Seroreactivity for spotted fever rickettsiae and co-infections with other tick-borne agents among habitants in central and southern Sweden.

Patients seeking medical care with erythema migrans or flu-like symptoms after suspected or observed tick bite in the southeast of Sweden and previously investigated for Borrelia spp. and/or Anaplasma sp. were retrospectively examined for serological evidence of rickettsial infection (Study 1). Twenty of 206 patients had IgG and/or IgM antibodies to Rickettsia spp. equal to or higher than the cut-off titre of 1:64. Seven of these 20 patients showed seroconversion indicative of recent or current infection and 13 patients had titres compatible with past infection, of which five patients were judged as probable infection. Of 19 patients with medical records, 11 were positive for Borrelia spp. as well, and for Anaplasma sp., one was judged as positive. Five of the 19 patients had antibodies against all three pathogens. Erythema migrans or rash was observed at all combinations of seroreactivity, with symptoms including fever, muscle pain, headache and respiratory problems. The results were compared by screening an additional 159 patients (Study 2) primarily sampled for the analysis of Borrelia spp. or Mycoplasma pneumoniae. Sixteen of these patients were seroreactive for Rickettsia spp., of which five were judged as recent or current infection. Symptoms of arthritis, fever, cough and rash were predominant. In 80 blood donors without clinical symptoms, approximately 1 % were seroreactive for Rickettsia spp., interpreted as past infection. The study shows that both single and co-infections do occur, which illustrate the complexity in the clinical picture and a need for further studies to fully understand how these patients should best be treated.

New insight into immunity and immunopathology of Rickettsial diseases.

Human rickettsial diseases comprise a variety of clinical entities caused by microorganisms belonging to the genera Rickettsia, Orientia, Ehrlichia, and Anaplasma. These microorganisms are characterized by a strictly intracellular location which has, for long, impaired their detailed study. In this paper, the critical steps taken by these microorganisms to play their pathogenic roles are discussed in detail on the basis of recent advances in our understanding of molecular Rickettsia-host interactions, preferential target cells, virulence mechanisms, three-dimensional structures of bacteria effector proteins, upstream signalling pathways and signal transduction systems, and modulation of gene expression. The roles of innate and adaptive immune responses are discussed, and potential new targets for therapies to block host-pathogen interactions and pathogen virulence mechanisms are considered.

Serological and blood culture investigations of Nepalese fever patients.

Serological testing of paired (i.e. admission and convalescent) sera from 103 fever patients in Kathmandu, Nepal, was performed to estimate the prevalence rates of scrub typhus, murine typhus, Leptospira and dengue virus antibodies and to determine their role in the cause of active infections. Blood cultures from 15 patients grew Salmonella enterica serovar Typhi, 8 grew S. Paratyphi A and 6 grew other bacteria. Diagnostic antibody levels were detected against murine typhus (27/103; 26%), scrub typhus (23/103; 22%), Leptospira (10/103; 10%) and dengue virus (8/103; 8%). Nineteen patients (18%) had diagnostically raised antibodies to more than one infectious agent. Seven S. Typhi (7/15; 47%) and two S. Paratyphi A (2/8; 25%) patients had significant scrub typhus, murine typhus, Leptospira or dengue virus IgM antibody titres. This study confirms the presence of leptospiral, rickettsial and dengue infections in Kathmandu as well as evidence for mixed infections with S. Typhi and Orientia tsutsugamushi or Rickettsia typhi. These infections should be kept in mind when considering the differential diagnoses of fever and empirical treatment options in Nepal. Many patients demonstrated static IgM antibody results between paired serum collections, suggesting recent rather than acutely active infections.

Serologic evidence of infection with ehrlichiae and spotted fever group rickettsiae among residents of Gag Island, Indonesia.

The causative agents of scrub and murine typhus are considered endemic to Indonesia. However, the presence of spotted fever group rickettsiae and ehrlichiae have not been previously described in this country. During an investigation of arthropod-borne diseases on Gag Island, located northwest of the island of New Guinea in eastern Indonesia, the prevalence of antibody to the etiologic agents of monocytic ehrlichiosis, spotted fever rickettsiosis, and scrub and murine typhus were determined. Analysis of 55 blood samples from residents of Gag Island showed seroreactivity to antigen preparations of Ehrlichia chaffeensis (7 of 48, 14.6%), two spotted fever group rickettsiae: Rickettsia rickettsii (5 of 48, 10.4%) and R. conorii (10 of 49, 20.4%), Orientia tsutsugamushi (5 of 53, 9.4%), and R. typhi (1 of 48, 2.1% [by an indirect immunofluorescence assay] and 1 of 50, 2.0% [by an enzyme-linked immunosorbent assay]). These results show serologic evidence of infection with ehrlichiae and spotted fever group rickettsiae for the first time in Indonesia in a location where the prevalence of antibody to O. tsutsugamushi and R. typhi was lower.

