Typhus pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]
Overview
Pathophysiology
Transmission
- Rickettsial agents are usually not transmissible directly from person to person except by blood transfusion or organ transplantation, although sexual and placental transmission has been proposed for Coxiella.
- Transmission generally occurs via an infected arthropod vector or through exposure to an infected animal reservoir host.
- Inhaling or inoculating conjunctiva with infectious material also causes infection.
| Type of Infection | Spread |
| Epidemic typhus | Body louse |
| Trench fever | Body louse |
| Murine typhus | Flea infested rats |
| Cat flea rickettsioses | Flea infested dogs and cats |
| Scrub typhus | Mites |
| Tick borne rickettsiosis | Ticks |
| Rickettsialpox | Mites |
| Anaplasmosis | Ixodes tick |
| Ehrlichiosis | Lone star tick |
| Q fever | Infected veterinary animals |
| Cat scratch disease | Infected cats |
| Oroya fever | Sandflies |
Incubation
- Incubation period of Typhus fever varies from one to two weeks.
Dissemination
- Following transmission, rickettsia are ingested by macrophages and polymorphonuclear cells. On ingestion, they replicate intracellularly inside the lysed cells and disseminate systemically.
Pathogensis
- The major pathology is caused by a vasculitis and its complications.
- On transmission, Rickettsia is actively phagocytosed by the endothelial cells of the small venous, arterial, and capillary vessels.
- It is followed by systemic hematogenous spread resulting in multiple localizing vasculitis.
- This process may cause result in occlusion of blood vessels and initiates inflammatory response (aggregation of leukocytes, macrophages, and platelets) resulting in small nodules.
- Occlusion of supplying blood vessels may cause gangrene of the distal portions of the extremities, nose, ear lobes, and genitalia.
- This vasculitic process causes destruction of the endothelial cells and leakage of the blood leading to volume depletion with subsequent hypovolemia and decreased tissue perfusion and, possibly, organ failure.
Immune response
- Higher-affinity leucocyte integrins (LFA-1 and Mac-1) binding to members of the immunoglobulin (Ig) mediate initial leucocyte contact with EC by capturing them from the bloodstream
- Cytokines like tumour necrosis factor-alpha, interleukin (IL)-1beta and IL-6 up-regulate cellular adhesion molecules (CAMs) on the surface of host leucocytes and endothelial cells (EC)
- CAMs help in leucocyte transmigration across the endothelium.[1]
- This is followed by characteristic rolling and firm tethering to the endothelium and enabling subsequent leucocyte diapedesis.
- Tumor necrosis factor α (TNF-α) produce on activation of cell mediated immunity, stimulates T lymphocytes and macrophages, which help in eliminating intracellular rickettsia. Virulent rickettsia tend to suppress the activity of tumor necrosis factor α (TNF-α) and IFN-gamma.
- Cytokines such as interleukin (IL) 12 promote production of Interferon γ (IFN-γ) responses. IFN-γ, which drives TH1-type responses and stimulates macrophage activation. Cytokines, which include , IL-6, IL-4and IL-10, down-regulate the protective response.
Genetics
There is no known genetic association to Typhus fever.
References
- ↑ Lasky LA (1995). "Selectin-carbohydrate interactions and the initiation of the inflammatory response". Annu. Rev. Biochem. 64: 113–39. doi:10.1146/annurev.bi.64.070195.000553. PMID 7574477.