When Leptospirosis Attacks the Nervous System: New Evidence From French Guiana

Leptospirosis, a bacterial infection transmitted through water contaminated with animal urine, is best known for attacking the kidneys and liver. But in French Guiana, an overseas territory of France wedged between Brazil and Suriname on the northeastern edge of South America, physicians have long suspected that the disease can also reach the nervous system. A new retrospective study published in PLOS Neglected Tropical Diseases now offers the most detailed picture yet of this poorly understood presentation, which researchers call neuroleptospirosis, and suggests that it may be both more common and more benign than clinicians have assumed.

The research team, led by Audrey Delahaye and colleagues working across healthcare facilities in French Guiana, analyzed the records of 146 consecutive patients hospitalized with laboratory-confirmed or probable leptospirosis between 2015 and 2021. Because there has never been an agreed-upon definition of neurological leptospirosis, the investigators set a deliberately strict threshold: patients qualified only if they showed neurological symptoms together with objective abnormalities in the cerebrospinal fluid, the clear liquid bathing the brain and spinal cord, or on neuroimaging. This conservative approach was designed to separate true invasion of the central nervous system from the headache and confusion that can accompany severe systemic infection without direct brain involvement.

Using these criteria, the team identified 18 cases of neuroleptospirosis among the 146 patients, or roughly 12 percent of the cohort. That figure translates into a mean annual incidence of 0.88 cases per 100,000 inhabitants, with a 95 percent confidence interval ranging from 0.52 to 1.39. In a population of fewer than 300,000 people, this makes neuroleptospirosis a rare but persistent feature of the local epidemic landscape, one that emergency physicians and intensivists in the territory are likely to encounter every year.

The clinical spectrum fell into three recognizable patterns. The overwhelming majority of cases, 14 of 18 patients or 78 percent, presented as meningitis, an inflammation of the membranes covering the brain that typically produces fever, severe headache, and neck stiffness. Three patients, or 17 percent, developed encephalitis, in which the brain tissue itself becomes inflamed, while a single patient, about 6 percent, showed a combined meningoencephalitic picture. This distribution mirrors what has been reported anecdotally in other tropical settings, but the French Guiana study is among the first to quantify it systematically in an Amazonian context.

The laboratory findings offer important clues about how the disease behaves when it reaches the nervous system. Lumbar puncture, the procedure used to sample cerebrospinal fluid, was performed in only 28 of the 146 patients, reflecting how rarely clinicians suspect neurological involvement in leptospirosis. Yet among those who underwent the procedure, pleocytosis, an abnormal rise in white blood cells within the fluid, was detected in 64 percent of cases. The median leukocyte count in the cerebrospinal fluid was 42 cells per cubic millimeter, with an interquartile range of 13 to 240, and when differential counts were available, lymphocytes dominated in 62 percent of samples. Protein levels were only mildly elevated, with a median of 0.51 grams per liter, and, critically, glucose concentrations remained normal, a pattern the researchers describe as the absence of hypoglycorrhachia.

That combination, a modest lymphocytic pleocytosis with mild protein elevation and preserved glucose, is a signature that overlaps with viral meningitis rather than with bacterial pyogenic infection. For clinicians working in endemic areas, the implication is that neuroleptospirosis can masquerade as a viral central nervous system infection, and that a history of exposure to freshwater, mud, or rodents in the weeks before symptom onset should prompt consideration of leptospirosis even when the cerebrospinal fluid profile looks benign. Brain magnetic resonance imaging, performed in eight of the neuroleptospirosis patients, revealed abnormalities in only two: one cerebral infarction, suggesting that the infection can occasionally compromise blood vessels in the brain, and one case of pachymeningitis, an inflammation of the dura mater, the tough outer membrane surrounding the brain.

Perhaps the most striking findings of the study concern who develops neurological involvement and what happens to them. Statistical analysis identified three factors independently associated with neuroleptospirosis. Patients younger than 30 years had more than five times the odds of neurological involvement compared with older patients, with an odds ratio of 5.56 and a confidence interval of 1.72 to 18. The absence of leukocytosis, an elevated white blood cell count in the blood during hospitalization, nearly tripled the odds, with an odds ratio of 3.29, and the absence of thrombocytopenia, a low platelet count, more than quadrupled them, with an odds ratio of 4.46. In other words, neuroleptospirosis tended to strike younger patients whose systemic inflammatory response was comparatively muted.

This profile carries a paradoxical message. Leptospirosis is notorious for its most severe forms, including Weil disease, a fulminant syndrome of jaundice, kidney failure, and hemorrhage that can kill even previously healthy adults. Yet the patients in this study whose infection reached the nervous system fared better than their counterparts with purely systemic disease. Neuroleptospirosis was associated with significantly lower odds of sepsis, with an odds ratio of 0.28, and none of the 18 neurological cases required admission to the intensive care unit or resulted in death. Under the diagnostic criteria applied by the researchers, neuroleptospirosis emerged as a presentation associated with favorable outcomes, a finding that should reassure clinicians but also caution them against assuming that neurological symptoms in leptospirosis automatically signal catastrophic illness.

The authors are careful to note the limits of their work. Because the study was retrospective and relied on clinicians having ordered lumbar punctures or brain imaging in the first place, the true frequency of neurological involvement may be underestimated; only 19 percent of the cohort underwent spinal taps, and milder cases managed without hospitalization would never have entered the analysis. The absence of a consensus definition also means that comparisons with other regions are difficult, since different studies have used different thresholds for what counts as neurological leptospirosis. The researchers call for prospective studies incorporating systematic cerebrospinal fluid analysis and microbiological testing, including molecular methods capable of detecting leptospiral DNA directly in the fluid, to clarify the pathophysiology and standardize diagnostic pathways.

For now, the practical takeaway for physicians in tropical endemic settings is one of heightened awareness. In French Guiana, where leptospirosis is a re-emerging public health threat driven by a humid tropical climate, abundant wildlife reservoirs, and frequent human exposure to contaminated water, a young patient with fever, headache, and a lymphocytic meningitis picture, but without the leukocytosis and thrombocytopenia that usually accompany severe leptospirosis, should prompt consideration of neuroleptospirosis in the differential diagnosis. Recognizing the entity matters not only for appropriate antibiotic treatment but also for avoiding unnecessary interventions, since the prognosis, according to this first systematic characterization, appears to be distinctly favorable. As climate change and urbanization expand the footprint of leptospirosis worldwide, understanding its neurological face will become increasingly important for clinicians far beyond the borders of French Guiana.

Subject of Research: Neurological involvement in leptospirosis patients in French Guiana

Article Title: Clinical features and outcomes of neuroleptospirosis in French Guiana: Insights from a retrospective study (2015–2021)

Article References: Clinical features and outcomes of neuroleptospirosis in French Guiana: Insights from a retrospective study (2015–2021). (n.d.). https://doi.org/10.1371/journal.pntd.0014263

Image Credits: AI Generated

DOI: 10.1371/journal.pntd.0014263

Keywords: leptospirosis, neuroleptospirosis, French Guiana, meningitis, encephalitis, cerebrospinal fluid, tropical medicine, PLOS Neglected Tropical Diseases, retrospective study, central nervous system infection, zoonotic disease, Clinical