Enhanced STI management to reduce genital inflammation and HIV risk

加强性传播感染管理，减少生殖器炎症和艾滋病毒风险

• 批准号: 8838882
• 负责人: Nigel Joel Garrett
• 金额: $ 13.26万
• 依托单位: CENTRE/AIDS PROGRAMME/RES/SOUTH AFRICA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-02-01 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8838882
• 关键词: Address; African; Am 80; Bacterial Vaginosis; Bedside Testings; Biological Assay; Caring; Chlamydia trachomatis; Communities; Detection; Diagnosis; Diagnostic tests; Dose; Drug resistance in tuberculosis; Ensure; Female; Genital system; Goals; HIV; HIV Infections; HIV risk; Home environment; Human; Individual; Infection; Inflammation; Inflammatory; Intervention; Left; Measurement; Measures; Modeling; Neisseria gonorrhoeae; Participant; Partner Notification; Play; Population; Province; Public Health; Reader; Recruitment Activity; Recurrence; Risk; Risk Reduction; Role; Sensitivity and Specificity; Sexual Partners; Sexually Transmitted Diseases; South Africa; Supervision; Syndrome; Technology; Testing; Trichomonas vaginalis; Tuberculosis; Ulcer; Urethra; Vaginal Discharge; Woman; base; cytokine; effective therapy; innovation; interest; novel; point-of-care diagnostics; population based; programs; public health relevance; success

 DESCRIPTION (provided by applicant): Sexually transmitted infections (STIs) are strongly associated with HIV risk. However, population based studies to manage STIs as a way of reducing HIV risk have had limited success. Recent studies show that elevated genital tract inflammatory cytokines are strongly associated with an increased risk of HIV acquisition, and STIs are one of the commonest causes of elevated genital tract cytokines. This interest in the role of cytokines in HIV acquisition has reinvigorated interest in STIs and whether better management strategies can have a role in HIV risk reduction. HIV and STIs extremely common in the South African province of KwaZulu-Natal (KZN) where there are many challenges with STI diagnosis and treatment, including the reliance on syndromic management, an approach based on the recognition of STI syndromes (vaginal discharge, urethral discharge and genital ulceration), followed by treatment targeting the common causes of the syndrome. This approach has a low sensitivity and specificity for detecting STIs, leaving 80-85% undiagnosed and untreated. Other challenges with current STI management include limited partner notification and treatment. At a population level, the result is that most STIs remain untreated and the burden of STIs within the community remains unchecked. Our goal is to determine if an innovative, enhanced program of STI management will result in a higher cure rate and a lower recurrence rate, with a subsequent reduction in genital inflammatory cytokines and hence HIV risk. This proof of concept study will be addressed by identifying individuals with STIs using an innovative, point-of-care diagnostic test (an automated, cartridge-based nucleic amplification assay (GeneXpert) for the simultaneous detection of N. gonorrhoeae and C. trachomatis. This technology has recently been introduced on a large scale across South Africa to detect tuberculosis (TB) and TB drug resistance, thereby accelerating diagnosis, treatment and enhancing public health initiatives to control TB. We will then measure 48 genital tract cytokines using Bio-Plex Pro Human Cytokine kits and a Bio-Plex MagPix Array Reader. We will then treat them immediately with appropriate therapy under direct supervision, giving the participants the same treatment to take home for their sexual partners (expedited partner therapy) and asking them to return after 6 weeks and 3 months for a test of cure. We will then test participants for genital tract inflammatory cytokines and determine if these have decreased. Overall, our innovative enhanced management package for STI care, offers the best opportunity to reduce STIs, by ensuring that the individual is cured and reducing the risk of reinfection using expedited partner therapy. This will allow us to determine whether genital inflammation can be reduced after effective STI treatment, and ultimately reduce the risk of HIV acquisition in SA and also in the USA.

 描述（由申请人提供）：性传播感染（STI）与艾滋病毒风险密切相关。然而，以人口为基础的研究管理性传播感染作为减少艾滋病毒风险的一种方式，取得的成功有限。最近的研究表明，生殖道炎性细胞因子升高与艾滋病毒感染风险增加密切相关，而性传播感染是生殖道细胞因子升高的最常见原因之一。这种对细胞因子在艾滋病毒感染中的作用的兴趣重新激发了对性传播感染以及更好的管理策略是否可以在降低艾滋病毒风险方面发挥作用的兴趣。艾滋病毒和性传播感染在南非的夸祖鲁-纳塔尔省（KZN）极为常见，在那里，性传播感染的诊断和治疗面临许多挑战，包括依赖综合症管理，这是一种基于对性传播感染综合症（阴道分泌物、尿道分泌物和生殖器溃疡）的认识，然后针对综合症的常见原因进行治疗的方法。这种方法检测性传播感染的敏感性和特异性较低，80-85%的人未被诊断和治疗。当前性传播感染管理的其他挑战包括有限合伙人通知和治疗。在人口一级，结果是大多数性传播感染仍然得不到治疗，社区内的性传播感染负担仍然得不到控制。我们的目标是确定创新的、增强的性传播感染管理计划是否会导致更高的治愈率和更低的复发率，从而减少生殖器炎症细胞因子，从而减少艾滋病毒风险。这项概念验证研究将通过使用创新的即时诊断测试（一种自动化的基于核酸扩增的核酸扩增检测（GeneXpert），用于同时检测N.淋球菌和C.沙眼这项技术最近在南非大规模推广，用于检测结核病和结核病耐药性，从而加快诊断、治疗和加强控制结核病的公共卫生举措。然后，我们将使用Bio-MagPix MagPix Array Reader和Bio-MagPix Pro Human Cytokine试剂盒测量48种生殖道细胞因子。然后，我们将在直接监督下立即对他们进行适当的治疗，给予参与者与他们的性伴侣相同的治疗（快速伴侣治疗），并要求他们在6周和3个月后返回进行治愈测试。然后，我们将测试参与者的生殖道炎性细胞因子，并确定这些细胞因子是否减少。总体而言，我们创新的STI护理强化管理包提供了减少STI的最佳机会，通过确保个人治愈并使用快速治疗减少再感染的风险。 伴侣治疗这将使我们能够确定有效的STI治疗后生殖器炎症是否可以减少，并最终降低SA和美国的HIV感染风险。