Sexually Transmitted Infections Adopting a Sexual Health Paradigm (2021) / Chapter Skim
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7 Biomedical Tools for STI Prevention and Management
7 Biomedical Tools for STI Prevention and Management
Pages 337-398
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From page 337... ...
7 Biomedical Tools for STI Prevention and Management Chapter Contents Introduction Tools for STI Diagnosis • Introduction • Approaches to STI Screening and Diagnosis • Gaps and Opportunities in STI Diagnosis Antimicrobial Tools for STI Treatment • Barriers to Therapeutic Innovation • Antimicrobial Therapy for Bacterial STIs • Antimicrobial Therapy for Viral STIs • Antimicrobial Therapy for Protozoan STIs • Gaps and Opportunities in STI Treatment Tools for STI Prevention • Condoms and Barrier Method Contraceptives • Other Contraceptive Measures • Multipurpose Prevention Technologies • Antibiotics for STI Prevention • Vaccines • Gaps and Opportunities in STI Prevention Conclusions and Recommendation Concluding Observations 337
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Translating these advances into widely available products is often impacted by a time-consuming preclinical and clinical regulatory process, which may take years and require millions of dollars. Corporate decision making regarding developing new biomedical tools for STI management also may be impacted by cost-related factors, such as the potential for STI-related stigma to hinder vaccine acceptance, relatively less costly single- rather than multiple-dose therapy for many STIs, and the desire for low-cost, public health pricing.
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will be the "Sexually Transmitted Infections Treat ment Guidelines." This report uses that language when referring to the guidelines anticipated in 2021 and the guidelines in general but the original "Sexually Transmitted Diseases Treatment Guidelines" title for the guidelines published in 2015 or earlier.
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. Biomedical tools also do not exist in a vacuum -- simply creating them will not ensure their uptake or proper use, so it is critical to think of them in the larger context -- that is, successful STI prevention strategies require effectively integrating evidence-based biomedical, behavioral, and structural interventions across the life span (see Figure 1-3 in Chapter 1)
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. Understanding high-risk behaviors and practices responsible for transmis sion can help target intervention strategies (e.g., risk reduction counseling and immediate antiretroviral therapy)
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to CDC and are used to identify infections and guide treatment. Since 1997, highly reliable NAATs, which biochemically amplify microbial DNA for pathogens such as chlamydia, gonorrhea, trichomonas, Mycoplasma genitalium, HPV, and herpes simplex virus type 2 (HSV-2)
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Syndromic approaches, however, fail to detect asymptomatic STIs and require that symptoms are bothersome enough to drive someone to seek care. In addition, multiple STI pathogens may underlie the most common STI syndromes (genital ulceration, vaginal discharge in women, and urethral discharge in men)
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For tests under development, a CLIA waiver would allow the test to be performed and interpreted outside of a laboratory by a "non-laboratorian," such as a nurse or health care worker, thereby reducing the time to results and treatment and helping to reduce transmission. Point-of-Care Tests POC tests are diagnostic tests that are completed at or near the time and place of patient care.
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; CLIA requires clinical labo ratories to be certified by CMS before they can complete diagnostic testing on human samples. The certificate type depends on the complexity of the diagnostic tests performed.
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. For example, POC tests have already changed the course of the HIV epidemic because the immediate results allow providers to implement rapid antiretroviral therapy or pre-exposure prophylaxis (PrEP)
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TABLE 7-1 Point-of-Care Tests Available and in Development for STIs DPP POC Medical Test for HIV GeneXpert Sexual Health ResistancePlus Syphilis Antibody and Syphilis OSOM Rapid POC Assay Io CT/NG CT/NG Test GC Rapid Test Serology TV Antigen Test Company Binx Health Cepheid Visby SpeeDx Syphilis Health Chembio Sekisui Check Platform Table Top Table Top None required Table Top Lateral flow Lateral flow Immunochroma Integrated Integrated Integrated PCR machine immunochromagraphic graphic Technology NAAT Real-time Real-time PlexPCR Antigen-antibody Antigen- Trichomonas vagi Small PCR PCR serology antibody nalis membrane molecule serology proteins chemistry Mouse antibodies Sample Self- and Swabs Self- and Swabs (cervical, Blood, plasma, Blood, plasma, Vaginal swabs Type clinician- (cervical, clinician- vaginal, serum serum collected self-collected collected pharyngeal, and vaginal swabs; vaginal) ; vaginal swabs ocular)
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10 min. Time Regulatory FDA, CE-IVD FDA, CE-IVD FDA pending CE-IVD FDA, FDA approved FDA, FDA pending CLIA waived CLIA waived NOTE: CE-IVD = European conformity investigational device; CLIA = Clinical Laboratory Improvement Amendments; CT = Chlamydia trachomatis; DPP = Dual Path Platform; FDA = Food and Drug Administration; NAAT = nucleic acid amplification test; NG = Neisseria gonorrhoeae; PCR = polymerase chain reaction; POC = point of care; TV = Trichomonas vaginalis.
