Influenza B Virus Transmission in Recipients of Kidney and Lung Transplants From an Infected Donor

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THE DONOR The 9-year-old donor had been febrile and probably had a seizure on the day of a submersion injury. He was declared brain dead after 60 hr of sedation, ventilation, and cooling. He did not have evidence of significant respiratory illness, was not immunized against influenza, and had not received antiviral agents. After allocation of kidneys, liver, and lungs, the organ procurement center was notified by the donor hospital that a donor nasopharyngeal aspirate demonstrated influenza B virus by immunofluorescence. Positive status was later confirmed by nested reverse- transcription polymerase chain reaction (RT-PCR) and cultures. At the time of notification, the lung recipient had native lung removal in progress. Organ recipient centers for liver and kidneys were notified of this risk and accepted the organs. Recipient clinical management details and investigative workup are summarized in Table 1.TABLE 1: Summary of the progress and management of all organ recipientsRENAL TRANSPLANT—KIDNEY 1 The recipient of kidney 1 was a 14-year-old boy with end-stage kidney disease secondary to hypoplastic kidneys. He had not received the 2008 seasonal influenza vaccine. This retrieved kidney was biopsied and was positive for influenza B RNA by RT-PCR. Initially, standard immunosuppression of basiliximab, mycophenolate, tacrolimus, and methylprednisone was used. A pretransplant dose of oseltamivir was given. After transplant, there was delayed graft function requiring peritoneal dialysis at 18 hr. Oseltamivir was administered daily. At 30-hr posttransplant, the patient developed severe respiratory distress and fever. By day 4, ventilation was required. A chest x-ray demonstrated widespread interstitial infiltrates (see Figure 1A, Supplemental Digital Content 1,https://links.lww.com/TP/A203). Because of delayed graft function, and this severe possibly infective illness, immunosuppression other than methylprednisone was withdrawn. Multiple RT-PCRs for influenza B RNA were performed on blood and tracheal aspirate samples. By day 6, oseltamivir was ceased as all investigations were negative. All other cultures and immunofluoresence studies were also negative. By day 6, the patient was extubated. A nonidentified infectious agent or an acute drug hypersensitivity reaction was proposed as a cause of the respiratory illnesses. On day 14, a renal biopsy, performed because of continued oliguria, demonstrated acute cellular rejection. Influenza B RNA was not detected in this biopsy. Following muro monah-CD3 (OKT3) and methylprednisone, renal function improved. Six months posttransplant, the patient's creatinine level was 67 μmol/L. Follow- up influenza serology did not demonstrate an increase in titers. LUNG TRANSPLANT The lung transplant recipient was a 17-year-old girl with end-stage lung disease because of neonatal onset pulmonary fibrosis. She had received yearly seasonal influenza vaccine. Induction therapy comprised steroids alone. After transplant, she received standard immunosuppression with cyclosporine, azathioprine, and methylprednisolone. Given the donor's influenza B status, oseltamivir was prescribed daily for 10 days in addition to routine broad spectrum antibiotic and inhaled antifungal therapy. The patient was noted to have widespread crackles on chest auscultation on postoperative day 0. Chest x-ray demonstrated diffuse bilateral interstitial infiltrates (see Figure 1B, Supplemental Digital Content 1,https://links.lww.com/TP/A203). During bronchoscopy, the airway anastomoses and distal bronchial tree were macroscopically normal, but bronchoalveolar lavage was tested positive for influenza B virus on direct immunofluorescence and culture on postoperative days 0 and 1 but negative by day 10. She was extubated successfully on day 6 and discharged on day 20. Spirometry improved from a forced expiratory volume in 1 sec/forced vital capacity (FVC) of 0.84/0.88 preoperatively to 1.89/2.04 by 6 months at which stage she was well and attending school. OTHER ORGAN RECIPIENTS The other kidney recipient showed no symptoms to suggest a donor-derived influenza infection. The liver recipient's posttransplant course was also unaltered by this donor-derived influenza risk. RESULTS OF INFLUENZA B VIRUS IDENTIFICATION Typing of influenza B virus in the explant kidney of recipient 1 and the lung recipient showed that the donor was B/Florida/4/2006 type (Table 1). Phylogenetic analysis based on partial nonstructural gene showed that the kidney and lung recipient strains were closely related with 98.9% amino acid identity across the partial nonstructural gene (see Figure 2, Supplemental Digital Content 2,https://links.lww.com/TP/A204). The strains shared more than 97.8% amino acid identity with B/Florida/4/2006, the influenza B-like strain in the Australian 2008 to 2009 influenza virus vaccine. DISCUSSION This case unfolded before the novel influenza A/H1N1 pandemic and the publication of recommendations for preventing donor-derived influenza infection (both seasonal and pandemic) (1, 2). Donor-derived influenza infection, however, has been documented rarely, with one reported case of influenza A transmission (3). To our knowledge, our case is the first report of influenza B transmission through lung transplantation. Although the recipient survived and is currently well, it is acknowledged that the outcome could have been different. Apart from acute risks, transplant- associated respiratory virus infection leading to bronchiolitis obliterans syndrome and graft dysfunction has been proposed as a potential longer term issue. However, there is no clear data to support influenza specifically as a causative agent in bronchiolitis obliterans syndrome (4). Given theoretical high likelihood of influenza transmission through lung transplantation, and potentially more significant recipient risk, a general recommendation by the transplantation society has been to defer a lung transplant in such a risk setting (1). Another approach, as recommended by The Australian Organ and Tissue Donation and Transplantation Authority, especially to be considered where recipient organ need is dire, is an individual case risk benefit analysis with informed consent (2). In our report, a donor kidney was shown to harbor influenza B virus during implantation, and although the recipient developed a respiratory illness, this was not related to influenza B. The presence of influenza in solid organs has been reported by authors in nontransplant settings (5). As far as we are aware, however, there are no reports of solid organ transplant transmission of influenza. This transmission risk remains to be clarified. Current guidelines recommend a cautious consideration to transplant in this risk setting (1, 2). Recognition of potentially influenza- infected donors, early donor screening, and antiviral use are the key initial steps in managing donor transmission risk of influenza viruses. If donation is to be considered, informed recipient consent is vital, with use of donor and recipient neuraminidase inhibitors (oseltamivir or zanamivir). This approach should be used in any donor influenza risk setting, regardless of subtype. Amelia K. Le Page1 Gad Kainer1 Allan R. Glanville2 Elise Tu3 Deepak Bhonagiri4 William D. Rawlinson3 1Department of Nephrology Sydney Children's Hospital Randwick, Australia 2The Lung Transplant Unit St. Vincent's Hospital Darlinghurst, Australia 3Virology Department of Microbiology SEALS, Prince of Wales Hospital Randwick, Australia 4NSW Organ and Tissue Donation Service St George Hospital Kogarah, Australia

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