MOLECULAR EPIDEMIOLOGY OF DRUG RESISTANCE AND POPULATION GENETIC STRUCTURE OF PLA -
Project Summary/Abstract
Malaria remains a serious public health problem in China. In the subtropical
Yunnan Province and the tropical Hainan Island of China, malaria has been the most
endemic with high transmission of both Plasmodium falciparum and P. vivax. However,
most of the attention in terms of research and interventions have been focused in
Africa and Southeast Asia, very few studies of malaria in China have been conducted.
Because of extensive use, chloroquine (CQ) has now lost its efficacy due to the
emergence of resistant strains in most parts of the world. Meanwhile, suspension of the
use of CQ has resulted in reappearance of CQ sensitivity. However, there were
differences in the evolution of CQ resistance between parasites from Yunnan and
Hainan, the exact mechanism needs to be investigated. Sulfadoxine-pyrimethamine
(SP) targets the dhfr and dhps genes of P. falciparum, and point mutations that confer
resistance have been widely reported worldwide. Documenting the identity and extent
of SP resistance is also critical for policy decisions regarding antimalarial drugs. In
addition, P. vivax causes a large burden of morbidity in the world including China but
traditionally has been understudied. Based on these, our long-term goal of this
proposal is 1) to identify single-nucleotide polymorphism (SNP) and characterize the
geographic distribution of genetic diversity, population structure, and haplotype
variability at drug resistant loci of P. falciparum from Yunnan and Hainan, China, 2) to
examine the geographic population structure, levels of genetic diversity of P. vivax
using microsatellite and SNP, and 3) to yield valuable information for making more
effective malaria control policies in China. In the past several years we have developed
the molecular methods to study the genetics, population diversity, and evolution of
malaria parasites, and have done some preliminary studies on malaria field isolates
from Yunnan and Hainan using genetic markers, thus enabling us to study the
molecular epidemiology of these important malaria parasites in this proposal. The
specific aims are to:
1. Determine genetic polymorphisms associated with CQ resistance (CQR) in P.
falciparum field isolates from Yunnan and Hainan provinces, China.
2. Determine the point mutation prevalence in the dhfr (pyrimethamine drug
resistance) and dhps (sulfadoxine drug resistance) genes associated with SP
resistance in P. falciparum field isolates from Yunnan and Hainan provinces, China.
3. Assess the changes of P. vivax genotypes using pvcsp, pvmsp1, pvmsp3-¿
genes, and microsatellite markers and determine the geographic structure and
specific epidemiological characteristics of P. vivax transmission in Yunnan and Hainan,
China.
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