The most common cause of fever in the child returned from international travel is the nonspecific viral illness.
It is imperative to consider treatable causes of fever (e.g., malaria) or fever etiologies at risk for decompensation and the need for supportive care (e.g., dengue).
Diagnostic evaluation and differential diagnosis should be driven by the history of pre-travel immunizations and receipt of prophylactic medication, region of travel, activities undertaken while abroad, return date, physical examination findings (including severity and duration), and knowledge of the most common pathogens seen in a given area.
A population at considerable risk for travel infections is termed “visiting friends and relatives” (VFRs), as these families often opt not to seek medical attention prior to travel.
Thick and thin smears for malaria are indicated for any febrile child returning from a malaria-endemic region. Negative smears do not exclude malaria, and if strong clinical suspicion exists, smears should be repeated every 6 to 12 hours.
Malaria treatment often is empiric, and chloroquine resistance should be assumed in almost all regions. Therapy for children with high-grade parasitemia may involve blood transfusion (or exchange transfusion) and treatment with a combination of parenteral agents. These may include clindamycin in addition to quinidine or quinine.
Typhoid fever is very common in travelers (especially from the Indian subcontinent and Asia). Diarrhea is not always seen. Bacteremia may be common. Increasing antibiotic resistance in Salmonella typhi isolates makes microbiologic confirmation and antibiotic susceptibility testing important.
Obtain stool culture from the child with diarrheal disease returned from international travel. Fluid resuscitation is the mainstay of therapy. Antimicrobial therapy (often macrolide-based) can reduce disease severity, symptom duration, and secondary spread within the household.
Dengue is extending its geographical distribution and is now seen in southern portions of the United States. It is a biphasic illness, with an initial nonspecific febrile illness with or without a viral exanthema. After a few days, hemorrhagic manifestations and symptoms corresponding to capillary leak are manifest, lasting 2 to 3 days. Treatment is supportive.
Zika virus infection is asymptomatic in most children and adults, but can present as a self-limited fever, conjunctivitis, myalgias, joint pain, and an influenza-like illness.
The emergency department (ED) is a common venue of care for children who are ill after a recent international travel. At least three categories of pediatric travelers can be identified: children returning home after travel, international adoptees, and recently arrived immigrants. Barriers to access to care, severity of illness, timing of symptom onset (weekends, holidays), and community referral patterns may result in children in all the above-mentioned groups presenting to the ED.
Individual VFRs often neglect to seek travel advice prior to trips under the preconception that children have residual immunity when returning to the family’s country of origin. Waning immunity, failure to develop effective long-term immune responses to certain infections (e.g., malaria), and lack of preventive strategies result in many of these children becoming ill. In the Houston area, for example, the single greatest risk factor for childhood malaria is being a VFR traveling to Nigeria; few of these children had received adequate malarial prophylaxis.1
It is also important for the ED provider to recognize the regional flavor for what is considered “local” (Table 67-1).2 Endemic diseases in one part of the United States may represent a travel infection in another. Families may neglect to mention trips to a given area if they are taken frequently or do not require much travel time (e.g., hunting trips) but the relevant definition of travel from an infectious disease’s standpoint is not contingent upon distance. It is any activity that places a person in contact with a set of microbial flora to which the person is not exposed in their everyday life. A list of non-mammalian vectors for different diseases is listed in Table 67-2.3
| Region | Diseases |
|---|---|
