Instability of the Trypanosoma brucei rhodesiense metacyclic variable antigen repertoire

Trypanosoma brucei rhodesiense undergoes antigenic variation in its mammalian host by changing the glycoprotein composing its surface coat. Trypanosome clones which have the same repertoire of variable antigen types (VATs) are said to belong to the same serodeme. Tsetse flies infected with a particular serodeme extrude infective metacyclic trypanosomes which express only a restricted part of this repertoire. As the only known acquired immunity in African trypanosomiasis is VAT-specific this limitation of metacyclic VAT (M-VAT) repertoire could be important in devising a vaccine. This possibility of immunoprophylaxis could depend, however, on whether or not the M-VAT repertoire is conserved over long periods of repeated cyclical transmission and between epidemics. Studies reported here on isolates made from an East African focus of sleeping sickness over a 20-yr period suggest substantial changes in the M-VATs expressed during this time. Furthermore, we have detected change in expression of 3 M-VATs during sequential tsetse transmission of a clone in the laboratory indicating a possible instability in the organization of M-VAT genes.     

Principles of the eradication or control of tsetse flies

The success of attempts to control African trypanosomiasis afflicting both men and animals through the destruction of the tsetse vector depends on a realistic assessment of human and ecological factors in infested regions. The complete eradication of tsetse is at present possible only in limited areas, and elsewhere the advantages of periodic control campaigns have to be weighed carefully against their cost.     

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.     

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.     

埃博拉病毒感染数量的一个数学模型

埃博拉病毒病(EVD)是严重的、往往致命的人类疾病,病死率高达90%.埃博拉病毒病疫情主要发生在中非和西非靠近热带雨林的边远村庄.该病毒通过野生动物传到人,并且通过人际间传播在人群中蔓延.病情严重的患者需要获得重症支持治疗,无论对人还是对动物都无可用的已获正式许可的特异性治疗办法或者疫苗.由于缺乏有效的治疗手段和人用疫苗,提高对感染埃博拉危险因素的认识以及个人可以采取一些保护措施,这是减少人类感染和死亡的唯一方法.本文建立一个埃博拉病毒的数学模型,对疫情进行实证分析;并且对疫情的发展也做了一个预测.     

埃博拉病毒病：流行病学、生态学、诊断、治疗及控制

 埃博拉病毒（Ebolavirus）是埃博拉病毒病（Ebola Virus Disease, EVD）的病原体,1976 年首次在非洲发现,目前确认该病毒包括5 个种,其中苏丹型（Sudan ebolavirus）、扎伊尔型（Zaire ebolavirus）、塔伊森林型（Taï Forest ebolavirus）和本迪布焦型（Bundibugyo ebolavirus）均有感染人发病的记录;莱斯顿型（Reston ebolavirus）可致人隐性感染,并与多起猕猴暴发疫情有关,曾在菲律宾的猪中检出。人类埃博拉病毒病的病死率为25%~90%,疫情均发生在非洲,主要集中在10°N-10°S 的非洲地区,本次西非疫情是规模最大的暴发流行,截至2014 年8 月20 日已报告2615 例病例。该病是动物源性传染病,目前证据支持果蝠可能为病毒的自然储存宿主。该病在人群中主要通过接触传播,有症状的病人才具有传染性。未采取正确防护措施的医护人员、家庭护理人员及接触病人血液、体液,或接触病人血液、体液等污染的物品,或接触病例尸体的人是高风险感染人群。本病起病急,早期表现为发热、厌食、虚弱无力等非特异性症状,可通过检测病毒核酸、抗原、抗体等方法确诊。目前尚无批准上市的特效药和疫苗,以对症和支持治疗为主。预防控制策略主要包括早期发现病例、及时调查处置、追踪和密切观察接触者,以及有效的医院内和社区的感染控制。     

An African primate lentivirus (SIVsm) closely related to HIV-2

The ancestors of the human immunodeficiency viruses (HIV-1 and HIV-2) may have evolved from a reservoir of African nonhuman primate lentiviruses, termed simian immunodeficiency viruses (SIV). None of the SIV strains characterized so far are closely related to HIV-1. HIV-2, however, is closely related to SIV (SIVmac) isolated from captive rhesus macaques (Macaca mulatta). SIV infection of feral Asian macaques has not been demonstrated by serological surveys. Thus, macaques may have acquired SIV in captivity by cross-species transmission from an SIV-infected African primate. Sooty mangabeys (Cercocebus atys), an African primate species indigenous to West Africa, however, are infected with SIV (SIVsm) both in captivity and in the wild (P. Fultz, personal communication). We have molecularly cloned and sequenced SIVsm and report here that it is closely related to SIVmac and HIV-2. These results suggest that SIVsm has infected macaques in captivity and humans in West Africa and evolved as SIVmac and HIV-2, respectively.     

