Ex Vivo Study of Leukocyte Responses in the Blood of Patients With Leptospirosis and ex Vivo Testing of a New Host-targeted Therapeutic Strategy to Restore Phagocytosis of Leptospira

NCT07611591 | Not Yet Recruiting

• 2 other identifiers: 2025-1462025-A02688-41
• Study Type: observational
• Target: 70
• Locations: 0 countries
• Sites: N/A

Brief Summary

Leptospirosis is a neglected zoonosis caused by pathogenic spirochetes of the genus \*Leptospira\*, occurring mainly in humid tropical and subtropical regions. With over one million cases and \~60,000 deaths annually, it is among the most dangerous bacterial zoonoses worldwide. Its nonspecific onset-fever, headache, myalgia-mimics influenza, dengue, and other acute febrile illnesses, making diagnosis difficult. Delayed antibiotic treatment can lead to severe forms (in \~10% of cases) characterized by hemorrhage and multi-organ failure. In 2023, New Caledonia reported 152 cases, with 85% hospitalized and a 2.6% mortality rate. This study aims to characterize the human host response and improve patient management. \*Leptospira\* evades innate immunity, triggering a strong anti-inflammatory IL-10 response and potentially ineffective phagocytosis. However, the WHO-recommended β-lactam antibiotics induce a Jarisch-Herxheimer reaction (JHR)-an acute inflammatory response occurring within hours of treatment-in over 50% of patients (LEPJAR study, PMID:40986630), the impact of which on phagocytosis is unknown.The NEUTROLEPTO study will be conducted in New Caledonia (NC) in patients with or without leptospirosis. Clinical and biological data will be collected at the time of suspected infection and 3 hours after antibiotic administration. Specifically, immune responses will be assessed through cytokine profiling and blood cell phenotyping, as well as by transcriptome analysis of infected patients before and after antibiotic treatment.

Conditions

Leptospirosis; Jarisch Herxheimer Reaction

Keywords

leptospirosis; Jarisch Herxheimer Reaction; Inflammation; ß-lactams antibiotics

Outcome Measures

Primary Outcomes (1)

• to compare the immune cell responses in the blood of patients hospitalized for leptospirosis with those of patients with another acute infection (MFA), both before and 3 hours after antibiotic treatment.

  Flow cytometric phenotyping of different cell populations, as well as their activation markers and intracellular cytokines and measurement of cytokines using ELISA or LUMINEX in the blood (H0 at enrollment and H3, 3 hours after antibiotic administration) of individuals suspected of having leptospirosis

  3 years

Secondary Outcomes (2)

• Test certain innovative host-based strategies aimed at restoring phagocytic responses against Leptospira in the blood of patients with leptospirosis.response.

  3 years

• Describe and characterise the Leptospira spp. strain

  3 years

Study Arms (2)

Individuals with symptoms of leptospirosis with a confirmed diagnosis of leptospirosis

Other: 24 ml blood sample at H0; Other: 16 ml blood sample at H3

Individuals with symptoms of leptospirosis with a diagnosis of an infection other than leptospirosis

Other: 24 ml blood sample at H0; Other: 16 ml blood sample at H3

Interventions

24 ml blood sample at H0 OTHER

24 ml blood sample at H0

Individuals with symptoms of leptospirosis with a confirmed diagnosis of leptospirosis; Individuals with symptoms of leptospirosis with a diagnosis of an infection other than leptospirosis

16 ml blood sample at H3 OTHER

16 ml blood sample at H3

Individuals with symptoms of leptospirosis with a confirmed diagnosis of leptospirosis; Individuals with symptoms of leptospirosis with a diagnosis of an infection other than leptospirosis

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: 50% male and 50%female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Individuals presenting at the emergency department of the Territorial Hospital Center of New Caledonia with signs and symptoms of leptospirosis:

You may qualify if:

• Be of legal age (18 years or older at the time of enrollment),
• Be capable of understanding and providing informed consent,
• Have received information and provided written consent,
• Be enrolled in a social security program.
• Be suspected of having leptospirosis

You may not qualify if:

• With a chronic inflammatory disease,
• Whose health condition is incompatible with additional blood draws totaling 40 ml,
• Receiving concomitant treatment with antibiotics and/or anti-inflammatory drugs, or undergoing medical treatment incompatible with the study's objectives,
• Pregnant or breastfeeding women.
• Hospitalized or having undergone surgery within the previous 7 days

Sponsors & Collaborators

• Institut Pasteur: lead
• Centre Hospitalier Territorial Gaston- Bourret: collaborator

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood sample

MeSH Terms

Conditions

Leptospirosis; Inflammation

Condition Hierarchy (Ancestors)

Spirochaetales Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 21, 2026
• First Posted: May 28, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): July 1, 2029
• Last Updated: May 28, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share