A Longitudinal Systems Biological Analysis of Naturally Acquired Malaria Immunity in Mali
29 de março de 2022 atualizado 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....
Visão geral do estudo
Status
Concluído
Condições
Descrição detalhada
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 estudo
Observacional
Inscrição (Real)
1188
Contactos e Locais
Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.
Locais de estudo
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Bamako, Mali
- University of Bamako, Faculty of Medicine, Pharmacy and Odontostomatology
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Critérios de participação
Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.
Critérios de elegibilidade
Idades elegíveis para estudo
3 meses a 40 anos (Filho, Adulto)
Aceita Voluntários Saudáveis
Sim
Gêneros Elegíveis para o Estudo
Tudo
Método de amostragem
Amostra de Probabilidade
População do estudo
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.@@@
Descrição
- 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).
Plano de estudo
Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.
Como o estudo é projetado?
Detalhes do projeto
Coortes e Intervenções
Grupo / Coorte |
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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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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
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Pf expression profiles
Prazo: 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 resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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serum cytokine profiles
Prazo: 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
Prazo: 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
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Investigadores
- Investigador principal: Peter D Crompton, M.D., National Institute of Allergy and Infectious Diseases (NIAID)
Publicações e links úteis
A pessoa responsável por inserir informações sobre o estudo fornece voluntariamente essas publicações. Estes podem ser sobre qualquer coisa relacionada ao estudo.
Publicações Gerais
- 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.
Datas de registro do estudo
Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.
Datas Principais do Estudo
Início do estudo (Real)
1 de maio de 2011
Conclusão Primária (Real)
28 de março de 2022
Conclusão do estudo (Real)
29 de março de 2022
Datas de inscrição no estudo
Enviado pela primeira vez
23 de março de 2011
Enviado pela primeira vez que atendeu aos critérios de CQ
23 de março de 2011
Primeira postagem (Estimativa)
24 de março de 2011
Atualizações de registro de estudo
Última Atualização Postada (Real)
31 de março de 2022
Última atualização enviada que atendeu aos critérios de controle de qualidade
29 de março de 2022
Última verificação
1 de março de 2022
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- 999911126
- 11-I-N126
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