Jarisch Herxheimer Reaction, Leptospirosis
Conditions
Keywords
leptospirosis, Jarisch Herxheimer Reaction, Inflammation, ß-lactams antibiotics
Brief summary
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.
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.
Interventions
OTHER24 ml blood sample at H0
24 ml blood sample at H0
OTHER16 ml blood sample at H3
16 ml blood sample at H3
Sponsors
Institut Pasteur
Centre Hospitalier Territorial Gaston- Bourret
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 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
| Measure | Time frame | Description |
|---|---|---|
| Test certain innovative host-based strategies aimed at restoring phagocytic responses against Leptospira in the blood of patients with leptospirosis.response. | 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 | 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. |
Outcome results
None listed