Impact of regional climate change on human health

The World Health Organisation estimates that the warming and precipitation trends due to anthropogenic climate change of the past 30 years already claim over 150,000 lives annually. Many prevalent human diseases are linked to climate fluctuations, from cardiovascular mortality and respiratory illnesses due to heatwaves, to altered transmission of infectious diseases and malnutrition from crop failures. Uncertainty remains in attributing the expansion or resurgence of diseases to climate change, owing to lack of long-term, high-quality data sets as well as the large influence of socio-economic factors and changes in immunity and drug resistance. Here we review the growing evidence that climate-health relationships pose increasing health risks under future projections of climate change and that the warming trend over recent decades has already contributed to increased morbidity and mortality in many regions of the world. Potentially vulnerable regions include the temperate latitudes, which are projected to warm disproportionately, the regions around the Pacific and Indian oceans that are currently subjected to large rainfall variability due to the El Ni?o/Southern Oscillation sub-Saharan Africa and sprawling cities where the urban heat island effect could intensify extreme climatic events.     

An earlier origin for the Acheulian

The Acheulian is one of the first defined prehistoric techno-complexes and is characterized by shaped bifacial stone tools. It probably originated in Africa, spreading to Europe and Asia perhaps as early as ～1?million years (Myr) ago. The origin of the Acheulian is thought to have closely coincided with major changes in human brain evolution, allowing for further technological developments. Nonetheless, the emergence of the Acheulian remains unclear because well-dated sites older than 1.4?Myr ago are scarce. Here we report on the lithic assemblage and geological context for the Kokiselei 4 archaeological site from the Nachukui formation (West Turkana, Kenya) that bears characteristic early Acheulian tools and pushes the first appearance datum for this stone-age technology back to 1.76?Myr ago. Moreover, co-occurrence of Oldowan and Acheulian artefacts at the Kokiselei site complex indicates that the two technologies are not mutually exclusive time-successive components of an evolving cultural lineage, and suggests that the Acheulian was either imported from another location yet to be identified or originated from Oldowan hominins at this vicinity. In either case, the Acheulian did not accompany the first human dispersal from Africa despite being available at the time. This may indicate that multiple groups of hominins distinguished by separate stone-tool-making behaviours and dispersal strategies coexisted in Africa at 1.76?Myr ago.     

New evolution: Inhibitors of fatty acid synthase and fat-reducing study

Obesity sweeps all over the world presently at an astonishing speed. The rate of the disease ascends in both the developed and developing countries. According to a recent report from the World Health Organization, it can be estimated that about 250 million adults are obese all over the world, and that at least 500 million adults are overweight[1]. In the United States, more than 10% of children are obese and more than 15% of children are overweight[2]. About 2%-7% annual medical expenses of the developed countries are used for obesity by conservative estimation[3].     

The spread of HIV-1 in Africa: sexual contact patterns and the predicted demographic impact of AIDS

The spread of HIV-1 in Africa is examined here in the light of recent information on the main epidemiological and behavioural determinants of transmission. Mathematical models incorporating demographic, epidemiological and behavioural processes are used to assess the potential demographic impact of the disease AIDS. These analyses highlight the significance of patterns of sexual behaviour, and in particular networks of sexual contact, on the predicted spread of infection. Current data reveal substantial variations in the degree of spread between and in countries, but new analyses support earlier predictions that in the worst-afflicted areas AIDS is likely to change population growth rates from positive to negative values in a few decades.     

Large-scale sequencing of human influenza reveals the dynamic nature of viral genome evolution

Influenza viruses are remarkably adept at surviving in the human population over a long timescale. The human influenza A virus continues to thrive even among populations with widespread access to vaccines, and continues to be a major cause of morbidity and mortality. The virus mutates from year to year, making the existing vaccines ineffective on a regular basis, and requiring that new strains be chosen for a new vaccine. Less-frequent major changes, known as antigenic shift, create new strains against which the human population has little protective immunity, thereby causing worldwide pandemics. The most recent pandemics include the 1918 'Spanish' flu, one of the most deadly outbreaks in recorded history, which killed 30-50 million people worldwide, the 1957 'Asian' flu, and the 1968 'Hong Kong' flu. Motivated by the need for a better understanding of influenza evolution, we have developed flexible protocols that make it possible to apply large-scale sequencing techniques to the highly variable influenza genome. Here we report the results of sequencing 209 complete genomes of the human influenza A virus, encompassing a total of 2,821,103 nucleotides. In addition to increasing markedly the number of publicly available, complete influenza virus genomes, we have discovered several anomalies in these first 209 genomes that demonstrate the dynamic nature of influenza transmission and evolution. This new, large-scale sequencing effort promises to provide a more comprehensive picture of the evolution of influenza viruses and of their pattern of transmission through human and animal populations. All data from this project are being deposited, without delay, in public archives.     

