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 (NEUTROLEPTO-NC)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Leptospirosis; Jarisch Herxheimer Reaction
• Intervention / Treatment: Other: 24 ml blood sample at H0; Other: 16 ml blood sample at H3

Detailed Description

The aim of the study is to compare the immune cell responses in the blood of patients hospitalized for leptospirosis with those of patients with another infection, before and 3 hours after antibiotic therapy.

Individuals presenting to the emergency department of the Territorial Hospital Center of New Caledonia with signs and symptoms of leptospirosis will be recruited:

-with a confirmed diagnosis of leptospirosis (Group 1),-

-with an infectious diagnosis other than leptospirosis (Group 2)

Blood and clinical data will be collected from all the participants.

• Study Type: Observational
• Enrollment (Estimated): 70

Participation Criteria

Eligibility Criteria

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

• 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:

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Individuals with symptoms of leptospirosis with a confirmed diagnosis of leptospirosis	Other: 24 ml blood sample at H0; 24 ml blood sample at H0; Other: 16 ml blood sample at H3; 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; 24 ml blood sample at H0; Other: 16 ml blood sample at H3; 16 ml blood sample at H3

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Test certain innovative host-based strategies aimed at restoring phagocytic responses against Leptospira in the blood of patients with leptospirosis.response.	Conduct ex vivo killing assays using patient blood in the presence of preparations based on so-called "natural" immunoglobulins to test a new host-targeted therapeutic strategy against leptospirosis.	3 years
Describe and characterise the Leptospira spp. strain	Measurement of bacterial load by PCR of the lipl32 gene, identification of the Leptospira spp. genogroup by bacterial DNA sequencing or other molecular biology methods (PCR) and/or of the serovar by MAT, sequencing of the bacterial mRNA.	3 years

Collaborators and Investigators

• Sponsor: Institut Pasteur
• Collaborators: Centre Hospitalier Territorial Gaston- Bourret

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): July 1, 2029

Study Registration Dates

• First Submitted: May 21, 2026
• First Submitted That Met QC Criteria: May 21, 2026
• First Posted (Actual): May 28, 2026

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Inflammation; leptospirosis; Jarisch Herxheimer Reaction; ß-lactams antibiotics
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Negative Bacterial Infections; Spirochaetales Infections; Pathological Conditions, Signs and Symptoms; Inflammation; Leptospirosis
• Other Study ID Numbers: 2025-146 (Ethics Committee of Shanghai Sixth People's Hospital); 2025-A02688-41 (Other Identifier: ID-RCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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