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Antibiotics for treating scrub typhus.

BACKGROUND: Scrub typhus is a cause of fever in regions of Asia and the Pacific. Recently, resistance to antibiotics has been reported. OBJECTIVES: To assess treatment regimens for scrub typhus through time to fever resolution and incidence of relapse. SEARCH STRATEGY: Cochrane Controlled Trials Register, MEDLINE, EMBASE, and contacted individual researchers for unpublished data. SELECTION CRITERIA: Randomised and pseudorandomised studies; patients diagnosed with scrub typhus defined by authors; any comparison of antibiotic regimens for treating scrub typhus. DATA COLLECTION AND ANALYSIS: Trial quality was assessed, and data abstracted by both reviewers. MAIN RESULTS: Three trials met the inclusion criteria. One small trial compared tetracycline against chloramphenicol. The other two trials compared doxycycline with tetracycline, and showed little difference in the proportion febrile at 48 hours, with no relapses after either drug. REVIEWER'S CONCLUSIONS: Tetracycline and doxycycline seem to be effective in treating scrub typhus. Further research is required to identify appropriate treatment in areas where Orientia tsutsugamushi resistant to doxycycline has been reported.

Anti-Bacterial Agents↗

Serological differentiation of murine typhus and epidemic typhus using cross-adsorption and Western blotting.

Differentiation of murine typhus due to Rickettsia typhi and epidemic typhus due to Rickettsia prowazekii is critical epidemiologically but difficult serologically. Using serological, epidemiological, and clinical criteria, we selected sera from 264 patients with epidemic typhus and from 44 patients with murine typhus among the 29,188 tested sera in our bank. These sera cross-reacted extensively in indirect fluorescent antibody assays (IFAs) against R. typhi and R. prowazekii, as 42% of the sera from patients with epidemic typhus and 34% of the sera from patients with murine typhus exhibited immunoglobulin M (IgM) and/or IgG titers against the homologous antigen (R. prowazekii and R. typhi, respectively) that were more than one dilution higher than those against the heterologous antigen. Serum cross-adsorption studies and Western blotting were performed on sera from 12 selected patients, 5 with murine typhus, 5 with epidemic typhus, and 2 suffering from typhus of undetermined etiology. Differences in IFA titers against R. typhi and R. prowazekii allowed the identification of the etiological agent in 8 of 12 patients. Western blot studies enabled the identification of the etiological agent in six patients. When the results of IFA and Western blot studies were considered in combination, identification of the etiological agent was possible for 10 of 12 patients. Serum cross-adsorption studies enabled the differentiation of the etiological agent in all patients. Our study indicates that when used together, Western blotting and IFA are useful serological tools to differentiate between R. prowazekii and R. typhi exposures. While a cross-adsorption study is the definitive technique to differentiate between infections with these agents, it was necessary in only 2 of 12 cases (16.7%), and the high costs of such a study limit its use.

Animals↗

Presence of antibodies to scrub typhus and murine typhus in dogs from Selangor, Peninsular, Malaysia.

Dog sera, collected from different communities throughout Selangor, Peninsular Malaysia, were investigated for the presence of antibodies to R. tsutsugamushi and R. typhi. Scrub typhus antibodies were present in animals from the rural areas only, whereas murine typhus antibodies were observed in equal numbers of dogs from both rural and metropolitan areas. Greater percentage of dogs from suburban areas had demonstrable antibody titers to murine typhus than from the urban area.

Animals↗

Mechanisms of immunity in typhus infections. VI. Differential opsonizing and neutralizing action of human typhus rickettsia-specific cytophilic antibodies in cultures of human macrophages.

Human peripheral blood monocytes were incubated in vitro for 6 days to allow time for transformation into macrophage-like cells. Cytophilic antibodies in typhus convalescent human serum were demonstrated by addition of Rickettsia mooseri or Rickettsia prowazeki to passively sensitized human peripheral blood monocyte-derived macrophages that were held at 4 degrees C. Rosettes of rickettsiae were found around macrophages sensitized with immune serum but not around macrophages that had been incubated with normal serum. Inhibition of rosette formation occurred if the macrophages were maintained in normal human serum before addition of immune human serum. Rosettes of R. mooseri were also formed around monocytes obtained from an individual infected with R. mooseri. If the antibody-sensitized macrophages were maintained at 34 degrees C, enhanced phagocytosis of R. mooseri or R. prowazeki occurred as compared with macrophages exposed to normal human serum before infection. However, the cytophilic antibody did not significantly inhibit the subsequent growth of R. prowazeki within the macrophages. This is in contrast to results obtained when R. prowazeki was mixed with immune serum before addition to the macrophage. In the latter case, growth of R. prowazeki was largely inhibited. The significance of antibody cytophilic for macrophages in typhus infections is discussed.

Adult↗

Mechanisms of immunity in typhus infections. I. Multiplication of typhus rickettsiae in human macrophage cell cultures in the nonimmune system: influence of virulence of rickettsial strains and of chloramphenicol.

Monocytes from the peripheral blood of nonimmune human subjects transformed in cell culture into macrophages with increased phagocytic capacity for killed typhus rickettsiae. When such cells were exposed to living virulent Rickettsia mooseri (Wilmington strain) or R. prowazeki (Breinl strain), or to the attenuated E strain of R. prowazeki, in the presence of medium containing normal human serum, all three strains readily entered the macrophage, but the subsequent fate varied according to strain and its virulence. Thus, R. mooseri grew readily to attain very high intracellular populations which eventually destroyed the macrophage in 3 to 5 days and escaped to infect other cells. Virulent R. prowazeki also grew at about the same rate for the first 2 to 3 days but then often abruptly ceased to multiply. Circumstantial evidence suggests a toxic effect on host cells by smaller numbers of R. prowazeki organisms than with R. mooseri. The attenuated E strain of R. prowazeki failed to grow in most cells and eventually disappeared, but did grow to substantial numbers in the very rare cell in some cultures, suggesting the presence of a few cells which may not be typical macrophages. The growth of R. mooseri in the macrophage cytoplasm was inhibited by chloramphenicol in the culture medium. When the drug was removed after 3 days, growth began after a lag period and assumed a normal rate.

Cells, Cultured↗

[The effect of various antibiotics on the formation of typhus antibodies following immunization with typhus vaccine].

It was shown that administration in the course of one week, before or after a single use of killed or chemical typhoid vaccine of dibiomycin, biomycin, or biomycin in combination with erythromycin in comparatively high doses produced no negative effect of the production of typhus antibodies and the intensity of antitoxic immunity in albino mice. The same antibiotics failed to influence the antibody formation in guinea pigs if they produced no toxic effect on the animals; but in case of development of toxic phenomena connected with the administration of the mentioned antibiotics a strong depression of antibody production was observed in guinea pigs.

Animals↗