Development of diagnostic tool for early stage of Schistosomal liver fibrosis in high risk population in Philippines.

• Project/Area Number: 15H05278
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 海外学術
• Research Field: Parasitology (including sanitary zoology)
• Research Institution: Nagasaki University
• Principal Investigator: KIKUCHI Mihoko 長崎大学, 熱帯医学研究所, 講師 (40336186)
• Co-Investigator(Kenkyū-buntansha): 千種 雄一 獨協医科大学, 医学部, 教授 (20171936) ; 中村 梨沙 長崎大学, 熱帯医学研究所, 助教 (50645801) ; 本間 季里 長崎大学, 医歯薬学総合研究科(医学系), 准教授 (70307940)
• Research Collaborator: Leonardo Lydia ; Tabios Kim Ian
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000); Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2017: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
• Keywords: 日本住血吸虫症 / 肝線維化症 / フィリピン共和国 / レイテ島 / バイオマーカー / フィリピン / 宮入貝 / 日本住血吸虫 / 日本住血吸虫性肝線維化症 / 診断マーカー / 免疫応答 / 早期診断 / 高リスク集団 / 予防法・治療法 / 住血吸虫性肝線維化症 / 疫学調査 / ハイリスク集団 / 超音波診断

Outline of Final Research Achievements

In Philiipines still have 28 state of Schistosoma japonica endemic area in 81 state and 12,000,000 people have risk of infection. Schistosomiasis is a parasitic disease caused by blood flukes. After Repeated infection was induced severe clinical form for liver fibrosis. There are no effective treatments to liver fibrosis except to inhibit to infection in the present state. In this study, a total of 75 individuals were recruited for the longitudinal study from the initial 895 people examined in the cross-sectional study in Lyte, the Philippines. At baseline, 31 patients had typical network Liver fibrosis (T3), 17 had mild and atypical hepatic fibrosis (T1&2), and 27 had no ultrasound detectable fibrosis in the liver (T0). It was analyzed physiologically active substance in the serum and expression kinetics of miRNA on each group. These results was suggested that possibility of miRNA-150-5p, miRNA-93-5p and a hyaluronic acid as a marker for Schistosomal liver fibrosis.

Academic Significance and Societal Importance of the Research Achievements

住血吸虫症感染後、数年を経てから発症する進行した肝線維化症は不可逆性であり、フィリピンの高度浸淫地における健康問題、経済的損失は多大である。肝線維化症憎悪に関係する早期診断用バイオマーカーを開発しようという試みは独創的である。本研究の結果、いくつかのバイオマーカーが有用である事が示唆された。実用化には、今後さらに検討を重ねる必要があるが、この成果は、日本住血吸虫症だけではなくメコン住血吸虫感染後に発症する肝線維化症対策に応用可能であると考えている。ツールとしての肝線維化症簡便診断法が開発される事で、治療法あるいは予防法における画期的な進展が期待できる。

