Mathieu Picardeau

About

Leptospirosis is a zoonotic bacterial disease found predominantly in impoverished populations inhabiting developing countries with tropical climates. Rodents are the main reservoir of the disease, excreting the bacteria in their urine. Humans are usually infected through contaminated water. Leptospirosis is estimated to cause more than one million severe cases with approximately 60,000 deaths per year. It is an emerging disease due to the growing number of inhabitants residing in urban slums and the increased frequency of extreme climatic events. Leptospirosis also affects animals worldwide, including livestock, and is therefore of economic importance. All control methods for leptospirosis implemented to date have been ineffective. The critical barrier to developing any effective interventions has been the limited understanding of pathogenesis of the disease. The “Biology of Spirochetes” Unit comprises the french National Reference Center for Leptospirosis and the WHO Collaborating Center for Research and Reference on Leptospirosis. The main missions of the NRC are to develop and improve diagnostic techniques, to perform epidemiological investigations, and to conduct the surveillance of leptospirosis in mainland France and in the French overseas territories (Martinique, Guadeloupe, Mayotte, etc). In mainland France, approximately 700 cases are diagnosed each year. In french overseas territories (New Caledonia, Martinique, Guadeloupe, Mayotte, La Réunion, French Polynesia, French Guyana), the incidence rate can be more than one hundred times that for mainland France. Since August 2023, confirmed and probable leptospirosis cases must be reported to the ARS (Agence Régionale de Santé) . Early laboratory diagnosis of leptospirosis is important to provide appropriate treatment of patients and to take rapid measures in case of an outbreak. Unfortunately, leptospirosis is often diagnosed late, due to its wide spectrum of symptoms, ranging from a flu-like syndrome to renal failure. The symptoms mimic the clinical presentations of many other diseases, including dengue fever and malaria. In addition, most cases of leptospirosis are currently detected by means of a complex and fastidious serological test, but antibodies are generally not detectable in the blood until about one week after the onset of symptoms. We developed an in-house ELISA with formalin-treated and boiled bacteria from the intermediate species Leptospira fainei as an antigen to detect Leptospira-specific IgM antibodies. Compared with positive and negative sera, the ELISA showed 94% sensitivity and 99% specificity. We also evaluated a prototype point of care strip test by using the same antigen for the serological diagnosis of leptospirosis in New Caledonia, mainland France, and the French West Indies. The sensitivity was 89.8% and the specificity 93.7%. The NRC for Leptospirosis is accredited to ISO 15189 standard since 2014 for the serological techniques (MAT and IgM ELISA). The NRC has access to a large collection, which is regularly enriched, of Leptospira strains from different origins. To advance our understanding of the biodiversity of Leptospira strains at the global level, we recently developed a core genome MLST (cgMLST) genotyping scheme applicable to the entire Leptospira genus. A database of cgMLST alleles was set-up and was made publicly accessible online (https://bigsdb.pasteur.fr/leptospira/) allowing for comparison and sharing of typing results among laboratories worldwide. Using this approach, we characterized the Leptospira strains circulating in several endemic countries including Cuba, Costa-Rica, Laos, and Sri-Lanka. We showed the existence of more than 40 new Leptospira species. We also applied Targeted genome capture (TGC) using L. interrogans oligonucleotide probes to enrich specific Leptospira nucleic acids in clinical samples isolated from patients having leptospirosis thus overcoming the time-consuming cultivation steps (more than 4 weeks of incubation are usually required).