Bridging of Neisseria gonorrhoeae lineages across sexual networks in the HIV pre-exposure prophylaxis era.
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ABSTRACT:
SUBMITTER: Williamson DA
PROVIDER: S-EPMC6728426 | biostudies-literature | 2019 Sep
REPOSITORIES: biostudies-literature
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Bridging of Neisseria gonorrhoeae lineages across sexual networks in the HIV pre-exposure prophylaxis era.
Williamson Deborah A DA Chow Eric P F EPF Gorrie Claire L CL Seemann Torsten T Ingle Danielle J DJ Higgins Nasra N Easton Marion M Taiaroa George G Grad Yonatan H YH Kwong Jason C JC Fairley Christopher K CK Chen Marcus Y MY Howden Benjamin P BP
Nature communications 20190905 1
Whole genome sequencing (WGS) has been used to investigate transmission of Neisseria gonorrhoeae, but to date, most studies have not combined genomic data with detailed information on sexual behaviour to define the extent of transmission across population risk groups (bridging). Here, through combined epidemiological and genomic analysis of 2,186N. gonorrhoeae isolates from Australia, we show widespread transmission of N. gonorrhoeae within and between population groups. We describe distinct tra ...[more]
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Project description:OBJECTIVES:Neisseria gonorrhoeae (NG) is a significant global public health concern due to rising diagnoses rates and antimicrobial resistance. Molecular combined with epidemiological data have been used to understand the distribution and spread of NG, as well as relationships between cases in sexual networks, but the public health value gained from these studies is unclear. We conducted a systematic review to examine how molecular epidemiological studies have informed understanding of sexual networks and NG transmission, and subsequent public health interventions. METHODS:Five research databases were systematically searched up to 31st March 2017 for studies that used sequence-based DNA typing methods, including whole genome sequencing, and linked molecular data to patient-level epidemiological data. Data were extracted and summarised to identify common themes. RESULTS:Of the 49 studies included, 82% used NG Multi-antigen Sequence Typing. Gender and sexual orientation were commonly used to characterise sexual networks that were inferred using molecular clusters; clusters predominantly of one patient group often contained a small number of isolates from other patient groups. Suggested public health applications included using these data to target interventions at specific populations, confirm outbreaks, and inform partner management, but these were mainly untested. CONCLUSIONS:Combining molecular and epidemiological data has provided insight into sexual mixing patterns, and dissemination of NG, but few studies have applied these findings to design or evaluate public health interventions. Future studies should focus on the application of molecular epidemiology in public health practice to provide evidence for how to prevent and control NG.
| S-EPMC5999358 | biostudies-literature
Project description:Approximately 1.1 million individuals in the United States are living with HIV/AIDS. HIV disproportionately affects young, black men who have sex with men (YBMSM). Recent biomedical advances, including the use of antiretroviral therapy as pre-exposure prophylaxis (PrEP), hold promise for preventing HIV infections. However, PrEP uptake remains slow among those most at-risk. To develop and test an intervention to address HIV disparities in YBMSM, we conducted qualitative interviews with 29 YBMSM from Jackson, Mississippi, to learn more about their views of PrEP. Twenty-nine PrEP-eligible YBMSM were enrolled and participated in either semistructured interviews or focus groups. They were asked about PrEP use, messaging, and promotion. Data were coded based on an iteratively developed coding scheme and entered into NVivo to facilitate thematic analysis. Our analysis identified the following three main themes: (1) the role of setting, context, and stigma in health care, (2) targeted PrEP messaging is further stigmatizing, and (3) recommendations for PrEP messaging and care. YBMSM in our sample felt highly stigmatized in their current environment and felt that PrEP messaging targeting YBMSM only enhanced their sense of marginalization. They concluded that broad and inclusive messaging would be just as relevant and cause less stigma. Our findings were somewhat surprising, as several prior studies benefited from using targeted materials to engage YBMSM in HIV prevention and PrEP uptake. The study's location may explain this difference in findings, which suggests the importance of considering local conditions and opinions when developing interventions for HIV prevention among minority populations.
