HIV 感染者中侵袭性非伤寒沙门氏菌引起全身细胞内感染：一种新兴的疾病发病机制。

Invasive non-typhoid salmonellae establish systemic intracellular infection in HIV-infected adults: an emerging disease pathogenesis.

机构信息

Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Liverpool, UK.

出版信息

Clin Infect Dis. 2010 Apr 1;50(7):953-62. doi: 10.1086/651080.

DOI:10.1086/651080

PMID:20180702

Abstract

BACKGROUND

Salmonellae are facultative intracellular pathogens. Non-typhoid salmonellae (NTS) cause self-limiting mucosal disease in immunocompetent adults but invasive, recurrent disease among human immunodeficiency virus (HIV)-infected adults in Africa. The importance of intracellular NTS infection in HIV is unknown.

METHODS

We performed quantitative pour-plate culture of blood samples obtained during febrile events among 495 Malawian adults on 871 occasions, and NTS were isolated at 158 events. Ninety-eight percent were HIV infected, with a median CD4 count of 67 cells/microL. Lysis of pour plates and gentamicin exclusion testing were used to investigate the presence of intracellular NTS in blood and bone marrow.

RESULTS

Total viable NTS counts in blood were low (1 colony-forming unit [CFU]/mL) but correlated independently with lower CD4 count and with IL-10 and IL-6 levels, especially at recurrence, suggesting failure to clear intracellular infection. Viable NTS load in blood and bone marrow were closely correlated at index events, but NTS were significantly concentrated in bone marrow, compared with blood samples, at recurrences (6 vs 1 CFU/mL), suggesting systemic tissue replication. Both lysis-pour-plating and gentamicin exclusion testing demonstrated intracellular infection with >1 CFU/cell in both blood and bone marrow specimens. Intracellular bacteria were demonstrated in bone marrow at both index and recurrent events, showing that this is an early and enduring feature of pathogenesis, but intracellular NTS were detected in blood only at index events, particularly in patients with a CD4 count <50 cells/microL. Intravascular NTS at recurrence may therefore reflect extracellular "overspill" from an intracellular sanctuary site, following failure of immunological control.

CONCLUSIONS

Invasive NTS have established a new and emerging pathogenesis in the context of HIV infection in Africa.

摘要

背景

沙门氏菌是兼性细胞内病原体。非伤寒沙门氏菌（NTS）在免疫功能正常的成年人中引起自限性黏膜疾病，但在非洲感染人类免疫缺陷病毒（HIV）的成年人中引起侵袭性、复发性疾病。细胞内 NTS 感染在 HIV 中的重要性尚不清楚。

方法

我们对 495 名马拉维成年人在 871 次发热事件中采集的血液样本进行了定量倾注平板培养，并在 158 次事件中分离出 NTS。98%的人感染了 HIV，中位 CD4 计数为 67 个细胞/μL。使用溶菌倾注平板和庆大霉素排除试验来研究血液和骨髓中是否存在细胞内 NTS。

结果

血液中总活 NTS 计数较低（1 个菌落形成单位 [CFU]/mL），但与较低的 CD4 计数以及 IL-10 和 IL-6 水平独立相关，尤其是在复发时，表明未能清除细胞内感染。指数事件时血液和骨髓中的活 NTS 负荷密切相关，但 NTS 在复发时明显集中在骨髓中，而不是血液样本中（6 与 1 CFU/mL），表明全身组织复制。溶菌倾注平板和庆大霉素排除试验均证明血液和骨髓标本中存在>1 CFU/细胞的细胞内感染。在指数和复发事件中均在骨髓中观察到细胞内细菌，表明这是发病机制的早期和持久特征，但仅在指数事件中在血液中检测到细胞内 NTS，尤其是在 CD4 计数<50 个细胞/μL 的患者中。因此，复发时的血管内 NTS 可能反映了免疫控制失败后，从细胞内避难所部位的细胞外“溢出”。