Advances in research of interchangeable immunization with live attenuated Japanese encephalitis vaccines and inactivated vaccines / 中华预防医学杂志

Japanese encephalitis (JE) virus is the leading cause of vaccine-preventable encephalitis in Asia and the Western Pacific, which mainly invades central nervous system. Vaccination is the most important strategy to prevent JE. Currently, both live attenuated Japanese encephalitis vaccines (JE-L) and inactivated vaccines (JE-I) are in use. Due to the supply of vaccines and the personal choice of recipients, there will be a demand for interchangeable immunization of these two vaccines. However, relevant research is limited. By reviewing domestic and foreign research evidence, this article summarizes the current situation of the interchangeable use of JE-L and JE-I, and makes recommendations when the interchangeable immunization is in urgent need, so as to provide reference for practical vaccination and policymaking in China.

Co-infection with cryptococcal meningitis and Japanese encephalitis in an immunocompetent patient: A case report

@#Cryptococcal meningitis is a severe infection in both immunocompetent and immunosuppressed hosts. This report is an unusual case of co-infection with cryptococcal meningitis and Japanese encephalitis in a seronegative human immunodeficiency virus patient. A 51-year-old human immunodeficiency virus-negative patient presented with high-grade fever, nausea, vomiting, and later on, behavioral changes. A lumbar puncture was performed and cerebrospinal fluid revealed the presence of Cryptococcus and Japanese encephalitis virus. Treatment commenced with intravenous amphotericin B and flucytosine. Her condition initially improved but later on deteriorated due to bacteremia (MRSA-mecA gene positive) and septic shock which resulted in the patient’s demise. The occurrence of this co-infection in the absence of HIV infection is rare and there was no documented case up to this date.

Comparson of the immunogenicity of genotypeⅠJapanese encephalitis virus subunit vaccine candidate antigens / 生物工程学报

To screen the best genotypeⅠJapanese encephalitis virus subunit vaccine candidate antigens, the prMEIII gene, the polytope gene and the prMEIII-polytope fusion gene of the GenotypeⅠJapanese encephalitis virus GS strain were cloned into prokaryotic expression vector pET-30a. The recombinant proteins were obtained after the induction and purification. The prepared recombinant proteins were immunized to mice, and the immunogenicity of the subunit vaccine candidate antigens was evaluated through monitoring the humoral immune response by ELISA, detecting the neutralizing antibody titer by plaque reduction neutralization test, and testing the cell-mediated immune response by lymphocyte proliferation assay and cytokine profiling. The recombinant proteins with the molecular weights of 35 (prMEIII), 28 (polytope antigen) and 57 kDa (prMEIII-polytope) induced strong humoral and cellular immune responses in mice. Compared with prMEIII-polytope and polytope proteins, the prMEIII protein induced a significant expression of IL-2 and IFN-γ (P0.05). The study suggests that the prMEIII protein can be used for the development of the Japanese encephalitis virus subunit vaccine.

Updates of adult immunization in Korea

An increase in the number of patients with infectious diseases in Korea, can be attributed to various factors, such as the prevalence of new infectious diseases of the 21st century, the re-emergence of past infectious diseases, an increase in the number of elderly individuals, patients with chronic diseases, immune deficiency, and globalization. In this context, vaccination becomes vital for the adult population. Although, the guidelines for adult immunization are currently being updated, the rate of adult vaccination remains lower than that of infant vaccination. At present, the major challenges for increasing the rate of adult immunization include negative views on the need for some immunizations and a lack of understanding of group immunity among the youth. Consequently, a successful immunization program will be required to direct efforts towards educating patients and spreading awareness. Based on the current guidelines and practical applications, varicella zoster; Japanese encephalitis; tetanus, diphtheria, and pertussis; pneumococcus; measles, mumps, and rubella; and hepatitis A vaccines could effectively be considered for adult vaccination.

Delayed Appearance of Pathognomonic Magnetic Resonance Image Findings in Japanese Encephalitis

No abstract available.

Japanese Encephalitis Presenting with Unilateral Medial Temporal Lobe Lesion

No abstract available.