| S-EPMC6839422 | biostudies-literature
Project description:BackgroundInterventions to promote HIV pre-exposure prophylaxis (PrEP) among Black sexual minority men (BSMM) are especially important, given the disproportionate HIV incidence and relatively low uptake of PrEP among BSMM.MethodsWe conducted a systematic literature review to identify the characteristics of interventions between 2016 and 2021 promoting PrEP use among BSMM. We synthesized these studies based on sample size, location, the use of peer-based delivery, and key intervention targets.ResultsOf the starting total 198 articles, 10 were included in the final review, with the majority of included studies being randomized controlled trials. We identified providing PrEP access, PrEP counseling, HIV and PrEP education, linkage to general health care, and peer-based support as key successful intervention components. The starkest difference between interventions with and without demonstrated PrEP improvements was the outcome: all interventions focused on PrEP initiation led to large improvements, but those focused on PrEP adherence did not. No other factors demonstrated distinct differences between successful and unsuccessful interventions.ConclusionWe identified notable differences in intervention efficacy between PrEP initiation and PrEP adherence outcomes; PrEP adherence is necessary for optimal HIV prevention. Future interventions promoting and measuring PrEP adherence, with a focus on cultural competence and peer components, are recommended.
| S-EPMC8871743 | biostudies-literature
Project description:BackgroundAfrica has the highest incidence of gonorrhea in the world. However, little is known about gonococcal populations in this continent or mechanisms of antimicrobial resistance (AMR).MethodsWhole-genome sequence data were analyzed from 103 Neisseria gonorrhoeae isolates from 73 patients, mainly men who have sex with men, from coastal Kenya. We annotated loci, defined the core genome, defined mechanisms of AMR, and performed phylogenetic analysis. For patients with multiple episodes of gonorrhea, we determined whether infections occurred with related strains.ResultsWe identified 3 clusters of isolates that are phylogenetically distinct from isolates found elsewhere. Plasmids were virtually ubiquitous: pTetM and pblaTEM were found in 97%, and 55% of isolates, respectively. This was associated with high doxycycline use for undiagnosed sexually transmitted infections. Twenty-three percent of multiple episodes of gonorrhea in the same individual were caused by a related strain, suggesting inadequate treatment or reinfection.ConclusionsThe prevalence of plasmid-mediated AMR in Kenyan gonococci contrasts with that in wealthy countries, where AMR is largely chromosomally mediated. Antimicrobials have a profound effect on the maintenance of lineages harboring plasmids. Doxycycline can select for tetracycline and penicillin resistance, through plasmid cooperation. Understanding the mechanisms of AMR in high-risk groups is required to inform treatment strategies.
| S-EPMC6057544 | biostudies-literature
Project description:Post-exposure prophylaxis with doxycycline (doxyPEP) is being introduced to prevent bacterial sexually transmitted infections (STIs). Pre-existing tetracycline resistance in Neisseria gonorrhoeae limits doxyPEP effectiveness against gonorrhea, and selection for tetracycline resistant lineages may influence prevalence of resistance to other antimicrobials via selection for multi-drug resistant strains. Using genomic and antimicrobial susceptibility data from 5,644 clinical isolates of N. gonorrhoeae , we assessed the near-term impact of doxyPEP on N. gonorrhoeae antimicrobial resistance. We found that the impact on antimicrobial resistance is likely to be influenced by the strength of selection for plasmid-encoded and chromosomally-encoded tetracycline resistance, as isolates with high-level, plasmid-encoded resistance had lower minimum inhibitory concentrations to other antimicrobials compared to isolates with low-level tetracycline resistance. The impact of doxyPEP may differ across demographic groups and geographic regions within the United States due to variation in pre-existing tetracycline resistance.
| S-EPMC10055447 | biostudies-literature
Project description:In Neisseria gonorrhoeae, the mosaic type of penA, which encodes penicillin-binding protein 2 (PBP 2), is associated with reduced susceptibility to oral cephalosporins. To investigate the relatedness of N. gonorrhoeae clinical isolates with reduced susceptibility, we sequenced the penA genes of 32 isolates. Five different amino acid sequence types of PBP 2 were identified, but all seemed to be derivatives of pattern X of PBP 2 (PBP 2-X). However, multilocus sequence typing of the isolates showed that the isolates belonged to six different sequence types. As PBP 2-X was identified in three different sequence types, horizontal transfer of the penA allele encoding PBP2-X was suggested. We demonstrated that the penA gene could be transferred from an isolate with reduced susceptibility to a sensitive isolate by natural transformation. Comparison of the sequence of the penA-flanking regions of 12 transformants with those of the donor and the recipient suggested that at least a 4-kb DNA segment, including the penA gene, was transferred. During horizontal transfer, some of the penA alleles also acquired variations due to point mutations and genetic exchange within the allele. Our results provide evidence that the capacity for natural transformation in N. gonorrhoeae plays a role in the spread of chromosomal antibiotic resistance genes and the generation of diversity in such genes.
