Atsushi Yamanaka

Mahidol University, Siayuthia, Bangkok, Thailand

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Publications (39)66.94 Total impact

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    ABSTRACT: Dengue virus (DENV) infection-enhancing antibodies are a hypothetic factor to increase the dengue disease severity. In this study, we investigated the enhancing antibodies against Indonesian strains of DENV-1-4 in 50 healthy inhabitants of central Thailand (Bangkok and Uthai Thani). Indonesia and Thailand have seen the highest dengue incidence in Southeast Asia. The infection history of each subject was estimated by comparing his/her neutralizing antibody titers against prototype DENV-1-4 strains. To resolve the difficulty in obtaining foreign live viruses for use as assay antigens, we used a recombinant system to prepare single-round infectious dengue viral particles based on viral sequence information. Irrespective of the previously infecting serotype(s), most serum samples showed significantly higher enhancement titers against Indonesian DENV-2 strains than against Thai DENV-2 strains, whereas the opposite effect was observed for the DENV-3 strains. Equivalent enhancing activities were observed against both DENV-1 and DENV-4. These results suggest that the genotype has an impact on enhancing antibody activities against DENV-2 and DENV-3, because the predominant circulating genotypes of each serotype differ between Indonesia and Thailand.
    No preview · Article · Dec 2015 · Microbes and Infection
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    ABSTRACT: Indonesia is one of the biggest dengue endemic countries, and, thus, is an important place to investigate the evolution of dengue virus (DENV). We have continuously isolated DENV in Surabaya, the second biggest city in Indonesia, since 2008. We previously reported sequential changes in the predominant serotype from DENV type 2 (DENV-2) to DENV type 1 (DENV-1) in November 2008 and from DENV-1 to DENV-2 in July 2013. The predominance of DENV-2 continued in 2014, but not in 2015. We herein phylogenetically investigated DENV-2 transitions in Surabaya between 2008 and 2014 to analyze the divergence and evolution of DENV-2 concomitant with serotype shifts. All DENV-2 isolated in Surabaya were classified into the Cosmopolitan genotype, and further divided into 6 clusters. Clusters 1-3, dominated by Surabaya strains, were defined as the "Surabaya lineage". Clusters 4-6, dominated by strains from Singapore, Malaysia, and many parts of Indonesia, were the "South East Asian lineage". The most recent common ancestor of these strains existed in 1988, coinciding with the time that an Indonesian dengue outbreak took place. Cluster 1 appeared to be unique because no other DENV-2 isolate was included in this cluster. The predominance of DENV-2 in 2008 and 2013-14 were caused by cluster 1, whereas clusters 2 and 3 sporadically emerged in 2011 and 2012. The characteristic amino acids of cluster 1, E-170V and E-282Y, may be responsible for its prevalence in Surabaya. No amino acid difference was observed in the envelope region between strains in 2008 and 2013-14, suggesting that the re-emergence of DENV-2 in Surabaya was due to the loss or decrease of herd immunity in the 5-year period when DENV-2 subsided. The South East Asian lineage primarily emerged in Surabaya in 2014, probably imported from other parts of Indonesia or foreign countries.
    Full-text · Article · Nov 2015 · Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases
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    ABSTRACT: Most candidate dengue vaccines currently under development induce neutralizing antibodies, which are considered important for immunoprotection. However, the concomitant induction of infection-enhancing antibodies is an unavoidable concern. In contrast, a neutralizing antibody developed for passive immunotherapy has been engineered to eliminate its enhancing activity. Therefore, a strategy for the long-term expression of enhancing-activity-free neutralizing antibodies may resolve this concern. A mouse monoclonal antibody, 7F4, of the IgG3 subclass and with no detectable enhancing activity, was selected as the model neutralizing antibody to evaluate the potential of this strategy. Equal amounts of commercial vector (pFUSE)-based plasmids containing 7F4 heavy (H)- or light (L)-chain variable region genes were mixed and used for the cotransfection of 293T cells and co-delivery into ICR and BALB/c mice. The recombinant plasmids were designed to express IgG2b or IgG3 subclass antibodies (p7F4G2b or p7F4G3, respectively). 293T cells transfected with 2μg of p7F4G2b or p7F4G3 produced approximately 15,000 or 800ng/ml IgG in the culture fluids, respectively. The dose is expressed as the total amount of H- and L-chain plasmids. Neutralizing antibody was detected dose-dependently in ICR mice inoculated with 50-200μg of p7F4G2b. A 1:2 dilution of sera from ICR and BALB/c mice inoculated with 100μg of p7F4G3 showed average plaque reduction levels of >70% on day 3 and >90% on days 5-9. BALB/c mice maintained detectable neutralizing antibody for at least 3 months. The neutralizing antibody expressed by p7F4G3 in mice showed no enhancing activity. Although the expression of neutralizing antibodies from immunoglobulin genes is a type of passive immunization, its durability can be utilized as a dengue vaccine strategy. This "proof-of-concept" study using a mouse model demonstrates that the enhancing-activity-free characteristic of this strategy augurs well for dengue vaccine development, although further improvement is required. Copyright © 2015. Published by Elsevier Ltd.
