Severe Non-Donor-Derived Lymphocytic Choriomeningitis Virus Infection in 2 Solid Organ Transplant Recipients

Abstract

Background: Lymphocytic choriomeningitis virus (LCMV) infection in immunocompromised hosts can result in disseminated disease, meningoencephalitis, and death. Published cases in transplant recipients have been traced to transmission from infected donors. We report 2 cases of serious, non-donor-derived LCMV infection in solid organ transplant recipients.

Methods: Initial identification of LCMV infection was done by using metagenomic next-generation sequencing (mNGS). Subsequent evaluations and confirmatory testing involved molecular diagnostics, serology, and phylogenetic analysis. A detailed epidemiologic investigation was conducted.

Results: LCMV was detected by mNGS in 2 solid organ transplant recipients from distinct donors. A heart transplant recipient (from donor 1) died of progressive, disseminated LCMV infection, while a kidney transplant recipient (from donor 2) with LCMV meningoencephalitis survived. A multistate laboratory and epidemiologic investigation of both donors and all their organ recipients was initiated. Postmortem samples were obtained from both donors, and pretransplant and/or posttransplant samples were obtained from 5 of the 6 organ recipients. mNGS, serologic, and real-time reverse-transcription polymerase chain reaction testing confirmed LCMV infection in both solid organ transplant recipients. Epidemiologic investigation revealed significant pretransplant rodent exposures for both LCMV-infected recipients. Laboratory studies for the other organ recipients from both donors were negative for LCMV infection.

Conclusions: Our investigations suggest that LCMV infection in 2 solid organ transplant recipients originated from rodent exposure preceding transplantation and were not donor derived. Although uncommon, healthcare providers should be aware of LCMV-associated serious and life-threatening illness in immunocompromised hosts. Diagnostic modalities are limited to reference laboratories.

Keywords: donor-derived; encephalitis; lymphocytic choriomeningitis virus; rodent; transplant.

Figure 1.

Timeline of symptom onset and laboratory testing in 2 unrelated lymphocytic choriomeningitis virus infections in solid organ transplant recipients. Plus and minus signs represent positive and negative results, respectively. Abbreviations: CSF, cerebrospinal fluid; Ig, immunoglobulin; mNGS, metagenomic next-generation sequencing; OD1, organ donor 1; OD2, organ donor 2; PCR, polymerase chain reaction; R1A, recipient 1A; R2A, recipient 2A.

Figure 2.

Phylogenetic tree for lymphocytic choriomeningitis virus (LCMV) long segment of samples from the 2 independent US transplant recipients who contracted LCMV. The phylogenetic history of the LCMV short segment was inferred using maximum-likelihood estimation (GTR + I). Samples from R1A are highlighted in blue, and the sample from R2A is highlighted in yellow. Bootstrap support (n = 1000) is indicated at internal nodes in red, and scale bars are in units of substitutions per site. Phylogenetic trees were generated using a nucleotide alignment of LCMV long segments. GenBank accession numbers are provided. An additional phylogenetic tree constructed from the LCMV short segment is included in the Supplementary materials.