Related Experiment Videos
Studies of the coagulation and complement systems during experimental Rocky Mountain spotted fever in rhesus monkeys
Abstract:
We studied the coagulation and complement systems during Rocky Mountain spotted fever in Macaca mulatta experimentally infected with Rickettsia rickettsii. Ninety-one percent of monkeys infected intravenously with a high dose (10(6) plaque-forming units [pfu]) and 56% of monkeys infected with low doses (10(-1)-10(2) pfu) of R. rickettsii died after two to four days of illness. With the onset of fever and rickettsemia, animals developed hyperfibrinogenemia, mild thrombocytopenia, prolonged prothrombin and activated thromboplastin times, and increased serum fibrin/fibrinogen degradation products (FDP). Rickettsemia, thrombocytopenia, and FDP were greater in fatally ill monkeys than in survivors. Hemolytic titers of the second and third components of complement were not depressed except in a single surviving monkey that developed peripheral gangrenous ecchymoses at a time when both rickettsemia and agglutinating antibody were present. Thus, although activation and consumption of complement may occur during Rocky Mountain spotted fever, the hemostatic disturbances in fulminant infections seem to be a direct effect of the infectious vasculitis.
Insights
Rocky Mountain spotted fever causes severe coagulation issues in monkeys. Hemostatic disturbances in severe cases appear to be a direct result of infectious vasculitis, not complement system activation.
Area of Science:
- Infectious Diseases
- Hematology
- Immunology
Background:
- Rocky Mountain spotted fever (RMSF) is a severe tick-borne illness caused by Rickettsia rickettsii.
- Coagulation and complement systems play crucial roles in host defense and disease pathogenesis.
- Understanding these systems during RMSF is vital for developing effective treatments.
Purpose of the Study:
- To investigate the role of coagulation and complement systems in Macaca mulatta experimentally infected with Rickettsia rickettsii.
- To determine the impact of R. rickettsii infection on hemostasis and complement activity.
- To differentiate the effects of infectious vasculitis from complement activation in RMSF pathogenesis.
Main Methods:
- Experimental infection of Macaca mulatta with varying doses of Rickettsia rickettsii.
- Monitoring of clinical signs, including fever and rickettsemia.
- Assessment of coagulation parameters: fibrinogen, prothrombin time, activated thromboplastin time, and fibrin/fibrinogen degradation products (FDP).
- Evaluation of complement system activity through hemolytic titers of complement components C2 and C3.
Main Results:
- High mortality rates observed in infected monkeys, particularly at high R. rickettsii doses.
- Development of hyperfibrinogenemia, mild thrombocytopenia, prolonged clotting times, and increased FDP during infection.
- More pronounced rickettsemia, thrombocytopenia, and FDP levels in fatally ill monkeys compared to survivors.
- Complement component titers were generally not depressed, except in one survivor with gangrenous ecchymoses.
Conclusions:
- Hemostatic disturbances in fulminant Rocky Mountain spotted fever are primarily attributed to infectious vasculitis caused by R. rickettsii.
- While complement activation may occur, it does not appear to be the main driver of coagulation abnormalities in severe RMSF.
- The study highlights the critical role of direct vascular damage in the pathophysiology of severe RMSF.