Obstetrics and Gynaecology - Research Publications
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ItemNear-to-patient-testing to inform targeted antibiotic use for sexually transmitted infections in a public sexual health clinic: the NEPTUNE cohort study(ELSEVIER, 2024-03)BACKGROUND: Empiric treatment of sexually transmitted infections can cause unnecessary antibiotic use. We determined if near-to-patient-testing (NPT) for Neisseria gonorrhoeae, Chlamydia trachomatis and Mycoplasma genitalium (MG) improved antibiotic-use for a range of clinical presentations. METHODS: Clients attending with non-gonococcal urethritis (NGU), proctitis, as STI-contacts, or for an MG-test-of-cure (MG-TOC) between March and December 2021 were recruited. Participants received near-to-patient-testing (NPT-group) for the three STIs using the GeneXpert® System (Cepheid), and concurrent routine-testing by transcription-mediated-amplification (TMA; Aptima, Hologic). Antibiotic-use among NGU or proctitis cases in the NPT-group was compared to clinic-controls undergoing routine-testing only. The proportion in the NPT-group who notified partners <24 hrs of their STI-specific result was calculated. FINDINGS: Among 904 consults by 808 NPT-participants, ≥1 STI was detected in 63/252 (25.0%) with NGU, 22/51 (43.1%) with proctitis, and 167/527 (31.7%) STI-contacts. MG was detected among 35/157 (22.3%) MG-TOC consults. Among NGU and proctitis cases, fewer in the NPT-group received empiric treatment compared to clinic-controls (29.4% [95% CI: 24.3-34.9%] vs 83.8% [95% CI: 79.2-87.8%], p < 0.001), resulting in more NPT-group cases appropriately treated (STI-specific drug/no drug appropriately; 80.9% [95% CI: 76.0-85.1%] vs 33.0% [95% CI: 27.7-38.6%], p < 0.001) and fewer mistreated (incorrect drug/treated but pathogen-negative; 17.8% [13.7-22.6%] vs 61.4% [55.6-66.9%], p < 0.001). Of 167/264 in the NPT-group with an STI who responded regarding partner-notification, 95.2% notified all/some partners; 85.9% notified them <24 hrs of the STI-specific result. INTERPRETATION: Near-to-patient-testing significantly improved antibiotic use and a high proportion of individuals rapidly notified partners of STI-specific results, highlighting the broad benefits of timely diagnostic strategies for STIs in clinical decision making and partner notification. FUNDING: ARC ITRP Hub-grant; NHMRC.
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ItemNo Preview AvailableDevelopment of a touchdown droplet digital PCR assay for the detection and quantitation of human papillomavirus 16 and 18 from self-collected anal samples(AMER SOC MICROBIOLOGY, 2023-12-12)The quantity of the human papillomavirus (HPV) is associated with disease outcome. We designed an accurate and precise digital PCR assay for quantitating HPV in anal samples, a sample type that is typically problematic due to the presence of PCR inhibitors.
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ItemNo Preview AvailablePerformance of Human Papillomavirus Attribution Algorithms to Predict Causative Genotypes in Anal High-Grade Lesions(OXFORD UNIV PRESS INC, 2023-06-15)BACKGROUND: Gay and bisexual men (GBM) are at increased risk of human papillomavirus (HPV)-associated anal high-grade squamous intraepithelial lesions (HSILs). Understanding the fractions of HSILs attributable to HPV genotypes is important to inform potential impacts of screening and vaccination strategies. However, multiple infections are common, making attribution of causative types difficult. Algorithms developed for predicting HSIL-causative genotype fractions have never been compared with a reference standard in GBM. METHOD: Samples were from the Study of the Prevention of Anal Cancer. Baseline HPV genotypes detected in anal swab samples (160 participants) were compared with HPV genotypes in anal HSILs (222 lesions) determined by laser capture microdissection (LCM). Five algorithms were compared: proportional, hierarchical, maximum, minimum, and maximum likelihood estimation. RESULTS: All algorithms predicted HPV-16 as the most common HSIL-causative genotype, and proportions differed from LCM detection (37.8%) by algorithm (with differences of -6.1%, +20.9%, -20.4%, +2.9%, and +2.2% respectively). Fractions predicted using the proportional method showed a strong positive correlation with LCM, overall (R = 0.73 and P = .002), and by human immunodeficiency virus (HIV) status (HIV positive, R = 0.74 and P = .001; HIV-negative, R = 0.68 and P = .005). CONCLUSIONS: Algorithms produced a range of inaccurate estimates of HSIL attribution, with the proportional algorithm performing best. The high occurrence of multiple HPV infections means that these algorithms may be of limited use in GBM.
