世卫组织头版紧急事件公共卫生风险评估

文摘   2025-01-10 12:16   甘肃  

近期动物和人类中流感A(H5)病毒事件的公共卫生风险评估

近期,美国H5禽流感造成较大关注,特别是发生死亡病例后,越来越多人关注禽流感的动态,包括国家疾控近期也在风险评估会上讲到 美国的禽流感疫情情况。

WHO在其官网的首页里,最新紧急事件里头版就是最新的禽流感风险评估,说明目前备受关注。那么到底风险评估有哪些要点呢?笔者绘制了思维导图进行了概述(除应对措施模块),一起来看看吧!

具体内容如下:



Updated joint FAO/WHO/WOAH public health assessment of recent influenza A(H5) virus events in animals and people

Assessment based on data as of 18 November 2024

FAO(世界粮农组织)/WHO(世界卫生组织)/WOAH(世界动物卫生组织)最新联合发布关于近期动物和人类中流感A(H5)病毒事件的公共卫生评估

基于2024年11月18日数据的评估

01
Key points摘要:


At the present time, based on available information, FAO-WHO-WOAH assess the global public health risk of influenza A(H5N1) viruses to be low, while the risk of infection for occupationally exposed persons is low to moderate depending on the risk mitigation measures in place and the local avian influenza epidemiological situation. Transmission between animals continues to occur and, to date, a growing yet still limited number of human infections are being reported. Although additional human infections associated with exposure to infected animals or contaminated environments are expected to occur, the overall public health impact of such infections at a global  level, at the present time, is minor.

根据目前获得的信息,FAO(世界粮农组织)/WHO(世界卫生组织)/WOAH(世界动物卫生组织)三方联合评估结果:

1.流感A(H5N1)病毒对全球公共卫生的风险为低,而职业暴露人群的感染风险则取决于所采取的降低风险措施情况以及当地的禽流感流行病学情况,为低到中等。

2.动物之间的传播仍在持续,迄今为止,已有越来越多但数量仍然有限的人类感染病例被报告。

3.尽管预计与感染动物或受污染环境接触相关的人类感染病例将会会增加,但目前这些感染对全球公共卫生的总体影响是轻微的。

This risk assessment from FAO, WHO, and WOAH updates the assessment of the risk of zoonotic transmission (for example, animal to human) considering additional information made available since the previous assessment of 14 August 2024. This update is limited to the inclusion of additional  information being made available globally. Due to the potential risk to human health and the farreaching implications of the disease on the health of wild birds, poultry, livestock and other animal  populations, the use of a One Health approach is essential to tackle avian influenza effectively, to monitor and characterize virus circulation, to prevent within species and to new species transmission, to reduce spread among animals, and to prevent human infections from exposure to animals.

来自粮农组织(FAO)、世界卫生组织(WHO)和世界动物卫生组织(WOAH)的这份风险评估更新了对人畜共患病传播风险(例如,动物到人类)的评估,考虑了自2024年8月14日上次评估以来提供的额外信息。本次更新仅限于纳入全球范围内提供的额外信息。鉴于疾病对人类健康的潜在风险以及对野生鸟类、家禽、牲畜和其他动物群体健康的深远影响,采用“健康共同体”方法对于有效应对禽流感、监测和描述病毒传播、防止种内和新物种传播、减少动物间的传播以及防止人类因接触动物而感染至关重要。

02
Infections in animals(动物中的感染)


In March 2024, influenza A(H5) clade 2.3.4.4b of subtype H5N1 virus was detected in unpasteurized milk samples and oropharyngeal swabs from dairy cattle for the first time in the USA.Influenza A(H5N1) virus detections continue to be reported through testing of dairy cattle exhibiting clinical  signs and with no apparent disease. While H5N1 clade 2.3.4.4b virus was introduced into North America in late 2021, analyses of virus sequence data from infected dairy cows has suggested that the ongoing circulation in dairy herds is linked to a single bird-to-dairy cow transmission event of a  B3.13 genotype A(H5N1) virus that occurred in late 2023 or early 2024. Thus far, this genotype has not been detected in cattle outside of the USA under field conditions.

