Fever in the returning child traveller: Highlights for health care providers

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BACKGROUND

Recreation, globalization, migration and the frequency of travel by Canadian families visiting friends and relatives (VFRs) overseas have increased international travel rates and risk for exposures to diseases not commonly seen in Canada and can present specific diagnostic challenges to clinicians upon their return. Although children travel abroad less frequently than adults, they bear a disproportionately high burden of travel-related infections ^[1]. As a group, VFRs are at higher risk for infection than other types of travellers because they:

• are less likely to seek pre-departure advice and more likely to travel for longer periods,
• are more likely to be exposed to local food, drink and infectious contacts, for longer periods
• often underappreciate the severity of certain endemic infections
• often underappreciate that immunity to malaria wanes over time ^[2][3]

The mortality of some travel-related illnesses, such as malaria, can be high when cases are unrecognized or improperly managed. Clinicians in Canada need to be able to identify serious, treatable infections in a timely manner, to consider risk for diseases that pose a public health risk, and to make appropriate arrangements for treatment and referral. Although this practice point focuses on travel-related illness, clinicians should be aware that many infections in returning child travellers are also common in Canada (i.e., influenza, viral gastroenteritis, otitis media).

The Canadian Paediatric Surveillance Program (CPSP) report for 2008-2009 and later data from CanTravNET surveillance for 2009-2011 showed that potentially life-threatening infections, such as dengue malaria and enteric fever, are commonly imported into Canada by returning travellers, especially VFRs ^[3][4][5].

Key resources [5] to help guide clinical assessment, management and referral of fever in the returning child traveller Centers for Disease Control and Prevention (CDC) http://wwwnc.cdc.gov/travel, Committee to Advise on Tropical Medicine and Travel  (CATMAT) https://www.canada.ca/en/public-health/services/catmat.html Public Health Agency of Canada (PHAC) travel health information: https://travel.gc.ca/travelling/health-safety/travel-health-notices Canadian Paediatric Society Global Child Health Curriculum, module 3: Fever in Returning Child Traveller: https://members.cps.ca/paediatric-education/global-child-health-curriculum/ Caring for Kids New to Canada (CKNC) https://kidsnewtocanada.ca Canadian Malaria Network:  https://www.canada.ca/en/public-health/services/travel-health/medical-access-artesunate-quinine-malaria-treatment.html

KEY COMPONENTS OF THE TRAVEL HISTORY

With every family seen in clinical practice, be sure to ask about travel outside of Canada in the previous 12 months. Each component of a travel history provides key information regarding potential disease exposure and can narrow differential diagnosis significantly. For example, given that incubation periods vary and infections may be seasonal, obtaining precise travel dates is essential for risk assessment and diagnosis.

Ask for specifics about:

• Travel details and disruptions: Including destinations, dates and timing of symptom onset
• Setting: Rural versus urban, living conditions, altitude, season (i.e., rainy or dry)
• Activities: VFR or professional, community involvement, environments
• Potential exposures: Food consumption and handling/preparation (with risk for exposure to unpasteurized dairy, meat, seafood); drinking water and fresh water sources  (i.e., for swimming, washing);  sick contacts; insect bites (especially mosquitos, ticks); animal bites or other animal exposures; sexual encounters (when appropriate)
• Pre-travel preparation: Counselling, vaccinations, malaria chemoprophylaxis, personal protective equipment (clothing, insect nets and repellant) 
• Medical care: Health care contacts and medications received while travelling and since return.

HOST RISK FACTORS

Careful attention should be paid to factors that put a child at greater risk for severe infection, including:

• Being unvaccinated or incompletely vaccinated
• Having a history of compromised or suppressed immunity  (e.g., splenic dysfunction)
• Low weight or poor nutritional status
• Very young age (i.e., less than one month)

PHYSICAL EXAMINATION

It is important to perform a complete physical examination, including vitals signs, but the absence of localized findings does not rule out a serious infection. Findings on exam that can be diagnostic clues when interpreted in context with travel history and incubation period are outlined in Table 1 ^[6][7].

