Lymphocytic choriomeningitis virus in western New South Wales

Clinical record

A 51‐year‐old man presented to Dubbo Health Service in February 2021 with a 24‐hour history of headache, neck stiffness, photophobia and lower abdominal rash. This was preceded by 4 weeks of myalgias and arthralgias affecting his lower back, left hip and left knee. He had no medical history or regular medications. He lived on a farm in central‐west New South Wales with significant zoonotic exposures, including cattle, horses and direct contact with mice and mice carcasses and secretions.

On examination, he was febrile to a temperature of 38.9°C, but otherwise haemodynamically stable. He had a normal neurological exam. His abdominal rash had resolved. There was mild left lower quadrant abdominal tenderness and right inguinal lymphadenopathy.

Investigations revealed leukocytosis (16.6 × 10⁹/L; reference interval [RI], 3.7–9.5 × 10⁹/L) and mild thrombocytopenia (149 × 10⁹/L; RI, 150–400 × 10⁹/L). Lumbar puncture revealed clear, colourless cerebral spinal fluid (CSF) with elevated protein (1.25 g/L; RI, 0.15–0.45 g/L) and low glucose levels (1.8 mmol/L; RI, 2.2–3.9 mmol/L). The CSF white cell count was elevated at 211 × 10⁶/L, with mononuclear cell predominance (209 × 10⁶/L; RI, < 5 × 10⁶/L). Gram stain showed no bacteria.

Serology and polymerase chain reaction (PCR) tests were negative for Coxiella burnetii, and serology was negative for Brucella spp and Leptospira spp. CSF PCR was negative for Neisseria meningitidis, Streptococcus pneumoniae, herpes simplex viruses, enterovirus, parechovirus, and varicella zoster virus. Cryptococcal antigens were not detected in CSF or blood.

Empirical cover for bacterial and viral meningitis was commenced, with ceftriaxone 2 g given every 12 hours, benzylpenicillin 2.4 g every 4 hours, acyclovir 1.1 g every 8 hours, and dexamethasone 10 mg every 6 hours. He was given doxycycline 100 mg every 12 hours to treat C. burnetii and leptospirosis.

Given the current western NSW mouse plague1 and our patient’s history and exposure, testing for lymphocytic choriomeningitis virus (LCMV) was undertaken at the Victorian Infectious Diseases Reference Laboratory.2 Serum, urine and CSF samples were sent to the laboratory for PCR testing, and LCMV RNA was detected on the CSF sample using the gel‐based PCR test targeting the N gene. On discharge our patient’s symptoms had resolved and he remains well.

Discussion

This is the first published case of locally acquired LCMV infection. Notably, it occurred in an immunocompetent adult and had a positive survival outcome.

LCMV is a single‐stranded RNA virus of the arenaviridae family.3 It is a rodent‐borne infection, most commonly carried by the common house mouse. Rodents infected vertically carry the virus asymptomatically for life.3 Mice in north‐eastern NSW are known to carry LCMV, with one study between 1989 and 1991 showing that 30–52% of mice in the Narrabri and Moree region had antibodies to LCMV.4 These authors predicted transmission to human populations in the event of a plague.4

LCMV particles are contained in rodent urine, faeces, secretions and blood, thus enabling transmission via contact with mice directly or with their bodily fluids and via inhalation of aerosolised secretions.3

Initial viral replication occurs within the lungs, before spreading haematogenously to the central nervous system (CNS). Here the virus replicates and stimulates a host immune response causing aseptic meningitis.5

Human infection has been recorded across America, Europe and Asia. LCMV infection has been described in one Australian case series.5 Three separate solid organ transplant recipients from the same donor (who recently returned from Europe) developed febrile illness and died. The three recipients were LCMV PCR‐positive and the donor was LCMV IgG‐ and IgM‐positive.3

LCMV is often asymptomatic in immunocompetent hosts. It is otherwise a biphasic illness. The initial febrile phase starts 7–14 days following exposure, lasting days to weeks. It is characterised by fevers, myalgias, nausea and vomiting. Systemic improvement occurs for 1–2 days, before the onset of the secondary CNS phase. This includes headache, photophobia, fever, nuchal rigidity, and rash, consistent with our patient’s presentation. More serious CNS manifestations include encephalitis, Guillain–Barré syndrome and transverse myelitis.5

Patients with LCMV infection may display leukopenia, thrombocytopenia and chest x‐ray infiltrates. CSF often demonstrates elevated protein, low glucose and lymphocyte predominant pleocytosis. The degree of pleocytosis is often higher than would otherwise be expected in viral meningitis. LCMV PCR testing can be performed on urine, serum and CSF. Treatment is generally supportive, but ribavirin has been used in a single immunocompromised patient with a positive survival outcome.5

Congenital LCMV, spread vertically following maternal infection, can have catastrophic fetal consequences. LCMV exhibits strong neurotropism, manifesting as spontaneous abortion, chorioretinitis, optic atrophy, hydrocephalus, microcephaly, or cerebellar hypoplasia.5

This case highlights LCMV as a potential diagnosis in patients presenting with a biphasic illness and murine exposure. The western NSW mouse plague may cause an increased incidence of LCMV, which is particularly concerning for immunosuppressed individuals and pregnant women. This is relevant for future mouse plague events in the area, with the potential for spread of LCMV across other parts of Australia.