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Wang, Yue,Kaneko, Osamu,Sattabongkot, Jetsumon,Chen, Jun-Hu,Lu, Feng,Chai, Jong-Yil,Takeo, Satoru,Tsuboi, Takafumi,Ayala, Francisco J,Chen, Yong,Lim, Chae Seung,Han, Eun-Taek Allen Press, etc.] 2011 The American journal of tropical medicine and hygi Vol.84 No.2
<P>Abstract. Plasmodium vivax msp1p, a paralog of the candidate vaccine antigen P. vivax merozoite surface protein 1, possesses a signal peptide at its N-terminus and two epidermal growth factor-like domains at its C-terminus with a glycosylphosphatidylinositol attachment site. The msp1p gene locus may have originated by a duplication of the msp1 gene locus in a common ancestor of the analyzed Plasmodium species and lost from P. yoelii, P. berghei, and P. falciparum during their evolutionary history. Full-length sequences of the msp1p gene were generally highly conserved; they had a few amino acid substitutions, one highly polymorphic E/Q-rich region, and a single-to-triple hepta-peptide repeat motif. Twenty-one distinguishable allelic types (A1-A21) of the E/Q-rich region were identified from worldwide isolates. Among them, four types were detected in isolates from South Korea. The length polymorphism of the E/Q-rich region might be useful as a genetic marker for population structure studies in malaria-endemic areas.</P>
Han, Eun Taek,Lee, Won Ja,Sattabongkot, Jetsumon,Jang, Jin Woo,Nam, Myoung Hyun,An, Seong Soo A.,Suh, InBum,Lim, Chae Seung Blackwell Publishing Ltd 2010 Tropical medicine & international health Vol.15 No.9
<P>Summary</P><P>The Ookinete surface proteins of <I>Plasmodium vivax (P. vivax)</I>, Pvs25 and Pvs28, were candidates for the transmission blocking vaccine (TBV), which exhibited great antigenic diversities among various isolates. Polymorphisms of these genes in the isolates from Republic of Korea (ROK) were analysed, which provided valuable baseline data for the field trials of TBV-based vaccines. A total of 98 isolates were collected over 11 years from 1996 to 2007. <I>pvs25</I> and <I>pvs28</I> genes from the above isolates were amplified, sequenced and compared against Sal-1 strain. Sequencing analysis of PCR products from <I>P. vivax pvs25</I> revealed two allelic types, Q97T130 and E97/T130 alleles with the frequencies of 54.5% and 45.5%, respectively, in comparison with Sal I type sequence (E97/I130). From <I>pvs28</I> gene, polymorphisms at M52L and T140S in the first and third EGF-like domains in comparison to Sal-1 strain were detected, respectively. Six GSGGE tandem repeats followed by GSGGDT or SSGGDT were identified at the end of the fourth EGF-like domain in all Korean isolates. Interestingly, different tandem repeats of amino acid substitutions were observed from isolates collected after 2006 in comparison with preceding years. The ROK isolates revealed limited sequence polymorphisms in <I>pvs25</I> and tandem repeats in <I>pvs28</I> in comparison with reported isolates from other nations. Current observations suggested the rapid progresses of genetic changes among Korean isolates.</P>
Prevalence of Drug Resistance-Associated Gene Mutations in Plasmodium vivax in Central China
Feng Lu,Bo Wang,Jun Cao,Jetsumon Sattabongkot,Huayun Zhou,Kwonkee Kim,Qi Gao,Eun-Taek Han 대한기생충학열대의학회 2012 The Korean Journal of Parasitology Vol.50 No.4
Resistance of Plasmodium spp. to anti-malarial drugs is the primary obstacle in the fight against malaria, and molecular markers for the drug resistance have been applied as an adjunct in the surveillance of the resistance. In this study, we investigated the prevalence of mutations in pvmdr1, pvcrt-o, pvdhfr, and pvdhps genes in temperate-zone P. vivax parasites from central China. A total of 26 isolates were selected, including 8 which were previously shown to have a lower susceptibility to chloroquine in vitro. For pvmdr1, pvcrt-o, and pvdhps genes, no resistance-conferring mutations were discovered. However, a highly prevalent (69.2%), single-point mutation (S117N) was found in pvdhfr gene. In addition, tandem repeat polymorphisms existed in pvdhfr and pvdhps genes, which warranted further studies in relation to the parasite resistance to antifolate drugs. The study further suggests that P. vivax populations in central China may still be relatively susceptible to chloroquine and sulfadoxine-pyrimethamine.
