal–oral and from contaminated objects Intense perianal itching Visual inspection, cellophane tape swab of anus upon waking. Albendazole, 400 milligrams single dose and repeat in 2 wk Mebendazole, 100 milligrams single dose and repeat in 2 wk Pyrantel pamoate, 11 milligrams/kg (up to 1 gram) single dose and repeat in 2 wk Trichuris trichiura (whipworm) Fecal–oral contamination Asymptomatic; or bloody diarrhea, rectal prolapse Stool examination. Albendazole, 400 milligrams daily for 3 d Mebendazole, 100 milligrams daily for 3 d or 500 milligrams single dose Ancylostoma duodenale and Necator americanus (hookworm) Contaminated soil, larvae penetrate the skin Severe anemia; cutaneous larva migrans Stool examination, may require serial exams. Albendazole, 400 milligrams single dose Albendazole, 400 milligrams twice a day for 3 d Pyrantel pamoate, 11 milligrams/kg (maximum, 1 gram) daily for 3 d Taenia solium (pork tapeworm), T. saginata (beef tapeworm), and Diphyllobothrium latum (fish tapeworm) Raw or undercooked pork or beef or fish Asymptomatic, abdominal pain, bowel obstruction; Taenia cysts in skin, eye, brain, heart (see “Cysticercosis” section, above) Stool examination or serology. Serology may be negative if cysts are calcified. Praziquantel, 5–10 milligrams/kg single dose Strongyloides stercoralis (threadworm) Contaminated soil, larvae penetrate skin Cough, pneumonia, and wheezing; abdominal pain, bloody diarrhea Stool examination or stool concentration methods; serology or sputum examination. Ivermectin, 100 micrograms/kg/d for 2 d Albendazole, 400 milligrams twice a day for 7 d Tintinalli_Sec13_p0997-1100.indd 1089 8/2/19 8:12 PM

nated soil, larvae penetrate skin Cough, pneumonia, and wheezing; abdominal pain, bloody diarrhea Stool examination or stool concentration methods; serology or sputum examination. Ivermectin, 100 micrograms/kg/d for 2 d Albendazole, 400 milligrams twice a day for 7 d Tintinalli_Sec13_p0997-1100.indd 1089 8/2/19 8:12 PM 1090 SECTION 13: Infectious Diseases minimal; a dry cough or eosinophilic pulmonary infiltrates may occur 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, as well as bowel obstruction. Wandering Ascaris also traverse internal organs, rarely leading to biliary obstruction, hepatic abscess, acute pancreatitis, acute appendicitis, or hypersensitivity pneumonitis. ENTEROBIASIS (PINWORM) Enterobiasis vermicularis is a common tropical disease caused by a small intestinal parasite transmitted by the fecal–oral route and is often acquired from contaminated objects such as toys, utensils, and bedding. It is a common disease among U.S. children and is more likely to be peridomestic rather than occur after tropical travel; hence, treatment of all housemates is recommended. The disease is characterized by intense perianal itching. Occasionally, worms may migrate to cause appendici tis, or via perianal migration, they may ultimately migrate to fallopian tubes and endometrium, causing inflammation and obstruction. TRICHURIS (WHIPWORM DISEASE) Whipworm ( Trichuris trichiura) is a nematode parasite of the large intestine distributed globally but most heavily in the tropics. Long-term travelers, former tropical residents, and visitors from the tropics are at high risk. It is obtained by ingesting contaminated soil or vegetables and is not transmissible from person to person. Light infestations are asymptomatic, and heavy infestations cause nonspecific abdominal symptoms, bloody diarrhea, and rectal prolapse. HOOKWORM Hookworm is a common chronic nematodal infection caused by Ancylostoma duodenale and Necator americanus , which are globally distributed but are most heavily found in the tropics and subtropics. Because symptoms require large worm burdens, it is a low risk among short-term travelers. Hookworm causes chronic, severe anemia, especially in children. The cutaneous form is called cutaneous larva migrans (see later section, “Diseases Commonly Associated With Eye or Skin Complaints”). Transmission is by direct skin contact with soil contaminated by human feces, often in children with poor footwear exposed to raw sewage. Filariform larvae penetrate the skin. Micro scopic examination of stool for eggs is the usual means of diagnosis. 66,67 CESTODES (TAPEWORMS) Among the cestodes, taeniasis and cysticercosis are the most pathologic. Infections occur worldwide, but especially in the tropics, and risk is high among children, the mentally disabled, and immigrants or visitors from endemic nations. Risk to travelers is low but is increased with consumption of undercooked pork, fish, or beef. Taenia solium and Taenia saginata (Pork and Beef Tapeworm) T. solium (pork tapeworm) is encountered in the United States in immigrants or visitors to or from Central America and the Middle East. T. saginata (beef tapeworm) is seen more often, especially in those who consume raw beef (e.g., steak tartare), particularly in Latin America, Eastern Europe, Africa, and Russia. Adult worms live in the small intestine. Infected patients can be asymptomatic or present with nausea and vomiting, headache, abdominal pain, pruritus, constipation, diarrhea, and intestinal obstruction. The larval stage of T. solium can cause clinical disease (cysticercosis), which can sometimes be fatal.

