Yellow fever

Yellow fever is a viral disease of typically short duration, spread by the bite of an infected mosquito, and caused by the yellow fever virus.黄热病（yellow fever）是一种通常病程较短的病毒性疾病，由受感染蚊虫叮咬传播，病原为黄热病病毒。

Symptoms include fever, chills, loss of appetite, nausea, muscle pain and headache, and in about 15% of people a toxic phase follows with jaundice, bleeding and kidney failure.症状包括发热、寒战、食欲减退、恶心、肌肉疼痛与头痛；约 15% 的患者进入中毒期，出现黄疸、出血与肾功能衰竭。

Terminology and classification

• Yellow fever takes its name from the jaundice and fever that characterise severe disease, and has been called "yellow jack", "yellow plague", the American Plague and vómito negro.黄热病之名源于重症所见的黄疸与发热，又称「黄杰克」、「黄瘟疫」、美洲瘟疫与黑呕（vómito negro）。
• The term "yellow jack" derives from the yellow quarantine flag flown by ships that were required to be isolated because of disease.「黄杰克」一词源于因疾病而须隔离的船舶所悬挂的黄色检疫旗。
• ICD-10 assigns the code A95 and ICD-11 (release 2025-01) places yellow fever at 1D47 in Chapter 01, Certain infectious or parasitic diseases.世界卫生组织 ICD-10 编码为 A95，ICD-11（2025-01 发布版）编为 1D47，属第 01 章「某些传染病或寄生虫病」。
• Cross-ontology identifiers include MeSH D015004, MONDO:0020502, Orphanet ORPHA:99829, Disease Ontology DOID:2947, UMLS C0043395 and NCIt C35547.跨本体标识包括 MeSH D015004、MONDO:0020502、Orphanet ORPHA:99829、疾病本体 DOID:2947、UMLS C0043395 与 NCIt C35547。
• Yellow fever is a haemorrhagic fever and an arthropod-borne viral infection, and is one of the diseases for which international vaccination certificates may be required.黄热病属出血热与虫媒病毒感染，也是少数可能被要求出示国际疫苗接种证明的疾病之一。
• The causative virus is the type species of the family Flaviviridae, an enveloped RNA virus 40 to 50 nm wide with a genome of about 10,862 nucleotides encoding a single polyprotein.病原病毒为黄病毒科（Flaviviridae）的模式种，是有包膜的 RNA 病毒，直径 40 至 50 nm，基因组约 10,862 个核苷酸，编码一条多聚蛋白。

History

• Yellow fever most likely originated in Africa, transmitted from nonhuman primates to humans, and spread to the Americas from the 17th century with the trafficking of enslaved Africans.黄热病最可能起源于非洲，由非人灵长类传给人，并自 17 世纪随被贩运的非洲奴隶传播至美洲。
• The first definitive outbreak in the New World was in 1647 on Barbados, and in 1685 Brazil suffered its first epidemic in Recife.新大陆首次明确暴发发生在 1647 年的巴巴多斯；1685 年巴西累西腓首次流行。
• The Yellow Fever Epidemic of 1793 in Philadelphia, then the capital of the United States, caused deaths exceeding 9% of the city's population.1793 年费城（时为美国首都）的黄热病流行造成该市逾 9% 人口的死亡。
• Carlos Finlay proposed in 1881 that yellow fever was transmitted by previously infected mosquitoes, and the US Army Yellow Fever Commission led by Walter Reed proved this hypothesis around 1900.1881 年 Carlos Finlay 提出黄热病由先前感染的蚊虫传播；约 1900 年由 Walter Reed 领导的美国陆军黄热病委员会证实了这一假说。
• In 1927 the yellow fever virus became the first human virus to be isolated, and Max Theiler completed the live attenuated 17D vaccine in 1937.1927 年黄热病病毒成为首个被分离出的人类病毒；Max Theiler 于 1937 年研制成功减毒活疫苗 17D。
• Theiler received the Nobel Prize in Physiology or Medicine in 1951, and the 17D vaccine is still in use.Theiler 因此获得 1951 年诺贝尔生理学或医学奖，17D 疫苗至今仍在使用。

