Fever After Returning from a Tropical Trip: A Complete Guide for Travelers and Healthcare Professionals

Fever is a universal symptom, but when it occurs after a stay in a tropical region, it takes on particular significance and requires immediate attention. While it may signal a mild and self-limiting illness, fever upon return from a trip can also be the first sign of a rapidly progressing and potentially fatal condition. Therefore, it is crucial to urgently assess any febrile state in a returning traveler. Healthcare professionals should be familiar with the main causes, preventive measures, and associated diagnostic and therapeutic approaches. Similarly, travelers should be aware of the potential risks and precautions to take before, during, and after their trip.

Understanding Traveler's Fever: Definitions and the Importance of Rapid Assessment

Fever following a trip to the tropics is the second most common reason for seeking medical care among travelers, accounting for 23% of cases, just behind digestive disorders (42%) and ahead of skin conditions (17%). This statistic underscores the importance of this symptom. A rapid and appropriate assessment is crucial, as some conditions can progress very quickly and be life-threatening. It is important to note that tropical diseases may be suspected even in patients who traveled several years prior, or who have not traveled at all, as in the case of "airport malaria."

Essential knowledge for healthcare professionals includes the ability to assess the patient’s general condition, conduct a thorough interview regarding travel history, and examine for potential skin manifestations. Travel recommendations are regularly updated, and it is essential for travelers and healthcare professionals to consult the guidelines issued by international organizations and national health authorities. In France, the High Council for Public Health and the National Institute for Health Surveillance (InVS) publish specific recommendations for travelers. The clinical approach to fever following a trip is divided into four fundamental steps, enabling an accurate diagnosis and ensuring appropriate management. First, it is necessary to consider common infections—that is, those not specifically related to travel to tropical regions—such as influenza, ENT (ear, nose, and throat) infections, pulmonary infections, or urinary tract infections. However, it is imperative to systematically screen for malaria in any febrile patient returning from the tropics, regardless of associated symptoms, because 10 to 30% of patients with malaria may present with cough, nausea, vomiting, diarrhea, or abdominal pain, thus mimicking more common infections. The second step involves screening for acute and dangerous conditions that require emergency treatment. These include malaria, enteric fever (typhoid, paratyphoid), rickettsiosis, amoebic liver abscess, meningitis or meningoencephalitis, African trypanosomiasis (rare), and viral hemorrhagic fever (rare). The third step then aims to diagnose conditions that, although rarely acute and dangerous, require specific treatment. These include leptospirosis, Lyme disease, brucellosis, schistosomiasis (Katayama fever), leishmaniasis, and Chagas disease. Finally, the fourth step involves considering conditions that do not require specific treatment, such as viral infections like viral hepatitis, dengue fever, chikungunya, and Zika, as well as other arboviruses. Conditions to consider: a wide spectrum of infections. The range of infections to consider when a traveler develops a fever after returning from a trip is vast and varies depending on the destination and the traveler’s activities. Cosmopolitan diseases are the most common, but it is always essential to rule out malaria. Among the conditions to be aware of are digestive infections and skin diseases, which are also very common upon returning from a trip. Specifically regarding diarrhea, it can be of bacterial origin (Campylobacter, Salmonella, Shigella, enterotoxigenic E. coli, enteroinvasive E. coli, Vibrio cholerae), parasitic (Giardia, Cryptosporidium, Cyclospora, Entamoeba histolytica), or viral. As for skin lesions, sources mention dermatophytosis, urticarial lesions (often linked to insect bites), migrating larvae, myiasis, and dengue fever. Tropical diseases can present as a fever, often accompanied by nonspecific symptoms. It is crucial to consider dengue, chikungunya, other arboviral diseases, HIV, rickettsiosis, brucellosis, Lyme disease, leptospirosis, visceral leishmaniasis, schistosomiasis, and other helminthiasis, as well as trypanosomiasis. Epidemiology is a key factor in guiding diagnosis. For example, Plasmodium falciparum is the most frequently identified pathogen during stays in sub-Saharan Africa, accounting for approximately 30% of fever cases upon return. In contrast, dengue is the primary cause in Southeast Asia (13%) and Latin America (8%). Non-P. falciparum malaria is more widespread (around 4–9% depending on the region). Rickettsial diseases are also present in all these areas (2–5%), and enteric fever is more common in Southeast Asia (3.4%). A significant proportion of cases remain attributed to other causes or are unknown, highlighting the complexity of differential diagnosis.

