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

马拉维的磺胺多辛-乙胺嘧啶 IPTp：对肠道和阴道微生物组的影响

• 批准号: 9164166
• 负责人: Ian Michael Carroll
• 金额: $ 22.8万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9164166
• 关键词: Affect; Africa South of the Sahara; Aftercare; Ancillary Study; Anti-Bacterial Agents; Bioinformatics; Birth; Characteristics; Chlamydia; Dose; Enrollment; Enteral; Fetus; Folic Acid Antagonists; Funding; Future; Individual; Infection; Intestines; Light; Low Birth Weight Infant; Malaria; Malawi; Mediating; Neisseria gonorrhoeae; Nutritional status; Outcome; Pregnancy; Pregnant Women; Preventive therapy; Process; Prospective Studies; Public Health; Pyrimethamine-Sulfadoxine; Randomized Controlled Trials; Reaction; Risk; Route; Running; Sampling; Sulfadoxine-pyrimethamine resistance; Swab; Taxon; Testing; Therapeutic; Trichomonas; Vagina; Woman; Work; abstracting; arm; deep sequencing; gut microbiome; microbial community; microbiome; microbiota; novel; pathogen; prevent; protective effect; rRNA Genes; tool; treatment effect; treatment group; trial comparing; vaginal microbiome

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.

马拉维的磺胺嘧啶-乙胺嘧啶IPTp：对肠道和阴道微生物的影响 摘要 在撒哈拉以南非洲，出生体重低等不良出生结果很常见。大部分都可以 因为疟疾。近20年来，孕妇一直服用治疗剂量的 磺胺嘧啶-乙胺嘧啶（SP）作为预防疟疾的间歇性预防治疗（IPTp）。 SP耐药疟疾已变得普遍;然而，矛盾的是，与SP的IPTp仍然保护， 不良生育后果。SP是一种具有广谱抗菌活性的抗叶酸剂。我们假设 SP的保护作用可能是由于对肠道或阴道微生物组的影响。作为第一 为了验证这一假设，我们将对50名孕妇进行一项辅助研究， 受试者在一个大型随机对照试验支持的总统疟疾倡议在马拉维 比较SP和双氢青蒿素-哌喹作为IPTp剂。粪便样本和阴道拭子 将获得并发送到生物技术研究所，在那里16 S核糖体RNA基因将由MiSeq进行深度测序， 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导致物种丰富度下降，个体微生物组图谱根据 治疗组。目前，鉴于越来越多的SP，正在讨论继续使用SP进行IPT p 阻力如果SP对出生结局的有益作用是由其抗菌作用介导的，我们的研究表明， 调查结果将支持继续部署IPTP-SP的论点。