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

我们在美拉尼西亚岛与撒哈拉以南非洲的隔离地区进行了疟疾研究，以调查人类，寄生虫，蚊子和环境之间的相互作用，以了解传播之间的关系，1.我们对裂殖子表面蛋白的研究-1等位基因表明，瓦努阿图的恶性疟原虫在岛屿上的遗传多样性总体上有限而稳定，岛屿之间的隔离程度较高，这意味着在基因库有限的情况下，例如在隔离人群中，疟疾疫苗将更有效。2.巴布亚新几内亚的东塞皮克人群显示，在东南亚岛屿和瓦努阿图之间，CYP 2C 19相关的弱代谢者（PM）的患病率中等。这表明遗传漂变是太平洋岛屿PM高流行率的主要因素。3.在马拉维，从氯喹（CHL）转换为磺胺嘧啶/在1993年的乙胺嘧啶（SP）治疗中，具有双dhps和三dhfr（五重）突变的寄生虫的患病率很高（78%），pfcrt K76 T的患病率降低（2%），2000年CHL疗效恢复。单倍型分析显示，野生型pfcrt等位基因的扩增是CHL敏感性恢复的主要遗传机制。4.在肯尼亚西部的高原边缘地区，我们的调查显示贫血在低地村庄的5岁以下儿童（34%）中最为常见，其次是育龄妇女（16%）。在5岁以下儿童中，贫血（海拔1440 m时为57%~ 2040 m时为11%）和恶性疟原虫（海拔31%~ 0%）的患病率与海拔高度显著相关，提示疟疾也是高原边缘区贫血的主要原因。降低疟疾流行率的措施将减少贫血和与艾滋病毒传播风险相关的输血需求。

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.