A Longitudinal Systems Biological Analysis of Naturally Acquired Malaria Immunity in Mali
29 de marzo de 2022 actualizado por: National Institute of Allergy and Infectious Diseases (NIAID)
Plasmodium falciparum (Pf) malaria remains a major cause of morbidity and mortality worldwide.
A malaria vaccine would contribute towards efforts to control and eliminate malaria.
Optimism that an effective malaria vaccine can be developed is derived in part from the observation that repeated Pf infections can induce protective immunity; however, the mechanisms underlying acquired malaria immunity remain unclear.
The goal of the current study is to apply systems biological tools to an observational cohort in an area of intense seasonal Pf transmission to gain insight into the mechanisms underlying naturally acquired malaria immunity.
This year-long observational-cohort study of 700 individuals (3 months and 25 years of age) will be conducted in the rural village of Kalifabougou, Mali, where Pf transmission is intense and seasonal.
Asymptomatic Pf infection and malaria episodes will be detected by passive and active surveillance.
Immune parameters of malaria-protected and -susceptible individuals will be assayed from blood samples collected at strategic time points relative to the malaria season.
The primary objective is to identify genome-wide expression profiles induced by Pf infection that are associated with protection from malaria.
Secondary objectives include identifying age-related (surrogate for cumulative Pf exposure) changes in Pf-induced gene-expression and serum cytokine profiles, and examining Pf-specific antibody profiles that are associated with protection from malaria using a protein microarray representing 2000 Pf proteins (40 percent of the Pf proteome).
Exploratory objectives for this study are to compare the magnitude and quality of the Pf-specific CD4 plus T cell response in malaria-protected and -susceptible individuals and determine how this response varies with age and among individuals before, during, and after malaria season, as well as compare various immune parameters in Pf-infected and uninfected individuals at the end of the dry season to investigate host immune factors associated with chronic asymptomatic Pf infection....
Descripción general del estudio
Estado
Terminado
Condiciones
Descripción detallada
Plasmodium falciparum (Pf) malaria remains a major cause of morbidity and mortality worldwide.
A malaria vaccine would contribute towards efforts to control and eliminate malaria.
Optimism that an effective malaria vaccine can be developed is derived in part from the observation that repeated Pf infections can induce protective immunity; however, the mechanisms underlying acquired malaria immunity remain unclear.
The goal of the current study is to apply systems biological tools to an observational cohort in an area of intense seasonal Pf transmission to gain insight into the mechanisms underlying naturally acquired malaria immunity.
This observational-cohort study of individuals (3 months and 40 years of age) will be conducted in the rural village of Kalifabougou, Mali, where Pf transmission is intense and seasonal.
Asymptomatic Pf infection and malaria episodes will be detected by passive and active surveillance.
Immune parameters of malaria-protected and -susceptible individuals will be assayed from blood samples collected at strategic time points relative to the malaria season.
The primary objective is to identify genome-wide expression profiles induced by Pf infection that are associated with protection from malaria.
Secondary objectives include identifying age-related (surrogate for cumulative Pf exposure) changes in Pf-induced gene-expression and serum cytokine profiles, and examining Pf-specific antibody profiles that are associated with protection from malaria using a protein microarray representing 2000 Pf proteins (approximately 40% of the Pf proteome).
Exploratory objectives for this study are to compare the magnitude and quality of the Pf-specific CD4+ T cell response in malaria-protected and -susceptible individuals and determine how this response varies with age and among individuals before, during, and after malaria season, as well as compare various immune parameters in Pf-infected and uninfected individuals at the end of the dry season to investigate host immune factors associated with chronic asymptomatic Pf infection.
Tipo de estudio
De observación
Inscripción (Actual)
1188
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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Bamako, Malí
- University of Bamako, Faculty of Medicine, Pharmacy and Odontostomatology
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
3 meses a 40 años (Niño, Adulto)
Acepta Voluntarios Saludables
Sí
Géneros elegibles para el estudio
Todos
Método de muestreo
Muestra de probabilidad
Población de estudio
All study subjects will be selected from the village of Kalifabougou, Mali.
Male and female volunteers 3 months to 40 years of age will be included.
This age range captures the period over which immunity to malaria is acquired in areas of intense Pf transmission like Mali.
There is no exclusion based on race, ethnicity, or gender.@@@
Descripción
- INCLUSION CRITERIA:
Individuals 3 months to 40 years of age are eligible to enter the study if they agree to:
- Live in Kalifabougou for the duration of the study (12 months).
- Have blood specimens stored for future studies.
EXCLUSION CRITERIA:
The following eligibility criteria are exclusionary:
- Anemia (hemoglobin less than 7 g/dL).
- Current use of antimalarials, corticosteroids, or other immuno-suppressants.
- Underlying heart disease, bleeding disorder, or other conditions that, in the judgment of the clinical investigators, could increase the risk to the study subjects.
- Fever greater than or equal to 37.5 degrees Celsius or evidence of an acute infection.
- Currently pregnant or planning to become pregnant during the study period.
(Asymptomatic Pf infection at enrollment is not exclusionary).