Molecular Cloning of Plasmodium vivax Calcium-Dependent Protein Kinase 4
Kyung-Mi Choi,Jung-Yeon Kim,Sung-Ung Moon,Hyeong-Woo Lee,Jetsumon Sattabongkot,Byoung-Kuk Na,Dae-Won Kim,Eun-Jung Suh,Yeon-Joo Kim,Shin-Hyeong Cho,Ho-Sa Lee,Ho-Gun Rhie,Tong-Soo Kim 대한기생충학열대의학회 2010 The Korean Journal of Parasitology Vol.48 No.4
A family of calcium-dependent protein kinases (CDPKs) is a unique enzyme which plays crucial roles in intracellular calcium signaling in plants, algae, and protozoa. CDPKs of malaria parasites are known to be key regulators for stage-specific cellular responses to calcium, a widespread secondary messenger that controls the progression of the parasite. In our study, we identified a gene encoding Plasmodium vivax CDPK4 (PvCDPK4) and characterized its molecular property and cellular localization. PvCDPK4 was a typical CDPK which had well-conserved N-terminal kinase domain and C-terminal calmodulin-like structure with 4-EF hand motifs for calcium-binding. The recombinant protein of EF hand domain of PvCDPK4 was expressed in Echerichia coli and a 34 kDa product was obtained. Immunofluorescence assay by confocal laser microscopy revealed that the protein was expressed at the mature schizont of P. vivax. The expression of Pv-CDPK4-EF in schizont suggests that it may participate in the proliferation or egress process in the life cycle of this parasite.
Xiaotao Zhao,Weerapong Thanapongtharm,Siam Lawawirojwong,Chun Wei,Yerong Tang,Yaowu Zhou,Xiaodong Sun,Jestumon Sattabongkot,Jaranit Kaewkungwal 대한기생충학ㆍ열대의학회 2020 The Korean Journal of Parasitology Vol.58 No.3
The heterogeneity and complexity of malaria involves political and natural environments, socioeconomic devel- opment, cross-border movement, and vector biology; factors that cannot be changed in a short time. This study aimed to assess the impact of economic growth and cross-border movement, toward elimination of malaria in Yunnan Province during its pre-elimination phase. Malaria data during 2011-2016 were extracted from 18 counties of Yunnan and from 7 villages, 11 displaced person camps of the Kachin Special Region II of Myanmar. Data of per-capita gross domestic prod- uct (GDP) were obtained from Yunnan Bureau of Statistics. Data were analyzed and mapped to determine spatiotemporal heterogeneity at county and village levels. There were a total 2,117 malaria cases with 85.2% imported cases; most im- ported cases came from Myanmar (78.5%). Along the demarcation line, malaria incidence rates in villages/camps in Myanmar were significantly higher than those of the neighboring villages in China. The spatial and temporal trends sug- gested that increasing per-capita GDP may have an indirect effect on the reduction of malaria cases when observed at macro level; however, malaria persists owing to complex, multi-faceted factors including poverty at individual level and cross-border movement of the workforce. In moving toward malaria elimination, despite economic growth, cooperative efforts with neighboring countries are critical to interrupt local transmission and prevent reintroduction of malaria via im- ported cases. Cross-border workers should be educated in preventive measures through effective behavior change com- munication, and investment is needed in active surveillance systems and novel diagnostic and treatment services during the elimination phase.