    Preview · Article · Aug 2015 · Vaccine
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    ABSTRACT: Indonesia has annually experienced approximately 100,000 reported cases of dengue fever (DF) and dengue hemorrhagic fever (DHF) in recent years. However, epidemiological surveys of dengue virus (DENV) have been limited in this country. One report indicated that dengue type 2 virus (DENV2) was the predominant circulating virus in 2003–2005 in Surabaya. In addition, our previous survey indicated that dengue type 1 virus (DENV1) displaced DENV2 in Surabaya in 2008 with subsequent genotype shifts from IV to I in 2009-2010. In the present study, we aimed at surveying the recent predominant DENV type and analyzing it phylogenetically. A total number of 659 isolates were obtained from 4974 dengue patient sera collected in Surabaya, in 2009-2014. Phylogenetic analyses of the complete envelope gene inrecent DENV1 isolates indicated the predominant genotype was genotype IV in 2011 and both genotypes IV and I in 2012 to June 2013. Shift of the predominant circulating DENV from DENV1 to DENV2 from July 2013 to December 2014. For DENV2, the predominant genotype in 2008 was "Cosmopolitan genotype". Although the predominant genotype in 2009-2014 was also "Cosmopolitan genotype", they were grouped into a different clade.
    Full-text · Conference Paper · May 2015
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    ABSTRACT: Four serotypes of dengue virus (DENV-1 to DENV-4) and their genotypes are distributed in tropical and subtropical regions. Indonesia has been recently suggested as the origin of some dengue virus genotypes. In Surabaya, the second biggest city of Indonesia, we previously reported a shift of the predominantly circulating serotype from DENV-2 to DENV-1 in November 2008, followed by a genotype shift of DENV-1 from genotype IV (GIV) to genotype I (GI) in September 2009, based on nucleotide sequences in the envelope protein coding region. Since then, GI strains had predominantly circulated until December 2010. In this report, we investigated further DENV-1 transitions in Surabaya during 2011-2013 in order to comprehend dengue dynamics during 2008-2013 in more detail. From January 2011 through December 2011, only GIV strains were isolated, indicating that a genotype shift again took place from GI to GIV. In January 2012, GI and GIV strains started co-circulating, which continued until June 2013. To further investigate this phenomenon, analysis was performed at a clade level. GI and GIV strains isolated in Surabaya formed four and three distinct clades, respectively. Concomitant with co-circulation, new clade strains appeared in both genotypes. In contrast, some previously circulating clades were not isolated during co-circulation, indicating clade shifts. Among our Surabaya isolates, nucleotide and amino acid differences in the E region were, respectively, 1.0-2.3% and 0.2-1.0% for GI isolates and 2.0-6.3% and 0.0-1.8% for GIV isolates. Several characteristic amino acid substitutions in the envelope ectodomain were observed in some clades. After July 2013, DENV-1 strains were not isolated and were replaced with DENV-2. This study showed that continuous shifts of more than one genotype resulted in their co-circulation and subsequent disappearance and suggested the relevance of clade replacement to genotype co-circulation and disappearance in Surabaya.
