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

NCT ID: NCT06945822

Last Updated: 2025-04-25

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 450 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-06-01
• Study Completion Date: 2029-07-01

Brief Summary

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.

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.

Conditions

Leptospirosis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

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.

Group Type: OTHER

Blood sample

Intervention Type: OTHER

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

Urine Sample

Intervention Type: OTHER

For all participants, a 5-ml urine sample at D0

Interventions

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

Intervention Type: OTHER

Urine Sample

For all participants, a 5-ml urine sample at D0

Intervention Type: OTHER

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Centre Terrritorial Hospitalier Gaston Bourret

UNKNOWN

Sponsor Role: collaborator

Institut Pasteur

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Frédéric Veyrier, PhD

Role: STUDY_DIRECTOR

Institut Pasteur de Nouvelle-Calédonie

Cécile Cazorla, MD

Role: PRINCIPAL_INVESTIGATOR

Centre Hospitalier Territorial Gaston-Bourret

Central Contacts

Anne Loarec, MD

Role: CONTACT

anloarec@pasteur.nc

+687 90 86 21

Frédéric Veyrier, PhD

Role: CONTACT

fveyrier@pasteur.nc

+687 273634

Other Identifiers

2024-A02827-40

Identifier Type: OTHER

Identifier Source: secondary_id

2024-077

Identifier Type: -

Identifier Source: org_study_id