Epidemiology

• In 2013 yellow fever was estimated to have caused 130,000 severe infections and 78,000 deaths in Africa.2013 年据估计黄热病在非洲造成 13 万例重症感染与 7.8 万例死亡。
• The WHO estimates about 200,000 cases of yellow fever worldwide each year, and approximately 90% of them occur in Africa.世界卫生组织估计全球每年约有 20 万例黄热病，其中约 90% 发生在非洲。
• Nearly a billion people live in areas of the world where the disease is common, and about 600 million live in endemic areas.近 10 亿人生活在黄热病流行地区，其中约 6 亿人处于流行区。
• The disease is common in tropical areas of South America and Africa but has historically not occurred in Asia.该病流行于南美与非洲的热带地区，但历史上未在亚洲出现。
• Since the 1980s the number of cases has increased, believed to result from fewer immune people, more urban dwellers, frequent human movement and climate change expanding mosquito habitat.自 1980 年代以来病例增多，被认为与免疫人群减少、城市人口增加、人口流动频繁以及气候变化扩大蚊虫栖息地有关。
• An estimated 90% of infections occur in Africa, and a 2016 outbreak originating in Angola was contained by a massive vaccination campaign.约 90% 的感染发生在非洲；2016 年始于安哥拉的暴发经大规模接种疫苗后被控制。
• In March and April 2016 eleven imported cases of the Angola genotype were reported in unvaccinated Chinese nationals in China, the first appearance of the disease in Asia in recorded history.2016 年 3 至 4 月，中国报告了 11 例未接种疫苗的中国籍人员输入的安哥拉基因型病例，为有记载以来亚洲首次出现该病。
• Phylogenetic analysis has identified seven genotypes of yellow fever virus, five occurring only in Africa and two in South America.系统发生分析已识别出 7 种黄热病病毒基因型，其中 5 种仅见于非洲，2 种见于南美。

Pathophysiology

• The virus is taken up by a female mosquito when it ingests the blood of an infected human or primate and travels to the salivary glands via the haemocoel.雌蚊吸食感染者或灵长类的血液时摄取病毒，病毒经血腔到达唾液腺。
• Three transmission cycles occur: the urban cycle involving Aedes aegypti, the sylvatic cycle involving forest mosquitoes, and the savannah or intermediate cycle in Africa.存在三种传播循环：涉及埃及伊蚊的城市型循环、涉及森林蚊虫的丛林型循环，以及非洲的草原型（中间型）循环。
• In South America the sylvatic cycle is the only way unvaccinated humans become infected, which explains the low incidence of urban cases on that continent.在南美，丛林型循环是未接种者感染的唯一途径，这解释了该洲城市型病例稀少的原因。
• After transmission the virus replicates in lymph nodes and infects dendritic cells, then reaches the liver and infects hepatocytes, causing eosinophilic degradation and Councilman bodies.传播后病毒先在淋巴结复制并感染树突状细胞，继而到达肝脏感染肝细胞，导致嗜酸性变性与 Councilman 小体形成。
• Yellow fever cannot be eradicated solely by vaccination because the sylvatic cycle involving wild primates and forest mosquitoes persists.由于涉及野生灵长类与森林蚊虫的丛林型循环持续存在，仅靠接种疫苗无法根除黄热病。
• Death may follow a cytokine storm, shock and multiple organ failure.死亡可继发于细胞因子风暴、休克与多器官衰竭。

Clinical features

• After an incubation period of three to six days, most cases cause only a mild illness with fever, headache, chills, back pain, fatigue and vomiting lasting three to six days.经 3 至 6 天潜伏期后，多数病例仅表现为轻症，包括发热、头痛、寒战、背痛、乏力与呕吐，持续 3 至 6 天。
• In about 15% of cases the disease enters a second, toxic phase with recurring fever, abdominal pain and jaundice caused by liver damage.约 15% 的病例进入第二中毒期，表现为发热复发、腹痛以及肝损伤所致的黄疸。
• Bleeding from the mouth, nose, eyes and gastrointestinal tract causes blood-containing vomit, known in Spanish as vómito negro.口、鼻、眼与胃肠道出血导致含血呕吐物，西班牙语称黑呕（vómito negro）。
• There may also be kidney failure, hiccups and delirium, and among those who develop jaundice the fatality rate is 20% to 50%.还可能出现肾功能衰竭、呃逆与谵妄；出现黄疸者的病死率为 20% 至 50%。
• The overall fatality rate is about 3% to 7.5%, while severe cases may exceed 50%.总体病死率约为 3% 至 7.5%，重症病例则可超过 50%。
• Surviving infection provides lifelong immunity, generally with no permanent organ damage.存活者获得终身免疫，一般不留永久性器官损伤。
• Complications during recovery may include jaundice, fatigue, heart rhythm problems, seizures and internal bleeding.康复期的并发症可包括黄疸、疲劳、心律失常、癫痫发作与内出血。
• Non-native people tend to develop more severe illness when infected, which is why vaccination is advised for travellers.非本地人群感染后往往病情更重，因此建议旅行者接种疫苗。