    Full-text · Article · Dec 2014 · Infection Genetics and Evolution
  • Atsushi Yamanaka · Ryosuke Suzuki · Eiji Konishi
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    ABSTRACT: Dengue fever and dengue hemorrhagic fever are endemic throughout tropical and subtropical countries. Four serotypes of dengue viruses (DENV-1 to DENV-4), each with several genotypes including various subclades, are co-distributed in most endemic areas. Infection-neutralizing and -enhancing antibodies are believed to play protective and pathogenic roles, respectively. Measurement of these functional antibodies against a variety of viral strains is thus important for evaluating coverage and safety of dengue vaccine candidates. Although transportation of live virus materials beyond national borders is increasingly limited, this difficulty may be overcome using biotechnology that enables generation of an antibody-assay antigen equivalent to authentic virus based on viral sequence information. A rapid system to produce flavivirus single-round infectious particles (SRIPs) was recently developed using a Japanese encephalitis virus (JEV) subgenomic replicon plasmid. This system allows production of chimeric SRIPs that have surface proteins of other flaviviruses. In the present study, SRIPs of DENV-1 (D1-SRIPs) were evaluated as an antigen for functional antibody assays. Inclusion of the whole mature capsid gene of JEV into the replicon plasmid provided higher D1-SRIP yields than did its exclusion in cases where a DENV-1 surface-protein-expressing plasmid was used for co-transfection of 293T cells with the replicon plasmid. In an assay to measure the balance between neutralizing and enhancing activities, dose (antibody dilution)-dependent activity curves in dengue-immune human sera or mouse monoclonal antibodies obtained using D1-SRIP antigen were equivalent to those obtained using DENV-1 antigen. Similar results were obtained using additional DENV-2 and DENV-3 systems. In a conventional Vero-cell neutralization test, a significant correlation was shown between antibody titers obtained using D1-SRIP and DENV-1 antigens. These results demonstrate the utility of D1-SRIPs as an alternative antigen to authentic DENV-1 in functional antibody assays. SRIP antigens may contribute to dengue vaccine candidate evaluation, understanding of dengue pathogenesis, and development of serodiagnostic systems.
    No preview · Article · Jun 2014 · Vaccine
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    Full-text · Article · May 2014 · Japanese journal of infectious diseases
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    ABSTRACT: Dengue virus infection manifests in three distinct forms in humans: dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. Infection with the virus is a fatal disease; no vaccine is available and prevention depends on interruption of the chain of transmission. The study of dengue viral transmission by mosquitoes is hindered due to the lack of an affordable animal model. In general, immuno-competent mice are used as a simple and inexpensive animal model, but mice are not susceptible to dengue virus infection and therefore viremia will not occur following the inoculation of the virus in such mice. Here, we report a method for creating artificial viremia in immuno-competent mice, and further demonstrate the use of viremic mice to simultaneously infect a large number of Aedes aegypti. We infected K562 cells with DENV-2 in the presence of an antibody against DENV-4. We then incubated the cells for 2 d before injecting the infected cells into C3H mice. After 5 h incubation, we allowed 100-150 female Aedes aegypti to feed on blood from the mice directly. We collected blood samples from the mice and from randomly selected Ae. aegypti at 2, 6, 12, and 24 h post-blood meal and screened the samples for DENV-2 genome as well as for virus concentration. Our procedure provided high virus concentrations in the mice for at least 7 h after viral inoculation. We found that 13 out of 14 randomly picked mosquitoes were infected with DENV-2. High concentrations of virus were detected in the mosquitoes until at least 12 h post-infection. Using the viremic immuno-competent mouse, we show that mass infection of Ae. aegypti is achievable. Compared to other infection techniques using direct inoculation, membrane-feeding, or immuno-deficient/humanized mice, we are confident that this method will provide a simpler and more efficient infection technique.
    Full-text · Article · Mar 2014 · Parasites & Vectors
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    ABSTRACT: A Japanese man suffered from acute respiratory tract infection after returning to Japan from Bali, Indonesia in 2007. Miyazaki-Bali/2007, a strain of the species of Nelson Bay orthoreovirus, was isolated from the patient's throat swab using Vero cells, in which syncytium formation was observed. This is the sixth report describing a patient with respiratory tract infection caused by an orthoreovirus classified to the species of Nelson Bay orthoreovirus. Given the possibility that all of the patients were infected in Malaysia and Indonesia, prospective surveillance on orthoreovirus infections should be carried out in Southeast Asia. Furthermore, contact surveillance study suggests that the risk of human-to-human infection of the species of Nelson Bay orthoreovirus would seem to be low.
