Brief Report: Lymphocytic Choriomeningitis Virus Transmitted Through Solid Organ Transplantation --- Massachusetts, 2008

Lymphocytic choriomeningitis virus (LCMV) is a rodent-borne arenavirus found worldwide. House mice (Mus musculus) are the natural reservoir, but LCMV also can infect other wild, pet, and laboratory rodents (e.g., rats, mice, guinea pigs, and hamsters). Humans can be infected through exposure to rodent excreta. Person-to-person transmission has occurred only through maternal-fetal transmission and solid organ transplantation (1--3). LCMV infection in humans can be asymptomatic or cause a spectrum of illness ranging from isolated fever to meningitis and encephalitis. Overall case fatality is <1%. Fetal infections can result in congenital abnormalities or death. Immunosuppressed patients, such as organ transplant recipients, can develop fatal hemorrhagic fever--like disease. Transmission of LCMV and an LCMV-like arenavirus via organ transplantation has been documented in three previous clusters (1,2). Of 11 recipients described in those clusters, 10 died of multisystem organ failure, with LCMV-associated hepatitis as a prominent feature. The surviving patient was treated with ribavirin (an antiviral with in vitro activity against LCMV) and reduction of immunosuppressive therapy. On April 15, 2008, an organ procurement organization (OPO) notified CDC of severe illness in two kidney transplant recipients from a common donor; at the time of notification, one of the recipients had died. Samples from the donor and both recipients were tested at CDC; on April 22, test results revealed evidence of acute LCMV infection in the donor and both recipients. This report summarizes the results of the subsequent public health investigation.

Organ Donor

The organ donor was a man aged 49 years with a history of alcohol abuse who was hospitalized in early March 2008 after a seizure. On admission, he was awake but confused and had a fever of 101.9°F (38.8°C). Chest radiography, lumbar puncture, and blood cultures were performed. The chest radiograph showed no evidence of pneumonia. Cerebrospinal fluid (CSF) contained 478 white blood cells/mm³ (96% lymphocytes), one red blood cell/mm³, 161 mg/dL protein, and 60 mg/dL glucose. The patient was treated empirically for possible herpes simplex encephalitis and bacterial meningitis with acyclovir, ceftriaxone, and vancomycin. Gram stain and culture for bacterial pathogens and herpes simplex virus-1/2 polymerase chain reaction (PCR) were negative in CSF. Blood cultures grew methicillin-resistant Staphylococcus aureus in one of four bottles. Two days later, on March 9, the patient experienced cardiac arrest; he was resuscitated but never regained consciousness. Nonsurvivable anoxic brain injury was determined, and life support was withdrawn.

Standard serologic donor screening tests showed no evidence of active infection with human immunodeficiency virus (HIV), hepatitis B and C viruses (HBV and HCV), human T-lymphotropic virus, and syphilis. In addition, HIV, HBV, and HCV nucleic acid tests were negative. An autopsy was not performed. After the donor met OPO criteria for organ donation and consent was obtained from the family, two kidneys were recovered for transplantation on March 13. No other organs or tissues were recovered for transplantation. On April 22, archived serum collected the day before death tested positive for anti-LCMV immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies by enzyme-linked immunosorbent assay (ELISA).

Kidney Recipient A

Kidney recipient A was a woman aged 70 years with end-stage renal disease caused by nephrotic syndrome; she received a kidney transplant from the donor in mid-March. She was readmitted 3 weeks posttransplant with lethargy and anorexia; she developed low-grade fever and shock, followed by hepatic insufficiency and multisystem organ failure. She died 4 weeks posttransplant. On April 22, archived whole blood collected on the day of death had evidence of acute LCMV infection by PCR and virus isolation. Multiple autopsy specimens, including liver, kidney, and spleen, stained positive for LCMV antigens by immunohistochemistry.

