Fever in a returning traveller

Fever in a returning traveller is a temperature of 38.0 degrees Celsius or over, or a history of fever, in a person who has been in a tropical or subtropical region within the past 12 months (most illness presents within 3 weeks).

Classification by incubation period

• Short, under 10 days: dengue, chikungunya, Zika, malaria (falciparum, usually within 1 month), influenza, typhoid and paratyphoid, rickettsial disease (scrub typhus, spotted fever), leptospirosis, arboviral encephalitis, yellow fever, viral haemorrhagic fevers (Lassa, Ebola, Marburg, Crimean-Congo), plague, and bacterial gastroenteritis.
• Intermediate, 10 to 21 days: malaria, typhoid, Q fever, brucellosis, leptospirosis, Katayama fever (acute schistosomiasis), acute HIV infection, hepatitis A and E, African trypanosomiasis, tick borne relapsing fever, and tularaemia.
• Long, over 21 days: malaria (Plasmodium vivax, ovale), hepatitis A, B and E, tuberculosis, amoebic liver abscess, visceral leishmaniasis, schistosomiasis, filariasis, brucellosis, rabies, and HIV.

Classification by syndrome

• Fever with diarrhoea: enteric fever, bacterial enteritis, amoebiasis, giardiasis.
• Fever with rash: dengue, measles, rickettsial disease, chikungunya, Zika, meningococcaemia, secondary syphilis, acute HIV infection.
• Fever with jaundice: hepatitis A and E, malaria, leptospirosis, yellow fever, amoebic liver abscess, cholangitis.
• Fever with bleeding: viral haemorrhagic fevers, severe dengue, leptospirosis, severe malaria, meningococcaemia.
• Fever with respiratory symptoms: influenza, COVID-19, pneumonia, Legionnaires disease, Middle East respiratory syndrome, tuberculosis, Q fever, melioidosis, Katayama fever.
• Fever with neurological features: cerebral malaria, bacterial meningitis, Japanese encephalitis, rabies, typhoid, trypanosomiasis.
• Fever with eschar: scrub typhus, African tick bite fever, anthrax.

Epidemiology. About 2% to 3% of travellers to low and middle income countries seek care for fever on return, with malaria the leading cause of tropical fever in those returning from sub-Saharan Africa, dengue the leading cause from Southeast Asia and Latin America, and enteric fever from South Asia. Cosmopolitan infections (respiratory viruses, urinary and gastrointestinal infections) remain common. Plasmodium falciparum is the most dangerous, with mortality under 1% when treated early, and severe disease in non immune travellers if diagnosis is delayed.

Mechanisms. Vector borne (mosquito, tick, flea, mite), food and water borne, contact with animals or water, sexual or blood exposure, and respiratory transmission. Non immune travellers develop severe disease more readily. Pretravel vaccination and chemoprophylaxis lower but do not remove risk.

Key distinctions. Fever with chills, sweats, headache and any exposure in an endemic area is malaria until 3 negative blood films over 48 hours. Biphasic fever with retro-orbital pain, myalgia, rash, leucopenia and thrombocytopenia suggests dengue. Prolonged stepwise fever, relative bradycardia and abdominal pain suggest enteric fever. Fever with eschar and regional lymphadenopathy suggests rickettsial disease.

Fever after freshwater exposure with conjunctival suffusion, jaundice and renal failure suggests leptospirosis. Fever, cough, urticaria and eosinophilia 3 to 8 weeks after freshwater exposure suggests Katayama fever. Fever with bleeding after contact with an infected patient or in a health care setting suggests a viral haemorrhagic fever.

History

• Travel: countries, regions and rural or urban areas visited, dates of arrival and return, length of stay, accommodation, and activities (freshwater swimming, caving, safaris, farm or market visits, hospital visits, trekking).
• Exposure: mosquito bites, tick bites, animal contact (bats, rodents, dogs, monkeys, livestock), raw milk or undercooked meat, untreated water, street food, sexual contact, tattoos, injections, medical procedures, and contact with ill people.
• Pretravel measures: malaria chemoprophylaxis (drug, adherence, missed doses), vaccination (yellow fever, hepatitis A, typhoid, rabies, Japanese encephalitis, meningococcal, polio, cholera, measles), repellents and bed nets.
• Symptoms: fever pattern and onset, rigors, headache, myalgia, arthralgia, rash, diarrhoea, jaundice, cough, dyspnoea, eschar, bleeding, neurological symptoms, urinary symptoms, and genital ulcers.
• Past history: immune status, HIV, splenectomy, pregnancy, sickle cell disease, G6PD deficiency, and previous malaria.
• Drugs: antimalarials taken, antibiotics taken (may delay positive results), and allergies.