| S-EPMC2826007 | biostudies-literature
Project description:Rectal pre-exposure prophylaxis (PrEP) will be a critical component of HIV prevention products due to the prevalence of unprotected receptive anal intercourse among men who have sex with men and heterosexual couples. Given the biological considerations of this compartment and the complexity of HIV infection, design of a successful rectal microbicide product faces a number of challenges. Important information is being compiled to begin to address deficits in knowledge toward design of rectal PrEP products for men and women. Aspects of formulation development and preclinical and clinical evaluation of rectal products studied to date are summarized in this review. This article is based on a presentation at the "Product Development Workshop 2013: HIV and Multipurpose Prevention Technologies," held in Arlington, Virginia on February 21-22, 2013. It forms part of a special supplement to Antiviral Research.
| S-EPMC3896093 | biostudies-literature
Project description:Pre-exposure prophylaxis (PrEP) has emerged as a promising strategy for preventing the transmission of HIV. Although only one formulation is currently approved for PrEP, research into both new compounds and new delivery systems for PrEP regimens offer intriguing challenges from the perspective of pharmacokinetic and pharmacodynamic modeling. This review aims to provide an overview the current modeling landscape for HIV PrEP, focused on PK/PD and QSP models relating to antiretroviral agents. Both current PrEP treatments and new compounds that show promise as PrEP agents are highlighted, as well as models of uncommon administration routes, predictions based on models of mechanism of action and viral dynamics, and issues related to adherence to therapy. The spread of human immunodeficiency virus (HIV) remains one of the foremost global health concerns. In the absence of a vaccine, other prophylactic strategies have been developed to prevent HIV transmission. One approach, known as pre-exposure prophylaxis (PrEP), allows HIV-negative individuals who are at high risk of exposure to the virus, be it through an HIV-positive sexual partner or through the shared use of drug injection equipment, to substantially reduce the risk of developing an HIV infection. PrEP is a relatively recent approach to combating the HIV epidemic, with the only currently approved treatment being Truvada, a daily oral antiretroviral (ARV) therapy initially indicated in the treatment of active HIV-1 infections, but approved for HIV PrEP in 2012. Although PrEP therapy has consistently demonstrated high efficacy in preventing HIV infection, this efficacy is dependent on patient adherence to the prescribed treatment regimen. This can present a significant problem in low- and middle-income countries, which may lack the infrastructure to provide sufficient access to PrEP medication to maintain daily dosing regimens. Furthermore, while the conventional approach has generally been to advocate for continuous administration akin to regimens used for viral suppression in infected patients, there has been some discussion of whether a better treatment paradigm might be to push for PrEP therapy primarily during those known periods of heightened exposure risk, while relying on post-exposure prophylaxis regimens to prevent infection after unanticipated exposures during low-risk periods. These considerations have led to a push for the development of long-duration and on-demand PrEP formulations, including subdermal and subcutaneous implants, slow-release intramuscular depot injections, vaginal and rectal antimicrobial gels, and intravaginal rings and dissolving films. PrEP therapy is a quickly evolving field, with a variety of antiretroviral compounds and formulations under investigation. This review aims to report on notable drugs and formulations from a pharmacokinetic/pharmacodynamic (PK/PD) modeling perspective. Given the nature of PrEP as a preventive therapy designed for long-term use, clinical trials for PrEP therapies can last for months or even years, particularly in the case of long-duration formulations. Furthermore, in contrast to antiretroviral trials in infected patients, pharmacodynamic endpoints in PrEP therapies are difficult to quantify, as the primary endpoint for efficacy is generally the rate of seroconversion. Computational modeling approaches offer flexible and powerful tools to provide insight into drug behavior in clinical settings, and can ultimately reduce the time, expense, and patient burden incurred in the development of PrEP therapies.
