Emergence of quinolone resistance and cephalosporin MIC creep in Neisseria gonorrhoeae isolates from a cohort of young men in Kisumu, Kenya, 2002 to 2009.

We evaluated antimicrobial resistance in Neisseria gonorrhoeae isolated from men enrolled in a randomized trial of male circumcision to prevent HIV. Urethral specimens from men with discharge were cultured for N. gonorrhoeae. MICs were determined by agar dilution. Clinical and Laboratory Standards Institute (CLSI) criteria defined resistance: penicillin, tetracycline, and azithromycin MICs of ≥2.0 µg/ml; a ciprofloxacin MIC of ≥1.0 µg/ml; and a spectinomycin MIC of ≥128.0 µg/ml. Susceptibility to ceftriaxone and cefixime was shown by an MIC of ≤0.25 µg/ml. Additionally, PCR amplification identified mutations in parC and gyrA genes in selected isolates. From 2002 to 2009, 168 N. gonorrhoeae isolates were obtained from 142 men. Plasmid-mediated penicillin resistance was found in 65%, plasmid-mediated tetracycline resistance in 97%, and 11% were ciprofloxacin resistant (quinolone-resistant N. gonorrhoeae [QRNG]). QRNG appeared in November 2007, increasing from 9.5% in 2007 to 50% in 2009. Resistance was not detected for spectinomycin, cefixime, ceftriaxone, or azithromycin, but MICs of cefixime (P = 0.018), ceftriaxone (P < 0.001), and azithromycin (P = 0.097) increased over time. In a random sample of 51 men, gentamicin MICs were as follows: 4 µg/ml (n = 1), 8 µg/ml (n = 49), and 16 µg/ml (n = 1). QRNG increased rapidly and alternative regimens are required for N. gonorrhoeae treatment in this area. Amid emerging multidrug-resistant N. gonorrhoeae, antimicrobial resistance surveillance is essential for effective drug choice. High levels of plasmid-mediated resistance and increasing MICs for cephalosporins suggest that selective pressure from antibiotic use is a strong driver of resistance emergence.

Abundant expression of HIV target cells and C-type lectin receptors in the foreskin tissue of young Kenyan men.

A biological explanation for the reduction in HIV-1 (HIV) acquisition after male circumcision may be that removal of the foreskin reduces the number of target cells for HIV. The expression of potential HIV target cells and C-type lectin receptors in foreskin tissue of men at risk of HIV infection were thus analyzed. Thirty-three foreskin tissue samples, stratified by Herpes simplex virus type 2 status, were obtained from a randomized, controlled trial conducted in Kenya. The samples were analyzed by confocal in situ imaging microscopy and mRNA quantification by quantitative RT-qPCR. The presence and location of T cells (CD3(+)CD4(+)), Langerhans cells (CD1a(+)Langerin/CD207(+)), macrophages (CD68(+) or CD14(+)), and submucosal dendritic cells (CD123(+)BDCA-2(+) or CD11c(+)DC-SIGN(+)) were defined. C-type lectin receptor expressing cells were detected in both the epithelium and submucosa, and distinct lymphoid aggregates densely populated with CD3(+)CD4(+) T cells were identified in the submucosa. Although the presence of lymphoid aggregates and mRNA expression of selected markers varied between study subjects, Herpes simplex virus type 2 serostatus was not the major determinant for the detected differences. The detection of abundant and superficially present potential HIV target cells and submucosal lymphoid aggregates in foreskin mucosa from a highly relevant HIV risk group demonstrate a possible anatomical explanation that may contribute to the protective effect of male circumcision on HIV transmission.