Diagnosis

• Yellow fever is most often a clinical diagnosis based on symptoms and travel history, and mild cases can only be confirmed virologically.黄热病多依据症状与旅行史作临床诊断，轻症只能通过病毒学方法确诊。
• Direct confirmation can be obtained by reverse transcription polymerase chain reaction amplifying the viral genome, or by isolating the virus in cell culture, which takes one to four weeks.可通过逆转录聚合酶链反应扩增病毒基因组直接确诊，或在细胞培养中分离病毒，后者需 1 至 4 周。
• Serologically, detection of specific IgM by enzyme-linked immunosorbent assay or a four-fold rise in IgG titre is considered sufficient indication of infection together with clinical symptoms.血清学上，酶联免疫吸附试验检出特异性 IgM 或 IgG 滴度升高 4 倍，结合临床症状即可作为充分指征。
• Because these tests can cross-react with other flaviviruses such as dengue virus, indirect methods cannot conclusively prove yellow fever infection.由于这些检测可与其他黄病毒（如登革病毒）发生交叉反应，间接方法不能确证黄热病感染。
• Liver biopsy can verify hepatocyte inflammation and necrosis, but because of the bleeding tendency it is advisable only post mortem.肝活检可证实肝细胞炎症与坏死，但鉴于出血倾向，仅在死后进行较为适宜。
• The differential diagnosis must distinguish yellow fever from other febrile illnesses such as malaria and from other viral haemorrhagic fevers such as Ebola, Lassa, Marburg and Junin viruses.鉴别诊断须将黄热病与其他发热性疾病（如疟疾）以及埃博拉、拉沙、马尔堡与胡宁病毒等其他病毒性出血热区分开。

Management

• No cure is known for yellow fever, and management is symptomatic with hospitalisation and intensive care as needed.目前尚无治愈方法，治疗为对症处理，必要时住院并给予重症监护。
• Passive immunisation after symptoms emerge is probably ineffective, and ribavirin, other antivirals and interferon are ineffective in patients.症状出现后给予被动免疫可能无效，利巴韦林（ribavirin）等抗病毒药与干扰素对患者亦无效。
• Symptomatic treatment includes rehydration and pain relief with paracetamol.对症治疗包括补液与使用对乙酰氨基酚（paracetamol）镇痛。
• Aspirin and other non-steroidal anti-inflammatory drugs are often avoided because of an increased risk of gastrointestinal bleeding from their anticoagulant effects.因抗凝作用增加胃肠道出血风险，阿司匹林与其他非甾体抗炎药常被避免使用。
• Vaccination is the mainstay of prevention, with protection beginning by the tenth day after administration in 95% of people.接种疫苗是预防的核心，95% 的人在接种后第 10 天即产生保护。
• The WHO now states that a single dose confers lifelong immunity, and recommends routine vaccination for people in affected areas between the 9th and 12th month after birth.世界卫生组织现认为单剂疫苗即可提供终身免疫，并建议流行区人群在出生后第 9 至 12 月龄常规接种。
• Prevention also includes insect repellents containing DEET or picaridin, permethrin-treated clothing, bed nets and mosquito control measures.预防还包括使用含避蚊胺（DEET）或派卡瑞丁的驱蚊剂、经氯菊酯处理的衣物、蚊帐与媒介控制措施。

Research and controversies

• The Yellow Fever Initiative launched by the WHO in 2006 vaccinated more than 105 million people in 14 West African countries, and no outbreaks were reported during 2015.世界卫生组织于 2006 年启动的黄热病倡议为 14 个西非国家的逾 1.05 亿人接种疫苗，2015 年期间未报告暴发。
• Fractional dosing of the vaccine is used as a dose-sparing strategy during outbreaks, and available evidence shows it induces an immune response similar to the standard full dose.疫情期间采用疫苗分剂量接种作为节约策略，现有证据显示其诱导的免疫反应与标准全剂量相似。
• In a hamster model, early administration of ribavirin reduced liver and spleen damage and normalised alanine aminotransferase levels.在仓鼠模型中，早期给予利巴韦林可减轻肝脾损伤并使丙氨酸氨基转移酶水平恢复正常。
• Infection was reduced in mosquitoes carrying the wMel strain of Wolbachia, suggesting a biological approach to vector control.携带 Wolbachia wMel 菌株的蚊虫感染率降低，提示存在生物性媒介控制途径。
• Mass vaccination cannot eliminate yellow fever because of the vast number of infected mosquitoes in urban areas, but it significantly reduces the number of people infected.由于城市地区受感染蚊虫数量庞大，大规模接种无法根除黄热病，但可显著减少感染者人数。