Hemostatic changes in Rocky Mountain spotted fever and Mediterranean spotted fever.

Rocky Mountain spotted fever and Mediterranean spotted fever are rickettsial infections primarily of endothelial cells that normally have a potent anticoagulant function. As a result of endothelial cell infection and injury, the hemostatic system is perturbed and shows changes that vary widely from a minor reduction in the platelet count (frequently) to severe coagulopathies, such as deep venous thrombosis and disseminated intravascular coagulation (rarely). Changes favoring a hypercoagulable state include endothelial injury and release of procoagulant components, activation of the coagulation cascade with thrombin generation, platelet activation, increased antifibrinolytic factors, consumption of natural anticoagulants, and possibly high levels of coagulation-promoting cytokines. Yet, most studies have been performed on endothelial cell cultures that provide nonphysiologic, reductionistic, experimental conditions. The lack of flow, platelets, and WBCs makes these experiments far from simulating the response of endothelial cells in the human body. Coagulopathies and thrombotic events should be considered as potential complications of severe Rocky Mountain spotted fever and Mediterranean spotted fever.     

Encephalitis associated with Rocky Mountain spotted fever

We present a fatal case of Rocky Mountain spotted fever. Despite the presence of clinical and laboratory evidence suggesting widespread vasculitis, pathologic lesions were found only in the central nervous system.     

Prophylactic treatment of Rocky Mountain spotted fever.

Prophylactic treatment of Rocky Mountain spotted fever with a single dose of oxytetracycline was investigated in guinea pigs. Disease was prevented when treatment was administered shortly before expected onset. Relapses occurred when treatment preceded expected onset by 48 h or more.     

Antibody response to Rocky Mountain spotted fever.

Various techniques were compared to determine the most sensitive method for detection of rocky Mountain spotted fever antibody. A radiometabolic technique for detection of Rocky Mountain spotted fever antibody is also described. In infected monkeys, the fluorescent antibody technique yielded the earliest evidence of seroconversion; with some monkeys the microagglutination procedure was equally effective. The fluorescent antibody and microagglutination measurements showed higher titers than those for complement fixation, Weil-Felix, or the radiometabolic techniques.     

Rocky Mountain spotted fever vaccine in an animal model.

Formalin-killed, purified Rickettsia rickettsii vaccine was evaluated in a guinea pig model of R. rickettsii infection. Vaccinated guinea pigs were partially protected by the vaccine when challenged with virulent, viable rickettsiae. Greater protection was observed when higher doses of vaccine were given and when frequent booster injections were administered. Stimulation of cell-mediated immunity to the vaccine antigens was variable and also appeared to be achieved more reproducibly with booster vaccinations. Serum antibody was elicited by high doses of vaccine and by booster vaccinations. The presence of serum antibody was useful in predicting immunity to challenge with R. rickettsii.     

A focus of Rocky Mountain spotted fever within New York City

In the spring and summer of 1987, four persons acquired Rocky Mountain spotted fever within New York City, an area in which the disease had not previously been known to be endemic. Three of the four patients were residents of the Soundview area of the Bronx. All diagnoses were confirmed by indirect fluorescent-antibody tests. Environmental investigation revealed that the tick vector for Rickettsia rickettsii, Dermacentor variabilis, was present in a local park. Of the 66 specimens of D. variabilis collected, 5 (8 percent) were positive for rickettsiae from the spotted fever group. Of an additional 96 specimens of D. variabilis, 5 (5 percent) were found positive for rickettsiae by a more specific monoclonal antibody assay. Eight additional New York City parks in all five boroughs were searched for ticks. D. variabilis was found in only one other park; of the 147 ticks collected there, none were positive for rickettsiae. These findings emphasize the focal nature of Rocky Mountain spotted fever and the need to consider that disease in the differential diagnosis of any obscure acute febrile illness, even in the absence of a history of travel to known endemic areas.     

New assay of protective activity of Rocky Mountain spotted fever vaccines.

Areas under the fever curves of guinea pigs inoculated with Rocky Mountain spotted fever vaccine over a restricted dose range and infected with a standardized dose of Rickettsia rickettsii varied linearly with log10 dose of vaccine. A calculator was programmed to plot fever curves and calculate the vaccine dose that reduced the fever of infected animals by 50%.     