Table 1: Findings on physical examination that may provide diagnostic clues
Symptom/Sign	Viral	Bacterial	Parasitic
Jaundice	Hepatitis A, B, E Viral hemorrhagic fever (VHF)	Typhoid fever Leptospirosis	Malaria
Lymph node enlargement	Epstein-Barr virus (EBV) Cytomegalovirus (CMV) HIV	Rickettsiae Brucellosis Mycobacterium tuberculosis (mTB)	Visceral leishmaniasis Trypanosomiasis
Diarrhea	Rotavirus	E. coli Shigella Salmonella Campylobacter Yersinia	Giardia Amebiasis
Hepatomegaly	Hepatitis A, B, E	Typhoid fever Leptospirosis	Malaria Amebiasis
Splenomegaly	EBV	Typhoid fever	Malaria Visceral leishmaniasis
Hemorrhagic Rash	Dengue VHF	Meningococccus Rocky Mountain spotted fever (RMSF)
Fever and rash	Dengue Chikungunya Acute HIV Measles Zika Viral exanthems (i.e., Roseola)	Rickettsiae Enteric fever  (Salmonella) Leptospirosis
Fever and low WBC count	Dengue Chikungunya	Rickettsiae Enteric fever  (Salmonella) Leptospirosis	Malaria
Fever and eosinophilia			Acute schistosomiasis Fascioliasis Strongyloidiasis Toxocariasis Trichinellosis Other parasites, particularly if child is immunocompromised
Fever onset >2 weeks	EBV CMV Acute HIV	Enteric fever (Salmonella) Brucellosis Toxoplasmosis Q fever mTB Leptospirosis	Malaria Visceral leishmaniasis Amoebic liver abscess
Fever onset <2 weeks	Viral upper or lower respiratory tract infections Viral gastroenteritis Arboviruses Hepatitis A	Acute otitis media Pneumonia Urinary tract infection Enteric fever Leptospirosis	Malaria

DIFFERENTIAL DIAGNOSIS

Three of the most important travel-related causes of fever are malaria (20% to 30% of cases, onset within 6 months of return), traveller’s diarrhea and enteric fever (10% to 20% and 2% to 7% respectively, onset within 60 days of return), and dengue (5%, within 14 days of return) ^[8][9]. Respiratory tract infections occur worldwide and are common, but it is important to exclude infections that are life-threatening or highly contagious.

Malaria

Malaria is an important cause of systemic febrile illness in the returning traveller. Malaria is transmitted by Anopheles mosquitoes, which bite in the evening and at night. Malaria is a medical emergency, with a mortality rates as high as 20% in Plasmodium falciparum malaria. If a febrile child has travelled in the last 6 months to an area where malaria is endemic, a malaria diagnosis must be excluded specifically. Symptoms in children are non-specific and may include fever and/or chills, headache, nausea with or without vomiting or diarrhea, lethargy, myalgia and abdominal pain. The risk for acquiring malaria is highest in Africa, but physicians should consult the CDC or PHAC websites (see the links above) for a complete list of countries where malaria is endemic. Diagnosis is made by microscopy +/- rapid diagnostic testing, when available. Initially, all children and youth with suspected P falciparum malaria should be admitted to hospital and treated presumptively for chloroquine-resistant malaria until speciation becomes available. Urgent consultation with an infectious disease expert should be sought. Access to artesunate or quinine for malaria treatment is through the Canadian Malaria Network ^[10]. Detailed information on the diagnostic criteria for severe malaria and treatment can be found through CATMAT ^[5][11] and the Canadian Paediatric Society ^[12].

Typhoid fever

Enteric (typhoid) fever is caused by infection with Salmonella typhi or Salmonella paratyphi  from water or food contaminated with feces. Travellers to endemic areas, such as the Indian subcontinent, Southeast Asia, South and Central America, Africa and Eastern Europe, are at high risk.

The incubation period is usually 7 to 14 days. Symptoms of typhoid fever may be biphasic, presenting initially as enterocolitis with diarrhea lasting several days, resolving, then recurring with more non-specific symptoms, including fever, chills, rash, diaphoresis, headache, myalgias, confusion, psychosis or apathy. Constipation occurs in 10% to 20% of cases, and about 20% of cases experience abdominal pain. Infected children may look unwell and show hepatosplenomegaly on exam. Leukopenia and thrombocytopenia may also be present. Blood culture is important for diagnosis, and more than one sample may be required to increase diagnostic yield ^[13].

Traveller’s diarrhea

Diarrhea is a common post-travel complaint and is typically caused by an enteric infection that can be viral, bacterial or parasitic. Symptoms can be acute (if onset is <2 weeks, rotavirus or bacterial infection is usually the cause), or chronic (>2 weeks i.e., post-infectious diarrhea, giardiasis). The main treatment consideration is hydration. There may be a role for antimicrobials when a child’s stools are bloody (dysenteric). For more on this topic, see the CATMAT statement on traveller’s diarrhea ^[14].

Dengue fever

Dengue is caused by a flavivirus, which is transmitted by mosquitoes that bite during the day and breed in stagnant water, usually in urban areas. Regions at high risk for dengue include Southeast Asia (especially Thailand), the South Pacific, Central America and the Caribbean.

