Africa, Central

非洲,Central
  • 文章类型: Journal Article
    抗疟疾药物耐药性的广泛发生威胁到非洲地区目前控制疟疾的努力。分子标记物监测有助于追踪耐药疟疾病例的出现和传播。
    从非洲中部输入浙江省的恶性疟原虫感染共237例,中国,在2016年至2021年之间,进行了调查。从每个患者的血液样本中提取基因组DNA,并使用巢式PCR检测k13,Pfcrt,和Pfmdr1基因。分析了分子标记的时空分布。
    观察到k13的有限多态性,包括两个非同义突变(D464E和K503E)和五个同义突变。Pfcrt的野生型CVMNK占主导地位(78.5%),而19.5%的样本含有突变单倍型,CVIET.Pfmdr1的点突变Y184F和单突变单倍型NF是最常见的。Pfcrt和Pfmdr1单倍型的地理分布显示出不同的模式,Pfcrt突变单倍型在加蓬(53.9%)和刚果(50.0%)更为常见,以及在喀麦隆更常见的Pfmdr1的野生单倍型,安哥拉,刚果。Pfcrt野生型CVMNK的患病率从2016-2017年的68.5-74.6%增加到2018-2021年的81.8-87.5%。野生型Pfmdr1的比例也从2016年的27.1%上升到2019年的38.5%。
    k13,Pfcrt,并证明了2016年至2021年间从中部非洲进口的恶性疟原虫寄生虫中的Pfmdr1多态性。我们的数据提供了最新证据,可用于调整中非和中国的抗疟疾药物政策。
    The widespread occurrence of anti-malarial drug resistance threatens the current efforts to control malaria in African regions. Molecular marker surveillance helps to track the emergence and spread of drug-resistant malaria cases.
    A total of 237 Plasmodium falciparum infections imported from central Africa to Zhejiang Province, China, between 2016 and 2021, were investigated. Genomic DNA was extracted from blood samples of each patient and nested PCRs was used to detect molecular markers in k13, Pfcrt, and Pfmdr1 genes. The spatial and temporal distributions of the molecular markers were analyzed.
    A limited polymorphism of k13 was observed, including two nonsynonymous (D464E and K503E) and five synonymous mutations. Wild-type CVMNK of Pfcrt predominated (78.5%), whereas 19.5% of the samples harbored the mutant haplotype, CVIET. The point mutation Y184F and the single mutant haplotype NF of Pfmdr1 were the most frequently observed. The geographical distributions of the Pfcrt and Pfmdr1 haplotypes displayed distinct patterns, with the mutant haplotype of Pfcrt more common in Gabon (53.9%) and Congo (50.0%), and wild haplotypes of Pfmdr1 more frequently found in Cameroon, Angola, and Congo. The prevalence of wild-type CVMNK of Pfcrt increased from 68.5-74.6% in 2016-2017 to 81.8-87.5% in 2018-2021. The proportion of wild-type Pfmdr1 also increased from 27.1% in 2016 to 38.5% in 2019.
    The geographical and temporal distribution of k13, Pfcrt, and Pfmdr1 polymorphisms in P. falciparum parasites imported from central Africa between 2016 and 2021 are demonstrated. Our data provide updated evidence that can be used to adjust anti-malarial drug policies in central Africa and China.