| Central and South America | Amebiasis, anthrax, Brucella, Campylobacter, Chagas disease, cholera, cutaneous larval migrans, cysticercosis, Echinococcus, filariasis, hepatitis A and B, hemorrhagic fever viruses, leishmaniasis (visceral, cutaneous), malaria, melioidosis, onchocerciasis, plague, rabiesb, Strongyloides, tetanus, typhoid and non-typhi Salmonella, yellow fever, Zika |
| Caribbean | Cholera, cutaneous larval migrans, dengue, diphtheria, filariasis, leishmaniasis (cutaneous), malaria, melioidosis, typhoid, non-typhi Salmonella, Zika |
| Western Europe | Brucella, leishmaniasis (visceral), Lyme disease, meningococcus, tick-borne encephalitis |
| Eastern Europe and former Soviet republics | Anthrax, Brucella, diphtheria, Echinococcus, hepatitis B and C, polio, tick-borne encephalitis |
| Mediterranean | Brucella, Echinococcus, hepatitis A, B, and C, Lyme disease, rickettsial diseases |
| Middle East and northern Africa | Anthrax, Brucella, Echinococcus, filariasis, leishmaniasis (cutaneous, visceral), onchocerciasis, rickettsial diseases Middle East respiratory syndrome coronavirus (MERS-CoV) |
| Sub-Saharan Africa | African tick-bite fever, amebiasis, anthrax, Brucella, Chikungunya, cholera, cutaneous larval migrans, cysticercosis, dengue, Ebola, Echinococcus, filariasis, hemorrhagic fever viruses, hepatitis (A, B, and C), leishmaniasis (visceral), malaria, meningococcus, onchocerciasis, plague, polio, rabiesb, schistosomiasis, tetanus, trypanosomiasis, typhoid and non-typhi Salmonella, yellow fever, Zika |
| Asia and Indian subcontinent | Amebiasis, Angiostrongyliasis, anthrax, Brucella, Chikungunya, cutaneous larval migrans, cysticercosis, dengue, Echinococcus, filariasis, hepatitis (A, B, and C), Japanese encephalitis, leishmaniasis (visceral), malaria, melioidosis, plague, rabiesb, schistosomiasis, tetanus, tick-borne encephalitis, tuberculosis, typhoid |
| Australia and New Zealand | Echinococcus, hepatitis C, Lyme disease, melioidosis, Rocky Mountain spotted fever, Strongyloides, tularemia |
| Pacific Islands | Angiostrongyliasis, dengue, filariasis, hepatitis (A, B, and C), Japanese encephalitis, malaria, Zika |
| Vector or Reservoirs | Diseases |
|---|---|
| Mosquitoes | Arboviral encephalitides (Eastern and Western equine encephalitis, filariasis, Japanese encephalitis, La Crosse encephalitis, St. Louis encephalitis, West Nile virus), dengue, malaria, Rift Valley fever, yellow fever, Zika |
| Flies | Filariasis (blackflies), leishmaniasis (sandflies), myiasis (fly larvae infestation), onchocerciasis/river blindness (blackflies), African trypanosomiasis (tsetse flies) |
| Fleas | Bartonella henselae, murine typhus, plague |
| Lice | Bartonella quintana, relapsing fever (Borrelia recurrentis), Rickettsia prowazekii (epidemic typhus) |
| Other insects | Triatomine (“kissing bugs”) for Chagas disease, biting midges (filariasis) |
| Helminths | Filariasis, onchocerciasis (river blindness) |
| Ticks | Anaplasmosis, babesiosis, Crimean-Congo hemorrhagic fever, ehrlichiosis, Lyme disease, Q fever, Rocky Mountain spotted fever and other rickettsioses, tick-borne encephalitides, tularemia |
| Snails | Angiostrongylus, schistosomiasis |
| Birds | Influenza, Q fever, Rift Valley fever, West Nile virus |
One way to conceptualize fever in the traveler is to subdivide diseases into three categories (Table 67-3).4–25 The first category represents diseases endemic to the United States, and thus the travel history represents a red herring. The most common cause of fever in returned travelers is a nonspecific viral illness or gastroenteritis.26 A subcategory is vaccine-preventable illness,27 such as hepatitis A, influenza, or measles. The latter specifically is very readily transmitted, and given the low vaccination rates in some portions of the United States28 may rapidly spread in a susceptible population. VFRs are more likely to have a vaccine-preventable disease than other groups.29 Another subcategory is disease seen in other parts of the country (e.g., babesiosis, Lyme). A final subcategory is sexually transmitted infections (STIs) acquired internationally (e.g., acute HIV infection), and should be on the differential diagnosis of the adolescent returning from abroad (see Chapter 89, Sexually Transmitted Diseases).
