Malaria risk: estimating clinical episodes of malaria

Estimates of the disease burden caused by malaria are crucial for informing malaria control programmes. Snow and colleagues claim that their estimate of 515 million cases of malaria caused by Plasmodium falciparum globally is up to 50% higher than that reported by the World Health Organization (WHO), and 200% higher for areas outside Africa. However, this comparison refers to the WHO's estimates from 1990 and 1998, and not to the range of 300 million to 500 million that the WHO has used since 2000 (ref. 2). Both groups agree that the burden of malaria disease outside Africa, especially in South Asia, is greater than was estimated in the 1990s.     

基于和声搜索的自适应滤波算法

针对子空间辨识方法,从状态空间模型向I/O差分方程转化的取向,使有关矩阵的维数增加,计算复杂度增大的问题,提出了用和声搜索算法辨识CARMA(Controlled Auto-Regressive Moving Average)模型子阶、时滞和参数的方案.该方案基于所提出的输入输出模型转化为状态空间模型的定理,使相应的状态空间模型在CARMA模型辨识之后也被辨识.以油井热洗为例,进行了自适应滤波估计.估计结果表明:该算法有较高的滤波和预报的精度,滤波和一步预报的误差方差的最大值在0.01以内,与子空间辨识方案相比,本方案的计算量约为前者的五分之一.     

Malaria in 2002

The burden of malaria is increasing, especially in sub-Saharan Africa, because of drug and insecticide resistance and social and environmental changes. Thus, there is an urgent need for vaccines, new drugs and insecticides. Parasite, mosquito and human genome projects are helping in the search for new control tools and international donors are developing new funding mechanisms that could make them available to poor countries. But these new tools will achieve their maximum impact only if additional resources are deployed to strengthen malaria research and control communities in countries where the new tools will be used.     

非线性最小二乘法分析疟疾发病率的变化趋势

应用非线性的最小二乘法的L-M算法分析全国流行性疟疾发病率随时间变化规律.结果发现:疟疾发病率呈现出大幅度的周期性变化和长期的缓慢增加.由于标准偏差较小,线性迭加二阶的傅里叶多项式可能代表疟疾发病率的真实变化规律.疟疾发病率周期性变化的周期约为1年,这与长期监测的结果相一致;而1%左右的增加率可能是由于近几年人口流动激增和严重的环境污染造成的。     

The global distribution of clinical episodes of Plasmodium falciparum malaria

Interest in mapping the global distribution of malaria is motivated by a need to define populations at risk for appropriate resource allocation and to provide a robust framework for evaluating its global economic impact. Comparison of older and more recent malaria maps shows how the disease has been geographically restricted, but it remains entrenched in poor areas of the world with climates suitable for transmission. Here we provide an empirical approach to estimating the number of clinical events caused by Plasmodium falciparum worldwide, by using a combination of epidemiological, geographical and demographic data. We estimate that there were 515 (range 300-660) million episodes of clinical P. falciparum malaria in 2002. These global estimates are up to 50% higher than those reported by the World Health Organization (WHO) and 200% higher for areas outside Africa, reflecting the WHO's reliance upon passive national reporting for these countries. Without an informed understanding of the cartography of malaria risk, the global extent of clinical disease caused by P. falciparum will continue to be underestimated.     

Climate change and the resurgence of malaria in the East African highlands

The public health and economic consequences of Plasmodium falciparum malaria are once again regarded as priorities for global development. There has been much speculation on whether anthropogenic climate change is exacerbating the malaria problem, especially in areas of high altitude where P. falciparum transmission is limited by low temperature. The International Panel on Climate Change has concluded that there is likely to be a net extension in the distribution of malaria and an increase in incidence within this range. We investigated long-term meteorological trends in four high-altitude sites in East Africa, where increases in malaria have been reported in the past two decades. Here we show that temperature, rainfall, vapour pressure and the number of months suitable for P. falciparum transmission have not changed significantly during the past century or during the period of reported malaria resurgence. A high degree of temporal and spatial variation in the climate of East Africa suggests further that claimed associations between local malaria resurgences and regional changes in climate are overly simplistic.     

