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

Trial statusNot yet recruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18+
SponsorInstitut Pasteur

About this trial

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.

Eligibility criteria

Qualifiers

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.

Disqualifiers

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.

Trial design

Treatments tested in this trial

  • 24 ml blood sample at H0
  • 16 ml blood sample at H3

Treatment groups

70 Participants
are divided into 2 treatment groups

Locations

This trial has no locations

Sponsors and collaborators

Institut Pasteur

Lead sponsor

Centre Hospitalier Territorial Gaston- Bourret

Collaborator