RESUMEN
BACKGROUND: Suppressive therapy in patients with genital herpes has been used in Japan since 2006. Susceptibility and resistance of herpes simplex virus (HSV)-2 to acyclovir were examined in genital isolates from patients receiving suppressive therapy and compared with those from those naïve to acyclovir and receiving episodic treatment with acyclovir. OBJECTIVE: The aim of this study was to analyze the effect of acyclovir use on the susceptibility to acyclovir and analysis of the thymidine kinase gene by acyclovir treatment. METHODS: Genital HSV isolates were obtained from three patients groups. Susceptibility to acyclovir, the frequency of acyclovir-resistant clones and mutations in the thymidine kinase gene of acyclovir-resistant clones were determined. RESULTS: Susceptibility to ACV was significantly higher in isolates from patients receiving suppressive therapy than those naïve to acyclovir and receiving episodic treatment, but the frequencies of resistant clones were similar among the three groups. Mutation in guanosine homopolymeric strings (G-string mutation) was significantly more frequent in clones during episodic treatment and suppressive therapy than clones from patients naïve to ACV. The frequency of G-string mutation was significantly less frequent in isolates from patients naïve to ACV than those experienced ACV therapy. CONCLUSION: The frequency of acyclovir-resistant mutants was not increased by episodic and suppressive therapy, but exposure to acyclovir significantly generated G-string mutations, possibly induced by acyclovir. Acyclovir therapy had no substantial effects on the susceptibility of HSV-2 or frequency of resistant virus but did generate subclinical G-string mutants in patients' HSV-2.
Asunto(s)
Aciclovir/uso terapéutico , Farmacorresistencia Viral/genética , Herpes Genital/tratamiento farmacológico , Herpesvirus Humano 2/fisiología , Timidina Quinasa/genética , Proteínas no Estructurales Virales/genética , Aciclovir/efectos adversos , Adulto , Anciano , Antivirales/efectos adversos , Antivirales/uso terapéutico , Femenino , Guanosina , Herpes Genital/virología , Herpesvirus Humano 2/efectos de los fármacos , Herpesvirus Humano 2/aislamiento & purificación , Humanos , Japón , Masculino , Persona de Mediana Edad , Mutación , Adulto JovenRESUMEN
We evaluated the correlation between the conventional manual serological testing method for syphilis and a novel automated serological testing method and between six different reagents used in the automated method. Twenty-six serum samples, which were positive on non-treponemal manual serological testing, were obtained from 19 patients with early syphilis. The samples were manually analyzed using the non-treponemal serological test for syphilis kit and automatically analyzed using six different reagents approved by the Ministry of Health, Labor and Welfare in Japan. Statistically significant correlations were observed between most of the reagents used in the automated testing (r = 0.652-0.996, P < 0.001), except for one combination of the reagents. In the simple regression analysis, the slope of the simple regression line (range, 0.014-3.040) and some of the regression coefficients were not equal to 1.0. Therefore, it is recommended that when the automated serological testing method is used to test for syphilis, the same reagent should be consistently selected to evaluate the changes in antibody titers. Statistically significant correlations were also observed between the manual method and all the reagents used in the automated method (r = 0.682-0.811, P < 0.001). In this case, the regression coefficients ranged 0.375-6.270, and the simple regression line intercept ranged -71.926 to 4.184. The regression coefficient and the intercept between the manual method and some of the reagents used in the automated method were not similar to the values described in the documentation attached to the reagents used in this study.