Mbacham W, Njikam N
Département de Biochimie, Université de Yaoundé, Cameroon.
Med Trop (Mars). 2007 Apr;67(2):183-7.
Molecular markers or gene mutations that are associated with resistance have been the recent focus for an attempt to promptly determine the establishment of resistance to known and currently used antimalaria drugs. For control managers, the effective management of malaria would involve strategies of interruption of the malaria transmission and/or improved therapeutic management of malaria. To place molecular markers within the context of control programs requires that one recognises the two data pools necessary for effective evidence-based policy change. These include data on socio-economic determinants on the one hand and biomedical data on the other. The markers for clinical efficacy of drugs have principally been genes either associated with transport or metabolism of the drug. In malaria those that have been the most characterised are the Pfcrt, Pfmdrl for the quinolines and the dhfr and dhps genes for the anti-folates. The PfATPase has been suggested to be involved in the recently developed artermisinine based combination therapies (ACT). To consider changes in drug policy, a control manager needs to address: efficacy, transmissibility, disease dynamics, safety, epidemics, tolerability and compliance. Except for safety and tolerability/compliance, molecular markers do provide useful information. However these markers still have to be validated alongside in vitro studies and in many different ecological settings and shown to be stable over time or associated with changing drug efficacy situations. Besides the evidence provided with these tools, the government will be required to ensure a mass education of the population and care providers, and fight against illicit street vendors. The governments will therefore still wary on the resources necessary to occasion an effective switch in drug policy especially at the district level and in the rural areas where meaningful, cost-effective programs are most needed.
与抗药性相关的分子标记或基因突变,已成为近期研究的焦点,旨在迅速确定对已知及当前使用的抗疟药物产生抗药性的情况。对于疟疾防控管理人员而言,有效的疟疾管理涉及疟疾传播阻断策略和/或改善疟疾治疗管理。要将分子标记应用于防控项目中,需要认识到基于有效循证政策变革所需的两个数据池。一方面是社会经济决定因素数据,另一方面是生物医学数据。药物临床疗效的标记主要是与药物转运或代谢相关的基因。在疟疾领域,研究最为深入的是与喹啉类药物相关的Pfcrt、Pfmdrl基因,以及与抗叶酸药物相关的dhfr和dhps基因。PfATPase被认为与最近开发的青蒿素联合疗法(ACT)有关。要考虑药物政策的变化,防控管理人员需要关注:疗效、传播性、疾病动态、安全性、疫情、耐受性和依从性。除了安全性和耐受性/依从性外,分子标记确实能提供有用信息。然而,这些标记仍需在体外研究以及许多不同生态环境中进行验证,并证明其随时间稳定或与药物疗效变化情况相关。除了这些工具提供的证据外,政府还需要确保对公众和医护人员进行大规模教育,并打击非法街头小贩。因此,政府在进行药物政策有效转变所需资源方面仍持谨慎态度,尤其是在最需要有意义且具有成本效益项目的地区和农村地区。