Medical history and clinical manifestations: key clues for diagnosis

• Where did the patient travel? It is important to know which countries were visited and whether they were urban or rural areas, as some diseases are endemic to specific regions.
• When did the trip take place? The length of stay, return date, and season of travel are crucial pieces of information, particularly for determining the incubation periods of diseases.
• Who is the patient? A traveler's medical history can affect their susceptibility to certain infections.
• How was the trip? This part of the medical history is particularly rich in clues:
  • Swimming or rafting: May indicate schistosomiasis or leptospirosis.
  • Food consumed: Consumption of unpasteurized milk may indicate brucellosis, while raw meat may indicate trichinellosis. Contaminated food and water are a very common and nonspecific mode of transmission for many pathogens.
  • Insect bites: Mosquitoes are vectors of malaria, dengue fever, and chikungunya. Ticks can transmit Rickettsia africae or Lyme disease. Fleas are associated with Rickettsia typhi, and tsetse flies with African trypanosomiasis. It should be noted that many patients do not remember being bitten.
  • Risky sexual contact or contact with blood (e.g., at the dentist or a tattoo parlor): May indicate HIV or hepatitis B infection.
  • Vaccinations received: It is important to know your vaccination status (hepatitis A, hepatitis B, typhoid fever, yellow fever), given that 3% of febrile illnesses following travel can be prevented by vaccination.
  • Medications taken: Taking malaria prophylaxis or antibiotics during the trip can alter the clinical presentation or diagnosis of certain diseases.

Incubation periods are valuable indicators. For example, dengue fever cannot be responsible for a fever starting 20 days after returning home, as its incubation period is 3 to 14 days. Similarly, a fever starting the day after a short 4-day stay in West Africa is not malaria, as the minimum incubation period is 7 days. The incubation period chart lists periods for bacterial dysentery (<7 days), dengue fever (7-14 days), malaria (7-21 days), visceral leishmaniasis (>4 weeks), among others. In addition to the medical history, a complete physical examination is crucial. Certain clinical manifestations are particularly helpful in the differential diagnosis:

• Skin rash: Can be observed in measles, arboviral diseases (dengue, Zika), rickettsial diseases, typhoid fever, or Lyme disease. The dengue rash is a notable example.
• Black skin lesion (eschar): Characteristic of certain rickettsial diseases (R. africae, R. conorii).
• Conjunctivitis: Associated with leptospirosis, rickettsial diseases, measles, and certain arboviral diseases (Zika).
• Lymphadenopathy: May indicate rubella, toxoplasmosis, CMV, or HIV infection; arboviral diseases; tuberculosis; leishmaniasis; or trypanosomiasis.
• Hepatomegaly: Suggests hepatitis, an amoebic abscess, flukes (Fasciola), leishmaniasis, or malaria.
• Splenomegaly: Common in malaria, leishmaniasis, and typhoid fever.
• Neurological signs: These may indicate serious conditions such as meningitis, encephalitis, trypanosomiasis, or malaria.

Paraclinical tests: confirming the diagnosis

Paraclinical examinations are essential for confirming the cause of a febrile illness following travel. A baseline assessment should be performed for each patient, supplemented by additional tests based on clinical suspicion or initial results.

The baseline assessment includes:

• A complete blood count (CBC), which may reveal anemia or thrombocytopenia, both of which are common in malaria.
• C-reactive protein (CRP), bilirubin, AST, ALT (liver enzymes), and creatinine (kidney function). Elevated transaminase levels are common in dengue fever, for example.
• Systematic malaria testing, including blood smears, thick blood films, and rapid antigen tests.
• Urine sediment.

