Fever in a returned traveller

History

• Pretravel
  • Vaccinations
  • Prophylaxis, e.g. malaria
  • Vector protection, including bed nets and mosquito spray
• Travel
  • Make explicit timeline of locations visited, for how long
  • Assess activities and exposures in each location
  • Food (especially street food) and water sources
  • Recreational water
  • Animals
  • Insect bites
  • Sex and other body fluid exposures
• Combine timeline of exposures with incubation periods to rule out diseases
  • Dengue: 3-5 days
  • Malaria: 7-21 days
  • Hepatitis A: 6 days to 6 weeks
  • Hepatitis B: 1-6 months
  • Typhoid: 7-21 days
  • Non-typhoidal Salmonella: 3-7 days

Differential Diagnosis

Most Common Conditions

Disease	%	Incubation	Diagnosis
Malaria	20-30%	7-30 days, or longer	thick-and-thin blood film examination or rapid antigen test
Acute diarrhea or gastroenteritis, including traveller's diarrhea	10-20%	days	bacterial stool cultures but primarily clinical diagnosis
Respiratory infections, including influenza	10-15%	days	NP swab for respiratory viruses
Dengue	5%	4 to 7 days	serology or PCR
Enteric fever	2-7%	6-30 days	blood culture
Skin and soft tissue infections	2-11%
Rickettsioses, including African tick bite fever and Mediterranean spotted fever	3%	1-2 weeks	serology or PCR
UTI or STI	2-3%		urinalysis and culture, urine NAAT for G&C
Viral hepatitis	3%	6 days to 6 weeks (HAV) 1-6 months (HBV)	serology or PCR
Mononucleosis or viral syndrome	4-25%	30 to 50 days	Monospot (if young), serology (EA-IgG/VCA-IgM), or PCR

Most Common by Location of Travel

• Sub-Saharan Africa: malaria, respiratory infections, diarrhea, skin and soft tissue infections
• Southeast Asia: dengue, respiratory infections, diarrhea, malaria
• South Central Asia: enteric fever, dengue, malaria, diarrhea
• South America: diarrhea, respiratory infections, dengue, malaria
• Central America and Caribbean: diarrhea, respiratory infections, dengue, malaria

Life-Threatening Infections

Disease	Incubation	Distribution	Exposures	Diagnosis
Viruses
Avian influenza	2-8 days	East and Southeast Asia	poultry	PCR
MERS-CoV	2-14 days	Arabian peninsula	infected humans or camels	PCR
Ebola, Lassa fever, or Marburg hemorrhagic fever	up to 22 days	Africa	infected humans and animals	PCR
Crimean-Congo hemorrhagic fever	1-9 days (tick) or 3-13 days (contact)	southern Europe, Middle East, Africa, northwestern China	Ixodes ticks or infected humans or animals	PCR
Yellow fever	3-8 days	South America and Africa	Aedes mosquitoes	PCR or IgM
Japanese encephalitis	5-15 days	Asia and western Pacific	Culex mosquitoes	IgM
Rift Valley fever	2-6 days	Africa and the Arabian peninsula	mosquitoes, or blood from infected animals	PCR or IgM
Rabies	20 to 60 days (usually 4 weeks)	worldwide	animal bite	saliva PCR; serum/CSF RFFIT; skin biopsy PCR or RFFIT
Bacteria
Anthrax	1 day (cutaneous) to 1-7 days (pulmonary)	Africa and Asia	infected animals or animal products	bacterial culture or PCR
Enteric fever	6-30 days	South and Southeast Asia	fecal-oral transmission	bacterial culture
Epidemic typhus	7-14 days	Central Africa, Asia, North and South America	human body lice, flying squirrel parasites, possibly ticks	IgM/IgG and PCR
Leptospirosis	2-29 days	worldwide but particularly South and Southeast Asia and South America	urine of infected animals	IgM/IgG and PCR
Louse-borne relapsing fever	4-14 days	Ethiopia, Eritrea, and Sudan	human body lice	blood film examination, IgM/IgG, or PCR
Melioidosis	1-21 days (but up to years)	South and Southeast Asia, northern Australia, and case reports from Africa and South America	contaminated soil or surface water	bacterial culture
Endemic typhus	7-14 days	worldwide but particularly Southeast Asia	rodent fleas	IgM/IgG or PCR
Oroya fever or Carrion disease	10 days to 7 months	South America, particularly Peru	sand flies	bacterial culture
Scrub typhus	6-20 days	Asia and northern Australia	chiggers	IgM/IgG or PCR
Rickettsial spotted fever	2-14 days	worldwide	mostly ticks	IgM/IgG or PCR
Plague	2-6 days (bubonic) or 1-3 days (pneumonic)	remote Africa, Asia, and South America	rodent fleas	bacterial culture
Protozoa
East African sleeping sickness	7-21 days	eastern and southern Africa	tsetse flies	blood film examination, lymph aspirate exam, or chancre biopsy
Falciparum malaria	7-30 days, or longer	African, Asia, South America	Anopheles mosquitoes	thick-and-thin blood film examination or rapid antigen test
Knowlesi malaria	10-14 days	Southeast Asia, particularly Borneo	Anopheles mosquitoes	thick-and-thin blood film examination

Investigations

• First-line
  • CBC
  • Liver enzymes and function, for viral hepatitis
  • Electrolytes, urea, and creatinine
  • Urinalysis, for proteinuria that would suggest Leptospirosis
  • Blood cultures x2, for enteric/typhoid fever
  • Thick and thin smears x3 over 3 days, for malaria
• Based on history and lab results
  • Urine culture
  • Stool culture and O&P
  • Hepatitis serologies
  • Serology for Zika, chikungunya, and dengue viruses, with repeat in 14 days if negative
  • C. difficile toxin
  • NP swab for influenza and other respiratory viruses that may circulate non-seasonally in other countries

Further Reading

• Freedman DO, et al. Spectrum of Disease and Relation to Place of Exposure among Ill Returned Travelers. N Engl J Med 2006; 354:119-130. doi: 10.1056/NEJMoa051331
• Boggild A, et al. Fever in the Returning International Traveller Initial Assessment Guidelines. CCDR. 2011;37(ACS-3):1-15. doi: 10.14745/ccdr.v37i00a03
• Jazuli F, Lynd T, Mah J, et al. Evaluation of a programme for ‘Rapid Assessment of Febrile Travelers’ (RAFT): a clinic-based quality improvement initiative. BMJ Open 2016;6:e010302. doi: 10.1136/bmjopen-2015-010302