我国血吸虫对吡喹酮抗药性研究之概要

血吸虫病是一种严重危害人类健康、影响社会经济发展的重大传染病,为全球公共卫生负担和危害最严重的被忽视的热带病之一。吡喹酮是20世纪70年代研制出的一种高效、低毒、价廉的广谱抗蠕虫口服药,为世界卫生组织（WHO）推荐的抗血吸虫的首选药物。吡喹酮在血吸虫病流行区现场大规模反复使用已超过40年,血吸虫是否会对吡喹酮产生抗药性引起国际社会极大担忧,为学术界关注的热点科学问题。针对血吸虫病防治中这一重大需求,自1996年起, 在国家科技支撑计划、国家自然科学基金、江苏省自然科学基金等项目基金资助下,我们在血吸虫病流行区现场和实验室,对血吸虫在吡喹酮药物的压力是否会产生抗药性、抗性虫株的生物学特性、抗性的检测、吡喹酮抗性的交叉抗药性及抗药性的预防和控制等科学问题进行较为系统的研究,本文就其研究及其意义作一概述。     

Évaluation du moxalactam par diffusion en milieu gélosé et à l’aide de l’automate Phoenix™ pour la détection de la résistance à la méticilline des staphylocoques à coagulase négative

ObjectivesThe categorization of methicillin susceptibility in coagulase-negative staphylococci (CoNS) is difficult. We decided to evaluate the performance of the Phoenix^TM system and the use of moxalactam by testing a large collection of strains.Material and methods186 CoNS were investigated in two panels. Panel A was composed of 51 CoNS strains, 31 mecA(−) and 20 mecA(+), which were tested on the Phoenix^TM system to determine a preliminary breakpoint for moxalactam. Panel B included 135 non duplicate CoNS strains selected from the collection of the laboratory which were tested on Phoenix so as strains from panel A. We performed disk diffusion, E-test for both panels. The mecA gene was determined by real time PCR method.ResultsWhatever the method, moxalactam was a better indicator drug for mecA(+) strains whereas cefoxitin was a better indicator drug for mecA(−) strains. For strains other than Staphylococcus saprophyticus, a moxalactam MIC > 16 mg/L was indicative of methicillin resistance. The breakpoint for moxalactam in association with oxacillin has been integrated into a decisional tree that can be used for the categorization of methicillin susceptibility in CoNS.DiscussionThe use of the Phoenix^TM and especially moxalactam offers a significant advantage in the determination of methicillin susceptibility (MS) in CoNS.     

Genetic mapping of the chloroquine-resistance locus on Plasmodium falciparum chromosome 7.

The resurgence of malaria in recent decades has been accompanied by the worldwide spread of resistance to chloroquine, a drug once uncontested as the first-line antimalarial agent because of its efficacy and low toxicity. Chloroquine-resistant strains of Plasmodium falciparum counter the drug by expelling it rapidly via an unknown mechanism. In the absence of explicit biochemical knowledge of this efflux mechanism, reverse genetics provides a powerful approach to the molecular basis of chloroquine resistance. Here we report genetic linkage analysis in which 85 restriction fragment length polymorphism markers were used to examine inheritance of the 14 P. falciparum chromosomes in a laboratory cross between a chloroquine-resistant and a chloroquine-sensitive parasite. Inheritance data from 16 independent recombinant progeny show that the rapid efflux, chloroquine-resistant phenotype is governed by a single locus within an approximately 400-kilobase region of chromosome 7. Identification and characterization of genes within this region should lead to an understanding of the chloroquine-resistance mechanism.     

三峡建坝后血吸虫病传播危险因素研究Ⅲ库区血吸虫病监测方案的研究

目的了解三峡库区血吸虫病传播危险因素,为三峡库区血吸虫病动态监测提供技术方案。方法在三峡库区进行钉螺生存模拟试验,调查库区流动人口、家畜血吸虫病传染源和钉螺输入库区的潜在危险因素,以及建坝后社会经济发展变化对血吸虫病传播的潜在影响因素,找出库区血吸虫病监测的重点。结果钉螺在三峡库区的适宜环境中能够生长繁殖;血吸虫病传染源主要是往返于血吸虫病流行区的流动人口;从血吸虫病疫区引进花草树木和牲畜,存在将钉螺和动物传染源输入库区的可能;库区社会经济发展可使血吸虫病传入的危险增加,三峡库区已成为血吸虫病的潜在流行区。结论三峡库区血吸虫病监测工作重点应是流动人口、引进的牲畜等血吸虫病传染源和钉螺输入因素的监测。     

Natural Polyreactive IgA and IgM Autoantibodies in Human Colostrum

Secretory antibodies against bacteria and viruses in human colostrum and milk are known to be important protective factors for the breast-fed infant. The authors have shown by enzyme immunoassay that colostrum contains IgA and IgM antibodies to a number of autoantigens: native DNA, actin, myosin, myoglobin, laminin, transferrin and thyroglobulin. These antibodies were polyspecific—those with anti-DNA reactivity immunopurified on a DNA-cellulose affinity column bound to a panel of self- and environmental antigens. The levels of natural autoantibodies in the immunoglobulin fraction of human colostrum were 3–10 times lower (when presented as antibody activity per μg of immunoglobulin) than in the immunoglobulin fraction of serum. The biological significance of the presence of B cells with autoantibody specificity in the mammary gland and of natural autoantibodies in colostrum and milk is not clear. It has been suggested that self-reacting autoantibodies in serum play a major role in the selection of the pre-immune B-cell repertoire and in the maintenance of the immune homeostasis. The authors hypothesize that the natural autoantibodies in colostrum and milk may contribute to the selection process of physiological repertoire during the early postnatal period in breast-fed infants. This could explain the lower frequency of allergic, inflammatory and autoimmune diseases and lymphomas which is seen in their later life when compared with that observed in children who have been formula-fed after birth.