K43TW012799
Project Grant
Overview
Grant Description
Molecular and cellular underpinnings of placental malaria - Project summary/abstract
Malaria in pregnancy poses significant threat to the wellbeing of the mother, fetus, and neonate.
In Sub-Saharan Africa, it kills 100,000 infants annually and accounts for about 20% of stillbirths.
These fetal adverse outcomes are mainly due to the sequestration of Plasmodium falciparum-infected erythrocytes in placental intervillous spaces, resulting in placental malaria (PM).
This happens even when malaria infection is asymptomatic and undetectable in maternal blood.
The burden of PM is worsened by rising resistance to intermittent preventive treatment with sulphadoxine-pyrimethamine (IPTP-SP), which is recommended for malaria chemoprophylaxis during pregnancy.
Indeed, our data show that many women on IPTP-SP who test malaria negative and are asymptomatic still have PM.
PM is associated with several adverse effects on the fetus, including fetal growth restriction, preterm birth, and neonatal morbidity and mortality.
The adverse outcomes are mainly due to placental injury and not fetal infection by Plasmodium falciparum, which is rare.
Since the placenta is inaccessible during pregnancy, the impact of PM on placental biology is unclear, and there are no tools for PM detection during pregnancy, representing a critical research gap.
These factors and the limited understanding of the effects of PM on placental function and physiology significantly hamper the development of effective PM interventions and diagnostic tools.
However, the placenta sheds vast amounts of extracellular vesicles into maternal circulation, offering a non-invasive readout of the fetal environment.
To comprehensively understand the cellular and molecular processes that underlie PM-driven placental pathobiology, we propose to leverage our well-defined placental biobank to:
1) Identify the transcriptomic signatures of PM-induced placental pathobiology, and
2) Identify PM-associated transcriptomic signatures in maternal circulation.
The latter will be implemented by profiling the transcriptome of maternally circulating placental extracellular vesicles and by identifying placenta-originated cell-free RNA in maternal circulation.
These analyses will uncover processes/factors underlying PM-induced placental pathobiology and those that can be targeted to prevent or mitigate PM.
The identified PM biomarkers will be leveraged to develop effective point-of-care tools for PM diagnosis in low-resource settings, which have the potential to significantly improve maternal and child health outcomes.
The proposed work will also build a strong foundation in research networks, infrastructure, skills, and data for follow-up studies on the pathobiology of PM and its consequences for the developing child.
Moreover, the strategies, experience, knowledge, tools, and platforms used in this study can be extended to other common placental infections in Sub-Saharan Africa.
Malaria in pregnancy poses significant threat to the wellbeing of the mother, fetus, and neonate.
In Sub-Saharan Africa, it kills 100,000 infants annually and accounts for about 20% of stillbirths.
These fetal adverse outcomes are mainly due to the sequestration of Plasmodium falciparum-infected erythrocytes in placental intervillous spaces, resulting in placental malaria (PM).
This happens even when malaria infection is asymptomatic and undetectable in maternal blood.
The burden of PM is worsened by rising resistance to intermittent preventive treatment with sulphadoxine-pyrimethamine (IPTP-SP), which is recommended for malaria chemoprophylaxis during pregnancy.
Indeed, our data show that many women on IPTP-SP who test malaria negative and are asymptomatic still have PM.
PM is associated with several adverse effects on the fetus, including fetal growth restriction, preterm birth, and neonatal morbidity and mortality.
The adverse outcomes are mainly due to placental injury and not fetal infection by Plasmodium falciparum, which is rare.
Since the placenta is inaccessible during pregnancy, the impact of PM on placental biology is unclear, and there are no tools for PM detection during pregnancy, representing a critical research gap.
These factors and the limited understanding of the effects of PM on placental function and physiology significantly hamper the development of effective PM interventions and diagnostic tools.
However, the placenta sheds vast amounts of extracellular vesicles into maternal circulation, offering a non-invasive readout of the fetal environment.
To comprehensively understand the cellular and molecular processes that underlie PM-driven placental pathobiology, we propose to leverage our well-defined placental biobank to:
1) Identify the transcriptomic signatures of PM-induced placental pathobiology, and
2) Identify PM-associated transcriptomic signatures in maternal circulation.
The latter will be implemented by profiling the transcriptome of maternally circulating placental extracellular vesicles and by identifying placenta-originated cell-free RNA in maternal circulation.
These analyses will uncover processes/factors underlying PM-induced placental pathobiology and those that can be targeted to prevent or mitigate PM.
The identified PM biomarkers will be leveraged to develop effective point-of-care tools for PM diagnosis in low-resource settings, which have the potential to significantly improve maternal and child health outcomes.
The proposed work will also build a strong foundation in research networks, infrastructure, skills, and data for follow-up studies on the pathobiology of PM and its consequences for the developing child.
Moreover, the strategies, experience, knowledge, tools, and platforms used in this study can be extended to other common placental infections in Sub-Saharan Africa.
Awardee
Funding Goals
THE JOHN E. FOGARTY INTERNATIONAL CENTER (FIC) SUPPORTS RESEARCH AND RESEARCH TRAINING TO REDUCE DISPARITIES IN GLOBAL HEALTH AND TO FOSTER PARTNERSHIPS BETWEEN U.S. SCIENTISTS AND THEIR COUNTERPARTS ABROAD. FIC SUPPORTS BASIC BIOLOGICAL, BEHAVIORAL, AND SOCIAL SCIENCE RESEARCH, AS WELL AS RELATED RESEARCH TRAINING AND CAREER DEVELOPMENT. THE RESEARCH PORTFOLIO IS DIVIDED INTO SEVERAL PROGRAMS THAT SUPPORT A WIDE VARIETY OF FUNDING MECHANISMS TO MEET PROGRAMMATIC OBJECTIVES.
Grant Program (CFDA)
Awarding / Funding Agency
Place of Performance
Kenya
Geographic Scope
Foreign
Related Opportunity
Analysis Notes
Amendment Since initial award the total obligations have increased 100% from $111,024 to $221,948.
Mount Kenya University was awarded
Placental Malaria Research: Molecular Insights & Diagnostic Tools
Project Grant K43TW012799
worth $221,948
from Fogarty International Center in September 2024 with work to be completed primarily in Kenya.
The grant
has a duration of 5 years and
was awarded through assistance program 93.989 International Research and Research Training.
The Project Grant was awarded through grant opportunity Emerging Global Leader Award (K43 Independent Clinical Trial Not Allowed).
Status
(Ongoing)
Last Modified 8/20/25
Period of Performance
9/1/24
Start Date
8/31/29
End Date
Funding Split
$221.9K
Federal Obligation
$0.0
Non-Federal Obligation
$221.9K
Total Obligated
Activity Timeline
Transaction History
Modifications to K43TW012799
Additional Detail
Award ID FAIN
K43TW012799
SAI Number
K43TW012799-1119721571
Award ID URI
SAI UNAVAILABLE
Awardee Classifications
Non-Domestic (Non-U.S.) Entity
Awarding Office
75NF00 NIH Fogarty International Center
Funding Office
75NF00 NIH Fogarty International Center
Awardee UEI
FPJCFJXS9LL9
Awardee CAGE
SVT29
Performance District
Not Applicable
Modified: 8/20/25