First fossil chimpanzee

There are thousands of fossils of hominins, but no fossil chimpanzee has yet been reported. The chimpanzee (Pan) is the closest living relative to humans. Chimpanzee populations today are confined to wooded West and central Africa, whereas most hominin fossil sites occur in the semi-arid East African Rift Valley. This situation has fuelled speculation regarding causes for the divergence of the human and chimpanzee lineages five to eight million years ago. Some investigators have invoked a shift from wooded to savannah vegetation in East Africa, driven by climate change, to explain the apparent separation between chimpanzee and human ancestral populations and the origin of the unique hominin locomotor adaptation, bipedalism. The Rift Valley itself functions as an obstacle to chimpanzee occupation in some scenarios. Here we report the first fossil chimpanzee. These fossils, from the Kapthurin Formation, Kenya, show that representatives of Pan were present in the East African Rift Valley during the Middle Pleistocene, where they were contemporary with an extinct species of Homo. Habitats suitable for both hominins and chimpanzees were clearly present there during this period, and the Rift Valley did not present an impenetrable barrier to chimpanzee occupation.     

Haemoglobin C protects against clinical Plasmodium falciparum malaria.

Haemoglobin C (HbC; beta6Glu --> Lys) is common in malarious areas of West Africa, especially in Burkina Faso. Conclusive evidence exists on the protective role against severe malaria of haemoglobin S (HbS; beta6Glu --> Val) heterozygosity, whereas conflicting results for the HbC trait have been reported and no epidemiological data exist on the possible role of the HbCC genotype. In vitro studies suggested that HbCC erythrocytes fail to support the growth of P. falciparum but HbC homozygotes with high P. falciparum parasitaemias have been observed. Here we show, in a large case-control study performed in Burkina Faso on 4,348 Mossi subjects, that HbC is associated with a 29% reduction in risk of clinical malaria in HbAC heterozygotes (P = 0.0008) and of 93% in HbCC homozygotes (P = 0.0011). These findings, together with the limited pathology of HbAC and HbCC compared to the severely disadvantaged HbSS and HbSC genotypes and the low betaS gene frequency in the geographic epicentre of betaC, support the hypothesis that, in the long term and in the absence of malaria control, HbC would replace HbS in central West Africa.     

Unmatched tempo of evolution in Southern African semi-desert ice plants

The Succulent Karoo is an arid region, situated along the west coast of southern Africa. Floristically this region is part of the Greater Cape Flora and is considered one of the Earth's 25 biodiversity hotspots. Of about 5,000 species occurring in this region, more than 40% are endemic. Aizoaceae (ice plants) dominate the Succulent Karoo both in terms of species numbers (1,750 species in 127 genera) and density of coverage. Here we show that a well-supported clade within the Aizoaceae, representing 1,563 species almost exclusively endemic to southern Africa, has diversified very recently and very rapidly. The estimated age for this radiation lies between 3.8 and 8.7 million years (Myr) ago, yielding a per-lineage diversification rate of 0.77-1.75 per million years. Both the number of species involved and the tempo of evolution far surpass those of any previously postulated continental or island plant radiation. Diversification of the group is closely associated with the origin of several morphological features and one anatomical feature. Because species-poor clades lacking these features occur over a very similar distribution area, we propose that these characteristics are key innovations that facilitated this radiation.     

生物多样性与传染病风险

近半个世纪以来,新发传染病(多为涉及多宿主的人兽共患病)正在以前所未有的速度不断增加,不仅严重威胁人类健康,还影响着农业生产和野生动物保护。因不同宿主对病原的传播能力具有种间差异,宿主群落结构能够显著地影响病原的传播动态和传染病风险。多样性,作为表征群落结构的重要指标之一,其和传染病风险间的关系(即多样性-疾病关系)是传染病生态学研究的核心问题之一。尤其是“稀释效应”(即提高宿主多样性能够降低疾病风险)的提出引发了广泛的关注。虽然稀释效应得到了众多实证研究的支持,但其普适性仍然存在争议。笔者围绕多样性-疾病关系,介绍稀释效应的生态学机制、普适性及其产生的前提条件。并就3个方向总结了稀释效应的研究进展:①稀释效应的尺度依赖性;②宿主局部灭绝风险和其病原传播能力间的关系;③多样性对疾病风险的身份效应。此外,还分析了近期关于多样性-疾病关系研究框架的拓展,即从物种多样性拓展到谱系多样性;从单一疾病风险拓展到疾病总负担。最后,就未来可能的研究方向提出展望,认为未来研究需探讨分析生境破碎化、非宿主以及群落功能多样性在多样性-疾病关系中的作用。     

Sequence of simian immunodeficiency virus from macaque and its relationship to other human and simian retroviruses