Co-infection of Dirofilaria immitis and Japanese encephalitis virus in a spotted seal (Phoca largha) in the Republic of Korea

A 10-year-old male spotted seal presented with loss of appetite and decreased activity. Grossly, the internal organs revealed several filarial nematodes in the right ventricle of the heart and the pulmonary vessels. Histopathological examination of the brain revealed moderate nonsuppurative meningoencephalitis with glial nodules and neuronophagia. Japanese encephalitis virus (JEV) of genotype I was isolated from the brain. All nematodes were identified as Dirofilaria immitis. This is the first clinical case of co-infection with D. immitis and JEV in a seal, suggesting that the seal, may be a dead-end host, like the human and horse, for JEV.

Recommended immunization schedule for children and adolescents: Committee on Infectious Diseases of the Korean Pediatric Society, 2018 / 소아과

The Committee on Infectious Diseases of the Korean Pediatric Society recommended immunization schedule for children and adolescents aged 18 years or younger in the 9th (2018) edition of Immunization guideline. This report provides the revised recommendations made by the committee and summarizes several changes from the 2015 guideline. National immunization program (NIP) launched a human papillomavirus (HPV) immunization for girls aged 12 years in 2016. NIP has also expanded age indication for inactivated influenza vaccine (IIV) to 12 years of age in the 2018-2019 season. Quadrivalent IIVs with a full dose (0.5 mL) are approved for all children of 6 months or older. Recommendations of live attenuated influenza vaccine were removed. For inactivated Japanese encephalitis vaccine, first 2 doses are considered as the primary series. Recommendations for use of newly introduced vaccines (diphtheria-tetanus-acellular pertussis/inactivated poliovirus/Haemophilus influenzae type b, 9-valent HPV, new varicella vaccine, new quadrivalent IIV, and attenuated oral typhoid vaccine) were added. Lastly, monitoring system for adverse events following immunization was updated. Other changes can be found in the 9th edition of Immunization guideline in detail.

Entomological investigation of Japanese encephalitis outbreak in Malkangiri district of Odisha state, India

BACKGROUND A severe outbreak of Japanese encephalitis (JE) and acute encephalitis syndrome (AES) with high case fatality was reported from Malkangiri district of Odisha state, India during September to November 2016 affecting 336 children with 103 deaths. OBJECTIVES The purpose of this study was to investigate the outbreak in the light of entomological determinants. METHODS Entomological investigation was carried out in 48 villages from four mostly affected Community Health Centres (CHCs) of Malkangiri district. Dusk collections of resting adults was done in villages from indoor and outdoor sites to record the density of mosquito species, including the known JE vectors, feeding behaviour, parity, dusk index and infection status with JE virus (JEV). FINDINGS The per man hour density and dusk index of JE vector species varied from 2.5 to 24.0 and 0.81 to 7.62, respectively in study villages. A total of 1136 mosquitoes belonging to six vector species were subjected to PCR and one pool of Culex vishnui was found to be positive for JEV. CONCLUSION The JE transmission in Malkangiri district was confirmed. Thorough screening of human blood samples of JE/AES suspected cases and JE vector mosquitoes for the presence of JEV during rainy season every year is recommended.

Serological and molecular epidemiology of Japanese encephalitis virus infections in swine herds in China, 2006–2012

Japanese encephalitis virus (JEV) is a mosquito-borne, zoonotic flavivirus causing viral encephalitis in humans and reproductive disorder in swine. JEV is prevalent throughout China in human; however, spatiotemporal analysis of JEV in Chinese swine herds has not been reported previously. Herein, we present serological and molecular epidemiological results and estimates of prevalence of JEV infections among swine herds in various regions of China. The results suggest that JEV infections are widespread and genotype I and III strains co-exist in the same regions. Therefore, there is an urgent need to monitor JEV infection status among swine herds in China.

