The Interest of Systematic Screening for Dengue, Chikungunya, and Zika, in Malaria-negative Return Travelers

Interest of Systematic Screening for Dengue, Chikungunya, and Zika, in Patients for Whom a Malaria Diagnosis is Negative, in the Event of a Recent Return From Travel: a Retrospective Study at the University Hospitals of Strasbourg, 2024-2025

International travel has increased dramatically in recent years. Vector-borne pathologies such as malaria and arboviruses are common etiologies of post-travel fever, which are prevalent in similar geographical areas (tropical and intertropical). Arboviruses, for "arthropod-borne viruses," are transmitted by the bite of blood-sucking vectors (mosquitoes, ticks, or sandflies). The dengue, chikungunya, and zika viruses are transmitted through the bite of an infected Aedes mosquito (Aedes aegypti and Aedes albopictus).

The establishment of Aedes albopictus (tiger mosquito), competent for transmitting these 3 viruses, since 2004 in mainland France and the transit of travelers carrying a virus allowed the appearance of the first autochthonous cases of dengue and zika. Each year, outbreaks of autochthonous cases of dengue fever are reported in the PACA, Occitanie, and Auvergne-Rhône Alpes regions, and a cluster of 3 Indigenous cases was reported in 2023 in the Paris region.

Since 2014, the tiger mosquito has been established in Bas-Rhin. Between 2014 and 2022, the vector was detected in around thirty municipalities around Strasbourg. In a department where the spread of the tiger mosquito is evolving rapidly, these data remind us that only an early diagnosis, delivered quickly, allows effective vector control measures to avoid generating autochthonous transmission.

In a previous study carried out at the Virology laboratory, we retrospectively analyzed the diagnosis of these 3 arboviruses after the exclusion of malaria in the context of recent travel over a period of 10 years (2014-2023). Among the 913 patients included, for 78% of cases (n=714), no testing for dengue, chikungunya, or zika was carried out, a proportion stable over 10 years.

These three arboviruses seem underdiagnosed, and we assume, given our previous results, that 8 to 10% of patients for whom, in the context of recent travel, a test for malaria comes back negative are imported cases of dengue, chikungunya, or zika. At the end of this retrospective study, we want to evaluate this sub-diagnosis on a larger sample to propose a review of practices and the establishment of Arbovirus-malaria "reflex testing." Currently, no French or similar European data is available, allowing us to evaluate this under-diagnosis, which constitutes a significant risk of the emergence of indigenous clusters in our territory.

The main objective of this study is to determine the infection rate by dengue, chikungunya, and zika viruses identified when the diagnosis is made after the exclusion of negative malaria in the context of recent travel among patients treated at the Strasbourg University Hospitals between January 1, 2024, and December 31, 2025.

The secondary objectives of this work are as follows:

Estimate the prevalence of different clinical symptoms (patient medical records) in retrospectively identified cases of dengue, chikungunya, and zika.

• Evaluate the onset time of symptoms in relation to the date of return/arrival from the area of stay of retrospectively identified cases of dengue, chikungunya, and zika.
• Evaluate the delay in the appearance of symptoms in relation to the date of taking the initial sample (the one leading to the diagnosis of negative malaria) of retrospectively identified cases of dengue, chikungunya, and zika.
• Study the laboratory results associated with the initial management of the patient (biochemical assessment and blood count) of retrospectively identified cases of dengue, chikungunya, and zika.
• Study the distribution of areas, periods, and reasons for staying in retrospectively identified dengue, chikungunya, and zika cases.

Study the municipalities of residence of positive cases in the areas where the tiger mosquito is established.