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The STI National Strategic Plan: 2021–2025 highlights POC tests as innovative
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. The committee concurs with the plan's assessment that the development and implementation of accessible, effective, and affordable POC tests promise to enhance rapid STI diagnosis and treatment (see Chapter 12 for more information)
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. Some NAAT assays in development include assays to evaluate antimicrobial susceptibility to azithromycin; this would allow precision treatment decisions regarding specific antibiotics (Gaydos and Melendez, 2020; Gaydos et al., 2019)
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. For highly sensitive and specific NAAT assays and new POC tests to have an impact on the STI epidemic, they must be prioritized for development (Eisinger et al., 2020)
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Development of new antimicrobials for other STIs has also slowed and is limited; Table 7-2 lists examples of current clinical trials for STI antibiotics. Decisions related to STI treatment are profoundly impacted by treatment guidelines issued by public health agencies.
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Given the state of technology, particularly the possibility of rapid online publication, disseminating updated guidelines could be a continuous rather than an episodic process. Antimicrobial Therapy for Bacterial STIs In the United States, STI control surveillance and public health management strategies have focused on the three most common and widely recognized STIs (gonorrhea, chlamydia, and syphilis)
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Location(s) Date Gonorrhea Trials A Phase III, Recruiting Phase Gepotidacin Random- Esti- 1.
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Location(s) Date A Multi-Center, Recruiting Phase Zoliflodacin 3 Random- Estimated 1.
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Syphilis Trials Trial Evaluating Recruiting Phase Cefixime 400 Randomized, Esti- 1. Sponsor: September the Clinical 1/2 mg PO and parallel mated 180 Quantitative Switzerland: World Health 30, 2021 Efficacy of benzathine assignment 18+-year- RPR titer Organization Cefixime for penicillin (2:1)
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Location(s) Date Clinical Trial Recruiting Phase Cefixime Randomized, Esti- 1.
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A Phase 4 Recruiting Phase Benzathine Randomized, Estimated 1. The Sponsor: March 1, Comparative 4 penicillin G parallel 560 proportion USA: National Institute of Al- 2022 Trial of 2.4 MU IM assignment 18+-year- of subjects lergy and Infectious Diseases Benzathine old men with a Penicillin G 2.4 and women serological Locations: Million Units with response USA: Alabama; Georgia; InAdministered untreated (defined diana; Louisiana; Maryland; as a Single Dose primary, as either Massachusetts; North Carolina; Versus Three secondary, a fourfold Pennsylvania; Washington Successive or early or greater Weekly Doses latent decline in for Treatment of syphilis RPR titer Early Syphilis in compared Subjects with to baseline or Without HIV or being Infection RPR-nega[NCT03637660]
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treatment NOTES: ClinicalTrials.gov search and study recruitment status are as of September 4, 2020. DSMB = Data and Safety Monitoring Board; IM = intramuscular; mg = milligram; MSM = men who have sex with men; MU = million units; NAAT = nucleic acid amplification test; PO = per os; RPR = rapid plasma regain; USA = United States of America.
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support from the federal government (BARDA5 and National Institute of Allergy and Infectious Diseases [NIAID]
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Unlike gonorrhea, antimicrobial resistance remains rare for chlamydia, but like gonorrhea, the efficacy of recommended therapy varies when genital infections are compared to other sites (see Table 7-2)
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Antimicrobial Therapy for Viral STIs Chronic, non-HIV viral infections, such as due to HSV and HPV, require a different array of antimicrobial agents. Though antimicrobial therapy does not cure these infections, it may hasten resolution of acute signs and symptoms and reduce the probability of sexual transmission.
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Rather, the substantial menu of pathogens requires an equally large variety of antimicrobial agents. Management of common STIs has been variously challenged by, among other things, progressive antimicrobial resistance (gonorrhea, trichomoniasis)
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. Among tools for STI prevention, condoms (when used correctly and consistently)
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Clinical trials in which high-risk populations used nonoxynol-9 detergent spermicides, however, demonstrate no clear, significant protective effect for bacterial STIs (Roddy et al., 1998, 2002; Wilkinson et al., 2002) and were associated with an increased risk of HIV in one trial (Van Damme et al., 2002)
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. Antibiotics for STI Prevention Effective STI treatment prevents transmission.
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In addition, if STI vaccine development is successful, strategies required for optimal deployment will be complicated, recognizing the uneven distribution of
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. Developing STI vaccines requires consideration of target populations at risk, including adolescents and young adults.
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The field to date has been unsuccessful with HSV-2 viral vaccines. Bacterial and parasitic STI vaccines against syphilis, gonorrhea, chlamydia, or trichomoniasis, to name a few, have been similarly unsuccessful, but clinical trials continue.
