Treatment of Q fever endocarditis: comparison of 2 regimens containing doxycycline and ofloxacin or hydroxychloroquine.

BACKGROUND: Q fever endocarditis, caused by Coxiella burnetii, is fatal in 25% to 60% of patients. Currently, treatment with a long-term tetracycline and quinolone regimen for at least 4 years is recommended, although relapses are frequent. METHODS: Between January 1987 and December 1997, the reference treatment of Q fever endocarditis was compared with one of doxycycline and hydroxychloroquine sulfate. Patients were treated by conventional therapy until May 1991 and then by the new regimen. Microimmunofluorescence was used for antibody-level determination for diagnosis and follow-up. RESULTS: Thirty-five patients were included in the study, 26 males and 9 females. Of 14 patients treated with a doxycycline and quinolone combination, 1 died, 7 relapsed (3 were re-treated and 4 switched to the new regimen), 1 is still being treated, and 5 were considered cured using this regimen only. The mean duration of therapy for cure in this group was 55 months (median, 60 months). Twenty-one patients received the doxycycline and hydroxychloroquine regimen: 1 patient died of a surgical complication, 2 are still being treated, 17 were cured, and 1 is currently being evaluated. Two patients treated for 12 months but none of the patients treated for longer than 18 months relapsed. The mean duration of treatment in this group was 31 months (median, 26 months). No significant differences were observed between the 2 regimens in terms of death, valve surgery, or tolerance. The mortality rate for both regimens in this study was 5%. CONCLUSION: Prescription of the doxycycline and hydroxychloroquine combination for at least 18 months allows shortening of the duration of therapy and reduction in the number of relapses.

Molecular phylogeny of the genus Bartonella: what is the current knowledge?

Species of the genus Bartonella are involved in an increasing variety of human diseases. In addition to the 14 currently recognized species, several Bartonella strains have been recovered from a wide range of wild and domestic mammals in Europe and America. Such a high diversity of geographic distributions, animal reservoirs, arthropod vectors and pathogenic properties makes clarification of our knowledge about the phylogeny of Bartonella species necessary. Phylogenetic data have been inferred mainly from 16S rDNA, 16S--23S rRNA intergenic spacer, citrate synthase and 60 kDa heat-shock protein gene sequences, which are available in GenBank. Comparison of phylogenetic organizations obtained from various genes allowed six statistically significant evolutionary clusters to be identified. Bartonella bacilliformis and Bartonella clarridgeiae appear to be divergent species. Bartonella henselae, Bartonella koehlerae and Bartonella quintana cluster together, as well as Bartonella vinsonii subsp. vinsonii and B. vinsonii subsp. berkhoffii. The fifth group includes bacteria isolated from various rodents that belong to native species from the New World and in the sixth, Bartonella tribocorum, Bartonella elizabethae and Bartonella grahamii are grouped with several strains associated with Old World indigenous rodents. The position of the other species could not be consistently determined. As some cat- or rodent-associated Bartonella appeared to cluster together, it has been suggested that these bacteria and their reservoir hosts may co-evolve. Lack of host specificity, however, seems to be frequent and may reflect the influence of vector specificity. Host or vector specificity may also explain the current geographic distribution of Bartonella species.

Clinical efficacy of chloroquine or sulfadoxine-pyrimethamine in children under five from south-western Uganda with uncomplicated falciparum malaria.

We conducted a 14-day study (during March-May 1998) to assess the efficacy of chloroquine and sulfadoxine-pyrimethamine (SP) for treating uncomplicated Plasmodium falciparum malaria in Uganda. Overall treatment failure rates were 43 (81.1%) of 53 chloroquine recipients and 16 (25.0%) of 64 SP patients. Strategies to improve the life-span of standard and affordable anti-malarial drugs are needed.

16S/23S rRNA intergenic spacer regions for phylogenetic analysis, identification, and subtyping of Bartonella species.