2024年3月,美国首次在未进行巴氏杀菌的牛奶样本和奶牛的口咽拭子中检测到甲型流感病毒H5N1亚型的H5(H5) 2.3.4.4b分支。 通过检测表现出临床症状的奶牛以及没有明显疾病的奶牛,持续检出了甲型流感A(H5N1)病毒。

尽管H5N1 2.3.4.4b病毒在2021年底引入北美,但对感染奶牛的病毒序列数据分析表明,持续在奶牛群中的传播事件与2023年底或2024年初发生的一次鸟类到奶牛的B3.13基因型的A(H5N1)病毒传播事件有关。迄今为止,在实地条件下未在美国以外的牛群中检测到这种基因型。

As of 18 November 2024, 599 dairy cattle herds in 15 states of the USA have tested positive for A(H5N1), with a significant surge of confirmed outbreaks in dairy cattle in the State of California reaching 383 herds since the first detection in late August 2024

截至2024年11月18日,在美国的15个州中,已有599个奶牛群对A(H5N1)病毒检测呈阳性,自2024年8月下旬首次发现以来,加利福尼亚州的奶牛群中确认的疫情暴发显著增加,达到383个群体。

The average incidence of clinical disease on affected farms ranges between 10 and 20% with main clinical signs including decreased milk production with abnormal milk, decreased feed intake, fever, dehydration, altered faecal consistency, respiratory distress, and abortions.8,9,10 Studies have shown that commercial milk  pasteurization inactivates the virus making it safe for human consumption

受影响农场上临床疾病的平均发病率在10%到20%之间,主要临床症状包括产奶量减少和牛奶异常、食欲下降、发热、脱水以及粪便改变、呼吸窘迫和堕胎。研究表明,商品化的牛奶巴氏消毒可以灭活病毒,使其可供人类安全食用。

The routes and modes of transmission between cattle, the duration of virus shedding as well as the  infectious period are under investigation, and while there have been advancements in our  understanding, this is still not well understood. Transmission between states in the USA has been  linked to cattle movements or possibly through feed and manure handling equipment, or on clothing  or footwear of people working or visiting farms.

已经在研究牛只之间的传播途径和方式、病毒排毒的持续时间以及感染期。尽管研究有所进展,但仍然不能完全理解。美国各州之间的传播与牛只迁移或可能通过饲料和肥料处理设备,或通过在农场工作或来访者的衣物或鞋子有关联。

Experimental studies of lactating dairy cattle and non-lactating heifers have been published and  have provided some insight into receptor distribution, viral replication kinetics, and infection routes.  Studies have indicated that alpha 2,3 sialic acid receptors (avian virus-type) are abundant in dairy cattle mammary tissue, consistent with the observation of high viral load in raw milk, and such  receptors have also been detected in the respiratory tract of dairy cattle.However, one study  addressing the receptor binding specificity of the mammary gland and respiratory tract of cows to  influenza A viruses (IAV) indicated that the upper respiratory tract of cows is devoid of receptors for  IAV. The same study demonstrated that the mammary gland of cows abundantly displays aviantype receptors for circulating H5 viruses while lacking human-type receptors. The lack of human-type  receptors in mammary tissue contradicts a previous study that solely relied on plant-derived lectins to identify receptors. Experimental inoculations of calves, heifers, and lactating cows  demonstrated greater potential of A(H5N1) viruses to infect and replicate in the mammary gland  than in the respiratory tract. In calves, intranasal inoculation with A(H5N1) B3.13 genotype virus  resulted in poor nasal replication and viral shedding and the observed clinical signs were mild and  there was no reported transmission to sentinel calves. While in lactating dairy cows, intramammary  inoculation with high doses of A(H5N1) viruses (B3.13 or a representative European wild bird isolate)  resulted in severe mammary gland infection with necrotizing mastitis, drastically reduced milk  production, with no nasal replication nor systemic infection。

对泌乳奶牛和非泌乳小母牛的实验研究已经发表,并提供了一些关于受体分布、病毒复制动力学和感染途径的观点。研究表明,α2,3唾液酸受体(禽流感病毒受体,血凝素(HA)的受体)在奶牛乳腺组织中丰富,这与观察到的生奶中高病毒载量一致,此类受体也在奶牛的呼吸道中被检测到。然而,一项研究指出,奶牛乳腺和呼吸道对流感A病毒(IAV)的受体结合特异性表明,奶牛的上呼吸道缺少流感A病毒IAV的受体。同一研究显示,奶牛的乳腺组织大量表达传播的H5病毒的鸟类型受体,而缺乏人类型受体。乳腺组织中缺乏人类型受体与之前仅依赖植物来源的凝集素来识别受体的研究相矛盾。实验接种小牛、小母牛和泌乳奶牛表明,A(H5N1)病毒在乳腺中感染和复制的潜力大于在呼吸道中。用A(H5N1) B3.13基因型病毒在小牛中鼻腔进行接种,导致鼻腔复制和病毒排出效果差,观察到的临床症状轻微,且没有向哨点小牛传播的报告。而在泌乳奶牛中,用高剂量的A(H5N1)病毒(B3.13或代表性的欧洲野鸟分离株)进行乳腺内接种,导致严重的乳腺感染和坏死性乳腺炎,显著降低奶产量,没有鼻腔复制也没有全身感染。

