MalariaNCT00669084
Innate and Acquired Resistance to Plasmodium Falciparum Malaria in Mali
An observational study of Malaria, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in Mali.
Trial summary
This study, sponsored by NIAID and the University of Bamako, Mali, will identify genetic and other factors that may protect against severe malaria in some children. Children between 6 months and 17 years of age who live in Kenieroba, Fourda or Bozokin villages in Mali may enroll in the study. Read more about this study
- Who is it for?
- Ages 6 months to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria
- How many people
- 1,718 participants
- Where
- 1 siteMali
- Study dates
- 21 Apr 2008to 19 Nov 2013
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months to 65 years
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- (Cohort Study)
- Resident of Kenieroba, Fourda, or Bozokin villages, and no plans to relocate away from the study village for the next 5 years.
- Willingness to participate in the study as evidenced by informed consent of parents or guardians of children, and willingness to bring children to study clinic if they develop fever or other symptoms of malaria.
- Age 6 months to 17 years.
- (Blood Collection Study)
- Children enrolled in the cohort study.
Show all 20Show fewer
- Willingness to participate in the study as evidenced by informed consent of parents or guardians of children.
- Age 2 years to 14 years.
- Hemoglobin level greater than or equal to 8.5g/dL.
- (Parasite Clearance Study)
- Children enrolled in the cohort study.
- Willingness to participate in the study as evidenced by informed consent of parents or guardians of children.
- Age 1 year to 17 years (inclusive).
- P. falciparum density greater than or equal to 10,000/microL.
- Present with their first episode of uncomplicated malaria of the 2010 transmission season or any episode during the 2012 transmission season.
- Resident of Kenieroba
- (Adult blood Collection Study)
- Willingness to participate in the study as evidenced by informed consent.
- Age 18 years to 65 years.
- Hemoglobin level greater than or equal to 8.5 g/dL
Who cannot join
- (Cohort Study)
- Any condition that in the opinion of the investigator would render the subject unable to comply with the protocol (e.g., psychiatric disease).
- Any health condition that in the opinion of the investigator would confound data analysis or pose unnecessary exposure risks to study personnel (e.g., individuals who are known to be HIV-infected or to have AIDS) or to the child (e.g., severe malnutrition).
- (Blood Collection Study)
- Any condition that in the opinion of the investigator would render the subject unable to comply with the protocol (e.g., psychiatric disease).
- Any health condition that in the opinion of the investigator would confound data analysis or pose unnecessary exposure risks to study personnel (e.g., individuals who are known to be HIV-infected or to have AIDS) or to the child (e.g., severe malnutrition).
Show all 13Show fewer
- (Parasite Clearance Study)
- Any condition that in the opinion of the investigator would render the subject unable to comply with the protocol (e.g., psychiatric diesase).
- Any health condition that in the opinion of the investigator would confound data analysis or pose unnecessary exposure risks to study personnel (e.g., individuals who are known to be HIV-infected or to have AIDS) or to the child (e.g., severe malnutrition).
- Pregnancy at the time of malaria episode.
- (Adult Blood Collection Study)
- Any condition that in the opinion of the investigator would render the subject unable to comply with the protocol (e.g., psychiatric disease)
- Any health condition that in the opinion of the investigator would confound data analysis or pose unnecessary exposure risks to study personnel (e.g., individuals who are known to be HIV-infected or to have AIDS.
Trial locations and contacts
1 site in 1 country.
Mali1 site
University of Bamako, Faculty of Medicine, Pharmacy and Odontostomatology
Bamako
About this study
Official title: Studies of Innate and Acquired Resistance to P. Falciparum Malaria in Mali
This study, sponsored by NIAID and the University of Bamako, Mali, will identify genetic and other factors that may protect against severe malaria in some children.
Children between 6 months and 17 years of age who live in Kenieroba, Fourda or Bozokin villages in Mali may enroll in the study. Participants have a blood sample collected by finger prick with a small needle. The blood is examined for gene variants that influence the severity of disease in children exposed to the malaria parasite.