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  • 文章类型: Journal Article
    从理论上讲,大气运输和沉积对养分的空间再分布可以作为一种大陆尺度的机制,可以抵消由于养分在中部非洲热带森林中积累生物量而导致的土壤肥力下降。然而,它在多大程度上影响森林中的碳汇仍然难以捉摸。在这里,我们使用陆地生物圈模型来量化中部非洲典型低地林地的大气氮和磷沉积变化对植物营养和生物量碳汇的影响。我们发现,自20世纪80年代以来,养分沉积的增加可能导致了过去四十年的碳汇,其程度与大气二氧化碳增加和气候变化的综合影响相似。此外,我们发现模拟的碳汇响应磷沉积的变化,但对氮沉积的影响较小。生态系统生产力对养分沉积变化的显着响应说明了可以控制中非碳汇的潜在机制。该地区需要监测养分沉积的数量和质量,考虑到人类土地利用导致的养分沉积变化。
    Spatial redistribution of nutrients by atmospheric transport and deposition could theoretically act as a continental-scale mechanism which counteracts declines in soil fertility caused by nutrient lock-up in accumulating biomass in tropical forests in Central Africa. However, to what extent it affects carbon sinks in forests remains elusive. Here we use a terrestrial biosphere model to quantify the impact of changes in atmospheric nitrogen and phosphorus deposition on plant nutrition and biomass carbon sink at a typical lowland forest site in Central Africa. We find that the increase in nutrient deposition since the 1980s could have contributed to the carbon sink over the past four decades up to an extent which is similar to that from the combined effects of increasing atmospheric carbon dioxide and climate change. Furthermore, we find that the modelled carbon sink responds to changes in phosphorus deposition, but less so to nitrogen deposition. The pronounced response of ecosystem productivity to changes in nutrient deposition illustrates a potential mechanism that could control carbon sinks in Central Africa. Monitoring the quantity and quality of nutrient deposition is needed in this region, given the changes in nutrient deposition due to human land use.
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  • 文章类型: Journal Article
    磺胺多辛-乙胺嘧啶(SP)耐药性会损害抗疟药的疗效。监测出口疟疾感染中的分子标志物提供了一种有效的方法来追踪疟疾流行国家耐药性的出现。检测到了2016年至2021年间从中部非洲进口的237例恶性疟原虫感染的Pfdhfr和Pfdhps的分子标记。分析了Pfdhfr和Pfdhps突变的时空分布。观察到Pfdhfr单核苷酸多态性(SNP)的高患病率(〜92.34%至99.10%)和三重突变单倍型I51R59N108的高频率。喀麦隆,赤道几内亚,加蓬显示I51R59N108的频率(〜96.61%至100.00%)高于其他国家(〜71.11%至88.10%)。从2016年到2021年,C59R和I51R59N108的患病率增加,而其他SNP或单倍型的患病率没有很大的波动。证明了大比例的PfdhpsSNP(A437G和K540E)。Pfdhps的SNP分布在国家之间有所不同,S436A在北方国家占主导地位,A437G在其他国家占主导地位。I431V的比例,A437G,三突变单倍型在2016年至2021年期间下降,而单突变单倍型的患病率从61.60%上升到73.68%。赋予部分抗性的Pfdhfr-Pfdhps等位基因的组合,全阻力,和对SP的超强抗性,如文中所定义,在63.64%中检测到,8.64%,和0.91%的样品,分别。在5.00%的样品中观察到八位Pfdhfr-Pfdhps等位基因(I51R59N108-V431A436G437K540G581S613)。我们证明了中部非洲各国高度抗SP的Pfdhfr基因的广泛地理分布和增加趋势以及Pfdhps突变体的不同空间模式。部分抗性的高流行率,完全抵抗,此处观察到的超抗性Pfdhfr-Pfdhps组合表明SP功效受损。需要增加分子监测来监测Pfdhfr和Pfdhps基因的变化状态。重要性监测耐药性对疟疾控制很重要,因为它的早期发现能够及时采取行动防止其传播并减轻其影响。在我们的研究中发现,2016年至2021年间,高抗性Pfdhfr基因的广泛地理分布和增加趋势令人担忧,并强调了监测其在中非最新状态的紧迫性。这项研究还说明了新突变体PfdhpsI431V的广泛传播以及部分抗性的高患病率,“\”完全抵抗,\"和\"超抗\"Pfdhfr-Pfdhps组合,表明中部非洲对SP疗效的迫切关注。这些发现在疟疾流行的中非国家令人震惊,其中SP被广泛用于妊娠期疟疾的间歇性预防性治疗(IPTp)和5岁以下婴儿疟疾的间歇性预防性治疗(IPTi),并敦促加强分子监测和应对耐药性威胁。
    Sulfadoxine-pyrimethamine (SP) resistance impairs the efficacy of antimalarial drugs. Monitoring molecular markers in exported malaria infections provides an efficient way to trace the emergence of drug resistance in countries where malaria is endemic. Molecular markers in Pfdhfr and Pfdhps of 237 Plasmodium falciparum infections imported from central Africa between 2016 and 2021 were detected. The spatial and temporal distributions of Pfdhfr and Pfdhps mutations were analyzed. A high prevalence of Pfdhfr single-nucleotide polymorphisms (SNPs) (~92.34% to 99.10%) and a high frequency of the triple mutation haplotype I51R59N108 were observed. Cameroon, Equatorial Guinea, and