A 53-year-old man residing in Connecticut, USA, with a history of well-controlled HIV and receiving antiretroviral therapy but with a chronically low CD4 count (150/µL) and percentage (14%), was admitted to the emergency department at Yale New Haven Hospital (New Haven, CT, USA) with a 2-day history of headache, nausea, and emesis. In the weeks leading up to admission, he had noted mice in his home. Approximately 2 weeks before admission, he cleaned mouse feces and urine with a vacuum while wearing gloves and a mask. At arrival to the hospital, he was febrile to 100.7°F but otherwise hemodynamically stable. Physical examination showed no neurologic deficits or nuchal rigidity. Laboratory data were notable for a hemoglobin of 11.2 g/dL (reference range 13.1–17.5), leukocyte count of 7,200/µL (reference range 4,000–10,000/µL), platelet count of 213,000/µL (reference range 150,000–400,000/µL), aspartate transaminase 59 U/L (reference range 10–35 U/L), and alanine aminotransferase 96 U/L (reference range 9–59 U/L). His HIV viral load was below the limit of detection (20 copies/mL) 1 month before admission.

The patient underwent a lumbar puncture after receiving empiric antibiotics for meningitis. Analysis of the cerebral spinal fluid (CSF) revealed a nucleated cell count of 500/µL in tube 1 and 495/µL in tube 4 (reference range 0–5/µL), which was lymphocyte predominant (≈85%). CSF protein was 116 mg/dL (reference range 15–45 mg/dL) and glucose was 66 mg/dL (reference range 40–70 mg/dL). Culture remained sterile and CSF was negative for herpes simplex virus by real-time PCR, West Nile virus IgM in CSF, and for 14 pathogens included on the BioFire FilmArray Meningitis/Encephalitis Panel (BioFire Diagnostics, LLC, https://www.biofiredx.com).

Because of concern for aseptic meningitis caused by LCMV, we sent CSF and whole blood samples to CDC for LCMV testing. LCMV IgM and IgG were determined by a CDC-developed ELISA, as previously described (2). For nucleic acid testing, in brief, samples were inactivated by using MagMAX Pathogen RNA/DNA Kit (ThermoFisher, https://www.thermofisher.com) and extracted on the KingFisher Duo Prime platform (ThermoFisher). Extracted samples were tested by using an qRT-PCR targeting the large segment of LCMV. RNA from samples positive by the LCMV qRT-PCR were selected for sequencing and subsequent phylogenetic analysis. RNA library sequencing, amplicon-based sequencing, and phylogenetic analysis were performed on the LCMV genome obtained from the CSF sample, as were additional laboratory methods (Appendix).

Figure 1

Figure 1. Maximum-likelihood analysis of the full large genome segment of lymphocytic choriomeningitis virus (LCMV) sample from a patient in Connecticut, USA (bold), compared with reference sequences. Branch nodes provide the bootstrap...

Figure 2

Figure 2. Maximum-likelihood analysis of the full small genome segment of lymphocytic choriomeningitis virus (LCMV) sample from a patient in Connecticut, USA (bold), compared with reference sequences. Branch nodes provide the bootstrap...

Analysis of the CSF showed that LCMV IgM and IgG ELISA results were both negative, but qRT-PCR results were positive. On blood collected 3 days after the CSF sample, LCMV IgM and IgG ELISA results were both positive (titer ≥1:400), and qRT-PCR results were negative. Sequence analysis of both the small and large segments showed the LCMV strain clustered to lineage I (Figures 1, 2). After confirming a diagnosis of LCMV meningitis in the patient, we discontinued empiric antibiotics and discharged him on hospitalization day 10. The patient’s headaches resolved approximately 5 days after discharge, and he made a complete recovery.

Despite minimal reporting requirements, LCMV is believed to be widespread throughout the United States and the world. As in the case we report, clinicians should maintain a high index of suspicion for LCMV infection in patients with identified rodent exposures and symptoms consistent with meningitis, especially in high-risk groups such as pregnant women and the immunocompromised. LCMV viremia occurs early and is transient but may seed the central nervous system. Thus, as occurred for the patient in this report, viral RNA may no longer be detectable in blood but may be detectable in CSF in patients with clinical signs and symptoms of LCMV. Consequently, for patients with suspected LCMV infection, parallel molecular and serologic testing of both blood and CSF is likely beneficial for early diagnosis and management.

By sequencing the full genome of an LCMV strain isolated from this patient and conducting a phylogenetic analysis, we have gained valuable insights into the evolutionary relationships and genetic diversity of LCMV. The obtained phylogenetic trees provide evidence for the relatedness of the patient's strain to other known LCMV strains and contributes to our understanding of the virus’s epidemiology. The LCMV strains we obtained group in clade I, which corresponds to the M. musculus domesticus host subspecies (1) and contains viruses from Asia, Europe, America, and Africa. The phylogenetic tree also shows that the strain identified in this patient was genetically distinct from strains that have been identified from other parts of the world.

No-cost molecular and serologic testing for LCMV is available to hospitals and health departments through CDC’s Viral Special Pathogens Branch (Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases). Increasing both community and healthcare provider awareness of LCMV and public health case reporting could improve surveillance efforts and clarify the true burden, risk factors, and distribution of LCMV infection in the United States.