Improving Neonatal health Through Rapid malaria testing in Early Pregnancy with high-sensitivity Diagnostics (INTREPiD)

通过妊娠早期快速疟疾检测和高灵敏度诊断来改善新生儿健康 (INTREPiD)

• 批准号: 10405395
• 负责人: Steve Myer Taylor
• 金额: $ 140.77万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10405395
• 关键词: Address; Africa South of the Sahara; Aftercare; Antimalarials; Area; Clinic; Clinical; Clinical Trials; Collaborations; Communicable Diseases; Complement; Country; Data; Democratic Republic of the Congo; Detection; Development; Diagnostic Sensitivity; Diagnostic tests; Discipline of obstetrics; Dose; Drug Kinetics; Enrollment; Epidemiology; Fetal Growth; First Pregnancy Trimester; Goals; Guidelines; Infant; Infection; Institution; Intercept; Intervention; Kenya; Left; Low Birth Weight Infant; Low Prevalence; Malaria; Malawi; Measures; Modeling; Neonatal Mortality; Neonatology; Outcome; Parasites; Placentation; Plasmodium falciparum; Population; Pregnancy; Pregnancy Outcome; Pregnant Women; Premature Birth; Prevention strategy; Preventive therapy; Prophylactic treatment; Pyrimethamine-Sulfadoxine; Randomized; Rapid diagnostics; Reporting; Resource-limited setting; Risk; Safety; Schedule; Second Pregnancy Trimester; Small for Gestational Age Infant; Testing; Third Pregnancy Trimester; Treatment Efficacy; Treatment Protocols; Update; Woman; adverse pregnancy outcome; antenatal; artemether; benflumetol; cohort; density; design; early pregnancy; effective therapy; efficacy testing; experience; fetal loss; high risk population; improved; infant death; infection risk; innovation; malaria infection; mathematical model; neonatal death; neonatal health; novel strategies; pharmacokinetics and pharmacodynamics; prenatal; prevent; primary outcome; screening; success; transmission process; treatment as usual; treatment strategy

Project Summary/Abstract Newborn health has improved globally but there remains a critical need in resource-limited settings to reduce neonatal mortality. Nearly all infant deaths in sub-Saharan Africa occur in babies that are small or low birthweight, which often result from antenatal infections with Plasmodium falciparum. These malaria effects can be partially mitigated by pregnancy-specific measures including the administration of monthly antenatal doses of sulfadoxine-pyrimethamine as intermittent preventive therapy during pregnancy (IPTp-SP), but these are not typically implemented until the 2nd trimester, and so do not mitigate the risks of infection in the 1st trimester. It is now feasible to include 1st trimester screening for malaria parasites owing to: i) updated WHO guidelines that recommend an expended schedule of 8 ANC contacts, with the first prior to 12 weeks gestation, ii) the availability of high-sensitivity malaria rapid diagnostic tests (HS-RDT) with enhanced detection of low-density infections, and iii) accumulated safety data that enable the use of Artemether-Lumefantrine (AL) for malaria treatment in the 1st trimester. We hypothesize that, compared to women who enter ANC and receive usual care, women who are screened in the 1st trimester with an HS-RDT will have a lower prevalence of a poor pregnancy outcome, and we will test this through the Improving Neonatal health Through Rapid malaria testing in Early Pregnancy with high-sensitivity Diagnostics (INTREPiD) study in Western Kenya and the Democratic Republic of the Congo (DRC). In Aim 1, the INTREPiD study will enroll women in the 1st trimester and randomize them 1:1 to usual care or to screening with an HS-RDT followed by treatment of positives with AL, and then follow them through delivery. Following the 1st trimester intervention, all women will receive usual ANC, including IPTp-SP. The primary outcome will be the composite outcome of low birthweight, small-for- gestational age, preterm birth, fetal loss, or neonatal death. In Aim 2, we will measure the therapeutic efficacy and pharmacokinetics of AL administration in the 1st trimester through a population PK study following standard AL dosing and compare PK parameters with historical controls. In Aim 3, we will use trial data to model the potential incremental benefits of enhanced-sensitivity diagnostics and alternate treatment regimens on the risk of an adverse pregnancy outcome in order to maximize the impact of our trial data. Collectively these data will guide the development and implementation of fresh approaches to intercept parasites early in pregnancy and thereby enhance pregnancy outcomes and newborn health.

项目概要/摘要 全球新生儿健康状况有所改善，但在资源有限的环境中仍然迫切需要减少 新生儿死亡率。撒哈拉以南非洲地区几乎所有婴儿死亡都发生在身材矮小的婴儿身上 出生体重，通常是由产前感染恶性疟原虫引起的。这些疟疾影响可以 通过针对怀孕的具体措施（包括每月产前剂量的管理）可以部分缓解 磺胺多辛-乙胺嘧啶作为妊娠期间歇性预防治疗 (IPTp-SP)，但这些并不是 通常实施到妊娠第二个月，因此不能降低妊娠第一个月的感染风险。它 现在可以将疟疾寄生虫纳入妊娠第一期筛查，因为： i) 更新了世卫组织指南， 建议 8 次 ANC 接触的扩展时间表，第一次在妊娠 12 周之前，ii) 提供高灵敏度疟疾快速诊断检测 (HS-RDT)，并增强低密度检测 感染，以及 iii) 积累的安全数据使蒿甲醚-卢美芴碱 (AL) 能够用于治疗疟疾 在妊娠的第一个三个月进行治疗。我们假设，与进入 ANC 并接受常规治疗的女性相比， 护理方面，在妊娠第一个月接受 HS-RDT 筛查的女性的贫困患病率较低 妊娠结果，我们将通过快速疟疾检测改善新生儿健康来测试这一点 肯尼亚西部和民主党的早期妊娠高灵敏度诊断 (INTREPiD) 研究 刚果共和国（DRC）。在目标 1 中，INTREPiD 研究将招募处于妊娠早期的女性， 将他们按 1:1 随机分配至常规护理或 HS-RDT 筛查，然后用 AL 治疗阳性， 然后跟随他们完成交付。在第一个三个月的干预之后，所有女性都将接受常规的治疗 ANC，包括 IPTp-SP。主要结果将是低出生体重、小体型的综合结果 胎龄、早产、胎儿流产或新生儿死亡。在目标 2 中，我们将衡量治疗效果 通过遵循标准的群体 PK 研究，了解 AL 给药在妊娠第一个月的药代动力学 AL 剂量并将 PK 参数与历史对照进行比较。在目标 3 中，我们将使用试验数据来建模 增强敏感性诊断和替代治疗方案对风险的潜在增量益处 不良妊娠结局，以便最大限度地发挥我们试验数据的影响。总的来说，这些数据将 指导制定和实施在怀孕早期拦截寄生虫的新方法 从而提高妊娠结局和新生儿健康。