    Full-text · Article · Mar 2014 · PLoS ONE
  • Tomohiro Ishikawa · Atsushi Yamanaka · Eiji Konishi
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    ABSTRACT: Genus flavivirus comprises many important human pathogens causing public health problems worldwide. Some flavivirus infections are characterized by a relatively high mortality rate and/or high sequelae rate in survivors. Because most flavivirus life cycles are maintained between arthropod vectors and amplifying/reservoir hosts in the absence of humans, eradication of flaviviruses might be extremely difficult. Flavivirus vaccine development is considered a reasonable method to combat flavivirus infections. Some vaccines have been successfully developed, but others have not, regardless of much effort. This review article describes currently available flavivirus vaccines against yellow fever, Japanese encephalitis, and tick-borne encephalitis. In addition, the current status of dengue and West Nile virus vaccine development is reviewed and problems regarding their development are discussed.
    No preview · Article · Jan 2014 · Vaccine
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    ABSTRACT: Dengue hemorrhagic fever (DHF) is a severe form of dengue fever (DF). Recent in vitro studies indicate that complement reduces the infection-enhancing activity of dengue antibodies, suggesting its in vivo role in controlling viremia levels and disease severity. In this study, the complement hemolytic activity (CH50) and levels of complement components and related factors in dengue patients in Indonesia were assessed. Based on the number of days since fever onset, DF patients were compared with patients at the DHF pre-critical phase who showed deterioration within 2 days. The mean CH50 values and levels of C2, C4, and factors B and H in the DHF pre-critical phase group were significantly lower than those in the DF group. The mean CH50 values were significantly correlated with C4, factor B, or factor H levels, indicating their responsibility for reduced CH50 values. Furthermore, a significantly higher proportion of the DHF pre-critical phase group (78%) than the DF group (33%) was positive for the nonstructural protein 1 (NS1) antigen. These results suggested that antibody-dependent enhancement of infection occurs during a period of low complement activity, which is associated with NS1 levels during the acute phase in some patients, thereby leading to increased viremia levels and greater disease severity.
    Full-text · Article · Sep 2013
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    Atsushi Yamanaka · Tomohiro Kotaki · Eiji Konishi
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    ABSTRACT: Dengue fever and its more severe form, dengue hemorrhagic fever, are major global concerns. Infection-enhancing antibodies are major factors hypothetically contributing to increased disease severity. In this study, we generated 26 monoclonal antibodies (MAbs) against the dengue virus type 1 Mochizuki strain. We selected this strain because a relatively large number of unique and rare amino acids were found on its envelope protein. Although most MAbs showing neutralizing activities exhibited enhancing activities at subneutralizing doses, one MAb (D1-IV-7F4 [7F4]) displayed neutralizing activities without showing enhancing activities at lower concentrations. In contrast, another MAb (D1-V-3H12 [3H12]) only exhibited enhancing activities, which were suppressed by pretreatment of cells with anti-FcγRIIa. Although antibody engineering revealed that antibody subclass significantly affected 7F4 (IgG3) and 3H12 (IgG1) activities, neutralizing/enhancing activities were also dependent on the epitope targeted by the antibody. 7F4 recognized an epitope on the envelope protein containing E118 (domain II), and had a neutralizing activity 10- to 1,000-fold stronger than previously reported human or humanized neutralizing MAbs targeting domains I and/or II. An epitope-blocking ELISA indicated that a dengue-immune population possessed antibodies sharing an epitope with 7F4. Our results demonstrating induction of these antibody species (7F4 and 3H12) in Mochizuki-immunized mice may have implications for dengue vaccine strategies designed to minimize induction of enhancing antibodies in vaccinated humans.
