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217 在印度,致死性脑炎最常见的病因是狂犬病 精选

已有 3436 次阅读 2018-7-12 18:42 |个人分类:狂犬病|系统分类:论文交流

 

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    狂犬病是一种迅速发展的脑炎性传染病,在印度,狂犬病是一个严重的公共卫生问题,每年引起2万多人死亡。尽管印度正在采取措施控制这种传染病,但由于暴露后预防措施不足,印度死亡人人数约占全球的35%。印度能控制狂犬病吗?下面是Sanjeet Bagcchi调查。

    2015年9月,来自西孟加拉邦一个村庄的9岁男孩Neeraj从一家政府医院回来,脸上带着痛苦的表情。他的父母非常焦虑,但他们试图对儿子掩饰他们的焦虑。他们担心的原因是几天前一只流浪狗咬了Neeraj。Neeraj的母亲卡玛拉说“从上周开始,这只狗就在我家附近咬了6个人,这条狗可能是疯狗。”她带着Neeraj去了政府医院,给他处理了伤口,并给他注射了狂犬病疫苗,用来预防他的父母称之为“恐水症”的疾病。卡玛拉知道这种病,因为她还是个孩子的时候,狂犬病就杀了她的一个亲戚。卡玛拉回忆说:“我的叔叔在被疯狗咬伤后死于狂犬病。”他补充说:“我当时在小学,我的老师让我的叔叔接种疫苗来预防恐水症。”然而,他拒绝接种疫苗,6个月后死亡。他不能喝水,当有人给他水时,他很害怕。这就是为什么我们在Neeraj被咬后立即将他送到医院进行狂犬病暴露后处置的原因,我不想冒任何风险。

    卡玛拉不知道别人在她的村庄也被流浪狗咬伤是否也接种了疫苗,她也不知道感染狂犬病的细节,但她是印度农村人之一,没有任何犹豫,就急于去政府医院给孩子进行狂犬病暴露后处置。由于印度各地的个人经历和宣传活动,最近这一趋势在印度得到了发展。现在,印度的一些人——比如卡玛拉——对与感染有关的狂犬病和神经问题有部分了解,但对与狂犬病相关的神经系统疾病和足够的暴露后预防措施的了解却很少。因此,每年印度估计的狂犬病发病率(2人/10万)至少在10年内没有下降。

    乌特帕尔·雅娜是印度加尔各答市的尼尔·拉坦·瑟卡医学院和医院耳鼻喉科的教授和系主任,她告诉《柳叶刀神经病学》杂志,“恐水症”这个词来源于希腊语,意为“害怕水”。他指出,恐水症是由狂犬病急性进行性脑脊髓炎引起的,可能是与狂犬病相关的脑干神经功能受损有关。雅娜解释说:“在这种情况下,由于咽部和喉部肌肉的疼痛痉挛,患者吞咽面临巨大的困难,这导致了病人对饮用水和液体的恐惧,这种恐惧加剧了肌肉痉挛,加重了病情。”

    根据世界卫生组织的报道,除了南极洲,狂犬病在所有大陆都存在。这是一种人畜共患病,由狂犬病病毒引起,最常见的宿主是家犬。狂犬病通过受感染动物的唾液或神经组织传播,通过破损的皮肤或粘膜进入人体,最常见的感染方式是通过咬伤。这种病毒在受伤部位的复制能力很差,但高度噬神经,可在神经元中快速复制,因为神经系统的免疫特点使它避开了适应性免疫系统,许多病人在没有可检测到的病毒抗体的情况下死亡。印度班加罗尔国家精神卫生和神经科学研究所神经病毒系的副教授马尼告诉《柳叶刀神经病学》杂志,许多发病机制已经被提出,但没有人知道狂犬病病毒是如何杀死人的。没有针对狂犬病的特定抗病毒治疗。一旦病人出现症状,死亡几乎总是不可避免。根据马尼的说法,全世界大约有15例狂犬病幸存者被报告。她说:“印度报告了6例狂犬病患者的存活病例。”不幸的是,他们都有严重的神经后遗症。狂犬病有两种主要的临床表现:脑炎狂犬病或经典型狂犬病,以脑炎、发烧、恐水症、呼吸痉挛、自主功能障碍为特征;麻痹性狂犬病,以神经痛和进行性虚弱为特征。然而,越来越多的证据表明,这些症状形成了一种单一的疾病。脑炎狂犬病最常见,病人中大约占80%。

    一旦出现神经系统症状,狂犬病几乎总是致命的,因此暴露后预防的及时性非常重要。由马尼领导的研究人员对印度11个州的狂犬病患者进行了统计。在他们的研究中,他们强调了加强意识以对抗国内狂犬病的必要性。马尼和同事总结说:“在印度,提高对充分暴露后预防措施的认识、增加狂犬病诊断设施、加强对人和动物狂犬病的监测、以显示真正的疾病负担,这些是控制这种致命疾病的关键。”

