The global rapid emergence of azithromycin/ceftriaxone resistant Neisseria gonorrhoeae threatens current recommend azithromycin/ceftriaxone dual therapy for gonorrhea to ensure effective treatment. Here, we identified the first two N. gonorrhoeae isolates with decreased ceftriaxone susceptibility in Thailand. Among 134 N. gonorrhoeae isolates collected from Thai Red Cross Anonymous Clinic, Bangkok, two isolates (NG-083 and NG-091) from urethral swab in male heterosexual patients had reduced susceptibility to ceftriaxone (MICs of 0.125 mg/L). Both were multidrug resistant and strong biofilm producers with ceftriaxone tolerance (MBEC > 128 mg/L). NG-083 and NG-091 remained susceptible to azithromycin (MIC of 1 mg/L and 0.5 mg/L, respectively). Reduced susceptibility to ceftriaxone was associated with alterations in PBP2, PBP1, PorB, MtrR, and mtrR promoter region. NG-083 belonged to sequence type (ST) 7235 and NG-091 has new allele number of tbpB with new ST. Molecular docking revealed ceftriaxone weakly occupied the active site of mosaic XXXIV penicillin-binding protein 2 variant in both isolates. Molecular epidemiology results revealed that both isolates display similarities with isolates from UK, USA, and The Netherlands. These first two genetically related gonococcal isolates with decreased ceftriaxone susceptibility heralds the threat of treatment failure in Thailand, and importance of careful surveillance.

BackgroundMen who have sex with men (MSM) are at high risk of developing human papillomavirus (HPV)-related anal cancer. We compared HPV genotypes in anal tissues (Bx) and anal liquid-based cytology fluid (LBC) from HIV-positive and HIV-negative MSM.MethodsBx (32 normal, 41 low-grade squamous intraepithelial lesions (LSIL) and 22 high-grade squamous intraepithelial lesions (HSIL)), along with LBC from the same visit, were selected from 61 HIV-positive and 34 HIV-negative MSM who enrolled into a prospective cohort in Bangkok, Thailand. HPV genotyping was performed on Bx and LBC.ResultsAny HPV and high-risk HPV (HR-HPV) prevalence were 63.2% and 60.0% in Bx and 71.6% and 62.1% in LBC, respectively. HIV-positive MSM had higher rates of HR-HPV genotypes detection (70.5% vs. 47.1%, p=0.03) in LBC than HIV-negative MSM. HPV16 (27%) was the most common HR-HPV found in HSIL tissue. In HIV-positive MSM, the frequency of HR-HPV detection increased with histopathologic grading in both Bx and LBC samples. HSIL was associated with the presence of any HR-HPV(OR 7.6 (95%CI 1.8–31.9); P=0.006) in LBC and in Bx((OR 5.6 (95%CI 1.4–22.7); P=0.02).ConclusionsOur data strongly support the integration of HR-HPV screening on LBC samples, along with HPV vaccination, into an anal cancer prevention program.

Background Rapid emergence of global azithromycin resistance, with ceftriaxone reduce susceptibility/resistant strains, threatens the current recommends dual therapy with ceftriaxone and azithromycin for gonorrhea to ensure effective treatment. Thailand is a major risk area for gonorrhea because it as a key destination for sex tourism industry, where antibiotic resistance gonorrhea can spread easily and quickly across the region. Here, we identified a first cluster of Neisseria gonorrhoeae isolates with decreased ceftriaxone susceptibility in Thailand. Methods A 134 N. gonorrhoeae isolates collected from Thai Red Cross Anonymous Clinic, Bangkok, during 2016–2018 were studied. Broth micro-dilution and plate dilution methods to define resistance or decreased susceptibilityaccording to CLSI guidelines. Select isolates were subjected to whole genome sequencing with an Illumina MiSeq V2 instrument and analysis using CLCBio Genomics Workbench v6.5. Molecular docking studies were carried out to understand binding mode analysis and orientation of ceftriaxone in the active site of PBP2. Biofilm formation measured by confocal laser scanning microscopy. Results Among the N. gonorrhoeae clinical isolates, two isolates had significant reduced susceptibility to ceftriaxone (MICs of 0.125 mg/L), which were isolated from urethral swab in male heterosexual patients. Both were multidrug resistance and strong biofilm producers with ceftriaxone tolerance (MBEC > 128 mg/L). One isolate was resistant to azithromycin (MIC of 1 mg/L), and other one remained susceptible (MIC of 0.5 mg/L). Reduced susceptibility to ceftriaxone associated with alterations in PBP2, PBP1, PorB, MtrR, and mtrR promoter region with one belonged to ST7235 and second one had new allele number of tbpB with new sequence type (ST). Ceftriaxone weakly occupy the active site of mosaic XXXIV penicillin-binding protein 2 (PBP2) variant in both. Molecular epidemiology results reviled that both isolates display similarities with isolates from UK, USA, and Netherlands. Conclusion This first cluster of genetically related gonococcal isolates with decreased ceftriaxone susceptibility may bring threat of treatment failure in Thailand. Also highlighted the importance of maintaining surveillance for antimicrobial resistance. Disclosures All Authors: No reported disclosures

Transgender women (TGW) are disproportionally affected by HIV infection, with a global estimated prevalence of 19.9%, often attributed to behavioral risk factors, with less known about biological factors. We evaluated potential biological risk factors for HIV acquisition in TGW at the sites of viral entry by assessing immune parameters of the neovaginal surface and gut mucosa. The neovagina in TGW, compared with the vagina in cisgender women (CW), shows distinct cell composition and may pose a more inflammatory environment, evidenced by increased CD4 + T cell activation and higher levels of soluble markers of inflammation (C-reactive protein, soluble CD30). Increased inflammation may be driven by microbiome composition, as shown by a greater abundance of Prevotella and a higher Shannon Diversity Index. In addition, we have observed higher frequency of CD4 + CCR5 + target cells and decreased DNA methylation of the CCR5 gene in the gut mucosa of TGW compared with CW and men who have sex with men, which was inversely correlated with testosterone levels. The rectal microbiome composition in TGW appears to favor a proinflammatory milieu as well as mucosal barrier disruption. Thus, it is possible that increased inflammation and higher frequencies of CCR5-expressing target cells at sites of mucosal viral entry may contribute to increased risk of HIV acquisition in TGW, with further validation in larger studies warranted.