Evaluation of mouse brain-derived, inactivated Japanese encephalitis vaccine

Japanese encephalitis (JE) is a serious encephalitis caused by JE virus. Approximately 20% of JE patients die and 50% patients recover with neuro-psychiatric sequelae. In Japan, the number of JE patients was over 1000 per year in 1960s; however, the number decreased dramatically and has been less than 10 since 1990. Ministry of Health, Labour and Welfare suspended the strong recommendation for vaccination with the mouse brain-derived JE vaccine, because of cases who developed acute disseminated encephalomyelitis (ADEM) after vaccination with JE vaccine. However, it has not been fully confirmed on scientific bases that ADEM was caused by mouse brain-derived JE vaccine. Tissue culture derived-JE vaccine is under development. It is expected that this new vaccine will come to the market soon and that the recommendation of universal vaccination with JE vaccine will be implemented at the earliest occasion.     

Sero-Molecular Epidemiology of Japanese Encephalitis in Zhejiang,an Eastern Province of China

BackgroundSporadic Japanese encephalitis (JE) cases still have been reported in Zhejiang Province in recent years, and concerns about vaccine cross-protection and population-level immunity have been raised off and on within the public health sphere. Genotype I (GI) has replaced GIII as the dominant genotype in Asian countries during the past few decades, which caused considerable concerns about the potential change of epidemiology characteristics and the vaccine effectiveness. The aim of this study was to investigate the prevalence of JE neutralizing antibody and its waning antibody trend after live attenuated JE vaccine immunization. Additionally, this study analyzed the molecular characteristics of the E gene of Zhejiang Japanese encephalitis virus (JEV) strains, and established genetic relationships with other JEV strains.Conclusion/SignificancesJE neutralizing antibody positive rates increase in age ≥10 years old population, likely reflecting natural infection or natural boosting of immunity through exposure to wild virus. JE seropositivity rates were quite low in <35 years old age groups in Zhejiang Province. Waning of neutralizing antibody after live attenuated vaccine immunization was observed, but the clinical significance should be further investigated. Both the peripheral antibody response and genetic characterization indicate that current live attenuated JE vaccine conferred equal neutralizing potency against GI or GIII of wild strains. GI has replaced GIII as the dominant genotype in Zhejiang in the past few decades. Although the chance of exposure to wild JE virus has reduced, the virus still circulates in nature; therefore, it is necessary to implement immunization program for children continually and to conduct surveillance activity periodically.     

Enzyme-linked immunosorbent assay for detection of serum antibody in children vaccinated with Japanese encephalitis vaccine

Serum antibodies in children who had been vaccinated with Japanese encephalitis (JE) vaccine were measured by enzyme-linked immunosorbent assay (ELISA) and neutralization (N) and hemagglutination-inhibition (HI) tests. Of 20 serum samples obtained after two shots of JE vaccine in the first year, all but one showed positive titers in the ELISA and N test, but five showed negative titers in the HI test. All 12 serum samples obtained after booster immunization with JE vaccine in the second year showed positive and considerably higher titers in all three tests. Moreover, a high correlation was found between the ELISA, N and HI titers. These results indicate that the ELISA is useful for detecting antibodies in subjects immunized with JE vaccine.     

Effectiveness of the Viet Nam Produced,Mouse Brain-Derived,Inactivated Japanese Encephalitis Vaccine in Northern Viet Nam

Background

Japanese encephalitis (JE) is a flaviviral disease of public health concern in many parts of Asia. JE often occurs in large epidemics, has a high case-fatality ratio and, among survivors, frequently causes persistent neurological sequelae and mental disabilities. In 1997, the Vietnamese government initiated immunization campaigns targeting all children aged 1–5 years. Three doses of a locally-produced, mouse brain-derived, inactivated JE vaccine (MBV) were given. This study aims at evaluating the effectiveness of Viet Nam''s MBV.

Methodology

A matched case-control study was conducted in Northern Viet Nam. Cases were identified through an ongoing hospital-based surveillance. Each case was matched to four healthy controls for age, gender, and neighborhood. The vaccination history was ascertained through JE immunization logbooks maintained at local health centers.

