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U.S. Department of Health and Human Services

Vaccines, Blood & Biologics

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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 / LEP


General Overview

Leishmaniasis is a disease caused by Leishmania parasites transmitted by the bite of certain species of sand fly in parts of South America, Africa, Southeast Asia, the Middle East, and Southern and Eastern Europe. Transfusions of blood from infected donors can also spread the parasite.

Depending on the specific type of the disease, a person with leishmaniasis can develop disfiguring ulcers in the skin, nose, mouth, or throat; or suffer potentially fatal spleen or liver damage.

United States military personnel or civilians stationed in areas of the world where leishmaniasis occurs are at risk of infection. This threat has increased in recent years because of extensive travel to these areas by US citizens.

There is no vaccine to prevent this infection and the parasites can develop resistance to the drugs available to treat the disease if they are used for a prolonged period of time.

Industry is currently developing vaccines and diagnostic tests for Leishmania infection that they will submit to FDA for evaluation.

One of the major obstacles to detecting the parasites in blood is that they occur in very low numbers. Therefore, we are developing methods using state-of-art technologies to solve that problem. In addition, we are developing tests that manufacturers can use to ensure the safety and effectiveness of such vaccines.


Scientific Overview

Blood-borne parasites such as Leishmania pose a serious public health risk worldwide either due to naturally acquired disease (Leishmaniasis) or through blood transfusion.

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 risk to public health, and especially to the US blood supply.

There are no FDA-licensed vaccines or screening tests for Leishmania parasites. Instead, travelers to endemic areas are deferred from donating blood and are covered under malaria donor deferral history questionnaire in areas where both diseases coexist. Thus, these individuals are lost as potential blood donors whether or not they are actually infected. 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.


Publications

J Infect Dis 2013 Apr;207(8):1328-38
A New Model of Progressive Visceral Leishmaniasis in Hamsters by Natural Transmission via Bites of Vector Sand Flies.
Aslan H, Dey R, Meneses C, Castrovinci P, Jeronimo SM, Oliva G, Fischer L, Duncan RC, Nakhasi HL, Valenzuela JG, Kamhawi S

J Immunol 2013 Mar 1;190(5):2138-49
Live attenuated Leishmania donovani p27 gene knockout parasites are nonpathogenic and elicit long-term protective immunity in BALB/c mice.
Dey R, Dagur PK, Selvapandiyan A, McCoy JP, Salotra P, Duncan R, Nakhasi HL

Mol Microbiol 2012 Oct;86(1):187-98
Deletion of mitochondrial associated ubiquitin fold modifier protein Ufm1 in Leishmania donovani results in loss of beta-oxidation of fatty acids and blocks cell division in the amastigote stage.
Gannavaram S, Connelly PS, Daniels MP, Duncan R, Salotra P, Nakhasi HL

PLoS Negl Trop Dis 2012 Oct;6(10):e1849
Leishmania donovani argininosuccinate synthase is an active enzyme associated with parasite pathogenesis.
Lakhal-Naouar I, Jardim A, Strasser R, Luo S, Kozakai Y, Nakhasi HL, Duncan RC

PLoS One 2012;7(9):e45288
Role of centrins 2 and 3 in organelle segregation and cytokinesis in Trypanosoma brucei.
Selvapandiyan A, Kumar P, Salisbury JL, Wang CC, Nakhasi HL

PLoS One 2012;7(8):e43533
Development of an aptamer-based concentration method for the detection of Trypanosoma cruzi in blood.
Nagarkatti R, Bist V, Sun S, Fortes de Araujo F, Nakhasi HL, Debrabant A

J Trop Med 2012;2012:631460
Immunity to visceral leishmaniasis using genetically defined live-attenuated parasites.
Selvapandiyan A, Dey R, Gannavaram S, Lakhal-Naouar I, Duncan R, Salotra P, Nakhasi HL

Antimicrob Agents Chemother 2012 Jan;56(1):518-25
Downregulation of mitogen-activated protein kinase 1 of Leishmania donovani field isolates is associated with antimony resistance.
Ashutosh, Garg M, Sundar S, Duncan R, Nakhasi HL, Goyal N

Mol Biol Int 2011;2011:428486
Identification and Characterization of Genes Involved in Leishmania Pathogenesis: The Potential for Drug Target Selection.
Duncan R, Gannavaram S, Dey R, Debrabant A, Lakhal-Naouar I, Nakhasi HL

Transfusion 2011 Aug;51(8):1855-71
FDA workshop on emerging infectious diseases: evaluating emerging infectious diseases (EIDs) for transfusion safety.
Atreya C, Nakhasi H, Mied P, Epstein J, Hughes J, Gwinn M, Kleinman S, Dodd R, Stramer S, Walderhaug M, Ganz P, Goodrich R, Tibbetts C, Asher D

PLoS Negl Trop Dis 2011 Mar 29;5(3):e943
Vaccines for the leishmaniases: proposals for a research agenda.
Costa CH, Peters NC, Maruyama SR, de Brito EC Jr, Santos IK

PLoS One 2011 Jan 14;6(1):e16156
Mitochondrial Associated Ubiquitin Fold Modifier-1 Mediated Protein Conjugation in Leishmania donovani.
Gannavaram S, Sharma P, Duncan RC, Salotra P, Nakhasi HL

Infect Immun 2010 Nov;78(11):4613-24
Multiple antigen peptide vaccines against Plasmodium falciparum malaria.
Mahajan B, Berzofsky JA, Boykins RA, Majam V, Zheng H, Chattopadhyay R, de la Vega P, Moch JK, Haynes JD, Belyakov IM, Nakhasi HL, Kumar S

Int J Antimicrob Agents 2010 Jul;36(1):50-7
Overexpression of histone H2A modulates drug susceptibility in Leishmania parasites.
Singh R, Kumar D, Duncan RC, Nakhasi HL, Salotra P

Mol Microbiol 2010 Jul;77(2):399-414
Characterization of a Leishmania stage-specific mitochondrial membrane protein that enhances the activity of cytochrome c oxidase and its role in virulence.
Dey R, Meneses C, Salotra P, Kamhawi S, Nakhasi HL, Duncan R

Parasitol Int 2010 Jun;59(2):262-4
Comparative in vivo expression of amastigote up regulated Leishmania genes in three different forms of Leishmaniasis.
Sharma P, Gurumurthy S, Duncan R, Nakhasi HL, Salotra P

Transfusion 2009 Dec;49(12):2759-71
Transfusion-transmitted babesiosis in the United States: summary of a workshop.
Gubernot DM, Nakhasi HL, Mied PA, Asher DM, Epstein JS, Kumar S

J Immunol 2009 Aug 1;183(3):1813-20
Intracellular Replication-Deficient Leishmania donovani Induces Long Lasting Protective Immunity against Visceral Leishmaniasis.
Selvapandiyan A, Dey R, Nylen S, Duncan R, Sacks D, Nakhasi HL

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):3290-301
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

     
 

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