Neuroinvasive St. Louis Encephalitis Virus Infection in Solid Organ Transplant Recipients.

In summer 2015, three unrelated solid organ transplant recipients in Phoenix, Arizona, had meningoencephalitis suggestive of West Nile virus (WNV) infection. Testing was inconclusive but was later confirmed as St. Louis encephalitis (SLE). We retrospectively reviewed clinical manifestations, treatment, and outcomes of these transplant recipients. Common symptoms were fever, rigors, diarrhea, headache, and confusion. One patient died 3 days after hospitalization. Therapy for the other two patients was initiated with interferon α-2b (IFN) and intravenous IgG (IVIG; IFN plus IVIG in combination). Both patients tested positive for WNV by serologic assay, but SLE virus (SLEV) infection was later confirmed by plaque reduction neutralization test at a reference laboratory. Clinical improvement was observed within 72 h after initiation of IFN plus IVIG. SLEV has been an uncommon cause of neuroinvasive disease in the United States. Accurate, timely diagnosis is hindered because of clinical presentation similar to neuroinvasive WNV and SLE, serologic cross-reactivity, and lack of a commercially available serologic assay for SLEV. There is currently no approved therapy for flaviviral neuroinvasive disease. Anecdotal reports indicate varying success with IFN, IVIG, or IFN plus IVIG in WNV neuroinvasive disease. The same regimen might be of value for immunocompromised persons with neuroinvasive SLEV infection.

St. Louis encephalitis in early infancy.

We describe a case of St. Louis encephalitis in a 19-day-old infant who presented with fever and seizure activity. To our knowledge, this is the youngest case of St. Louis encephalitis ever reported.

Effect of interferon-alpha2b therapy on St. Louis viral meningoencephalitis: clinical and laboratory results of a pilot study.

The safety and potential efficacy of interferon (IFN)-alpha2b were determined for 15 patients during an outbreak of meningoencephalitis due to St. Louis encephalitis (SLE) virus. Clinical and laboratory results were compared with those of 17 untreated patients who were admitted to the same hospital during this nonrandomized preliminary trial. Quadriplegia, quadriparesis, or respiratory insufficiency persisted after the first week of hospitalization, for 11 of 17 untreated patients and for only 2 of 15 treated patients. These complications existed after the second week of hospitalization for 5 of the 17 untreated patients and for 1 of the 15 treated patients. Transient neutropenia and/or mild hepatitis occurred in 11 treated patients. Early initiation of IFN-alpha2b therapy may reduce the severity and duration of complications due to previously untreatable flavivirus meningoencephalitis. A prospective randomized controlled trial is warranted.

Antibody and interleukin-12 treatment in murine models of encephalitogenic flavivirus (St. Louis encephalitis, tick-borne encephalitis) and alphavirus (Venezuelan equine encephalitis) infection.

Early and sustained treatment with interleukin-12 (IL-12) ameliorated disease in a mouse model of infection with the encephalitogenic flavivirus, St. Louis encephalitis virus (SLEV, Japanese encephalitis serogroup). However, this effect was not reproduced in murine infections with either the flavivirus tick-bore encephalitis virus (TBEV) or the alphavirus Venezuelan equine encephalitis virus (VEEV). IL-12 exacerbated TBEV disease when used in conjunction with monoclonal antibody (mAb), suggesting an enhancement of immunopathology, and was without clinical effects in VEEV infection. These data confirm the need to fully understand the pathogenesis of viral infection before cytokine intervention may be employed as a broad-spectrum antiviral therapy.

Interferon-alpha protects mice against lethal infection with St Louis encephalitis virus delivered by the aerosol and subcutaneous routes.

In common with other flaviviruses, there is no specific therapy for St Louis encephalitis (SLE) virus infections. A number of cases have occurred where infection may have been acquired by the aerosol route in laboratory accidents. The recombinant human interferon hybrids IFN-alpha A/D (Roche Laboratories) and IFN-alpha B/D (Ciba-Geigy) have activity in murine models. Given for several days around the time of exposure to the virus or shortly after, these compounds reduce the mortality from SLE virus administered to mice subcutaneously by up to 70%. In an aerosol model of SLE disease, the mortality was reduced to 30-50% compared to 100% in controls, depending on the challenge level of virus. These results suggest that interferon-alpha could be used to reduce the mortality from SLE infection after known exposure to the virus.