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ItemNo Preview AvailableQuantitation of Mycoplasma genitalium using droplet digital PCR(OXFORD UNIV PRESS, 2023-06-01)Mycoplasma genitalium is a sexually transmitted infection with increasing concerns around antimicrobial resistance. Droplet digital PCR (ddPCR) is a rapid quantification method with high precision that may be useful for absolute quantitation of bacteria in samples. This study aimed to develop a ddPCR assay for the quantification of M. genitalium. ddPCR targeting the gene mgpB was established and analysed using the QX100 ddPCR system. The assay was evaluated against quantitated DNA standards, and then in comparison to an established quantitative PCR performed on the Lightcycler 480 II. DNA template of increasing complexity was used, including synthetic double stranded DNA, DNA extracts from laboratory-cultured M. genitalium strains (n = 17) and DNA from M. genitalium-positive clinical samples (n = 21). There was a strong correlation between ddPCR concentration estimates and measured DNA standards (r2 = 0.997), and between ddPCR and qPCR quantitation for different templates (r2 ranging from 0.953 to 0.997). ddPCR reliably detected template in a range from <10 copies per reaction to >104 copies per reaction and demonstrated linearity over dilution series. Concentration estimates by ddPCR were reproducibly less than those determine by qPCR. ddPCR demonstrated precise and reproducible quantitation of M. genitalium with a variety of templates.
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ItemEvaluation of TIB Molbiol LightMix® assays for detection of Mycoplasma genitalium and key resistance mutations for macrolides and fluoroquinolones(Oxford University Press, 2023-11-01)The LightMix® Modular Mycoplasma Macrolide and LightMix® Modular parC Fluoroquinolone Resistance assays (TIB Molbiol) were evaluated using sequential Mycoplasma genitalium positive (n = 125) and negative (n = 93) clinical samples. Results were compared to the results of an established commercial assay (ResistancePlus MG assay, SpeeDx Pty Ltd) or Sanger sequencing (for parC). Detection of M. genitalium by the TIB Molbiol assay had a high agreement with the reference assay, with a positive percent agreement (PPA) of 97.6 [95% confidence interval (CI): 93.1-99.5] and negative percent agreement (NPA) of 95.7 (95% CI: 89.5-98.8). From 105 positive samples, macrolide resistance detection had a PPA of 100% (95% CI: 93.7-100) and NPA of 81.3% (95% CI: 67.4-91.1). For the detection of fluroquinolone resistance mutation G248T/S83I or "other mutation" in the quinolone resistance determinant region, from 95 samples there was 100% (95% CI: 86.3-100) sensitivity and 100% (95% CI: 94.5-100) specificity. The understanding of the basis for fluoroquinolone treatment failure is still developing; it is therefore important to use the output of parC-based resistance assays with caution to avoid the inappropriate use of antibiotic therapies, especially considering the limited number of alternative treatments.
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ItemA single dose of quadrivalent HPV vaccine is highly effective against HPV genotypes 16 and 18 detection in young pregnant women eight years following vaccination: an retrospective cohort study in Fiji(ELSEVIER, 2023-08)BACKGROUND: In 2008/9, Fiji vaccinated >30,000 girls aged 9-12 years with the quadrivalent human papillomavirus (4vHPV) vaccine coverage for at least one dose was >60% (one dose only was 14%, two dose only was 13%, three doses was 35%). We calculated vaccine effectiveness (VE) of one, two and three doses of 4vHPV against oncogenic HPV genotypes 16/18, eight years following vaccination. METHODS: A retrospective cohort study was undertaken (2015-2019) in pregnant women ≤23 years old, eligible to receive 4vHPV in 2008/9, with confirmed vaccination status. The study was restricted to pregnant women due to the cultural sensitivity of asking about sexual behavior in Fiji. For each participant a clinician collected a questionnaire, vaginal swab and genital warts examination, a median eight (range 6-11) years post vaccination. HPV DNA was detected by molecular methods. Adjusted VE (aVE) against the detection of vaccine HPV genotypes (16/18), the comparison group of non-vaccine genotypes (31/33/35/39/45/51/52/56/58/59/66/68), and genital warts were calculated. Covariates included in the adjusted model were: age, ethnicity and smoking, according to univariate association with any HPV detection. FINDINGS: Among 822 participants the prevalence of HPV 16/18 in the unvaccinated, one, two and three-dose groups were 13.3% (50/376), 2.5% (4/158), 0% (0/99) and 1.6% (3/189), respectively; and for the non-vaccine high-risk genotypes, the detection rate was similar across dosage groups (33.2%-40.4%, p = 0.321). The aVE against HPV 16/18 for one, two and three doses were 81% (95% CI; 48-93%), 100% (95% CI; 100-100%), and 89% (95% CI; 64-96%), respectively. Prevalence of HPV 16/18 was lower among women with longer time since vaccination. INTERPRETATIONS: A single dose 4vHPV vaccine is highly effective against HPV genotypes 16 and 18 eight years following vaccination. Our results provide the longest duration of protection for reduced dose 4vHPV schedule in a low- or middle-income country in the Western Pacific region. FUNDING: This study was supported by the Bill & Melinda Gates Foundation and the Department of Foreign Affairs and Trade of the Australian Government and Fiji Health Sector Support Program (FHSSP). FHSSP is implemented by Abt JTA on behalf of the Australian Government.