    Preview · Article · Sep 2013 · Journal of Virology
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    ABSTRACT: Dengue viruses have spread throughout tropical and subtropical countries, and vaccine development is urgently needed. However, one concern is that induction of insufficient levels of neutralizing antibodies in vaccinees may increase disease severity because of a hypothetical mechanism termed antibody-dependent enhancement of infection. This study used two distinct genotype strains of dengue virus types 1 and 3 (DENV1 and DENV3, respectively) to compare antibody responses in a mouse-DNA vaccine model. As expected, a conventional neutralization test using Vero cells showed higher antibody titers in homologous rather than heterologous combinations of genotype strains used for mouse immunization and the neutralization test, for each of DENV1 and DENV3. However, our assay system using K562 cells to measure the balance of neutralizing and enhancing antibodies indicated that Vero cell-neutralizing antibody titers did not always correlate with enhancing activities observed at subneutralizing doses. Rather, induction of enhancing activities depended on the genotype strain used for mouse immunization. The genotype/strain difference also affected IgG subclass profiles and potentially the composition of antibody species induced in mice. This study suggests that enhancing activities of dengue virus-induced neutralizing antibodies may vary according to the genotype and has implications for vaccine antigen development.
    No preview · Article · Aug 2013 · Microbes and Infection
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    ABSTRACT: Increasing attention is being devoted to ecological and evolutionary relationships between insect-specific flaviviruses and globally important human-pathogenic flaviviruses such as dengue viruses. One such insect flavivirus, cell-fusing agent virus (CFAV), remains poorly investigated. In this study, we isolated 13 and 16 CFAV strains from Aedes aegypti mosquitoes collected in Thailand in 2008 and 2012, respectively, and performed genetic and evolutionary analyses based on gene regions encoding the envelope protein (E) and nonstructural proteins 3 (NS3) and 5 (NS5). Consistent with previously reported CFAV strains, E, NS3 and NS5 regions comprised 1,290, 1,761 and 2,664 nucleotides, respectively. Nucleotide and amino acid identities of these three regions were >98% among the 29 isolates, and approximately 95-96% and 96-99%, respectively, between the isolates and previously reported CFAV strains. When amino acid sequences from representative strains of six insect-specific and seven mosquito-borne flaviviruses were compared, average identities of 14.9%, 31.8% and 44.3% were calculated for E, NS3 and NS5 regions, respectively. Phylogenetic analysis based on nucleotide and amino acid data indicated that the Thai CFAV isolates of the current study were distinct from previously reported CFAV strains from Indonesia and Puerto Rico. Analysis of each gene region consistently uncovered a clade made up of nearly the same subset of Thai CFAV isolates; this result, and the isolation of CFAV from mosquitoes reared from larvae, suggest that the virus is maintained by vertical transmission and conserved in a particular environment without considerable evolutionary alteration. The most recent common ancestor of the Thai CFAV isolates in this study was dated to 11-27 years ago, and is estimated to have diverged 46-86 years ago from previously reported CFAV strains. Superinfection with CFAV of Aedes mosquitoes carrying dengue viruses present in Thailand for over 50 years has most likely taken place.
    No preview · Article · Jul 2013 · Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases
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    ABSTRACT: : Japanese encephalitis virus (JEV) is a fatal disease in Asia. Pigs are considered to be the effective amplifying host for JEV in the peridomestic environment. Bali Island and Java Island in Indonesia provide a model to assess the effect of pigs on JEV transmission, since the pig density is nearly 100-fold higher in Bali than Java, while the geographic and climatologic environments are equivalent in these areas. We surveyed antibodies to JEV among 123 pigs in Mengwi (Bali) and 96 pigs in Tulungagung (East Java) in 2008 by the hemagglutination-inhibition (HAI) test. Overall prevalences were 49% in Bali and 6% in Java, with a significant difference between them (P < 0.001). Monthly infection rates estimated from age-dependent antibody prevalences were 11% in Bali and 2% in Java. In addition, 2-mercaptoethanol-sensitive antibodies were found only from Bali samples. Further, the average HAI antibody titer obtained from positive samples was significantly higher in Bali (1:52) than Java (1:10; P < 0.001). These results indicated that JEV transmission in nature is more active in Bali than East Java. Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus distributed throughout Asia. It causes Japanese encephalitis (JE), with an estimated 30,000 to 50,000 cases and 10,000 deaths reported every year (1). JEV exists in a transmission cycle between Culex mosquitoes and birds in nature. In a peridomestic environment, pigs are considered to be an effective amplifying host. Bali Island is adjacent to Java Island in the Indonesian archipelago. Based on statistics of the pig population in In-donesia, 2008 (2), a large number of pigs (899,582 heads) existed in Bali Island (5,633 km 2), whereas only a small pig population (227,953 heads) was raised in Java Island (127,499 km 2). The majority of Balinese and Javanese are Hindu and Muslim, respectively, which probably affects the number of pigs raised in the respective islands. The densities of pigs are nearly 100-fold different at 160 and 1.79 heads/km 2 in Bali and Java, respectively. Rural areas containing rice fields and pig farms provide an almost complete environment to main-tain and amplify JEV in the presence of vector mosquitoes in both Bali (3) and Java (4). Reflecting the difference in swine populations, confirmed JE cases have been reported mainly from Bali (5,6) and only recently from Java (7,8). Therefore, pigs may act as an impor-tant amplifier in these islands. However, no antibody surveys among pigs have been published from Bali or East Java, to the best of our knowledge. The present small survey of JEV antibodies was carried out using pig sera collected in Bali and East Java. Serum samples were collected from 123 pigs at a farm in Mengwi of Bali and 96 pigs at a farm in Tulungagung (East Java province) of Java in 2008. Samples in Bali were col-lected in the dry season (August), while samples in Java were collected in the rainy season (March through April). Since pigs are considered to have frequent natural exposures, the ages of subjects were limited to 1–6 months, and approxi-mately 20 individuals were used in each age group (Table 1), except for Java samples aged 6 months (unavailable) and 1 month (the number was half that of other groups). The pigs were housed in these farms under similar environments where the farms were 3,000–5,000 m 2 in area and adjacent to rice fields. These two study sites were located in a single area designated the East Java/Bali region from agricultural and climatologic aspects (9), providing equivalent environments involved in transmission of JEV by vector mosquitoes. Hemagglutination-inhibition (HAI) assay was performed by a micro-modification of the method of Clarke and Casals (10), with 4 hemagglutinin units of the JEV antigen (Nakayama strain; Denka Seiken, Niigata, Japan). Sera with an HAI antibody titer of 1:10 or higher were considered positive, and those with 1:20 or higher were treated with 2-mercaptoethanol (2-ME) to detect 2-ME-sensitive antibodies. When the difference between HAI antibody titers before and after treatment with 2-ME was 4-fold or greater, the sample was determined to contain IgM antibodies to JEV. Overall, 60 (49%) of 123 pigs in Bali and 6 (6%) of 96 pigs in Java were positive for HAI antibodies, showing a sig-nificant difference between them (P < 0.001 by the chi-square test with the Yates' correction factor; Table 1). Comparisons in each age group also detected significant differences between Bali and Java, except for pigs aged 1 month. The antibody prevalence increased with age, except for Bali subjects aged 2 months or less, which were probably affected by maternal antibodies: the duration of maternal antibodies in most pig-lets is 2 months (11,12). Average monthly infection rates estimated from age-dependent antibody prevalences were 11% in Bali and 2% in Java, supposing that sterile immunity due to maternal antibodies is negligible and that these pig 59 populations were infected at the same frequency during 6 months. Moreover, 5–24% of pigs aged over 3 months in Bali with an average of 13% (11/83) possessed IgM antibodies, and this percentage was comparable to the monthly infection rate estimated as described above (11%). HAI antibody titers were distributed from <1:10 to 1:640 in Bali samples, whereas the maximum antibody titer in Java samples was 1:10. The average HAI antibody titer obtained from positive samples was significantly higher in Bali (1:52) than Java (1:10; P < 0.001 by the Student's t test). The significantly higher qualitative (antibody prevalence) and quantitative (antibody titer) results obtained with Bali samples compared to Java samples relate to the difference in pig density between Bali and Java. One report available on a JEV antibody survey among pigs in Indonesia indicated a prevalence of as high as approximately 90%, but the survey was done in West Java and Central Java in the early of 1970s (or before) with pig subjects of older ages (6 to 24 months old; 13). In addition, one report from Bali Island described an antibody prevalence of approximately 70%, but this was described as "unpublished data" without details (6). The serodiagnostic method used in the present study (HAI test) detects antibodies cross-reactive to dengue viruses, which are also distributed in the present survey areas. However, vector mosquitoes that can transmit dengue viruses (Aedes aegypti and Aedes albopictus) are anthrophilic, and the rural area has low human densities, particularly around pig farms, with only low levels of dengue virus activity, if any. Thus, it is highly probable that the antibodies detected by an HAI test using JEV antigens were those against JEV, although the pos-sibility of measuring cross-reactive dengue antibodies is not completely ruled out. In conclusion, natural JEV activities were significantly more prevalent in Bali than Java. High percentages of pigs were infected before age 6 months in Bali, which may provide a large number of infected mosquitoes in nature. Although less active in Java, JEV did circulate and produce relatively high antibody prevalences among humans (14).