Depending on the clinical suspicion, further tests may be necessary:

• Stool examination (white blood cell count, parasite screening, culture) in cases of digestive problems.
• Blood cultures to identify bacteria, particularly in cases of suspected typhoid fever.
• Specific viral and/or bacterial serology for infections such as arboviruses (dengue, chikungunya), rickettsial diseases, leptospirosis, amoebiasis, HIV, and syphilis. For dengue fever, the rapid test (NS1 antigen detection) is sensitive from the first days of fever, and specific IgM antibodies appear after 5 to 7 days.
• Parasite serology tests, particularly for screening for helminthiasis following a stay in a tropical region.
• PCR (polymerase chain reaction) tests for the direct detection of pathogens, such as Zika or Ebola.
• A urine culture.
• A lumbar puncture in cases of neurological involvement (suspected meningitis or encephalitis).
• A chest X-ray or abdominal ultrasound may be indicated. Abdominal ultrasound is sensitive for amebic liver abscess, although not specific. It is important to note that in cases of fever with eosinophilia, the most common cause in travelers is acute schistosomiasis. Other helminthiases should also be considered, such as trichinellosis, fascioliasis (liver flukes), toxocariasis, as well as strongyloidiasis, ascariasis, and hookworm infection during the migration phase. Malaria management: an absolute priority. Malaria is an absolute priority in the evaluation of any fever upon return from tropical travel. It should be systematically investigated, regardless of associated symptoms, in anyone who has stayed in an endemic area. The diagnosis can be suspected even several months after returning, and in 2% of cases, it can occur more than a year after the trip. A detailed medical history is crucial for malaria: Country visited: Three-quarters of cases diagnosed in Switzerland are contracted in Africa, where Plasmodium falciparum accounts for 85% of cases. In Asia and Latin America, P. falciparum accounts for 17–22% of cases. Date of stay: The minimum incubation period is one week. 95% of malaria attacks occur within two months of returning from travel.
• Malaria prophylaxis: It is important to know whether adequate prophylaxis was taken or not, or whether antibiotic treatment (cotrimoxazole, tetracyclines, macrolides, fluoroquinolones) with partial antimalarial activity was being administered.

The clinical manifestations of malaria are often nonspecific, mimicking the flu with fever, headache, chills, profuse sweating, and muscle aches. Several factors make the diagnosis more likely: inadequate or absent malaria prophylaxis, splenomegaly, anemia (<12 g/dL), and thrombocytopenia (<150 G/L). It should be noted that 40% of malaria patients are afebrile at the first consultation, which reinforces the importance of systematic screening. The diagnosis is based on a blood smear, a thick blood film, and, if necessary, a rapid test. Additional blood tests are indicated: complete blood count, blood glucose, sodium, bilirubin, ALT, creatinine, lactate, and prothrombin time, as well as a urinalysis. It is essential to know that cases of malaria due to P. vivax, P. ovale, P. knowlesi, and P. malariae can also present with sometimes severe clinical manifestations and require immediate management and treatment. Management depends on the results of the malaria test: If the result is negative, but there is strong suspicion, it is recommended to repeat two additional tests within 24 hours, especially if the stay was in an area of ​​high transmission. If the result is positive and there are no signs of severity or other criteria for hospitalization, outpatient treatment can be considered, with clinical and parasitemia monitoring at 24 hours. It is crucial to monitor the progression, as the clinical condition can deteriorate rapidly in 2-3 days in adults and in less than 24 hours in children.

The severity criteria for malaria require immediate hospitalization and intravenous treatment:

• Clinical manifestations: Prostration, altered consciousness, respiratory distress (acidotic respiration), multiple seizures, cardiovascular collapse (BP <70 mmHg), radiological pulmonary edema, abnormal bleeding, jaundice (total bilirubin >50 μmol/L), hemoglobinuria.
• Biological manifestations: Severe anemia (Hb <8 g/dL), hypoglycemia (<2.2 mmol/L), metabolic acidosis (plasma bicarbonate <15 mmol/l), acute renal failure (without improvement after rehydration) with diuresis <400 ml/24h and creatinine >265 μmol/l, hyperlactatemia (>5 mmol/l), hyperparasitemia (>5%). Parasitemia may be falsely low in cases of recent insufficient antimalarial treatment or the use of antibiotics with antimalarial activity.

