Overview

This trial is active, not recruiting.

Condition plasmodium falciparum
Sponsor National Institute of Allergy and Infectious Diseases (NIAID)
Start date March 2011
Trial size 1000 participants
Trial identifier NCT01322581, 11-I-N126, 999911126

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Time perspective prospective

Primary Outcomes

Measure
Identify genome-wide expression profiles induced by Pf infection thatare associated with malaria immunity.
time frame: Blood will be collected by venipuncture at the time of the first research-defined malaria episode. Blood collection by venipuncture will be repeated 7 days after the first research-defined malaria episode.

Eligibility Criteria

Male or female participants from 3 months up to 40 years old.

- 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).

Additional Information

Official title A Longitudinal Systems Biological Analysis of Naturally Acquired Malaria Immunity in Mali
Principal investigator Peter D Crompton, M.D.
Description 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 700 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 percent 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.
Trial information was received from ClinicalTrials.gov and was last updated in April 2016.
Information provided to ClinicalTrials.gov by National Institutes of Health Clinical Center (CC).