Emergence of a Novel Mammarenavirus Closely Related to Lassa Virus in a Patient with Meningoencephalitis in Chad

Patient Information
A 37-year-old man presented to a health center in N’Djamena, Chad, with acute onset of occipital headaches, vomiting, and generalized asthenia. The patient had recently traveled from France to Chad and spent approximately three months in the country, primarily in the N’Djamena area with brief stays in Ouaddaï (Abéché) and Borkou (Faya-Largeau) regions. Initial clinical examination revealed fever and photophobia without evidence of neck stiffness. No prior relevant medical history was reported.

Diagnosis
The patient was initially evaluated in Chad, but was repatriated to France for further management 5 days after symptom onset and admitted to a neurology ward. Over the next two days, he developed confusion and convulsions necessitating transfer to the intensive care unit (ICU).

Metatranscriptomic sequencing of cerebrospinal fluid (CSF) obtained on day 9 post-symptom onset identified viral sequences closely related to Lassa virus (genus Mammarenavirus). The sequences covered the entire small (S) segment and nearly all (98%) of the large (L) segment of the viral genome, showing 77.3% homology with Lassa virus S segment and 75.0% with L segment sequences. Reverse-transcriptase polymerase chain reaction (RT-PCR) targeting Old World mammarenavirus consensus sequences confirmed viral RNA presence in CSF obtained on days 6 and 8, but no viral RNA was detected in plasma or urine samples at later time points.

Serologic assays detected Lassa virus–specific IgM and IgG antibodies in plasma, consistent with active infection.

Electron microscopy of virus isolated from CSF demonstrated typical mammarenavirus spherical particles with ribosomes present, confirming viral morphology. Viral neutralization assays using patient plasma sample at day 22 showed neutralizing activity.

Whole genome sequencing revealed the virus shares 84.8% to 86.6% amino acid sequence homology in nucleoprotein with Lassa virus lineages, with lower homology observed in other Old World mammarenaviruses, supporting that this is a novel mammarenavirus closely related but distinct from Lassa virus.

Differential Diagnosis
The initial presentation of fever, headache, vomiting, photophobia, and subsequent neurological deterioration warranted consideration of several central nervous system (CNS) infections:

– Lassa fever: Given sequence similarity and endemicity in nearby Nigeria, Lassa virus infection is plausible. However, no prior reports exist from Chad and clinical features were atypical.
– Viral meningoencephalitis due to other agents: Herpes simplex virus, enteroviruses, arboviruses (e.g., West Nile, chikungunya), and other emerging viruses were considered and ruled out by molecular diagnostics.
– Bacterial meningitis/encephalitis: Clinical presentation lacked classic meningeal signs and CSF culture and Gram stain were negative.
– Parasitic infections: Such as cerebral malaria were ruled out based on negative microscopy and clinical course.

Treatment and Management
Supportive neurological care was provided including ICU monitoring, management of seizures, and mechanical ventilation. The patient was intubated and sedated during the initial phase but clinically improved, allowing extubation on day 12. No specific antiviral therapy for mammarenavirus infection was administered as Lassa fever antivirals (e.g., ribavirin) have limited proven efficacy in atypical presentations and confirmation of a novel virus was achieved retrospectively.

Subsequently, the development of tetraventricular communicating hydrocephalus with transependymal resorption suggested sequelae of meningoencephalitis. This was managed surgically by ventriculoperitoneal shunt placement.

Outcome and Prognosis
The patient was discharged from hospital on day 26 post-symptom onset without residual neurological deficits except ideomotor slowing and dysmetria. Follow-up imaging 15 days after discharge revealed progression of hydrocephalus requiring neurosurgical intervention.

There was no evidence of transmission among close contacts. Long-term prognosis involves monitoring for potential neurological sequelae related to hydrocephalus and encephalitis.

Discussion
This case describes the isolation and characterization of a novel pathogenic mammarenavirus closely related to Lassa virus identified in a patient with meningoencephalitis in Chad. Lassa virus itself has not previously been documented in Chad, although geographical proximity to Nigeria, a Lassa fever endemic country, suggests possible regional spread or undetected circulation.

The patient’s clinical presentation differed from typical Lassa fever syndrome, which usually includes hemorrhagic fever and multisystem involvement; instead, meningoencephalitis predominated, and viral RNA was detected exclusively in CSF. This aligns with isolated reports of Lassa virus manifesting as CNS disease.

Genomic analyses demonstrated that the virus clusters outside established Lassa virus lineages, indicating it is a novel species in the mammarenavirus genus based on nucleotide sequence criteria (<80% S segment and <76% L segment homology with known viruses). Furthermore, the virus shared less than 88% nucleoprotein amino acid identity with other mammarenaviruses.

The case underscores the need for active surveillance and research to identify reservoirs, likely rodents, and comprehend transmission dynamics. This finding has important public health implications given the potential for emergence of new mammarenaviruses capable of causing severe human disease.

The absence of recognized secondary cases suggests limited human-to-human transmissibility, but further studies are needed to ascertain epidemiological risks.

This report expands the spectrum of mammarenavirus infections affecting humans and highlights the vital role of unbiased metagenomic sequencing in identifying emerging pathogens presenting with atypical neurologic syndromes.

References
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