Although West Nile virus (WNV) has been a prominent mosquito-transmitted infection in North America for twenty years, no human vaccine has been licensed. With a cumulative number of 24,714 neurological disease cases and 2314 deaths in the U.S. since 1999, plus a large outbreak in Europe in 2018 involving over 2000 human cases in 15 countries, a vaccine is essential to prevent continued morbidity, mortality, and economic burden. Currently, four veterinary vaccines are licensed, and six vaccines have progressed into clinical trials in humans. All four veterinary vaccines require multiple primary doses and annual boosters, but for a human vaccine to be protective and cost effective in the most vulnerable older age population, it is ideal that the vaccine be strongly immunogenic with only a single dose and without subsequent annual boosters. Of six human vaccine candidates, the two live, attenuated vaccines were the only ones that elicited strong immunity after a single dose. As none of these candidates have yet progressed beyond phase II clinical trials, development of new candidate vaccines and improvement of vaccination strategies remains an important area of research.

West Nile virus (WNV) is a mosquito-borne infectious disease that can produce potentially life-threatening meningoencephalitis in immunocompromised individuals. In 2017, there were 536 human cases of WNV in California, with 43 fatalities reported to the California Department of Public Health. Peak mosquito transmission periods are in the late summer and early fall when mosquitoes are maximally viremic. In addition to risk factors such as advanced age, malignancy, or prior organ transplantation, the probability of progression to severe, neuroinvasive disease has been reported to be significantly higher in individuals suffering from lymphoma receiving rituximab in addition to other oncologic treatments. Here, we describe the case of a patient who recently received chemotherapy with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone for diffuse large B-cell lymphoma, complicated by meningoencephalitis due to seronegative neuroinvasive WNV infection, ultimately resulting in death.