Laboratory-acquired Rocky Mountain spotted fever. The hazard of aerosol transmission.

Nine patients with laboratory-acquired Rocky Mountain spotted fever were seen during the period 1971 to 1976. Investigation of each case revealed either definite or probable exposure to an aerosol containing infectious rickettsiae; in no case was there evidence of parenteral exposure either by accidental self-inoculation or by tick bite. These illnesses are believed to represent infection acquired via the respiratory route. This report emphasizes the aerosol hazard of Rickettsia rickettsii in the laboratory and discusses the possibility of respiratory transmission of Rocky Mountain spotted fever in nature. The illness occurred only in personnel who had received either no vaccination or the primary series of the commercial (Lederie) vaccine against this infection. Other personnel who had received the primary series with multiple booster vaccinations demonstrated increased immunity as measured by humoral antibody titers and rickettsial antigen-induced lymphocyte transformation; no cases of clinical disease developed in these multiply-vaccinated personnel.     

Rocky Mountain spotted fever. Gastrointestinal and pancreatic lesions and rickettsial infection

Recent clinical studies have shown a high incidence of nausea, vomiting, diarrhea, and abdominal pain in Rocky Mountain spotted fever (RMSF), and case reports have documented rickettsial infection and vascular injury in the small intestine, appendix, and gallbladder. To determine the incidence and distribution of Rickettsia rickettsii and rickettsial lesions that might be the basis for these clinical manifestations of RMSF, tissues that were available from the stomach, small intestine, colon, and pancreas in fatal cases of RMSF were examined. Lesions were identified in pancreatic tissue in 91% of cases and in tissue obtained from the stomach, small intestine, and colon in all cases. Most tissues were judged to be only moderately injured. Organisms of R rickettsii were demonstrated by immunofluorescence in 14 (50%) of 28 cases and, when identified, correlated topographically with the location of vascular injury. These observations support the concept of rickettsial vascular injury of the gastrointestinal (GI) tract and pancreas leading to GI signs and symptoms in RMSF.     

Rocky Mountain spotted fever: a disease in need of microbiological concern.

Rocky Mountain spotted fever, a life-threatening tick-transmitted infection, is the most prevalent rickettsiosis in the United States. This zoonosis is firmly entrenched in the tick host, which maintains the rickettsiae in nature by transovarian transmission. Although the incidence of disease fluctuates in various regions and nationwide, the problems of a deceptively difficult clinical diagnosis and little microbiologic diagnostic effort persist. Many empiric antibiotic regimens lack antirickettsial activity. There is neither an effective vaccine nor a generally available assay that is diagnostic during the early stages of illness, when treatment is most effective. Microbiology laboratories that offer only the archaic retrospective Weil-Felix serologic tests should review the needs of their patients. Research microbiologists who tackle these challenging organisms have an array of questions to address regarding rickettsial surface composition, structure-function analysis, and pathogenic and immune mechanisms, as well as laboratory diagnosis.     

Preparation of Rocky Mountain spotted fever vaccine suitable for human immunization.

Rocky Mountain spotted fever vaccine was produced from rickettsiae grown in chicken embryo cells in roller bottle cultures. The rickettsiae were concentrated and purified by passage through a sucrose gradient and inactivated with formalin. This vaccine satisfactorily passed preinactivation and final container testing and is believed to be superior to the presently available yolk sac vaccine.     

Evaluation of a killed Rocky Mountain spotted fever vaccine in cynomolgus monkeys.

A nonhuman primate model of Rocky Mountain spotted fever infection was developed in cynomolgus monkeys (Macaca fascicularis) infected by the subcutaneous route or by aerosol. Clinical responses, hematology and serum chemistry values, and pathological findings were similar to those found in humans ill with Rocky Mountain spotted fever. The clinical model was then used to test the efficacy of a killed Rocky Mountain spotted fever vaccine grown in chicken embryo cells. Monkeys were immunized with varying dilutions of the vaccine with a two-dose schedule and then challenged at 2 months with virulent Rickettsia rickettsii by the subcutaneous route or by aerosol. The undiluted vaccine totally protected monkeys against both challenges, even at extremely high doses.