Common west African HLA antigens are associated with protection from severe malaria

A large case-control study of malaria in West African children shows that a human leucocyte class I antigen (HLA-Bw53) and an HLA class II haplotype (DRB1*1302-DQB1*0501), common in West Africans but rare in other racial groups, are independently associated with protection from severe malaria. In this population they account for as great a reduction in disease incidence as the sickle-cell haemoglobin variant. These data support the hypothesis that the extraordinary polymorphism of major histocompatibility complex genes has evolved primarily through natural selection by infectious pathogens.     

基于共轭梯度迭代算法受控AR模型的参数辨识

推导了单输入单输出系统的辅助模型,它有助于减少计算量和提高共轭梯度迭代算法（新算法）的收敛速度.相比于受控移动平均模型中所提出的交互式随机梯度算法,新算法用更少的迭代步骤就可求出模型的参数估计.另外,新算法能避免出现矩阵的逆矩阵形式.对新算法与双共轭梯度算法进行比较,并给出数值实例检验新算法的有效性.     

Malaria early warnings based on seasonal climate forecasts from multi-model ensembles

The control of epidemic malaria is a priority for the international health community and specific targets for the early detection and effective control of epidemics have been agreed. Interannual climate variability is an important determinant of epidemics in parts of Africa where climate drives both mosquito vector dynamics and parasite development rates. Hence, skilful seasonal climate forecasts may provide early warning of changes of risk in epidemic-prone regions. Here we discuss the development of a system to forecast probabilities of anomalously high and low malaria incidence with dynamically based, seasonal-timescale, multi-model ensemble predictions of climate, using leading global coupled ocean-atmosphere climate models developed in Europe. This forecast system is successfully applied to the prediction of malaria risk in Botswana, where links between malaria and climate variability are well established, adding up to four months lead time over malaria warnings issued with observed precipitation and having a comparably high level of probabilistic prediction skill. In years in which the forecast probability distribution is different from that of climatology, malaria decision-makers can use this information for improved resource allocation.     

Inhibition of P. falciparum growth in human erythrocytes by monoclonal antibodies

Malaria is increasing in incidence and prevalence in most tropical areas and is a major problem for both individuals and communities. Current malaria research is aimed at developing vaccines and, for this, it may be useful to define Plasmodium antigen(s) related to the development of a protective immune response in the host. Monoclonal antibodies have recently been shown to interfere with rodent malaria infection (Plasmodium berghei) at the sporozoite or merozoite stage. We have now raised monoclonal antibodies against single antigenic determinant(s) of Plasmodium falciparum and report that some of them inhibit the growth of erythrocytic forms of P. falciparum in vitro.     

Convergence Analysis of Forgetting Gradient Algorithm by Using Martingale Hyperconvergence Theorem

Introduction　　Considerthefollowinglineartime-varyingsystem[1,2],A(t,z-1)y(t)=B(t,z-1)u(t) v(t)(1)where{u(t)}and{y(t)}aretheinputandoutputsequencesofthesystem,respectively,{v(t)}isastochasticnoisesequence,andz-1representstheunitbackwardshiftoperator,i.e.,z-1y(t)=y(t-1),A(t,z-1)andB(t,z-1)aretime-varyingcoefficientpolynomialsintheunitbackwardshiftoperatorz-1,andA(t,z-1)=1 a1(t)z-1 a2(t)z-2 … ana(t)z-na,B(t,z-1)=b1(t)z-1 b2(t)z-1 … bnb(t)z-nb.Definetheinformationvector(t)andthetime-varyin…     

Inhibition by chloroquine of a novel haem polymerase enzyme activity in malaria trophozoites.