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ItemPrevalence and risk factors for human papillomavirus infection among female sex workers in Hanoi and Ho Chi Minh City, Viet Nam: a cross-sectional study(WORLD HEALTH ORGANIZATION, REGIONAL OFFICE WESTERN PACIFIC, 2022)OBJECTIVE: Female sex workers (FSWs) are at high risk of human papillomavirus (HPV) infections and cervical cancer due to their high number of sexual partners. The objectives of this study were to determine the prevalence of HPV and identify risk factors for high-risk HPV infection among FSWs in Hanoi and Ho Chi Minh City (HCMC), Viet Nam. METHODS: A cross-sectional study was conducted in Hanoi and HCMC between December 2017 and May 2018. We surveyed and screened 699 FSWs aged 318 years for HPV infection and abnormal cytology. A multivariable modified Cox regression model was used to determine risk factors for high-risk HPV infection. RESULTS: The overall prevalence of any HPV, high-risk HPV and HPV-16/18 infection in the 699 FSWs was 26.3%, 17.6% and 4.0%, respectively, and were similar in both cities. Multiple infections were identified in 127 participants (69.0%). HPV-52 was the most prevalent (7%), followed by HPV-58 (6%). Abnormal cytology was detected in 91 participants (13.0%). FSWs who are divorced (adjusted prevalence ratio [aPR]: 1.96, 95% confidence interval [CI]: 1.01-3.81), widowed (aPR: 3.26, 95% CI: 1.49-7.12) or living alone (aPR: 1.85, 95% CI: 1.01-3.39) were associated with a higher prevalence of high-risk HPV infection. DISCUSSION: Almost one in five FSWs in Viet Nam are infected with high-risk HPV. This highlights the importance of prevention strategies such as HPV vaccination and screening in this high-risk group.
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ItemNo Preview AvailableImpact of 16S rRNA Single Nucleotide Polymorphisms on Mycoplasma genitalium Organism Load with Doxycycline Treatment(AMER SOC MICROBIOLOGY, 2022-05-17)Doxycycline targets the 16S rRNA and is widely used for the treatment of sexually transmitted infections. While it is not highly effective at eradicating Mycoplasma genitalium infections, it can reduce organism load. The aim of this study was to investigate the association between single nucleotide polymorphisms (SNPs) in the 16S rRNA gene of M. genitalium and change in organism load. M. genitalium samples were collected from 56 men prior to commencing doxycycline and at a median of 13 of 14 doses. These were sequenced for the 16S rRNA, and the association between 16S rRNA SNPs and change in organism load was determined. 16S rRNA sequences were available for 52/56 (92.9%) M. genitalium-infected men, of which 20 (38.5%) had an undetectable load, 26 (50.0%) had a decrease in M. genitalium load (median change of 105-fold), and 6 (11.5%) had an increase in load (median change of 5-fold). The most common SNPs identified were A742G (10/52 [19.2%]), GG960-961TT/C (7/52 [13.5%]), and C1435T (28/52 [53.8%]) (M. genitalium numbering). None were associated with a change in organism load (P = 0.76, 0.16, and 0.98, respectively). Using pooled published data from 28 isolates, no clear relationship between the SNPs and doxycycline MIC was identified. In conclusion, the low efficacy of doxycycline against M. genitalium does not appear to be due to variation in the 16S rRNA gene.
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ItemNo Preview AvailableparC Variants in Mycoplasma genitalium: Trends over Time and Association with Moxifloxacin Failure(AMER SOC MICROBIOLOGY, 2022-05-17)Prevalence, trends, and treatment outcome estimates were generated for parC variants in macrolide-resistant Mycoplasma genitalium. Among 539 cases, the most common amino acid change was S83I, which increased from 13% in 2012 to 2013, to 23% in 2019 to 2020 (Ptrend = 0.046). From 381 moxifloxacin treatments, failure occurred in 58.7% (95% confidence interval [CI], 46.7 to 69.9) of cases with S83I. Other changes affecting S83 or D87 were uncommon and minor contributors to failure. The absence of S83I was highly predictive of moxifloxacin cure (96.4%; 95% CI, 93.7 to 98.2), highlighting diagnostic potential.
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