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

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.

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Key information

Conditions

Leptospirosis Bacterial Infections Bacterial Infections and Mycoses Gram-Negative Bacterial Infections Infections Inflammation Jarisch Herxheimer Reaction Pathologic Processes Pathological Conditions, Signs and Symptoms Spirochaetales Infections

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

24 ml blood sample at H0

Other

24 ml blood sample at H0

16 ml blood sample at H3

Other

16 ml blood sample at H3

Primary outcomes

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.

Time frame: 3 years

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

Secondary outcomes

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

Time frame: 3 years

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.
Describe and characterise the Leptospira spp. strain

Time frame: 3 years

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.

Sponsors and collaborators

Lead sponsor

Institut Pasteur

Industry

Collaborators

Centre Hospitalier Territorial Gaston- Bourret

Registry information

Acronym: NEUTROLEPTO-NC

Important dates

Study start: 2026
Primary completion: 2029
Study completion: 2029
First posted: May 28, 2026
Registry last updated: May 28, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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