Characterizing the Host Response to Leptospirosis for Better Diagnosis and Prognosis - NIHFI (NIHFI)

Leptospirosis is a zoonosis found worldwide, but particularly in humid subtropical and tropical zones. It is caused by pathogenic bacteria of the Leptospira species of the spirochete family. It is estimated that there are over a million cases of leptospirosis worldwide each year, with 60,000 deaths. These figures place leptospirosis among the most dangerous bacterial zoonoses in the world.

The disease affects the most disadvantaged populations, and also inflicts its burden on domestic and farm animals. To this day, however, leptospirosis remains a neglected disease, poorly understood because it has been little studied.

Human leptospirosis initially presents as a febrile syndrome, with fever, headache, myalgia and joint pain. These symptoms are very similar to those observed in influenza, dengue fever and other acute febrile illnesses, making diagnosis very difficult.

Delayed initiation of antibiotic therapy, a treatment recommended by the WHO, is associated with the development of severe forms of leptospirosis. Indeed, in 10% of cases, leptospirosis evolves into severe forms, which are still poorly described, but which result in haemorrhage, multivisceral failure (lungs, kidneys, liver) and a drastic increase in the case-fatality rate. In 2023, 152 cases of leptospirosis were reported in New Caledonia. Of these, 130 people (85%) were hospitalized and 4 deaths were recorded (2.6%).

For patients suffering from leptospirosis, it is therefore important to be able to make the diagnosis quickly, ideally as soon as symptoms appear. It is also crucial to be able to monitor, or even prevent, the development of severe forms of the disease, to ensure optimal patient care.

Study Overview

• Status: Not yet recruiting
• Conditions: Leptospirosis
• Intervention / Treatment: Other: Blood sample; Other: Urine Sample

Detailed Description

The goal of this study is to identify diagnostic and prognostic biomarkers based on host response to human leptospirosis in New Caledonia. To achieve this goal, Individuals coming to the emergency department of the Centre Hospitalier Territorial de Nouvelle-Calédonie will be recruited either with suspected leptospirosis with signs and symptoms or healthy showing no infectious signs.

For febrile patients with confirmed (group 1) or refuted (group 2) diagnosis of leptospirosis:

• At D0: a 20-ml blood sample and a 5-ml urine sample
• At D1, D3 and D15: a 20-ml blood sample

For healthy patients (group 3):

• At D0: a 20-ml blood sample and a 5-ml urine sample
• At D15: a 20-ml blood sample.

The analyses to be carried out are :

• Host-pathogen sequencing,
• Metagenomics,
• Transcriptomics,
• Metabolomics,
• And cytokine assays to study the host immune response.

• Study Type: Interventional
• Enrollment (Estimated): 450
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Anne Loarec, MD; Phone Number: +687 90 86 21; Email: anloarec@pasteur.nc
• Study Contact Backup: Name: Frédéric Veyrier, PhD; Phone Number: +687 273634; Email: fveyrier@pasteur.nc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

For all participants :

• Be able to consent,
• Have received information and given written consent,
• Be covered by a social security plan. For groups 1 & 2: febrile individuals
• Have suspected leptospirosis associated with fever (axillary temperature over 38°C) and a clinical picture of suspected leptospirosis (myalgia, headache...). After inclusion, febrile participants will be divided into 2 groups when the diagnosis of leptospirosis is confirmed. The 2 groups are defined as follows:

Group 1: leptospirosis

- Individual with leptospirosis confirmed by PCR, MAT, or isolation (2013 Center For Disease Control and Prevention (CDC) laboratory criteria for a confirmed diagnosis).

Group 2: MFA, with absence of leptospirosis

All individuals in Group 2 will have tests as part of their MFA diagnosis, depending on their symptomatology:

• Other acute bacterial zoonotic infection: Infection confirmed by paired serology or double PCR (2 targets).
• Acute arboviral infection: dengue, chikungunya or Zika virus confirmed by CDC Trioplex PCR in a patient with consistent serology or positive 2nd target PCR.
• Acute respiratory viral infection: Viral agent confirmed by MFA multiplex PCR. For group 3: healthy individuals
• Apyretic individuals, no symptoms of infection or inflammatory disease in the last 28 days.

Exclusion Criteria:

individuals :

• with a chronic inflammatory disease,
• undergoing concomitant antibiotic and/or anti-inflammatory treatment, or under medical care incompatible with the purpose of the study,
• pregnant or breast-feeding women,
• persons deprived of their liberty by a judicial or administrative decision, persons under psychiatric care and persons admitted to a health or social institution,
• Adults subject to a legal protection measure or unable to express their consent
• Persons not affiliated to a social security scheme or beneficiaries of such a scheme
• Hospitalized for more than 48 hours,
• Hospitalized or operated on in the previous 7 days.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Individuals coming to the emergency department of the CHT; Individuals coming to the emergency department of the Centre Hospitalier Territorial de New Caledonia: Either with suspected leptospirosis with signs and symptoms; Or healthy and coming for a traumatology and orthopedics consultation, and showing no infectious signs.	Other: Blood sample; For febrile patients with confirmed (group 1) or refuted (group 2) diagnosis of leptospirosis: - At D0, D1, D3 and D15 a 20-ml blood sample For healthy patients (group 3): - At D0 and D15: a 20-ml blood sample; Other: Urine Sample; For all participants, a 5-ml urine sample at D0

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identify diagnostic and prognostic biomarkers based on host response to human leptospirosis in New Caledonia.	transcriptome study by sequencing host mRNA at different times, in the blood and urine of individuals suspected of having leptospirosis	4 years
Identify diagnostic and prognostic biomarkers based on host response to human leptospirosis in New Caledonia.	level of cytokines present at different times, in the blood and urine of individuals suspected of having leptospirosis	4 years
Identify diagnostic and prognostic biomarkers based on host response to human leptospirosis in New Caledonia.	identification of the Leptospira spp. serogroup by sequencing bacterial DNA or PCR at different times, in the blood and urine of individuals suspected of having leptospirosis	4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Develop and validate biomarkers that have already been identified for accurate diagnosis of leptospirosis of varying clinical severity.	Transcriptome study using host mRNA sequencing	4 years
Develop and validate biomarkers that have already been identified for accurate diagnosis of leptospirosis of varying clinical severity.	Level of cytokines or other markers previously identified as biomarkers of severity.	4 years

Collaborators and Investigators

• Sponsor: Institut Pasteur
• Collaborators: Centre Terrritorial Hospitalier Gaston Bourret
• Investigators: Study Director: Frédéric Veyrier, PhD, Institut Pasteur de Nouvelle-Calédonie; Principal Investigator: Cécile Cazorla, MD, Centre Hospitalier Territorial Gaston-Bourret

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2025
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): July 1, 2029

Study Registration Dates

• First Submitted: April 18, 2025
• First Submitted That Met QC Criteria: April 18, 2025
• First Posted (Actual): April 25, 2025

Study Record Updates

• Last Update Posted (Actual): April 25, 2025
• Last Update Submitted That Met QC Criteria: April 18, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: biomarkers; infection; New Caledonia
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Negative Bacterial Infections; Spirochaetales Infections; Leptospirosis; Weil Disease
• Other Study ID Numbers: 2024-077; 2024-A02827-40 (Other Identifier: ID-RCB)

Drug and device information, study documents

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