In 2006, the annual number of Koreans traveling internationally increased to 11 million. With this increased number of Koreans traveling to developing countries, various infectious diseases have been reported to be imported into Korea. Immunization is an important tool for the prevention of such diseases. Vaccination offered to international travelers is divided into 3 categories, i.e., obligatory vaccination, vaccines against diseases with an increased risk in developing countries, and routine vaccination. Vaccination that is obligatory for travelers includes yellow fever vaccine for travelers entering yellow fever-endemic areas and meningococcal vaccination for pilgrims traveling to Saudi Arabia. Recent reports of the adverse event following yellow fever vaccination, i.e., vaccine-associated viscerotropic disease, pose a caution in the administration of yellow fever vaccine to the elderly or individuals with thymic diseases. Protein-conjugated meningococcal vaccines are generally preferred; however, polysaccharide vaccines are also effective in short-term travelers. The vaccinations recommended for the health of travelers include administration of hepatitis A (HAV), meningococcal, typhoid, rabies, tick-borne encephalitis, and plague vaccines. As many young Korean adults lack immunity against hepatitis A, the administration of the HAV vaccine is recommended for all Korean individuals in their 20s and all Korean seronegative individuals in their 30s. The risk of acquiring typhoid fever is high among travelers traveling to the rural areas of developing countries for 2 weeks or more. The rabies vaccine may be recommended for travelers traveling for longer than 3 months and animal handlers. Both tick-borne encephalitis and plague are rarely encountered among Korean travelers; furthermore, vaccines for these diseases are not available in Korea. As Japanese encephalitis is endemic in Korea, vaccination against encephalitis is not essential for Korean adults. Pre-travel counseling is an important opportunity for catch-up vaccination of healthy travelers who missed routine vaccinations.
Adult ; Aged ; Animals ; Communicable Diseases ; Counseling ; Developing Countries ; Encephalitis ; Encephalitis, Japanese ; Encephalitis, Tick-Borne ; Hepatitis A ; Humans ; Immunization ; Korea ; Meningococcal Vaccines ; Plague ; Rabies ; Rabies Vaccines ; Saudi Arabia ; Typhoid Fever ; Vaccination ; Vaccines ; Whooping Cough ; Yellow Fever ; Yellow Fever Vaccine

BACKGROUND: The genus Flavivirus consists of many emerging arboviruses, including Dengue virus (DV), Japanese encephalitis virus (JEV) and West Nile virus (WNV). Effective preventive vaccines remain elusive for these diseases. Mice are being increasingly used as the animal model for vaccine studies. However, the pathogenic mechanisms of these viruses are not clearly understood. Here, we investigated the interaction of DV and JEV with murine bone marrow-derived dendritic cells (bmDC). METHODS: ELISA and FACS analysis were employed to investigate cytokine production and phenotypic changes of DCs obtained from bone marrow following flavivirus infection. RESULTS: We observed that these viruses altered the cytokine profile and phenotypic markers. Although both viruses belong to the same family, JEV-infected bmDC produced anti-inflammatory cytokine (IL-10) along with pro-inflammatory cytokines, whereas DV infection induced production of large amounts of pro-inflammatory cytokines (IL-6 and TNF-alpha) and no IL-10 from murine bmDCs. Both flaviviruses also up-regulated the expression of co-stimulatory molecules such as CD40, CD80 and CD86. JEV infection led to down-regulation of MHC II expression on infected bmDCs. We also found that cytokine production induced by JEV and DV is MyD88-dependent. This dependence was complete for DV, as cytokine production was completely abolished in the absence of MyD88. With regard to JEV, the absence of MyD88 led to a partial reduction in cytokine levels. CONCLUSION: Here, we demonstrate that MyD88 plays an important role in the pathogenesis of flaviviruses. Our study provides insight into the pathogenesis of JEV and DV in the murine model.
Animals ; Arboviruses ; Bone Marrow ; Cytokines* ; Dendritic Cells* ; Dengue Virus ; Down-Regulation ; Encephalitis Virus, Japanese ; Enzyme-Linked Immunosorbent Assay ; Flavivirus Infections ; Flavivirus* ; Humans ; Interleukin-10 ; Interleukin-6 ; Mice ; Models, Animal ; Tumor Necrosis Factor-alpha ; Vaccines ; West Nile virus