| Category | Disease | Regionality | Incubation Period | Elements of the History | Symptoms |
|---|---|---|---|---|---|
| Endemic to the United States | Nonspecific viral illnesses | None, except seasonality associated with some of respiratory viruses | Variable; usually 3–10 d | Ask about influenza, measles, varicella immunization | Variable |
| Acute diarrhea3 | Minimal | 1–10 d | Ask about specific activities (hiking, camping) for Giardia, Cryptosporidium, food (and ice) consumption for enteric pathogens, hepatitis A immunization status, and antibiotic use for Clostridium difficile, especially in older children | Bloody or nonbloody diarrhea; malaise, fever; may have dehydration, especially in younger children | |
| Babesoisis (Babesia microti)4 | Northeast, upper Midwest | 1–4 wk | More common May–October; contact with ticks (Ixodes scapularis, also the vector for Lyme) or mice (white-footed mouse is primary reservoir) It is generally thought that ticks need to feed for >48 h to effectively transmit disease | Fever, chills, myalgias, nausea, headache, nonproductive cough; may also have jaundice Illness much more severe in asplenic patients, other immunocompromised hosts, or chronic heart, hepatic, or lung disease | |
| Lyme (Borrelia burgdorferi)5 | Northeast, Mid-Atlantic states, upper Midwest, Pacific coast | 3–30 d | More common late spring-summer months; contact with ticks (I. scapularis, also the vector for babesiosis) or deer (white-tailed deer is primary reservoir) It is generally thought that ticks need to feed for >48 h to effectively transmit disease | Stage 1: erythema migrans (EM) at site of bite, fever, malaise, myalgias, arthralgias, regional adenopathy Stage 2: multiple EM, cranial nerve palsies, meningitis, headache, AV block, myocarditis, oligoarticular arthritis Stage 3: more chronic neurological (encephalopathy) and arthritic (refractory joint pain) symptoms | |
| Hantavirus6 | Southwest; other foci in Brazil, Argentina, Chile, China | 2–4 wk | Exposure to rodents (excreta), especially inside homes | Fever, nausea, shock, abdominal pain; conjunctival, central nervous system, or GI hemorrhages occur in one-third of patients. Death may result from renal failure or respiratory distress syndrome. | |
| Murine typhus (Rickettsia typhi)7 | Texas Gulf Coast, California; also seen in Africa, Southeast Asia, Mediterranean | 1–2 wk | Vector is the rat flea; reservoir = rodents. In suburban areas, domestic cats, opossums, and cat fleas maintain the life cycle | Fever, headache, rash in 20%–80% (pruritic, maculopapular, starting on trunk and spreading peripherally with sparing of palms/soles), arthralgia, cough, hepatomegaly G6PD patients are at risk for more severe disease | |
Rocky Mountain spotted fever (Rickettsia rickettsii)8 | Southeast, southern Midwest; over 50% of US cases from Oklahoma, Tennessee, Arkansas | 2–14 d | Tick exposure (Dermacentor = dog, wood ticks); most need to feed a minimum of 4–6 h to transmit disease | “Classic” triad of fever, rash, and headache seen in a minority of children; also may see myalgia, vomiting, abdominal pain, photophobia Rash after 2–5 d of fever: initially blanching erythematous macules on wrists/ankles, then spreads centrally and becomes petechial | |
| Almost exclusively imported | Amebiasis (Entamoeba histolytica)9 | Latin America, southern Asia, western/southern Africa | 2 d–4 mo, but can remain latent for years | Ask about water sources when traveling | Many patients may be asymptomatic, but should be treated to prevent invasive disease Colitis: several weeks of crampy abdominal pain, weight loss, watery, or bloody diarrhea Liver abscess: fever, cough, right upper quadrant pain, referred shoulder pain (more common in adults) |
| Chikungunya (togavirus)10 | Africa, India, Southeast Asia | 1–12 d | Aedes mosquito; diagnosis made by excluding other diseases found in the same regions | Fever, headache, myalgia, acute and chronic arthralgia (symmetrical, multiple joints affected), rash (erythematous, petechial, erythroderma, or desquamation; often lasts 2–3 d, and does not spare palms/soles); seizures and neurologic complications more common in children | |
| Cholera (Vibrio cholerae)11 | Most cases in Africa, Indian subcontinent, Southeast Asia; outbreaks common after disasters (Haiti) | 2–5 d | Ask about drinking untreated water, eat poorly cooked or raw food (especially seafood), and where traveled within a country | Most infections asymptomatic or with mild gastroenteritis Severe cases: painless, nonbloody rice-water stools, hypovolemic shock | |
| E. coli O157:H711 | Worldwide; most US cases in southwestern, western, and northeastern states | 3–9 d | Linked to undercooked beef and a variety of vegetables | Watery diarrhea that becomes bloody after 1–5 d; severe abdominal pain, usually afebrile Hemolytic uremic syndrome (HUS) | |
