Suzanne M. Garland

Objective: Molecular typing can identify relationships between M. genitalium strains and antimicrobial resistance and demographic data. We examined the association of mgpB sequence types (STs) with sex/sexual orientation, antimicrobial resistance and geographical location for M. genitalium in Australia. Methods: Sequence data derived from previous studies in Victoria and Queensland were obtained from 170 M. genitalium samples for the mgpB, 23 S rRNA, and parC genes. An additional 55 M. genitalium samples from Victoria were sequenced for the same three genes in this study. A combined data set of 225 samples collected between 2017 and 2019 were examined for associations between mgpB ST and (i) sex/sexual orientation, (ii) macrolide and fluoroquinolone resistance, and (iii) geographical location using chi-square test. Results: Overall, 66 mgpB STs were identified; the most common were ST-7 (17.9%), ST-4 (11.6%), ST-105 (11.6%), and ST-2 (5.4%). There was a strong association between ST and sex/sexual orientation; ST-4 and ST-105 were most common among men-who-have-sex-with-men (p < 0.0001) while ST-7 among women (p < 0.0001). There was a strong association between ST and macrolide resistance (p = 0.0028). Fluoroquinolone resistance was less common (28.0%) and did not differ by STs (p = 0.20). There was no association between ST and geographic location (p = 0.056). Conclusions: In this Australian study, four mgpB STs were common and were strongly associated with sex/sexual orientation and macrolide resistance. This relationship was not seen for fluoroquinolone resistance nor geographic location. These findings highlight the sporadic nature of resistance, indicating a need for effective treatment approaches combined with routine antimicrobial resistance surveillance.

Objective: Women living with HIV (WLWH) are among those at highest risk for cervical cancer development, thereby making this a key population for primary and secondary prevention. Human papillomavirus (HPV) nucleic acid (DNA or RNA) tests, which have been clinically validated, are supported by the World Health Organization (WHO) as the preferred method for cervical screening for all women, although HPV DNA is preferred in WLWH until further evidence demonstrates that HPV RNA is equivalent. We sought to describe current guidelines for HPV-based cervical cancer screening for WLWH. Methods: This paper outlines current recommendations and the state of knowledge regarding HPV-based cervical cancer screening for WLWH. Results: Current recommendations and the state of knowledge have been subdivided into the following topics: cervical screening and triage; treatment; additional considerations; and challenges and opportunities. Conclusions: The International Papillomavirus Society supports the WHO recommendations regarding HPV-based screening for all women, including WLWH. As data to support best practices in WLWH are limited, we strongly encourage continued research into this important topic.

Background: Mycoplasma genitalium is a sexually transmitted bacterium of increasing concern due to issues around antimicrobial resistance. Resistance is typically mediated by SNPs; however, the difficulty of isolation and culture of M. genitalium limits the ability to analyse the impact of individual mutations. Objective: The aim of this study was to generate and characterize antibiotic-resistant M. genitalium mutants in vitro to understand the development of macrolide resistance in this bacterium. Methods: Sequential MIC assays for azithromycin were performed using the laboratory strain of M. genitalium (G37) grown in Hayflick medium. Bacteria were enumerated by droplet digital PCR (ddPCR) targeting mgpB, and a new ddPCR assay was established to detect specific mutations in the 23S rRNA gene. MICs of selected macrolide antibiotics were determined in Hayflick medium. Whole genome sequencing (WGS) was performed on the Oxford Nanopore MinION. Results: After eight passages in azithromycin, a novel 23S rRNA gene mutation, G2057A (Escherichia coli numbering), was detected. The mutant did not display a detectable growth defect and had elevated MICs to azithromycin (8-fold), josamycin (8-fold) and erythromycin (16- to 32-fold). WGS did not identify other mutations likely to contribute to reduced macrolide susceptibility. Conclusions: A novel 23S rRNA gene mutation was identified in M. genitalium. This variation is found in Mycoplasma hominis, which is intrinsically resistant to certain macrolides. While this mutation has not been observed clinically in M. genitalium, these findings have expanded our understanding of resistance mechanisms within the Mollicutes, in particular the propensity for M. genitalium to develop resistance, even in low concentrations of antibiotic, and the interaction of azithromycin with the ribosome.

Recently, the International Papillomavirus Society convened a working group on cervical human papillomavirus latency, which resulted in an updated understanding of the human papillomavirus natural history. While the previous human papillomavirus natural history model considered human papillomavirus detection to be a result of human papillomavirus acquisition or possibly reinfection, and loss of human papillomavirus detection to be a result of viral clearance, the updated understanding of the human papillomavirus natural history is more nuanced. Thus, human papillomavirus detection may occur as a result of autoinoculation, deposition from a recent sex act, or as a redetection of a previously acquired infection. Similarly, loss of human papillomavirus detection likely reflects immune control rather than complete viral clearance. As it is practically impossible to identify the "true" source of a new human papillomavirus detection or determine why human papillomavirus is no longer detectable, we propose that healthcare providers and researchers use the terminology human papillomavirus detected vs human papillomavirus not detected. Moreover, we describe the updated understanding in a clinical context. Specifically, we discuss the potential implications of the updated understanding regarding clinical counseling in screening, recommendations on cervical screening, and human papillomavirus vaccination. We also suggest key phrases that healthcare providers may use when counseling women attending routine human papillomavirus-based cervical screening.

The WHO has given a permissive recommendation for an off-label one-dose human papillomavirus (HPV) vaccine schedule to prevent cervical cancer, based on evidence of comparable protection to two or three doses of vaccine. While neutralizing antibodies are thought to be the primary mechanism of protection, the persistence of immunity and whether other antibody-mediated mechanisms of protection are involved is unclear. Using systems serology, we investigated HPV antibody responses in serum from Fijian girls who were unvaccinated or received one, two or three doses of quadrivalent HPV vaccine six years earlier. We also evaluated their HPV antibody responses 28 days following a dose of bivalent HPV vaccine. After six years, one dose induced lower antibody concentrations but similar antibody profiles and phagocytic function as two or three doses. Following bivalent vaccine, antibody concentrations, particularly IgG1/IgG3, antibody profiles and phagocytic function were similar between previously vaccinated girls, indicating immune memory after one dose. Cross-reactive antibody responses against non-vaccine genotypes (HPV31/33/45/52/58) were lower following one dose than two or three doses. These findings provide novel insights into serological immunity and recall responses following one-dose HPV vaccination.