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Countering the rise of syphilis: A role for doxycycline post-exposure prophylaxis?

ABSTRACT: Doxycycline post-exposure prophylaxis (PEP) holds the potential to mitigate increasing rates of syphilis among sexual minority men (SMM) in the US yet has received limited attention. Since evaluation of this intervention in actual populations is not currently feasible, we used agent-based models (ABM) to assess the population-level impact of this strategy. We adapted ABM of HIV and HPV transmission, representing a population of 10,230 SMM in Philadelphia, Pennsylvania, US. Parameter inputs were derived from the literature, and ABM outputs during the pre-intervention period were calibrated to local surveillance data. Intervention scenarios varied doxycycline uptake by 20, 40, 60, 80 and 100%, while assuming continued condom use and syphilis screening and treatment. Under each intervention scenario, we incorporated treatment adherence at the following levels: 0, 20, 40, 60, 80 and 100%. Long-term population impact of prophylactic doxycycline was measured using the cumulative incidence over the 10-year period and the percentage of infections prevented attributable to doxycycline at year 10. An uptake scenario of 20% with an adherence level of 80% would reduce the cumulative incidence of infections by 10% over the next decade, translating to 57 fewer cases per 1000 SMM. At year 10, under the same uptake and adherence level, 22% of infections would be prevented due to doxycycline PEP in the instances where condoms were not used or failed. Findings suggest that doxycycline PEP will have a modest impact on syphilis incidence when assuming a reasonable level of uptake and adherence. Doxycycline PEP may be most appropriate as a secondary prevention measure to condoms and enhanced syphilis screening for reducing infections among SMM.

SUBMITTER: Tran NK

PROVIDER: S-EPMC8688295 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Women in Africa face disproportionate risk of human immunodeficiency virus (HIV) acquisition, accounting for more than half of new infections in Africa and similarly face a disproportionate burden of sexually transmitted infections (STIs). Very high STI prevalence is being observed globally, especially among people taking pre-exposure prophylaxis (PrEP) for HIV prevention. Doxycycline post-exposure prophylaxis (dPEP) has been proposed as an STI prevention strategy to reduce chlamydia, syphilis, and possibly gonorrhea, and trials are ongoing among cisgender men who have sex with men (MSM) and transgender women who are taking PrEP in high-income settings. We designed and describe here the first open-label trial to determine the effectiveness of dPEP to reduce STI incidence among cisgender women. We are conducting an open-label 1:1 randomized trial of dPEP versus standard of care (STI screening and treatment and risk-reduction counseling without dPEP) among 446 Kenyan women aged ≥ 18 and ≤ 30 years old women taking PrEP. Women are followed for 12 months, with quarterly STI testing, treatment, and adherence counseling. The primary trial outcome will be the combined incidence of Chlamydia trachomatis, Neisseria gonorrhoeae, and Treponema pallidum, compared between the randomized groups. We will also assess dPEP acceptability, tolerability, safety, impact on sexual behavior, adherence, and occurrence of antimicrobial resistance (AMR) in N. gonorrhoeae and C. trachomatis isolates. Finally, we will estimate cost per incident STI case and complications averted accounting for nonadherence and benefits relative AMR or side effects. The results of this trial may have immediate implications for the global epidemic of STIs and sexual health. If effective, dPEP could put STI prevention into women's hands. While dPEP may be able to prevent STIs, it carries important risks that could counter its benefits; global debate about the balance of these potential risks and benefits requires data to inform policy and implementation and our study aims to fill this gap. ClinicalTrials.gov NCT04050540 .

Project description:With the rise of the second pandemic wave of the novel influenza A (H1N1) virus in the current season in the Northern Hemisphere, pandemic plans are being carefully re-evaluated, particularly for the strategic use of antiviral drugs. The recent emergence of oseltamivir-resistant in treated H1N1 patients has raised concerns about the prudent use of neuraminidase inhibitors for both treatment of ill individuals and post-exposure prophylaxis of close contacts.We extended an established population dynamical model of pandemic influenza with treatment to include post-exposure prophylaxis of close contacts. Using parameter estimates published in the literature, we simulated the model to evaluate the combined effect of treatment and prophylaxis in minimizing morbidity and mortality of pandemic infections in the context of transmissible drug resistance.We demonstrated that, when transmissible resistant strains are present, post-exposure prophylaxis can promote the spread of resistance, especially when combined with aggressive treatment. For a given treatment level, there is an optimal coverage of prophylaxis that minimizes the total number of infections (final size) and this coverage decreases as a higher proportion of infected individuals are treated. We found that, when treatment is maintained at intermediate levels, limited post-exposure prophylaxis provides an optimal strategy for reducing the final size of the pandemic while minimizing the total number of deaths. We tested our results by performing a sensitivity analysis over a range of key model parameters and observed that the incidence of infection depends strongly on the transmission fitness of resistant strains.Our findings suggest that, in the presence of transmissible drug resistance, strategies that prioritize the treatment of only ill individuals, rather than the prophylaxis of those suspected of being exposed, are most effective in reducing the morbidity and mortality of the pandemic. The impact of post-exposure prophylaxis depends critically on the treatment level and the transmissibility of resistant strains and, therefore, enhanced surveillance and clinical monitoring for resistant mutants constitutes a key component of any comprehensive plan for antiviral drug use during an influenza pandemic.

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Countering the rise of syphilis: A role for doxycycline post-exposure prophylaxis?

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