Study Overview

• Status: Active, not recruiting
• Conditions: Arbovirus Infections
• Intervention / Treatment: Biological: The retrospective analyses planned for these samples consist of serological analysis and molecular analysis (RT-PCR ) according to the date of symptoms ons

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

Study Locations

• France
  • Strasbourg, France, 67 000
    • Hôpitaux Universitaires de Strasbourg - Laboratoire de Virologie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Any person, man or woman, aged over 18, treated at the University Hospitals of Strasbourg from January 2024 to December 2025, having received a blood sample as part of the treatment, for a diagnosis of malaria upon return from a recent trip whose result was negative. Any person who has already consented or has not objected to their biological resources being preserved in the "Microbiology" biocollection and reused for scientific research.

Description

Inclusion criteria:

• Adult subject (≥18 years old), man or woman
• Supported at Strasbourg University Hospital between 01/01/2024 and 12/31/2025
• Having received a blood sample as part of the treatment for which the test for malaria was negative, following a recent return from a trip (≤ 31 days)
• Having already given their consent for their biological resources to be preserved in the "Microbiology" biocollection and reused for scientific research purposes.

Exclusion criteria:

• Minor subject (< 18 years old)
• Adult patient for whom a test for malaria came back positive during initial treatment
• Patient having expressed his opposition to participating in the study
• Inability to provide the subject with informed information (subject in an emergency situation, difficulty understanding the subject, etc.)
• Subject under judicial protection
• Subject under guardianship or curatorship

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Malaria negative return travelers; Any person, man or woman, aged over 18, treated at the University Hospitals of Strasbourg from January 2024 to December 2025, having received a blood sample as part of the treatment, for a diagnosis of malaria upon return from a recent trip whose result was negative. Any person who has already consented or has not objected to their biological resources being preserved in the "Microbiology" biocollection and reused for scientific research.

Biological: The retrospective analyses planned for these samples consist of serological analysis and molecular analysis (RT-PCR ) according to the date of symptoms ons; Serological tests detecting IgM and IgG

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The detection rate of dengue virus, zika virus, or chikungunya virus infection in samples from the subjects studied.	Patients and samples will be selected based on diagnostic activity data from the Medical Mycology Parasitology laboratory. The corresponding production statistics will be produced using the laboratory information system (LIS), glims software from 01/01/2024 to 12/31/2025. The retrospective analyses planned for these samples will all be carried out within the microbiology technical platform by the Virology laboratory without any sample transfer. Serological tests detecting IgM and IgG will be carried out using the following commercial ELISA kits: Vidas® Anti-chikungunya IgM and IgG; Vidas® Anti-dengue IgM and IgG; Virclia® Anti-Zika IgM and IgG NS1 antigen detection will be carried out using the Abbott® Bioline Dengue duo test. RT-PCR will be carried out using the following kits: EVAg Primers, Probes (Lyoph-P&P) and Positive control for dengue virus detection, chikungunya virus detection and zika virus detection (adapted to Hologic PantherFusion OpenAccess).	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Distribution of the clinical symptoms and the biological findings	To estimate the prevalence of different clinical symptoms (patient medical records) in retrospectively identified cases of dengue, chikungunya and zika.	36 months

Collaborators and Investigators

• Sponsor: University Hospital, Strasbourg, France

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2025
• Primary Completion (Actual): August 1, 2025
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: October 17, 2024
• First Submitted That Met QC Criteria: October 17, 2024
• First Posted (Actual): October 21, 2024

Study Record Updates

• Last Update Posted (Actual): August 8, 2025
• Last Update Submitted That Met QC Criteria: August 4, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Dengue; Chikungunya; Post-travel infections; Zika disease; Arbovirus screening
• Additional Relevant MeSH Terms: Vector Borne Diseases; Mosquito-Borne Diseases; Infections; RNA Virus Infections; Virus Diseases; Protozoan Infections; Parasitic Diseases; Flavivirus Infections; Flaviviridae Infections; Hemorrhagic Fevers, Viral; Alphavirus Infections; Togaviridae Infections; Malaria; Dengue; Chikungunya Fever; Arbovirus Infections
• Other Study ID Numbers: IV-0198

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No