On 29 October 2024, the USDA National Veterinary Services Laboratories confirmed A(H5N1) virus  detection in swine from a backyard farm in Oregon State where A(H5N1) virus was also confirmed in  poultry on 25 October. The farming operation had a mix of poultry and livestock (including five  swine, sheep and goats) that had been in close contact and sharing water sources, housing, and  equipment. Although the swine did not express any clinical signs, they were euthanized for further  diagnostic analysis. Two of the five swine tested positive for A(H5N1) virus by polymerase chain  reaction (PCR). Partial genome sequencing indicated the A(H5N1) belonged to the D1.2 genotype,  similarly to the infected poultry on the same farm, and not the B3.13 genotype.20 The detection of  H5N1 virus in two pigs in Oregon State was not unexpected given the close contact between infected  poultry and pigs on the farm likely enabling a poultry-to-swine transmission event. Nonetheless,  avian influenza detections in pigs warrant attention as they can act as "mixing vessels" for genetic  reassortment of avian and human influenza viruses, potentially creating new strains with pandemic  potential. The mechanisms underlying A(H5N1) virus adaptation to pigs and the potential for  efficient and sustained transmissibility among pigs are yet to be understood. Several experimental  infections studies conducted in pigs with A(H5N1) clade 2.3.4.4b viruses showed that mammalianderived A(H5N1) virus strains demonstrated higher potential for replication, pathogenicity, and  transmissibility as compared to avian-derived A(H5N1) virus strains

2024年10月29日,美国农业部国家兽医服务实验室确认,在俄勒冈州的一个后院农场的猪中检测到A(H5N1)病毒。此前,该农场的家禽在10月25日也确认了A(H5N1)病毒的存在。这个农场混合养殖了家禽和牲畜(包括五头猪、绵羊和山羊),它们之间有密切接触,并共用水源、住所和设备。尽管这些猪没有表现出任何临床症状,但它们还是被安乐死以进行进一步的诊断分析。通过聚合酶链反应(PCR)检测,五头猪中有两头对A(H5N1)病毒呈阳性。部分基因组测序表明,A(H5N1)属于D1.2基因型,与同一农场感染的家禽相似,而不是B3.13基因型。在俄勒冈州的两头猪中检测到H5N1病毒并不出乎意料,因为农场中感染的家禽和猪之间的密切接触很可能导致了从家禽到猪的传播事件。尽管如此,猪体内检测到的禽流感病毒仍需引起关注,因为它们可以作为禽流感和人流感病毒基因重组的“混合容器”,可能产生具有大流行潜力的新毒株。A(H5N1)病毒适应猪的机制以及在猪之间高效和持续传播的潜力尚待理解。在猪身上进行的几项实验性感染研究表明,哺乳动物来源的A(H5N1)病毒株与禽源A(H5N1)病毒株相比,显示出更高的复制、致病性和传播潜力。

Nonetheless, avian-derivedA(H5N1) virus isolated in the USA in 2022 replicated successfully in the lungs of pigs with pulmonary  lesions consistent with IAV infection and A(H5N1) virus transmission to at least one naive pig  through direct contact was observed using mammalian isolates (racoon and red fox) from the USA

2022年在美国分离出的禽源的A(H5N1)病毒在具有与IAV感染一致的肺部病变的猪体内成功复制,并且通过使用来自美国的哺乳动物分离物(浣熊和红狐)观察到至少一只未接触过病毒的猪通过直接接触传播了A(H5N1)病毒。

Detections of A(H5) in mammals, other than dairy cattle, and wild and domestic birds continue to be  reported in the USA and in other countries worldwide. Since 2021, clade 2.3.4.4b H5 virus circulation  in wild and migratory birds and poultry resulted in numerous separate infections of wild carnivorous  and scavenging mammals, domestic cats and dogs, marine mammals, and seabirds in various  countries and territories. Clade 2.3.4.4b virus infections in mammals in the Americas, Asia and  Europe have often resulted in severe disease with neurological signs in some species.24Notably, the  wild marine mammal populations along the Atlantic and Pacific coastlines of the Americas  weathered an important H5N1 epizootic leading to mass mortality events, particularly in Argentina,  Chile, and Peru.25Amino acid changes potentially associated with increased virulence, transmission,  or adaptation to mammalian hosts have been identified in H5N1 viruses responsible for the spillover  events in marine mammals, and scientific publications suggested the occurrence of mammal-tomammal transmission events supported by epidemiological, ecological, and phylogenetic data

