HUMAN AND MALARIA PARASITE DIVERSITIES IN RELATION TO THE THERAPEUTIC EFFICACY OF ANTIMALARIALS ON ISLANDS IN THE ASIA AND PACIFIC

1.我们对瓦努阿图恶性疟原虫裂殖子表面蛋白-1等位基因的研究表明，岛屿上的恶性疟原虫的遗传多样性总体上是有限和稳定的，岛屿之间的隔离程度很高，这意味着在基因库有限的地方，疟疾疫苗将更有效，就像在孤立的人口中一样。2.巴布亚新几内亚的East Sepik种群显示，在东南亚岛屿和瓦努阿图之间，与CYP2C19相关的不良代谢物(PM)中等流行，表明遗传漂移是太平洋岛屿PM高患病率的主要因素。3.在马拉维，1993年从氯喹(CHL)改为磺胺多辛/乙胺(SP)导致具有双DHP和三DHFR(五重)突变的寄生虫的流行率很高(78%)，随着CHL疗效的恢复，pfcrt K76T的流行率下降(2%)。单倍型分析表明，野生pfcrt等位基因的扩大是CHL敏感性最近恢复的主要遗传机制。4.在肯尼亚西部的高原边缘，我们的调查显示，贫血最常见的是5岁以下的儿童(34%)，其次是低地村庄的育龄妇女(16%)。在[小于或等于]5岁儿童中，贫血(从海拔1440米的57%到海拔2040米的11%)和恶性疟原虫(从31%到0%)的患病率与海拔高度显著相关，这表明疟疾也是高原边缘地区贫血的主要原因。因此，减少疟疾流行的措施将减少贫血和与艾滋病毒传播风险有关的输血需求。

We do the studies of malaria in isolated areas on Island Melanesia in comparison with Sub-Saharan Africa to investigate the interactions among diversities of humans, parasites, mosquitoes and environment to understand relations among transmission, immunity and disease.1.Our studies on merozoite surface protein-1 alleles of P.falciparum in Vanuatu suggested generally limited and stable genetic diversity on islands and a high degree of isolation between the islands, implying that malaria vaccines will be more effective where there is a limited gene pool, as in isolated populations.2.The East Sepik populations of PNG showed a moderate prevalence of CYP2C19-related poor metabolizer (PM), between Island Southeast Asia and Vanuatu, suggesting genetic drift is a main factor of the high prevalence of PM in the Pacific islands.3.In Malawi the switching from chloroquine (CHL) to sulfadoxine/pyrimethamine (SP) in 1993 resulted in a high prevalence rate (78%) of parasites with double dhps and triple dhfr (quintuple) mutations and a reduction in the prevalence of pfcrt K76T (2%) with the recovery of CHL efficacy in 2000. A haplotype analysis revealed that an expansion of wild pfcrt allele is the primary genetic mechanism for the recent recovery of the CHL sensitivity.4.In the highland fringe of Western Kenya our survey showed that anemia was most common in children 【less than or equal】5 years of age (34%) followed by women of childbearing age (16%) in the lowland villages. In children 【less than or equal】5 years, both anemia (ranged from 57% at 1440m to 11% at 2040m) and P.falciparum (from 31% to 0%) prevalence significantly correlated with altitude, suggesting malaria is also the main cause of anemia in the highland fringe areas. Measures that reduce the prevalence of malaria will consequently reduce anemia and the need for blood transfusions associated with the risk of HIV transmission.