Because of the growing incidence of AIDS (acquired immune deficiency syndrome), the need for studies on animal models is urgent. Infection of chimpanzees with the retroviral agent of human AIDS, the human immunodeficiency virus (HIV), will have only limited usefulness because chimpanzees are in short supply and do not develop the disease. Among non-human primates, both type D retroviruses and lentiviruses can be responsible for immune deficiencies. The D-type retroviruses, although important pathogens in macaque monkey colonies, are not satisfactory as a model because they differ in genetic structure and pathophysiological properties from the human AIDS viruses. The simian lentivirus, previously referred to as simian T-cell lymphotropic virus type III (STLV-III), now termed simian immunodeficiency virus (SIV) is related to HIV by the antigenicity of its proteins and in its main biological properties, such as cytopathic effect and tropism for CD4-bearing cells. Most importantly, SIV induces a disease with remarkable similarity to human AIDS in the common rhesus macaques, which therefore constitute the best animal model currently available. Natural or experimental infection of other monkeys such as African green monkeys or sooty mangabeys has not yet been associated with disease. Molecular approaches of the SIV system will be needed for biological studies and development of vaccines that could be tested in animals. We have cloned and sequenced the complete genome of SIV isolated from a naturally infected macaque that died of AIDS. This SIVMAC appears genetically close to the agent of AIDS in West Africa, HIV-2, but the divergence of the sequences of SIV and HIV-2 is greater than that previously observed between HIV-1 isolates.     

Transmission intensity and impact of control policies on the foot and mouth epidemic in Great Britain

The foot and mouth disease (FMD) epidemic in British livestock remains an ongoing cause for concern, with new cases still arising in previously unaffected areas. Epidemiological analyses have been vital in delivering scientific advice to government on effective control measures. Using disease, culling and census data on all livestock farms in Great Britain, we analysed the risk factors determining the spatiotemporal evolution of the epidemic and of the impact of control policies on FMD incidence. Here we show that the species mix, animal numbers and the number of distinct land parcels in a farm are central to explaining regional variation in transmission intensity. We use the parameter estimates thus obtained in a dynamical model of disease spread to show that extended culling programmes were essential for controlling the epidemic to the extent achieved, but demonstrate that the epidemic could have been substantially reduced in scale had the most efficient control measures been rigorously applied earlier.     

Woody cover and hominin environments in the past 6 million years

The role of African savannahs in the evolution of early hominins has been debated for nearly a century. Resolution of this issue has been hindered by difficulty in quantifying the fraction of woody cover in the fossil record. Here we show that the fraction of woody cover in tropical ecosystems can be quantified using stable carbon isotopes in soils. Furthermore, we use fossil soils from hominin sites in the Awash and Omo-Turkana basins in eastern Africa to reconstruct the fraction of woody cover since the Late Miocene epoch (about 7 million years ago). (13)C/(12)C ratio data from 1,300 palaeosols at or adjacent to hominin sites dating to at least 6 million years ago show that woody cover was predominantly less than ～40% at most sites. These data point to the prevalence of open environments at the majority of hominin fossil sites in eastern Africa over the past 6 million years.     

The wMel Wolbachia strain blocks dengue and invades caged Aedes aegypti populations

Dengue fever is the most important mosquito-borne viral disease of humans with more than 50 million cases estimated annually in more than 100 countries. Disturbingly, the geographic range of dengue is currently expanding and the severity of outbreaks is increasing. Control options for dengue are very limited and currently focus on reducing population abundance of the major mosquito vector, Aedes aegypti. These strategies are failing to reduce dengue incidence in tropical communities and there is an urgent need for effective alternatives. It has been proposed that endosymbiotic bacterial Wolbachia infections of insects might be used in novel strategies for dengue control. For example, the wMelPop-CLA Wolbachia strain reduces the lifespan of adult A. aegypti mosquitoes in stably transinfected lines. This life-shortening phenotype was predicted to reduce the potential for dengue transmission. The recent discovery that several Wolbachia infections, including wMelPop-CLA, can also directly influence the susceptibility of insects to infection with a range of insect and human pathogens has markedly changed the potential for Wolbachia infections to control human diseases. Here we describe the successful transinfection of A. aegypti with the avirulent wMel strain of Wolbachia, which induces the reproductive phenotype cytoplasmic incompatibility with minimal apparent fitness costs and high maternal transmission, providing optimal phenotypic effects for invasion. Under semi-field conditions, the wMel strain increased from an initial starting frequency of 0.65 to near fixation within a few generations, invading A. aegypti populations at an accelerated rate relative to trials with the wMelPop-CLA strain. We also show that wMel and wMelPop-CLA strains block transmission of dengue serotype 2 (DENV-2) in A. aegypti, forming the basis of a practical approach to dengue suppression.