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Description Participants Measure(s) Location(s)
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if immuni- mated 50 cell cross-reactive United Kingdom: 2022 Reactive Antigens and sation of 18–25-year- responses against University of Anti-Gonococcal Anti- individuals old men or Neisseria gonorrhoeae Oxford bodies in Key Popula- at risk for women tions in Kenya gonococcal Location: [NCT04297436] infec- Kenya: Kilifi tion with 4CMenB (Bexsero)
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A Multi-Centre Ran- Not yet Phase 3 4CMenB Random- Esti- 1. To measure wheth- Sponsor: February domised Controlled Trial recruiting (Bexsero)
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Date Institute for Global Recruiting Phase 4 4CMenB vac- Single Esti- 1. The change in Sponsor: February Health and Infectious cine (Bexsero)
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old women tions and laboratory Serum Institut 2017 and Placebo Controlled Al(OH) 3, and safety of adjuvanted Clinical Trial of the placebo chlamydia vaccine Location: Safety of SSI's Adjuvant- United Kingdom: ed Chlamydia Vaccine London CTH522 in Healthy Women Aged 18 to 45 Years [NCT02787109]
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Date Herpes Simplex Virus Trials Safety and Efficacy of Active, not Phase 1 Six HSV 2 Random- Esti- 1. Number of partici- Sponsor: May 2021 4 Investigational HSV recruiting and 2 formulations ized, mated 381 pants with immedi- France: Sanofi 2 Vaccines Administered sequential 18–55-year- ate adverse events Pasteur by Intramuscular Route assignment old, HSV-2 2.
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AESI = adverse events of special interest; HSV-2 = herpes simplex virus type 2; IgA = Immunoglobulin A; IgG = Immunoglobulin G; IgM = Immunoglobulin M; MAAE = medically attended adverse event; SAE = serious adverse event; USA = United States of America.
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. Herpes simplex virus type 2 (HSV-2)
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No active clinical trials for syphilis vaccines exist; however, current research on vaccine development focuses on a better understanding of surface-exposed treponemal proteins and a better determination of the best correlates of immunity (NIAID, 2019)
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, a true failure of public health and health care. Stakeholders in STI Vaccine Development NIH and CDC NIH has the most visible U.S.
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See the section in Chapter 12 on Public–Private Partnerships for STI Prevention and Control for more information. STI Vaccines and Risk Compensation Increasing access to antiretroviral therapy for people living with HIV and to HIV PrEP for vulnerable, HIV-seronegative populations has been associated with rising STI incidence in MSM in some studies (Ramchandani and Golden, 2019)
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. The challenges in developing, implementing, and ensuring widespread use of STI prevention tools highlights the need for accurate and available diagnostic and treatment tools, as well as concurrent behavioral and structural interventions.
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Increas ing antimicrobial resistance has threatened the continued efficacy and ease of STI treatment and the pipeline for development of both new antimicrobials and vaccines for STI prevention and treatment has been constrained by an unfavorable business case that includes an expensive and time-consuming regulatory pathway to approval and widespread availability. Conclusion 7-2: Syndromic diagnosis and treatment for persons with genito urinary symptoms remain common.
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, but after unacceptable failure rates, delafloxacin and solithromycin are no longer being evaluated. Similarly, other than the noteworthy exception of vaccines for HPV, which have been marketed for cancer rather than STI prevention, STI vaccine research and other prevention tools (e.g., antibiotic PrEP, expedited partner therapy)
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Developing these drugs and vaccines for STI management and prevention has been, in part, constrained by the impact of perceived STI-related stigma on assessment of potential markets and a costly and time-consuming regulatory pathway. New and existing biomedical tools will need to be integrated with behavioral and structural interventions across the life span to have the greatest effect on the STI epidemic.
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2021. At home testing for sexually transmitted infections during the COVID-19 pandemic.
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Sexually Transmitted Infections 87(4)
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2012. The challenge of developing a herpes simplex virus 2 vaccine.
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Sexually Transmitted Infections 93(S4)
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2020. Sexually Transmitted Infections National Strategic Plan for the United States: 2021-2025.
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2019. Preferred product attributes of potential multipurpose prevention technologies for unintended pregnancy and sexually transmitted infections or HIV among U.S.
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2020. Development of vaccines against the sexually transmitted infections gonorrhoea, syphilis, chlamydia, herpes simplex virus, human immunodeficiency virus and Zika virus.
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2018. Post-exposure prophylaxis with doxycycline to prevent sexually transmitted infections in men who have sex with men: An open label randomised substudy of the ANRS IPERGAY trial.
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2019. Spoken remarks: Presented at Meeting 3 of the Committee on Preven tion and Control of Sexually Transmitted Infections in the United States.
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Sexually Transmitted Infections 82(Suppl 5)
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2007. Training modules for the syndromic management of sexually transmitted infections.
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2002. Nonoxynol-9 spermicide for prevention of vaginally acquired HIV and other sexually transmitted infections: Systematic review and meta-analysis of randomised controlled trials including more than 5000 women.
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