Gabon showed a higher frequency (~96.61% to 100.00%) of I51R59N108 than other countries (~71.11% to 88.10%). The prevalence of C59R and I51R59N108 increased while that of other SNPs or haplotypes did not fluctuate greatly from 2016 to 2021. Large proportions of Pfdhps SNPs (A437G and K540E) were demonstrated. The SNP distribution of Pfdhps differed between countries, with S436A dominating in northern countries and A437G dominating in others. The proportions of I431V, A437G, and the triple mutant haplotype declined between 2016 and 2021, whereas the prevalence of the single mutant haplotype rose from 61.60% to 73.68%. Combinations of Pfdhfr-Pfdhps alleles conferring partial resistance, full resistance, and superresistance to SP, as defined in the text, were detected in 63.64%, 8.64%, and 0.91% of the samples, respectively. The octuple Pfdhfr-Pfdhps allele (I51R59N108-V431A436G437K540G581S613) was seen in 5.00% of the samples. We demonstrated the wide geographic spread and increasing trends in highly SP-resistant Pfdhfr genes and varying spatial patterns of Pfdhps mutants across countries in central Africa. The high prevalences of partially resistant, fully resistant, and superresistant Pfdhfr-Pfdhps combinations observed here indicated impaired SP efficacy. Increased molecular surveillance is required to monitor the changing status of the Pfdhfr and Pfdhps genes. IMPORTANCE Monitoring drug resistance is important for malaria control because its early detection enables timely action to prevent its spread and mitigate its impact. The wide geographic spread and the increasing trend of highly resistant Pfdhfr genes between 2016 and 2021 found in our study are worrisome and emphasize the urgency to monitor their updated status in central Africa. This study also illustrated the wide spread of the novel mutant Pfdhps I431V as well as the high prevalence of \"partially resistant,\" \"fully resistant,\" and \"superresistant\" Pfdhfr-Pfdhps combinations, indicating the urgent concern for SP efficacy in central Africa. These findings are alarming in central African countries where malaria is endemic, where SP was is widely used for the intermittent preventive treatment of malaria in pregnancy (IPTp) and the intermittent preventive treatment of malaria in infants below 5 years of age (IPTi), and urge enhanced molecular surveillance and responses to the threat of drug resistance.
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  • 文章类型: Journal Article
    Yellow fever (YF) is a major public-health problem in Africa. Yellow fever virus (YFV), the etiological agent responsible for the disease, exhibits clear delineation of phylogeography between East/Central Africa and West Africa. In order to decipher the genetic nature of the YFV epidemic between these areas, we performed a genome-wide study on its African isolates using the McDonald-Kreitman (MK) test in combination with the type II functional divergence analysis. The results showed that adaptive genetic diversifications have occurred on viral nonstructural protein 1 (NS1) and NS5, which are essential for viral genome replication and immune antagonism, with the East/Central African-West African epidemic split. On both proteins, a number of amino acid replacements have been favored by functional divergence. These findings could help to bridge the gap between the phylogeographic delineation and niche adaptation underlying the YFV-epidemic across Africa and shed light on viral determinants of this process.