Seroprevalence of Dengue Virus Antibody in Korea

PURPOSE: The number of dengue fever cases is rising due to increasing overseas travel. Vaccination makes severe dengue fever in seronegative individuals after vaccination when they exposure to wild-type dengue virus. We investigated the seroepidemiology of the dengue virus for monitoring of Korean dengue virus immunity and establishing the prevention of dengue infection. METHODS: The study was based on 446 residual sera collected from 98 infants (2 months to 1 year old), 152 adolescents (13 to 19 years old), 90 adults (20 to 50 years old), and 106 elderly participants (more than 65 years old) for other studies. Antibody levels for dengue virus immunoglobulin G (IgG) in each age group were measured using an enzyme-linked immunosorbent assay (ELISA). For each dengue virus IgG positive or equivocal result, an IgG ELISA was performed for Japanese encephalitis virus. RESULTS: Of the 446 serum samples, only 1 (0.2%) adolescent had a positive result from the dengue IgG antibody test. In the dengue virus IgG antibody test, 14 (3.1%) samples showed equivocal results (10 adolescents and 4 elderly). In the 1 positive case of dengue virus IgG, the Japanese encephalitis IgG test was also positive. In the 14 equivocal cases of dengue virus IgG, there were 6 positive, 3 equivocal, and 5 negative of Japanese encephalitis IgG. CONCLUSIONS: The seroprevalence rate of dengue virus was very low in Koreans. This study provides important data for establishing the policy for preventive measures of dengue fever. It will be necessary to continuously monitor for dengue virus immunity.

The Relationship between Japanese Encephalitis and Environmental Factors in China Explored Using National Surveillance Data / 生物医学与环境科学（英文）

Japanese encephalitis (JE) is a serious public health issue. This study was undertaken to better understand the relationship between JE distribution and environmental factors in China. JE data from 2005 to 2010 were retrieved from National Notifiable Disease Report System. ArcGIS, remote sensing techniques, and R software was used to exhibit and explore the relationship between JE distribution and environmental factors. Our results indicated that JE cases were mostly concentrated in warm-temperate, semitropical and tropical zones with annual precipitation > 400 mm; Broad-leaved evergreen forest, shrubs, paddy field, irrigated land, dryland, evergreen coniferous forest, and shrubland were risk factors for JE occurrence, and the former five were risk factors for counties with high JE incidence. These findings will inform the effective allocation of limited health resources such as intensive vaccination, surveillance and training in areas with high environmental risk factors.

Review of the Incidence of Japanese Encephalitis in Foreign-Born and Korean Nationals Living in the Republic of Korea, 2007–2016

The Japanese encephalitis (JE) vaccine was introduced to the national immunization program in 1985, which has led to a dramatic decrease in the number of reported cases, but JE continues to occur in foreign nationals residing in or traveling to Korea. Although the incidence is low, this study demonstrated that more Koreans were infected with JE than foreign-born expatriates. The incidence rates of Korean-born nationals were between 0.01 and 0.08 cases per 100,000. In contrast, the incidence rates of foreign-born nationals ranged between 0 and 0.26 cases per 100,000. The incidence rates clearly showed that foreign-born expatriates were more at risk, which underscores the importance of vaccination. We recommend heightened surveillance among JE-susceptible individuals and promote vaccination among foreign-born nationals living in Korea.

The 2nd Meeting of National Control Laboratories for Vaccines and Biologicals in the Western Pacific

The Second Meeting of the National Control Laboratories for Vaccines and Biologicals in the Western Pacific, was jointly organized by the National Institute of Food and Drug Safety Evaluation of the Ministry of Food and Drug Safety in the Republic of Korea, and by the World Health Organization Regional Office for the Western Pacific. In the National Lot Release Systems session countries including Canada, China, Japan, Malaysia, Vietnam, and the Republic of Korea, all shared information on their current Lot Release Systems, including current practices and developments in risk-based official lot release of vaccines. In the session on Quality Control of Blood Products, experts from the National Institute for Biological Standards and Control shared quality control and research results for; blood coagulation factor VIII products, and the measurement of procoagulant activity in immunoglobulin products. Representatives from Japan proposed a regional collaborative study to test aggregated immunoglobulin free from complement activity. A cell-based Japanese encephalitis vaccine potency assay was proposed by representatives from Korea and they also called for voluntary participation of other National Control Laboratories in a collaborative study, on the first Korean Gloydius anti-venom standard. Participants agreed in general to continue communicating, and coordinate presentation of the study results.

