Mild Lassa Fever, Severe Brain Symptoms: Nigerian Case Reveals Hidden Neurological Toll

A 29-year-old woman from Owo, a town in Nigeria’s Ondo State that sits at the heart of the global Lassa fever burden, walked into the accident and emergency department of the Federal Medical Centre with what looked like an ordinary tropical febrile illness. She had endured five days of fever, and in the hours before arrival she had begun vomiting and suffering diarrhoea. But the finding that transformed her presentation from routine to alarming was neurological: a new-onset focal seizure witnessed as she reached the hospital. Over the following days, clinicians documented profound emotional lability, fine tremors and a persistent, refractory insomnia that resisted even intravenous benzodiazepine sedation. What makes her case extraordinary, and the subject of a case report now published in BMC Infectious Diseases, is that her blood tests suggested her infection was, by conventional measures, mild.

Quantitative reverse transcription polymerase chain reaction testing returned cycle threshold values of 35 and 36, numbers that indicate a very low systemic viral burden. In the arithmetic of viral haemorrhagic fevers, high viraemia generally tracks with severe disease and poor outcomes, while low viral loads are usually reassuring. Yet this patient, with barely detectable virus circulating in her blood, was experiencing some of the most severe neuropsychiatric distress her care team had encountered in Lassa fever. The dissociation between her laboratory values and her clinical state is the central puzzle of the report, authored by Amos Egbedion Unuane of the Federal Medical Centre in Owo and Ambrose Alli University in Ekpoma, together with colleagues from microbiology, community medicine, chemical pathology and psychiatry departments in Nigeria.

The epidemiological backdrop matters. Nigeria remains the global epicentre of Lassa fever, an arenavirus infection transmitted to humans primarily through contact with food or household items contaminated by the urine and faeces of Mastomys rodents, particularly the multimammate mouse Mastomys natalensis. The disease has traditionally been classified as a viral haemorrhagic illness, characterised by systemic symptoms and the potential for catastrophic bleeding. But the authors note that evolving clinical patterns suggest neuropsychiatric manifestations are becoming increasingly prominent, particularly in Ondo, Edo and Bauchi States. Crucially, these neurological and psychiatric features often appear in patients who lack classic haemorrhagic signs, creating a real risk that they will be misdiagnosed as primary psychiatric disorders or as complicated malaria.

That diagnostic trap played out in this very case. The patient’s initial presentation was misread as complicated malaria, a mistake the authors describe as emblematic of the challenges facing clinicians in endemic hotspots, where atypical presentations of Lassa fever are increasingly documented. Malaria is far more common and its symptoms overlap broadly with early Lassa fever, so the default assumption in a febrile patient is understandable. But the presence of a focal seizure, followed by escalating psychiatric symptoms, should have served as a red flag. The report argues that acute psychiatric changes, refractory insomnia and seizures should be treated as critical clinical clues that warrant prompt evaluation for Lassa fever, even when haemorrhage is absent and viral loads are low.

The timeline of the infection adds another instructive detail. Seven days before her hospital admission, the patient had identified and disposed of a Mastomys species rodent at her residence. This history of rodent contact, obtained through careful clinical interviewing, provided the epidemiological link that ultimately pointed the diagnostic workup toward Lassa fever. In endemic regions, the authors suggest, such environmental histories should be actively sought in any patient presenting with fever and unexplained neurological or psychiatric features, because the window for effective treatment narrows rapidly as the infection progresses.

Treatment followed established protocols. The patient received a full course of intravenous ribavirin, the only widely available specific antiviral therapy for Lassa fever, alongside targeted supportive and symptomatic management. The response was gratifying: she achieved complete clinical recovery, with resolution of all neurological and psychiatric deficits. The outcome demonstrates that even severe neuropsychiatric complications of Lassa fever can be reversible when the diagnosis is made and appropriate therapy is delivered, reinforcing the argument that early recognition of atypical presentations is not merely an academic exercise but a determinant of survival and long-term neurological health.

The mechanistic implications of the case are perhaps its most scientifically provocative element. The authors propose two non-exclusive explanations for the marked clinico-biological dissociation they observed. The first is direct viral neurotropism: the possibility that Lassa virus, an Old World arenavirus, can invade and replicate within cells of the central nervous system, causing injury that is invisible to measurements of viral RNA in peripheral blood. The second is a sequestered neuro-inflammatory response, in which immune activity within the brain and spinal cord proceeds independently of the systemic viral burden measured in the bloodstream. Either scenario would explain how a patient with cycle threshold values of 35 and 36, indicating minimal circulating virus, could manifest seizures, tremors, emotional instability and insomnia so severe that sedation failed.

Central nervous system involvement in Lassa fever is not entirely without precedent, but the timing described in this report is notable. The authors emphasise that central nervous system morbidity may present early in the clinical course of the disease, even in the absence of an overt systemic crisis. This challenges the conventional staging of the illness, in which neurological complications are typically regarded as late phenomena of severe, high-viraemia disease. If early neuropsychiatric involvement is more common than previously appreciated, the true burden of Lassa fever-related neurological injury in endemic regions may be substantially underestimated, both because such cases go undiagnosed and because survivors with psychiatric sequelae may never be linked back to their antecedent infection.

The practical consequences of this case report extend into public health policy. The authors call for the integration of neuro-phenotyping, the systematic characterisation of neurological and psychiatric features, into revised clinical management strategies for Lassa fever. They also stress the urgency of stringent environmental rodent control, since prevention of infection at its source remains the most reliable safeguard in communities where Mastomys rodents live in close proximity to human dwellings and food stores. For frontline hospitals in Ondo, Edo, Bauchi and beyond, the message is that a febrile patient with new seizures, agitation or intractable insomnia deserves consideration of Lassa fever regardless of whether bleeding is present or viral load assays suggest a mild infection.

The report, published open access on 12 September 2026 after acceptance by BMC Infectious Diseases, was conducted in accordance with the Declaration of Helsinki, with an ethical exemption from the Health Research Ethics Committee of the Federal Medical Centre, Owo, and written informed consent from the patient for publication. It received no specific external funding. Its authors, drawn from the Federal Medical Centre’s departments of medical microbiology, community medicine, chemical pathology and psychiatry, along with Ambrose Alli University and Achievers University, argue that their single case carries a broad warning: neuropsychiatric symptoms may be significant in Lassa fever even without haemorrhage or high viral loads. In a disease that infects thousands of Nigerians each year and remains dramatically under-reported, recognising the brain as an early and independent target of the virus could reshape triage, testing and treatment across the endemic belt.

Subject of Research: Neuropsychiatric complications of clinically mild, low-viraemia Lassa fever in Nigeria

Article Title: Neuropsychiatric complications of clinically mild lassa fever with low viraemia: a case report from a global hotspot in Owo, Ondo State, Nigeria

Article References: Unuane, A. E., Oko-Uromi, D. O., Adedosu, N. A., Ayodeji, O. O., Raji, S. O., Osagbaekhoe, A. A., & Azegbeobor, J. O. (2026). Neuropsychiatric complications of clinically mild lassa fever with low viraemia: a case report from a global hotspot in Owo, Ondo State, Nigeria. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14434-9

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14434-9

Keywords: Lassa fever, neuropsychiatric, Mastomys natalensis, low viraemia, seizure, insomnia, ribavirin, Nigeria, Owo, viral neurotropism, malaria misdiagnosis, rodent control