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
Cohortes e Intervenciones
Grupo / Cohorte |
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observational cohort
This observational-cohort study of individuals (3 months and 40 years of age) will be conducted in the rural village of Kalifabougou, Mali, where Pf transmission is intense and seasonal
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Pf expression profiles
Periodo de tiempo: Triannual cross-sectional surveys and convalescence visits
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Identify genome-wide progression profiles induced by Plasmonium falciparum infection that are assocaited with malaria immunity
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Triannual cross-sectional surveys and convalescence visits
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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serum cytokine profiles
Periodo de tiempo: Triannual cross-sectional surveys and convalescence visits
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Examine the relationship between age (surrogate for cumulative Pf exposure) and the gene-expression and serum cytokine profilesinduced by Pf infection.
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Triannual cross-sectional surveys and convalescence visits
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Pf-specific antibody profiles
Periodo de tiempo: Triannual cross-sectional surveys and convalescence visits
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Identify Pf-specific antibody profiles that are associated with malaria immunity by using a protein microarray representing 2000 Pf proteins (approx.
40% of the Pf proteome), and determine how these profiles change with age.
The objective is to validate and extend findings from a preliminary study performed in the nearby village of Kambila, Mali, where a protein microarray containing approx.
23% of the Pf proteome was used to profile Pf-specific antibody responses in children and adults before and after the 6-month malaria season
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Triannual cross-sectional surveys and convalescence visits
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Investigadores
- Investigador principal: Peter D Crompton, M.D., National Institute of Allergy and Infectious Diseases (NIAID)
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Publicaciones Generales
- Tran TM, Aghili A, Li S, Ongoiba A, Kayentao K, Doumbo S, Traore B, Crompton PD. A nested real-time PCR assay for the quantification of Plasmodium falciparum DNA extracted from dried blood spots. Malar J. 2014 Oct 4;13:393. doi: 10.1186/1475-2875-13-393.
- Tran TM, Ongoiba A, Coursen J, Crosnier C, Diouf A, Huang CY, Li S, Doumbo S, Doumtabe D, Kone Y, Bathily A, Dia S, Niangaly M, Dara C, Sangala J, Miller LH, Doumbo OK, Kayentao K, Long CA, Miura K, Wright GJ, Traore B, Crompton PD. Naturally acquired antibodies specific for Plasmodium falciparum reticulocyte-binding protein homologue 5 inhibit parasite growth and predict protection from malaria. J Infect Dis. 2014 Mar 1;209(5):789-98. doi: 10.1093/infdis/jit553. Epub 2013 Oct 16.
- Doumbo S, Tran TM, Sangala J, Li S, Doumtabe D, Kone Y, Traore A, Bathily A, Sogoba N, Coulibaly ME, Huang CY, Ongoiba A, Kayentao K, Diallo M, Dramane Z, Nutman TB, Crompton PD, Doumbo O, Traore B. Co-infection of long-term carriers of Plasmodium falciparum with Schistosoma haematobium enhances protection from febrile malaria: a prospective cohort study in Mali. PLoS Negl Trop Dis. 2014 Sep 11;8(9):e3154. doi: 10.1371/journal.pntd.0003154. eCollection 2014 Sep.
- Molina-Cruz A, Raytselis N, Withers R, Dwivedi A, Crompton PD, Traore B, Carpi G, Silva JC, Barillas-Mury C. A genotyping assay to determine geographic origin and transmission potential of Plasmodium falciparum malaria cases. Commun Biol. 2021 Sep 30;4(1):1145. doi: 10.1038/s42003-021-02667-0.
- Guha R, Mathioudaki A, Doumbo S, Doumtabe D, Skinner J, Arora G, Siddiqui S, Li S, Kayentao K, Ongoiba A, Zaugg J, Traore B, Crompton PD. Plasmodium falciparum malaria drives epigenetic reprogramming of human monocytes toward a regulatory phenotype. PLoS Pathog. 2021 Apr 6;17(4):e1009430. doi: 10.1371/journal.ppat.1009430. eCollection 2021 Apr.
- Obeng-Adjei N, Larremore DB, Turner L, Ongoiba A, Li S, Doumbo S, Yazew TB, Kayentao K, Miller LH, Traore B, Pierce SK, Buckee CO, Lavstsen T, Crompton PD, Tran TM. Longitudinal analysis of naturally acquired PfEMP1 CIDR domain variant antibodies identifies associations with malaria protection. JCI Insight. 2020 Jun 18;5(12):e137262. doi: 10.1172/jci.insight.137262.
- Liu EW, Skinner J, Tran TM, Kumar K, Narum DL, Jain A, Ongoiba A, Traore B, Felgner PL, Crompton PD. Protein-Specific Features Associated with Variability in Human Antibody Responses to Plasmodium falciparum Malaria Antigens. Am J Trop Med Hyg. 2018 Jan;98(1):57-66. doi: 10.4269/ajtmh.17-0437. Erratum In: Am J Trop Med Hyg. 2018 Feb;98(2):636.
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Actual)
1 de mayo de 2011
Finalización primaria (Actual)
28 de marzo de 2022
Finalización del estudio (Actual)
29 de marzo de 2022
Fechas de registro del estudio
Enviado por primera vez
23 de marzo de 2011
Primero enviado que cumplió con los criterios de control de calidad
23 de marzo de 2011
Publicado por primera vez (Estimar)
24 de marzo de 2011
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
31 de marzo de 2022
Última actualización enviada que cumplió con los criterios de control de calidad
29 de marzo de 2022
Última verificación
1 de marzo de 2022
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- 999911126
- 11-I-N126
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .