Venereology

Background/Objective: High-risk human papillomavirus (hrHPV) is an established causative agent for the malignant transformation of cervical cells that can be detected using the Papanicolaou (Pap) smear test. A call by the World Health Organization (WHO) for global collective efforts towards eliminating cervical cancer has endorsed hrHPV DNA testing as an alternative screening test. The objective of this study was to determine the diagnostic utility of hrHPV DNA testing in detecting high-grade cervical intraepithelial lesions (HSILs) in unvaccinated women with abnormal Pap smears and histopathologically confirmed CIN3 and carcinoma. Methods: This study included 111 cervical tissues with a histopathological confirmation of the cervical intraepithelial neoplasia grade (CIN3) and malignancy. Tissues were sectioned, dewaxed, and digested, and DNA was extracted and tested for hrHPV using the Abbott RealTime HR HPV assay. Pap smear results associated with the tissue samples were extracted from corresponding clinical records, and data was analyzed using R-statistical software. Results: Extracted Pap smear records for the 111 cervical tissue samples indicated that 89 (80.2%) had a high-grade intraepithelial lesion (Pap-HSIL), 20 (18%) had squamous cell carcinoma (Pap-SCC), and two (1.8%) had Pap-adenocarcinoma. A total of 68/89 (76.4%) of Pap-HSIL, 15/20 (75%) of Pap-SCC, and ½ (50%) of Pap-adenocarcinoma cases had detectable hrHPV DNA. Conclusions: This study’s findings demonstrate that the Pap smear is still a valuable screening test especially for detecting both hrHPV-dependent and -independent cervical dysplasia in unvaccinated populations. While considerations are made to improve cervical cancer screening, including the introduction of hrHPV DNA testing in national cervical cancer screening programs, there is a need for the careful interpretation of molecular testing results for clinical intervention. This is especially important for hrHPV-independent cervical dysplasia screening, since this can have dire implications for clinically asymptomatic women.

Background: The increasing prevalence of antibiotic-resistant Mycoplasma genitalium poses a significant challenge to global public health, necessitating the exploration of alternative therapeutic strategies, including vaccine development. Methods: In this study, we employed an immuno-informatics-based reverse vaccinology approach augmented with artificial intelligence-driven tools, to identify and characterize potential B-cell and T-cell epitopes from the hypothetical proteins (HPs) retrieved from the genome of the MG_G37T strain, a previously uncharacterized yet promising vaccine target. Using multiple softwares, a systematic pipeline was utilized to assess the sub-cellular localization, antigenicity, and allergenicity of the selected proteins. Results: Sub-cellular localization analysis identified the presence of several outer membrane and extracellular proteins in the genome of MG_G37T, indicating their surface association and accessibility to immune surveillance. Antigenicity and allergenicity prediction tools led to the identification of two top-scoring hypothetical proteins (fig|2097.71.peg.1 (UniProt ID: P22747) and fig|2097.70.peg.33 (UniProt ID: Q57081)) that demonstrated strong antigenic potential, non-allergenic properties, and suitability as vaccine candidates. Epitope mapping and structural modeling analyses further validated the immunogenic potential of these epitopes, highlighting their ability to interact with host immune components effectively. Comparative analyses with mouse allelic regions indicated the potential translational relevance of these predicted epitopes for preclinical studies. Conclusions: In particular, this study highlights the potential of these two hypothetical proteins as a promising vaccine candidate and provides a strong reason for experimental validation towards the design and development of effective vaccines to combat M. genitalium infections in the era of antimicrobial resistance.

Background: There is an urgent need for novel treatment options for Neisseria gonorrhoeae. Methenamine is an interesting urinary antiseptic with a very low propensity to induce antimicrobial resistance. Methods: We assessed the MICs of methenamine-hippurate for 18 N. gonorrhoeae isolates. We then assessed the in vivo efficacy of methenamine-hippurate against N. gonorrhoeae using the Galleria mellonella infection model. Results: We found that all the gonococcal isolates had a methenamine-hippurate MIC of 300 mg/L. This MIC was not higher in isolates with higher ceftriaxone MICs. No toxicity of methenamine at the doses tested was found, and doses as low as 200 mg/kg were effective in the G. mellonella model. Conclusions: Further studies in mice and humans are required to assess if methenamine-hippurate could be used to treat gonococcal urethritis alone or in combination with other agents such as ceftriaxone.