NCT01322581

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

Completed Last updated 31 March 2022

What this trial tests

trial in Malaria in 1,188 participants. Completed in 29 March 2022.

Timeline

1 May 2011

Primary endpoint
28 March 2022

29 March 2022

Quick facts

Lead sponsor	National Institute of Allergy and Infectious Diseases (NIAID)
Status	Completed
Study type	OBSERVATIONAL
Enrollment	1,188
Start date	1 May 2011
Primary completion	28 March 2022
Estimated completion	29 March 2022
Sites	1 location across Mali

Conditions studied

• Malaria — all drugs for Malaria →

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Who can join

Adults 3 Months to 40, any sex, with Malaria. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own 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 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....

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. An intensive longitudinal cohort study of Malian children and adults reveals no evidence of acquired immunity to Plasmodium falciparum infection.
   Tran TM, Li S, Doumbo S, Doumtabe D, et al · · 2013 · cited 217× · PMID 23487390 · DOI 10.1093/cid/cit174
2. Naturally acquired antibodies specific for Plasmodium falciparum reticulocyte-binding protein homologue 5 inhibit parasite growth and predict protection from malaria.
   Tran TM, Ongoiba A, Coursen J, Crosnier C, et al · · 2014 · cited 100× · PMID 24133188 · DOI 10.1093/infdis/jit553
3. Transcriptomic evidence for modulation of host inflammatory responses during febrile Plasmodium falciparum malaria.
   Tran TM, Jones MB, Ongoiba A, Bijker EM, et al · · 2016 · cited 80× · PMID 27506615 · DOI 10.1038/srep31291
4. A Molecular Signature in Blood Reveals a Role for p53 in Regulating Malaria-Induced Inflammation.
   Tran TM, Guha R, Portugal S, Skinner J, et al · · 2019 · cited 77× · PMID 31492649 · DOI 10.1016/j.immuni.2019.08.009
5. Design and implementation of multiplexed amplicon sequencing panels to serve genomic epidemiology of infectious disease: A malaria case study.
   LaVerriere E, Schwabl P, Carrasquilla M, Taylor AR, et al · · 2022 · cited 75× · PMID 35437908 · DOI 10.1111/1755-0998.13622
6. Treatment of Chronic Asymptomatic Plasmodium falciparum Infection Does Not Increase the Risk of Clinical Malaria Upon Reinfection.
   Portugal S, Tran TM, Ongoiba A, Bathily A, et al · · 2017 · cited 64× · PMID 28362910 · DOI 10.1093/cid/ciw849
7. Plasmodium falciparum malaria drives epigenetic reprogramming of human monocytes toward a regulatory phenotype.
   Guha R, Mathioudaki A, Doumbo S, Doumtabe D, et al · · 2021 · cited 57× · PMID 33822828 · DOI 10.1371/journal.ppat.1009430
8. Plasmodium falciparum-specific IgM B cells dominate in children, expand with malaria, and produce functional IgM.
   Hopp CS, Sekar P, Diouf A, Miura K, et al · · 2021 · cited 54× · PMID 33661303 · DOI 10.1084/jem.20200901