Effects of metronidazole plus intermittent preventive treatment of malaria in pregnancy on birth outcomes: a randomised controlled trial in Zambia

甲硝唑加妊娠期疟疾间歇性预防治疗对出生结局的影响：赞比亚的一项随机对照试验

• 批准号: MR/S004998/1
• 负责人: Daniel Chandramohan
• 金额: $ 343.49万
• 依托单位: London School of Hygiene & Tropical Medicine
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FS004998%2F1
• 关键词: Effects; metronidazole; plus; intermittent; preventive

In areas of East and Southern Africa, malaria infection during pregnancy and curable sexually transmitted and reproductive tract infections (STIs/RTIs) are very common. About one-third of women in the sub-region are infected with malaria parasites during pregnancy, one-half of them have bacterial vaginosis (BV) and one-quarter are infected with trichomonas vaginalis (TV). All of these cause adverse birth outcomes. Malaria parasites sequester in the placenta and, therefore, taking conventional blood test may not detect the infection. Thus, the World Health Organization recommends that women who live in malaria-endemic areas receive intermittent preventive treatment (IPTp) using sulphadoxine-pyrimethamine (SP) during their second and third trimesters of pregnancy. However, malaria parasites have developed resistance against SP. An alternative to SP, dihydroartemisinin-piperaquine (DP), has been shown to clear malaria parasites from pregnant women better than SP. However, SP appears also to confer some protection against non-malaria causes of adverse birth outcomes including curable STIs/RTIs. So a switch from SP to DP might not be best. It is possible that SP or DP - if combined with treatment against BV and TV metronidazole (MTZ), a medicine that is also safe to administer in the second and third trimesters of pregnancy - may be better than providing SP, the current standard of care. To examine this, we are proposing a three-arm trial, partially placebo-controlled, that will compare SP plus MTZ placebo versus SP plus MTZ versus DP plus MTZ in a geographic area of north-east Zambia where malaria transmission is high, malaria parasite-resistance to SP is high, and the prevalence of BV and TV in pregnant women is also high. As part of the main trial, we will also conduct a full economic evaluation of trial interventions establish costs, the incremental cost-effectiveness, and acceptability of the three study treatments using discrete choice experiments. We will ask prospective participants if they will provide vaginal swabs and stool samples which we will use to characterise the effect of treatment across trial arms on the vaginal and intestinal microbiota communities, vaginal and intestinal bacterial loads and identify potential triggers of preterm birth that are related to inflammation. Finally, we will also measure the drug sensitivity of several pathogens implicated with vaginal discharge, lower abdominal pain, or genital ulcers.

在东非和南部非洲地区，怀孕期间感染疟疾和可治愈的性传播感染和生殖道感染非常普遍。该次区域约三分之一的妇女在怀孕期间感染疟疾寄生虫，其中一半患有细菌性阴道病，四分之一感染阴道毛滴虫。所有这些都会导致不良的出生结果。 疟疾寄生虫隔离在胎盘中，因此，进行常规血液测试可能无法检测到感染。因此，世界卫生组织建议生活在疟疾流行地区的妇女在怀孕的第二个和第三个三个月期间接受使用磺胺嘧啶-乙胺嘧啶的间歇性预防性治疗。然而，疟疾寄生虫已经对SP产生了抗药性。SP的替代品双氢青蒿素-哌喹（DP）已被证明比SP更好地清除孕妇体内的疟疾寄生虫。然而，SP似乎也对不良出生结果的非疟疾原因（包括可治愈的性传播感染/生殖道感染）提供了一些保护。因此，从SP到DP的切换可能不是最好的。SP或DP -如果与抗BV和TV甲硝唑（MTZ）（一种在妊娠中期和妊娠晚期也安全的药物）的治疗相结合-可能比提供SP（目前的护理标准）更好。为了检验这一点，我们提出了一个三臂试验，部分安慰剂对照，将比较SP加MTZ安慰剂与SP加MTZ与DP加MTZ在赞比亚东北部的地理区域，疟疾传播率高，疟疾寄生虫对SP的耐药性高，BV和TV在孕妇中的患病率也很高。作为主试验的一部分，我们还将使用离散选择实验对试验干预措施进行全面的经济学评价，确定三种研究治疗的成本、增量成本效益和可接受性。我们将询问潜在参与者是否提供阴道拭子和粪便样本，我们将使用这些样本来验证试验组治疗对阴道和肠道微生物群群落、阴道和肠道细菌负荷的影响，并确定与炎症相关的早产潜在触发因素。最后，我们还将测量与阴道分泌物、下腹部疼痛或生殖器溃疡有关的几种病原体的药物敏感性。