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An event is serious (based on the ICH definition) when the patient outcome is:
* death
* life-threatening
* hospitalisation
* disability
* congenital anomaly
* other medically important event
A 60-year-old man developed West Nile virus (WNV) infection during immunosuppressive treatment with mycophenolic acid, tacrolimus and methylprednisolone. Subsequently, he developed graft failure during empiric treatment with aciclovir for suspected herpes encephalitis [not all routes and dosages stated; durations of treatments to reactions onsets not stated].
The man from the Greater Halle/Leipzig area of Germany, who had history kidney transplant due to terminal renal insufficiency secondary to hypertensive nephropathy, admitted to a hospital in Germany from another hospital with a high fever and chills without any other complaints. Procalcitonin and C-reactive protein were in the normal range. Blood count was normal. He tested negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on PCR from respiratory secretions. The standard triple immunosuppressive therapy comprising tacrolimus 4 mg/day, mycophenolic acid 720 mg/day and methylprednisolone 4 mg/day at that time was already reduced to a mycophenolic acid-free 2-fold combination. The tacrolimus level was in the target range (4−6 ng/mL).
The man's treatment was started with empirical broad-spectrum antibiotic therapy with ceftriaxone and moxifloxacin. However, high fever persisted. No infectious aetiology was detected in the imaging diagnostics (abdominal sonography, X-ray thorax and echocardiography) or the virological, microbiological and serological testings. On day 6 after admission, he suddenly developed neurological symptoms in the form of balance and orientation disorders. With the suspicion of cerebellar syndrome, cerebrospinal puncture were performed. Increased protein and pleocytosis with granulocytic and lymphocytic cell were detected in the cerebrospinal fluid. With the suspicion of infectious meningoencephalitis in immunosuppression, the immunosuppressive therapy was discontinued. For suspected herpes encephalitis, he started receiving parenteral aciclovir [acyclovir]. During the following days, the previously stable graft function deteriorated to oliguric graft failure (Acute Kidney Injury Network 3). An acute graft rejection due to reduced immunosuppression was suspected. He received methylprednisolone shock therapy. No pathogens were detected. Aciclovir was considered as contributory factor to graft failure. Additionally, molecular biological detection of herpes simplex virus in the cerebrospinal fluid failed. Therefore, aciclovir was discontinued. No other pathogens including varicella-zoster virus, Epstein-Barr virus, cytomegalovirus, parechovirus, enterovirus, human herpes virus-6/-7/-8, mumps virus and Aspergillus spp. were detected. After methylprednisolone treatment, there was an improvement in the graft function as well as a decrease in neurological symptoms. Histopathology showed a severe, diffuse, potentially reversible acute tubuluse pumipel damage with herd-shaped lymphoplasmic interstitial inflammation in the kidney punch cylinder. Focally mild tubulitis in the sense of borderline rejection, mild global glomerulosissclerosis (5/24), tubulatrophy and interstitial fibrosis (~15−20%) moderate to severe arteriorentoriosclerosis was noted. No evidence of an acute humoral or vascular rejection reaction was noted. Owing to the absence of a satisfactory diagnosis and several previously reported cases of WNV infections in the Greater Halle/Leipzig area, the virological analysis spectrum was extended to cover the WNV. WNV RNA was detected in his urine using RT-PCR at two different times (day 0 and day+ 8). However, WNV RT-PCR of blood and cerebrospinal fluid was negative. Over time, acute WNV infection was detected serologically. He was diagnosed with WNV infection, and the immunosuppression therapy was considered as risk factor for WNV infection. The direct sequencing of the PCR amplificate from the urine resulted in a WNV sequence showing a 100% sequence identity with another WNV line 2 strain, which was detected in a bird in Germany. The phylogenetic analysis of the NS5 gene sequences of different WNV strains showed a close relationship to the recently described WNV line 2 strains from the same geographic region. Subsequently, he fully recovered from the WNV infection, and the transplant was restored to original condition (restitutio ad integrum). He continued immunosuppression in reduced form with a daily administration of tacrolimus, mycophenolate and methylprednisolone.