恶性疟原虫氯喹抗性机制研究进展

目的目前疟原虫抗药性已成为全球性严重的公共卫生问题,现有的抗疟药物大部分已产生程度不同的抗药性。研究药物抗性产生的分子机制对研制新型抗疟药、降低抗性产生速率以及对抗性实施监测都具有重要意义。氯喹作为最早发现和使用的最为有效抗疟药物,在大规模用于疟疾治疗后,恶性疟原虫陆续产生对氯喹的抗药性,并且抗性虫株在全球范围迅速播散。近二十年来对氯喹作用机制和抗药性产生的分子机制的研究已取得很大进展。本文将讨论近年来有关氯喹抗性产生相关的分子机制,尤其是与抗药性密切相关的两个基因,即恶性疟原虫氯喹抗性转运蛋白基因（Pfcrt）与恶性疟原虫多药物抗性基因-1（Pfmdr1）的研究进展。     

青蒿素类药物治疗间日疟的研究进展

疟疾作为一种致死性很高的全球性寄生虫病,一直被全世界所关注,疟疾的控制也被列入全球三大公共卫生问题之一。由于长期抗疟药的使用,目前恶性疟原虫对主要抗疟药物普遍产生抗药性,青蒿素类药物是在氯喹、奎宁抗药性产生后的主要替代治疗药。而对于间日疟原虫引起的疟疾的治疗,却与恶性疟原虫大不相同,本文针对间日疟的青蒿素治疗现状及进展情况进行了综述。     

恶性疟原虫对氯喹抗药性的流行病学及IPT的研究进展

氯喹作为最早发现和使用的最为有效的抗疟药物,在大规模用于疟疾治疗后,恶性疟原虫陆续对它产生抗药性,并且抗性虫株在全球范围迅速播散。近年来的研究显示氯喹可用于疟疾的周期性预防疗法。本文综述了氯喹抗药性流行病学的研究,抗药性产生的机制及周期性预防疗法（Intermittent preventive treatment,IPT）的研究新进展。     

恶性疟原虫青蒿素抗疟药抗性研究进展

疟疾是由疟原虫感染引起的一种传染病,是全球最重要的公共卫生问题之一。世界卫生组织（WHO）推荐以青蒿素为基础的联合疗法（artemisinin-based combination therapies, ACTs）作为疟疾流行地区的非复杂性恶性疟的一线治疗。青蒿素及其衍生物的应用在降低全球疟疾发病率方面发挥了不可或缺的作用。但近年来,青蒿素类药物抗性的出现与扩散使全球疟疾的控制与消除面临巨大挑战。目前,与青蒿素抗药性关系最为密切的是恶性疟原虫第13号染色体上K13基因的突变,但近些年不断有研究表明K13并不能解释所有的青蒿素抗性。本文综述近年来恶性疟原虫对青蒿素产生抗性研究领域的相关研究进展,包括青蒿素抗药性的定义、检测方法、抗性相关的分子标记等。此外,本文所讨论的某些问题仍存在争议,还需深入研究。     

恶性疟原虫氯喹抗性相关基因的研究进展

恶性疟原虫产生氯喹抗性是疟疾防治中遇到的主要难题之一。存在于恶性疟原虫5号染色体上的多药抗药性基因1 (pfmdr1)和7号染色体上的cg2基因和pfcrt基因被认为是氯喹抗性相关基因。本文就其研究进展作一综述。     

疟原虫的抗性与抗疟药的进展

近十多年来在非洲、印度支那及南美洲等地的疟疾特别是恶性疟原虫对抗疟药产生抗性与交叉抗性,造成了疟疾的复发和流行,影响了疟疾的预防和治疗,这是消灭疟疾工作中的一个严重问题。因此克服抗性、寻找新药是当前国内外研究的一个重要课题。     

