Centers for Disease Control and Prevention, Dengue Branch, San Juan, Puerto Rico, USA.
US Public Health Service, Silver Springs, Maryland, USA.
Clin Infect Dis. 2021 Jul 15;73(2):e345-e354. doi: 10.1093/cid/ciaa837.
Death in patients with chikungunya is rare and has been associated with encephalitis, hemorrhage, and septic shock. We describe clinical, histologic, and immunohistochemical findings in individuals who died following chikungunya virus (CHIKV) infection.
We identified individuals who died in Puerto Rico during 2014 following an acute illness and had CHIKV RNA detected by reverse transcriptase-polymerase chain reaction in a pre- or postmortem blood or tissue specimen. We performed histopathology and immunohistochemistry (IHC) for CHIKV antigen on tissue specimens and collected medical data via record review and family interviews.
Thirty CHIKV-infected fatal cases were identified (0.8/100 000 population). The median age was 61 years (range: 6 days-86 years), and 19 (63%) were male. Death occurred a median of 4 days (range: 1-29) after illness onset. Nearly all (93%) had at least 1 comorbidity, most frequently hypertension, diabetes, or obesity. Nine had severe comorbidities (eg, chronic heart or kidney disease, sickle cell anemia) or coinfection (eg, leptospirosis). Among 24 fatal cases with tissue specimens, 11 (46%) were positive by IHC. CHIKV antigen was most frequently detected in mesenchymal tissues and mononuclear cells including tissue macrophages, blood mononuclear cells, splenic follicular dendritic cells, and Kupffer cells. Common histopathologic findings were intra-alveolar hemorrhage and edema in the lung, chronic or acute tenosynovitis, and increased immunoblasts in the spleen. CHIKV infection likely caused fatal septic shock in 2 patients.
Evaluation of tissue specimens provided insights into the pathogenesis of CHIKV, which may rarely result in septic shock and other severe manifestations.
基孔肯雅热患者死亡较为罕见,其与脑炎、出血和感染性休克相关。我们描述了基孔肯雅病毒(CHIKV)感染后死亡患者的临床、组织学和免疫组织化学表现。
我们鉴定了 2014 年波多黎各在急性疾病后死亡且通过逆转录-聚合酶链反应在生前或死后血液或组织标本中检测到 CHIKV RNA 的个体。我们对组织标本进行组织病理学和免疫组织化学(IHC)检查以检测 CHIKV 抗原,并通过病历回顾和家属访谈收集医疗数据。
确定了 30 例 CHIKV 感染致死病例(每 10 万人中有 0.8 例)。中位年龄为 61 岁(范围:6 天-86 岁),19 例(63%)为男性。死亡发生于疾病发作后中位时间 4 天(范围:1-29 天)。几乎所有(93%)患者至少合并 1 种合并症,最常见的为高血压、糖尿病或肥胖症。9 例患者有严重的合并症(如慢性心脏或肾脏疾病、镰状细胞贫血)或合并感染(如钩端螺旋体病)。在 24 例有组织标本的致死病例中,11 例(46%)通过 IHC 检测为阳性。CHIKV 抗原最常检测到间质组织和单核细胞中,包括组织巨噬细胞、血液单核细胞、脾滤泡树突状细胞和枯否细胞。常见的组织病理学表现为肺内肺泡出血和水肿、慢性或急性腱鞘炎以及脾脏中免疫母细胞增多。CHIKV 感染可能导致 2 例患者发生致命性感染性休克。
组织标本评估提供了 CHIKV 发病机制的见解,其可能罕见导致感染性休克和其他严重表现。