Marma Aung Swi Prue, Mita Toshihiro, Eto Hideaki, Tsukahara Takahiro, Sarker Sumon, Endo Hiroyoshi
Department of International Affairs and Tropical Medicine, Faculty of Medicine, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan.
Parasitol Int. 2010 Jun;59(2):178-82. doi: 10.1016/j.parint.2010.01.003. Epub 2010 Jan 22.
In Bangladesh, despite the official introduction of artemisinin combination therapy in 2004, chloroquine+sulfadoxine/pyrimethamine has been used for the treatment of uncomplicated malaria. To assess the distribution of pfcrt, pfmdr1, dhfr, and dhps genotypes in Plasmodium falciparum, we conducted hospital- and community-based surveys in Bandarban, Bangladesh (near the border with Myanmar) in 2007 and 2008. Using nested PCR followed by digestion, 139 P. falciparum isolates were genotyped. We found fixation of a mutation at position 76 in pfcrt and low prevalence of a mutation at position 86 in pfmdr1. In dhfr, the highest pyrimethamine resistant genotype quadruple mutant was found in 19% of isolates, which is significantly higher prevalence than reported in a previous study in Khagrachari (1%) in 2002. Microsatellite haplotypes flanking dhfr of the quadruple mutants in Bangladesh were identical or very similar to those found in Thailand and Cambodia, indicating a common origin for the mutant in these countries. These observations suggest that the higher prevalence of the dhfr quadruple mutant in Bandarban is because of parasite migration from Myanmar. However, continuous use of sulfadoxine/pyrimethamine would have also played a role through selection for the dhfr quadruple mutant. These results indicate an urgent need to collect molecular epidemiological information regarding dhfr and dhps genes, and a review of current sulfadoxine/pyrimethamine usage with the aim of avoiding the widespread distribution of high levels of resistant parasites in Bangladesh.
在孟加拉国，尽管2004年已正式引入青蒿素联合疗法，但氯喹+磺胺多辛/乙胺嘧啶仍被用于治疗非复杂性疟疾。为评估恶性疟原虫中pfcrt、pfmdr1、dhfr和dhps基因型的分布情况，我们于2007年和2008年在孟加拉国班达班（靠近缅甸边境）开展了基于医院和社区的调查。通过巢式PCR随后进行酶切，对139株恶性疟原虫分离株进行了基因分型。我们发现pfcrt基因第76位的突变已固定，而pfmdr1基因第86位的突变发生率较低。在dhfr基因中，发现19%的分离株存在最高的乙胺嘧啶抗性基因型四重突变，这一发生率显著高于2002年在卡格拉乔里进行的一项研究中所报告的发生率（1%）。孟加拉国四重突变体dhfr侧翼的微卫星单倍型与在泰国和柬埔寨发现的单倍型相同或非常相似，表明这些国家的突变体有共同起源。这些观察结果表明，班达班dhfr四重突变体的较高发生率是由于寄生虫从缅甸迁移所致。然而，持续使用磺胺多辛/乙胺嘧啶也可能通过选择dhfr四重突变体而发挥了作用。这些结果表明迫切需要收集有关dhfr和dhps基因的分子流行病学信息，并审查当前磺胺多辛/乙胺嘧啶的使用情况，以避免在孟加拉国广泛传播高抗性寄生虫。