恶性疟原虫对青蒿素类药物抗药性的研究进展

恶性疟是一种致死性很高的全球性寄生虫病。长期抗疟治疗引起恶性疟原虫对氯喹等主要抗疟药物普遍产生抗药性，青蒿素类药物是在氯喹抗药性产生之后的主要替代治疗药，也是至今唯一没有出现普遍抗药性的抗疟药，但有研究提示青蒿素类药物的敏感性正逐渐下降，抗性产生是不可避免的。为有效预防和控制恶性疟对青蒿素类药物抗药性的产生及传播，对其抗性机制研究迫在眉睫。目前的研究发现，除pfatp6，tctp等，疟原虫的电子传递链也可能是青蒿素类药物的作用靶点，而恶性疟原虫对其抗药性的产生可能与pfmdrl，pfcrt，pfatp6，tctp，cg10等基因及其突变有关，但至今尚未明确真正的抗性相关基因。     

恶性疟治疗的前景

全世界每年死于疟疾的病人超过 2 0 0万。WHO已将非洲、东南亚的恶性疟列为全球疾病控制的重点。治疗恶性疟的难点在于其对新抗疟药极易产生抗药性 ,以及多重抗药性虫株的迅速蔓延。1　恶性疟原虫的抗药机理195 7年首先在泰国观察到疟原虫对氯喹抗药。195 9年相继在哥伦比亚、委内瑞拉发现疟原虫抗药性 ,而后几乎世界所有的恶性疟疾流行区均报告疟原虫对不同的抗疟药产生抗药性。1.1　抗叶酸盐类属于该类的药物有乙胺嘧啶 (pyrimethamine ,PYR)、氯胍 (proguanil,PG )、磺胺多辛 (sulfadoxine ,SDX)、磺胺甲氧吡嗪 (sulfalene)等。PYR…     

抗疟药物的合理联用

<正> 自1961年发现恶性疟的抗氯喹虫株以来,抗药性疟疾日益增多,有的地区已严重到必须改变常规治疗的地步。因此,除了积极发展新药之外,还应当重视联合用药,力求更合理地利用现有药物,使之发挥更有效的抗疟作用,并防止产生抗药性。一、疟原虫的抗药性及其特点 (一)疟原虫可产生抗药性的药物已经证实,恶性疟原虫对几乎所有的抗疟药都能产     

芜荑抗疟作用实验研究：二,对抗药虫株的效应

近十几年来世界各主要疟疾流行区不断出现抗药性恶性疟原虫株,为寻找治疗抗药性疟疾的替换新药,我们做了芜荑亲脂性提取物丙(C)的三个组分对于抗药疟原虫株的效应观察,通过动物疟疾模型证实前述三个组分能抑制抗氯喹株鼠伯氏疟原虫的生长发育,是一种有苗头的药物,值得进一步研究,有希望为临床提供一种对于抗药性疟原虫株所致疟疾的有效药物。     

Artemisinin-based combination therapies for uncomplicated malaria

There has been a relentless increase in resistance of malaria parasites to conventional antimalarial drugs, including chloroquine, sulfadoxine-pyrimethamine and mefloquine. In response to this situation, short-course artemisinin-based combination therapies (ACTs) have been developed. The World Health Organization has endorsed ACT as first-line treatment where the potentially life-threatening parasite Plasmodium falciparum is the predominant infecting species. ACTs combine the rapid schizontocidal activity of an artemisinin derivative (artesunate, artemether or dihydroartemisinin) with a longer-half-life partner drug. Although the use of chloroquine and sulfadoxine-pyrimethamine as partners in ACT improves their efficacy, this may only have value as a short-term measure in patients with a degree of immunity to malaria. Alternative currently available partner drugs include mefloquine, lumefantrine and piperaquine. Artesunate-mefloquine is highly effective but is expensive and side effects (mainly neurotoxicity) can be problematic. Artemether-lumefantrine, the only ACT available in Australia, appears less effective than artesunate-mefloquine and needs to be administered with food to ensure adequate bioavailability. Dihydroartemisinin-piperaquine is highly effective, well tolerated and relatively inexpensive. The goal of potent, safe, easy-to-administer and inexpensive ACTs may see trioxolanes in place of artemisinin derivatives, as well as novel partner drugs such as pyronaridine or naphthoquine, in the future.     