Read more
Children who develop a fever or other symptoms of malaria are evaluated and treated in Kenieroba s health center for up to 5 years from entering the study, or until they reach 18 years of age. The children are treated with artesunate and amodiaquine. Children with severe disease are treated with quinine. One tablespoon of blood is drawn from the children for study.
At the end of the dry season and the wet season, a subset of 200 healthy children are asked to provide 1 or 2 tablespoons of blood, drawn through a needle placed in a vein in the arm. Additional research blood samples may be requested from children between 2 and 17 years old. Blood will not be taken from any child more than twice a year.
...
Read the detailed description
Hemoglobin (Hb) and red blood cell (RBC) polymorphisms that give rise to HbS, HbC, alpha-thalassemia, G6PD-deficiency, and ABO blood groups occur at high frequency in Mali. To determine whether these Hb/RBC polymorphisms are associated with protection against mild malaria and malaria-associated anemia, we will conduct a cohort study in Mali. Approximately 1300 children will be genotyped for five Hb/RBC polymorphisms and followed for 5 years to compare mean incidence rates for mild malaria, stratified by polymorphism. Differences between Hb levels during acute malaria episodes and at baseline will be calculated to determine if Hb/RBC polymorphisms influence the degree of malaria-associated anemia. To investigate whether Hb/RBC polymorphisms impair monocyte activation, we will obtain parasites from children with malaria, culture them in RBCs of different genotype, and compare the parasitized RBCs for their ability to activate monocytes in vitro. Plasma samples from children with malaria will also be compared for their levels of monocyte-derived cytokines. A variety of single nucleotide polymorphisms (SNPs) in immune response genes have recently been identified in African populations. To determine whether these polymorphisms are associated with protection against severe malaria, we will compare the prevalence of SNPs in groups of children with severe or mild malaria. Blood Collection Study. Components of the innate immune system (e.g., Toll-like receptors) expressed on antigen presenting cells (APC) provide the first line of defense against microbial infection and frame the nature and scale of adaptive immune responses. To investigate whether APC from malaria-experienced individuals respond to TLR ligands in vitro stimulation assays, we will obtain blood samples from 100 healthy children in the dry season and again in the wet season. Immunological memory is a key feature of adaptive immunity and involves memory T cells. Clinical trials in which malaria-nafve human volunteers were vaccinated with merozoite MSP-1 antigens enabled us to study the development of immunological memory by measuring memory T cell cytokine production and expression of surface activation markers. To investigate whether memory T cells from malaria-experienced individuals respond similarly to AMA-I/MSP-1 ligands in vitro stimulation assays, we will obtain blood samples from an additional 100 healthy children in the dry season and again in the wet season. These collections of paired samples will enable us to explore the possibility that TLR- and AMA-1/MSP-l-induced immune responses are boosted during a transmission season and increase with age (a surrogate for disease controlling immunity).
- Conditions
- Malaria
- Keywords
- Innate Immunity, Malaria, Plasmodium, Hemoglobinopathy, G6PD Deficiency
- Medical subject headings
- Malaria, Hemoglobinopathies, Glucosephosphate Dehydrogenase Deficiency
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2008 (estimated)
- Study start21 Apr 2008
- Study completion19 Nov 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for MalariaStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Time perspective
- Prospective
- Enrolment
- 1,718 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Investigators
- Rick M Fairhurst, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00669084
- Sponsor's protocol ID
- 999908120
- Other IDs
- 08-I-N120
- Status last verified
- 19 Nov 2013
- First submitted
- 26 Apr 2008
- Last updated
- 17 Dec 2019
- Results posted
- No
Publications
Fairhurst RM, Baruch DI, Brittain NJ, Ostera GR, Wallach JS, Hoang HL, Hayton K, Guindo A, Makobongo MO, Schwartz OM, Tounkara A, Doumbo OK, Diallo DA, Fujioka H, Ho M, Wellems TE. Abnormal display of PfEMP-1 on erythrocytes carrying haemoglobin C may protect against malaria. Nature. 2005 Jun 23;435(7045):1117-21. doi: 10.1038/nature03631.
