红内期疟原虫血红素代谢研究进展

血红素是生物体内一类关键代谢因子,疟原虫具有自身合成血红素途径,但红内期疟原虫的生长发育依赖于外源性血红素代谢--食物泡对血红蛋白的摄入消化。食物泡内血红素代谢主要包括血红蛋白转运摄入、血红蛋白酶解产生血红素、血红素聚合为疟色素及食物泡对血红素的转运4个方面。抗疟药如青蒿素、氯喹和阿托伐醌等的杀疟机制与此过程密切相关,该文综述了该代谢过程的4个主要环节、关键代谢酶,以及抗疟药对其影响和可能的作用机制研究,将为类似药物的合理利用和机制研究提供思路参考。     

Fake antimalarials in Southeast Asia are a major impediment to malaria control: multinational cross-sectional survey on the prevalence of fake antimalarials

OBJECTIVE: To assess the prevalence of counterfeit antimalarial drugs in Southeast (SE) Asia. DESIGN: Cross-sectional survey. SETTING: Pharmacies and shops selling antimalarial drugs in Myanmar (Burma), Lao PDR, Vietnam, Cambodia and Thailand. MAIN OUTCOME MEASURES: Proportion of artemisinin derivatives or mefloquine containing drugs of substandard quality. RESULTS: Of the 188 tablet packs purchased which were labelled as 'artesunate' 53% did not contain any artesunate. All counterfeit artesunate tablets were labelled as manufactured by 'Guilin Pharma', and refinements of the fake blisterpacks made them often hard to distinguish from their genuine counterparts. No other artemisinin derivatives were found to be counterfeited. Of the 44 mefloquine samples, 9% contained <10% of the expected amount of active ingredient. CONCLUSIONS: An alarmingly high proportion of antimalarial drugs bought in pharmacies and shops in mainland SE Asia are counterfeit, and the problem has increased significantly compared with our previous survey in 1999-2000. This is a serious threat to public health in the region.     

Efficacy of chloroquine, amodiaquine, sulphadoxine-pyrimethamine and combination therapy with artesunate in Mozambican children with non-complicated malaria

This paper reports a two‐phase study in Manhiça district, Mozambique: first we assessed the clinical efficacy and parasitological response of Plasmodium falciparum to chloroquine (CQ), sulphadoxine–pyrimethamine (SP) and amodiaquine (AQ), then we tested the safety and efficacy in the treatment of uncomplicated malaria, of three combinations: AQ + SP, artesunate (AR) + SP and AQ + AR. Based on the WHO (1996, WHO/MAL/96.1077) in vivo protocol, we conducted two open, randomized, clinical trials. Children aged 6–59 months with axillary body temperature ≥37.5 °C and non‐complicated malaria were randomly allocated to treatment groups and followed up for 21 days (first and second trial) and 28 days (first trial). The therapeutic efficacy of AQ (91.6%) was better than that of SP (82.7%) and CQ (47.1%). After 14 days, 69% of the strains were parasitologically resistant to CQ, 21.4% to SP and 26% to AQ. Co‐administration of AQ + SP, AR + SP and AQ + AR was safe and had 100% clinical efficacy at 14‐day follow‐up. The combination therapies affected rapid fever clearance time and reduced the incidence of gametocytaemia during follow‐up.     

A randomized, controlled trial of artemisinin-piperaquine vs dihydroartemisinin-piperaquine phosphate in treatment of falciparum malaria

Objective:The study aimed to evaluate and compare the efficacy and safety of dihydroartemisininpiperaquine phosphate(Artekin) and artemisinin-piperaquine(Artequick) in the treatment of uncomplicated falciparum malaria.Methods:A total of 103 uncomplicated falciparum malaria patients were enrolled and randomly assigned to two groups:52 cases in the Artequick group,and 51 cases in the Artekin group.The patients in the Artequick group were administered with Artequick,twice in 24 h,whereas the patients in the...     

Drug Combinations in the Treatment of Malaria

Summary

The knowledge of the plasmodium life-cycle is essential for the use of antimalarial drugs and their combinations. The antimalarial drugs currently available can act on one or more stages of parasitic development, but only on its proliferative phases. The combinations of drugs in the treatment of malaria aim at three distinct objectives: a) action on different stages of parasitic life-cycle; b) enhancement of antiparasitic activity; and c) prevention of drug resistance.

