Subclinical generation of acyclovir-resistant herpes simplex virus with mutation of homopolymeric guanosine strings during acyclovir therapy.

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.

Inter-rater reliability of self-reported response on foreskin status in questionnaire among Japanese adult men.

OBJECTIVES: To determine whether foreskin status is a measurable marker for evaluating the effect of the foreskin on sexually transmitted infections. METHODS: Inter-rater comparison of the responses on foreskin status and circumcision in a self-report questionnaire with the findings of a physical examination by an experienced well-trained urologist was performed for patients who visited a healthcare facility in Kanagawa, Japan. Foreskin status was defined using a five-point graphical scale based on the degree to which the foreskin covers the foreskin and the glans penis in a non-erectile condition: type 1, a fully exposed glans penis; types 2-4, the glans penis partly covered by the foreskin and type 5, phimosis. Linear weighted κ and per cent agreement were used to evaluate the reliability of responses. RESULTS: Among 188 participants who were evaluated about their foreskin status, linear weighted κ and per cent agreement were 0.74% and 68.4%, respectively. Linear weighted κ improved from 0.74 to 0.80 when the number of categories was changed to three. All the self-reported responses on circumcision were in agreement with the findings of the physical examination. Seventeen participants (9.0%) had been circumcised, and among them, three (17.6%) had approximately one-half of their glans penis covered by the foreskin. In 90 among the 171 uncircumcised participants (52.6%), the foreskin did not cover the glans penis. CONCLUSIONS: The self-reported response on foreskin status in this questionnaire has sufficient reliability to replace physical examination, and this questionnaire can facilitate further studies about the effect of foreskin on sexually transmitted infections.

[Detection of Chlamydia trachomatis and Neisseria gonorrhoeae in urine samples of males and females by the strand displacement amplification (SDA) method].

Urine samples collected from 422 males and 53 females visiting a clinic in Kawasaki City who were suspected to have sexually transmitted infection were tested for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae by BD ProbeTecET (SDA method). The detection rates of C. trachomatis by the SDA method and polymerase chain reaction (PCR) method (control) were as high as 98.1% for C. trachomatis, and as high as 99.4% for N. gonorrhoeae, and the concordance rate of detection of both bacterial species was high. The detection sensitivity and specificity of the SDA method were 90.6 and 99.3%, respectively for C. trachomatis and 98.7% and 100% for N. gonorrhoeae, when PCR was used as the standard method. There were no differences in these results between males and females. The number of patients showing a discrepancy of the results obtained between the SDA method and the PCR method was 9 for C. trachomatis and 1 for N. gonorrhoeae, but the results of redetermination by the SDA method tended to coincide with those of the PCR method. Urine samples tested by the SDA method were positive for N. gonorrhoeae even in patients in whom the culture of secretions from the male urethra was negative for N. gonorrhoeae. Based on these results, the BD ProbeTecET (SDA method) was confirmed to have the equivalent capability to the PCR method for the detection of C. trachomatis and N. gonorrhoeae in urine samples.

Antimicrobial resistance in clinical isolates of Neisseria subflava from the oral cavities of a Japanese population.

A recent study indicated that Neisseria subflava, one of the commensal Neisseria species, may play an important role in the emergence of Neisseria gonorrhoeae strains with chromosomally mediated resistance to penicillin or cephalosporin by the horizontal genetic exchange of penA genes encoding the target site for penicillin or cephalosporin. The present investigation examined the antimicrobial susceptibility of 45 isolates of N. subflava from the oral cavities of Japanese men and women to various agents used for the treatment of gonococcal infections. Of the 45 isolates, 40 (88.9%) and 4 (8.8%) were intermediately resistant and resistant to penicillin, respectively, with the minimal inhibitory concentration (MIC)(50) and MIC(90) of penicillin being 0.5 mg/l and 1 mg/l, respectively. Of the 45 isolates, 13 (28.9%) and 14 (31.1%) were resistant to tetracycline and ciprofloxacin, respectively, and 3 (6.7%) showed reduced susceptibility to cefixime (although the susceptibility category was not determined). These results indicate that several isolates of N. subflava have acquired resistance or intermediate resistance to various antimicrobial agents, including penicillin, cephalosporin, tetracycline, and ciprofloxacin. The present study may thus confirm that N. subflava may be involved in the emergence of N. gonorrhoeae strains with either intermediate or total resistance to penicillin or cephalosporin by the horizontal genetic exchange of the penA gene.