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[人类和兽医学中的轮状病毒]

[Rotaviruses in human and veterinary medicine].

作者信息

Dodet B, Heseltine E, Mary C, Saliou P

机构信息

Fondation Marcel-Mérieux, Lyon, France.

出版信息

Sante. 1997 May-Jun;7(3):195-9.

PMID:9296811
Abstract

Rotaviruses are the commonest cause of diarrhea and are responsible for more than 25% of all deaths from diarrhea worldwide. Children become infected early in life and most infections in infants older than 3 months are symptomatic. These viruses account for 18 million cases of moderate or severe disease and 900,000 deaths each year. The incidence of rotaviral disease is similar in developed and developing countries but the number of deaths is higher in developing countries. Infections occur throughout the year in developing countries but are seasonal in developed countries, occurring mainly between October and March. The mean age at first infection is 6 to 9 months in developing countries and 9 to 15 months in developed countries. The greater severity of infections in developing countries is associated with malnutrition, lower hygiene standards and the lactose malabsorption and deficiencies of zinc and vitamin A that accompany diarrhea. Many mixed infections also increase the severity of the rotavirus infection. The clinical symptoms of the disease in hospitalized patients are diarrhea, vomiting and dehydration. There is more vomiting than with bacterial infections. The severity of the clinical symptoms depends on the virulence of different strains. The disease is more severe and persistent in patients with reduced immunity. Age also has an effect. All children may have rotavirus in their feces but the percentage of children developing diarrhea is highest at an age of 3 to 6 months and decreases steadily thereafter. Rotaviruses can survive in air and may remain on surfaces for several hours. They are thus often responsible for nosocomial infections. Rotavirus was first identified in cattle in 1969. The virulence of the strain and the age of the calf at infection are important in the pathogenesis of rotaviral infection in cattle. Replacement of villous enterocytes is slow in newborn calves. This means that newborn calves are susceptible to disease caused by strains that are only moderately virulent. They are, however, protected during the first days of life by antibodies transmitted via the colostrum. There is competition between the rate of replication of rotavirus and replacement of enterocytes in older animals so only more virulent strains cause diarrhea in six-week-old calves. Adult animals become resistant to disease, but not to infection. The rotavirus genome consists of 11 segments of double-stranded RNA. Genetic recombination between these segments occurs naturally and can be reproduced in vitro. Recombinants between human and bovine strains have been identified but the epidemiological importance of this is unknown. The genomic segments encode 6 structural proteins (VP) and 5 non-structural proteins (NSP). VP6, the major capsid antigen, present can be used to identify groups of rotaviruses. The presence of VP7 indicates that the virus belongs to the G (glycoprotein) group of serotypes. There are 14 G serotypes, 10 of which can infect humans. The four main G serotypes are G1 to G4, with G1 accounting for 60% of human serotypes. The presence of VP4 identifies the P (protease-sensitive) serotype. The serotypes have different geographic distributions with G1P8 responsible for more than 50% of epidemics worldwide. The WHO project for the control of rotaviral infections focuses on avoiding fecal contamination. This is achieved by ensuring high standards of food hygiene, sewage treatment and chlorinated running water and by introducing vaccination when vaccines become available. Recombinant animal (bovine or simian) and human rotaviruses are currently being tested in phase III studies. Attenuated live human viruses, including cold-adapted strains are being tested in phase I trials. The quadrivalent recombinant rhesuslhuman vaccine had only mild side-effects in children and was effective, giving 82-92% protection against severe diarrhea over two years and 50% protection on average. (ABSTRACT TRUNCATED)

摘要

轮状病毒是腹泻最常见的病因,全球超过25%的腹泻死亡病例由其导致。儿童在幼年时期就会受到感染,3个月以上婴儿的大多数感染都会出现症状。这些病毒每年导致1800万例中度或重度疾病以及90万例死亡。轮状病毒疾病在发达国家和发展中国家的发病率相似,但发展中国家的死亡人数更高。在发展中国家,感染全年都有发生,但在发达国家具有季节性,主要发生在10月至次年3月。在发展中国家,首次感染的平均年龄为6至9个月,在发达国家为9至15个月。发展中国家感染更为严重与营养不良、卫生标准较低以及腹泻伴随的乳糖吸收不良、锌和维生素A缺乏有关。许多混合感染也会增加轮状病毒感染的严重程度。住院患者该疾病的临床症状为腹泻、呕吐和脱水。与细菌感染相比,呕吐更为常见。临床症状的严重程度取决于不同毒株的毒力。免疫力低下的患者病情更为严重且持续时间更长。年龄也有影响。所有儿童的粪便中都可能有轮状病毒,但出现腹泻的儿童比例在3至6个月龄时最高,之后稳步下降。轮状病毒可在空气中存活,可能在物体表面停留数小时。因此,它们常导致医院感染。1969年首次在牛身上发现轮状病毒。毒株的毒力以及感染时小牛的年龄在牛轮状病毒感染的发病机制中很重要。新生小牛绒毛肠上皮细胞的替换缓慢。这意味着新生小牛易受仅具有中等毒力的毒株引起的疾病影响。然而,在出生后的头几天,它们受到通过初乳传递的抗体的保护。在年龄较大的动物中,轮状病毒的复制速度与肠上皮细胞的替换之间存在竞争,因此只有毒力更强的毒株才会在6周龄的小牛中引起腹泻。成年动物对疾病产生抵抗力,但不会对感染产生抵抗力。轮状病毒基因组由11段双链RNA组成。这些片段之间的基因重组自然发生,并且可以在体外重现。已鉴定出人和牛毒株之间的重组体,但其流行病学重要性尚不清楚。基因组片段编码6种结构蛋白(VP)和5种非结构蛋白(NSP)。主要衣壳抗原VP6的存在可用于识别轮状病毒组。VP7的存在表明该病毒属于G(糖蛋白)血清型组。有14种G血清型,其中10种可感染人类。四种主要的G血清型是G1至G4,其中G1占人类血清型的60%。VP4的存在确定P(蛋白酶敏感)血清型。这些血清型具有不同的地理分布,G1P8导致全球超过50%的疫情。世界卫生组织控制轮状病毒感染的项目侧重于避免粪便污染。这通过确保高标准的食品卫生、污水处理和加氯自来水供应以及在有疫苗时引入疫苗接种来实现。重组动物(牛或猴)和人轮状病毒目前正在进行III期研究测试。减毒活人类病毒,包括冷适应毒株正在进行I期试验。四价重组恒河猴/人疫苗在儿童中只有轻微副作用且有效,在两年内对严重腹泻的保护率为82%至92%,平均保护率为50%。

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