In this regard, complementary, additive and potentiating combinations have been used, sometimes on an empiric basis. The potentiating combinations seem the most logical and effective, but some of them are not rational due to pharmacokinetic differences between the proposed components.     

Water-soluble trioxanes as potent and safe antimalarial agents

A series of synthetic C-3-aryl and C-12-benzyloxy 1,2,4-trioxane analogues is reported by Posner and co-workers to possess potent antimalarial activity versus Plasmodium falciparum in vitro and versus Plasmodium berghei in vivo in the mouse model of malaria. Several carboxylic acid containing derivatives within these two classes were shown to be superior to the semi-synthetic artemisinin derivative artelinic acid. In addition, one of the compounds claimed is not only more potent than artelinic acid in vivo but also has significantly higher water solubility and lower toxicity. On the basis of these encouraging results, these new, water-soluble peroxide analogues represent useful leads for further drug development.     

Randomized controlled trial of a traditional preparation of Artemisia annua L. (Annual Wormwood) in the treatment of malaria

The Chinese medicinal plant Artemisia annua L. (Annual Wormwood) contains the antimalarial compound artemisinin. The locally grown herb may offer an additional tool for the control of malaria, especially in poor countries where modern antimalarial drugs are often unavailable. In an open, randomized, controlled pilot trial, we investigated the efficacy and safety of traditional tea preparations of Artemisia annua in the treatment of uncomplicated malaria. Treatment resulted in a quick resolution of parasitaemia and of clinical symptoms. After 7 d of medication, cure rates were on average 74% for the Artemisia preparations compared with 91% for quinine. However, recrudescence rates were high in the Artemisia groups. Therefore, monotherapy with Artemisia annua L. cannot be recommended as alternative to modern antimalarials, but may deserve further investigation.     

Malaria in pregnancy: a literature review

Pregnant women are more likely than nonpregnant women to become infected with malaria and to have severe infection. The effects of malaria during pregnancy include spontaneous abortion, preterm delivery, low birth weight, stillbirth, congenital infection, and maternal death. Malaria is caused by the four species of the protozoa of the genus Plasmodium, which is transmitted by the bite of the female Anopheline mosquito, congenitally, or through exposure to infected blood products. This article reviews the epidemiology, pathology, clinical symptoms, diagnosis, and treatment of malaria in pregnant women. Interventions to prevent malaria include intermittent preventive treatment, insecticide-treated nets, and case management of malaria infection and anemia.     

Interaction of berbamine and chloroquine or artemisinin against chloroquine-sensitive and -resistant plasmodium falciparum in vitro

Antimalarial activity of berbamine (BB), alone or in combination with chloroquine (CQ) or artemisinin (qinghaosu, QHS), was studied using CQ-sensitive and -resistant strains of Plasmodium falciparum in vitro. BB was found to have antimalarial effects with IC₅₀ values of 603 and 359 nM, respectively, for the drug-sensitive and -resistant strains of P. falciparum, indicating that BB exhibited some selective antimalarial activity against the drug-resistant parasite. Its antimalarial efficacy and selectivity appeared to be less than that of tetrandrine (TT), however, when BB was combined with CQ, an antagonistic interaction was found against the CQ-sensitive parasite, while a potentiating antimalarial action was observed with the CQ-resistant parasite. When BB was tested in combination with QHS, a complex interaction was found—one was additive for the CQ-sensitive parasite and the other was potentiating for the CQ-resistant parasite. The above data suggested that the BB combination with either CQ or QHS is a promising candidate for an antimalarial remedy to treat at least CQ-resistant falciparum parasites which cause malaria. © 1993 wiley-Liss, Inc.     

抗疟化合物含哌嗪侧链的四氢萘酚Mannich碱的合成

设计合成了9个含哌嗪侧链的四氢萘酚Mannich碱化合物(Ⅵ_(1～9))。初筛结果表明,(Ⅵ_(5,6,9))对鼠疟的抑制作用与氯喹相当、而其余化合物均不如氯喹。