在美国及其他国家,除了乳牛之外的哺乳动物和野生及家禽鸟类中,A(H5)的检测报告仍在持续。自2021年以来,2.3.4.4b H5病毒在野生和迁徙鸟类以及家禽中的传播导致了在不同国家和地区的野生食肉和食腐哺乳动物、家猫和狗、海洋哺乳动物以及海鸟中发生了许多独立的感染。在美洲、亚洲和欧洲的哺乳动物中,2.3.4.4b病毒的感染通常导致一些物种出现严重的疾病,伴有神经系统症状。值得注意的是,美洲大西洋和太平洋沿岸的野生海洋哺乳动物种群经历了一场重要的H5N1流行病,导致了大规模的死亡事件,特别是在阿根廷、智利和秘鲁。在导致海洋哺乳动物溢出事件的H5N1病毒中,已经鉴定出可能与病毒毒力增加、传播能力增强或适应哺乳动物宿主相关的氨基酸变化,科学出版物表明,基于流行病学、生态学和系统发育数据支持的哺乳动物之间的传播事件已经发生。

Between August and September 2024, avian influenza outbreaks were reported in captive wild  felines in two zoos in southern Viet Nam. These led to the death of at least 47 tigers, three lions and  a leopard, and were confirmed to be caused by a reassortant clade 2.3.2.1c A(H5N1) virus containing  clade 2.3.4.4b gene segments. None of the zoo staff members in close contact with the infected  animals experienced any respiratory symptoms.28, 29 Previous influenza A(H5N1) outbreaks in felines,  characterized by severe pneumonia and high mortality, have been associated with the feeding of  infected poultry and likely tiger-to-tiger transmission.

2024年8月至9月期间,在越南南部的两个动物园中报告了圈养野生猫科动物的禽流感爆发。这些爆发导致至少47只老虎、三只狮子和一只豹死亡,确认是由含有2.3.4.4b基因片段的重组2.3.2.1c A(H5N1)病毒引起的。与感染动物密切接触的动物园工作人员没有出现任何呼吸道症状。以前在猫科动物中的流感A(H5N1)爆发,表现为严重的肺炎和高死亡率,与喂食感染的家禽有关,并可能发生了老虎之间的传播。

03
Detections in humans(人类中的感染)


Since the last joint assessment of August 2024 and as of 27 November 2024, an additional 49 human  cases of infection with A(H5) viruses have been reported. Of these, 45 were reported from the USA:  28 in persons with exposure to A(H5N1)-infected dairy cattle in California, 15 in persons with  exposure while involved in depopulation of A(H5N1)-infected commercial poultry farms, and two in persons with unknown exposure at the time of reporting. Samples from three cases related to  poultry depopulation in the State of Colorado were confirmed to contain A(H5N1) clade 2.3.4.4b,  genotype B3.13, virus while cases related to poultry depopulation in the State of Washington  contained viruses belonging to the D1.1 genotype

自2024年8月的最近一次联合评估以来,截至2024年11月27日,又报告了49例人类感染A(H5)病毒的病例。其中,45例来自美国:加利福尼亚州有28例是接触感染A(H5N1)病毒的奶牛的人,15例是在处理感染A(H5N1)病毒的商业家禽农场的扑杀工作中接触的人,还有两例在报告时暴露情况未知。与科罗拉多州家禽扑杀相关的三例样本被确认含有A(H5N1) clade 2.3.4.4b,基因型B3.13的病毒,而与华盛顿州家禽扑杀相关的病例则含有属于D1.1基因型的病毒。

Intensive epidemiological investigation of the case with unknown exposure in the State of Missouri  could not identify any animal or animal product exposure. Five health care workers in contact with  the case were shown to be A(H5N1) seronegative, the case and one household contact who  reported symptoms with the same onset date were weakly A(H5N1) seropositive。The timing of symptom onsets supports a single common exposure, which at present remains unknown, rather  than human-to-human transmission

密苏里州对未知暴露病例细致的流行病学调查未能识别出任何动物或动物产品暴露。与病例接触的五名卫生工作者显示为A(H5N1)血清阴性,病例和一名报告了相同起始日期症状的家庭接触者被发现弱阳性A(H5N1)血清。症状发生的时间支持目前尚不清楚的单一常见暴露,而不是人际传播

All but one of the detected cases in the USA have reported mild symptoms, including conjunctivitis  and mild respiratory symptoms, and recovered without hospitalization. The one exception who had  comorbidities reported gastrointestinal symptoms and was hospitalized.