Principal Findings

Thirty cases and 120 controls were enrolled. The effectiveness of the JE vaccine was 92.9% [95% CI: 66.6–98.5]. Confounding effects of other risk variables were not observed.

Conclusions

Our results strongly suggest that the locally-produced JE-MBV given to 1–5 years old Vietnamese children was efficacious.     

Duration of neutralizing antibody titer after Japanese encephalitis vaccination

In paired serum samples collected from 17 children, we measured neutralizing antibody (NTAb) titers after the second series of routine Japanese encephalitis (JE) vaccination in Japan to estimate the duration of NTAb titer when children did not receive the third series of routine vaccination by applying a random coefficient model. We also measured NTAb titers in adult serum samples to confirm the duration of NTAb titer estimated in the analysis of pediatric serum samples. In the absence of the third series of routine vaccination, 18% (3/17), 47% (8/17), 82% (14/17) and 100% (17/17) of children were estimated to become NTAb negative at 5, 10, 15, and 20 years after the second series of routine vaccination, respectively. Of 38 adults, 39.5% (15/38) became NTAb negative; the percentage was somewhat lower than that of antibody-negative children. The results suggested that JE vaccination schedule should be reevaluated in the future.     

Epidemiology of Japanese Encephalitis in the Philippines: A Systematic Review

BackgroundJapanese encephalitis virus (JEV) is an important cause of encephalitis in most of Asia, with high case fatality rates and often significant neurologic sequelae among survivors. The epidemiology of JE in the Philippines is not well defined. To support consideration of JE vaccine for introduction into the national schedule in the Philippines, we conducted a systematic literature review and summarized JE surveillance data from 2011 to 2014.MethodsWe conducted searches on Japanese encephalitis and the Philippines in four databases and one library. Data from acute encephalitis syndrome (AES) and JE surveillance and from the national reference laboratory from January 2011 to March 2014 were tabulated and mapped.ResultsWe identified 29 published reports and presentations on JE in the Philippines, including 5 serologic surveys, 18 reports of clinical cases, and 8 animal studies (including two with both clinical cases and animal data). The 18 clinical studies reported 257 cases of laboratory-confirmed JE from 1972 to 2013. JE virus (JEV) was the causative agent in 7% to 18% of cases of clinical meningitis and encephalitis combined, and 16% to 40% of clinical encephalitis cases. JE predominantly affected children under 15 years of age and 6% to 7% of cases resulted in death. Surveillance data from January 2011 to March 2014 identified 73 (15%) laboratory-confirmed JE cases out of 497 cases tested.SummaryThis comprehensive review demonstrates the endemicity and extensive geographic range of JE in the Philippines, and supports the use of JE vaccine in the country. Continued and improved surveillance with laboratory confirmation is needed to systematically quantify the burden of JE, to provide information that can guide prioritization of high risk areas in the country and determination of appropriate age and schedule of vaccine introduction, and to measure the impact of preventive measures including immunization against this important public health threat.     

Preventive strategies for frequent outbreaks of Japanese encephalitis in Northern India

Japanese encephalitis (JE) remains the most important cause of acute viral encephalitis and continues to spread to hitherto unaffected regions like Indonesia, Pakistan and Australia. Approximately 60% of the world population inhabits JE endemic areas. Despite its restricted range mostly in the developing countries, a high annual incidence of 50,000 cases and about 10,000 deaths has been reported. Disease can be fatal in 25% cases. Magnitude of the problem is even more alarming since the survivors are left with serious long-term neuropsychiatric sequelae. Almost every two years, epidemics of JE occur in Indian subcontinent with a high mortality. JE virus infection results in different disease manifestations in host from mild subclinical febrile illness to clinical infections leading to encephalitis. No antiviral treatment is so far available for JE. The prevention of JE can be achieved by controlling the vector or by immunization regime. The vector control in the rural areas, which are the worst affected ones, is practically almost impossible. Three vaccines that have been implicated against JE include inactivated mouse brain derived, inactivated cell culture derived and cell culture derived live attenuated JE vaccine. But each has its own limitation. Currently, attempts to synthesize recombinant DNA vaccine are being made. New therapeutics are on the way of development like use of minocycline, short interfering RNA, arctigenin, rosmarinic acid, DNAzymes etc. However, the immune mechanisms that lead to JE are complex and need to be elucidated further for the development of therapeutics as well as safe and efficacious JE vaccines.     