Criteria for hospitalization include the presence of at least one severity criterion (Table 6) or the presence of factors such as vomiting, parasitemia >2% in a non-immune individual, marked deterioration of general condition, pregnancy, immunosuppression, asplenia, age over 60, or living alone at home.

The first-line treatment for uncomplicated malaria is artemether + lumefantrine (Riamet®), administered as 4 tablets twice a day for 3 days. This treatment is contraindicated in cases of prolonged QT interval (congenital, due to electrolyte disturbances, or drug-induced). Alternatives include atovaquone + proguanil (Malarone® or Atovaquone Plus Spirig HC®) at a dose of 4 tablets daily for 3 days. Chloroquine (base) can be used for malaria caused by P. vivax, P. ovale, or P. malariae, unless P. vivax is resistant. It is recommended to keep the patient under observation for at least one hour after the first dose due to the risk of vomiting, and to take artemether + lumefantrine or atovaquone + proguanil with food or a glass of milk to improve absorption. In cases of pregnancy, hospitalization is preferable. If signs of severe illness or uncontrollable vomiting occur, emergency hospitalization is indicated for intravenous treatment with artesunate. For P. vivax or P. ovale infections, the addition of primaquine may be considered to prevent relapses, taking into account contraindications (G6PD deficiency, pregnancy). loading="lazy">

Other common illnesses and their management: typhoid fever, amoebic abscess, and dengue fever

In addition to malaria, other tropical diseases are commonly encountered and require specific treatment. Among them, typhoid fever, amoebic liver abscess, and dengue fever are particularly noteworthy.

Enteric fever (typhoid or paratyphoid)

Travelers to all developing countries are at risk of enteric fever, but the risk is particularly high in South Asia (e.g., India, Nepal). Vaccination (Vivotif® or TyphimVi®) is 60 to 70% effective. Typical clinical symptoms include fever, a discrepancy between pulse and body temperature, constipation or diarrhea, a dry cough, and abdominal pain. The primary diagnostic test for enteric fever is blood culture, which has a sensitivity of approximately 80% during the first week of fever but decreases thereafter. Stool culture is positive in one-third to two-thirds of cases between the second and fourth weeks. A complete blood count (CBC) may show a normal or decreased white blood cell count, and C-reactive protein (CRP) is elevated. It is important to note that serology is not considered necessary for diagnosis. Management varies depending on the patient’s general condition: If the general condition is poor or in the event of complications, Ceftriaxone 2 g/day intravenously is administered for 10 to 14 days. If the general condition is stable, Ciprofloxacin 500 mg twice daily for 14 days is an option. Azithromycin, with a 1-g loading dose followed by 500 mg once daily for 6 days, is preferred for typhoid or paratyphoid fever acquired in South Asia, due to fluoroquinolone resistance.

Amoebic Liver Abscess

Amoebic liver abscess most often occurs without associated colon involvement and is significantly more common in men. The main clinical symptoms are right upper quadrant pain and hepatomegaly. A pleuropulmonary syndrome involving the right lower lobe is present in 30% of cases.