The incubation period for dengue varies from 2 to 14 days. Symptoms may include high fever, chills, headache, myalgias and a classic erythematous reticulate rash over the thorax, face and flexion areas. Lymphocytosis, neutropenia and elevated aminotransferases are also characteristic signs of dengue infection. However, all these symptoms can be caused by other arboviruses. Repeat dengue infections can present as hemorrhagic dengue or as shock syndrome, with hyponatremia, hypoproteinemia and circulatory collapse.

Management of dengue is supportive, including rest, fluids, antipyretics, analgesia and transfusion, when indicated. Bacterial sepsis and malaria should always be ruled out. Use of steroids, non-steroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid (ASA, aspirin) should be avoided due to bleeding risk ^[15].

Other infections

In non-immune or unvaccinated children, infectious hepatitis is a consideration.

In recent years, emerging pathogens such as Chikungunya virus and Zika virus, and highly transmissible infections, such as viral hemorrhagic fever (e.g., Ebola), coronaviruses (e.g., Middle East Respiratory Syndrome-CoV), have garnered widespread attention. Consult the CDC or PHAC websites for up-to-date information on emerging travel-related infections or local outbreaks (e.g., measles, Dengue).

GENERAL APPROACH TO CARE FOR THE RETURNING CHILD TRAVELLER WITH FEVER

1. Take an initial travel history.

2. Institute isolation precautions based on presenting symptoms ^[16].

3. Obtain a detailed history of exposures and perform a full physical exam, including skin examination.

4. Conduct the following investigations to rule out malaria and other life-threatening or serious infections ^[7][17]:

• Complete blood count with differential: liver enzymes; electrolytes; creatinine
• Malaria smears ± antigen detection testing, when available (immediately and at least 2 subsequent samples over 24 to 48 hours when the child has visited a malaria-endemic area)
• Blood culture (ensure adequate weight or age-based volume collected)
• Urinalysis +/– urine culture

Consider:

• Stool culture for enteropathogens x 1 (Salmonella, Shigella, Campylobacter, Yersinia, E coli O157:H7)
• Chest x-ray
• Stool for ova and parasites, particularly if diarrhea is chronic or patient is immunocompromised (Cyclospora, Cryptosporidium, Entamoe bahistolytica, Giardia)
• Viral serology: Acute serology should be saved in the laboratory and paired with convalescent serology if a diagnosis has not been reached within 10 to 14 days. Examples: Dengue serology when fever onset occurs within 14 days of return from South or Southeast Asia, Latin America or some areas of the Caribbean; Chikungunya serology when a child has returned from  travel to Southeast Asia, Latin America or the Carribean; Zika virus or arboviruses ^[13].

***Ensure that travel history is included on all lab and radiologic requisitions.

5. Management

When travel history includes a malaria-endemic area and the child is unwell or lab diagnosis may be delayed, empiric treatment for P falciparum malaria should be initiated presumptively (http://publications.gc.ca/collections/collection_2014/aspc-phac/HP40-102-2014-eng.pdf), including broad-spectrum antibiotics with gram-negative coverage. Remember that a well-appearing child with P falciparum malaria can deteriorate quickly, and malaria can also present as a co-infection with pneumonia or bacteremia ^[11]. In critically ill cases or when a child’s condition is worsening, prompt consultation with an infectious diseases specialist is warranted. Also, supportive therapy, such as fluids for severe diarrheal illness, should be initiated promptly.

When malaria and bacteremia have been excluded in the well-appearing, clinically stable child, initiate targeted therapy based on the individual’s history, physical exam and results of investigations and make arrangements for adequate follow-up.

Acknowledgements

This practice point was reviewed by the Infectious Diseases and Immunization Committee, the Community Paediatrics Committee and executive members of the Paediatric Emergency Section of the Canadian Paediatric Society.

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CANADIAN PAEDIATRIC SOCIETY GLOBAL CHILD AND YOUTH HEALTH SECTION

Executive members: Dominic Allain MD (President), Robert Bortolussi MD (Past President), Mahli Brindamour MD (President-Elect), Andrea Evans MD (Member-at-Large), Jennifer Turnbull MD (Secretary-Treasurer), Ashley Vandermorris MD (Member-at-Large)

Liaisons: Funmbi Babalola MD (CPS Residents Section)

Principal authors: Tobey Audcent MD, Andrew Hunter MD

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References

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Disclaimer: The recommendations in this position statement do not indicate an exclusive course of treatment or procedure to be followed. Variations, taking into account individual circumstances, may be appropriate. Internet addresses are current at time of publication.