The incidence of human malaria has increased during the past 20 years; 270 million people are now estimated to be infected with the parasite. An important contribution to this increase has been the appearance of malaria organisms resistant to quinoline-containing antimalarials such as chloroquine and quinine. These drugs accumulate in the acid food vacuoles of the intraerythrocytic-stage malaria parasite, although the mechanism of their specific toxicity in this organelle is uncertain. The primary function of the food vacuole is the proteolysis of ingested red cell haemoglobin to provide the growing parasite with essential amino acids. Haemoglobin breakdown in the food vacuole releases haem, which if soluble can damage biological membranes and inhibit a variety of enzymes. Rather than degrading or excreting the haem, the parasite has evolved a novel pathway for its detoxification by incorporating it into an insoluble crystalline material called haemozoin or malaria pigment. These crystals form in the food vacuole of the parasite concomitant with haemoglobin degradation, where they remain until the infected red cell bursts. The structure of haemozoin comprises a polymer of haems linked between the central ferric ion of one haem and a carboxylate side-group oxygen of another. This structure does not form spontaneously from either free haem or haemoglobin under physiological conditions, and the biochemistry of its formation is unclear. Here we report the identification and characterization of a haem polymerase enzyme activity from extracts of Plasmodium falciparum trophozoites, and show that this enzyme is inhibited by quinoline-containing drugs such as chloroquine and quinine. This provides a possible explanation for the highly stage-specific antimalarial properties of these drugs.     

Identification of an antimalarial synthetic trioxolane drug development candidate

The discovery of artemisinin more than 30 years ago provided a completely new antimalarial structural prototype; that is, a molecule with a pharmacophoric peroxide bond in a unique 1,2,4-trioxane heterocycle. Available evidence suggests that artemisinin and related peroxidic antimalarial drugs exert their parasiticidal activity subsequent to reductive activation by haem, released as a result of haemoglobin digestion by the malaria-causing parasite. This irreversible redox reaction produces carbon-centred free radicals, leading to alkylation of haem and proteins (enzymes), one of which--the sarcoplasmic-endoplasmic reticulum ATPase PfATP6 (ref. 7)--may be critical to parasite survival. Notably, there is no evidence of drug resistance to any member of the artemisinin family of drugs. The chemotherapy of malaria has benefited greatly from the semi-synthetic artemisinins artemether and artesunate as they rapidly reduce parasite burden, have good therapeutic indices and provide for successful treatment outcomes. However, as a drug class, the artemisinins suffer from chemical (semi-synthetic availability, purity and cost), biopharmaceutical (poor bioavailability and limiting pharmacokinetics) and treatment (non-compliance with long treatment regimens and recrudescence) issues that limit their therapeutic potential. Here we describe how a synthetic peroxide antimalarial drug development candidate was identified in a collaborative drug discovery project.     

T-cell control of Epstein-Barr virus-infected B cells is lost during P. falciparum malaria

Endemic Burkitt's lymphoma, a tumour of children in which B lymphocytes are infected with Epstein-Barr virus (EBV), is common in areas of Africa where malaria is holoendemic. The tumour is characterized by chromosome translocations; usually the terminal portion of chromosome 8 containing the c-myc gene is translocated to chromosome 14, near the enhancer of the immunoglobulin heavy-chain locus. Less frequent are translocations of chromosome 8 to the kappa light-chain locus of chromosome 2 or to the lambda light-chain locus of chromosome 22. In vitro, EBV induces B cells to proliferate and secrete immunoglobulin and antibody. However, in vivo the infected B lymphocytes are under immunological control, so that abnormal proliferation is found only in immunosuppressed patients. Such patients are subsequently liable to develop lymphomas. Burkitt believed that the tumour he had described resulted from interaction between a virus(es) and a "reticuloendothelial system altered by chronic and heavy infection by malarial or other parasites". We report here that during an attack of Plasmodium falciparum malaria, T-cell subpopulations are radically altered so that, in vitro, B lymphocytes infected with EBV proliferate abnormally to secrete large amounts of immunoglobulin and antibody. This phenomenon offers some explanation for the increased incidence of Burkitt's tumour and the high levels of immunoglobulin found in people living in areas where P. falciparum malaria is common.     