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  • 文章类型: Journal Article
    Tuberculosis (TB) incidence and mortality rates are still high in Sub-Saharan Africa, and the knowledge about the current patterns is valuable for policymaking to decrease the TB burden. Based on the Global Burden of Disease (GBD) study 2019, we used a Joinpoint regression analysis to examine the variations in the trends of TB incidence and mortality, and the age-period-cohort statistical model to evaluate their risks associated with age, period, and cohort in males and females from Cameroon (CAM), Central African Republic (CAR), Chad, and the Democratic Republic of the Congo (DRC). In the four countries, TB incidence and mortality rates displayed decreasing trends in men and women; except for the males from DRC that recorded an almost steady pattern in the trend of TB incidence between 1990 and 2019. TB incidence and mortality rates decreased according to the overall annual percentage changes over the adjusted age category in men and women of the four countries, and CAM registered the highest decrease. Although TB incidence and mortality rates increased with age between 1990 and 2019, the male gender was mainly associated with the upward behaviors of TB incidence rates, and the female gender association was with the upward behaviors of TB mortality rates. Males and females aged between 15-54 and 15-49 years old were evaluated as the population at high risks of TB incidence and mortality respectively in CAM, CAR, Chad, and DRC. The period and cohort relative risks (RRs) both declined in men and women of the four countries although there were some upward behaviors in their trends. Relatively to the period and cohort RRs, females and males from CAM recorded the most significant decrease compared to the rest of the countries. New public health approaches and policies towards young adults and adults, and a particular focus on elderlies\' health and life conditions should be adopted in CAM, CAR, DRC, and Chad to rapidly decrease TB incidence and mortality in both genders of the four countries.
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  • 文章类型: Journal Article
    随着生物多样性危机的继续,我们必须加倍努力,理解和遏制推动物种濒临灭绝的压力。一个主要驱动因素是不可持续的野生动物贸易。国际监管物种的贸易获得了最多的研究关注,但这只占贸易物种的一小部分,我们有可能无法理解不受监管的合法贸易的规模和影响。尽管是合法的,贸易通过直接收集对野生物种施加压力,引入的病原体,入侵物种。较小的物种丰富的脊椎动物,比如爬行动物,鱼,和两栖动物,由于法规的空白,可能特别容易受到交易的影响,小分布,和新物种的需求。这里,我们结合了来自五个来源的数据:六种语言的在线网络搜索,濒危物种国际贸易公约(CITES)贸易数据库,执法管理信息系统(LEMIS)贸易库存,自然保护联盟的评估,和最近的文献综述,描述两栖动物的全球贸易,还按目的使用地图,包括肉,宠物,药用,和研究。我们显示有1215种物种正在交易(占两栖动物物种的17%),几乎是以前记录数字的三倍,345受到威胁,和100个数据不足或未经评估。贸易物种起源热点包括南美,中国,和中非;消息来源表明,42%的两栖动物来自野外。新描述的物种可以快速交易(平均时滞6.5年),包括受威胁和未评估的物种。两栖动物贸易的规模和有限的监管,与连接压力的三联画配对(收集,病原体,入侵物种),需要重新审视野生动物贸易现状,预防原则在野生动物贸易方面的应用,并重新推动实现全球生物多样性目标。
    在过去的几十年里,异国情调的宠物已经变得更加普遍。在2008年的英国,爬行动物和两栖动物比狗更受欢迎,超过八百万人被囚禁.但是,尽管几乎所有的宠物猫和宠物狗都是在圈养下出生和繁殖的,异国情调的宠物通常来自野外,将物种及其栖息地置于危险之中。一项名为《濒危物种国际贸易公约》(CITES)的国际贸易协定旨在防止不可持续的动物贸易。但是为了获得CITES保护,物种依赖于数据显示野生动物贸易威胁着它们的生存。此外,他们的范围国家需要首先提出他们被列入名单。对于大多数野生动物物种来说,没有关于人口规模或人口减少的数据。在两栖动物的情况下,CITES仅监管2.5%的物种贸易。这使得其余的国家没有受到总体国际贸易法规的保护。为了保护这些动物,研究人员需要找出哪些物种在贸易中,他们来自哪里,有多少人已经受到威胁。为了解决这个问题,休斯,马歇尔和斯特林结合了五个来源的数据,包括官方CITES交易记录,最近的研究和在线搜索六种语言的两栖动物销售。数据显示了至少1,215种两栖动物的贸易证据,占所有两栖动物的17%。这个数字比以前的估计高出三倍。在贸易中的物种中,超过五分之一的人容易灭绝,濒临灭绝,或极度濒危。对于另外100个交易物种,人口数据不可用.此外,对交易个体起源的分析表明,大约42%来自野外。世界上热带地区的贸易物种数量最多,但是数据显示全球各地都在进行交流。不可持续的野生动物贸易可能对野生动物造成毁灭性后果。它已经导致至少21种爬行动物灭绝,两栖动物物种的数据未知。为了防止更多的物种灭绝,合法的野生动植物贸易应遵循预防原则。而不是允许人们交易一个物种,直到TES管理它,对于尚未评估或受到威胁的物种,全面禁止应生效。只有当评估表明该物种不会导致主要种群减少时,该物种的贸易才能恢复,或安全,圈养繁殖设施可以保证。
