Pogosta disease

Pogosta disease is a mosquito-borne alphavirus infection that occurs in late summer in Finland and causes rash, fever and arthralgia波戈斯塔病是一种由蚊媒传播的甲病毒感染，在芬兰夏末发生，引起皮疹、发热与关节痛。

It is caused by Sindbis virus and is known as Ockelbo disease in Sweden and Karelian fever in Russia该病由辛德毕斯病毒引起，在瑞典称为奥克尔博病，在俄罗斯称为卡累利阿热。

No antiviral drug or licensed vaccine is available, so management is symptomatic and prevention depends on avoiding mosquito bites目前没有抗病毒药物或获批疫苗，因此治疗以对症为主，预防依赖避免蚊虫叮咬。

Terminology and classification

• The name Pogosta comes from the old parish village of Ilomantsi in eastern Finland, which is sometimes called Pogosta and where the disease was first detected in 1974波戈斯塔这一名称来自芬兰东部伊洛曼齐的古老教区村，该地有时被称为波戈斯塔，1974年该病首次在此被发现。^[1]
• Ockelbo disease is named after the Swedish municipality of Ockelbo, and Karelian fever refers to the Karelian region where Russian cases were recognised奥克尔博病以瑞典奥克尔博市命名，卡累利阿热则指俄罗斯病例被识别的卡累利阿地区。^[1]
• Pogosta disease belongs to the arthropod-borne viral fevers and is not a separate rare-disease entry in Orphanet, because it is endemic rather than uniformly ultra-rare波戈斯塔病属于虫媒病毒性发热，并非 Orphanet 中的独立罕见病条目，因为其呈地方性流行而非普遍极罕见。^[1]
• ICD-10 assigns it to A92.8, other specified mosquito-borne viral fevers, while ICD-11 uses 1D4Y for other specified arthropod-borne viral fevers with the agent extension XN0D6 for Sindbis virus《国际疾病分类》第十版将其归入 A92.8，即其他特指的蚊媒病毒性发热，第十一版则以 1D4Y 表示其他特指的虫媒病毒性发热，并用病原体扩展码 XN0D6 标注辛德毕斯病毒。^[1]
• Cross-references include Wikidata Q4346007 and the virological taxonomy of Sindbis virus as an Alphavirus in the family Togaviridae交叉参照包括 Wikidata Q4346007，以及辛德毕斯病毒作为披膜病毒科甲病毒属成员的病毒学分类。^[1]
• The clinical case definition requires acute rash and joint symptoms after mosquito exposure in an endemic area, with laboratory confirmation by serology or nucleic acid testing临床病例定义要求在流行区蚊虫暴露后出现急性皮疹与关节症状，并通过血清学或核酸检测进行实验室确认。^[2]

History

• Sindbis virus was first isolated from Culex mosquitoes in 1952 in the Nile delta near the village of Sindbis in Egypt, which gave the virus its name辛德毕斯病毒于1952年首次从埃及尼罗河三角洲辛德毕斯村附近的库蚊中分离，病毒由此得名。^[1]
• The first human cases were described in Uganda in 1961, followed by South Africa in 1963 and Australia in 1967, establishing the virus as a cause of rash-arthritis syndromes首批人类病例于1961年在乌干达报告，随后1963年南非与1967年澳大利亚相继报告，从而确认该病毒可引起皮疹-关节炎综合征。^[1]
• In Finland the disease was first detected in 1974 in Ilomantsi, and the name Pogosta disease was adopted for the local syndrome在芬兰，该病于1974年在伊洛曼齐首次被发现，当地综合征遂采用波戈斯塔病这一名称。^[1]
• During the 1980s and 1990s serosurveys and registry analyses showed that cases clustered in eastern Finland and recurred in multi-year cycles二十世纪八十至九十年代的血清学调查与登记分析显示，病例集中于芬兰东部，并以多年周期反复出现。^[3]
• In 2002 a Sindbis virus strain was isolated from patients during a large Finnish outbreak, which confirmed the long-suspected aetiology of Pogosta disease2002年芬兰一次大规模暴发期间从患者体内分离出辛德毕斯病毒株，证实了长期以来对波戈斯塔病病因的推测。^[1]
• The 2021 outbreak again drew attention to the disease, and contemporary reviews now frame it as a climate-sensitive arbovirus of northern Europe2021年的暴发再次引起对该病的关注，当代综述将其视为北欧对气候敏感的虫媒病毒病。^[2]