PubMed 15973412Guindo A, Fairhurst RM, Doumbo OK, Wellems TE, Diallo DA. X-linked G6PD deficiency protects hemizygous males but not heterozygous females against severe malaria. PLoS Med. 2007 Mar;4(3):e66. doi: 10.1371/journal.pmed.0040066.
PubMed 17355169Luzzatto L, Usanga FA, Reddy S. Glucose-6-phosphate dehydrogenase deficient red cells: resistance to infection by malarial parasites. Science. 1969 May 16;164(3881):839-42. doi: 10.1126/science.164.3881.839.
PubMed 4889647Suresh RV, Deng B, Gebremicale Y, Roche K, Miura K, Long C. Mesenchymal stem cells of the bone marrow raise infectivity of Plasmodium falciparum gametocytes. mBio. 2023 Dec 19;14(6):e0223223. doi: 10.1128/mbio.02232-23. Epub 2023 Nov 1.
PubMed 37909740Lopera-Mesa TM, Doumbia S, Konate D, Anderson JM, Doumbouya M, Keita AS, Diakite SA, Traore K, Krause MA, Diouf A, Moretz SE, Tullo GS, Miura K, Gu W, Fay MP, Taylor SM, Long CA, Diakite M, Fairhurst RM. Effect of red blood cell variants on childhood malaria in Mali: a prospective cohort study. Lancet Haematol. 2015 Apr;2(4):e140-9. doi: 10.1016/S2352-3026(15)00043-5. Epub 2015 Mar 24.
PubMed 26687956Lopera-Mesa TM, Doumbia S, Chiang S, Zeituni AE, Konate DS, Doumbouya M, Keita AS, Stepniewska K, Traore K, Diakite SA, Ndiaye D, Sa JM, Anderson JM, Fay MP, Long CA, Diakite M, Fairhurst RM. Plasmodium falciparum clearance rates in response to artesunate in Malian children with malaria: effect of acquired immunity. J Infect Dis. 2013 Jun 1;207(11):1655-63. doi: 10.1093/infdis/jit082. Epub 2013 Feb 28.
PubMed 23448727Mita-Mendoza NK, van de Hoef DL, Lopera-Mesa TM, Doumbia S, Konate D, Doumbouya M, Gu W, Anderson JM, Santos-Argumedo L, Rodriguez A, Fay MP, Diakite M, Long CA, Fairhurst RM. A potential role for plasma uric acid in the endothelial pathology of Plasmodium falciparum malaria. PLoS One. 2013;8(1):e54481. doi: 10.1371/journal.pone.0054481. Epub 2013 Jan 22.
PubMed 23349902Lopera-Mesa TM, Mita-Mendoza NK, van de Hoef DL, Doumbia S, Konate D, Doumbouya M, Gu W, Traore K, Diakite SA, Remaley AT, Anderson JM, Rodriguez A, Fay MP, Long CA, Diakite M, Fairhurst RM. Plasma uric acid levels correlate with inflammation and disease severity in Malian children with Plasmodium falciparum malaria. PLoS One. 2012;7(10):e46424. doi: 10.1371/journal.pone.0046424. Epub 2012 Oct 5.
PubMed 23071567
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Studies of Innate and Acquired Resistance to P. Falciparum Malaria in Mali
- ClinicalTrials.gov ID
- NCT00669084
- Acronym / sponsor ID
- 999908120
- Conditions
- Malaria
- Keywords
- Innate Immunity, Malaria, Plasmodium, Hemoglobinopathy, G6PD Deficiency
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1,718 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 21 Apr 2008
- Study completion
- 19 Nov 2013
- First posted
- 29 Apr 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study, sponsored by NIAID and the University of Bamako, Mali, will identify genetic and other factors that may protect against severe malaria in some children.