在美国检测到的所有病例中,除了一例有并发症的患者报告了胃肠症状并被住院治疗外,其余病例均报告了轻度症状,包括结膜炎和轻微的呼吸道症状,并且在无需住院的情况下康复。

A recent sero-study in 115 persons in Colorado and Michigan working on dairy farms during A(H5N1)  outbreaks among dairy cattle found that eight (7.0%) had serologic evidence of recent infection  (seropositive, ≥40 antibody titres to H5 2.3.4.4b by both micro-neutralization and hemagglutination  inhibition assays). These seropositive individuals reporting working with dairy cattle or in the milking  parlour, and four reported being ill when A(H5) was detected among the dairy cattle

在科罗拉多州和密歇根州的115名在A(H5N1)禽流感爆发期间在乳牛场工作的人员中进行的一项血清学研究发现,有8人(7.0%)有近期感染的血清学证据(血清阳性,通过微量中和和血凝抑制试验对H5 2.3.4.4b的抗体滴度≥40)。这些血清阳性个体报告说他们与乳牛或在挤奶厅工作,在乳牛中检测到A(H5)时,四人报告生病了。

Three human cases of clade 2.3.2.1c A(H5N1) virus infection were reported from Cambodia since the  last update of August 2024. All were hospitalized; two recovered and the other died. All three cases  had exposure to sick or dead backyard poultry. On 13 November, one human case of domestically acquired A(H5N1) infection was confirmed by  Canadian authorities in a young person without underlying conditions. The condition of the case was  reported as critical. There are several ongoing investigations to better understand the exposures of  this case, and so far investigations have not been able to identify the source of exposure. The virus  from the case belonged to clade 2.3.4.4b, specifically the D1.1 genotype, which was similar to viruses  concurrently affecting poultry in the region

自2024年8月的最后一次更新以来,柬埔寨报告了三例2.3.2.1c A(H5N1)病毒的感染病例。所有病例均住院治疗;其中两人康复,另一人死亡。这三例病例均有接触病弱或死亡的家禽。

11月13日,加拿大当局确认了一例在无基础疾病年轻人中获得的A(H5N1)感染病例。该病例的状况被报告为危急。目前正在进行多项调查以更好地了解该病例的暴露情况,但迄今为止,调查尚未能确定暴露来源。该病例的病毒属于2.3.4.4b分支,具体为D1.1基因型,与该地区同时影响家禽的病毒相似。

04
Virus characteristics(病毒特征)


Regular monitoring and screening of viral sequences from birds has rarely found markers of  mammalian adaptation in clade 2.3.4.4b viruses; those that have been detected are mainly in the  polymerase proteins of the virus. These polymerase markers have been more frequently detected in  viruses from mammals. As of 4 November 2024, none of the virus sequences from dairy cattle in the  USA have well-recognized markers in the HA gene associated with a switch in receptor preference  despite continued circulation of the virus. Additional studies on some B3.13 A(H5N1) viruses indicate  no differences in receptor binding, pH fusion or thermostability compared to other non-B3.13 avian  A(H5N1) viruses, and that these viruses retain their avian influenza virus phenotype

对禽类病毒序列的常规监测和筛查很少发现2.3.4.4b病毒系中有哺乳动物适应性的标记;检测到的这些标记主要位于病毒的聚合酶蛋白中。这些聚合酶标记在哺乳动物病毒中被更频繁地检测到。截至2024年11月4日,尽管病毒仍在传播,但美国乳牛的病毒序列中尚未发现与受体偏好性转变相关的HA基因中的公认标记。对一些B3.13 A(H5N1)病毒的额外研究表明,与其它非B3.13禽类A(H5N1)病毒相比,在受体结合、pH融合或热稳定性方面没有差异,并且这些病毒保持了其禽流感病毒表型。

Available virus sequences from human cases have shown some genetic markers that may reduce  susceptibility to neuraminidase inhibitors (antiviral medicines such as oseltamivir) or endonuclease  inhibitors (such as baloxavir marboxil). While these changes may reduce antiviral susceptibility in  laboratory testing the clinical impact of these genetic changes requires further studies.

来自人类病例的可用病毒序列显示了一些遗传标记,这些标记可能降低对神经氨酸酶抑制剂(如奥司他韦等抗病毒药物)或内切酶抑制剂(如巴洛沙韦)的敏感性。虽然这些变化可能在实验室测试中降低了抗病毒的敏感性,但这些遗传变化的临床影响需要进一步研究。

Experimental studies with A(H5N1) clade 2.3.4.4b viruses, including a B3.13 virus from the human  case in Texas, have shown variable transmission between ferrets by direct contact, but no or inefficient transmission via respiratory droplets in most studies.Ferrets infected with  a non-B3.13 A(H5N1) clade 2.3.4.4b virus via the ocular route did experience severe disease and  were able to transmit the virus to other ferrets via direct contact; these contact animals also  developed severe disease。 Currently circulating A(H5N1) viruses would need further genetic changes to gain the ability to spread efficiently among humans via respiratory droplets, consistent  with the current level of risk to public health, which is low

