Fever Upon Return 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 upon return from a tropical trip is the second most common reason for consultation among travelers, accounting for 23% of cases, just after digestive disorders (42%) and before dermatological 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 can be suspected even in patients who have 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 about the 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 of 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 a fever upon returning from a trip is broken down into four fundamental steps, allowing for an accurate diagnosis and ensuring appropriate management. First, it is necessary to consider common infections, that is, those not specifically related to tropical travel, 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 spectrum of infections to consider when faced with a fever upon 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 manifest as a fever, often accompanied by less specific 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: essential clues for diagnosis

• Where did the patient travel? It is important to know which countries were visited and whether they were cities 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? The traveler's medical history can influence susceptibility to certain infections.
• How was the trip? This part of the medical history is particularly rich in clues:
  • Swimming or rafting: May point towards schistosomiasis or leptospirosis.
  • Food consumed: Ingestion of unpasteurized milk may suggest brucellosis, while raw meat may indicate trichinellosis. Contaminated food and water are a very common and nonspecific mode of transmission for many germs.
  • 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.
  • Riskful sexual contact or blood contact (dentist, tattoo): May suggest HIV or hepatitis B infection.
  • Vaccinations received: Knowing vaccination status (hepatitis A, hepatitis B, typhoid fever, yellow fever) is important, given that 3% of post-travel febrile illnesses are preventable 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), rickettsioses, typhoid fever or borreliosis. 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 amebic abscess, flukes (fasciola), a Leishmaniasis or malaria.
• Splenomegaly: Frequent in malaria, leishmaniasis, and enteric fever.
• Neurological signs: Involve serious pathologies such as meningitis, encephalitis, trypanosomiasis, or malaria.

Paraclinical examinations: confirming the diagnosis

Paraclinical examinations are essential to confirm the etiological diagnosis of a febrile state upon return from travel. A baseline assessment should be performed for each patient, supplemented by additional tests depending on clinical suspicion or initial results.

The baseline assessment includes:

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

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

• Stool examination (leukocyte count, parasite screening, culture) in case of digestive problems.
• Blood cultures to identify bacteria, particularly in cases of suspected enteric fever.
• Specific viral and/or bacterial serology for infections such as arboviruses (dengue, chikungunya), rickettsioses, leptospirosis, amoebiasis, HIV, 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 after a stay in a tropical region.
• PCR (polymerase chain reaction) tests for the direct detection of pathogens, for example, for Zika or Ebola.
• A urine culture.
• A lumbar puncture in case of neurological involvement (suspected meningitis or encephalitis).
• A chest X-ray or ultrasound 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 helminthiasis 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 precise medical history is crucial for malaria: Country visited: Three-quarters of cases diagnosed in Switzerland are contracted in Africa, where Plasmodium falciparum is responsible for 85% of cases. In Asia and Latin America, P. falciparum is responsible 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 ongoing.

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.

Hospitalization criteria 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, 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 severity 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 (G6PDH deficiency, pregnancy). loading="lazy">

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

Beyond malaria, other tropical illnesses are frequently encountered and require specific management. Among them, enteric fever, amoebic liver abscess, and dengue fever are particularly noteworthy.

Enteric fever (typhoid or paratyphoid)

The risk of enteric fever exists for travelers in all developing countries, but it is particularly high in South Asia (e.g., India, Nepal). Vaccination (Vivotif® or TyphimVi®) offers 60 to 70% efficacy. Typical clinical manifestations include fever, pulse-temperature dissociation, constipation or diarrhea, a dry cough, and abdominal pain. The cardinal 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 normal or decreased white blood cell count, and C-reactive protein (CRP) is elevated. It is important to note that serology is considered unnecessary for diagnosis. The management varies depending on the patient's general condition: If the general condition is poor or in case 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 1g 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 Hepatic Abscess

Amoebic hepatic abscess most often presents without associated colonic involvement and has a marked male predominance. The main clinical manifestations are right upper quadrant pain and hepatomegaly. A pleuropulmonary syndrome with right lower lobe involvement 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 examinations that reveal the presence of the 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 are those of 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 (non-steroidal 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 upon return from travel. However, their potential for person-to-person transmission represents a major health risk, requiring the rapid implementation of specific measures in case of suspicion.

Viral hemorrhagic fever should be considered in well-defined situations:

• Presence of a fever associated with hemorrhages (nosebleeds, rectal bleeding, hematomas).
• History of contact with a suspected or confirmed case of viral hemorrhagic fever.
• Return from an epidemic or highly endemic area for these viruses.

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

The

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

• Hepatitis A and B: Recommended for many destinations, especially in countries with poor hygiene.
• Typhoid fever: Recommended for stays in Asia and Africa and in Latin America, especially in rural areas or during extended stays. The effectiveness is 60-70%.
• Yellow fever: Mandatory 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 extended stays in sub-Saharan Africa.
• Rabies: Recommended for travelers exposed to animals, particularly in Asia and Africa.
• Japanese encephalitis: Recommended for extended rural stays in Asia.
• Tick-borne encephalitis: Recommended for forested areas of Central and Eastern Europe.
• COVID-19 : La vaccination est recommandée et doit être à jour pour tout voyage international.

Au-delà des maladies vectorielles et hydriques, d'autres risques divers existent et nécessitent une vigilance :

• Parasitoses : Certaines parasitoses, comme la schistosomiase, sont contractées par contact avec l'eau douce contaminée. Il est essentiel d'éviter la baignade en eau douce stagnante.
• Contacts avec des animaux : Morsures, griffures ou simples contacts peuvent transmettre des maladies (rage, brucellose). Il est conseillé de ne pas approcher ni nourrir les animaux.
• Accidents et noyades : Première cause de mortalité et de morbidité chez les voyageurs. La prudence est de mise, notamment lors des activités sportives.
• Envenimations et contacts végétaux : Certaines zones présentent des risques de morsures de serpents, scorpions ou d'insectes venimeux, ainsi que des réactions cutanées au contact de certaines plantes.

En résumé, bien que les maladies cosmopolites soient les plus fréquentes, il est impératif d'écarter toujours le paludisme en cas de fièvre au retour d'un voyage tropical. En présence d'une première recherche de paludisme négative après un séjour dans une zone de forte transmission, deux recherches supplémentaires à moins de 24 heures d'intervalle sont nécessaires. Si le patient présente une altération marquée de l'état général et que le paludisme est exclu, il convient de discuter un traitement présomptif contre la fièvre entérique et éventuellement les rickettsioses. Une préparation minutieuse avant le départ et une vigilance accrue pendant et après le voyage sont les clés d'un séjour sûr et d'un retour en bonne santé.

Source

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