Absence of Neuroinvasive Disease in a Liver Transplant Recipient Who Acquired West Nile Virus (WNV) Infection from the Organ Donor and Who Received WNV Antibodies Prophylactically

Morelli, Cristina; Sambri, Vittorio; Grazi, Gian Luca; Gaibani, Paolo; Pierro, Anna; Cescon, Matteo; Ercolani, Giorgio; Cavrini, Francesca; Rossini, Giada; Capobianchi, Maria Rosaria; Di, Antonino; Menzo, Stefano; Pagliaro, P; Ghinelli, F; Lazzarotto, Tiziana; Landini, Maria Paola; Pinna, Antonio Daniele

doi:10.1086/655146

Cited by 50 publications

(41 citation statements)

References 15 publications

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“…However, the blood of this tested organ donor was negative for WNV by nucleic acid amplification (NAT). In contrast, WNV testing of deceased organ donors in the United States is currently not required (28) and, therefore, was not done in the other six donors who lived in the United States or in another Italian donor before organ procurement (22). Retrospectively, only four (50%) of the eight donors tested positive for WNV by serum PCR, and only three of the eight donors (38%) tested positive for serum WNV IgM.…”

Section: Review Of Clinical Diagnostic and Therapeutic Features Of mentioning

confidence: 99%

Donor-Derived West Nile Virus Infection in Solid Organ Transplant Recipients

et al. 2014

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We describe four solid-organ transplant recipients with donor-derived West Nile virus (WNV) infection (encephalitis 3, asymptomatic 1) from a common donor residing in a region of increased WNV activity. All four transplant recipients had molecular evidence of WNV infection in their serum and/or cerebrospinal fluid (CSF) by reverse transcription polymerase chain reaction (RT-PCR) testing. Serum from the organ donor was positive for WNV IgM but negative for WNV RNA, whereas his lymph node and spleen tissues tested positive for WNV by RT-PCR. Combination therapy included intravenous immunoglobulin (4 cases), interferon (3 cases), fresh frozen plasma with WNV IgG (2 cases), and ribavirin (1 case). Two of the four transplant recipients survived. Review of the 20 published cases of organ-derived WNV infection found that this infection is associated with a high incidence of neuroinvasive disease (70%) and severe morbidity and mortality (30%). Median time to onset of symptomatic WNV infection was 13 days after transplantation (range 5–37 days). Initial unexplained fever unresponsive to antibiotic therapy followed by rapid onset of neurologic deficits was the most common clinical presentation. Confirmation of infection was made by testing serum and CSF for both WNV RNA by RT-PCR and WNV IgM by serological assays. Treatment usually included supportive care, reduction of immunosuppression, and frequent intravenous immunoglobulin. The often negative results for WNV by current RT-PCR and serological assays and the absence of clinical signs of acute infection in donors contribute to the sporadic occurrence of donor-derived WNV infection. Potential organ donors should be assessed for unexplained fever and neurological symptoms, particularly if they reside in areas of increased WNV activity.

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Section: Review Of Clinical Diagnostic and Therapeutic Features Of mentioning

confidence: 99%

Donor-Derived West Nile Virus Infection in Solid Organ Transplant Recipients

et al. 2014

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“…Recent studies implicating dysregulated CNS inflammation as a major cause of WNV-induced mortality suggested that immunomodulatory drugs may be beneficial (Getts et al, 2008;King et al, 2011;Wang et al, 2011). Several reports have documented the success of IVIG (intravenous immunoglobulins) as a treatment for patients with WNV CNS infections (Agrawal & Petersen, 2003;Kumar et al, 2004;Makhoul et al, 2009;Morelli et al, 2010;Rhee et al, 2011;Saquib et al, 2008;Shimoni et al, 2012;Wadei et al, 2004;Yango et al, 2014). Studies in murine models using low doses of IVIG preparations that contained high titres of WNV neutralizing antibodies confirmed robust protection from WNV encephalitis (Ben-Nathan et al, 2003.…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory activity of intravenous immunoglobulins protects against West Nile virus encephalitis

Srivastava

Ramakrishna

Cantin

2015

Journal of General Virology

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West Nile virus (WNV), an important global human pathogen, targets neurons to cause lethal encephalitis, primarily in elderly and immunocompromised patients. Currently, there are no approved therapeutic agents or vaccines to treat WNV encephalitis. Recent studies have suggested that inflammation is a major contributor to WNV encephalitis morbidity. In this study we evaluated the use of IVIG (intravenous immunoglobulins -a clinical product comprising pooled human IgG) as an anti-inflammatory treatment in a model of lethal WNV infection. We report here that IVIG and pooled human WNV convalescent sera (WNV-IVIG) inhibited development of lethal WNV encephalitis by suppressing central nervous system (CNS) infiltration by CD45 high leukocytes. Pathogenic Ly6C high CD11b + monocytes were the major infiltrating subset in the CNS of infected control mice, whereas IVIG profoundly reduced infiltration of these pathogenic Ly6C high monocytes into the CNS of infected mice. Interestingly, WNV-IVIG was more efficacious than IVIG in controlling CNS inflammation when mice were challenged with a high-dose inoculum (10 5 versus 10 4 p.f.u.) of WNV. Importantly, adsorption of WNV E-glycoprotein neutralizing antibodies did not abrogate IVIG protection, consistent with virus neutralization not being essential for IVIG protection. These findings confirmed the potent immunomodulatory activity of generic IVIG, and emphasized its potential as an effective immunotherapeutic drug for encephalitis and other virus induced inflammatory diseases.

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“…These show that the course of the disease in patients with neurological symptoms improved and that treated patients survived [59,106,181]. At present, limited amounts of specific immunoglobulin preparations are available that were produced in Israel from WNV antibodypositive plasma.…”

Section: Use Of Immunoglobulinsmentioning

confidence: 88%

“…Transmission of WNV to recipients of organ transplants was reported from Italy in 2009, while the organ donor showed no sign of infection and no WNV genome could be detected by PCR in the blood of the donor [106][107][108]. Donor screening by PCR is performed due to the epidemiological situation in Italy.…”

Section: Further Transmission Routes (Iatrogenic Motherchild Transpmentioning

confidence: 99%

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West Nile Virus

2013

Transfus Med Hemother

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Absence of Neuroinvasive Disease in a Liver Transplant Recipient Who Acquired West Nile Virus (WNV) Infection from the Organ Donor and Who Received WNV Antibodies Prophylactically

Cited by 50 publications

References 15 publications

Donor-Derived West Nile Virus Infection in Solid Organ Transplant Recipients

Donor-Derived West Nile Virus Infection in Solid Organ Transplant Recipients

Anti-inflammatory activity of intravenous immunoglobulins protects against West Nile virus encephalitis

West Nile Virus

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