    As the biodiversity crisis continues, we must redouble efforts to understand and curb pressures pushing species closer to extinction. One major driver is the unsustainable trade of wildlife. Trade in internationally regulated species gains the most research attention, but this only accounts for a minority of traded species and we risk failing to appreciate the scale and impacts of unregulated legal trade. Despite being legal, trade puts pressure on wild species via direct collection, introduced pathogens, and invasive species. Smaller species-rich vertebrates, such as reptiles, fish, and amphibians, may be particularly vulnerable to trading because of gaps in regulations, small distributions, and demand of novel species. Here, we combine data from five sources: online web searches in six languages, Convention on International Trade in Endangered Species (CITES) trade database, Law Enforcement Management Information System (LEMIS) trade inventory, IUCN assessments, and a recent literature review, to characterise the global trade in amphibians, and also map use by purpose including meat, pets, medicinal, and for research. We show that 1215 species are being traded (17% of amphibian species), almost three times previous recorded numbers, 345 are threatened, and 100 Data Deficient or unassessed. Traded species origin hotspots include South America, China, and Central Africa; sources indicate 42% of amphibians are taken from the wild. Newly described species can be rapidly traded (mean time lag of 6.5 years), including threatened and unassessed species. The scale and limited regulation of the amphibian trade, paired with the triptych of connected pressures (collection, pathogens, invasive species), warrants a re-examination of the wildlife trade status quo, application of the precautionary principle in regard to wildlife trade, and a renewed push to achieve global biodiversity goals.
    In the last few decades, exotic pets have become much more common. In the UK in 2008, reptiles and amphibians were more popular than dogs, with over eight million in captivity. But while almost all pet cats and dogs are born and bred in captivity, exotic pets are often taken from the wild, putting species and their habitats at risk. An international trade agreement called the Convention on International Trade in Endangered Species (CITES) strives to prevent unsustainable animal trade. But to get CITES protection, species depend on data showing that wildlife trade threatens their survival. In addition, their range countries need to first propose them to be listed. For most wild animal species, there are no data on population size or population decline. In the case of amphibians, CITES regulates the trade of just 2.5% of species. This leaves the rest with no protection from overarching international trade regulations. To protect these animals, researchers need to find out which species are in trade, where they are coming from, and how many are already threatened. To address this, Hughes, Marshall and Strine combined data from five sources, including official CITES trade records, recent research and an online search for amphibian sales in six languages. The data showed evidence of trade in at least 1,215 amphibian species, representing 17% of all amphibians. The figure is three times higher than previous estimates. Of the species in trade, more than one in five is vulnerable to extinction, endangered, or critically endangered. For a further 100 of the traded species, data on population were unavailable. Moreover, analysis of the origins of traded individuals showed that around 42% came from the wild. Tropical parts of the world had the highest number of species in trade, but the data showed exchanges happening across the globe. Unsustainable wildlife trade can have devastating consequences for wild animals. It has already driven at least 21 reptile species to extinction, and data of amphibian species are unknown. To prevent further species going extinct, legal wildlife trade should follow the precautionary principle when it comes to wildlife trade. Rather than allowing people to trade a species until CITES regulates it, a blanket ban should come into force for species that have not been assessed or are threatened. Trade would be able to resume for a species only when assessments show that it would not cause major population decline, or secure, captive breeding facilities can be guaranteed.