Species of the genus Bartonella are currently recognized in growing numbers and are involved in an increasing variety of human diseases, mainly trench fever, Carrion's disease, bacillary angiomatosis, endocarditis, cat scratch disease, neuroretinitis, and asymptomatic bacteremia. Such a wide spectrum of infections makes it necessary to develop species and strain identification tools in order to perform phylogenetic and epidemiological studies. The 16S/23S rRNA intergenic spacer region (ITS) was sequenced for four previously untested species, B. vinsonii subsp. arupensis, B. tribocorum, B. alsatica, and B. koehlerae, as well as for 28 human isolates of B. quintana (most of them from French homeless people), six human or cat isolates of B. henselae, five cat isolates of B. clarridgeiae, and four human isolates of B. bacilliformis. Phylogenetic trees inferred from full ITS sequences of the 14 recognized Bartonella species using parsimony and distance methods revealed high statistical support, as bootstrap values were higher than those observed with other tested genes. Five well-supported lineages were identified within the genus and the proposed phylogenetic organization was consistent with that resulting from protein-encoding gene sequence comparisons. The ITS-derived phylogeny appears, therefore, to be a useful tool for investigating the evolutionary relationships of Bartonella species and to identify Bartonella species. Further, partial ITS amplification and sequencing offers a sensitive means of intraspecies differentiation of B. henselae, B. clarridgeiae, and B. bacilliformis isolates, as each strain had a specific sequence. The usefulness of this approach in epidemiological investigations should be highlighted. Among B. quintana strains, however, the genetic heterogeneity was low, as only three ITS genotypes were identified. It was nevertheless sufficient to show that the B. quintana population infecting homeless people in France was not clonal.

Phylogenetic position of Bartonella vinsonii subsp. arupensis based on 16S rDNA and gltA gene sequences.

The nucleotide sequences of the genes encoding 16S rRNA and citrate synthase (gltA) from a recently described member of the genus Bartonella, Bartonella vinsonii subsp. arupensis, isolated from mice and from the blood of a patient suffering from bacteraemia, were determined and compared with sequences of the 16S rDNA and gltA genes of other members of the genus Bartonella in order to determine its relative phylogenetic position. B. vinsonii subsp. arupensis appeared to be closely related to B. vinsonii subsp. vinsonii, another rodent-associated taxon, and to B. vinsonii subsp. berkhoffii, which was described recently in dogs.

Production of interleukin-10 and transforming growth factor beta by peripheral blood mononuclear cells in Q fever endocarditis.

The pathophysiology of Q fever endocarditis is characterized by the suppression of antigen-specific cell-mediated immune responses. We investigated the production of interleukin-10 (IL-10) and transforming growth factor beta (TGF-beta), known to interfere with the development of protective cell immunity. IL-10 was markedly released by unstimulated peripheral blood mononuclear cells (PBMC) from patients with Q fever endocarditis. This release resulted from the upregulation of IL-10 gene transcription. Similarly, the release of TGF-beta1 and TGF-beta2 was significantly higher in patient PBMC than in control cells, but the expression of their respective mRNA was not enhanced in patient cells. In contrast, lipopolysaccharide-stimulated transcription and release of IL-10 and TGF-beta were similar in patients and controls. The release of IL-10 by PBMC but not that of TGF-beta was correlated with the clinical status of the patients. First, IL-10 production was correlated with specific antibody levels. Second, IL-10 release remained elevated in patients prone to relapse. Taken together, our results suggest that the release of IL-10 and TGF-beta is upregulated in Q fever endocarditis. IL-10 might be considered as a marker of disease relapses and might be instrumental in monitoring the efficiency of the treatment.

Survey of the seroprevalence of Bartonella quintana in homeless people.

Trench fever is caused by Bartonella (Rochalimaea) quintana, a small gram-negative rod that is transmitted by body lice. Recently, B. quintana infections in homeless patients have been reported in the United States and Europe. From October 1993 to October 1994, the seroprevalence of antibodies to B. quintana was assessed by indirect immunofluorescence in a prospective study of 221 nonhospitalized homeless people, 43 hospitalized homeless patients (cases), 250 blood donors, and 57 hospitalized matched controls. Four (1.8%) of 221 nonhospitalized homeless people tested had titers of > 1:100. Of the 43 cases, seven (16%) had serological titers of > or = 1:100. None of the 250 serum samples from blood donors contained antibodies to B. quintana. The presence of antibodies to B. quintana in cases was significantly associated with the presence of body lice, exposure to cats, headaches, eastern European origin, and pain in the legs. This study demonstrates the presence of antibodies to B. quintana in the homeless population and should alert physicians that B. quintana might be an etiologic agent of fever in homeless patients.