Examination

• Vital signs, level of consciousness, hydration, and oxygen saturation. Check for shock.
• General: jaundice, pallor, lymphadenopathy, hepatosplenomegaly, rash (type and distribution), eschar, petechiae, conjunctival suffusion, oral ulcers, bites, wounds, and skin infections.
• Cardiorespiratory: murmurs, crackles, effusions.
• Abdomen: tenderness (liver, right iliac fossa), organomegaly, ascites.
• Neurological: meningism, focal signs, seizures, papilloedema.
• Genital and anal examination when sexually transmitted infection is possible.
• Isolation and infection control: apply contact and droplet precautions until viral haemorrhagic fever, measles and respiratory pathogens are excluded.

Red flags

• Any fever after travel to a malaria area (an emergency until excluded).
• Impaired consciousness, seizures, shock, respiratory distress, jaundice, bleeding, severe anaemia, or acute kidney injury (severe malaria and other severe infection).
• Fever with bleeding, hypotension, or multi organ failure after contact with a possible viral haemorrhagic fever (travel to areas with outbreak in the preceding 21 days, contact with patients, bats, or care in a local health facility).
• Fever with rash, cough and conjunctivitis (measles) in a non immune person.
• Fever with respiratory symptoms after travel to Middle East or areas with avian influenza (specific isolation and public health notification).
• Meningism or reduced consciousness.
• Warning signs of severe dengue: abdominal pain, persistent vomiting, mucosal bleeding, lethargy, liver enlargement, rising haematocrit with rapidly falling platelets around day 3 to 7.
• Pregnancy, children under 5 years, asplenia, immunosuppression, and age over 65 years.
• Fever with jaundice and oliguria (leptospirosis, severe malaria).
• Fever with a rapidly spreading skin lesion or eschar with systemic illness.

Special groups

• Children: malaria progresses fast, so treat urgently. Hypoglycaemia is common.
• Pregnancy: malaria and hepatitis E have high mortality. Avoid doxycycline, primaquine and some other drugs.
• Immunosuppressed and HIV: broaden search for opportunistic infection.
• Visiting friends and relatives: highest risk for malaria and typhoid, often unvaccinated and without prophylaxis.
• Migrants returning: tuberculosis, HIV, hepatitis B, strongyloides and schistosomiasis.
• Region specific: dengue is common in tropical cities, melioidosis in Southeast Asia and northern Australia, scrub typhus in Asia-Pacific, and Lassa fever in West Africa.

Parasitic

• Malaria (falciparum, vivax, ovale, malariae, knowlesi).
• Amoebic liver abscess and invasive amoebiasis.
• Visceral leishmaniasis, African trypanosomiasis, and American trypanosomiasis.
• Acute schistosomiasis (Katayama fever), strongyloides hyperinfection.
• Babesiosis and toxoplasmosis.

Bacterial

• Enteric fever (typhoid and paratyphoid).
• Rickettsial infections: scrub typhus, spotted fever group, murine typhus, Q fever.
• Leptospirosis and other spirochaetal diseases (relapsing fever).
• Brucellosis, melioidosis, tuberculosis, plague, and tularaemia.
• Bacterial gastroenteritis, cholera, and bacterial meningitis (meningococcal, pneumococcal).
• Legionnaires disease, typhus, and anthrax.
• Sexually transmitted infection: acute HIV, secondary syphilis, gonococcal and chlamydial infection.

Viral

• Dengue, chikungunya, Zika, yellow fever, West Nile virus, Japanese encephalitis, tick borne encephalitis.
• Viral haemorrhagic fevers: Ebola, Marburg, Lassa, Crimean-Congo, Rift Valley fever.
• Influenza, COVID-19, Middle East respiratory syndrome, avian influenza, measles, mumps, varicella.
• Hepatitis A, B and E, acute HIV seroconversion, cytomegalovirus, Epstein-Barr virus, rabies.

Noninfectious

• Drug fever, deep vein thrombosis and pulmonary embolism.
• Heat stroke, sickle cell crisis, and adrenal crisis.
• Systemic lupus erythematosus, vasculitis, adult-onset Still disease, inflammatory bowel disease.
• Lymphoma and other malignancy.
• Thyroid storm and sarcoidosis.

Step 1. Triage and isolate. Assess airway, breathing, circulation and consciousness. Check capillary glucose. Identify patients needing isolation and protective precautions (suspected viral haemorrhagic fever, measles, respiratory pathogens). Take a detailed exposure history with dates.

