Travellers provide new isolates for malaria research

Over 1,300 cases of imported malaria have been reported in the UK annually for thepast 10 years。A few of these unfortunate travellers have recently contributed blood samples that may have long term beneficial consequences for future research into many aspects of the biology of the malaria parasite,Plasmodium falciparum.This is because Colin Sutherland and his team, based at the London School of Tropical Medicine and Hygiene, have established连续培养七个新分离株, all of African origin, from these samples.

2010年,大多数由疟疾造成的660,000人死亡发生在2010年。P. falciparum感染,特别是在居住在撒哈拉以南非洲的婴儿中令人惊讶的是,这个数字是个好消息,因为它自2000年以来代表非洲的死亡率下降了33%。但是,疟疾控制的历史是乐观主义之一,紧随其后,人们担心通过杀虫剂的部署而获得的进步治疗的床网以及通过使用联合药物治疗提供的治疗成功可能是短暂的。

The combination of an artemisinin derivative and a longer-lasting drug is currently the first line treatment for falciparum malaria recommended by WHO; but resistance to artemisinin isreported to be spreading。Drug failure takes the form of a delayed clearance phenotype, where ring stages of the parasite remain dormant. This has led to some debate concerning the term resistance, as used in this context 1-3, but regardless of the terminology used, a greater understanding of this new phenotype is urgently needed.

我们对恶性疟疾红细胞阶段的生物学的了解,包括对耐药性的研究,培养能力已促进P. falciparum in vitro.The culture systems in common usage are based on that reported by Trager and Jensen in 19764 and most clones grown in laboratories worldwide today were established in the 1980s and have thus been laboratory adapted for decades. Their usefulness in shedding light on current questions, such as determination of markers for the presence of resistance to artemisinin derivatives, may thus be limited. Furthermore, despite the fact that most clinical cases of malaria occur on the African continent, the majority of these cultures either originated from isolates whose source was Asia, or are one of the two widely used clones (NF 54 and a derivative, 3D7) that were isolated in the Netherlands and are of unknown geographical origin. By contrast, Sutherland’s new cultures were of West or East African origin. Finally, for those interested in sexual stages or mosquito infections, many of the clones in current usage are not reliable producers of infective gametocytes.

从新收集的分离株中建立恶性疟原虫寄生虫的文化适应克隆很具有挑战性,因此,萨瑟兰团队的成功将受到称赞。这项成就可能归因于他们在培养第一个分离株后改变生长培养基的决定。七个分离株中有六种是使用培养基改编成培养物的,其中人类血清的百分比被降低,并补充了血清替代品,COLLAX II的完整培养基,如is currently recommended

Of particular interest to those researchers working on the sexual stages of malaria is the news that one isolate readily produced gametocytes when the parasitaemia was increased beyond 2%.

所有七个稳定物都可以在European Malaria Reagent Repositoryas an open resource.

The medical and travel history of the seven donors is reported in thisarticle。考虑到大多数患者在地方性地区度过的短暂时间,有趣的是,所有分离株都是多克隆的。嵌套PCR分析确定除一个分离株外,所有分离株均由四到六个克隆组成。作者指出,多克隆性(一个个体中的几个克隆的存在)可能是由于传染性(孢子岩)阶段的一次接种而导致的,因为蚊子可能被几个不同的克隆感染。这强调了非洲分离株的复杂性,并可能使治疗方案复杂化,例如,其中一个克隆具有不同的生长模式或耐药性。

培养物用于筛选分离株以应对各种药物。据报道,对抗疟疾的敏感性以及耐药性标记的单倍型也是如此。七个孤立的五个对氯喹敏感,并在用lumefantrine挑战时记录了各种反应,该反应与Artemether结合使用。在非洲尚未报道以延迟清除表型为特征的青蒿素耐药性,所有分离株对内氧化二氢丙氨酸蛋白和OZ277均敏感。

Hopefully, these newly established isolates will prove of value to the malaria community and this report will pave the way for the establishment of further isolates in culture.

参考

  1. Ferreira, P.E., Culleton, R., Gil, J.P. and Meshnick, S.R. 2013. Artemisinin resistance in Plasmodium falciparum: what is it really? Trends in Parasitology, 29: 7, 318-320.
  2. Dondorp,A.M. and Ringwald, P. 2013. Artemisinin resistance is a clear and present danger. Trends in Parasitology, 28: 8, 359-360.
  3. Krishna, S. and Kremsne, P.G. 2013. Artemisinin needs to be defined rigorously to be understood: response to Dorndorp and Ringwald. Trends in Parasitology, 29: 8, 361-362.
  4. Trager W. and Jensen J.B. 1976. Human malaria parasites in continuous culture. Science, 193: 673-675.

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