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.
Adolescent ; Adult ; Aged ; Dengue Virus ; Dengue ; Encephalitis Virus, Japanese ; Encephalitis, Japanese ; Enzyme-Linked Immunosorbent Assay ; Fever ; Humans ; Immunoglobulin G ; Infant ; Korea ; Prevalence ; Seroepidemiologic Studies ; Severe Dengue ; Vaccination

Three dimensional structures of envelope protein from Korean isolates and Nakayama-NIH strain of Japanese encephalitis virus (JEV) were deduced by a computer program (HyperChem 4.0 Chemplus 1.0) based on the data of the three dimentional structure of Tick-borne encephalitis virus. In the three dimensional structure of envelope protein, neutralizing epitope and T-helper cell recognition site of C-terminal region of Korean isolates were structually similar to those of Nakayama-NIH but the N-terminal region was not. Korean JE isolates were compared with Nakayama-NIH strain by using cross-neutralization antibody test. Neutralizing activities of Korean isolates derived from guinea pigs were higher than those of Nakayama-NIH strain against Korean isolates, although the polyclonal antibody titers of Nakayama-NIH showed 1:160 to 1:640 against Korean isolates. According to the results from three dimentional structures and cross-neutralization analyses, the antigenic difference between Korean JE isolates and Nakayama-NIH strain may be dependent on structural difference of envelope protein.
Animals ; Encephalitis Virus, Japanese ; Encephalitis Viruses* ; Encephalitis Viruses, Tick-Borne ; Encephalitis* ; Guinea Pigs ; Korea*

Haemophagocytic lymphohistiocytosis (HLH) is a potentially fatal disorder resulting from uncontrolled hyperinflammatory response. There had been increase in cases of one of the secondary form of HLH, i.e., infectionassociated haemophagocytic syndrome (IAHS) in severe dengue in recent years. However, the condition remains under diagnosed due to lack of awareness compounded by the lack of validated diagnostic criteria. Severe hepatitis with prolonged cytopenias, severe hyperferritinemia, hypofibrinogenemia and persistent fever were evident in all four cases reported. All the subjects survived with supportive care and adjuvant steroid therapy. Prospective controlled studies are needed to develop diagnostic criteria and management protocol for IAHS in severe dengue.
Severe Dengue

Background: Dengue, a mosquito-borne flavivirus, is hyperendemic in the Philippines. One of its rare complication is dengue encephalitis, characterized by altered sensorium, elevated liver enzymes, and high dengue-specific antibody titers. Previously known as non-neurotropic, dengue presents with an increasing incidence of neurologic manifestations. Objective: To describe the clinico-demographic profile and outcome of laboratory-confirmed dengue encephalitis patients. Methods: This is a retrospective study that used purposive sampling to describe laboratory-confirmed dengue encephalitis cases aged 0-18 years. The clinico-demographic profiles and outcomes were collected using chart review, and variables were analyzed using descriptive statistics. Results: 14 laboratory-confirmed cases were reviewed. Most (57%) were males aged 3 days-15 years. Fever lasted 3-11 days. Following nonspecific signs and symptoms, neurological manifestations developed within 1-5 days, the most common being seizures (71%). Majority (57%) had anemia. All, except one, exhibited leukopenia and thrombocytopenia. Elevated liver enzymes, bleeding parameter derangements, electrolyte, and glucose imbalances were noted. All were seropositive for dengue IgM, and 5 dengue IgM in the CSF. Most common EEG findings showed generalized slowing. Neuroimaging reports were normal in some or showed cerebral edema in the others. Half of the patients recovered fully, 3 showing partial recovery from neurologic changes, and 3 others had neurologic sequelae. One infant expired. Conclusions and Recommendations Dengue encephalitis should be considered in patients living in an endemic country, presenting with fever with neurologic changes or elevated liver enzymes, with a risk for developing neurologic sequelae or death.
Severe Dengue

