Balamuthia mandrillaris Transmitted Through Organ Transplantation --- Mississippi, 2009

Balamuthia mandrillaris Transmitted Through Organ Transplantation --- Mississippi, 2009
Weekly
September 17, 2010 / 59(36);1165-1170


On December 14, 2009, a physician in Mississippi contacted CDC to report possible transplant-transmitted encephalitis in two kidney transplant recipients who shared the same organ donor. Histopathologic testing of donor autopsy brain tissue at CDC showed amebae, and subsequent testing of specimens from the donor and the two kidney recipients confirmed transmission by transplantation of Balamuthia granulomatous amebic encephalitis (GAE), a rare disease caused by Balamuthia mandrillaris, a free-living ameba found in soil (1). One kidney recipient, a woman aged 31 years, died; the other recipient, a man aged 27 years, survived with neurologic sequelae. Recipients of the heart and liver from the same donor received preemptive therapy and have shown no signs of infection. The donor, a previously healthy boy aged 4 years, was presumed to have died from acute disseminated encephalomyelitis (ADEM), an autoimmune neurologic disease, after infection with influenza A. An investigation was conducted by the state health departments in Mississippi, Kentucky, Florida, and Alabama and CDC to characterize the cases, elucidate possible exposures in the donor, and develop recommendations for early detection and prevention. This is the first reported transmission of Balamuthia by organ transplantation. Clinicians should be aware of Balamuthia infection as a potentially fatal cause of encephalitis. Organ procurement organizations (OPOs) and transplant centers should be aware of the potential for Balamuthia infection in donors with encephalitis of uncertain etiology, and OPOs should communicate this elevated risk for infection to transplant centers so they can make an informed risk assessment in the decision to accept an organ.

Organ Donor

The organ donor, a boy aged 4 years from Kentucky, was living with relatives in Mississippi in October 2009, when he developed a transient febrile illness. He was diagnosed with influenza A infection by rapid influenza test on October 25 and prescribed antivirals; his symptoms resolved without hospitalization. On November 3, the boy had sudden onset of headache and seizures and was hospitalized (Table 1). Cerebrospinal fluid (CSF) demonstrated lymphocytic pleocytosis (170 white blood cells/mm3) and normal protein (29 mg/dL); magnetic resonance imaging (MRI) of the brain showed numerous small enhancing lesions and edema (Table 2). An extensive search for viral, bacterial, and fungal etiologies of encephalitis was unrevealing. His clinical presentation, CSF findings, and MRI were thought to be most consistent with a diagnosis of ADEM, an immune-mediated encephalitis that can follow influenza or other infections. He was treated symptomatically and discharged on November 6.

The boy was readmitted on November 10 with recurrent seizures. MRI of the brain demonstrated progression of several of the enhancing lesions; CSF again demonstrated lymphocytic pleocytosis (150 cells/mm3) and normal protein (44 mg/dL) (Table 2). He was treated for presumed worsening ADEM with intravenous corticosteroids and immunoglobulin. He developed subarachnoid hemorrhage and brain stem herniation on November 18 and was pronounced brain dead the next day. His heart, liver, and kidneys were transplanted into four recipients at three different transplant centers on November 20. On December 16, histopathologic examination of the donor's brain tissue at CDC revealed the presence of abundant amebae morphologically suggestive of Balamuthia (Figure); empiric treatment for both kidney recipients was initiated later that day, in consultation with CDC. On December 17, immunohistochemical and indirect immunofluorescent stains (Figure) revealed antigens of free-living amebae in the donor's brain tissue; polymerase chain reaction (PCR) results confirmed Balamuthia infection.

Kidney Recipient A

Kidney recipient A, a woman aged 31 years, underwent transplantation for end-stage renal disease resulting from hypertension and diabetes. On December 10, post-transplant day (PTD) 20, she reported onset of right leg twitching and neck spasms, numbness, headache, nausea, and seeing flashing lights (Table 1). She was evaluated in an emergency department, where she was treated with benzodiazepines and discharged with muscle relaxants; no neuroimaging or lumbar puncture was performed. On December 12, she was found unresponsive at home and taken back to the emergency department, where she had a generalized seizure and was admitted; the next day, she was transferred to the intensive-care unit. MRI of the brain demonstrated numerous ring-enhancing lesions. CSF initially showed a normal white blood cell count (3 cells/mm3) and elevated protein (75 mg/dL); however, another specimen collected on December 15 revealed a neutrophilic pleocytosis (507 cells/mm3) and increased protein (142 mg/dL) (Table 2). On December 16, she underwent brain biopsy. On December 18, histopathologic examination of the brain tissue at CDC revealed amebae; immunohistochemical stains detected antigens of free-living amebae, and PCR confirmed Balamuthia infection. She was treated with pentamidine, sulfadiazine, flucytosine, fluconazole, and azithromycin. Miltefosine, an antileishmanial and antineoplastic agent, was added on December 25 under an emergency investigational new drug (IND) protocol. Despite several weeks of intensive care, she deteriorated neurologically and died on February 3 (PTD 75).

Kidney Recipient B

Kidney recipient B, a man aged 27 years, underwent transplantation for end-stage renal disease resulting from focal segmental glomerulosclerosis. On December 10 (PTD 20), he had sudden onset of severe headache and vomiting and was examined at a local emergency department early the next morning, where he was diagnosed with sinusitis and discharged on amoxicillin-clavulanic acid (Table 1). Later that day, he developed altered mental status and seizures and was admitted to a regional hospital. A lumbar puncture was performed; CSF demonstrated 1 white blood cell/mm3 and slightly elevated protein (69 mg/dL) (Table 2). On December 13, he was transferred to the intensive-care unit at the same hospital as kidney recipient A. CSF that day revealed mild pleocytosis (19 cells/mm3) and slightly increased protein (74 mg/dL). MRI of the brain showed numerous ring-enhancing lesions. The man was treated with the same combination of drugs as kidney recipient A, including miltefosine obtained under IND. Balamuthia infection was confirmed by PCR and culture on a CSF specimen drawn December 29. After 2 months in a coma, the man had a slow but significant recovery of cognitive and motor function and was discharged to a rehabilitation facility on April 28 (PTD 159). He was discharged home June 11. His neurologic sequelae included residual right arm paralysis, bilateral leg weakness, and intermittent vision loss; however, he performed most activities of daily living independently.

Heart Recipient

The heart recipient, a boy aged 2 years, underwent transplantation for restrictive cardiomyopathy. When the kidney recipients were diagnosed with Balamuthia GAE, the boy was asymptomatic. On December 17 (PTD 27), he was hospitalized for evaluation. MRI of the brain was normal, and testing of CSF, serum, and endomyocardial tissue at CDC showed no evidence of Balamuthia infection. The boy was treated for presumed Balamuthia exposure with a 6-week course of intravenous pentamidine, azithromycin, and fluconazole, followed by 5 weeks of oral azithromycin. He remains well.

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Balamuthia mandrillaris Transmitted Through Organ Transplantation --- Mississippi, 2009