使用A(H5N1) 2.3.4.4b亚型病毒的实验研究,包括来自德克萨斯州人类病例的B3.13病毒,显示通过直接接触在雪貂之间传播情况不一,但在大多数研究中通过呼吸道飞沫的传播不存在或者传播效率较低。 通过眼部途径感染非B3.13 A(H5N1) 2.3.4.4b亚型病毒的雪貂确实经历了严重疾病,并且能够通过直接接触将病毒传播给其他雪貂;这些接触动物也发展出严重疾病。目前流行的A(H5N1)病毒需要进一步的基因改变,才能通过呼吸道飞沫在人类中有效传播,这与目前对公共卫生的低风险水平是一致的。

Other A(H5) virus clades such as 2.3.2.1c46 and 2.3.2.1a continue to circulate and evolve in poultry in  geographically restricted regions. Three A(H5N1) human cases have been detected in Cambodia  since the previous assessment. The detected viruses were identified as reassortant influenza  A(H5N1) viruses that were also detected in poultry in Cambodia, Lao People’s Democratic Republic47 and Viet Nam, and previously detected in human cases reported from Cambodia since late 2023 and  Viet Nam in 2024. This reassortant virus has HA and NA genes from clade 2.3.2.1c viruses, while its  internal genes belong to clade 2.3.4.4b viruses. The viruses were similar to those detected in  captive tigers and leopards in Viet Nam.

其他A(H5)病毒谱系,如2.3.2.1c46和2.3.2.1a,在地理上受限的地区继续在禽类中传播和进化。自上次评估以来,在柬埔寨检测到三例A(H5N1)人类病例。检测到的病毒被鉴定为重配的流感A(H5N1)病毒,这些病毒也在柬埔寨、老挝人民民主共和国和越南的禽类中被检测到,并且之前在2023年底和2024年越南报告的人类病例中被检测到。这种重配病毒具有来自2.3.2.1c谱系病毒的HA和NA基因,而其内部基因属于2.3.4.4b谱系病毒。这些病毒与在越南被圈养的老虎和豹子中检测到的病毒相似。

Based on limited seroprevalence information available on A(H5) viruses, human population  immunity against the HA of H5 viruses is expected to be minimal; human population immunity  targeting the N1 neuraminidase is found to be present although the impact of this immunity is yet to  be understood.

基于对A(H5)病毒有限的血清流行率信息,预期人类对H5病毒的血凝素(HA)的免疫能力将会很低;尽管如此,发现人类对N1神经氨酸酶存在免疫,但这种免疫的影响尚待理解。

05
Candidate vaccine viruses (CVV)(候选疫苗毒株)


The WHO Global Influenza Surveillance and Response System (GISRS), in collaboration with animal  health partners (FAO, WOAH, OFFLU (Joint WOAH-FAO network of expertise on animal influenza)  and others), continue to evaluate candidate vaccine viruses for pandemic preparedness purposes  both bi-annually and on an ad hoc basis. Regular genetic and antigenic characterization of  contemporary zoonotic influenza viruses are published here with the most recent update on A(H5)  CVVs published in September following the WHO Consultation on the Composition of Influenza Virus  Vaccines for Use in the 2025 Southern Hemisphere Influenza Season.  While the majority of circulating clade 2.3.4.4b viruses reacted well to at least one of the postinfection ferret antisera raised against the existing CVVs, an increasing proportion of clade 2.3.2.1c  viruses from Cambodia and Viet Nam had reduced reactivity with post-infection ferret antiserum  raised against an existing CVV. Thus, a new CVV from clade 2.3.2.1c was proposed. The list of  available zoonotic influenza candidate vaccine viruses (CVVs) which include A(H5N1) viruses and  potency testing reagents is updated on the WHO website.

世界卫生组织全球流感监测和应对系统(GISRS),与动物健康合作伙伴(粮农组织(FAO)、世界动物卫生组织(WOAH)、OFFLU(世界动物卫生组织和粮农组织关于动物流感专家网络的联合组织)以及其他合作伙伴)继续合作,定期(每半年一次)和临时对候选疫苗病毒进行评估,以备大流行应对之需。在此处发布最新的当代动物源性流感病毒的常规遗传和抗原特性描述,最近一次关于A(H5) 候选疫苗毒株的更新是在世界卫生组织关于2025年南半球流感季节流感病毒疫苗组成的咨询会后于九月份发布的。

尽管大多数流通的2.3.4.4b系病毒对至少一种针对现有候选疫苗毒株产生的感染后雪貂抗血清反应良好,但来自柬埔寨和越南的越来越多的2.3.2.1c系病毒与针对现有候选疫苗毒株产生的感染后雪貂抗血清的反应性降低。因此,提出了一个新的来自2.3.2.1c系的候选疫苗毒株。包括A(H5N1)病毒和效力测试试剂在内的可用动物源性流感候选疫苗毒株(CVVs)列表在世界卫生组织网站上进行了更新。

06
Assessment of current public health risk posed by influenza A(H5N1) viruses(甲型H5N1流感病毒对当前公共卫生风险的评估)


1. What is the global public health risk of additional human cases of infection with avian influenza  A(H5) viruses? 

Despite the high and increasing number of A(H5) clade 2.3.4.4b outbreaks and detections in  animals and increasing human exposures to the virus at the human-animal-environment  interface, there have been relatively few human infections reported to date.  