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  • 文章类型: Journal Article
    背景:从流行地区返回的非流行地区的旅行相关疟疾对诊断和治疗提出了重要挑战。向新无疟疾国家输入的疟疾构成了疟疾重新传入和潜在复苏的进一步威胁。对于那些前往恶性疟原虫患病率高的地方的人,建议预防这种寄生虫,而复发性疟疾的因果预防往往被忽视。
    方法:我们分析了上林县高热患者中的一组输入性疟疾,广西,中国,他们最近有去过西非和中非的旅行史。通过显微镜诊断出疟疾,随后通过物种和亚种特异性PCR确认。使用由42个单核苷酸多态性组成的条形码对间日疟原虫进行基因分型。
    结果:对344例PCR证实的疟疾病例的调查显示,除了恶性疟原虫是主要的寄生虫种类外,复发性寄生虫卵疟原虫和间日疟原虫约占这些输入病例的40%。在114例卵卵圆瓶感染中,65.8%和34.2%分别为卵卵卵圆虫和卵圆虫。分别,在西非和中非,这两个亚种的比例约为2:1。使用遗传条形码对14个间日疟原虫分离株进行的系统发育分析表明,11个与来自东非的间日疟原虫种群形成了不同的进化枝。
    结论:本研究为Duffy阴性血型占优势的地区间日疟原虫的活跃传播提供了支持。由于复发性疟疾占进口疟疾的很大一部分,应该提倡对有前往西非和中非的旅行目的地的旅行者进行因果预防。
    BACKGROUND: Travel-related malaria in non-endemic areas returning from endemic areas presents important challenges to diagnosis and treatment. Imported malaria to newly malaria-free countries poses further threats of malaria re-introduction and potential resurgence. For those traveling to places with high Plasmodium falciparum prevalence, prophylaxis against this parasite is recommended, whereas causal prophylaxis against relapsing malaria is often overlooked.
    METHODS: We analyzed a cluster of imported malaria among febrile patients in Shanglin County, Guangxi Province, China, who had recent travel histories to Western and Central Africa. Malaria was diagnosed by microscopy and subsequently confirmed by species- and subspecies-specific PCR. Plasmodium vivax was genotyped using a barcode consisting of 42 single nucleotide polymorphisms.
    RESULTS: Investigations of 344 PCR-confirmed malaria cases revealed that in addition to Plasmodium falciparum being the major parasite species, the relapsing parasites Plasmodium ovale and P. vivax accounted for ~40% of these imported cases. Of the 114 P. ovale infections, 65.8% and 34.2% were P. ovale curtisi and P. ovale wallikeri, respectively, with the two subspecies having a ~2:1 ratio in both Western and Central Africa. Phylogenetic analysis of 14 P. vivax isolates using a genetic barcode demonstrated that 11 formed a distinct clade from P. vivax populations from Eastern Africa.
    CONCLUSIONS: This study provides support for active P. vivax transmission in areas with the predominant Duffy-negative blood group. With relapsing malaria making a substantial proportion of the imported malaria, causal prophylaxis should be advocated to travelers with a travel destination to Western and Central Africa.
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  • 文章类型: Journal Article
    Imported cases of infectious disease provide invaluable information about epidemiological conditions abroad, and should guide treatment decisions at home and abroad. Here, we examined cases of malaria imported from Africa to China for mutations eroding the efficacy of sulfadoxine-pyrimethamine (SP), sometimes used as an intermittent preventive treatment during for pregnant women and infants.