Epidemiology

• Between 1981 and 1996, 2,183 serologically confirmed Pogosta disease cases were recorded in Finland, with an annual incidence of 2.7 per 100,000 and 18 per 100,000 in the most endemic part of North Karelia1981年至1996年间，芬兰共记录2183例血清学确诊的波戈斯塔病，年发病率为每十万分之2.7，在北卡累利阿最流行地区达每十万分之18。^[3]
• From 2000 to 2019 an average of 91 cases were reported each year, ranging from 8 to 597, corresponding to a national incidence of about 1.7 per 100,0002000年至2019年间年均报告91例，范围从8例到597例，相当于全国发病率约每十万分之1.7。^[4]
• The 2002 outbreak in North Karelia reached an incidence of 81 per 100,000, one of the highest rates ever documented for Sindbis virus infection2002年北卡累利阿暴发的发病率达每十万分之81，是辛德毕斯病毒感染有记录的最高发病率之一。^[5]
• The 2021 Finnish outbreak comprised 566 laboratory-confirmed cases and was concentrated in the same eastern municipalities as earlier epidemics2021年芬兰暴发包含566例实验室确诊病例，并集中于与既往流行相同的中东部市镇。^[2]
• Outbreaks have historically occurred at roughly seven-year intervals, although the 2021 epidemic showed that this periodicity is not strict历史上暴发大致每隔七年出现一次，但2021年流行表明这种周期性并不严格。^[1]
• A Finnish serosurvey conducted between 1999 and 2003 found an age-standardised seroprevalence of 5.2 per cent, indicating that many infections are mild or asymptomatic1999年至2003年的一项芬兰血清学调查发现年龄标化血清阳性率为5.2%，提示许多感染较轻或无症状。^[6]
• Sindbis virus is maintained in birds, and 27.4 per cent of grouse sampled in Finland were seropositive, supporting a role for wild galliform birds as amplifying hosts辛德毕斯病毒在鸟类中维持循环，芬兰采样鸡形目鸟类中27.4%血清阳性，支持野生鸡形目鸟类作为放大宿主。^[6]
• Human incidence is highest in people who pick berries, work outdoors or spend summer evenings near mosquito-infested wetlands in endemic regions在流行区采摘浆果、从事户外工作或在夏夜停留于蚊虫密集湿地附近的人群发病率最高。^[5]

Pathophysiology

• Sindbis virus is an enveloped virus with a positive-sense single-stranded RNA genome of about 11.7 kilobases, organised into two open reading frames辛德毕斯病毒是一种有包膜病毒，基因组为正链单股 RNA，长约11.7千碱基，分为两个开放阅读框。^[1]
• The virus is transmitted mainly by Culex and Culiseta mosquitoes, and wild birds serve as the principal amplifying reservoir while humans are incidental hosts该病毒主要由库蚊与脉毛蚊传播，野生鸟类是主要放大宿主，人类为偶然宿主。^[4]
• After a mosquito bite the incubation period is usually less than seven days, after which a brief low-level viraemia develops and seeds skin, joint and muscle tissue蚊虫叮咬后潜伏期通常少于七天，随后出现短暂低水平病毒血症，并播散至皮肤、关节与肌肉组织。^[1]
• Because viraemia is low and short-lived, direct viral detection in blood is insensitive, and the immune response rather than viral replication is thought to drive persistent joint symptoms由于病毒血症水平低且持续时间短，血液直接检测病毒不敏感，持续关节症状被认为更多由免疫反应而非病毒复制驱动。^[7]
• IgM antibodies appear within the first week and IgG antibodies persist for years, so seroconversion or a fourfold titre rise is the main diagnostic evidence of recent infectionIgM 抗体在发病第一周内出现，IgG 抗体可持续数年，因此血清转换或抗体滴度四倍升高是近期感染的主要诊断依据。^[7]
• The maculopapular rash reflects dermal infection and perivascular inflammation, while arthralgia is associated with synovial inflammation and immune-complex deposition斑丘疹反映真皮感染与血管周围炎症，关节痛则与滑膜炎症及免疫复合物沉积相关。^[1]

Clinical features

• Acute infection typically presents with an itchy maculopapular rash over the trunk and limbs, mild fever and joint pain that is worst in the wrists, hips, knees and ankles急性感染通常表现为躯干与四肢瘙痒性斑丘疹、轻度发热以及以腕、髋、膝与踝关节最明显的关节痛。^[1]
• Nausea, headache, myalgia and general malaise are common, and basic blood counts and inflammatory markers are usually within normal limits恶心、头痛、肌痛与全身不适常见，基础血象与炎症指标通常正常。^[1]
• Children usually have a milder illness and may present with rash alone, without objective joint swelling儿童病情通常较轻，可能仅表现为皮疹而无客观关节肿胀。^[1]
• Asymptomatic infection is not uncommon, which explains why seroprevalence is much higher than the reported incidence无症状感染并不少见，这解释了为何血清阳性率远高于报告发病率。^[6]
• Extra-articular symptoms usually resolve within one to two weeks, but joint manifestations can persist for months or years and occasionally evolve into chronic arthritis关节外症状通常在1至2周内消退，但关节表现可持续数月甚至数年，偶尔发展为慢性关节炎。^[1]
• Fatal infections have not been reported, although severe fatigue and prolonged arthralgia can cause substantial loss of work capacity尚未见致死性感染报告，但严重疲乏与迁延性关节痛可造成显著的工作能力损失。^[1]
• The differential diagnosis includes chikungunya, Ross River and Barmah Forest virus infections, dengue, rubella, parvovirus B19, Lyme disease, early rheumatoid arthritis and gout鉴别诊断包括基孔肯雅热、罗斯河病毒与巴马森林病毒感染、登革热、风疹、细小病毒 B19 感染、莱姆病、早期类风湿关节炎与痛风。^[2]