Of the human cases of A(H5) detections reported since the beginning of 2021, the majority were  infections in people associated with exposure to A(H5) viruses through direct or indirect contact with infected animals, or contaminated environments, such as live poultry markets or other  premises with infected animals. Severity of illness has ranged from mild to fatal, with the  majority of recent cases reporting mild illness. The exception is the recent case reported from  Canada, in a young person with no underlying conditions, reported as critical. Thus far, among  these cases, there has been no reported or identified human-to-human transmission through  follow up epidemiologic, virologic and serologic investigations. Investigations for some of the  cases continue

禽流感A(H5)病毒增加人类感染病例的全球公共卫生风险是什么?

尽管禽流感A(H5) 2.3.4.4b亚型在动物中的暴发和检测数量高且不断增加,并且人类在人-动物-环境界面上的病毒暴露不断增加,但迄今为止报告的人类感染病例相对较少。

在2021年初以来报告的A(H5)检测病例中,大多数是通过直接或间接接触受感染动物,或受污染的环境或其他受感染动物的场所,与A(H5)病毒相关的人感染。疾病的严重程度从轻微到致命不等,最近的大多数病例报告为轻度疾病。唯一例外的是加拿大最近报告的危重症病例是一个无潜在疾病的年轻人。到目前为止,在这些病例中,没有通过后续流行病学、病毒学和血清学调查报告确定具有人与人传播。对其中一些案件的调查仍在继续

Current virologic and epidemiologic information indicates that these viruses remain avian  influenza viruses without established adaptations to mammalian hosts and have not acquired  the capacity for sustained transmission between humans.  

The epidemiological situation has changed with the ongoing spread of A(H5) virus in the USA  dairy cattle population. Persons exposed to affected dairy cattle and other infected animals may  be in prolonged and close contact with potentially contaminated surfaces and animal products.  As long as A(H5) viruses continue to be detected in wild and domestic birds and mammals,  including dairy cattle, and related environments, including in unpasteurized/raw milk, further  human cases are expected, particularly amongst exposed individuals not wearing appropriate  personal protective equipment and/or in environments where mitigation measures are not in  place. Further studies on the detection of A(H5N1) in two pigs in the USA is needed in order to  better understand the risk posed by this finding. 

Based on currently available information, FAO-WHO-WOAH assesses the global public health risk  of influenza A(H5) viruses as low. Although additional human infections associated with  exposure to infected animals or contaminated environments are expected to occur, they remain  limited in the general population and the overall current public health impact of such infections  at a global level is minor, considering the surveillance, response, mitigation and control  measures in place.

当前的病毒学和流行病学信息表明,这些病毒仍然是禽流感病毒,尚未在哺乳动物宿主中建立适应性,并且尚未获得在人类之间持续传播的能力。

随着A(H5)病毒在美国奶牛群体中的持续传播,流行病学情况已经发生了变化。接触受影响的奶牛和其他感染动物的人可能会长时间且密切地接触可能被污染的表面和动物产品。只要A(H5)病毒继续在野生和家禽以及包括奶牛在内的哺乳动物中被检测到,以及在相关环境中,包括未巴氏杀菌/生牛奶中被检测到,预计将进一步出现人类病例,特别是在未佩戴适当个人防护装备的暴露个体中,以及在没有采取控制措施的环境中。需要进一步研究在美国发现的两头猪体内检测到A(H5N1)的情况,以便更好地理解这一发现所构成的风险。

基于目前可用的信息,FAO-WHO-WOAH联合评估流感A(H5)病毒的全球公共卫生风险为低。尽管预计与接触感染动物或被污染环境相关的额外人类感染将继续发生,但这些感染在一般人群中仍然有限,并且考虑到现有的监测、应对、缓解和控制措施,这些感染在当前全球公共卫生影响方面是次要的。

However, while the risk of infection to the general public is low, among persons with exposure  to infected birds or mammals or contaminated environments, the risk of infection can range  from low to moderate, depending on nature of the exposure, the duration of exposure, the  consistent and appropriate use of personal protective equipment, and the use of other  response, mitigation and control measures particularly in environments where animals are kept.  

