Analysis of risk factors for fatal Rocky Mountain Spotted Fever: evidence for superiority of tetracyclines for therapy. (17/166)

Epidemiologic and clinical characteristics of fatal and nonfatal cases of Rocky Mountain spotted fever (RMSF) were compared to identify risk factors for death caused by this disease. Confirmed and probable RMSF cases reported through US national surveillance for 1981-1998 were analyzed. Among 6388 RMSF patients, 213 died (annual case-fatality rate, 3.3%; range, 4.9% in 1982 to 1.1% in 1996). Use of tetracycline-class antibiotics for treatment of RMSF increased significantly in the 1990s, compared with use in the 1980s. Older patients, patients treated with chloramphenicol only, patients for whom tetracycline antibiotics were not the primary therapy, and patients for whom treatment was delayed > or =5 days after the onset of symptoms were at higher risk for death. Although the case-fatality rate was lower in the 1990s than in the 1980s, risk factors for fatal RMSF were similar. Despite the availability of effective antibiotics, RMSF-related deaths continue to occur because of delayed diagnosis and failure to use appropriate therapy.  (+info)

Indirect hemagglutination test for detection of antibody to Rickettsia rickettsii in sera from humans and common laboratory animals. (18/166)

Antibody production in humans and three species of laboratory animals infected with Rickettsia rickettsii was determined with the indirect hemagglutination test. Rabbits, guinea pigs, and mice were inoculated with R. rickettsii and bled at intervals. Antibody which agglutinated both fresh and glutaraldehyde-fixed sheep erythrocytes sensitized with antigen prepared either from purified rickettsiae or from infected yolk sacs was found in rabbit sera at all intervals tested (10 to 59 days postinfection). Antibody which agglutinated fresh but not glutaraldehyde-fixed erythrocytes sensitized with either of the above antigens was detected in guinea pig sera obtained 7, 14, and 28 days postinfection. Antibody was found in mice inoculated with 5.6 x 10(6) plaque-forming units of R. rickettsii but not in mice given 5.6 x 10(2) plaque-forming units. Peak indirect hemagglutination titers occurred in nonvaccinated human Rocky Mountain spotted fever patients about 3 weeks after onset of illness, and antibody was still detectable after 1 year. Both human immunoglobulin G and human immunoglobulin M antibodies agglutinated sensitized cells, but immunoglobulin M antibodies apparently were more efficient. The indirect hemagglutination test is useful for the titration of human, rabbit, guinea pig, and mouse antibodies when the appropriate erythrocytes are used.  (+info)

Evaluation of a killed Rocky Mountain spotted fever vaccine in cynomolgus monkeys. (19/166)

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.  (+info)

Short report: concurrent Rocky Mountain spotted fever in a dog and its owner. (20/166)

A sequential occurrence of Rocky Mountain spotted fever (RMSF) in a dog and its owner is described. Diagnosis of RMSF in the animal guided subsequent testing for and diagnosis of the same disease in the human patient. Previous reports of concurrent RMSF in dogs and their owners are reviewed, and the epidemiologic significance of this occurrence is discussed.  (+info)

Evidence of spotted fever group rickettsiae in state of Rio de Janeiro, Brazil. (21/166)

Ticks were obtained from dogs from February to September of 1999 at weekly intervals, in the County of Pirai, State of Rio de Janeiro. Four hundred seventy four ixodids were taxonomically identified, 103 Amblyomma cajennense, seven Amblyomma ovale, 209 Rhipicephalus sanguineus, and 155 Amblyomma sp. An hemolymph test associated with Giemsa's stain revealed two specimens in 163 ticks tested (R. sanguineus and Amblyomma sp), containing rickettsia-like organisms. Direct immunofluorescence verified the presence of spotted fever group rickettsia in one specimen of R. sanguineus. Considering the limited information on rickettsiosis in Brazil, principally in relation to the vectors involved in perpetuating it in foci, these preliminary results give us an idea on the importance of infection in ticks, allowing to expand our knowledge on this zoonosis.  (+info)