在卫星干扰源定位系统中信号时间差计算的小波变换方法

在卫星干扰源的卫星定位理论中,需要通过计算信号的时间差和多普勒频差来确定卫星干扰源的位置.测量两颗相近位置卫星的时间差和多普勒频率差的精度,决定了卫星定位的准确度.本文研究计算时间差的信号处理及其计算.利用小波变换方法计算两个信号的相关特性可以减少计算的数据量,同时可以根据需要,很快得出所需要的信号时间差.     

Transgenic anopheline mosquitoes impaired in transmission of a malaria parasite

Malaria is estimated to cause 0.7 to 2.7 million deaths per year, but the actual figures could be substantially higher owing to under-reporting and difficulties in diagnosis. If no new control measures are developed, the malaria death toll is projected to double in the next 20 years. Efforts to control the disease are hampered by drug resistance in the Plasmodium parasites, insecticide resistance in mosquitoes, and the lack of an effective vaccine. Because mosquitoes are obligatory vectors for malaria transmission, the spread of malaria could be curtailed by rendering them incapable of transmitting parasites. Many of the tools required for the genetic manipulation of mosquito competence for malaria transmission have been developed. Foreign genes can now be introduced into the germ line of both culicine and anopheline mosquitoes, and these transgenes can be expressed in a tissue-specific manner. Here we report on the use of such tools to generate transgenic mosquitoes that express antiparasitic genes in their midgut epithelium, thus rendering them inefficient vectors for the disease. These findings have significant implications for the development of new strategies for malaria control.     

Cell-mediated immunity in the liver of mice vaccinated against malaria.

Mice can be protected against several species of lethal malaria infection by vaccination, and their recovery correlates well with increased anti-malarial antibody levels, particularly IgG (ref.2). However, there is also a good correlation between protection by vaccines and priming for delayed-type hypersensitivity in the skin, although there is no obvious explanation for this effect. We now report an apparent relationship between protection and a cell-mediated immune response involving the migration of various types of cell capable of killing malaria parasites in vitro to the liver. We suggest that the effect of vaccination is to bring together parasites, specific antibody and nonspecific cytotoxic cells, and that the liver may be a major site for their interaction.     

关于系统时滞、阶数和系数的在线辨识

针对时滞,阶数和系数皆未知的离散时间线性随机控制系统(ARMAX模型),提出一种对时滞,阶数和系数同时进行递推估计的算法.在一定的条件下该算法能保证时滞,阶数和系数的估计都具有强一致性,而且系数估计具有较快的收敛速度.     

无钟高炉炉料分布预测模型

为提高无钟高炉炉喉料面的预测精度,建立了考虑炉料运动的炉料分布数学模型.在分析炉料运动的基础上,指出了炉料运动是影响炉料堆积过程的重要因素,采用尺寸比1:10的无钟布料器模型试验分析了不同炉料分速度对炉料堆积行为的影响,建立了考虑炉料运动因素的料堆轮廓预测模型,并通过数值方法确定了料堆的位置和料面轮廓曲线,应用于料面形状的预测.结果表明:炉料的运动是造成料堆两侧堆积角差异、料堆横截面面积变化以及料面轮廓改变的重要原因,料堆轮廓采用直线段和曲线相结合的方式进行构造,炉料的堆积角和曲线过渡区域长度作为重要的模型参数均考虑了炉料速度的影响,模型构造的轮廓接近真实料堆形状,应用该模型实现了炉喉料面的准确预测.     

SD大鼠心气虚证动物模型的建立与评价

目的　探讨心气虚证动物模型的建立方法。方法　SD大鼠 4 0只采用基础进食量 2 4d ,每日按自身体重的5 %强迫负重游泳至力竭 ,大剂量灌服心得安 2 4mg 10 0g等综合方法建立心气虚证动物模型 ,其中 2 0只作为人参药物反证组。并设立正常对照组 4 0只 ,以进一步证明所建立模型是心气虚证动物模型。结果　与正常对照组比较 ,模型组大鼠心脏收缩功能和舒张功能均有所下降 ,反映虚证的SOD含量减少 ,MDA含量增加。而所有定量指标均发生了符合心气虚证的变化。结论　采用基础进食量、强迫负重游泳及大剂量灌服心得安的综合方法建立心气虚证动物模型是可行的