Fatal Case of West Nile Neuroinvasive Disease in Bulgaria.
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ABSTRACT:
SUBMITTER: Baymakova M
PROVIDER: S-EPMC5189127 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Cases of West Nile neuroinvasive disease (WNND) in Spain increased in summer 2020. Here we report on this increase and the local, regional and national public health measures taken in response. We analysed data from regional surveillance networks and the National Epidemiological Surveillance Network, both for human and animal West Nile virus (WNV) infection. During the 2020 season, a total of 77 human cases of WNV infection (median age 65 years; 60% males) were detected in the south-west of Spain; 72 (94%) of these cases developed WNND, presenting as meningoencephalitis, seven of which were fatal. In the previous two decades, only six human cases of WNND were detected in Spain. Reduced activities for vector control this season, together with other factors, might have contributed to the massive increase. Public health measures including vector control, campaigns to raise awareness among physicians and the general population, and interventions to ensure the safety of donations of blood products, organs, cells and tissues were effective to reduce transmission. Going forward, maintenance of vector control activities and an update of the vector-borne diseases response plan in Spain is needed.
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Project description:BackgroundWest Nile Virus (WNV) is a mosquito-borne flavivirus that has caused ongoing seasonal epidemics in the United States since 1999. It is estimated that ≤1% of WNV-infected patients will develop neuroinvasive disease (West Nile encephalitis and/or myelitis) that can result in debilitating morbidities and long-term sequelae. It is essential to collect longitudinal information about the recovery process and to characterize predicative factors that may assist in therapeutic decision-making in the future.MethodsWe report a longitudinal study of the neurological outcomes (as measured by neurological examination, Glascow Coma Scale, and Modified Mini-Mental State Examination) for 55 subjects with WNV neuroinvasive disease (confirmed by positive CSF IgM) assessed on day 7, at discharge, and on days 14, 30, and 90. The neurological outcome measures were coma (presence and degree), global cognitive status, presence of cranial neuropathy, tremors and/or weakness.ResultsAt initial clinical presentation 93% presented with a significant neurological deficit (49% with weakness, 35% with tremor, and 16% with cranial neuropathy). The number of patients with a cognitive deficit fell from 25 at initial evaluation to 9 at their last evaluation. Cranial neuropathy was present in 9 at onset and in only 4 patients at study conclusion. Of the 19 patients who had a tremor at enrollment, 11 continued to exhibit a tremor at follow-up. Seven patients died after initial enrollment in the study, with 5 of those having presented in a coma. The factors that predict either severity or long-term recovery of neurological function include age (older individuals were weaker at follow-up examination), gender (males recovered better from coma), and presentation in a coma with cranial nerve deficits (had a poorer recovery particularly with regard to cognition).ConclusionsThis study represents one of the largest clinical investigations providing prospectively-acquired neurological outcomes data among American patients with WNV central nervous system disease. The findings show that the factors that influence prognosis from the initial presentation include age, gender, and specific neurological deficits at onset.Trial registrationClinicalTrials.gov identifier: NCT00138463 and NCT00069316.
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Project description:West Nile virus (WNV) infection results in a diverse spectrum of outcomes, and host genetics are likely to influence susceptibility to neuroinvasive disease (West Nile neuroinvasive disease (WNND)). We performed whole-exome sequencing of 44 individuals with WNND and identified alleles associated with severe disease by variant filtration in cases, kernel association testing in cases and controls and single-nucleotide polymorphism (SNP) imputation into a larger cohort of WNND cases and seropositive controls followed by genome-wide association analysis. Variant filtration prioritized genes based on the enrichment of otherwise rare variants, but did not unambiguously implicate variants shared by a majority of cases. Kernel association demonstrated enrichment for risk and protective alleles in the human leukocyte antigen (HLA)-A and HLA-DQB1 loci that have well understood roles in antiviral immunity. Two loci, HERC5 and an intergenic region between CD83 and JARID2, were implicated by multiple imputed SNPs and exceeded genome-wide significance in a discovery cohort (n=862). SNPs at two additional loci, TFCP2L1 and CACNA1H, achieved genome-wide significance after association testing of directly genotyped and imputed SNPs in a discovery cohort (n=862) and a separate replication cohort (n=1387). The context of these loci suggests that immunoregulatory, ion channel and endothelial barrier functions may be important elements of the host response to WNV.
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