当前位置: X-MOL 学术Mycoses › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Landmark Clinical Observations and Immunopathogenesis Pathways Linked to HIV and Cryptococcus Fatal Central Nervous System Co‐infection
Mycoses ( IF 4.9 ) Pub Date : 2020-06-19 , DOI: 10.1111/myc.13122
Samuel Okurut 1, 2 , David R Boulware 3 , Joseph Olobo 4 , David B Meya 1, 3, 5
Affiliation  

Cryptococcal meningitis remains one of the leading causes of death among HIV‐infected adults in the fourth decade of HIV era in sub‐Saharan Africa, contributing to 10%–20% of global HIV‐related deaths. Despite widespread use and early induction of ART among HIV‐infected adults, incidence of cryptococcosis remains significant in those with advanced HIV disease. Cryptococcus species that causes fatal infection follows systemic spread from initial environmental acquired infection in lungs to antigenaemia and fungaemia in circulation prior to establishment of often fatal disease, cryptococcal meningitis in the CNS. Cryptococcus person‐to‐person transmission is uncommon, and deaths related to blood infection without CNS involvement are rare. Keen to the persistent high mortality associated with HIV‐cryptococcal meningitis, seizures are common among a third of the patients, altered mental status is frequent, anaemia is prevalent with ensuing brain hypoxia and at autopsy, brain fibrosis and infarction are evident. In addition, fungal burden is 3‐to‐4‐fold higher in those with seizures. And high immune activation together with exacerbated inflammation and elevated PD‐1/PD‐L immune checkpoint expression is immunomodulated phenotypes elevated in CSF relative to blood. Lastly, though multiple Cryptococcus species cause disease in this setting, observations are mostly generalised to cryptococcal infection/meningitis or regional dominant species (C neoformans or gattii complex) that may limit our understanding of interspecies differences in infection, progression, treatment or recovery outcome. Together, these factors and underlying mechanisms are hypotheses generating for research to find targets to prevent infection or adequate therapy to prevent persistent high mortality with current optimal therapy.

中文翻译:

与 HIV 和隐球菌致命中枢神经系统合并感染相关的标志性临床观察和免疫发病机制

隐球菌性脑膜炎仍然是撒哈拉以南非洲 HIV 时代第四个十年中 HIV 感染成人死亡的主要原因之一,占全球 HIV 相关死亡的 10%–20%。尽管在 HIV 感染的成年人中广泛使用和早期诱导 ART,但在晚期 HIV 疾病患者中,隐球菌病的发病率仍然很高。导致致命感染的隐球菌物种在从肺部初始环境获得性感染到循环中的抗原血症和真菌血症之后进行全身性传播,然后在中枢神经系统中形成通常致命的疾病,即隐球菌性脑膜炎。隐球菌人与人之间的传播并不常见,与血液感染相关而没有中枢神经系统受累的死亡也很少见。热衷于与 HIV 隐球菌脑膜炎相关的持续高死亡率,三分之一的患者经常癫痫发作,精神状态经常改变,贫血很普遍,随后脑缺氧,尸检时,脑纤维化和梗塞很明显。此外,癫痫患者的真菌负担要高出 3 到 4 倍。高免疫激活连同加剧的炎症和升高的 PD-1/PD-L 免疫检查点表达是脑脊液中相对于血液升高的免疫调节表型。最后,虽然在这种情况下多种隐球菌引起疾病,但观察结果大多概括为隐球菌感染/脑膜炎或区域优势物种(新型隐球菌或 gattii 复合体),这可能会限制我们对感染、进展、治疗或恢复结果的种间差异的理解。一起,
更新日期:2020-06-19
down
wechat
bug