Sulfadoxine-Pyrimethamine IPTp in Malawi: Effects on the gut and vaginal microbiomes

马拉维的磺胺多辛-乙胺IPTp：对肠道和阴道微生物区系的影响 摘要 低出生体重等不良出生结局在撒哈拉以南非洲很常见。其中很大一部分可以 归因于疟疾。近20年来，孕妇一直被给予治疗性剂量的 磺胺多辛(SP)作为预防疟疾的间歇预防疗法(IPTp)。 具有SP耐药性的疟疾已经变得普遍；然而，矛盾的是，带有SP的IPTp仍然能够保护人们免受 不良的分娩结局。SP是一种具有广谱抗菌活性的抗叶酸。我们假设 SP的保护作用可能与其对肠道或阴道微生物群的影响有关。作为第一次 为了验证这一假设，我们将对50名孕妇进行辅助研究 马拉维总统疟疾倡议支持的大型随机对照试验的受试者 比较SP和双氢青蒿素-哌喹作为IPTp试剂的效果。粪便样本和阴道拭子会 在那里16S核糖体RNA基因将被MiSeq和 QIIME分析。将检查处理对α和β多样性的影响。我们希望能找到 SP导致物种丰富度降低，单个微生物群聚在一起 治疗组。目前，随着SP的增加，人们正在讨论继续将SP用于IPTp的问题 抵抗。如果SP对出生结局的有益影响是通过其抗菌作用来调节的，我们的 调查结果将支持继续部署IPTp-SP的论点。

Sulfadoxine-Pyrimethamine IPTp in Malawi: Effects on the gut and vaginal microbiomes Abstract Adverse birth outcomes, such as low birth weight, are common in sub-Saharan Africa. Much of it can be attributed to malaria. For nearly 20 years, pregnant women have been given therapeutic doses of sulfadoxine-pyrimethamine (SP) as intermittent preventive therapy (IPTp) to protect against malaria. SP-resistant malaria has become widespread; yet, paradoxically, IPTp with SP remains protective against adverse birth outcomes. SP is an antifolate with broad-spectrum antibacterial activity. We hypothesize that the protective effect of SP could be due to an effect on the gut or vaginal microbiome. As a first step toward testing this hypothesis, we will conduct an ancillary study on 50 pregnant women who are subjects in a large randomized control trial supported by the President’s Malaria Initiative in Malawi comparing SP and dihydroartemisinin-piperaquine as IPTp agents. Fecal samples and vaginal swabs will be obtained and sent to UNC where the 16S ribosomal RNA gene will be deep-sequenced by MiSeq and analyzed by QIIME. The effects of treatment on α- and β-diversity will be examined. We expect to find that SP causes decreased species richness and that individual microbiome profiles cluster according to treatment group. Currently the continued use of SP for IPTp is being debated in light of increasing SP resistance. If the beneficial effect of SP on birth outcome is mediated by its antibacterial effects, our findings would support the argument for continued IPTp-SP deployment.