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.
Study Type
OBSERVATIONAL
Enrollment
70
24 ml blood sample at H0
16 ml blood sample at H3
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
Time frame: 3 years
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.
Time frame: 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.
Time frame: 3 years
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