| S-EPMC7005100 | biostudies-literature
Project description:BACKGROUND:Despite evidence supporting pre-exposure prophylaxis (PrEP) efficacy, there are concerns regarding the feasibility of widespread PrEP implementation among men who have sex with men (MSM). To inform the development of targeted PrEP delivery guidelines, sexual risk trajectories among HIV-negative MSM were characterized. METHODS:At semiannual visits from 2003 to 2011, HIV-negative MSM (N = 419) participating in the Multicenter AIDS Cohort Study provided data on sexual risk behaviors (SRBs) since their last visit. Based on their reported behaviors, participants were assigned a SRB score at each visit as follows: 0 = no insertive or receptive anal intercourse, 1 = no unprotected insertive or receptive anal intercourse, 2 = only unprotected insertive anal intercourse, 3 = unprotected receptive anal intercourse with 1 HIV-negative partner, 4 = condom serosorting, 5 = condom seropositioning, and 6 = no seroadaptive behaviors. Group-based trajectory modeling was used to examine SRB scores (<4 vs. ?4) and identify groups with distinct sexual risk trajectories. RESULTS:Three sexual risk trajectory groups were identified: low-risk (n = 264; 63.0%), moderate-risk (n = 96; 22.9%; mean duration of consecutive high-risk intervals ?1 year), and high-risk (n = 59; 14.1%; mean duration of consecutive high-risk intervals ?2 years). Compared to low-risk group membership, high-risk group membership was associated with younger age (in years) [adjusted odds ratio (AOR) = 0.92, 95% confidence interval (CI): 0.88 to 0.96], being White (AOR = 3.67, 95% CI: 1.48 to 9.11), earning an income ?$20,000 (AOR = 4.98, 95% CI: 2.13 to 11.64), distress/depression symptoms (Center for Epidemiologic Studies Depression Scale ? 16) (AOR = 2.36, 95% CI: 1.14 to 4.92), and substance use (AOR = 2.00, 95% CI: 1.01 to 3.97). CONCLUSIONS:Screening for the sociodemographic and behavioral factors described above may facilitate targeted PrEP delivery during high-risk periods among MSM.
| S-EPMC4026016 | biostudies-literature
Project description:In Australia, gonococcal isolates are monitored for antimicrobial susceptibilities. In Western Australia (WA), gonorrhoea notification rates increased by 63 % between 2013 and 2016, with the steepest increase occurring between 2015 and 2016, before stabilizing at this higher baseline between 2017 and 2020. This increased prevalence was associated with antimicrobial-susceptible (AMS) lineages. To understand the provenance of these isolates causing gonorrhoea in WA, whether they were introduced or expanded from endogenous lineages, 741 isolates were collected in 2017 and characterized by both iPLEX typing and whole genome sequencing (WGS). Antibiograms and genocoding of the isolates revealed that AMS isolates were most prevalent in the remote regions, while the urban/rural regions were characterized by antimicrobial-resistant (AMR) isolates. iPLEX typing identified 78 iPLEX genotypes (WA-1 to WA-78) of which 20 accounted for over 88 % of isolates. WA-10 was the most frequently identified genotype in the urban/rural regions whilst WA-29 was the most frequently identified genotype in the remote regions. Genotypes WA-38, WA-52 and WA-13 accounted for 81 % (n=36/44) of the azithromycin-resistant N. gonorrhoeae (AziR) isolates. A representative isolate of each iPLEX genotype and AMR biotype was whole genome sequenced and analysed using MLST, NG-MAST and NG-STAR, and the novel core genome clustering Ng_cgc_400 typing scheme. Five predominant Bayesian population groups (termed BPG-1 to 5) were identified in the study collection. BPG-1 and BPG-2 were associated with AMS isolates from the remote regions. BPG-1 and BPG-2 were shown to be unique to the remote regions based on a minimum spanning tree against 4000 international isolates. AMS isolates in urban/rural regions were dominated by international lineages. AziR and Cef DS (decreased susceptibility to ceftriaxone) was concentrated in three urban/rural genomic groups (BPG-3, 4 and 5). Azithromycin minimum inhibitory concentrations (0.5-16 mg l-1) correlated with the accumulation of mtrR mutations or/and the fraction of 23S rRNA C2611T mutated copies. The majority of isolates in BPG-3, 4 and 5 could be correlated with known AMR lineages circulating globally and nationally. In conclusion, the surge in AMS isolates in WA in 2017 was due to importation of international AMS lineages into urban/rural regions, whilst the local AMS lineages persisted largely in the remote regions. Bridging between the urban/rural and remote regions was relatively rare, but continued surveillance is required to prevent ingress of AMR strains/lineages into the remote regions of WA.
| S-EPMC10132056 | biostudies-literature