Kidney Recipient B

Kidney recipient B was a man aged 57 years with end-stage renal disease caused by hypertension; he received a kidney transplant from the donor in mid-March. He was readmitted 2 weeks posttransplant with fever and developed multisystem organ failure with severe hepatitis. His immunosuppressive medications were discontinued, he was given 1 dose of intravenous immunoglobulin, and ribavirin was started after acute LCMV infection was confirmed on April 22 (6 weeks posttransplant), when his serum tested positive for anti-LCMV IgM by ELISA. The serum also tested positive for LCMV by virus isolation, and a liver biopsy was positive for LCMV antigens by immunohistochemistry. Whole blood tested positive for LCMV by PCR, and the sequence was an exact match to the fragment amplified from the first kidney recipient. The patient had severe coagulopathy and developed multiple bacteremias in addition to LCMV viremia. He died 10 weeks posttransplant despite intensive supportive care.

Public Health Investigation

Results of laboratory testing indicated that the donor was the source of LCMV infection. The subsequent public health investigation included an assessment of the donor's potential sites of exposure to rodents, medical record review, and dissemination of educational information about LCMV to the general, medical, and public health communities. No test for LCMV infection is approved by the Food and Drug Administration for organ donor screening. In addition to LCMV, other pathogens have been transmitted by organ transplantation with fatal results; in some of these clusters, the donors have been asymptomatic. However, donors with aseptic meningitis or encephalitis pose a recognizable risk for transmitting infections that might be fatal to recipients. Risks and benefits to potential transplant recipients in offering and accepting organs from such donors should be considered carefully.

Health-care providers should consider LCMV infection in patients with aseptic meningitis and encephalitis and in organ transplant recipients with unexplained fever, hepatitis, or multisystem organ failure. Transplant centers and OPOs should be aware of the risk for organ transplant-transmitted infections, report poor outcomes promptly, and initiate appropriate testing.

Persons with rodent contact should be aware of LCMV and take measures to prevent infection. Clinicians should ask about history of rodent contact in patients with aseptic meningitis.

Specific guidelines for rodent control are available at http:// www.cdc.gov/rodents. Additional information about LCMV and its prevention is available at http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/lcmv.htm. Information regarding organ donation is available at http://www.optn.org/about/donation.

Reported by: A Barry, MD, J Gunn, P Tormey, T McCarthy, MD, J Pendarvis, MPH, Boston Public Health Commission; F Delmonico, MD, L Sussman, S Fitzpatrick, MSPA, New England Organ Bank, Newton; A Gautam, MD, C Sulis, MD, Boston Medical Center; M Wong, MD, S Pillai, MD, M Arya, MD, I Stillman, MD, SB Wright, MD, S Karp, MD, P Goodell, MD, Beth Israel Deaconess Medical Center, Boston; A DeMaria, MD, C Brown, DVM, M Cumming, MS, B Matyas, MD, Massachusetts Dept of Public Health; M Hull, MD, Office of Chief Medical Examiner, Commonwealth of Massachusetts. Special Pathogens Br, Infectious Diseases Pathology Br, Div of Viral and Rickettsial Diseases, National Center for Zoonotic, Vector-Borne, and Enteric Diseases; Office of Blood, Organ, and Other Tissue Safety, Div of Healthcare Quality Promotion, National Center for Preparedness, Detection, and Control of Infectious Diseases; S Schillie, MD, EIS Officer, CDC.

References

1. Fischer SA, Graham MB, Kuehnert MJ, et al. Transmission of lymphocytic choriomeningitis virus by organ transplantation. N Engl J Med 2006;354:2235--49.
2. Palacios G, Druce J, Du L, et al. A new arenavirus in a cluster of fatal transplant-associated diseases. N Engl J Med 2008;358:991--8.
3. Enria D, Mills JN, Flick R, et al. Arenavirus infections. In: Tropical infectious diseases: principles, pathogens, and practice. Guerrant RL, Walker DH, Weller PF, eds. Philadelphia, PA: Elsevier; 2006:734--55.

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Date last reviewed: 7/23/2008