Malaria chemoprophylaxis in travellers to east Africa: a comparative prospective study of chloroquine plus proguanil with chloroquine plus sulfadoxine-pyrimethamine

As malaria caused by Plasmodium falciparum has become resistant to chloroquine alternative drug regimens need to be developed. The prophylactic efficacy against malaria and the side effects of chloroquine phosphate 500 mg weekly with proguanil hydrochloride 200 mg daily was compared with the efficacy of chloroquine 500 mg weekly with sulfadoxine 500 mg-pyrimethamine 25 mg weekly in a randomised study of Scandinavian travellers to Kenya and Tanzania during 1984-5. A total of 767 subjects (416 male and 351 female; 384 taking chloroquine phosphate with proguanil hydrochloride and 383 taking chloroquine with sulfadoxine-pyrimethamine) completed a diary on the breakthrough of malaria and the side effects of treatment while taking the drugs. They were also asked to make thick blood films when symptoms like those of malaria occurred, which were sent to and analysed in Denmark. Four subjects taking chloroquine with proguanil hydrochloride and three taking chloroquine with sulfadoxine-pyrimethamine developed falciparum malaria, which was verified microscopically. Side effects were reported by 36 subjects taking chloroquine phosphate with proguanil hydrochloride and 55 taking the other regimen (p = 0.043). The side effects of both regimens were generally mild, but the combination of chloroquine phosphate with proguanil hydrochloride is recommended because it results in fewer side effects. As breakthroughs of malaria occurred at the earliest after seven weeks self treatment should not be recommended for travellers staying only a short time. Thick blood films are useful for diagnosis of suspected cases of malaria, can be prepared by non-specialists in Africa, and can be analysed successfully after long delays.     

疟疾化学治疗的研究现状

疟疾是一种以蚊为传播媒介的重要虫媒传染病,是现在全球最重要的寄生虫病之一。为了降低疟疾带来的危害,抗疟药大量的应用于疟疾的预防与治疗,但为避免抗疟药在治疗中的广泛应用产生的抗药性,应采用合理的治疗方案,达到治疗疟疾并延缓抗药性产生的效果。随着疟疾抗药性的提高,新药的研发也迫在眉睫。该文对疟疾化学治疗的现状予以综述。     

Therapeutic efficacy of chloroquine or amodiaquine in combination with sulfadoxine-pyrimethamine for uncomplicated falciparum malaria in Papua New Guinea

Resistance of Plasmodium falciparum to chloroquine is widespread in Papua New Guinea. At a meeting in Port Moresby in October 1997, it was decided to explore a possible change of the current first-line treatment of uncomplicated malaria with chloroquine alone (amodiaquine for children under five years) to chloroquine or amodiaquine in combination with sulfadoxine-pyrimethamine (S-P). To assess the therapeutic efficacy of the new drug combination in Papua New Guinea, a study was carried out in 1998-1999 at five hospital outpatient departments. From the 513 patients enrolled for the study, 95 defaulted from follow-up. Of the remaining 418, 399 (95.5%) had an adequate clinical response (ACR). Out of the 19 patients who did not have an ACR, 3 (0.7% of the total) developed severe signs in the first 24 hours and were treated in hospital; they were regarded as early treatment failures. The remaining 16 did not complete the study on the basis of various exclusion criteria but were not excluded from the analysis. From these results it was concluded that the combination was effective and a decision was taken in May 2000 to introduce the two-drug combination regimens as the standard first-line treatment of uncomplicated malaria, including falciparum malaria, in Papua New Guinea.     

The role of prophylactic antimalarial in the reduction of placental parasitemia among pregnant women in Calabar, Nigeria

Introduction:

Intermittent preventive treatment of malaria with sulfadoxine-pyrimethamine is a recommendation of the World Health Organization as part of the malaria control strategy in pregnancy in areas with malaria burden.

