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

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.

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.

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