Rapid Molecular Diagnosis and Detection of Emerging Infectious Diseases in Patients With Tropical Fever

Frequently, travelers returning from tropical countries seek medical advice in the emergency department (ED) for acute fever. While the systematic search for malaria is well anchored in clinical practice in France, further diagnostic testing for infectious diseases (ID) is less codified. Besides, the clinical presentation of many tropical and emerging infectious pathologies (EID) is often similar, presenting challenges for a positive diagnosis in those patients.

Indeed, besides testing for malaria all patients with fever and a travel history in tropical regions in the last 3 months, there are, to our knowledge, no French guidelines on the diagnosis strategy of fever in the returning traveler. A few studies have proposed a syndromic testing strategy for patients admitted to ICU, but literature still lacks data on the efficiency of syndromic testing strategies in patients without severity criteria consulting at the ED. Other expert committees and literature on the topic usually recommend to collect a detailed clinical history including nature of travel, relevant activities and exposure, and physical findings, and then prescribe laboratory tests according to each situation. However, this common-sense clinical approach may not be adapted to the peculiar situation of emergency departments where the expertise of clinicians in infectious and tropical diseases may vary and time constraints do not always allow clinicians to collect a detailed history and examination. Moreover, even a careful medical history and physical examination may mislead clinicians in case of atypical clinical presentations or unexpected infections.

A recent study conducted in Spain, Switzerland and Belgium has shown that among travelers with acute undifferentiated febrile illnesses, 132/455 (29.0%) had viral infections, including 108/455 (23.7%) arboviruses, 96/455 (21.1%) malaria and 82/455 (18.0%) bacterial infections. A review of travel-related infections in 103,739 patients consulting in different European clinics between 1998 and 2018 reported an increase in arboviral infections over the last decade, with dengue, chikungunya and zika virus infections being almost as frequent as malaria between 2013 and 2018. A similar percentage of patients presented a viral syndrome with or without rash, in which the etiological agent could not be identified, emphasizing the gaps in our current testing strategy.

The diagnosis of respiratory viruses, including SARS-CoV-2, influenza, and respiratory syncytial virus (RSV), is often overlooked in returning travelers consulting in the emergency department (ED), despite being transmitted either year-long in tropical countries or during the rainy season, concomitantly with malaria. Rickettsial diseases, such as spotted fever or scrub typhus for example, represented 2% of febrile returning travelers in a recent article but are exceptionally sought after in the diagnostic process of patients consulting in the emergency department. Some of these patients with rickettsial diseases had no characteristic eschar. Likewise hemorrhagic fevers and, particularly Lassa fever, whose prevalence has been increasing in recent years in Nigeria are seldomly tested.

It is thus an open question whether a broader and more systematic microbiological laboratory testing strategy could enhance the number of diagnosis and thus the management of patients in this population. Indeed, improving our diagnostic strategy is crucial because the lack of a precise diagnosis in many of these patients prevents the implementation of appropriate diagnostic therapeutic measures. These measures obviously include antimicrobial treatments, but also additional investigations, specialized monitoring, and the initiation of a follow-up of acute or chronic infections. Indeed, the visit in the ED of those febrile travelers represents a unique opportunity to screen for chronic viral infections (such as HIV, hepatitis B and C), as well as acute hepatitis due to HAV or HEV, as this population of travelers is particularly at risk.