Aim:

This study set out to appraise the effectiveness of this regimen in the prevention of placental parasitemia among parturients in Calabar, Nigeria.

Materials and Methods:

Pretested, precoded questionnaires were administered to eligible women at the antenatal clinic and later updated at the labor ward. Intermittent preventive treatment was administered under direct observation at the clinic, while packed cell volume, placental parasitemia, and other laboratory tests were measured at the labor ward.

Results:

The gross presence of placental malaria in the intermittent preventive treatment (IPT)-treated and the control groups was 10.6% and 11.3% respectively (P=0.76). Anemia occurred in 3.1% of the IPT-treated group compared to 11.7% among the control group (P=0.000). Only 7.9% of the IPT-treated women had moderate to severe placental parsitemia whereas as many as 53.2% of women in the control group had moderate to severe parasitemia (P=0.000).

Conclusion:

Intermittent preventive treatment of malaria with sulfadoxine-pyrimethamine was associated with significant reduction in the degree of placental parasitemia among women in the IPT-treated group, although it did not completely eradicate placental malaria in the treatment group.     

我国主要传疟媒介抗药性研究进展

杀虫剂在农业及传染性疾病防控工作中广泛而大量的应用,在降低虫媒传染病的同时也导致了媒介对杀虫剂耐药现象的发生。中国于2010年启动全国消除疟疾行动计划,提出到2020年全国实现消除疟疾目标,传疟按蚊抗药性的出现,成为我国消除疟疾工作中面临的重要问题。本文对我国主要传疟媒介抗药性的检测方法、按蚊抗性水平、蚊媒对杀虫剂的抗性机制的研究进展进行综述,以期为我国消除疟疾媒介防控策略的制订提供参考依据。     

Malaria: a case report in Oklahoma and a review of prophylaxis for travelers

Most cases of malaria in the United States, including the case described below, are due to travelers not taking proper prophylactic medications. With a potentially long incubation period, patients are frequently misdiagnosed (often with viral syndrome or pharyngitis) and correct treatment is delayed. Effective preventative medicines include Malarone, mefloquine, and doxycycline. Chloroquine, a staple of malaria prevention in the past, now has very limited usefulness due to drug resistance.     

青蒿素类药物治疗疟疾研究进展

疟疾是一种在世界范围内广泛传播的寄生虫病,其中以恶性疟对人体健康威胁最大。尽管采取多种控制措施,但疟疾仍然是重大的公共卫生问题。据世界卫生组织统计,2016年全球发生疟疾2.16亿例,并导致44.5万人死亡。因此对疟疾的早期诊断和有效治疗显得尤为重要。青蒿素是一种来源于我国传统药用植物黄花蒿的抗疟药物,其发现以来作为疟疾治疗的特效药得到了广泛使用,为全球控制疟疾发挥了非常重要的作用。本文就青蒿素类药物治疗疟疾的作用机理、药物代谢和临床应用等方面的研究进展进行综述。     

Development of the New antimalarial Drug Pyronaridine：A Review

This report outlines the structure scheme and development of a new antimalarial drug pryonaridine,which was synthesized from either 2-aminopyridine or pyridine.A series of in vivo and in vitro experimental studies and the assessment of toxicity revealed pyronaridine to be a promising agent against erybthrocytic stage of malaria parasites.It exhibited low toxicity and had no corss-resistance to chloroquine.Chlinical administration in malaria cases showed high efficacy and mild side-effects.In order to retard the development of resistance of Plasmodium falciparum to pyronaridine,a combination of pyronaridine/sulfadoxine/pyrimethamine was used in the treatment of chloroquine-resistant falciarum malaria in Hainan Province.Further in vivo test was carried out to monitor the sensitivity of Pfalciparum to this combined formula for 5 years(1986-1990)in Diaoluo area where chloquineresistant falciparum malaria was prevalent.Drug resistance was not demonstrated in this field study.