Encephalitis Caused by Pathogens Transmitted through Organ Transplants, United States, 2002–2013 - Volume 20, Number 9—September 2014 - Emerging Infectious Disease journal - CDC

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Encephalitis Caused by Pathogens Transmitted through Organ Transplants, United States, 2002–2013 - Volume 20, Number 9—September 2014 - Emerging Infectious Disease journal - CDC

Volume 20, Number 9—September 2014

Synopsis

Encephalitis Caused by Pathogens Transmitted through Organ Transplants, United States, 2002–2013

On This Page

• West Nile Virus
• Rabies Virus
• Lymphocytic Choriomeningitis Virus
• Balamuthia mandrillaris Amebae
• Discussion
• Suggested Citation

Figures

• Figure 1
• Figure 2
• Figure 3
• Figure 4
• Figure 5

Tables

• Table

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• PDF[532 KB - 9 pgs]

Sridhar V. Basavaraju , Matthew J. Kuehnert, Sherif R. Zaki, and James J. Sejvar

Author affiliations: Centers for Disease Control and Prevention, Atlanta, Georgia, USA

Suggested citation for this article

Abstract

The cause of encephalitis among solid organ transplant recipients may be multifactorial; the disease can result from infectious or noninfectious etiologies. During 2002–2013, the US Centers for Disease Control and Prevention investigated several encephalitis clusters among transplant recipients. Cases were caused by infections from transplant-transmitted pathogens: West Nile virus, rabies virus, lymphocytic choriomeningitis virus, and Balamuthia mandrillaris amebae. In many of the clusters, identification of the cause was complicated by delayed diagnosis due to the rarity of the disease, geographic distance separating transplant recipients, and lack of prompt recognition and reporting systems. Establishment of surveillance systems to detect illness among organ recipients, including communication among transplant center physicians, organ procurement organizations, and public health authorities, may enable the rapid discovery and investigation of infectious encephalitis clusters. These transplant-transmitted pathogen clusters highlight the need for greater awareness among clinicians, pathologists, and public health workers, of emerging infectious agents causing encephalitis among organ recipients.

More than 500,000 solid organ transplants have been performed worldwide, and >28,000 are performed annually in the United States (1). Improvements in immune-modulating therapy, critical care medicine, and surgical techniques have led to the increased success of organ transplantations, and more patients are now eligible for these procedures. In the United States, >100,000 patients are currently on organ transplant waiting lists (1).

The risk for infections caused by pathogens transmitted through solid organ or tissue transplants (hereafter referred to as donor-derived or transplant-transmitted infections) has been recognized for decades and remains a worldwide public health problem (2). The gravity of these infections took on greater focus after the HIV epidemic emerged in the 1980s (3). Infections caused by other donor-derived pathogens in transplant recipients are often asymptomatic or may result in nonspecific signs and symptoms, including unexplained fever or end-organ injury (4). Because of immunosuppression and underlying co-existing conditions in transplant recipients, these infections can be severe and fatal. The recognition of this risk led to the screening of donors for some infectious agents (e.g., HIV and hepatitis B and C), which made the organ supply substantially safer. However, a residual transmission risk persists, which might be further reduced by the use of new technologies, such as nucleic acid testing (NAT) (5).

Since 2002, several types of emerging donor-derived infections have been reported with increasing frequency among solid organ transplant recipients seeking medical care for encephalitis. These cases can present a diagnostic challenge for clinicians and highlight the need to increase awareness among transplant clinicians regarding the necessity for prompt recognition and treatment of transplant-transmitted infections.

The signs and symptoms of encephalitis vary, depending on the region of the brain involved, but most cases are characterized by global cerebral dysfunction or focal neurologic deficits (6). Diagnosing the cause of encephalitis in transplant recipients may be particularly difficult because the cardinal sign of encephalitis (alteration of mental status) can be attributed to numerous other systemic processes. In addition, there are other noninfectious causes of encephalitis, including toxic, metabolic, neoplastic, and autoimmune processes. The signs and symptoms of donor-derived infections can be obscured by co-existing conditions in the transplant recipient, or they can appear more abruptly than in natural infection because of a higher inoculum of organisms and immunosuppression in the transplant recipient. Thus, transplant-transmitted pathogens may be an underrecognized cause of encephalitis.

Since 2002, the US Centers for Disease Control and Prevention (CDC) has investigated clusters of encephalitis among transplant recipients. Cases have been caused by emerging pathogens, including West Nile virus (WNV) (7,8), rabies virus (9), lymphocytic choriomeningitis virus (LCMV) (10), andBalamuthia mandrillaris amebae (11). The cases highlight the difficulties in diagnosing or recognizing clusters of infectious encephalitis among transplant recipients. We review the emerging infectious agents known to cause transplant-transmitted encephalitis, as described from several recent outbreak clusters reported to and investigated by CDC, and suggest methods for better identifying possible donor-derived infections.

Dr Basavaraju is a medical officer in the Office of Blood, Organ, and Other Tissue Safety, US Centers for Disease Control and Prevention. His primary research interests are transfusion- and transplant-transmitted infections.

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Figures

• Figure 1. Photomicrographs showing histopathologic features and immunolocalization of West Nile virus antigens in central nervous system tissue from a kidney transplant recipient with transplant-transmitted West Nile virus infection. A) Central...
• Figure 2. Photomicrographs showing histopathologic features and immunolocalization of rabies virus antigens in central nervous system tissue from a kidney transplant recipient with donor-derived rabies infection. A. Typical intracytoplasmic eosinophilic inclusions...
• Figure 3. Photomicrographs showing histopathologic features and immunolocalization of lymphocytic choriomeningitis virus (LCMV) antigens in liver tissue from a liver transplant recipient with donor-derived LCMV infection. A) Massive hepatic necrosis, without...
• Figure 4. Brain images showing contrast-enhanced lesions in the right occipital and left parietal lobes of a 4-year-old boy with encephalitis caused by infection with Balamuthia mandrillaris amebae. A) T2-weighted fluid-attenuated...
• Figure 5. Photomicrographs showing histopathologic features and immunolocalization of Balamuthia mandrillaris antigens in central nervous system tissue from a donor with B. mandrillaris infection. A) Typical amebic trophozoites with prominent karyosomes...

Table

• Table. Infectious agents associated with encephalitis reported among clusters of solid organ transplant recipients in the United States, 2002–2013

Suggested citation for this article: Basavaraju SV, Kuehnert MJ, Zaki SR, Sejvar JJ. Encephalitis caused by pathogens transmitted through organ transplants, United States 2002–2013. Emerg Infect Dis. 2014 Sept [date cited]. http://dx.doi.org/10.3201/eid2009. 131332

DOI: 10.3201/eid2009.131332