The diagnosis is primarily confirmed by positive serology in more than 85% of cases. Abdominal ultrasound, and possibly CT scan, are sensitive but nonspecific tests that reveal the presence of an abscess. Management involves treatment with metronidazole, administered at 750 mg intravenously or orally, three times a day for 10 days, followed by paromomycin at 500 mg three times a day for 5 days. Dengue fever is a viral disease caused by four distinct serotypes, transmitted by mosquitoes in tropical and subtropical countries. It is increasingly diagnosed in febrile travelers. The classic clinical manifestations of dengue fever include severe flu-like symptoms, with high fever lasting 1 to 6 days, headaches, muscle aches, joint pain, and a skin rash (present in 50% of patients, often after the fever). Complications, primarily hemorrhagic, are very rare in travelers. They generally appear on the last day of the fever or the following day and include severe abdominal pain, hypotension, and hemorrhagic manifestations. Individuals who have already had an episode of dengue are at the highest risk of developing complicated forms. The diagnosis of dengue relies on serology (specific IgM detectable from the 5th to 7th day after the onset of fever) and a rapid test for the circulating NS1 antigen, which confirms dengue in the first few days with a sensitivity of approximately 80%. Biologically, thrombocytopenia and leukopenia are most pronounced on the 3rd to 4th day after the onset of fever, and elevated transaminases, sometimes with overt hepatitis, are observed. There is no specific treatment or vaccine for dengue. Management primarily focuses on ensuring adequate hydration. Paracetamol can be prescribed for fever and pain, but NSAIDs (nonsteroidal anti-inflammatory drugs) and especially aspirin should be avoided due to the risk of bleeding.

Viral hemorrhagic fevers: a rare but serious emergency

Viral hemorrhagic fevers, including Ebola, Marburg, Crimean-Congo hemorrhagic fever, and Lassa fever, are extremely rare diagnoses among travelers returning from abroad. However, their potential for person-to-person transmission poses a major health risk, requiring the rapid implementation of specific measures in cases of suspected infection.

Viral hemorrhagic fever should be considered in specific situations:

• Fever accompanied by bleeding (nosebleeds, rectal bleeding, bruises).
• History of contact with a suspected or confirmed case of viral hemorrhagic fever.
• Return from an area where these viruses are prevalent or highly endemic.

The diagnosis in cases of clinical suspicion requires thorough analysis of samples (routine blood tests, serological and molecular biology tests).

The

Vaccinations play a major role in prevention and are tailored to the destination and specific risks:

• Hepatitis A and B: Recommended for many destinations, especially in countries with poor hygiene.
• Typhoid fever: Recommended for travel to Asia, Africa, and Latin America, especially in rural areas or during extended stays. The vaccine is 60–70% effective.
• Yellow fever: Required for some destinations and strongly recommended for others in endemic areas (Africa and South America).
• Meningococcal meningitis: Recommended for pilgrims traveling to Mecca and for those planning extended stays in sub-Saharan Africa.
• Rabies: Recommended for travelers who have been exposed to animals, particularly in Asia and Africa.
• Japanese encephalitis: Recommended for extended stays in rural areas of Asia.
• Tick-borne encephalitis: Recommended for forested areas of Central and Eastern Europe.
• COVID-19: Vaccination is recommended and must be up to date for all international travel.

In addition to vector-borne and waterborne diseases, there are various other risks that require vigilance:

• Parasitic diseases: Some parasitic diseases, such as schistosomiasis, are contracted through contact with contaminated freshwater. It is essential to avoid swimming in stagnant freshwater.
• Contact with animals: Bites, scratches, or even simple contact can transmit diseases (rabies, brucellosis). It is advisable not to approach or feed the animals.
• Accidents and drownings: The leading cause of death and injury among travelers. Caution is advised, especially during sports activities.
• Poisoning and contact with plants: In some areas, there is a risk of snake, scorpion, or venomous insect bites, as well as skin reactions from contact with certain plants.

In summary, although widespread diseases are the most common, it is essential to always rule out malaria in cases of fever following travel to a tropical region. If an initial malaria test is negative after a stay in a high-transmission area, two additional tests must be performed within 24 hours of each other. If the patient exhibits marked deterioration in general condition and malaria has been ruled out, presumptive treatment for enteric fever and possibly rickettsial diseases should be considered. Careful preparation before departure and increased vigilance during and after the trip are the keys to a safe stay and a healthy return.

Source

https://www.hug.ch/sites/interhug/files/2022-09/strategie_fievre_voyage.pdf