Japanese encephalitis vaccines--needs, flaws and achievements

Japanese encephalitis causes serious health problems in countries in Southeast Asia, where the causative virus is endemic. Whereas most adults living in this region have acquired immunity, children are at high risk of infection. Childhood mass immunization programs with first-generation mouse brain-derived vaccines efficiently reduced Japanese encephalitis incidence in affected countries, but immunization recommendations have mostly been abolished in Japan owing to the occurrence of severe side effects. Thus, there is a pressing need for safer vaccines to keep the disease under control. The safety profile of the current vaccines, together with the relatively low incidence, makes the risk/benefit ratio unfavorable for immunization of travelers to Southeast Asia, despite the high mortality once the clinical disease has developed. As Asian countries become increasingly popular travel destinations, the availability of well-tolerated vaccines would likely shift the ratio towards immunization. Currently, there is one second-generation inactivated cell-culture-grown vaccine in late-stage clinical development that is approaching licensing in developed countries.     

Regional Variation in Pig Farmer Awareness and Actions Regarding Japanese Encephalitis in Nepal: Implications for Public Health Education

Japanese encephalitis (JE) is a mosquito-borne zoonotic disease that has pigs as the major amplifying hosts. It is the most important cause of viral encephalitis in people in Nepal and is spreading in its geographic distribution in that country. Pig farming is increasing in Nepal due to reducing cultural biases against pigs and government programs to support pig farming for poverty alleviation. Major strategies for JE prevention and control include education, vector control, and immunization of people and pigs. This study used a survey of 400 pig farmers in 4 areas of Nepal with different JE and pig farming histories to explore regional variations in farmer awareness and actions towards JE, the association of awareness and actions with farm and farmer variables, and the implications of these associations for public health education. Exposure to JE risk factors was common across pig farms and pig farming districts but there were significant district level differences in knowledge and practices related to on-farm JE risk reduction. Social factors such as literacy, gender, and cultural practices were associated with farmer attitudes, knowledge and practices for JE control. JE vaccine uptake was almost non-existent and mosquito control steps were inconsistently applied across all 4 districts. Income was not a determining factor of the differences, but all farmers were very poor. The low uptake of vaccine and lack of infrastructure or financial capacity to house pigs indoors or away from people suggest that farmer personal protection should be a priority target for education in Nepal. This study re-enforces the need to attack root causes of people’s personal disease prevention behaviours and take into account local variation in needs and capacities when designing health or agriculture education programs.     

Neutralizing antibody responses to Japanese encephalitis vaccine in children

Two shots of the current Japanese encephalitis (JE) vaccine were given to children and their immune responses to the Nakayama strain (the vaccine strain) and two wild strains (JaGAr-01 and E-50) of JE virus were examined by neutralizing (N) antibody titrations. Seventy vaccinees had no N antibody to JE virus before the first vaccination and were bled one month after the second vaccination. The N antibody responses to the JaGAr-01 and E-50 strains were found to be similar and to be less than that to the Nakayama strain after the second vaccination: the geometric mean titers (GMT) of N antibodies to the JaGAr-01 and E-50 strains (as logarithms) were 1.87 and 1.75, respectively, while the GMT to the Nakayama strain was 2.89. The seroconversion rates to the Nakayama, JaGAr-01 and E-50 strains were 70/70 (100%), 69/70 (99%) and 68/70 (97%), respectively, after the second vaccination. Twenty-seven of the 70 vacciness were also bled before the second vaccination. Most of them showed a considerably high N antibody response against the Nakayama strain and only one vaccinee failed to show seroconversion after the first vaccination. However, the antibody response to the E-50 strain appeared to be rather low and 9 of 25 vaccinees did not show any seroconversion. Similarly 3 of 25 failed to show any seroconversion against the JaGAr-01 strain. These results indicate that at the initial immunization two shots, at least, of the current JE vaccine are necessary to stimulate effective immune responses to wild strains of JE virus.     