The pandemic potential of these viruses requires enhanced vigilance, especially in animal  populations where animal to animal transmission is known to occur (poultry and dairy cattle),  and close monitoring in animals and humans. It remains essential that, while farmers enhance  biosecurity on their farms, governments focus efforts on strengthening surveillance in  susceptible animal populations and in persons exposure to infected animals, to prevention and  mitigation efforts to reduce and/or stop animal to animal transmission and reduce  environmental contamination, to prevention efforts to stop animals to human transmission and  to improve communication with at risk persons and provide occupationally exposed persons  with and train in the use of personal protective equipment.

然而,尽管对公众的感染风险较低,但在接触过感染的鸟类或哺乳动物或受污染环境的人群中,由于接触的性质、接触的持续时间、个人防护装备的一致和适当使用,以及其他应对、缓解和控制措施,特别是在动物被饲养的环境中,感染风险可以从低到中等不等。

病毒的流行病潜力需要提高警惕,特别是在已知动物之间传播发生的动物群体中(如家禽和奶牛),以及在动物和人类中进行加强监测。

在农民加强农场卫生安全的同时,政府应集中努力加强在易感动物群体和接触感染动物的人群中的监测,以预防和缓解措施减少和/或停止动物之间的传播并减少环境污染,以预防措施阻止动物到人类的传播,并改善与高风险人群的沟通,并为职业暴露人员提供和培训个人防护装备的使用。

There has been no reported human-to-human transmission of A(H5) viruses since 2007,  although there may be knowledge gaps in investigations around identified human infections. In  2007 and the years prior, small clusters of A(H5) virus infections in humans were reported,  including limited human to human transmission from patients to health care workers. At the  present time sustained human-to-human transmission has not been reported of A(H5) viruses.

The A(H5) viruses currently detected in mammals, including in human cases, largely retain  genomic and biological characteristics of avian influenza viruses and remain well-adapted to  spread among birds. Except for in-host obtained amino acid mutations in polymerase proteins,  there is still limited evidence for adaptation to mammals and humans even when transmission in  mammals has been suspected.54 No changes in receptor binding tropism have been consistently  observed that would increase binding to receptors in the human upper respiratory tract which  would increase the probability of transmission to and among people. In addition, available  preliminary sero-studies and sero-investigations have not identified human-to-human  transmission of A(H5N1) in the USA. Therefore, sustained human-to-human transmission of the  currently circulating A(H5N1) viruses is considered unlikely without further genetic changes in  the virus. This is actively being assessed by agencies in affected Member States, FAO, WHO,  WOAH and partners.

WHO, together with FAO and WOAH, continues to evaluate A(H5) viruses closely and will reassess the risk associated with the currently circulating A(H5) viruses as more information  becomes available.  

Further antigenic characterization of A(H5) viruses, including in relation to the existing CVVs, and  development of specific reagents are being prioritized at the WHO Collaborating Centres and  Essential Regulatory Laboratories of GISRS in collaboration with public health, animal health, and  veterinary sector colleagues

自2007年以来,尚未报告A(H5)病毒的人际传播,尽管在已知人类感染的调查中可能存在认知空白。在2007年及之前,报告了人类中A(H5)病毒小规模的感染群集,包括从患者到医护人员的有限的人际传播。目前,尚未报告A(H5)病毒的持续人际传播。目前在哺乳动物中检测到的A(H5)病毒,包括在人类病例中,主要保留了禽流感病毒的基因组和生物学特征,并且仍然适应在鸟类中传播。即使在哺乳动物中的传播被怀疑时,除了在宿主内获得的聚合酶蛋白的氨基酸突变外,对哺乳动物和人类适应的证据仍然有限。没有一致观察到改变受体结合趋向性的变化,这会增加与人类上呼吸道受体的结合,从而增加传播给人类及人际间传播的可能性。此外,现有的初步血清学研究和血清学调查尚未在美国识别出A(H5N1)的人际传播。因此,除非病毒发生进一步的遗传变化,否则目前流行的A(H5N1)病毒的持续人际传播被认为是不太可能的。受影响成员国的机构、粮农组织(FAO)、世界卫生组织(WHO)、世界动物卫生组织(WOAH)及其合作伙伴正在积极评估这一点。

世界卫生组织(WHO)与粮农组织(FAO)和世界动物卫生组织(WOAH)继续密切评估A(H5)病毒,并将在更多信息可用时重新评估当前流行的A(H5)病毒相关的风险。

对A(H5)病毒的进一步抗原特性描述,包括与现有候选疫苗毒株(CVVs)的关系,以及特定试剂的开发,正在世界卫生组织合作中心和世界卫生组织全球流感监测和应对系统GISRS的基本监管实验室优先进行,与公共卫生、动物卫生和兽医部门的同事们合作。

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