Diagnosis

• Diagnosis rests on a compatible exposure history in an endemic area during late summer, together with laboratory evidence of Sindbis virus infection诊断依赖夏末在流行区有相符暴露史，并结合辛德毕斯病毒感染的实验室证据。^[2]
• Enzyme immunoassay or immunofluorescence for IgM and IgG is the usual first-line test, and plaque reduction neutralisation can confirm specificity when cross-reactivity is suspected针对 IgM 与 IgG 的酶免疫分析或免疫荧光是常用一线检测，疑似交叉反应时可用空斑减少中和试验确认特异性。^[7]
• Reverse-transcription polymerase chain reaction is specific but insensitive in immunocompetent patients because viraemia is low and brief, so a negative result does not exclude the diagnosis逆转录聚合酶链反应具有特异性，但在免疫功能正常患者中因病毒血症低且短暂而不敏感，因此阴性结果不能排除诊断。^[7]
• Paired acute and convalescent sera showing seroconversion or a fourfold rise in antibody titre provide stronger evidence than a single IgM result急性期与恢复期配对血清显示血清转换或抗体滴度四倍升高，比单次 IgM 结果提供更强证据。^[7]
• In endemic countries cases are notified to public health authorities, and ECDC and national institutes such as THL publish surveillance guidance and seasonal alerts在流行国家，病例需向公共卫生部门报告，欧洲疾病预防控制中心与芬兰健康与福利研究所等国家机构发布监测指南与季节性警报。^[4]

Management

• There is no specific antiviral therapy, and management is supportive with rest, fluids and adequate analgesia目前没有特异性抗病毒治疗，处理以休息、补液与充分镇痛等支持治疗为主。^[1]
• Paracetamol is preferred for fever and mild pain, while ibuprofen or naproxen can be used for arthralgia when there is no contraindication发热与轻度疼痛首选对乙酰氨基酚，无禁忌时可用布洛芬或萘普生缓解关节痛。^[1]
• Persistent arthralgia may benefit from physiotherapy, graded exercise and short courses of non-steroidal anti-inflammatory drugs, but evidence specific to Sindbis virus is limited持续性关节痛可从物理治疗、渐进性运动与短期非甾体抗炎药中获益，但针对辛德毕斯病毒的特异性证据有限。^[1]
• Corticosteroids and immunosuppressants are not routinely recommended because there is no controlled evidence that they alter the course of Pogosta disease不常规推荐糖皮质激素与免疫抑制剂，因为没有对照证据表明它们可改变波戈斯塔病的病程。^[1]
• Prevention relies on mosquito avoidance, including DEET or picaridin repellents, long sleeves, insecticide-treated nets and removal of standing water near dwellings预防依赖避免蚊虫叮咬，包括使用避蚊胺或派卡瑞丁驱蚊剂、穿长袖衣物、使用杀虫剂处理蚊帐以及清除住宅附近积水。^[1]
• No vaccine is licensed, although candidate vaccines have shown immunogenicity in preclinical and early clinical studies and remain a research priority目前没有获批疫苗，尽管候选疫苗在临床前与早期临床研究中显示免疫原性，仍是研究重点。^[8]
• The prognosis is good, with no reported deaths, but a minority of patients develop prolonged or chronic arthralgia that requires long-term follow-up预后良好，尚无死亡报告，但少数患者出现迁延性或慢性关节痛，需要长期随访。^[1]

Research and controversies

• The drivers of the roughly seven-year epidemic cycle are still debated, with hypotheses including avian herd immunity, mosquito abundance and climate variability约七年流行周期的驱动因素仍有争议，假说包括鸟类群体免疫、蚊虫丰度与气候变异。^[4]
• Spatial modelling in Finland has identified vector, host and environmental predictors of human infection risk, which may support targeted surveillance and public warnings芬兰的空间模型已识别出人类感染风险的媒介、宿主与环境预测因子，可支持针对性监测与公众预警。^[4]
• The low and transient viraemia limits molecular diagnosis, and improved antigen or antibody assays are needed to diagnose cases earlier and more reliably低而短暂的病毒血症限制了分子诊断，需要改进抗原或抗体检测以更早、更可靠地诊断病例。^[7]
• Climate change and land-use change may expand the range of the mosquito vectors and alter the timing of outbreaks in northern Europe气候变化与土地利用变化可能扩大蚊媒分布范围，并改变北欧暴发的时间格局。^[1]
• Vaccine development, antiviral screening and prospective cohorts for chronic arthralgia remain the main unmet research needs for this neglected arbovirus疫苗研发、抗病毒药物筛选与慢性关节痛的前瞻性队列，仍是这一被忽视虫媒病毒的主要未满足研究需求。^[8]

^{[3] [4] [2] [1] [7] [8] [6] [5]}