| Hemorrhagic fevers other than dengue (e.g., Ebola, Marburg)12 | Ebola: central/west Africa Marburg: west Africa Lassa: west Africa Also seen in South America (e.g., Argentinian, Bolivian, Venezuelan hemorrhagic fever | 2–21 d | Animal exposure: bats (Marburg), rodents (Lassa, South American hemorrhagic fevers); exposure to blood products (Ebola) | Fever, myalgia, headache, vomiting, diarrhea, abdominal or chest pain, mental status changes Rash begins around day 5 (usually on trunk), progressing from erythema to petechiae as disseminated intravascular coagulation evolves | |
| Leishmaniasis (Leishmania species, protozoa)13 | 90% of cases in Bangladesh, Brazil, Ethiopia, India, Nepal, and Sudan, but endemic in 70 countries | Weeks–months for cutaneous; months–years for visceral and mucosal | Transmitted by the phlebotomine sandfly, with domestic and stray dogs as reservoirs | Cutaneous (in 80% of travelers): papule progresses to nodule, then ulcer (most common on face, extremities); painless, but locally destructive Visceral (= kala-azar): fever, weight loss, hepatosplenomegaly Mucosal: ulcerative lesions near nose and mouth, very locally destructive and disfiguring | |
| Malaria (Plasmodium species, most importantly P. falciparum)14 | Central and northern South America, sub-Saharan Africa, Southeast Asia and Indian subcontinent | 7–30 d | Vector = Anopheles mosquitoes (feed at dusk and at night) Ask about specific regions of travel (compare to CDC website) and ask if child received malaria prophylaxis during the trip | Fever, vomiting, headache, abdominal pain, malaise, jaundice; hepatosplenomegaly Fever in children returning from malaria-endemic areas should be considered malaria until proven otherwise | |
| Rabies (rhabdovirus)15 | Most human cases occur in Africa, Asia, and the Indian subcontinent | 1–3 mo (longer incubation period for bites to distal extremities) | Most common reservoir in the United States is the bat due to high immunization rates in dogs, cats Raccoons, skunks, foxes are other vectors domestically Internationally, dogs are the most common vector, though described in a variety of mammals | Begins with neuropathic pain at site of infection, then fever and headache, progressing to altered mentation, hallucination, hydrophobia, aerophobia | |
Schistosomiasis (Schistosoma mansoni, hematobium, japonicum)16 | 85% of cases in Africa; others in Middle East, Southeast Asia | 2 wk–3 mo (acute form), months–years (chronic form) | Swimming, bathing, and wading in contaminated freshwater; contact with infected snail vectors | Acute infection = Katayama syndrome: fever, headache, myalgias, diarrhea, cough, painful hepatosplenomegaly Chronic infection results from host immune response to schistosome eggs, which lodge in end organs and provoke an eosinophilic, granulomatous response, which may result in hepatic fibrosis, bladder calcification, and hematuria | |
| Strongyloides (Strongyloides stercoralis, a nematode)17 | Endemic in Latin America, Southeast Asia, sub-Saharan Africa | 3–4 wk | Immunocompromised hosts are at risk for hyperinfection, characterized by a high number of worms (especially in the lungs), or by worms in ectopic sites (e.g., the brain), or both | Skin: migratory, serpiginous urticarial rash (larva currens), most commonly involving perianal region and torso GI: anorexia, nausea/vomiting, bloating, abdominal pain Pulmonary: cough, shortness of breath | |
| Typhoid fever (S. enterica serotype typhi)18 | Highest case rates in Indian subcontinent; also seen in Asia, sub-Saharan Africa, western South America | 1–4 wk | Ask about water supply (and if they received the oral typhoid vaccine) | Fever, chills, headache, malaise, abdominal pain, anorexia, transient rose spots (erythematous, blanchable), confusion, convulsions (more common in preschool-aged children Complications include GI bleeding or perforation or typhoid encephalopathy | |
| Yellow fever (Flavivirus)19 | Central and South America, central Africa | 3–16 d | Vector = Aedes mosquitoes (feed morning and evening) | Most patients are asymptomatic Most common symptoms: sudden-onset fever, chills, headache, back pain, myalgias, weakness. 15% progress to severe disease: jaundice, disseminated intravascular coagulation, multiorgan system failure | |
| Zika (Flavivirus) | Central and South America, central Africa, South Pacific, Asia | 2-14 d | Vector = Aedes mosquitoes (feed morning and evening) | Most patients are asymptomatic Most common symptoms: fever, pruritic rash, arthralgias of the hands/feet, myalgias, conjunctival injection | |
