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群的影响

• 批准号: 9305834
• 负责人: Ian Michael Carroll
• 金额: $ 19万
• 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 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9305834
• 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; Prospective Studies; Public Health; Pyrimethamine-Sulfadoxine; Randomized Controlled Trials; Reaction; Risk; Route; Running; Sampling; Sulfadoxine-pyrimethamine resistance; Swab; Testing; Therapeutic; Trichomonas; Vagina; Woman; Work; 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.

马拉维中的亚磺糖苷 - 甲胺IPTP：对肠道和阴道微生物的影响 抽象的 不良的出生结果，例如低出生体重，在撒哈拉以南非洲很常见。大部分可能是 归因于疟疾。近20年来，孕妇得到了理论剂量 亚磺糖苷 - 甲胺（SP）作为间歇性预防疗法（IPTP）以防止疟疾。 SP抗性疟疾已普遍存在；然而，自相矛盾的是，带有SP的IPTP仍然受到保护 不利的出生结果。 SP是具有广谱抗菌活性的抗叶酸。我们假设 SP的受保护作用可能是由于对肠道或阴道微生物组的影响。首先 迈向检验这一假设的一步，我们将对50名孕妇进行辅助研究 总统在马拉维的疟疾倡议支持的大型随机对照试验中的受试者 将SP和Dihydroartemisin-Piperaquine与IPTP剂进行比较。粪便样品和阴道拭子将 获得并发送到UNC，其中16S核糖体RNA基因将由Miseq和 由Qiime分析。将检查治疗对α-和β多样性的影响。我们希望找到 SP会导致物种的丰富度提高，并且根据 治疗组。目前，鉴于增加SP 反抗。如果SP对出生结果的有益作用是由其抗菌作用介导的，那么我们 调查结果将支持继续进行IPTP-SP部署的论点。