Low population Japanese encephalitis virus (JEV) seroprevalence in Udayapur district, Nepal, three years after a JE vaccination programme: A case for further catch up campaigns?

The live attenuated Japanese encephalitis (JE) vaccine SA14-14-2 has been used in Nepal for catch-up campaigns and is now included in the routine immunisation schedule. Previous studies have shown good vaccine efficacy after one dose in districts with a high incidence of JE. The first well-documented dengue outbreak occurred in Nepal in 2006 with ongoing cases now thought to be secondary to migration from India. Previous infection with dengue virus (DENV) partially protects against JE and might also influence serum neutralising antibody titres against JEV. This study aimed to determine whether serum anti-JEV neutralisation titres are: 1. maintained over time since vaccination, 2. vary with historic local JE incidence, and 3. are associated with DENV neutralising antibody levels. We conducted a cross-sectional study in three districts of Nepal: Banke, Rupandehi and Udayapur. Udayapur district had been vaccinated against JE most recently (2009), but had been the focus of only one campaign, compared with two in Banke and three in Rupandehi. Participants answered a short questionnaire and serum was assayed for anti-JEV and anti-DENV IgM and IgG (by ELISA) and 50% plaque reduction neutralisation titres (PRNT50) against JEV and DENV serotypes 1-4. A titre of ≥1:10 was considered seropositive to the respective virus. JEV neutralising antibody seroprevalence (PRNT50 ≥ 1:10) was 81% in Banke and Rupandehi, but only 41% in Udayapur, despite this district being vaccinated more recently. Sensitivity of ELISA for both anti-JEV and anti-DENV antibodies was low compared with PRNT50. DENV neutralising antibody correlated with the JEV PRNT50 ≥1:10, though the effect was modest. IgM (indicating recent infection) against both viruses was detected in a small number of participants. We also show that DENV IgM is present in Nepali subjects who have not travelled to India, suggesting that DENV may have become established in Nepal. We therefore propose that further JE vaccine campaigns should be considered in Udayapur district, and similar areas that have had fewer vaccination campaigns.

Ploidy and karyotype complexity are powerful prognostic indicators in the Ewing's sarcoma family of tumors: a study by the United Kingdom Cancer Cytogenetics and the Children's Cancer and Leukaemia Group.

Ewing's sarcoma family tumors (ESFT) are characterized by the presence of EWSR1-ETS fusion genes. Secondary chromosome changes are frequently described, although their clinical significance is not clear. In this study, we have collected and reviewed abnormal karyotypes from 88 patients with primary ESFT and a rearrangement of 22q12. Secondary changes were identified in 80% (70/88) of tumors at diagnosis. Multivariate analysis showed a worse overall and relapse free survival (RFS) for those with a complex karyotype (overall survival, P = 0.005; RFS, P = 0.04), independent of metastatic disease. Univariate survival analysis showed that a chromosome number above 50 or a complex karyotype was associated with a worse overall survival (>50 chromosomes, P = 0.05; complex karyotype, P = 0.04). There was no association between type of cytogenetic abnormality and the presence of metastatic disease at diagnosis. Univariate and multivariate survival analysis of a small subgroup with trisomy 20 indicated that trisomy 20 was associated with a worse overall and RFS. There was no difference in outcome associated with other recurrent trisomies (2, 5, 7, 8, or 12) or the common recurrent secondary structural rearrangements (deletions of 1p36, 9p12, 17p13, and 16q, and gain of 1q), although numbers were small. These data demonstrate the continued value of cytogenetics as a genome-wide screen in ESFT and illustrates the potential importance of secondary chromosome changes for stratification of patients for risk. Specifically, karyotype complexity appears to be a powerful predictor of prognosis, and the presence of trisomy 20 may be a marker of a more aggressive subset of this group.