    Full-text · Dataset · Feb 2013
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    ABSTRACT: Indonesia has annually experienced approximately 100,000 reported cases of dengue fever (DF) and dengue hemorrhagic fever (DHF) in recent years. However, epidemiological surveys of dengue virus (DENV) have been limited in this country. One report indicated that dengue type 2 virus(DENV2) was the predominant circulating virus in 2003–2005 in Surabaya. In addition, our previous survey indicated that dengue type 1 virus (DENV1) displaced DENV2 in Surabaya in 2008 with subsequent genotype shifts from IV to I in 2009-2010. In the present study, we aimed at surveying the recent predominant DENV type and analyzing it phylogenetically. A total number of 313 isolates were obtained from 968 dengue patient sera collected in Surabaya and Sidoarjo, in 2011-2012. Phylogenetic analyses of the complete envelope gene inrecent DENV1 isolates indicated the predominant genotype was genotype IV in 2011 and both genotypes IV and I in 2012. For DENV2, the predominant genotype in 2008 was "Cosmopolitan genotype". Although the predominant genotype in 2011-2012 was also "Cosmopolitan genotype", they were grouped into a different clade. The shift of DENV types and genotypes may have increased, and will potentially continue to increase the proportion of DHF cases among the total number of dengue cases, as well as the total number of dengue patients. This indicates the need for continuous surveillance of circulating viruses to predict the risk of DHF and DF.
    Full-text · Conference Paper · Jan 2013
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    ABSTRACT: Background. Thymoma is often associated with various autoimmune disease, and pure red cell aplasia occurs in 5% of thymoma patients. Pure red cell aplasia is classified into several groups, and in secondary pure red cell aplasia, it has various causes, however, there have been few reports on the association of development of pure red cell aplasia and chemotherapy. Cases. Case 1, a 36-year-old man was administrated induction chemotherapy with cisplatin and amrubicin for invasive thymoma (WHO type B2, Masaoka classification III). Thymoma decreased in size, but he suffered from severe anemia, and pure red cell aplasia was diagnosed based on data from peripheral blood examination and bone marrow aspiration. Administration of cyclosporin and corticosteroid improved his anemia. Case 2, a 45-year-old woman was given chemotherapy with cisplatin and amrubicin for invasive thymoma (WHO type B1, Masaoka classification IVa). Thymoma decreased in size, but she suffered from severe anemia, and pure red cell aplasia was diagnosed based on data from peripheral blood examination and bone marrow aspiration. Administration of cyclosporin and corticosteroid improved her anemia. Conculsion. We experienced two cases of pure red cell aplasia appeared during chemotherapy for invasive thymoma. It is important to observe the patients during or even after chemotherapy by keeping the possible appearance of pure red cell aplasia in mind.
    No preview · Article · Jan 2013 · Haigan
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    ABSTRACT: Four types of dengue viruses (DENV1–4), which have several genotypes individually, are distributed throughout tropical and subtropical areas of the world. Although infection with one type of DENV protects individuals from subsequent homotypic infection, secondary heterotypic infection may increase the disease severity. Antibody-dependent enhancement of infection has been hypothesized as a cause of increased viremia levels which are generally believed to parallel the disease deterioration. Therefore, analyzing the balance of neutralizing and enhancing activities is important in order to understand the status of enhancing antibodies in endemic populations. In the previous INiTha forum, we preliminarily reported a comparison of serum antibody responses in dengue patients infected with different virus types or genotypes in Indonesia. In this report, comparisons were made in more detail. Thirty-two sera collected from patients in Surabaya 2008-2012 were used in this study. These patients were proven to be infected with any of four DENVs (DENV2, DENV4, DENV1 genotype I, DENV1 genotype IV) by means of virus isolation from sera. Thus, the balance of neutralizing and enhancing activities of these 32 sera were analyzed homologously and heterologously using 4 different virus isolates, totaling 128 combinations of ADE assays. Neutralizing and enhancing activities were different, depending on the virus strain. Heterologous combinations of virus and serum tended to exhibit stronger enhancing activity than homologous combinations in accordance with the fact that subsequent heterotypic infection may cause severer diseases. However, some homologous combinations exhibited stronger enhancing activity than heterologous ones. Furthermore, heterologous combinations exhibited neutralizing activities at the dilution where homologous combinations exhibited enhancing activity. Discussion will be made on the difference observed in these serum samples.
