Project/Area Number |
16406012
|
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 | International Medical Centre of Japan |
Principal Investigator |
KANO Shigeyuki International Medical Center of Japan (Research Institute), Department of Appropriate Technology Development and Transfer, Director, 適正技術開発移転研究部, 部長 (60233912)
|
Co-Investigator(Kenkyū-buntansha) |
KAWAZU Shin-ichiro Department of Appropriate Technology Development and Transfer, Laboratory of Appropriate Technology Development, Chief, 適正技術開発移転研究部・適正技術開発研究室, 室長 (60312295)
HATABU Toshimitsu Gunma University, School of Medicine, Assistant Professor, 医学部, 助手 (60344917)
|
Project Period (FY) |
2004 – 2006
|
Project Status |
Completed (Fiscal Year 2006)
|
Budget Amount *help |
¥13,300,000 (Direct Cost: ¥13,300,000)
Fiscal Year 2006: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2005: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥6,400,000 (Direct Cost: ¥6,400,000)
|
Keywords | malaria / Drug resistance / genome / epidemiology / Asia / International collaboration research / Thailand: Laos: Vietnam: Philippines / マラリア / タイ:ラオス:ベトナム:フィリピン:ミャンマー |
Research Abstract |
A mutation from Lys to Thr in the codon 76 of Plasmodium falciparum chloroquine resistant transporter protein (PfCRT) is associated with CQ resistance, and the genotype is used as a molecular marker to monitor the distribution and frequency of the CQ resistant malaria. In the present study, selection of the resistant strain in mixed cultures of a drug resistant strain (K1 which shows K76T) and a susceptible strain (FCR-3 which shows 76K) under a low chloroquine pressure (<80nM) was nicely observed in vivo using real-time PCR analysis. Then, we analyzed the frequency of the mutation in codon 72-76 of the pfcrt gene and 3 microsatellite (MS) DNA markers flanking the pfcrt, using P. falciparum isolates from the Philippines, Thailand, and southern part of Vietnam. Thirty-nine isolates from Thailand showed identical K76T but 6 out of 13 isolates from the Philippines showed mixed type. Twenty-seven of 39 isolates from Vietnam showed CQ susceptible genotype coding CVMNK, while other 10 did CQ resistance type (CVIET, CVIDT, CVMDT). The other 2 isolates were proved to be mixed with CQ susceptible/resistant. In the further analysis of the Vietnam isolates, the MS DNA markers of the CQ susceptible isolates were revealed to be highly polymorphic, while those of CQ resistant isolates were less polymorphic. One of the CQ resistant isolates (CVIET) had a different MS DNA pattern from K1 (CQ resistant strain; CVIET) from Thailand. The other CQ resistant isolate types (CVIDT, CVMDT) shared the same MS DNA patterns and these patterns were different from those of the CQ susceptible isolates nor K1. These results showed that the origin of the CQ resistant isolates in Vietnam might not be due to an introduction of the isolates from Thailand. Instead, it is suggested that the CQ resistant mutations possibly occurred within Vietnam.
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