Longitudinal Analysis of Plasmodium Falciparum-Specific Immunity in Travelers and Immigrants From Malaria Endemic Areas to the United States

NCT02153996 | Terminated

• 2 other identifiers: 14012114-I-0121
• Study Type: observational
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

Plasmodium falciparum malaria is a major cause of morbidity and mortality in tropical and sub-tropical areas worldwide. Repeated P. falciparum infections in endemic areas induce protective immunity, thus providing optimism that an effective malaria vaccine can be developed. Key to the development of such a vaccine is an understanding of the immune mechanisms underlying protection and the longevity of these responses in the absence of continuous P. falciparum exposure. Anecdotal evidence suggests clinical immunity to malaria wanes within months to years after an immune individual leaves an endemic area. A detailed, systematic description of the quality and longevity of the P. falciparum-specific humoral and cellular immune responses in such individuals over time in the absence of ongoing exposure is lacking. This protocol will attempt to fill this knowledge gap through comprehensive longitudinal immunological analyses of two populations of healthy adult volunteers: 1) naive travelers returning from malaria endemic areas recently treated (within 2 weeks) for acute P. falciparum malaria and referred from hospitals in the metropolitan Washington DC area; and 2) immigrants from malaria endemic areas living in the metropolitan Washington DC area with serologic evidence of past P. falciparum exposure. In both groups, venipuncture and possibly apheresis will be performed for the isolation of plasma, RNA and peripheral blood mononuclear cells (PBMCs) which will be analysed to understand the components of innate and adaptive immunity to malaria. Na(SqrRoot) ve travelers returning from malaria endemic areas recently treated for acute malaria will undergo venipuncture at enrollment, then once every 2 weeks for 2 months, then every 3 months for 1 year, and then every 6 months for up to 5 years. Immigrants will be seen every three months for one year and then every six months for up to 5 years. All subjects who return to the U.S. from a malaria endemic area will be evaluated within two weeks of return for repeat venipuncture and will restart the same sequence of blood draws as naive travelers. Optional apheresis will be performed on both na(SqrRoot) ve travelers and immigrants at enrollment, at 1, 6, and 12 months, then yearly therafter. The primary objective is to estimate the quality and longevity of P. falciparum-specific humoral and cellular immune responses in the absence of ongoing P. falciparum exposure in both returned na(SqrRoot) ve travelers and immigrants. The secondary objective is to compare the P. falciparum-specific humoral and cellular immune response in na(SqrRoot) ve travelers and immigrants to individuals in malaria-endemic areas enrolled in ongoing LIG protocols in Mali. ...

Conditions

Malaria

Keywords

Malaria Immunity Longevity

Outcome Measures

Primary Outcomes (1)

• Estimate the quality and longevity of P. falciparum-specific humoral and cellular immune responses in the absence of ongoing P. falciparum exposure.

  Five years

Secondary Outcomes (1)

• Compare the P. falciparum-specific humoral and cellular immune response in na(SqrRoot) ve travelers and immigrants to age and sex matched individuals in malaria-endemic areas enrolled in ongoing LIG protocols in Mali.

  5 years

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All Subjects: Age 18-65
• Agree to have blood specimens stored for future research and genetic studies
• Malaria endemicity will be defined according to CDC Yellow Book criteria available at:
• http://wwwnc.cdc.gov/travel/yellowbook/2014/chapter-3-infectious-diseases-related-totravel/malaria#3929
• NaIve travelers returning from malaria endemic areas recently treated for malaria:
• Treated for acute P. falciparum malaria within 4 weeks of enrolling in this study as determined by clinical and microbiologic evidence (including blood smear) of infection as indicated by medical records
• Immigrants from malaria endemic areas:
• Confirmation of having lived in a malaria endemic area through documentation or verifiable detailed immigration history.
• Evidence of past P. falciparum exposure with positive AMA -1 ELISA.

You may not qualify if:

• History of HIV and/or hepatitis C.
• Inadequate peripheral venous access
• Current use of the steroid equivalent of prednisone 20mg/day or more or other systemic immunosuppressants
• Underlying heart disease, lung disease, bleeding disorder, or other conditions that, in the judgment of the investigator, contraindicates study participation
• Temperature greater than or equal to 37.5 (Infinite)C or other clinical evidence of an acute infection
• Currently pregnant (positive urine beta-HCG) or breastfeeding

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Trape JF, Rogier C, Konate L, Diagne N, Bouganali H, Canque B, Legros F, Badji A, Ndiaye G, Ndiaye P, et al. The Dielmo project: a longitudinal study of natural malaria infection and the mechanisms of protective immunity in a community living in a holoendemic area of Senegal. Am J Trop Med Hyg. 1994 Aug;51(2):123-37. doi: 10.4269/ajtmh.1994.51.123.

  PMID: 8074247 BACKGROUND

• Perignon JL, Druilhe P. Immune mechanisms underlying the premunition against Plasmodium falciparum malaria. Mem Inst Oswaldo Cruz. 1994;89 Suppl 2:51-3. doi: 10.1590/s0074-02761994000600013.

  PMID: 7565132 BACKGROUND

• Deloron P, Chougnet C. Is immunity to malaria really short-lived? Parasitol Today. 1992 Nov;8(11):375-8. doi: 10.1016/0169-4758(92)90174-z.

  PMID: 15463545 BACKGROUND

MeSH Terms

Conditions

Malaria

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• Eugene W Liu, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2014
• First Posted: June 3, 2014
• Study Start: May 15, 2014
• Primary Completion: March 15, 2016
• Study Completion: March 15, 2016
• Last Updated: December 17, 2019

Record last verified: 2016-03-15

Locations

US (1)