Research Products

• [Int'l Joint Research] University of the Philippine(フィリピン)
• [Int'l Joint Research] フィリピン大学公衆衛生学部/フィリピン大学生物学研究所/レイテ島住血吸虫研究所(フィリピン)
• [Int'l Joint Research] University of the Philippines/College of Public Health/Dept. Parasitology(フィリピン)
• [Int'l Joint Research] University of Philippine(フィリピン)
• [Journal Article] Elevated IL-17 levels in semi-immune anaemic mice infected with Plasmodium berghei ANKA. (2018)
  • Author(s): Helegbe GK, Huy NT, Yanagi T, Shuaibu MN, Kikuchi M, Cherif MS, Hirayama K.
  • Journal Title: Malar J. Volume: 17(1) Issue: 1 Pages: 109-109
  • DOI: 10.1186/s12936-018-2257-x
  • NAID: 120006987330
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Intestinal Inflammation-Mediated Clearance of Amebic Parasites Is Dependent on IFN-γ (2018)
  • Author(s): Shimokawa C, Senba M, Kobayashi S, Kikuchi M, Obi S, Olia A, Hamano S, Hisaeda H
  • Journal Title: Journal of Immunology Volume: 200 Issue: 3 Pages: 1101-1109
  • DOI: 10.4049/jimmunol.1700806
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Usefulness of environmental DNA for detecting Schistosoma mansoni occurrence sites in Madagascar. (2018)
  • Author(s): Sato MO, Rafalimanantsoa A, Ramarokoto C, Rahetilahy AM, Ravoniarimbinina P, Kawai S, Minamoto T, Sato M, Kirinoki M, Rasolofo V, De Calan M, Chigusa Y.
  • Journal Title: Int J Infect Dis. Volume: 76 Pages: 817-823
  • DOI: 10.1016/j.ijid.2018.08.018
  • NAID: 120006539308
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Evaluation of <i>Schistosoma japonicum</i> thioredoxin peroxidase-1 as a potential circulating antigen target for the diagnosis of Asian schistosomiasis (2018)
  • Author(s): Macalanda AMC, Angeles JMM, Moendeg KJ, Dang AT, Higuchi L, Inoue N, Xuan X, Kirinoki M, Chigusa Y, Leonardo LR, Villacorte EA, Rivera PT, Goto Y, Kawazu SI.
  • Journal Title: Journal of Veterinary Medical Science Volume: 80 Issue: 1 Pages: 156-163
  • DOI: 10.1292/jvms.17-0579
  • NAID: 130006331072
  • ISSN: 0916-7250, 1347-7439
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Characterization of Schistosoma japonicum CP1412 protein as a novel member of the ribonuclease T2 molecule family with immune regulatory function. (2017)
  • Author(s): Ke XD, Shen S, Song LJ, Yu CX, Kikuchi M, Hirayama K, Gao H, Wang J, Yin X, Yao Y, Liu Q, Zhou W.
  • Journal Title: Parasite and Vectors. Volume: 10(1) Issue: 1 Pages: 89-89
  • DOI: 10.1186/s13071-016-1962-y
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Geographic strain differentiation of Schistosoma japonicum in the Philippines using microsatellite markers. (2017)
  • Author(s): Moendeg KJ, Angeles JMM, Nakao R, Leonardo LR, Fontanilla IKC, Goto Y, Kirinoki M, Villacorte EA, Rivera PT, Inoue N, Chigusa Y, Kawazu SI
  • Journal Title: PLoS Negl. Trop. Dis. Volume: 11 Issue: 7 Pages: e0005749-e0005749
  • DOI: 10.1371/journal.pntd.0005749
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Schistosomiasis in the Philippines: Challenges and some successes in Control. (2016)
  • Author(s): Lydia Leonardo, Yuichi Chigusa, Mihoko Kikuchi, Naoko Kato-Hayashi, Shin-ichiro Kawazu, Jose Ma Angeles, Ian Kendrich Fontanilla, Ian Kim Tabios, Kharleezelle Moendeg, Yasuyuki Goto, Raffy Jay Fornillos, Pebbles Grayle Tamayo and James Christoper Chua
  • Journal Title: Southeast Asian journal of tropical medicine and public health Volume: 47(4) Pages: 651-666
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Immunogenicity and anti-fecundity effect of nanoparticle coated glutathione S-transferase (SjGST) DNA vaccine against murine Schistosoma japonicum infection. (2015)
  • Author(s): Mbanefo EC, Kumagai T, Kodama Y, Kurosaki T, Furushima-Shimogawara R, Cherif MS, Mizukami S, Kikuchi M, Huy NT, Ohta N, Sasaki H, Hirayama K.
  • Journal Title: Parasitol Int. Volume: 64 Issue: 4 Pages: 24-31
  • DOI: 10.1016/j.parint.2015.01.005
  • Peer Reviewed / Open Access
• [Journal Article] Detection of active schistosome infection by cell-free circulating DNA of Schistosoma japonicum in highly endemic areas in Sorsogon Province, the Philippines (2014)
  • Author(s): Kato-Hayashi N, Leonardo LR, Arevalo NL, Tagum MNB, Apin J, Agsolid LM, Chua JC, Villacorte EA, Kirinoki M, Kikuchi M, Ohmae H, Haruki K, Chigusa Y
  • Journal Title: Acta Tropica Volume: 141 Pages: 178-183
  • DOI: 10.1016/j.actatropica.2014.05.003
  • Peer Reviewed / Open Access / Acknowledgement Compliant