Studies to Evaluate Blood Safety: Risk of Transmission of Parasites such as Trypanosoma cruzi through Blood Transfusion

Principal Investigator: Alain Debrabant, PhD
Office / Division / Lab: OBRR / DETTD / LBPUA

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Overview

Public Health Issue: The protozoan parasite Trypanosoma cruzi (T. cruzi) is the causative agent of Chagas disease. It is estimated that 90 million people are at risk for this disease mostly in Central and South America. Of the 16-20 million infected individuals, 50,000 die each year and all others become asymptomatic carriers. Several documented cases of T. cruzi transmission by blood transfusion or organ transplantation have been reported in North America. In order to reduce the risk of transmission by blood transfusion in the US, the FDA licensed in December 2006 the first blood screening test for the presence of T. cruzi antibodies in blood.

Regulatory Contribution: It is anticipated that the entire US blood supply will be screened for the presence of T. cruzi antibodies in the near future and ultimately tested for all major blood borne parasites. Our research program contributes to our better understanding of T. cruzi biology and pathogenesis, which is important to make informed regulatory decisions regarding this blood borne pathogen. Further it will facilitate evaluation of the sensitivity and specificity of blood screening tests for T. cruzi and other related blood borne pathogens.

Research Approach: Our research program includes the identification of new parasite targets that could be exploited for drug and vaccine development, or for parasite detection in blood and blood products. The selection of targets for detection assays is based on the high copy number of nucleic acid target sequences in parasite genomes for nucleic acid-based assays and on the role of parasite proteins in infectivity and host immunity for protein-based assays. In addition, new technologies to concentrate parasites from infected blood prior to testing or to eliminate parasites by filtration are being evaluated. Our goal is to improve the sensitivity of nucleic acid- or parasite protein-based assays and further enhance blood safety.

Mission Relevance & Outcomes: Knowledge gained from these studies will be applicable to the evaluation of the sensitivity and specificity of novel blood screening tests and testing platforms. Such studies will contribute to increase the safety of the US blood supply and decrease the risk of transmission of parasitic agents by blood transfusion or organ transplantation.

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Publications

Science 2008 Aug 15;321(5891):970-4
In vivo imaging reveals an essential role for neutrophils in leishmaniasis transmitted by sand flies.
Peters NC, Egen JG, Secundino N, Debrabant A, Kimblin N, Kamhawi S, Lawyer P, Fay MP, Germain RN, Sacks D

Proc Natl Acad Sci U S A 2008 Jul 22;105(29):10125-30
Quantification of the infectious dose of Leishmania major transmitted to the skin by single sand flies.
Kimblin N, Peters N, Debrabant A, Secundino N, Egen J, Lawyer P, Fay MP, Kamhawi S, Sacks D

J Cell Sci 2008 Jan 1;121(Pt 1):99-109
Conservation of the pro-apoptotic nuclease activity of endonuclease G in unicellular trypanosomatid parasites.
Gannavaram S, Vedvyas C, Debrabant A

Eukaryot Cell 2007 Oct;6(10):1745-57
Characterization of metacaspases with trypsin-like activity and their putative role in the programmed cell death in the protozoan parasite Leishmania.
Lee N, Gannavaram S, Selvapandiyan A, Debrabant A

J Immunol 2006 Sep 15;177(6):3525-33
Leishmania antigens are presented to CD8+ T Cells by a transporter associated with antigen processing-independent pathway in vitro and in vivo.
Bertholet S, Goldszmid R, Morrot A, Debrabant A, Afrin F, Collazo-Custodio C, Houde M, Desjardins M, Sher A, Sacks D

Indian J Med Res 2006 Mar;123(3):455-66
Genetically modified live attenuated parasites as vaccines for leishmaniasis.
Selvapandiyan A, Duncan R, Debrabant A, Lee N, Sreenivas G, Salotra P, Nakhasi HL

Mol Biochem Parasitol 2006 Feb;145(2):147-57
Cloning and characterization of angiotensin converting enzyme related dipeptidylcarboxypeptidase from Leishmania donovani.
Goyal N, Duncan R, Selvapandiyan A, Debrabant A, Baig MS, Nakhasi HL

Infect Immun 2005 Oct;73(10):6620-8
Antigen requirements for efficient priming of CD8+ T cells by leishmania major-infected dendritic cells.
Bertholet S, Debrabant A, Afrin F, Caler E, Mendez S, Tabbara KS, Belkaid Y, Sacks DL

J Biol Chem 2004 Jun 11;279(24):25703-10
Centrin gene disruption impairs stage specific basal body duplication and cell cycle progression in Leishmaniac.
Selvapandiyan A, Debrabant A, Duncan R, Muller J, Salotra P, Sreenivas G, Salisbury JL, Nakhasi HL

Int J Parasitol 2004 Feb;34(2):205-17
Generation of Leishmania donovani axenic amastigotes: their growth and biological characteristics.
Debrabant A, Joshi MB, Pimenta PF, Dwyer DM