    根据去年发表在《全球狂犬病负担》(the global burden of rabies)上的一项研究,全球每年约有59000人死于狗咬伤引起的狂犬病。该研究指出,印度占全球狂犬病负担的35%,估计每年有20847人死于狂犬病。然而,由于印度人没有义务向政府上报狂犬病病例,因此有可能出现病例报告不足,导致死亡人数低估。全球狂犬病控制联盟(Global Alliance for Rabies Control)的科学主任路易丝泰勒(Louise Taylor)对《柳叶刀神经病学》(Lancet Neurology)杂志表示, “狂犬病也是贫穷社区的一种疾病,所以人们往往得不到治疗,或者在得到诊断后就回家死去。”因此,在大多数犬类狂犬病流行国家,很难找到人类病例数的数据。

    为了减轻狂犬病的负担,专家们一致认为,印度等国家需要重视暴露后预防,并提高对狂犬病的认识。根据对全球狂犬病负担的研究,这种疾病是完全可以预防的,可以通过对咬伤患者进行及时的暴露后预防措施来预防,并且可以通过大规模的家犬免疫来控制狂犬病流行。泰勒指出,预防人类狂犬病的最可持续和公平的方法是通过给狗群接种疫苗和打破传播的循环来消除该病。她认为这一策略是可行的,它在高收入国家都行得通,最近,通过这一策略,在拉丁美洲的大多数国家狂犬病都被消除了。

    2014年11月,印度国家疾病控制中心在9个州开展了全国狂犬病控制项目,拨款5亿卢比(约500万美元)用于促进人类暴露后预防和大规模狗疫苗接种运动。然而,专家们认为,卫生工作者和普通民众对该病的认识以及疫苗的充分供应与疫苗接种运动同样重要。

    在马尼看来,在我们考虑在印度控制犬类狂犬病之前,主要的重点应该放在对卫生保健工作者和普通公众的教育上——提高人们对接触犬类的危险性的认识,以及迫切需要立即寻求医疗帮助。然而,她补充说,对于暴露后预防,农村地区的主要障碍是缺乏足够的疫苗供应,特别是拯救生命的狂犬病免疫球蛋白更缺。正如她所说,“狂犬病仍然是印度最常见的致命性脑炎。因此,这是一种重要的神经系统疾病,值得认真关注和控制。这的确是全球狂犬病联盟发出的关键信息之一,该联盟将于2016年9月28日确定为第十个世界狂犬病日,这是为纪念路易·巴斯德(Louis Pasteur),他是1885年开发出第一种狂犬病疫苗的研究人员。

 

 

    Lancet Neurol. 2016 Jul;15(8):793-794. doi: 10.1016/S1474-4422(16)30083-7.

Rabies: the most common cause of fatal encephalitis in India.

 

Bagcchi S.

PMID: 27302357

 

Rabies, a rapidly progressing encephalitis, is a substantial public health problem in India, responsible for more than 20000 deaths every year. Although steps are being taken to contain the disease, India still carries over 35% of the global burden of rabies, due to inadequate post-exposure prophylaxis. Will India be able to control rabies? Sanjeet Bagcchi investigates.

In September, 2015, Neeraj, a 9-year-old boy from a village in West Bengal, was returning from a government hospital with a look of pain on his face. His parents were anxious, but they were trying to hide their anxiety from their son. The reason for their concern was a stray dog that had bitten Neeraj a few days before. “Since last week, the dog has bitten six people in our neighbourhood; it has probably gone mad,” said Kamala, Neeraj's mother, who took Neeraj to the government hospital to have his wounds dressed and to have him vaccinated against rabies—a disease his parents called hydrophobia. Kamala knew about the disease, as it had killed one of her relatives when she was a child. “My uncle died of hydrophobia after he was bitten by a mad dog,” recalled Kamala, adding “I was in primary school and my teachers asked my uncle to take the vaccine for hydrophobia. However, he refused to take the vaccine, and died 6 months later. He couldn't drink water and became frightened when somebody gave him water”, she recounted. “That was the reason we took Neeraj to the hospital for rabies vaccine immediately after he was bitten; I don't want to take any risks.”

Kamala didn't know whether the other people in her village who were also bitten by the stray dog underwent vaccination, nor did she know the details of rabies infection, but she is one of the rural Indian individuals who, without any hesitation, would rush to a government hospital for vaccination to prevent rabies after a potential exposure. This trend has developed in India in recent times, thanks to personal experiences and awareness campaigns across the country. Now, some people in India—such as Kamala—are partially aware about rabies and neurological problems associated with the infection but awareness of rabies-related neurological disorder and adequate post-exposure prophylaxis are mostly absent. As a result, the estimated annual incidence of rabies in India (two per 100000 population) has not fallen in at least a decade.

Utpal Jana, professor and head of the Department of Otorhinolaryngology at the Nil Ratan Sircar Medical College and Hospital (Kolkata, India), told The Lancet Neurology that hydrophobia—the commonly known manifestation of rabies—is a term that takes its origin from the Greek word hydrophobos, which means dreading water. He points out that hydrophobia is caused by the acute progressive encephalomyelitis that occurs in rabies and might be a consequence of rabies-related neuronal dysfunction in the brainstem. Jana explains that “in this condition, due to painful spasms of the muscles of the pharynx and larynx, patients face substantial difficulties in swallowing. This leads to a kind of fear of drinking water and liquids; and this fear worsens the muscle spasms, aggravating the condition.”