Immunoprofiling of the Tryptophan-Rich Antigen Family in <i>Plasmodium vivax</i>
Wang, Bo,Lu, Feng,Cheng, Yang,Chen, Jun-Hu,Jeon, Hye-Yoon,Ha, Kwon-Soo,Cao, Jun,Nyunt, Myat Htut,Han, Jin-Hee,Lee, Seong-Kyun,Kyaw, Myat Phone,Sattabongkot, Jetsumon,Takashima, Eizo,Tsuboi, Takafumi,H American Society for Microbiology 2015 Infection and immunity Vol.83 No.8
<P>Tryptophan-rich antigens (TRAgs) are an antigen family that has been identified in human and rodent malaria parasites. TRAgs have been proposed as candidate antigens for potential vaccines. The <I>Plasmodium vivax</I> TRAg (PvTRAg) family includes 36 members. Each PvTRAg contains a tryptophan-rich (TR) domain in the C-terminal region. In this study, we recombinantly expressed all 36 PvTRAgs using a cell-free expression system, and, for the first time, profiled the IgG antibody responses against all PvTRAgs in the sera from 96 vivax malaria patients and 40 healthy individuals using protein microarray technology. The mean seropositive rate for all PvTRAgs was 60.3%. Among them, nine PvTRAgs were newly identified in this study and showed a seropositive rate of >50%. Five of them, PvTRAg_13, PvTRAg_15, PvTRAg_16, PvTRAg_26, and PvTRAg_29, produced higher levels of IgG antibody, even in low-endemicity countries. In addition, the results of an immunofluorescence analysis suggest that PvTRAgs are, at least in part, associated with caveola-vesicle complexes, a unique structure of <I>P. vivax</I>-infected erythrocytes. The mechanism of formation and the function of these abundant membrane structures are not known. Further investigation aimed at determining the functions of these proteins would lead to a better understanding of the blood-stage biology of <I>P. vivax</I>.</P>
Variable number of tandem repeats of 9 Plasmodium vivax genes among Southeast Asian isolates
Wang, B.,Nyunt, M.H.,Yun, S.G.,Lu, F.,Cheng, Y.,Han, J.H.,Ha, K.S.,Park, W.S.,Hong, S.H.,Lim, C.S.,Cao, J.,Sattabongkot, J.,Kyaw, M.P.,Cui, L.,Han, E.T. Verlag fur Recht und Gesellschaft 2017 Acta tropica Vol.170 No.-
<P>The variable number of tandem repeats (VNTRs) provides valuable information about both the functional and evolutionary aspects of genetic diversity. Comparative analysis of 3 Plasmodium falciparum genomes has shown that more than 9% of its open reading frames (ORFs) harbor VNTRs. Although microsatellites and VNTR genes of P. vivax were reported, the VNTR polymorphism of genes has not been examined widely. In this study, 230 P. vivax genes were analyzed for VNTRs by SERV, and 33 kinds of TR deletions or insertions from 29P. vivax genes (12.6%) were found. Of these, 9 VNTR fragments from 8 P. vivax genes were used for PCR amplification and sequence analysis to examine the genetic diversity among 134 isolates from four Southeast Asian countries (China, Republic of Korea, Thailand, and Myanmar) with different malaria endemicity. We confirmed the existence of extensive polymorphism of VNTR fragments in field isolates. This detection provides several suitable markers for analysis of the molecular epidemiology of P. vivax field isolates. (C) 2017 Elsevier B.V. All rights reserved.</P>
Sakamoto, Hirokazu,Takeo, Satoru,Takashima, Eizo,Miura, Kazutoyo,Kanoi, Bernard N.,Kaneko, Takamasa,Han, Eun-Taek,Tachibana, Mayumi,Matsuoka, Kazuhiro,Sattabongkot, Jetsumon,Udomsangpetch, Rachanee,Is Elsevier 2018 Parasitology international Vol.67 No.2
<P><B>Abstract</B></P> <P>The target molecules of antibodies against falciparum malaria remain largely unknown. Recently we have identified multiple proteins as targets of immunity against <I>Plasmodium falciparum</I> using African serum samples. To investigate whether potential targets of clinical immunity differ with transmission intensity, we assessed immune responses in residents of low malaria transmission region in Thailand. Malaria asymptomatic volunteers (Asy: n=19) and symptomatic patients (Sym: n=21) were enrolled into the study. Serum immunoreactivity to 186 wheat germ cell-free system (WGCFS)-synthesized recombinant <I>P. falciparum</I> asexual-blood stage proteins were determined by AlphaScreen, and subsequently compared between the study groups. Forty proteins were determined as immunoreactive with antibody responses to 35 proteins being higher in Asy group than in Sym group. Among the 35 proteins, antibodies to MSP3, MSPDBL1, RH2b, and MSP7 were significantly higher in Asy than Sym (unadjusted p<0.005) suggesting these antigens may have a protective role in clinical malaria. MSP3 reactivity remained significantly different between Asy and Sym groups even after multiple comparison adjustments (adjusted p=0.033). Interestingly, while our two preceding studies using African sera were conducted differently (e.g., cross-sectional vs. longitudinal design, observed clinical manifestation vs. functional activity), those studies similarly identified MSP3 and MSPDBL1 as potential targets of protective immunity. This study further provides a strong rationale for the application of WGCFS-based immunoprofiling to malaria vaccine candidate and biomarker discovery even in low or reduced malaria transmission settings.</P> <P><B>Highlights</B></P> <P> <UL> <LI> WGCFS generated <I>P. falciparum</I> recombinant proteins are immunoreactive to human sera from low endemic Thailand. </LI> <LI> Four <I>P. falciparum</I> antigens are plausible targets of clinical immunity. </LI> <LI> WGCFS and AlphaScreen system are invaluable tools for malaria vaccine candidate and biomarker discovery. </LI> </UL> </P>