and Russia. Adult worms live in the small intestine. Infected patients can be asymptomatic or present with nausea and vomiting, headache, abdominal pain, pruritus, constipation, diarrhea, and intestinal obstruction. The larval stage of T. solium can cause clinical disease (cysticercosis), which can sometimes be fatal. Taenia cysts may be found in subcutaneous tissue, the eye, brain, and heart and can cause seizures and hydrocephalus. Radiographs of the soft tissues may reveal curvilinear calcifications indicative of cysts, and cysts can be seen in the meninges and brain parenchyma on CT scanning. For discussion of neurocysticercosis see the earlier “Cysticercosis” section. Dipylidium caninum is discussed in Chapter 161. Diphyllobothrium latum (Fish Tapeworm) Diphyllobothrium latum (fish tapeworm) is encountered in those consuming raw fish (e.g., sushi and sashimi) or gefilte fish. Diphyllobothrium can compete with the host for vitamin B12, and patients can develop pernicious anemia. Most patients are asymptomatic, but some develop intestinal or biliary obstruction.69 STRONGYLOIDES Strongyloides stercoralis infects the small intestine. Distribution is worldwide, but infection is most common in humid tropics. Infection can develop in overseas military personnel, refugees, or immigrants. The risk is low in short-term travelers. Most infections cause minimal GI symptoms, occasional dyspnea, or hemoptysis with migration, or no symptoms. However, severe disseminated disease may occur in immu nocompromised patients and cause hyperinfection with multiorgan symptoms, including meningitis, and septic shock. An upper GI series may reveal a deformed duodenal bulb, and Strongyloides may be confused with ulcer disease.  DISEASES COMMONLY ASSOCIATED WITH EYE OR SKIN COMPLAINTS Skin complaints among travelers are common and nonspecific and have many causes. Travel-related skin disease is generally caused by one of the following: (1) exacerbations of previous conditions (e.g., atopic dermatitis, psoriasis); (2) environmental conditions (e.g., photosen sitivity, contact allergies); or (3) infective organisms causing infesta tions or infections. 16 The distribution and timing of the dermatosis may aid diagnosis of rashes associated with systemic illness (Table 162-14).71 Among rashes reported by travelers, most are minor problems, such as sunburn, phototoxic/sensitivity reactions, insect bites, and prickly heat, and are often self-limiting and necessitate symptomatic care. The most common tropical travel dermatoses in ill individuals requiring therapy are cutaneous larva migrans, insect bites including bites with bacterial superinfections, abscesses, and allergic reactions. 72 The risk of serious conditions tends to increase with the amount of time spent overseas, and thus short-term travelers rarely contract dermatoses such as filariasis, Buruli ulcer, yaws, and leprosy (Hansen’s disease). To fur ther aid diagnosis, travelers with dermatoses can fit into five syndromic and morphologic categories (Table 162-15). Management includes arranging biopsy for patients with chronic ulcerative lesions. Beware of the rare patient presenting with anxiety of parasitosis regardless of travel history. The following are select dermatoses associated with tropical exposures.