| Infections seen in US, but more common internationally | Campylobacter (C. jejuni)11 | Worldwide; one of the most common bacterial causes of diarrhea in the United States | 1–11 d (usually 2–4 d) | Contaminated or undercooked food (especially poultry) or water; contact with infected animals (especially kittens or puppies) | Diarrhea (often bloody), abdominal cramps, fever 1/1000 leads to Guillain–Barré; smaller percentages develop reactive arthritis or iritis |
| Cysticercosis (Taenia solium)20 | Central and South America, sub-Saharan Africa, Indian sub-continent and Southeast Asia | Months–years | Pork consumption; vegetarians and persons not eating pork can acquire infection from fecal-oral contamination with eggs from carriers | Seizures for neurocysticercosis (lesions average 1–2 cm in diameter); visual loss if ophthalmic involvement; massive cyst burden in muscles can present at pseudohypertrophy | |
| Dengue21 | Central and South America, Caribbean, Southeast Asia In US, cases reported in Florida, South Texas | 4–10 d | Vector = Aedes mosquitoes (feed morning and evening) | Stage 1: fever, headache, myalgia, transient rash, mild hemorrhagic manifestations Stage 2: systemic vascular leak with pleural effusions, ascites, hypotension; hemorrhagic manifestations most common Stage 3: recover phase starting 2–3 d after stage 2; may see pruritic maculopapular rashes | |
| Leptospirosis (Spirochetes, several pathogenic species)22 | Worldwide distribution, higher incidence in tropical climates | 2–28 d | Contact with contaminated water (ask about swimming, rafting, kayaking) or exposure to urine or other body fluids of rodents, cattle, dogs, goats, horses, opossums, raccoons, rodents, swine, sheep Outbreaks have been seen after flooding | Fever, chills, headache, retro-orbital pain, myalgias, vomiting, abdominal pain, jaundice, conjunctival suffusion, rash | |
| Salmonella, non-typhi23 | Most common bacterial cause of food-borne infections in the United States | 12–36 h | Many animal reservoirs (reptiles, poultry, pigs, cattle); ask about contaminated or undercooked food | Fever, diarrhea (may be bloody), cramping abdominal pain, vomiting Reactive arthritis and iritis occur in a small percentage as postinfectious phenomenon | |
| Shigella (Shigella flexneri, sonnei)11 | Worldwide | 12 h–7 d (usually 1–3 d) | In addition to travel, also associated with daycare center attendance | Fever, diarrhea (may be bloody), crampy abdominal pain, vomiting Reactive arthritis and iritis occur in a small percentage as postinfectious phenomenon | |
| Tuberculosis (Mycobacterium tuberculosis)24 | Worldwide, but 90% of burden is in developing nations. Over 50% of cases in US from New York, California, Texas, Florida | Weeks–months (shorter incubation in infants and immunocompromised children | Ask about tuberculosis contacts (families will rarely volunteer this) and about persons at risk for TB: homeless, incarcerated, HIV positive, previously treated for TB | Fever, malaise, cough; hemoptysis and night sweats rare in children Most common sites of extrapulmonary disease: lymphadenopathy and meningitis |
The second category reflects illnesses that are not endemic to the United States and are almost exclusively imported (e.g., malaria, yellow fever, most cases of typhoid, some cases of dysentery). The history both of travel and of activities performed and location within a given country are essential to identifying the cause of fever. The spectrum of symptoms may overlap with common domestic diseases (e.g., gastroenteritis) or the child may present with fever without localizing signs.
The third category is for illnesses seen both domestically and internationally (e.g., tuberculosis [TB], non-typhi Salmonella, and some diseases that are now emerging in the United States, such as dengue).30 These diseases may be more or less common in the region where the child resides. Finally, infectious diseases whose incubation period is long are unlikely to drive presentation to the ED with symptoms referable to a recent trip (e.g., TB in older children and adolescents).
Historical elements that should be queried include use of prophylactic medications, receipt of vaccines prior to travel, activities, areas, and duration of travel, and timing of return.
It is insufficient to simply ask if a prophylactic medication was given prior to departure; specific questions regarding adherence should be asked. For example, a child may have been prescribed chloroquine and subsequently traveled to an area where all Plasmodium species are chloroquine resistant. Some antimalarial prophylaxis medications are administered daily, whereas others are given weekly, leading to a lower likelihood that a family will remember to administer the weekly medication. Finally, most antimalarials are intended to be started before arrival to the region of travel and continued after returning home for maximum efficacy.
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