Changes of Epidemiological Characteristics of Japanese Encephalitis Viral Infection and Birds as a Potential Viral Transmitter in Korea

Japanese encephalitis (JE) cases have been increasingly reported recently especially in Seoul and its vicinity. Pigs are known as amplifying host of JE virus (JEV), but do not play an important role in these recent events because pig-breeding is not common in Seoul. The distribution and the density of migratory birds are correlated with JE cases in cities and they might be highly potential hosts contributing to transmit JEV in metropolitan areas. JE genotype and sero-prevalence in birds should be determined for the verification of the transmission route of JEV in the recent sporadic occurrence of JE cases in Seoul.

Investigation of Children with No Vaccinations Recorded on the National Immunization Registry Information System

PURPOSE: To improve the quality of the vaccination program, analyze the cause and identify the influencing factors for not being registered in the National Immunization Registry Information System even once. METHODS: We conducted one-on-one household visit interview surveys after, using a list supplemented with addresses from the Ministry of the Interior. We identified the basic respondent information, information on relevant children (those born in 2012), the reasons for omission from computerized vaccination registration, and the actual residence of the registered children. RESULTS: The total number of unvaccinated children born in 2012 was 1,870. The final contact result of the household surveys was 1,254 successful contacts, 51 refused to be interviewed, and 565 were not found. The reason for missed vaccination registration was 928 cases of long-term stay overseas, 241 cases of missing registration owing to intentional refusal of vaccination, and 57 cases of illness. A comparison of complete vaccination rates between non-registrants and those of computerized registrants revealed rates of 17.9% and 96.3% for the 3 doses hepatitis B vaccine, 14.9% and 95.6% for the 4doses DTaP vaccine, 16.1% and 97.4% for the 3 doses polio vaccine, and 3.9% and 92.5% for the 3 (or 2) doses Japanese encephalitis vaccine, respectively. CONCLUSION: Vaccination is the most effective national health policy and one of the most remarkable accomplishments in medical history. Through great effort, Korea has started to transcribe vaccination records since 2000, and the records are now reaching a considerable level. However, there is an unregistered population of around 0.3%. Several measures can be taken to improve the registration rate in the vaccination records, such as managing non-registrants through education and interviews, and sharing vaccination data with foreign countries. The non-registrant management plan should include periodically compiling a list of children who are not registered in the National Immunization Registry Information System, conducting of household visits using survey forms, and data analysis to establish appropriate measures.

Exacerbation of Japanese Encephalitis by CD11c(hi) Dendritic Cell Ablation Is Associated with an Imbalance in Regulatory Foxp3⁺ and IL-17⁺CD4⁺ Th17 Cells and in Ly-6C(hi) and Ly-6C(lo) Monocytes

Japanese encephalitis (JE) is neuroinflammation characterized by uncontrolled infiltration of peripheral leukocytes into the central nervous system (CNS). We previously demonstrated exacerbation of JE following CD11c(hi) dendritic cell (DC) ablation in CD11c-DTR transgenic mice. Moreover, CD11c(hi) DC ablation led to abnormal differentiation of CD11b⁺Ly-6C(hi) monocytes and enhanced permeability of the blood-brain barrier (BBB), resulting in promoting the progression of JE. Here, we examined changes in lymphoid and myeloid-derived leukocyte subpopulations associated with pro- and anti-inflammation during JE progression. The analyses of this study focused on regulatory CD4⁺Foxp3⁺ regulatory T cells (Tregs), IL-17⁺CD4⁺ Th17 cells, and CD11b⁺Ly-6C(hi) and Ly-6C(lo) monocytes. CD11c(hi) DC ablation resulted in the accumulation of IL-17⁺CD4⁺ Th17 cells in the CNS, thereby leading to lower ratio of Tregs to Th17 cells. This result was corroborated by the higher expression levels of IL-17 and RORγT in CD4⁺ T cells from the brains of CD11c(hi) DC-ablated mice. In addition, CD11c(hi) DC-ablated mice showed higher frequency and total number of inflammatory CD11b⁺Ly-6C(hi) monocytes, whereas CD11b⁺Ly-6C(lo) monocytes were detected with lower frequency and total number in CD11c(hi) DC-ablated mice. Furthermore, CD11c(hi) DC ablation altered the phenotype and function of CD11b⁺Ly-6C(lo) monocytes, resulting in lower levels of activation marker and anti-inflammatory cytokine (IL-10 and TGF-β) expression. Collectively, these results indicate that CD11c(hi) DC ablation caused an imbalance in CD4⁺ Th17/Treg cells and CD11b⁺Ly-6C(hi)/Ly-6C(lo) monocytes in the lymphoid tissue and CNS during JE progression. This imbalanced orchestration of pro- and anti-inflammatory leukocytes following CD11c(hi) DC ablation may contribute to the exacerbation of JE.