    Full-text · Conference Paper · Dec 2012
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    Kris Cahyo Mulyatno · Atsushi Yamanaka · Ngadino · Eiji Konishi
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    ABSTRACT: The resistance of Aedes aegypti mosquitoes to insecticides threatens dengue virus control efforts. In this study, Ae. aegypti larvae collected from 12 subdistricts in Surabaya, Indonesia, where dengue is endemic, were tested for resistance to the organophosphate, temephos. Susceptibility testing, performed according to World Health Organization (WHO) methods, showed all field strains were resistant to temephos at a dose of 0.012 mg/l, with mortality rates at 24 hours of 22% to 60%. Another susceptibility test to determine median lethal time (LT50) indicates resistance ratios ranging from 2.2 to 8.5. Although incipient resistance was detected at a dosage of 1 mg/l, as determined by the LT50, mortalities higher than 80% within 24 hours were detected using the WHO method in nine subdistricts of Surabaya, indicating temephos at 1 mg/l is still effective in field conditions in these areas. In three subdistricts (Tambaksari, Gubeng and Sawahan), the mortality rates were under 80%, indicating possible resistance to temephos.
    Full-text · Article · Oct 2012 · The Southeast Asian journal of tropical medicine and public health
  • Fithriyah Sjatha · Yamato Takizawa · Atsushi Yamanaka · Eiji Konishi
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    ABSTRACT: Dengue viruses are mosquito-borne viruses that cause dengue fever and dengue hemorrhagic fever, both of which are globally important diseases. These viruses have evolved in a transmission cycle between human hosts and mosquito vectors in various tropical and subtropical environments. We previously isolated three strains of dengue type 1 virus (DENV1) and 14 strains of dengue type 3 virus (DENV3) during an outbreak of dengue fever and dengue hemorrhagic fever in Jakarta, Indonesia in 1988. Here, we compared the nucleotide sequences of the entire envelope protein-coding region among these strains. The isolates were 97.6-100% identical for DENV1 and 98.8-100% identical for DENV3. All DENV1 isolates were included in two different clades of genotype IV and all DENV3 isolates were included in a single clade of genotype I. For DENV1, three Yap Island strains isolated in 2004 were the only strains closely related to the present isolates; the recently circulated Indonesian strains were in different clades. Molecular clock analyses estimated that ancestors of the genotype IV strains of DENV1 have been indigenous in Indonesia since 1948. We predict that they diverged frequently around 1967 and that their offspring distributed to Southeast Asia, the Western Pacific, and Africa. For DENV3, the clade containing all the present isolates also contained strains isolated from other Indonesian regions and other countries including Malaysia, Singapore, China, and East Timor from 1985-2010. Molecular clock analyses estimated that the common ancestor of the genotype I strains of DENV3 emerged in Indonesia around 1967 and diverged frequently until 1980, and that their offspring distributed mainly in Southeast Asia. The first dengue outbreak in 1968 and subsequent outbreaks in Indonesia might have influenced the divergence and distribution of the DENV1 genotype IV strains and the DENV3 genotype I strains in many countries.
    No preview · Article · Aug 2012 · Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases

Publication Stats

257 Citations
66.94 Total Impact Points

Institutions

  • 2012-2015
    • Mahidol University
      • Faculty of Tropical Medicine
      Siayuthia, Bangkok, Thailand
    • Kobe Medical Center
      Kōbe, Hyōgo, Japan
  • 2008-2013
    • Airlangga University
      • Institute of Tropical Disease
      Surabaya, West Java, Indonesia
  • 2010
    • Kobe University
      Kōbe, Hyōgo, Japan
  • 2009
    • Kobe International University
      Kōbe, Hyōgo, Japan