Step 2. First line tests (all patients)

• Malaria: rapid diagnostic test and thick and thin blood films, read the same day; if negative, repeat every 12 to 24 hours for a total of 3 sets. Report parasitaemia percentage. Use polymerase chain reaction to identify species.
• Full blood count and differential (anaemia, thrombocytopenia, leucopenia, eosinophilia, atypical lymphocytes), C-reactive protein, urea, creatinine, electrolytes, glucose, liver tests, lactate dehydrogenase, creatine kinase, lactate, and coagulation.
• Blood cultures (two sets, before antibiotics), urine analysis and culture, and stool culture and microscopy for ova, cysts and parasites if diarrhoea.
• Chest radiograph, and ECG where indicated.
• HIV test with counselling, and syphilis serology.
• Pregnancy test in women of reproductive age.

Step 3. Targeted tests

• Dengue: NS1 antigen and polymerase chain reaction (days 1 to 5), then IgM and IgG serology; monitor haematocrit and platelets.
• Typhoid: blood cultures, bone marrow culture if negative after antibiotics, stool and urine culture, and polymerase chain reaction where available. Widal test is unreliable.
• Rickettsial disease: polymerase chain reaction of eschar swab or blood, and paired serology (do not wait for results to treat).
• Leptospirosis: polymerase chain reaction of blood and urine, microscopic agglutination test with paired sera.
• Viral haemorrhagic fever and other high consequence infection: discuss with the national reference laboratory and infectious diseases before sampling; use specific procedures for collection and transport.
• Chikungunya, Zika, West Nile virus, and Japanese encephalitis: polymerase chain reaction and serology by timing.
• Hepatitis A, B and E serology; hepatitis E polymerase chain reaction.
• Schistosomiasis: serology (may be negative in early disease), eosinophil count, stool and urine microscopy for eggs after 6 to 8 weeks.
• Brucellosis, Q fever, melioidosis, and leishmaniasis: culture and serology; bone marrow or splenic aspirate in visceral leishmaniasis.
• Amoebic liver abscess: ultrasound or CT and amoebic serology.
• Strongyloides serology and stool tests in patients needing corticosteroids.
• Respiratory polymerase chain reaction panel (influenza, COVID-19, Middle East respiratory syndrome coronavirus) when relevant.
• Lumbar puncture for meningism or encephalopathy after malaria is excluded or treated.
• Imaging as directed: chest radiograph, abdominal ultrasound, CT.

Step 4. Interpretation. A single negative malaria film or rapid test does not exclude malaria; repeat. Thrombocytopenia with fever supports malaria or dengue. Leucopenia with raised transaminases suggests dengue, rickettsial disease or viral hepatitis. Eosinophilia suggests helminth infection but is usually absent in acute malaria or typhoid. Coinfection (malaria with bacteraemia, typhoid with malaria) is common, so continue the search after finding one pathogen.

Limits. Rapid tests may be negative in low parasitaemia or in some Plasmodium species; zoonotic Plasmodium knowlesi can be misread as malariae. Serology has delays and cross reactions. Antibiotic or antimalarial pretreatment reduces culture and smear yield. Up to a quarter of cases remain undiagnosed.

Immediate. Resuscitate by severity: oxygen, crystalloid 250 to 500 mL boluses with reassessment, capillary glucose (treat hypoglycaemia with 50 mL of 50% dextrose, or 2 mL/kg of 10% dextrose in children), and control of seizures with lorazepam 4 mg intravenously (0.1 mg/kg in children, maximum 4 mg). Apply isolation measures. Notify public health authorities of reportable infection. Start empirical treatment for malaria and bacterial sepsis in severe cases while awaiting results.