Historical review and surveillance of Japanese encephalitis, Republic of Korea, 2002–2004

Japanese encephalitis virus (JEV), transmitted by culicine mosquitoes, is endemic throughout much of South‐East Asia, extending to the Korean Peninsula. The zoonotic cycle is from large water birds to culicine mosquitoes, with swine as an amplifying host and man as an incidental host. Culex tritaeniorhynchus, the primary JEV vector in the Republic of Korea, populations peak in late August through to early September when most cases of Japanese encephalitis (JE) are reported. Cx. tritaeniorhynchus were observed near the Demilitarized Zone in each of the years that mosquitoes were assayed for JEV. Each year that vector mosquitoes were assayed for JEV, minimum field infection rates (number of JEV positive mosquites/1000 Cx. tritaeniorhynchus assayed) ranged from 0.31 to 3.27. The epidemiology of JE has been recorded in Korea for more than half a century, from 1949 to 2005. During a major epidemic in 1949, there were 5616 cases and 2729 deaths reported, with levels persisting near epidemic levels of 1000 cases annually thereafter until 1969. Following the introduction and government mandated mass immunization in 1971, JE decreased dramatically. Since 1984, 0–6 cases of JE have been reported each year. However, continued evidence of mosquitoes positive for JEV indicates that JE continues to be a civilian and military health threat to immunocompromised persons in Korea, as well as non‐immune US soldiers, civilians and their family members.     

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

Background

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.

Methodology/Principal Findings

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%).

Conclusion/Significance

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.     

A single intramuscular injection of recombinant plasmid DNA induces protective immunity and prevents Japanese encephalitis in mice

Plasmid vectors containing Japanese encephalitis virus (JEV) premembrane (prM) and envelope (E) genes were constructed that expressed prM and E proteins under the control of a cytomegalovirus immediate-early gene promoter. COS-1 cells transformed with this plasmid vector (JE-4B clone) secreted JEV-specific extracellular particles (EPs) into the culture media. Groups of outbred ICR mice were given one or two doses of recombinant plasmid DNA or two doses of the commercial vaccine JEVAX. All mice that received one or two doses of DNA vaccine maintained JEV-specific antibodies 18 months after initial immunization. JEVAX induced 100% seroconversion in 3-week-old mice; however, none of the 3-day-old mice had enzyme-linked immunosorbent assay titers higher than 1:400. Female mice immunized with this DNA vaccine developed plaque reduction neutralization antibody titers of between 1:20 and 1:160 and provided 45 to 100% passive protection to their progeny following intraperitoneal challenge with 5,000 PFU of virulent JEV strain SA14. Seven-week-old adult mice that had received a single dose of JEV DNA vaccine when 3 days of age were completely protected from a 50, 000-PFU JEV intraperitoneal challenge. These results demonstrate that a recombinant plasmid DNA which produced JEV EPs in vitro is an effective vaccine.     

Epidemiological situation of measles in Japan and measures for its control

In 2007, measles outbreak occurred mainly among teen/twenties in Japan, and many high-school, universities and colleges were closed to reduce spread of measles. Some high school students became measles when they were in foreign countries where measles has been eliminated, visited as school excursion. Since introducing measles vaccine as routine immunization, number of measles has been reduced remarkably in Japan. However, we had measles outbreak in 2001, and total annual patients number were estimated 200-300 thausands mainly among young infants. The main reason was low immunization coverage of measles at 1 year old, and operation to give measles vaccine as "the gift for 1 year old birthday" has been introduced widely. Then immunization coverage at this age was increased up from 50-60% (2001) to 80-90% (2006) and total measles number was estimated less than 10,000 at 2005 and 2006, however, measles outbreak occurred this time among teen/twenties in 2007. The total number of adult measles (more than 15 y.o.) were higher than the number of them at 2001 outbreak. To discontinue outbreak and to eliminate measles, enhancement of measles control activities has been introduced in Japan. Two doses policy with measles and rubella (MR) vaccine at 1 y.o. and before elementary school has been introduced since 2006 and further, supplementary immunization with MR at 1st grade in junior high school and 3rd grade in high school for 5 years from 2008 will start to eliminate measles by 2012. Reporting system will be also changed from sentinels system to notify to all measles cases system. In this paper, present epidemiological situation on measles in Japan, measles elimination strategy in WPRO, and plan for measles elimination in Japan are described.     