an fit into five syndromic and morphologic categories (Table 162-15). Management includes arranging biopsy for patients with chronic ulcerative lesions. Beware of the rare patient presenting with anxiety of parasitosis regardless of travel history. The following are select dermatoses associated with tropical exposures. TABLE 162-14 Cutaneous Manifestations of Selected Infections Appearance of Lesion Possible Diagnosis Maculopapular rash Dengue fever Viral hemorrhagic fevers Leptospirosis Acute human immunodeficiency virus infection Erythema chronicum migrans Lyme disease Rose spots Typhoid fever Pustules Disseminated gonococcal infection Petechiae, ecchymoses, hemorrhage Meningococcemia Dengue fever Viral hemorrhagic fevers Yellow fever Rocky Mountain spotted fever Epidemic louse-borne typhus Leptospirosis Eschar Tick or scrub typhus Anthrax Ulcer Tularemia Cutaneous diphtheria Urticaria Helminthic infections Tintinalli_Sec13_p0997-1100.indd 1090 8/2/19 8:12 PM

, ecchymoses, hemorrhage Meningococcemia Dengue fever Viral hemorrhagic fevers Yellow fever Rocky Mountain spotted fever Epidemic louse-borne typhus Leptospirosis Eschar Tick or scrub typhus Anthrax Ulcer Tularemia Cutaneous diphtheria Urticaria Helminthic infections Tintinalli_Sec13_p0997-1100.indd 1090 8/2/19 8:12 PM CHAPTER 162: Global Travelers 1091 TABLE 162-15 Syndromic Categories of Travel-Related Dermatoses With Select Examples •   Fever and rash (petechial or hemorrhagic): dengue fever, arboviruses, rickettsial infections (e.g., scrub typhus), chikungunya, meningococcemia, leptospirosis, malaria, and erythema multiforme caused by drug reaction or common infection •   Papular eruptions: insect bites, persistent lesions (chiggers), scabies, allergic drug reactions, cercarial dermatitis (swimmers), Pseudomonas folliculitis (hot-tubbing), onchocerciasis (long-term travel) •   Persistent nodules: furunculosis, myiasis (movement within the lesion), chancroid, syphilis, systemic parasites/fungi •   Migratory swellings or skin lesions: cutaneous larva migrans, strongyloidiasis (fast moving and often on the buttocks), urticaria from various causes, and Loa loa (rarely) •   Ulcerative lesions: pyodermas, spider bites, chancroid and syphilis, cutaneous leishmaniasis FILARIASIS: ONCHOCERCIASIS AND LOA LOA  ONCHOCERCIASIS (RIVER BLINDNESS) River blindness is a chronic, nonfatal filarial disease leading to subcuta neous skin changes and blindness. It is caused by Onchocerca volvulus, a nematode transmitted by the female black fly, Simulium species, found near fast-moving rivers predominantly in sub-Saharan Africa as well as small foci in Y emen, Venezuela, and Brazil. Symptoms may take up to 18 months to appear and include intractable pruritus, altered skin pigmentation, skin nodules, lymphadenitis, and gradual visual impair ment leading to blindness. Adult female worms reside in 2- to 3-cm painless nodules in skin and bones near joints, and release microfilariae that migrate through the skin, causing intense pruritus when they die, leading to chronic dermatitis, edema, and skin atrophy. Skin pigment changes result in “leopard skin, ” whereas loose pelvic skin is called “hanging groin. ” Blindness is a result of microfilariae migrating to the eye, invading it, and causing permanent damage when they die. Diag nosis is made by identification of microfilariae from a fresh skin biopsy, from nodule biopsies, or in the urine. Slit-lamp examination may reveal microfilariae in the cornea, anterior chamber, or vitreous. Treatment of choice is ivermectin, which kills microfilariae but does not kill the adult worm, thus requiring repeated dosing, suppressing microfilariae release from adults and preventing spread to eyes and skin.  LOA LOA (EYE WORM) Loiasis is caused by a filarial nematode confined to the rain forests of western and central Africa in a distribution that overlaps with that of onchocerciasis. It is a low risk to short-term travelers but should be suspected among immigrants, refugees, visiting nationals, and expatri ates living several months or more in endemic zones. Among travelers, worm burden is usually low, and symptoms are related to hypersen sitivity syndromes and not serious disease. The adult worms inhabit subcutaneous tissues, move about freely, and can live for up to 18 years after the patient’s last possible exposure. They are spread from the bite of the Chrysops fly. Infections are usually asymptomatic; however, at times, infections cause painful or itchy subcutaneous swellings near the face and extremities known as Calabar swellings. Occasionally a worm passes across the eye under the conjunctiva, causing intense irritation, pain, and swelling of the periorbital tissues.