Children between 6 months and 17 years of age who live in Kenieroba, Fourda or Bozokin villages in Mali may enroll in the study. Participants have a blood sample collected by finger prick with a small needle. The blood is examined for gene variants that influence the severity of disease in children exposed to the malaria parasite.
Children who develop a fever or other symptoms of malaria are evaluated and treated in Kenieroba s health center for up to 5 years from entering the study, or until they reach 18 years of age. The children are treated with artesunate and amodiaquine. Children with severe disease are treated with quinine. One tablespoon of blood is drawn from the children for study.
At the end of the dry season and the wet season, a subset of 200 healthy children are asked to provide 1 or 2 tablespoons of blood, drawn through a needle placed in a vein in the arm. Additional research blood samples may be requested from children between 2 and 17 years old. Blood will not be taken from any child more than twice a year.
...
Detailed description
Hemoglobin (Hb) and red blood cell (RBC) polymorphisms that give rise to HbS, HbC, alpha-thalassemia, G6PD-deficiency, and ABO blood groups occur at high frequency in Mali. To determine whether these Hb/RBC polymorphisms are associated with protection against mild malaria and malaria-associated anemia, we will conduct a cohort study in Mali. Approximately 1300 children will be genotyped for five Hb/RBC polymorphisms and followed for 5 years to compare mean incidence rates for mild malaria, stratified by polymorphism. Differences between Hb levels during acute malaria episodes and at baseline will be calculated to determine if Hb/RBC polymorphisms influence the degree of malaria-associated anemia. To investigate whether Hb/RBC polymorphisms impair monocyte activation, we will obtain parasites from children with malaria, culture them in RBCs of different genotype, and compare the parasitized RBCs for their ability to activate monocytes in vitro. Plasma samples from children with malaria will also be compared for their levels of monocyte-derived cytokines. A variety of single nucleotide polymorphisms (SNPs) in immune response genes have recently been identified in African populations. To determine whether these polymorphisms are associated with protection against severe malaria, we will compare the prevalence of SNPs in groups of children with severe or mild malaria. Blood Collection Study. Components of the innate immune system (e.g., Toll-like receptors) expressed on antigen presenting cells (APC) provide the first line of defense against microbial infection and frame the nature and scale of adaptive immune responses. To investigate whether APC from malaria-experienced individuals respond to TLR ligands in vitro stimulation assays, we will obtain blood samples from 100 healthy children in the dry season and again in the wet season. Immunological memory is a key feature of adaptive immunity and involves memory T cells. Clinical trials in which malaria-nafve human volunteers were vaccinated with merozoite MSP-1 antigens enabled us to study the development of immunological memory by measuring memory T cell cytokine production and expression of surface activation markers. To investigate whether memory T cells from malaria-experienced individuals respond similarly to AMA-I/MSP-1 ligands in vitro stimulation assays, we will obtain blood samples from an additional 100 healthy children in the dry season and again in the wet season. These collections of paired samples will enable us to explore the possibility that TLR- and AMA-1/MSP-l-induced immune responses are boosted during a transmission season and increase with age (a surrogate for disease controlling immunity).
Study design
- Time perspective
- Prospective
Who may qualify
- Ages
- 6 months to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (20 listed)
- (Cohort Study)
- Resident of Kenieroba, Fourda, or Bozokin villages, and no plans to relocate away from the study village for the next 5 years.
- Willingness to participate in the study as evidenced by informed consent of parents or guardians of children, and willingness to bring children to study clinic if they develop fever or other symptoms of malaria.
- Age 6 months to 17 years.
- (Blood Collection Study)
Key exclusion criteria (13 listed)
- (Cohort Study)
- Any condition that in the opinion of the investigator would render the subject unable to comply with the protocol (e.g., psychiatric disease).
- Any health condition that in the opinion of the investigator would confound data analysis or pose unnecessary exposure risks to study personnel (e.g., individuals who are known to be HIV-infected or to have AIDS) or to the child (e.g., severe malnutrition).
