The Incidence of Japanese Encephalitis in Taiwan—A Population-Based Study

<div><p>Background</p><p>A mass Japanese encephalitis (JE) vaccination program targeting children was launched in Taiwan in 1968, and the number of pediatric JE cases substantially decreased thereafter. The aim of this study was to elucidate the long-term trend of JE incidence, and to investigate the age-specific seroprevalence of JE-neutralizing antibodies.</p><p>Methodology/Principal Findings</p><p>A total of 2,948 laboratory-confirmed JE cases that occurred between 1966 and 2012 were analyzed using a mandatory notification system managed by the Centers for Disease Control, Taiwan. A total of 6,594 randomly-sampled serum specimens obtained in a nationwide population-based survey in 2002 were analyzed to estimate the seroprevalence of JE-neutralizing antibodies in the general population. The average annual JE incidence rate of the group aged 30 years and older was 0.167 cases per 100,000 people between 2001 and 2012, which was higher than the 0.052 cases per 100,000 people among those aged under 30 years. These seroepidemiological findings indicate that the cohort born between 1963 and 1975, who generally received two or three doses of the vaccine and were administered the last booster dose more than 20 years ago, exhibited the lowest positive rate of JE-neutralizing antibodies (54%). The highest and second highest antibody rates were observed, respectively, in the oldest unvaccinated cohort (86%) and in the youngest cohort born between 1981 and 1986, who received four doses 10–15 years ago (74%).</p><p>Conclusion/Significance</p><p>Over the past decade, the main age group of the confirmed JE cases in Taiwan shifted from young children to adults over 30 years of age. People who were born between 1963 and 1975 exhibited the lowest seroprevalence of JE-neutralizing antibodies. Thus, the key issue for JE control in Taiwan is to reduce adult JE cases through a cost-effective analysis of various immunization strategies.</p></div

Incidence rates and onset age distributions of Japanese Encephalitis confirmed cases in Taiwan, 2002–2012.

a<p>The incidence rate is the number of JE confirmed cases per 100,000 population at risk.</p>b<p>There were two JE confirmed cases have been received 1 dose of vaccine in 2008 and one has been vaccinated with 3 doses, in 2012.</p

Age-specific incidence rates of Japanese Encephalitis during 1966–2012.

<p>Age-specific incidence rates of Japanese Encephalitis during 1966–2012.</p

Japanese Encephalitis incidence rates among different birth cohorts during 1966–2012.

<p>Japanese Encephalitis incidence rates among different birth cohorts during 1966–2012.</p

The cases number of Japanese Encephalitis and incidence rate in Taiwan during 1966–2012.

<p>The cases number of Japanese Encephalitis and incidence rate in Taiwan during 1966–2012.</p

Phylogenetic and Evolutionary History of Influenza B Viruses, which Caused a Large Epidemic in 2011–2012, Taiwan

<div><p>The annual recurrence of the influenza epidemic is considered to be primarily associated with immune escape due to changes to the virus. In 2011–2012, the influenza B epidemic in Taiwan was unusually large, and influenza B was predominant for a long time. To investigate the genetic dynamics of influenza B viruses during the 2011–2012 epidemic, we analyzed the sequences of 4,386 influenza B viruses collected in Taiwan from 2004 to 2012. The data provided detailed insight into the flux patterns of multiple genotypes. We found that a re-emergent TW08-I virus, which was the major genotype and had co-circulated with the two others, TW08-II and TW08-III, from 2007 to 2009 in Taiwan, successively overtook TW08-II in March and then underwent a lineage switch in July 2011. This lineage switch was followed by the large epidemic in Taiwan. The whole-genome compositions and phylogenetic relationships of the representative viruses of various genotypes were compared to determine the viral evolutionary histories. We demonstrated that the large influenza B epidemic of 2011–2012 was caused by Yamagata lineage TW08-I viruses that were derived from TW04-II viruses in 2004–2005 through genetic drifts without detectable reassortments. The TW08-I viruses isolated in both 2011–2012 and 2007–2009 were antigenically similar, indicating that an influenza B virus have persisted for 5 years in antigenic stasis before causing a large epidemic. The results suggest that in addition to the emergence of new variants with mutations or reassortments, other factors, including the interference of multi-types or lineages of influenza viruses and the accumulation of susceptible hosts, can also affect the scale and time of an influenza B epidemic.</p> </div

Phylogentic analysis of HA genes and distribution of various genotypes.

<p>(A) Phylogenetic topology of the HA genes from multiple genotypes of influenza B viruses from 2007 to 2012 in Taiwan. The phylogenetic trees were constructed using the neighbor-joining method with 1000 bootstrap replications. Branch values of more than 70 are indicated. Based on the phylogenetic analyses and the amino acid signatures of HA genes, the circulating Yam88 viruses were classified into three genotypes, TW08-I, TW08-II, and TW08-III, which are represented by the viruses B/Taiwan/3798/2007, B/Taiwan/30/2008 and B/Taiwan/2563/2008, respectively. The major amino acid signatures of each genotype are as the following: 63K, 123A and 266M for TW08-I; 165I, 180Y, 244D and 266M for TW08-II; and 244S and 266M for TW08-III. (B) The monthly distribution of various genotypes. The monthly numbers of each genotype are shown as a line chart. The inserts indicate the ratios of the three genotypes in 2008, 2010 and 2011.</p

Data from the laboratory-based surveillance network in Taiwan from 2004 to 2012.

<p>(A) The monthly distributions of the influenza isolates, including A(H1N1), A(H3N2), A(H1N1)pdm09 and influenza B viruses, are shown as bars. Positive rates of confirmed cases are also shown in the line chart. (B) The dynamic changes in influenza B activity. The monthly positive rates of influenza B represent the percentage of confirmed influenza B cases among all reported and tested cases in a specific month. The predominance of influenza B was calculated by dividing the number of all influenza viruses by the number of confirmed influenza B viruses. (C) The lineage distribution of influenza B viruses. The Victoria (Vic87) and Yamagata (Yam88) lineages isolated from 2004 to 2012 were classified based on their HA genes. The numbers of influenza B viruses analyzed each month are shown as bars, and the monthly ratio of each lineage is shown as a line chart.</p

Antigenic analysis of the Yamagata lineage influenza B viruses by hemagglutination inhibition assay.

*<p>Passage history of virus was indicated by the number; e.g. viruses of second generation propagated in MDCK cells from clinical specimens were indicated as C2.</p

Diagram representing the evolutionary histories of Yamagata-lineage influenza B viruses in Taiwan.

<p>The genome compositions of various genotypes are based on the phylogenetic topographies in Fig. 3, and the genotype definitions and representative viruses are described in the legends of Fig. 2 and 3. The gene segments of the viruses are presented in the order of PB1, PB2, PA, HA, NP, NA, M, and NS (from top to bottom). The circulation time period of each genotype is also illustrated. Blue arrows represent possible evolutionary pathways of genotype development. Green arrows represent reassortment between BE98 and existing genotypes. For example, the TW04-II was generated through reassortment between CA00 virus, providing PB2, PA, NP and NS segments and BE98 virus, providing PB1, HA, NA and MP segments. The red arrow indicates the acquisition of segments from YA98 through reassortment. CA00: B/Canada/16188/2000-like viruses; BE98: B/Beijing/76/98-like viruses; YA98: B/Yamanashi/166/98-like viruses.</p