Passive surveillance as an instrument to identify risk factors for fatal Rocky Mountain spotted fever: is there more to learn? (22/166)

National surveillance for Rocky Mountain spotted fever (RMSF) dates from 1920; however, the collection of detailed epidemiologic, clinical, and laboratory data on RMSF by using case report forms began in 1970. Despite issues with compliance and changes in case definitions, surveillance data have permitted researchers to assess risk factors for fatal RMSF quantitatively. Factors consistently associated with increased risk of death include severity of disease, older age, lack of tick bite, absence of classic symptoms, delay in diagnosis and initiation of appropriate antibiotic treatment, and treatment with chloramphenicol only. In several studies, treatment with a tetracycline has been shown to be protective. The continuation of current passive surveillance activities may allow researchers to refine their estimates of risk but is unlikely to produce novel results. Modified surveillance activities could focus on evaluating the risk for fatal RMSF among special populations, monitoring appropriate antibiotic use, and assessing new diagnostic tests.  (+info)

Assessing the magnitude of fatal Rocky Mountain spotted fever in the United States: comparison of two national data sources. (23/166)

To assess the magnitude of fatal Rocky Mountain spotted fever (RMSF) and to evaluate the completeness of national surveillance for this occurrence from 1983 through 1998, two independent sources of RMSF mortality data were analyzed using a capture-recapture method. Two hundred twenty-four deaths reported through RMSF case report forms (CRFs) were compared with 304 RMSF-associated deaths recorded in the United States multiple cause-of-death (MCD) database. Demographic, geographic, seasonal, and temporal characteristics of decedents were remarkably similar between sources. Median annual deaths ascertained from CRF and MCD data sources were 11 (range = 5-35) and 18 (range = 5-39), respectively. Decedents were matched between sources by year, state, age, sex, race, and month-of-death; 111 deaths were matched to both sources, and percent concordance between CRFs and MCD data during the 16-year study period was 27% (range = 7-45%). An estimated 612 RMSF-associated deaths occurred during the study period (median = 37 per year, range = 16-64), suggesting that approximately 400 fatal cases of RMSF went unreported to national surveillance during the period 1983-1998, for an estimated completeness of CRF reporting of 36%.  (+info)

Nuclear factor kappa B protects against host cell apoptosis during Rickettsia rickettsii infection by inhibiting activation of apical and effector caspases and maintaining mitochondrial integrity. (24/166)

Apoptotic host cell death is a critical determinant in the progression of microbial infections and outcome of resultant diseases. The potentially fatal human infection caused by Rickettsia rickettsii, the etiologic agent of Rocky Mountain spotted fever, involves the vascular endothelium of various organ systems of the host. Earlier studies have shown that survival of endothelial cells (EC) during this infection depends on their ability to activate the transcription factor nuclear factor kappa B (NF-kappa B). Here, we investigated the involvement of caspase cascades and associated signaling pathways in regulation of host cell apoptosis by NF-kappa B. Infection of cultured human EC with R. rickettsii with simultaneous inhibition of NF-kappa B induced the activation of apical caspases 8 and 9 and also the executioner enzyme, caspase 3, whereas infection alone had no significant effect. Inhibition of either caspase-8 or caspase-9 with specific cell-permeating peptide inhibitors caused a significant decline in the extent of apoptosis, confirming their importance. The peak caspase-3 activity occurred at 12 h postinfection and led to cleavage of poly(ADP-ribose) polymerase, followed by DNA fragmentation and apoptosis. However, the activities of caspases 6 and 7, other important downstream executioners, remained unchanged. Caspase-9 activation was mediated through the mitochondrial pathway of apoptosis, as evidenced by loss of transmembrane potential and cytoplasmic release of cytochrome c. These findings suggest that activation of NF-kappa B is required for maintenance of mitochondrial integrity of host cells and protection against infection-induced apoptotic death by preventing activation of caspase-9- and caspase-8-mediated pathways. Targeted inhibition of NF-kappa B may therefore be exploited to enhance the clearance of infections with R. rickettsii and other intracellular pathogens with similar survival strategies.  (+info)