Ignite Creation Date:
2024-05-05 @ 5:00 PM
Last Modification Date:
2024-10-26 @ 9:27 AM
Study NCT ID:
NCT00368810
Status:
COMPLETED
Last Update Posted:
2017-07-02
First Post:
2006-08-22
Brief Title:
Study of Factors Involved in Resistance to Severe Malaria
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Response to Plasmodium Falciparum-Derived TLR Ligands in Severe and Uncomplicated Malaria in Mali
Status:
COMPLETED
Status Verified Date:
2006-11-30
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will examine whether resistance to severe malaria is associated with weakening of a specific immune response TLR-mediated pro-inflammatory cytokine response Some children with mild malaria go on to develop severe disease while others do not The study will analyze certain substances in the blood to try to determine what factors may protect against severe malaria
Healthy children and children 3 - 10 years of age with severe malaria who are being treated at lH pital Gabriel Toure in Mamako Mali West Africa may be eligible for this study Participants have a mall sample of blood drawn from a vein and from two finger pricks
Healthy children and children 3 - 10 years of age with severe malaria who are being treated at lH pital Gabriel Toure in Mamako Mali West Africa may be eligible for this study Participants have a mall sample of blood drawn from a vein and from two finger pricks
Detailed Description:
Malaria remains an important public health threat responsible for over two million deaths annually the majority among African children The mechanisms underlying resistance to the most severe manifestations of malaria remain elusive Severe malaria has been associated with high levels of pro-inflammatory cytokines that may contribute to the pathogenesis of cerebral malaria severe anemia and acidosis This response is thought to be driven primarily by glycosylphosphatidylinositol GPI anchors derived from erythrocyte-stage Plasmodium falciparum It has been suggested that antibodies against GPI are responsible for resistance to severe malaria which has led to efforts to develop a GPI-based vaccine An alternative explanation for the development of resistance to severe malaria is down regulation of the innate pro-inflammatory response by repeated ligation of toll-like receptors TLR by GPI or other putative P falciparum-derived TLR ligands such as hemozoin This cross-sectional study at lHopital Gabriel Toure in Bamako Mali proposes to test the hypothesis that resistance to severe malaria is associated with an attenuation of the TLR-mediated pro-inflammatory cytokine response After informed consent is obtained from the participants parent or guardian 2-3 mL of venous blood will be drawn from each of 60 children 40 children presenting with acute P falciparum infection 20 severe and 20 uncomplicated and 20 healthy P falciparum uninfected controls The blood will be tested for antibody titers against GPI and Merozoite Surface Protein-1 MSP-1 Peripheral blood mononuclear cells PBMCs will be isolated and cultured with GPI hemozoin lipoteichoic acid LTA lipopolysaccharide LPS and cytosine-guanine dinucleotide CpG At 24 hours supernatant will be collected and the following cytokines measured IL-1 IL-6 IL-8 IL-10 IL-12 and TNF-alpha A clearer understanding of the responsiveness to TLR ligands in children from malaria endemic areas may provide information on potential intervention strategies such as GPI-based vaccines or the use of TLR agonists as vaccine adjuvants
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 06-I-N104 | None | None | None |