Live Viral Vaccine Neurovirulence Screening: Current and Future Models.

Live viral vaccines are one of the most successful methods for controlling viral infections but require strong evidence to indicate that they are properly attenuated. Screening for residual neurovirulence is an important aspect for live viral vaccines against potentially neurovirulent diseases. Approximately half of all emerging viral diseases have neurological effects, so testing of future vaccines will need to be rapid and accurate. The current method, the monkey neurovirulence test (MNVT), shows limited translatability for human diseases and does not account for different viral pathogenic mechanisms. This review discusses the MNVT and potential alternative models, including in vivo and in vitro methods. The advantages and disadvantages of these methods are discussed, and there are promising data indicating high levels of translatability. There is a need to investigate these models more thoroughly and to devise more accurate and rapid alternatives to the MNVT.

Long-term, West Nile virus-induced neurological changes: A comparison of patients and rodent models.

West Nile virus (WNV) is a mosquito-borne virus that can cause severe neurological disease in those infected. Those surviving infection often present with long-lasting neurological changes that can severely impede their lives. The most common reported symptoms are depression, memory loss, and motor dysfunction. These sequelae can persist for the rest of the patients' lives. The pathogenesis behind these changes is still being determined. Here, we summarize current findings in human cases and rodent models, and discuss how these findings indicate that WNV induces a state in the brain similar neurodegenerative diseases. Rodent models have shown that infection leads to persistent virus and inflammation. Initial infection in the hippocampus leads to neuronal dysfunction, synapse elimination, and astrocytosis, all of which contribute to memory loss, mimicking findings in neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). WNV infection acts on pathways, such as ubiquitin-signaled protein degradation, and induces the production of molecules, including IL-1ß, IFN-γ, and α-synuclein, that are associated with neurodegenerative diseases. These findings indicate that WNV induces neurological damage through similar mechanisms as neurodegenerative diseases, and that pursuing research into the similarities will help advance our understanding of the pathogenesis of WNV-induced neurological sequelae.

Persistence of yellow fever virus-specific neutralizing antibodies after vaccination among US travellers.

Background: Few studies have assessed the duration of humoral immunity following yellow fever (YF) vaccination in a non-endemic population. We evaluated seropositivity among US resident travellers based on time post-vaccination. Methods: We identified serum samples from US travellers with YF virus-specific plaque reduction neutralization testing (PRNT) performed at CDC from 1988 to 2016. Analyses were conducted to assess the effect of time since vaccination on neutralizing antibody titer counts. Results: Among 234 travellers who had neutralizing antibody testing performed on a specimen obtained ≥1 month after vaccination, 13 received multiple YF vaccinations and 221 had one dose of YF vaccine reported. All 13 who received more than one dose of YF vaccine had a positive PRNT regardless of the amount time since most recent vaccination. Among the 221 travellers with one reported dose of YF vaccine, 155 (70%) were vaccinated within 10 years (range 1 month-9 years) and 66 (30%) were vaccinated ≥10 years (range 10-53 years) prior to serum collection. Among the 155 individuals vaccinated, <10 years prior to serum collection, 146 (94%) had a positive PRNT compared with 82% (54/66) of individuals vaccinated ≥10 years prior to serum collection (P = 0.01). Post-vaccination PRNT titers showed a time-dependent decrease. Individuals with immunocompromising conditions were less likely to have a positive PRNT (77%) compared with those who were not immunocompromised (92%; P = 0.04). Conclusion: Although the percentage of vaccinees with a positive PRNT and antibody titers decreased over time, a single dose of YF vaccine provided long-lasting protection in the majority of US travellers. A booster dose could be considered for certain travellers who are planning travel to a high risk area based on immune competence and time since vaccination.

Knowledge and use of prevention measures for chikungunya virus among visitors - Virgin Islands National Park, 2015.

BACKGROUND: In June 2014, the mosquito-borne chikungunya virus (CHIKV) emerged in the U.S. Virgin Islands (USVI), a location where tourists comprise the majority of the population during peak season (January-April). Limited information is available concerning visitors' CHIKV awareness and prevention measures. METHODS: We surveyed a convenience sample of Virgin Islands National Park visitors aged ≥18 years. Respondents completed a questionnaire assessing CHIKV knowledge, attitudes, and practices; health information-seeking practices; and demographics. RESULTS: Of 783 persons contacted, 443 (57%) completed the survey. Fewer than half (208/441 [47%]) were aware of CHIKV. During trip preparation, 28% of respondents (126/443) investigated USVI-specific health concerns. Compared with persons unaware of CHIKV, CHIKV-aware persons were more likely to apply insect repellent (134/207 [65%] versus 111/231 [48%]; p < 0.001), wear long-sleeves and long pants (84/203 [41%] versus 57/227 [25%]; p < 0.001), and wear insect repellent-treated clothing (36/204 [18%] versus 22/227 [10%]; p = 0.02). CONCLUSIONS: The majority of visitors surveyed did not research destination-related health concerns and were unaware of CHIKV. However, CHIKV awareness was associated with using multiple prevention measures to reduce disease risk. These findings underscore the importance of providing tourists with disease education upon destination arrival.