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.

项目总结/摘要 新生儿健康在全球范围内有所改善，但在资源有限的环境中， 新生儿死亡率在撒哈拉以南非洲，几乎所有的婴儿死亡都发生在小婴儿或低婴儿身上。 出生体重，这往往是由于产前感染恶性疟原虫。这些疟疾效应可以 通过针对怀孕的措施，包括每月进行产前剂量管理， 磺胺嘧啶-乙胺嘧啶作为间歇性预防性治疗在怀孕期间（IPTP-SP），但这些都不是 通常实施到第二个三个月，因此不能减轻第一个三个月感染的风险。它 现在可以将妊娠早期疟疾寄生虫筛查包括在内，原因是：i）更新了世卫组织的指导方针， 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， 感染，和iii）累积的安全数据，使得蒿甲醚-苯芴醇（AL）能够用于疟疾 在第一个三个月的治疗。我们假设，与进入ANC并接受常规治疗的女性相比， 在妊娠早期接受HS-RDT筛查的女性， 我们将通过“通过快速疟疾检测改善新生儿健康”项目对此进行测试。 在肯尼亚西部和民主共和国进行的早期妊娠高敏诊断（INTREPiD）研究 刚果共和国。在目标1中，INTREPiD研究将招募妊娠早期的女性， 将他们1：1随机分配到常规护理或HS-RDT筛查，然后用AL治疗阳性， 然后跟着他们送货在第一个三个月的干预后，所有女性都将接受常规的 ANC，包括IPTp-SP。主要结局将是低出生体重、小- 胎龄、早产、胎儿丢失或新生儿死亡。在目标2中，我们将测量治疗效果 通过遵循标准的群体PK研究， AL给药，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模拟 增强敏感性诊断和替代治疗方案对风险的潜在增量效益 不良妊娠结局，以便最大限度地发挥我们试验数据的影响。这些数据将 指导制定和实施新的方法，在怀孕早期拦截寄生虫， 从而改善妊娠结果和新生儿健康。