A Longitudinal Systems Biological Analysis of Naturally Acquired Malaria Immunity in Mali

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT01322581
First received: March 23, 2011
Last updated: April 5, 2014
Last verified: January 2014
  Purpose

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.


Condition
Plasmodium Falciparum
Malaria

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: A Longitudinal Systems Biological Analysis of Naturally Acquired Malaria Immunity in Mali

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 1000
Study Start Date: March 2011
Detailed 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 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 (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.

  Eligibility

Ages Eligible for Study:   3 Months to 25 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

Individuals 3 months to 25 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).

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01322581

Locations
Mali
University of Bamako, Faculty of Medicine, Pharmacy and Odontostomatology
Bamako, Mali
Sponsors and Collaborators
Investigators
Principal Investigator: Peter D Crompton, M.D. National Institute of Allergy and Infectious Diseases (NIAID)
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT01322581     History of Changes
Other Study ID Numbers: 999911126, 11-I-N126
Study First Received: March 23, 2011
Last Updated: April 5, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Plasmodium Falciparum
Genome-Wide Expression
Antibody Profiling by Protein Microarray
Multiplex Cytokine Analysis
Children and Adults
Malaria

Additional relevant MeSH terms:
Malaria
Protozoan Infections
Parasitic Diseases

ClinicalTrials.gov processed this record on September 16, 2014