Improving the Safety of Blood and Blood Related Products by Reducing the Risk of Transfusion-Transmission of Leishmania Parasites

Principal Investigator: Hira Nakhasi, PhD
Office / Division / Lab: OBRR / DETTD / LBPUA

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Overview

Public Health Issue: The blood borne parasites such as Leishmania pose a serious public health risk worldwide either due to naturally acquired disease (Leishmaniasis) or through blood transfusion. Visceral form of leishmaniasis is fatal if not treated. Approximately 12 million people are infected worldwide, with more than half a million new clinical cases reported annually. In the US, immigration from and travel to endemic countries by the general public, but particularly US military personnel, pose a serious public heath safety risk especially to blood safety.

Regulatory Contribution: At present there are no FDA-licensed vaccines or screening tests for Leishmania parasite. Instead donors traveling to endemic areas are deferred for the exposure and are covered under malaria donor deferral history questionnaire in areas where both diseases coexist, and are thus lost as potential blood donors. For example, military staff and civilians traveling to Iraq and Afghanistan are deferred for one year from the date of departure from those countries due to possible exposure to Leishmania parasites. Vaccines and diagnostic tests for Leishmania are being developed and evaluated by the FDA. Studies undertaken at FDA will support evaluations of the safety and efficacy of Leishmania vaccines and blood donor screening tests.

Research Approach: This research program develops strategies for evaluation of parasite vaccine safety and efficacy. Development of vaccine candidates in various animal models is used to increase our understanding of parameters impacting infectivity, identify biomarkers of parasite virulence, while increasing our knowledge about protective immunity against such parasite vaccine candidates. Evaluation of safety of such vaccine candidates is focused on the development of biomarkers of parasite virulence. These studies also allow us to identify genes and antigens used either for nucleic acid or antibody based (serological) detection of Leishmania infection in blood. Further, through the use of new technologies based both on nucleic acid and serological detection this laboratory develops and evaluates multiplex assays that allow detection of Leishmania simultaneously with other blood-borne pathogens so as to minimize the use of blood for testing. These activities will support the safety of the blood supply and in future will allow donors to be reentered that have been solely deferred on the basis of theoretical exposure, thus enhancing blood availability. Such technologies for multiple pathogen detection have also been adapted to identify potential bioterror pathogens as well, contributing toward protecting the blood supply from these agents.

Mission Relevance & Outcomes: These studies will be useful in evaluating the safety of parasite vaccines and ensure the safety and availability of the nations blood supply through evaluation of donor screening assays. Further, this research is part of FDA's Critical Path Research that provides proof-of-concept for Leishmania vaccine development, as well as Leishmania detection and sample preparation methodologies.

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Publications

J Biol Chem 2008 Nov 14;283(46):31871-83
Centrins, cell cycle regulation proteins in human malaria parasite plasmodium falciparum.
Mahajan B, Selvapandiyan A, Gerald NJ, Majam V, Zheng H, Wickramarachchi T, Tiwari J, Fujioka H, Moch JK, Kumar N, Aravind L, Nakhasi HL, Kumar S

Transfusion 2008 Sep;48(9):1787-98
A Leishmania minicircle DNA footprint assay for sensitive detection and rapid speciation of clinical isolates.
Selvapandiyan A, Duncan R, Mendez J, Kumar R, Salotra P, Cardo LJ, Nakhasi HL

Parasitology 2007 Oct;134(Pt 11):1527-39
Transcriptome analysis during the process of in vitro differentiation of Leishmania donovani using genomic microarrays.
Srividya G, Duncan R, Sharma P, Raju BV, Nakhasi HL, Salotra P

Mol Biol Cell 2007 Sep;18(9):3290-3301
Centrin1 Is Required for Organelle Segregation and Cytokinesis in Trypanosoma brucei.
Selvapandiyan A, Kumar P, Morris JC, Salisbury JL, Wang CC, Nakhasi HL

Biochem Biophys Res Commun 2007 May 18;356(4):1017-23
Microarray multiplex assay for the simultaneous detection and discrimination of hepatitis B, hepatitis C, and human immunodeficiency type-1 viruses in human blood samples.
Hsia CC, Chizhikov VE, Yang AX, Selvapandiyan A, Hewlett I, Duncan R, Puri RK, Nakhasi HL, Kaplan GG

Int J Parasitol 2006 Aug;36(9):1037-48
Protein disulfide isomerase assisted protein folding in malaria parasites.
Mahajan B, Noiva R, Yadava A, Zheng H, Majam V, Mohan KV, Moch JK, Haynes JD, Nakhasi H, Kumar S

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

Microbes Infect 2006 Mar;8(3):637-44
Upregulation of surface proteins in Leishmania donovani isolated from patients of post kala-azar dermal leishmaniasis.
Salotra P, Duncan RC, Singh R, Subba Raju BV, Sreenivas G, 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

J Mol Diagn 2005 Oct;7(4):486-94
A multiplex polymerase chain reaction microarray assay to detect bioterror pathogens in blood.
Tomioka K, Peredelchuk M, Zhu X, Arena R, Volokhov D, Selvapandiyan A, Stabler K, Mellquist-Riemenschneider J, Chizhikov V, Kaplan G, Nakhasi H, Duncan R

J Mol Diagn 2005 May;7(2):268-75
A novel semiquantitative fluorescence-based multiplex polymerase chain reaction assay for rapid simultaneous detection of bacterial and parasitic pathogens from blood.
Selvapandiyan A, Stabler K, Ansari NA, Kerby S, Riemenschneider J, Salotra P, Duncan R, Nakhasi HL

Curr Mol Med 2004 Sep;4(6):611-21
The application of gene expression microarray technology to kinetoplastid research.
Duncan RC, Salotra P, Goyal N, Akopyants NS, Beverley SM, Nakhasi HL

J Clin Microbiol 2004 Apr;42(4):1739-1741
DNA Polymorphism Assay Distinguishes Isolates of Leishmania donovani That Cause Kala-Azar from Those That Cause Post-Kala-Azar Dermal Leishmaniasis in Humans.
Sreenivas G, Subba Raju BV, Singh R, Selvapandiyan A, Duncan R, Sarkar D, Nakhasi HL, Salotra P

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

Exp Parasitol 2004 Mar-Apr;106(3-4):110-8
Arbitrary-primed PCR for genomic fingerprinting and identification of differentially regulated genes in Indian isolates of Leishmania donovani.
Sreenivas G, Singh R, Selvapandiyan A, Negi NS, Nakhasi HL, Salotra P