According to WHO, rabies is endemic in all the continents except Antarctica. It is a zoonotic disease, caused by rabies virus (of the Rhabdoviridae family and Lyssavirus genus) and the most common reservoir of the virus is domestic dogs. Rabies is transmitted through the saliva or neural tissue of infected animals and enters the human body through broken skin or the mucosa, most commonly through bites. The virus replicates poorly at the site of injury, but is highly neurotropic and replicates quickly in neurons, where it avoids the adaptive immune system due to the immune privilege of the nervous system—many patients die without detectable antibodies against the virus. Reeta Subramaniam Mani, Associate Professor at the Department of Neurovirology, National Institute of Mental Health and Neurosciences (Bangalore, India) told The Lancet Neurology that many mechanisms of pathogenesis have been proposed for rabies, but nobody knows how exactly the rabies virus kills. “No specific antiviral therapy exists for rabies. Once a patient is symptomatic, death is almost always certain”, she explained. According to Mani, about 15 cases of people surviving rabies have been reported worldwide. “Six cases of survival from rabies have been reported from India” she said, adding, “we have been involved in 5 cases. Sadly, all of them have severe neurological sequelae.” There are two major clinical manifestations of rabies: encephalitic or classical rabies, characterised by encephalopathy, fever, hydrophobia, inspiratory spasms, and autonomic dysfunction, and paralytic rabies, characterised by neuropathic pain and progressive weakness. However, there is increasing evidence suggesting that these symptoms form a spectrum of a single disease. The symptoms of encephalitic rabies are the most common, accounting for roughly 80% of cases.

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Dogs are the most common reservoir of the rabies virus

Copyright © 2016 CDC/Science Photo Library

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Patient being given a rabies vaccination

Copyright © 2016 Dr P Marazzi/Science Photo Library

Once neurological symptoms manifest, rabies is almost always fatal, highlighting the importance of early post-exposure prophylaxis. Researchers led by Mani carried out an audit of human cases of rabies from 11 states in India. In their study, they emphasised the necessity of enhanced awareness to combat rabies in the country. Mani and co-workers concluded that, in India, “increasing awareness about adequate post-exposure prophylaxis, additional rabies diagnostic facilities, and enhanced human and animal rabies surveillance to indicate the true disease burden are essential to control this fatal disease.”

According to a study published last year on the global burden of rabies, rabies from dog bites leads to an estimated 59000 human deaths annually around the globe. India accounts for 35% of the global burden of rabies, with an estimated 20847 people dying from the disease each year, the study noted. However, since it is not necessary across all of India to notify government authorities about cases of rabies, there is the possibility that new cases are being inadequately reported, leading to underestimation. Louise Taylor, Scientific Director of the Global Alliance for Rabies Control told The Lancet Neurology, that rabies “is also a disease of poor communities, so often people fail to seek treatment, or return home to die when they receive the diagnosis. Data on human case numbers for rabies in most canine rabies endemic countries are therefore notoriously difficult to find.”

To reduce the burden of rabies, experts agree that countries such as India need to place emphasis on post-exposure prophylaxis and boost awareness. According to the study on the global burden of rabies, “the disease is entirely preventable through prompt administration of post-exposure prophylaxis to bite victims and can be controlled through mass vaccination of domestic dogs.” Taylor pointed out that the most sustainable and equitable way to prevent human rabies deaths is to eliminate the disease at its source, by vaccinating the dog population and breaking the cycle of transmission. She thinks that this strategy can work, “it has worked across high income countries, and more recently, [with this strategy, rabies] has been eliminated from most countries of Latin America.”

In November, 2014, the Indian government's National Centre for Disease Control rolled out the National Rabies Control Programme in nine states, allocating a fund of 500 million rupees (about 5 million) to promote both post-exposure prophylaxis in humans and mass vaccination of dogs. However, experts believe that awareness of the disease among health workers and the general population and adequate supply of the vaccine are equally as important as vaccination campaigns.

In Mani's opinion, “before we even think of canine rabies control in India, the major focus should be [on the] education of health-care workers and the lay public alike—to increase awareness about the seriousness of any exposure to dogs and the urgency of seeking immediate medical help.” However, she added that, for post-exposure prophylaxis, the major stumbling block in rural areas is the lack of an adequate supply of vaccines, especially the life-saving rabies immunoglobulins. As she put it, “rabies continues to be the most common fatal encephalitis in India. Hence, it is an important neurological illness that warrants serious attention and control measures”. This is indeed one of the key messages of the Global Rabies Alliance that will oversee the tenth World Rabies Day on Sept 28, 2016, an event held on the anniversary of the death of Louis Pasteur, the investigator who developed the first rabies vaccine in 1885.

 




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