Examining the mechanisms and optimization of malaria chemoprevention strategies to improve birth outcomes in Africa
检查疟疾化学预防策略的机制和优化,以改善非洲的出生结果
基本信息
- 批准号:10642646
- 负责人:
- 金额:$ 12.29万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-07-19 至 2025-06-30
- 项目状态:未结题
- 来源:
- 关键词:AffectAfricaAnti-Inflammatory AgentsAntibioticsAntimalarialsAutomobile DrivingBirthBirth WeightCharacteristicsChemopreventionClinical TrialsCommunicable DiseasesConduct Clinical TrialsDataDoseEpidemiologistEpidemiologyFalciparum MalariaGoalsHealth PolicyHeterogeneityIndividualInflammationInterventionInvestigationLow Birth Weight InfantMalariaMalaria preventionMaternal and Child HealthMediatingMediationMediatorMentorshipMeta-AnalysisMethodsModelingOutcomeParasite resistancePharmaceutical PreparationsPlasmodium falciparumPopulationPositioning AttributePregnancyPregnant WomenPrevention strategyPreventive treatmentPropertyPyrimethamineRandomized, Controlled TrialsRecommendationRegimenReproductive Tract InfectionsResearchResearch PersonnelRiskSafetySexual TransmissionSiteStatistical MethodsSulfadoxineSulfadoxine-pyrimethamine resistanceTestingTrainingTranslatingWomanWorld Health Organizationadverse birth outcomesarmcareergut microbiomeimprovedinfant deathintervention effectnovelpersonalized approachpolicy recommendationpreventstatisticsvaginal microbiome
项目摘要
PROJECT ABSTRACT
Reducing the global burden of low birthweight (LBW) remains a high priority for the World Health
Organization (WHO). In Africa, malaria in pregnancy contributes to approximately 20% of LBW cases and
affects nearly 12 million pregnancies every year. To curb the risk of malaria and LBW in Africa, the WHO
recommends intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp with SP), a malaria
chemoprevention strategy for pregnant women living in malaria-endemic settings. However, over the past two
decades, widespread parasite resistance to SP has called for an urgent need to identify alternative
antimalarials that could replace SP. While several antimalarials have been studied to date, the most promising
candidate appears to be dihydroartemisinin-piperaquine (DP). Randomized controlled trials from our group and
others have shown DP to be safe in pregnant women and far superior to SP in preventing malaria. Yet, these
studies yield conflicting results on whether DP is superior to SP in preventing LBW. Mediation analyses
conducted by our group confirm that the reason for this paradoxical finding is that SP, an antimalarial with
known antibiotic and anti-inflammatory properties, improves LBW through mechanisms independent of its
antimalarial activity (e.g., potentially through preventing sexually transmitted and reproductive tract infections,
changing the gut or vaginal microbiome, and reducing maternal inflammation). Moreover, upon further
investigation, the benefits of IPTp with either DP or SP appear to be context-specific, largely driven by the
heterogeneity of the ‘non-malarial’ effects of SP between sites. Thus, in order to inform WHO on the optimal
IPTp regimen, which may require a tailored approach for each setting, further evidence is needed to define the
mechanisms driving the non-malarial effects of SP and for whom and where prevention of the malarial and
‘non-malarial’ mechanisms are most relevant. The objectives of this K99/R00 are to: characterize the
mechanisms that mediate the effect of SP and DP on birthweight (Aim 1), assess the extent to which these
mechanisms and other factors are causing heterogeneity between sites (Aim 2), and develop a model to
estimate which antimalarial combination (either DP, SP, or a combination of DP+SP) would be the most
optimal regimen for each unique epidemiological setting (Aim 3). Our research will leverage existing data from
eight clinical trials conducted across ten study sites. The proposal will build on the applicant’s background in
malaria, clinical trials, and epidemiology and include new training in: (1) the potential ‘non-malarial’ targets of
SP affecting maternal and child health, (2) advanced computational statistics, (3) causal inference methods to
target and tailor interventions. The training plan will be guided by an exemplary mentorship team who are
experts in the field of causal inference, statistics, malaria, and maternal and child health. The combined
research and training plan will competitively position the applicant for a successfully independent research
career as an infectious disease epidemiologist focused on improving global maternal and child health policies.
项目摘要
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Michelle Roh其他文献
Michelle Roh的其他文献
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{{ truncateString('Michelle Roh', 18)}}的其他基金
The impact of vector control interventions on adverse birth outcomes.
病媒控制干预措施对不良出生结局的影响。
- 批准号:
9900569 - 财政年份:2018
- 资助金额:
$ 12.29万 - 项目类别:
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