Serologic evidence of respiratory and rickettsial infections among Somali refugees.

Somali refugees living in a camp located in Djibouti were studied in October 1991 and May 1992. The refugees had been living at the camp for about two years. The median age of volunteers was 25 years, of whom 69% were female. Paired sera obtained seven months apart were evaluated by complement fixation, microimmunofluorescence, indirect fluorescent antibody, streptococcal antibody, and enzyme-linked immunosorbent assay techniques for evidence of pathogen infection. Fifty-two percent, 31.3%, 8.0%, 5.9%, and 25.4% of the volunteers had serologic evidence for pre-enrollment infection with Chlamydia pneumoniae, Mycoplasma pneumoniae, Rickettsia typhi, R. conorii, and Coxiella burnetti, respectively. Similarly, 43.5%, 5.2%, 6.1%, 10.7%, 15.8%, and 11.9% of the volunteers studied had serologic evidence for new infection with Streptococcus pyogenes, C. pneumoniae, M. pneumoniae, R. typhi, R. conorii, and Cox. burnetii, respectively. These data suggest that the studied pathogens may be endemic in displaced populations living in the Horn of Africa.

Epidemiologic observations on infection with Rochalimaea species among cats living in Baltimore, Md.

Cats from several sources in Baltimore, Md, were tested for seropositivity to Rochalimaea henselae and R quintana. Co-infection with Toxoplasma gondii or feline immunodeficiency virus was assessed as a risk factor for infection with Rochalimaea spp. Of 592 cats tested, 87 (14.7%) were seropositive for one or both Rochalimaea spp, although titers to R henselae were significantly higher than those to R quintana. Prevalence of seropositivity increased significantly with cat age and weight and was associated with seropositivity to T gondii but was not associated with gender. Prevalence of seropositivity was similar (12.5 to 14.4%) among groups of cats with some history of human contact but was higher among feral cats (44.4%). Whether cats are reservoirs or mechanical vectors of Rochalimaea spp that can cause diseases in people is still uncertain, but these findings indicated widespread infection of cats and suggested possible modes of transmission for Rochalimaea spp among cats.

Relative chemokine and adhesion molecule expression in Mediterranean spotted fever and African tick bite fever.

OBJECTIVES: Mediterranean spotted fever (MSF) caused by Rickettsia conorii (R. conorii) is a potential lethal disease while African tick bite fever (ATBF) caused by Rickettsia africae is a self-limiting flu-like illness. We hypothesized that different inflammatory potential in endothelial cells could contribute to the different clinical features in these rickettsioses. METHODS: We analyzed the effect of heat-inactivated R. africae and R. conorii on the mRNA and protein levels of monocyte chemoattractant protein (MCP)-1, interleukin (IL)-8 and adhesion molecules in endothelial cells. Serum samples from patients with MSF (n=16) and ATBF (n=15) were collected before and after therapy. RESULTS: R. conorii induced a marked increase in MCP-1, IL-8, and adhesion molecules in endothelial cells, involving toll-like receptor 4 activation. In contrast, R. africae induced MCP-1 expression, but only modest or no responses were seen on IL-8 and adhesion molecules. Comparable to the in vitro response, levels of IL-8 and adhesion molecules showed no or only a modest increase in ATBF patients while these inflammatory markers were markedly elevated during MSF. CONCLUSIONS: Our findings suggest a superior inflammatory potential of R. conorii as compared to R. africae in endothelial cells, potentially related to the more severe inflammation in MSF comparing ATBF.

Serological response to "Rochalimaea henselae" antigen in suspected cat-scratch disease.

There are no generally accepted diagnostic tests for cat-scratch disease (CSD), the cause of which is unknown. During the development of an indirect fluorescence antibody (IFA) test for detection of antibodies to "Rochalimaea henselae", sera from patients with CSD were found to have high titres to R henselae antigens. Further tests with this assay showed that 36 (88%) of 41 patients with suspected CSD had serum titres of 64 or more to R henselae antigen, that there was a low prevalence (3%) of substantial titres to R henselae in healthy controls (n = 107), and that the immune responses to R henselae antigens were specific. These data suggest that the R henselae IFA test, or other serological assays based on R henselae, may be useful for diagnosis of CSD.

Ehrlichia chaffeensis and Rochalimaea antibodies in Kawasaki disease.

Sera from 38 patients with Kawasaki disease were tested for immunofluorescent antibodies to Ehrlichia chaffeensis, Rochalimaea henselae, and R. quintana Oklahoma. Only 2.5% of the patients tested positive for E. chaffeensis, and 5% were positive for R. henselae and R. quintana Oklahoma. Our data suggest that Ehrlichia and Rochalimaea spp. do not play a unique role in the etiology of Kawasaki disease.