Malaria

• Severe falciparum malaria (impaired consciousness, shock, acidosis, hypoglycaemia, parasitaemia over 2%, jaundice with other organ dysfunction, renal impairment, pulmonary oedema, bleeding, haemoglobin under 70 g/L): artesunate 2.4 mg/kg intravenously at 0, 12 and 24 hours, then once daily (children under 20 kg: 3 mg/kg for each dose) for a minimum of 3 doses and until oral therapy can be taken, followed by a complete oral course of artemether with lumefantrine or another artemisinin combination. Admit to intensive care. Monitor glucose, parasitaemia every 12 hours, lactate, creatinine, and haemoglobin (delayed haemolysis for 4 weeks after artesunate). Avoid corticosteroids, and give fluids cautiously because of pulmonary oedema.
• Uncomplicated falciparum malaria: artemether 20 mg with lumefantrine 120 mg, four tablets (adult over 35 kg) orally at 0, 8, 24, 36, 48 and 60 hours with fatty food (dose by weight bands in children), or dihydroartemisinin 40 mg with piperaquine 320 mg, 3 to 4 tablets once daily for 3 days (weight based), or atovaquone 250 mg with proguanil 100 mg, four tablets once daily for 3 days (not if prophylaxis failure with this drug). Repeat parasite count at 48 to 72 hours and day 7.
• Vivax and ovale malaria: chloroquine 600 mg base orally then 300 mg at 6, 24 and 48 hours (where sensitive) or an artemisinin combination in resistant areas, followed by radical cure with primaquine 30 mg base daily for 14 days (or 0.5 mg/kg daily) after confirming normal glucose-6- phosphate dehydrogenase (tafenoquine 300 mg once is an alternative with normal enzyme level). Contraindicated in pregnancy and lactation.
• Knowlesi malaria: artemisinin combination, and intravenous artesunate if severe.
• Pregnancy: first trimester quinine 600 mg every 8 hours for 7 days with clindamycin 450 mg every 8 hours for 7 days for uncomplicated disease (artemisinin combinations are now used in all trimesters in many settings); artesunate for severe disease in any trimester.
• Children: artemether with lumefantrine by weight (5 to under 15 kg: 1 tablet; 15 to under 25 kg: 2 tablets; 25 to under 35 kg: 3 tablets, at the same time schedule), and monitor glucose.
• Chemoprophylaxis for future travel and counselling.

Enteric fever (typhoid and paratyphoid)

• Uncomplicated: azithromycin 1 g orally on day 1, then 500 mg daily for 6 days (children: 20 mg/kg daily, maximum 1 g, for 7 days), or ceftriaxone 2 g intravenously once daily for 10 to 14 days (children 75 mg/kg daily, maximum 2 g). Fluoroquinolones are for susceptible isolates only (ciprofloxacin 500 mg twice daily for 7 days), since resistance is high in South Asia. Extensively drug resistant strains: meropenem 1 g every 8 hours with azithromycin, specialist advice.
• Severe (shock, encephalopathy): add dexamethasone 3 mg/kg intravenously over 30 minutes then 1 mg/kg every 6 hours for 8 doses. Surgery for perforation.
• Carrier state follow up with stool cultures.

Dengue

• No specific antiviral. Fluid management by phase. Without warning signs: oral fluids (2.5 L daily in adults), paracetamol 1 g every 6 hours (maximum 4 g daily), avoid aspirin and nonsteroidal drugs, and daily review during the critical phase (days 3 to 7) with full blood count. With warning signs or severe dengue: admit, isotonic crystalloid 5 to 7 mL/kg/hour for 1 to 2 hours then reduce to 3 to 5 mL/kg/hour for 2 to 4 hours and then 2 to 3 mL/kg/hour, directed by haematocrit, urine output and haemodynamics. Shock: 10 to 20 mL/kg boluses over 15 to 30 minutes. Give blood for significant bleeding. Platelet transfusion only for severe bleeding, not for counts alone.

Rickettsial disease (scrub typhus, spotted fever, murine typhus)

• Doxycycline 100 mg orally or intravenously twice daily for 7 days (or 3 days after defervescence, minimum 5 days). Children over 8 years: 2.2 mg/kg twice daily; under 8 years, doxycycline is used for up to 7 days with benefit outweighing risk in severe disease. Pregnancy: azithromycin 500 mg daily for 3 to 5 days, or chloramphenicol where unavailable. Start on suspicion, since delay increases mortality.

Leptospirosis

• Mild: doxycycline 100 mg twice daily for 7 days, or amoxicillin 500 mg three times daily for 7 days, or azithromycin 500 mg daily for 3 days.
• Severe: benzylpenicillin 1.5 million units intravenously every 6 hours, or ceftriaxone 2 g once daily, for 7 days. Supportive care with renal replacement therapy and ventilation as required. Jarisch-Herxheimer reaction can occur.

Viral haemorrhagic fevers and high consequence infection

• Isolate immediately in a single room with a dedicated toilet. Limit staff to those trained with full personal protective equipment, and contact the national infectious disease and public health authorities before any sampling. Supportive management: oxygen, fluids, correction of electrolytes and coagulopathy. Specific treatments are given through specialist units: ribavirin 30 mg/kg intravenously loading dose (maximum 2 g), then 16 mg/kg every 6 hours for 4 days, then 8 mg/kg every 8 hours for 6 days, for Lassa fever and Crimean-Congo haemorrhagic fever; monoclonal antibodies for Ebola virus disease. Also give antimalarials and antibiotics for coexisting infection. Trace contacts for 21 days.