sops fly. Infections are usually asymptomatic; however, at times, infections cause painful or itchy subcutaneous swellings near the face and extremities known as Calabar swellings. Occasionally a worm passes across the eye under the conjunctiva, causing intense irritation, pain, and swelling of the periorbital tissues. Diagnosis is made by clinical presentation and by evaluating daytimedrawn blood for distinctively sheathed microfilariae and high-grade eosinophilia. Treatment for microfilariae and adult worms is diethylcarbamazine citrate. Screen for coinfection with onchocerciasis, which requires treatment first, given that diethylcarbamazine citrate is con traindicated in the treatment of onchocerciasis due to an inflammatory response that could induce blindness. In patients with very high micro filariae counts, diethylcarbamazine citrate may induce a sudden severe hypersensitivity and encephalitic syndrome, so treatment is begun with a very small dose, or a test-and-not-treat strategy for individuals with high microfilarial loads can be employed. 75 Albendazole can also be used to treat loiasis. Surgical excision is not recommended because multiple worms may not be visible. Subconjunctival worms, however, can be removed from the eye with analgesia and fine tweezers. CREEPING ERUPTION (CUTANEOUS LARVA MIGRANS) Erythematous “creeping eruption” commonly occurs among tropical travelers and beach resort vacationers who walk barefoot or sit in beach sand contaminated by dog feces harboring the parasite Ancylostoma braziliense. 77 The lesions are typically slow moving, tracking, and ser piginous and are a result of an inflammatory reaction from the worm, which is unable to complete its growth cycle in humans (it is only an effective parasite of dogs or cats). Pruritus causes sleeplessness and restlessness. Bacterial superinfection is not uncommon. Diagnosis is based on clinical presentation, and no serology is available. Treatment consists of albendazole or ivermectin. CUTANEOUS LEISHMANIASIS Cutaneous leishmaniasis is the most important cause of chronic skin ulceration in the world and is spread by sandflies in tropical and subtropical regions of Latin America, Africa, the Middle East, and Asia. This should be suspected among travelers such as military personnel, biologists, ecotourists, and adventure travelers, and should be part of the differential diagnosis of nonhealing cutaneous ulcers among travelers, foreign visitors, and immigrants from endemic areas. Although there are a variety of subtypes causing varying infections, the common presentation is of a small papule slowly enlarging and forming a painless shallow skin ulcer with a noticeable rolled edge like a volcano, with a raised edge and central crater, often with a scab. Diagnosis is made by tissue biopsy of the indurated ulcer margin or scraping of the base with material placed on a slide followed by Giemsa stain. Many forms are self-limiting; often observation alone is preferred, or lesions can be treated with heat application or paromomycin topical ointment. More serious forms can be treated with liposomal amphotericin B or sodium stibogluconate. Treatment response may vary with involved species and geographic distribution. LYMPHATIC FILARIASIS Lymphatic filariasis is caused by nematodes (Wuchereria bancrofti,  Brugia malayi, and  Brugia timori) residing in the subcutaneous tissues and lymphatics. It is common to South America, Africa, and Asia. The risk to short-term travelers is low, although cases have been imported by longterm travelers. It is transmitted by flies or mosquitoes permitting larvae to enter the puncture wound during their blood meal. Adult filariae then reside in lymphatics and produce microfilariae that migrate to the bloodstream at night.

. The risk to short-term travelers is low, although cases have been imported by longterm travelers. It is transmitted by flies or mosquitoes permitting larvae to enter the puncture wound during their blood meal. Adult filariae then reside in lymphatics and produce microfilariae that migrate to the bloodstream at night. First, symptoms develop after 6 months to 5 years. The most common symptom is recurrent bouts of “filarial fevers” lasting 2 to 3 weeks, associated with warmth and tenderness overlying a lym phatic vessel, followed by retrograde lymphangitis. The most frequently affected sites are extremities, breasts, and spermatic cord. As more attacks occur, lymphatics are chronically damaged, and the consequence is elephantiasis. “Nocturnal asthma” can occur with associated tropical pulmonary eosinophilia. Diagnosis depends on finding the sheathed microfilariae in a nocturnal peripheral blood smear. Serology is often useful in mild infections. Treatment is diethylcarbamazine citrate, which can cause hypersensitivity reactions with antigen liberation. Because of this, testing for coinfection with onchocerciasis and Loa loa is important to prevent adverse effects. Symptoms can be reduced by starting with a small dose. Repeated treatment may be necessary. 79,80  DISEASES COMMONLY ASSOCIATED WITH PULMONARY COMPLAINTS Returning travelers frequently develop respiratory complaints such as persistent cough, sinus congestion, and fever. Common local respira tory pathogens including viral causes such as influenza and bacterial infections are the most common etiologies. Risk factors for pulmonary Tintinalli_Sec13_p0997-1100.indd 1091 8/2/19 8:12 PM