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 also results in loss of intravascular volume 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.