- (Blood Collection Study)
- Any condition that in the opinion of the investigator would render the subject unable to comply with the protocol (e.g., psychiatric disease).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2019.
- Background: PubMed 15973412Fairhurst RM, Baruch DI, Brittain NJ, Ostera GR, Wallach JS, Hoang HL, Hayton K, Guindo A, Makobongo MO, Schwartz OM, Tounkara A, Doumbo OK, Diallo DA, Fujioka H, Ho M, Wellems TE. Abnormal display of PfEMP-1 on erythrocytes carrying haemoglobin C may protect against malaria. Nature. 2005 Jun 23;435(7045):1117-21. doi: 10.1038/nature03631.
- Background: PubMed 17355169Guindo A, Fairhurst RM, Doumbo OK, Wellems TE, Diallo DA. X-linked G6PD deficiency protects hemizygous males but not heterozygous females against severe malaria. PLoS Med. 2007 Mar;4(3):e66. doi: 10.1371/journal.pmed.0040066.
- Background: PubMed 4889647Luzzatto L, Usanga FA, Reddy S. Glucose-6-phosphate dehydrogenase deficient red cells: resistance to infection by malarial parasites. Science. 1969 May 16;164(3881):839-42. doi: 10.1126/science.164.3881.839.
- Derived from this study: PubMed 37909740Suresh RV, Deng B, Gebremicale Y, Roche K, Miura K, Long C. Mesenchymal stem cells of the bone marrow raise infectivity of Plasmodium falciparum gametocytes. mBio. 2023 Dec 19;14(6):e0223223. doi: 10.1128/mbio.02232-23. Epub 2023 Nov 1.
- Derived from this study: PubMed 26687956Lopera-Mesa TM, Doumbia S, Konate D, Anderson JM, Doumbouya M, Keita AS, Diakite SA, Traore K, Krause MA, Diouf A, Moretz SE, Tullo GS, Miura K, Gu W, Fay MP, Taylor SM, Long CA, Diakite M, Fairhurst RM. Effect of red blood cell variants on childhood malaria in Mali: a prospective cohort study. Lancet Haematol. 2015 Apr;2(4):e140-9. doi: 10.1016/S2352-3026(15)00043-5. Epub 2015 Mar 24.
- Derived from this study: PubMed 23448727Lopera-Mesa TM, Doumbia S, Chiang S, Zeituni AE, Konate DS, Doumbouya M, Keita AS, Stepniewska K, Traore K, Diakite SA, Ndiaye D, Sa JM, Anderson JM, Fay MP, Long CA, Diakite M, Fairhurst RM. Plasmodium falciparum clearance rates in response to artesunate in Malian children with malaria: effect of acquired immunity. J Infect Dis. 2013 Jun 1;207(11):1655-63. doi: 10.1093/infdis/jit082. Epub 2013 Feb 28.
- Derived from this study: PubMed 23349902Mita-Mendoza NK, van de Hoef DL, Lopera-Mesa TM, Doumbia S, Konate D, Doumbouya M, Gu W, Anderson JM, Santos-Argumedo L, Rodriguez A, Fay MP, Diakite M, Long CA, Fairhurst RM. A potential role for plasma uric acid in the endothelial pathology of Plasmodium falciparum malaria. PLoS One. 2013;8(1):e54481. doi: 10.1371/journal.pone.0054481. Epub 2013 Jan 22.
- Derived from this study: PubMed 23071567Lopera-Mesa TM, Mita-Mendoza NK, van de Hoef DL, Doumbia S, Konate D, Doumbouya M, Gu W, Traore K, Diakite SA, Remaley AT, Anderson JM, Rodriguez A, Fay MP, Long CA, Diakite M, Fairhurst RM. Plasma uric acid levels correlate with inflammation and disease severity in Malian children with Plasmodium falciparum malaria. PLoS One. 2012;7(10):e46424. doi: 10.1371/journal.pone.0046424. Epub 2012 Oct 5.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rick M Fairhurst, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Malaria, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in Mali.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Mali. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00669084, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2019.