Improvement of indirect enzyme-linked immunosorbent assay for detection of Japanese encephalitis virus antibodies in swine sera

Japanese encephalitis (JE) is an important zoonosis caused by the mosquito-transmitted JE virus (JEV), which is a causative agent of reproductive failure in pregnant sows. Detection of JEV antibodies in swine is performed by hemagglutination inhibition (HI), virus neutralization (VN), and the plaque reduction neutralization test (PRNT). The most stringent PRNT is the 90% endpoint PRNT (PRNT₉₀). These conventional assays are difficult to carry out in diagnostic laboratories with insufficient instruments or cell culture systems. An alternative assay that is easily conducted and time efficient is required. In this study, we improved the indirect enzyme-linked immunosorbent assay (I-ELISA) with clarified antigen for the detection of JEV antibodies. The I-ELISA results obtained from 175 swine serum samples were compared with HI, VN, and PRNT₉₀ results. The sensitivity of I-ELISA was 91.8%, 95.0%, and 94.7% compared with HI, VN, and PRNT₉₀ results, respectively. The specificity of I-ELISA was 92.2%, 94.7%, and 94.7% compared with HI, VN, and PRNT₉₀ results, respectively. Moreover, the I-ELISA results were significantly correlated with the HI (r = 0.93), VN (r = 0.95), and PRNT₉₀ (r = 0.92) results. These results suggest that the improved I-ELISA is useful for serosurveillance of JEV in swine.

Domestic and international trend of vector-borne disease

The incidence of vector-borne diseases has increased with climate change and developments of transportation. Malaria was eliminated in the early 1980s in Korea, but one domestic case was reported in 1993. The number of patients increased to 4,142 in 2002, and less than 700 cases of malaria are reported annually nowadays. Additionally, approximately 70 to 80 imported malaria cases were reported annually, and most of them are Plasmodium falciparum infections from Africa. Annually, 20 to 40 cases of Japanese encephalitis are reported, and the incidence is high in individuals between the ages of 40 and 59. Moreover, 313 cases of dengue fever were imported in 2016, and most of them were from Southeast Asia. In 2016, 11,000 cases of scrub typhus were reported, and most of the patients were older than 50. The number of reported cases of severe fever with thrombocytopenia syndrome has been increasing since 2013, mostly in patients older than 60. It is important to avoid vectors for the prevention, and for the doctors to diagnose the apatients as soon as possible.

Ecological characteristics and current status of infectious disease vectors in South Korea

In light of global climate change, the seasonal and geographical distribution of vector species, especially mosquitoes, chigger mites, and ticks, are of great importance for human beings residing in rural and urban environments. A total of 12 species belonging to 4 genera have been identified as vector mosquitoes in the Republic of Korea. The most common of the 56 mosquito species in this country from 2013 through 2015 was found to be a malaria vector, Anopheles sinensis s.l. (species ratio [SR] 52%); followed by a potential vector of West Nile virus, Aedes vexans nipponii (SR 38%); a Japanese encephalitis vector, Culex tritaeniorhynchus (SR 6%); a West Nile virus vector, Culex pipiens (SR 3%); and a dengue and Zika virus vector, Ae. albopictus (SR 0.3%). Of the scrub typhus vectors, Leptotrombidium scutellare is the predominant chigger mite in Gyongnam province and Jeju island, whereas L. pallidum is the predominant species in other areas of Korea. Ticks were found to be prevalent in most environmental conditions, and high levels of their activity were consistently observed from May to September. Haemaphysalis species of ticks were mostly collected in grasslands, whereas Ixodes species were frequently found in coniferous forests. Haemaphysalis longicornis, known as the main vector of severe fever with thrombocytopenia syndrome, was the predominant species and was widely distributed throughout the country.