Influenza and respiratory infection

• Oseltamivir 75 mg orally twice daily for 5 days (10 days in severe or immunocompromised patients). Renal dose: creatinine clearance 31 to 60 mL/min, 30 mg twice daily; 11 to 30 mL/min, 30 mg once daily; 10 mL/min or under, 30 mg as a single dose. For bacterial pneumonia give amoxicillin with clavulanic acid 1.2 g intravenously every 8 hours plus clarithromycin 500 mg twice daily. Q fever: doxycycline 100 mg twice daily for 14 days. Melioidosis: ceftazidime 2 g every 6 to 8 hours or meropenem 1 g every 8 hours for at least 10 to 14 days, followed by co-trimoxazole 960 mg twice daily for 3 to 6 months.

Acute schistosomiasis (Katayama fever)

• Praziquantel 40 mg/kg orally in 2 divided doses on the same day, given after 6 to 8 weeks from exposure (to cover adult worms) and repeated after 4 to 6 weeks. Prednisolone 20 to 40 mg daily for 5 days when symptoms are severe, evidence being limited. Avoid praziquantel in the early phase when it can worsen reactions without steroid cover.

Amoebic liver abscess

• Metronidazole 800 mg orally three times daily (or 500 mg intravenously every 8 hours) for 7 to 10 days, then paromomycin 500 mg three times daily for 7 days. Aspirate for abscess over 5 cm, left lobe lesions, or no response at 72 hours.

Other infections

• Brucellosis: doxycycline 100 mg twice daily with rifampicin 600 to 900 mg daily for 6 weeks (or with streptomycin 1 g intramuscularly daily for the first 14 to 21 days).
• Visceral leishmaniasis: liposomal amphotericin B 3 mg/kg on days 1 to 5, 14 and 21, under specialist care.
• Acute HIV infection: confirm with antigen and antibody test and viral load; start antiretroviral therapy with specialist advice.
• Hepatitis A and E: supportive; ribavirin may be used for chronic hepatitis E in immunosuppressed patients.
• Cholera: oral rehydration, doxycycline 300 mg single dose or azithromycin 1 g single dose.
• Meningitis: ceftriaxone 2 g every 12 hours with dexamethasone 10 mg every 6 hours for 4 days, started before or with the first antibiotic dose.
• Typhus and relapsing fever: doxycycline, with Jarisch-Herxheimer reaction precautions.

Special populations

• Pregnancy: severe malaria and hepatitis E have high mortality; treat promptly and use obstetric input. Avoid doxycycline, primaquine, tafenoquine, fluoroquinolones and ribavirin where possible.
• Children: use weight based doses, check glucose, and apply early hospital care for malaria in under 5 years.
• Older adults: reduce doses for renal function and monitor for fluid overload.
• Renal and hepatic impairment: dose adjust; monitor levels; avoid nephrotoxins.
• Immunosuppressed: extend treatment and test for opportunistic infection.

Monitoring. Vital signs and consciousness every 1 to 4 hours in severe illness, capillary glucose every 4 to 6 hours in malaria, parasite counts every 12 to 24 hours, haematocrit and platelets daily in dengue, creatinine, electrolytes, liver tests, haemoglobin, culture results, and response at 48 to 72 hours. Referral and escalation.

Infectious diseases or tropical medicine for all febrile travellers requiring admission and for any diagnostic uncertainty. Intensive care for severe malaria, shock, respiratory failure and bleeding. National and public health authorities for suspected viral haemorrhagic fever, measles, Middle East respiratory syndrome, avian influenza, typhoid, cholera, and tuberculosis. Haematology, nephrology and surgery as indicated.

Admission criteria. Suspected or confirmed falciparum malaria (admit all non immune patients), severe features, dengue with warning signs, enteric fever with complications or vomiting, suspected viral haemorrhagic fever, pregnancy, children, immunosuppression, and inability to take oral therapy or reliable follow up.

Discharge and follow up. Discharge uncomplicated, well patients only after the malaria screen is negative three times or treatment is established, and review within 24 to 48 hours. Complete the full course. Advise on prevention for future travel, vaccination, and prophylaxis. Safety net advice: return for persistent or recurrent fever, confusion, drowsiness, severe headache, yellow eyes, dark urine, bleeding, breathlessness, persistent vomiting, or reduced urine output.