乙型脑炎病毒及其疫苗的研究进展

流行性乙型脑炎是由乙型脑炎病毒引起的、经蚊虫传播的严重危害中枢神经系统的人畜共患急性传染病,其重症病死率高,易造成永久性的神经系统后遗症,严重威胁着人类的健康。目前尚无特效的治疗流行性乙型脑炎的方法,控制蚊虫传播和免疫接种是当前的主要防御手段。简要综述了乙型脑炎病毒的基因组结构、结构蛋白与非结构蛋白功能、基因分型,以及流行性乙型脑炎疫苗的研究进展。     

A Chimeric Dengue Virus Vaccine using Japanese Encephalitis Virus Vaccine Strain SA14-14-2 as Backbone Is Immunogenic and Protective against Either Parental Virus in Mice and Nonhuman Primates

The development of a safe and efficient dengue vaccine represents a global challenge in public health. Chimeric dengue viruses (DENV) based on an attenuated flavivirus have been well developed as vaccine candidates by using reverse genetics. In this study, based on the full-length infectious cDNA clone of the well-known Japanese encephalitis virus live vaccine strain SA14-14-2 as a backbone, a novel chimeric dengue virus (named ChinDENV) was rationally designed and constructed by replacement with the premembrane and envelope genes of dengue 2 virus. The recovered chimeric virus showed growth and plaque properties similar to those of the parental DENV in mammalian and mosquito cells. ChinDENV was highly attenuated in mice, and no viremia was induced in rhesus monkeys upon subcutaneous inoculation. ChinDENV retained its genetic stability and attenuation phenotype after serial 15 passages in cultured cells. A single immunization with various doses of ChinDENV elicited strong neutralizing antibodies in a dose-dependent manner. When vaccinated monkeys were challenged with wild-type DENV, all animals except one that received the lower dose were protected against the development of viremia. Furthermore, immunization with ChinDENV conferred efficient cross protection against lethal JEV challenge in mice in association with robust cellular immunity induced by the replicating nonstructural proteins. Taken together, the results of this preclinical study well demonstrate the great potential of ChinDENV for further development as a dengue vaccine candidate, and this kind of chimeric flavivirus based on JE vaccine virus represents a powerful tool to deliver foreign antigens.     

Induction of Protective Immunity against Japanese Encephalitis in Mice by Immunization with a Plasmid Encoding Japanese Encephalitis Virus Premembrane and Envelope Genes

A DNA vaccine plasmid containing the Japanese encephalitis (JE) virus premembrane (prM) and envelope (E) genes (designated pcDNA3JEME) was evaluated for immunogenicity and protective efficacy in mice. Two immunizations of 4-week-old female ICR mice with pcDNA3JEME by intramuscular or intradermal injections at a dose of 10 or 100 μg per mouse elicited neutralizing (NEUT) antibodies at titers of 1:10 to 1:20 (90% plaque reduction), and all immunized mice survived a challenge with 10,000 50% lethal doses of the P3 strain of JE virus. A single immunization with 100 μg of pcDNA3JEME did not elicit detectable NEUT antibodies but induced protective immunity. Spleen cells obtained from BALB/c mice immunized once with 10 or 100 μg of pcDNA3JEME contained JE virus-specific memory cytotoxic T lymphocytes (CTLs). BALB/c mice maintained detectable levels of memory B cells and CTLs for at least 6 months after one immunization with pcDNA3JEME at a dose of 100 μg. The CTLs induced in BALB/c mice immunized twice with 100 μg of pcDNA3JEME were CD8 positive and recognized mainly the envelope protein. These results indicate that pcDNA3JEME has the ability to induce a protective immune response which includes JE virus-specific antibodies and CTLs.     

