METHODS: Samples were obtained from 172/192 children presenting to a site in rural India with acute encephalitis syndrome.
RESULTS: Using the reference VT ELISA, infection with Japanese encephalitis virus (JEV) was confirmed in 44 (26%) patients, with central nervous system infection confirmed in 27 of these; seven patients were dengue seropositive. Of the 121 remaining patients, 37 (31%) were JEV negative and 84 (69%) were JEV unknown because timing of the last sample tested was <10 day of illness or unknown. For patient classification with XCyton, using cerebrospinal fluid alone (the recommended sample), sensitivity was 77.8% (59.2-89.4) with specificity of 97.3% (90.6-99.2). For Panbio ELISA, using serum alone (the recommended sample), sensitivity was 72.5% (57.2-83.9) with specificity of 97.5% (92.8-99.1). Using all available samples for patient classification, sensitivity and specificity were 63.6% (95% CI: 48.9-76.2) and 98.4% (94.5-99.6), respectively, for XCyton ELISA and 75.0% (59.3-85.4) and 97.7% (93.3-99.2) for Panbio ELISA.
CONCLUSION: The two commercially available ELISAs had reasonable sensitivities and excellent specificities for diagnosing JEV.
METHODS: We performed targeted capture and next-generation sequencing of 85 cancer susceptibility genes on germline DNA from 198 patients with pleural, peritoneal, and tunica vaginalis MM.
RESULTS: Twenty-four germline mutations were identified in 13 genes in 23 (12%) of 198 patients. BAP1 mutations were the most common (n = 6; 25%). The remaining were in genes involved in DNA damage sensing and repair (n = 14), oxygen sensing (n = 2), endosome trafficking (n = 1), and cell growth (n = 1). Pleural site (odds ratio [OR], 0.23; 95% CI, 0.10 to 0.58; P < .01), asbestos exposure (OR, 0.28; 95% CI, 0.11 to 0.72; P < .01), and older age (OR, 0.95; 95% CI, 0.92 to 0.99; P = .01) were associated with decreased odds of carrying a germline mutation, whereas having a second cancer diagnosis (OR, 3.33; 95% CI, 1.22 to 9.07; P = .02) significantly increased the odds. The odds of carrying a mutation in BAP1 (OR, 1,658; 95% CI, 199 to 76,224; P < .001), BRCA2 (OR, 5; 95% CI, 1.0 to 14.7; P = .03), CDKN2A (OR, 53; 95% CI, 6 to 249; P < .001), TMEM127 (OR, 88; 95% CI, 1.7 to 1,105; P = .01), VHL (OR, 51; 95% CI, 1.1 to 453; P = .02), and WT1 (OR, 20; 95% CI, 0.5 to 135; P = .049) were significantly higher in MM cases than in a noncancer control population. Tumor sequencing identified mutations in a homologous recombination pathway gene in 52% (n = 29 of 54).
CONCLUSION: A significant proportion of patients with MM carry germline mutations in cancer susceptibility genes, especially those with peritoneal MM, minimal asbestos exposure, young age, and a second cancer diagnosis. These data support clinical germline genetic testing for patients with MM and provide a rationale for additional investigation of the homologous recombination pathway in MM.