Dengue ; Humans ; Severe Dengue

There were 714 cases of dengue haemorrhagic fever and 1 death. The age of patients from 2-10 years old, none of them over 15 years old. The morbidity of III, IV degrees concentrated in Hon Dat, Tan Hiep, An Ninh, Rach Gia and also the districts that had the greatest morbidity, 56 cases of shock. The Steering Board issued a number of guideline documents and established preventive plan right at the beginning of the year with medical speciality. There were 28 cases of Japanese encephalitis, 25 cases with the age from 13 months - 5 years old, 3 cases with the age from 6-11 years old, 64% male and 36% female. The Pasteurs Institute of Ho Chi Minh City coordinated with the local authority to control the disease transmission in order to isolate virus and propagate measures of mosquito killing and hygienic methods around living area.
Dengue ; Encephalitis ; Encephalitis, Japanese

BACKGROUNDTo compare the biological characteristics of West Nile virus (WNV) and Japanese encephalitis virus (JEV), including cells sensitivity, pathogenicity, viral morphology, as well as the results of immunological and molecular biological detection.

METHODSCytopathic effect (CPE) and pathogenicity were observed in C6/36 cells and in suckling mice inoculated intracerebrally with the WNV or JEV, respectively. The sliced tissue samples for electron microscopic examination were prepared for the morphologic observation of the viruses. Serum antibody to WNV or JEV was detected using indirect immunofluorescence assay (IFA), and the viral RNA was analyzed by RT-PCR method.

RESULTSWNV or JEV-caused CPE was characterized by cell fusion and cell shedding, respectively. There was no significant difference in the pathogenicity to suckling mice between WNV and JEV. The morphologic observation showed that the shape and size of the two virions were similar. WNV and JEV were found to have antigenic cross-reactivity. The viral RNA could be detected from both WNV and JEV samples with universal primer set, but only nucleoside fragments of corresponding virus could be amplified when specific primers were used.

CONCLUSIONCPE in C6/36 cell and detection of the viral RNA should be useful in discrimination of WNV and JEV, and simultaneously examining the titers of serum antibodies against WNV and JEV may be helpful to diagnosis of infection with these agents.

Animals ; Brain ; virology ; Cell Line ; Diagnosis, Differential ; Encephalitis Virus, Japanese ; immunology ; isolation & purification ; Encephalitis, Japanese ; diagnosis ; virology ; Flavivirus Infections ; diagnosis ; virology ; Immunoglobulin G ; blood ; Mice ; Mice, Inbred BALB C ; West Nile virus ; immunology ; isolation & purification

Zika virus was first isolated in from nonhuman primate in 1947. It is in the genus Flavivirus, closely related to other flavivirus like Dengue, West Nile, Yellow fever and Japanese encephalitis virus. Since 2007 epidemic in Yap island, zika virus infections had spread to the countries in Micronesia and South Pacific. In 2015, Zika virus outbreak occurred in Brazil and now more than 40 countries in American continents reported autochthonous infection. The virus is transmitted mainly by Ae. aegypti mosquito with many other Aedes mosquito species known as vector. Recently, Zika virus infection is known to cause severe neurological complications and congenital malformation. In this paper, we will review current knowledge on Zika virus history, biology, clinical characteristics and preventive method.
Aedes ; Biology ; Brazil ; Culicidae ; Dengue ; Encephalitis Virus, Japanese ; Flavivirus ; Methods ; Microcephaly ; Micronesia ; Primates ; Yellow Fever ; Zika Virus Infection* ; Zika Virus*