Yellow fever/Japanese encephalitis chimeric viruses: construction and biological properties

A system has been developed for generating chimeric yellow fever/Japanese encephalitis (YF/JE) viruses from cDNA templates encoding the structural proteins prM and E of JE virus within the backbone of a molecular clone of the YF17D strain. Chimeric viruses incorporating the proteins of two JE strains, SA14-14-2 (human vaccine strain) and JE Nakayama (JE-N [virulent mouse brain-passaged strain]), were studied in cell culture and laboratory mice. The JE envelope protein (E) retained antigenic and biological properties when expressed with its prM protein together with the YF capsid; however, viable chimeric viruses incorporating the entire JE structural region (C-prM-E) could not be obtained. YF/JE(prM-E) chimeric viruses grew efficiently in cells of vertebrate or mosquito origin compared to the parental viruses. The YF/JE SA14-14-2 virus was unable to kill young adult mice by intracerebral challenge, even at doses of 10(6) PFU. In contrast, the YF/JE-N virus was neurovirulent, but the phenotype resembled parental YF virus rather than JE-N. Ten predicted amino acid differences distinguish the JE E proteins of the two chimeric viruses, therefore implicating one or more residues as virus-specific determinants of mouse neurovirulence in this chimeric system. This study indicates the feasibility of expressing protective antigens of JE virus in the context of a live, attenuated flavivirus vaccine strain (YF17D) and also establishes a genetic system for investigating the molecular basis for neurovirulence determinants encoded within the JE E protein.     

不同年份生产的乙型脑炎减毒活疫苗SA14-14-2基因稳定性研究

为了研究不同年份生产的乙型脑炎减毒活疫苗病毒E蛋白基因稳定性,从分子水平控制乙型脑炎减毒活疫苗质量,确保疫苗安全性,本研究分析了不同年份生产的乙脑活疫苗病毒E蛋白基因核苷酸序列及编码的氨基酸序列,并与该疫苗原始种子、主种子、工作种子、乙脑病毒强、弱毒株进行比较。结果显示不同年份生产的乙脑活疫苗病毒E蛋白基因核苷酸序列与其原始种子、主种子、工作种子和基因库中登录的乙脑病毒弱毒株SA14-14-2的相应序列完全一致,与乙脑病毒强毒株SA14的E蛋白氨基酸序列比较有9个位点氨基酸发生了改变。不同年份生产的乙脑活疫苗病毒E蛋白基因稳定性表明该疫苗质量稳定、安全。     

昆明市西山区2009年人群4种免疫抗体水平的监测分析

为了解昆明市西山区2009年健康人群中麻疹IgG、白喉IgG、乙肝表面抗原、乙肝表面抗体、乙脑IgG的免疫水平,评价预防接种效果,按卫生部《预防接种工作规范》(2005年版)人群免疫水平监测方法开展了调查。结果显示,白喉抗体总阳性率57.67%,1～4岁组白喉抗体阳性率为89.71%,白喉疫苗在计划免疫人群中实施效果较好,其它人群未能达到免疫成功率;麻疹抗体总阳性率69.71%,未能达到保护水平,而1～6岁组麻疹抗体阳性率为88.10%,达到计划免疫规程人群抗体阳性率85%的指标;乙肝表面抗原阳性率1.57%,乙肝抗体阳性率75.55%,但1～6岁组抗体阳性率较高,然后随年龄增加而降低;乙脑全人群抗体阳性率为70.53%,经过多次乙脑强化免疫,在人群中构建了较为有效的免疫屏障。西山区四种疫苗预防接种工作在国家免费所针对人群中实施效果较好,学龄前人群抗体阳性率较高,除乙脑疫苗接种人群外其它人群因未开展加强免疫工作,未能形成有效抗体免疫屏障,需定期开展重点人群强化免疫工作。