Pathogenesis and Clinical manifestations of Francisella tularensis

Pathogenesis ofFrancisella tularensis

• Francisella tularensisis carried by many species of wild rodents, rabbits, beavers.
• 人类通过吸入感染性气溶胶或摄入受污染的水，通过昆虫载体以及被自己吃过感染动物的食肉动物咬伤而被感染感染动物的尸体感染。
• Humans are infected by fewer than 50 organisms by either aerosol or cutaneous routes.
• F. tularensis亚种。tularensisis the most virulent for humans, with an infectious dose of less than 10 colony forming units.
• The pathogens invade the host either through microtrauma in the skin or through the mucosa.
• An ulcerous lesion develops at the portal of entry that also affects the local lymph nodes (ulceroglandular, glandular, or oculoglandular form).
• Through lymphogenous and hematogenous dissemination, the pathogens then spread to parenchymatous organs, in particular reticuloendothelial system (RES) such as the spleen and liver.
• F. tularensisis an intracellular pathogen that can survive in the cells of the reticuloendothelial system, where it resides after a bacteremic phase because the organism inhibits phagosome–lysosome fusion through secretion of proteins that facilitate bacterial escape from the phagosome and subsequent replication in the macrophage cytosol.
• The polysaccharide rich capsule ofF. tularensisis a necessary component for expression of full virulence, allowing the organism to avoid immediate destruction by polymorphonuclear neutrophils and is antiphagocytic in nature.
• The capsule protects the bacteria from complement-mediated killing during the bacteremia phase of disease.
• 与其他革兰氏阴性细菌产生的内毒素相比，该细菌还会产生内毒素活性较低。
• 一个strong, innate immune response with production of interferon-γ and tumor necrosis factor (TNF) is important for controlling bacterial replication in macrophages in the early phase of infection.
• 在疾病后期激活巨噬细胞以激活巨噬细胞以进行细胞内杀害所必需的特定T细胞免疫。然而，对于消除兼性细胞内病原体而言，体液免疫不太重要。

临床表现ofFrancisella tularensis

• 与之相关的疾病F.tularensis, is称为tUlaremia.
• 临床表现取决于传播方式，感染生物体的毒力，宿主的免疫状态以及从感染到诊断和治疗的时间长度。
• Disease caused byF.tularensisis subdivided into several forms based on the clinical presentation given as:

1. Ulceroglandular tularemia

• Ulceroglandular tularemia is the most common manifestation.
• The skin lesion, which starts as a painful papule at the site of the tick bite or direct inoculation of the organism into the skin.
• The papule then ulcerates and has a necrotic center and raised border.
• 通常也存在局部淋巴结病和菌血症。

2. Glandular tularemia

• It involves primarily swollen lymph nodes with no other localized symptoms

3. Oculoglandular tularemia

• 动眼菌血症是该疾病的一种专业形式，是眼睛直接污染的结果。
• .The organism can be introduced into the eyes, for example, by contaminated fingers or through exposure to water or aerosols.
• Affected patients have a painful conjunctivitis and regional lymphadenopathy (swollen cervical lymph nodes).

4. Pneumonictularemia

• 肺炎症状是由于吸入感染性气溶胶而引起的，并且与高发病率和死亡率有关。
• Patients present with atypical pneumonia and typically has systemic signs of sepsis.

5. Oropharyngeal tularemia

• It occurs following ingestion of contaminated undercooked meat.
• It is characterized by membranous pharyngitis with cervical lymphadenopathy

6. Typhoidal tularemia

• 临床表现包括伴有败血病的急性疾病。
• 死亡率是30%到60%。
• There is no ulcer or lymphadenopathy.

7. Gastrointestinaldisease

• 它发生在摄取F.tularensisand is not very common clinical form.