    A total of 208 blood samples were collected from P. falciparum-infected workers who had returned from Western and Central Africa to Guangxi Province Frequency distribution. Samples were analyzed for the mutations in dhfr and dhps genes by PCR -sequencing. The prevalence of dhfr and dhps polymorphisms was analyzed. Among the isolates, polymorphisms were detected in mutants N51I, C59R, S108N and I164L of Pfdhfr and I431V, S436 A/F, A437G, K540 E/N, A581G and A613T of pfdhps.
    Mutations promoting drug resistance were widespread in this cohort. For pfdhfr and pfdhps, wild types were equally rare among patients returned from Western Africa and Central Africa. A triple-mutant dhfr haplotype was most prevalent (>70%). We report for the first time mutation I164L-dhfr and I431V-dhps in Ghana, and for the first time we found A581G to exceed a clinically-relevant threshold that may counter-indicate current clinical practices. For Pfdhps, the double-mutant IAGKAA was high prevalent haplotype in Ghana, Western Africa. The single-mutant ISGKAA was a majority haplotype in Cameroon. Alarmingly, a \"super resistance\" quintuple mutant was detected, for the first time, in parasites of West African origin (defined by IAGKAA/IRNI in combination with pfdhps 581G and dhfr I164L). This may limit the efficacy of this drug combination for even intermittent clinical applications.
    These data are cause for great concern and call for continued surveillance of the efficacy of SP in source and recipient populations, and should be considered when developing treatment policy for imported malaria cases in China and elsewhere.
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  • 文章类型: Journal Article
    暂无摘要。
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  • 文章类型: Journal Article
    针对埃博拉病毒(EBOV)的许可疫苗仍然不可用,尽管西非2014-2016年爆发的EBOV病导致超过11,000人死亡。过去的研究表明,表达EBOV糖蛋白(GP)的重组疫苗病毒能够保护非人灵长类动物(NHP)免受致命的EBOV攻击。然而,这些疫苗表达了在中非发现的基于GP的EBOV病毒变体,与西非发现的Makona变体具有97.3%的氨基酸同源性。我们先前的研究表明,在中国的临床试验中,表达MakonaEBOVGP(MakGP)的重组腺病毒血清型5(Ad5)载体疫苗是安全且具有免疫原性的。但目前尚不清楚该疫苗是否能预防EBOV感染。这里,我们证明,用Ad5-MakGP免疫的豚鼠产生了强烈的体液反应,并且可以防止暴露于豚鼠适应的EBOV。Ad5-MakGP还在NHP中引发特异性B-和T-细胞免疫,并且在免疫后4周攻击动物时赋予100%保护。这些结果支持了该候选物的进一步临床开发,并强调了Ad5-MakGP在未来EBOV疾病爆发中作为预防措施的实用性。
    A licensed vaccine against Ebola virus (EBOV) remains unavailable, despite >11 000 deaths from the 2014-2016 outbreak of EBOV disease in West Africa. Past studies have shown that recombinant vaccine viruses expressing EBOV glycoprotein (GP) are able to protect nonhuman primates (NHPs) from a lethal EBOV challenge. However, these vaccines express the viral GP-based EBOV variants found in Central Africa, which has 97.3% amino acid homology to the Makona variant found in West Africa. Our previous study showed that a recombinant adenovirus serotype 5 (Ad5)-vectored vaccine expressing the Makona EBOV GP (MakGP) was safe and immunogenic during clinical trials in China, but it is unknown whether the vaccine protects against EBOV infection. Here, we demonstrate that guinea pigs immunized with Ad5-MakGP developed robust humoral responses and were protected against exposure to guinea pig-adapted EBOV. Ad5-MakGP also elicited specific B- and T-cell immunity in NHPs and conferred 100% protection when animals were challenged 4 weeks after immunization. These results support further clinical development of this candidate and highlight the utility of Ad5-MakGP as a prophylactic measure in future outbreaks of EBOV disease.
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