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  5. Improving the Safety of Blood and Blood Related Products by Reducing the Risk of Transfusion-Transmission of Leishmania Parasites
  1. Biologics Research Projects

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.

Co-infection of HIV and visceral leishmaniasis has led to the reemergence of visceral leishmaniasis in Leishmania non-endemic countries.

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 and biomarkers of immunity 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.


Sci Rep 2017 Jul 5;7(1):4718
Whole genome sequencing of live attenuated Leishmania donovani parasites reveals novel biomarkers of attenuation and enables product characterization.
Gannavaram S, Torcivia J, Gasparyan L, Kaul A, Ismail N, Simonyan V, Nakhasi HL

Cell Immunol 2016 Nov;309:37-41
Role of pro-inflammatory cytokine IL-17 in Leishmania pathogenesis and in protective immunity by Leishmania vaccines.
Banerjee A, Bhattacharya P, Joshi AB, Ismail N, Dey R, Nakhasi HL

Sci Rep 2016 Sep 14;6:33059
Gene deleted live attenuated Leishmania vaccine candidates against visceral leishmaniasis elicit pro-inflammatory cytokines response in human PBMCs.
Avishek K, Kaushal H, Gannavaram S, Dey R, Selvapandiyan A, Ramesh V, Negi NS, Dubey US, Nakhasi HL, Salotra P

PLoS Negl Trop Dis 2016 Aug 31;10(8):e0004963
Live attenuated Leishmania donovani centrin knock out parasites generate non-inferior protective immune response in aged mice against visceral leishmaniasis.
Bhattacharya P, Dey R, Dagur PK, Joshi AB, Ismail N, Gannavaram S, Debrabant A, Akue AD, KuKuruga MA, Selvapandiyan A, McCoy JP Jr, Nakhasi HL

Am J Trop Med Hyg 2016 Jul 6;95(1):109-19
Differential Role of Leptin as an Immunomodulator in Controlling Visceral Leishmaniasis in Normal and Leptin-Deficient Mice.
Maurya R, Bhattacharya P, Ismail N, Dagur PK, Joshi AB, Razdan K, McCoy JP Jr, Jill A, Dey R, Nakhasi HL

Transfusion 2016 Jun;56(6 Pt 2):1537-47
Multiplex detection and identification of viral, bacterial, and protozoan pathogens in human blood and plasma using a high-density resequencing pathogen microarray platform.
Kourout M, Fisher C, Purkayastha A, Tibbetts C, Winkelman V, Williamson P, Nakhasi HL, Duncan R

Front Immunol 2016 May 13;7:187
Modulation of innate immune mechanisms to enhance Leishmania vaccine-induced immunity: role of coinhibitory molecules.
Gannavaram S, Bhattacharya P, Ismail N, Kaul A, Singh R, Nakhasi HL

J Appl Microbiol 2016 Apr;120(4):1119-29
Standardized methods to generate mock (spiked) clinical specimens by spiking blood or plasma with cultured pathogens.
Dong M, Fisher C, Anez G, Rios M, Nakhasi HL, Hobson JP, Beanan M, Hockman D, Grigorenko E, Duncan R

Parasit Vectors 2016 Apr 30;9(1):250
Application of rapid in vitro co-culture system of macrophages and T-cell subsets to assess the immunogenicity of dogs vaccinated with live attenuated Leishmania donovani centrin deleted parasites (LdCen-/-).
Viana KF, Fiuza JA, Gannavaram S, Dey R, Selvapandiyan A, Bartholomeu DC, Silveira-Lemos DD, Bueno LL, Dutra WO, Fujiwara RT, Nakhasi HL, Giunchetti RC

Methods Mol Biol 2016;1403:623-38
Methods to evaluate the preclinical safety and immunogenicity of genetically modified live-attenuated Leishmania parasite vaccines.
Gannavaram S, Bhattacharya P, Dey R, Ismail N, Avishek K, Salotra P, Selvapandiyan A, Satoskar A, Nakhasi HL

PLoS Negl Trop Dis 2016 Jan 11;10(1):e0004322
Intradermal immunization of Leishmania donovani centrin knock-out parasites in combination with salivary protein LJM19 from sand fly vector induces a durable protective immune response in hamsters.
Fiuza JA, Dey R, Davenport D, Abdeladhim M, Meneses C, Oliveira F, Kamhawi S, Valenzuela JG, Gannavaram S, Nakhasi HL

Infect Immun 2015 Oct;83(10):3800-15
Genetically modified live attenuated L.donovani parasites induce innate immunity through classical activation of macrophages that direct Th1 response in mice.
Bhattacharya P, Dey R, Dagur PK, Kruhlak M, Ismail N, Debrabant A, Joshi AB, Akue A, Kukuruga M, Takeda K, Selvapandiyan A, McCoy JP Jr, Nakhasi HL

Proc Natl Acad Sci U S A 2015 Jul 28;112(30):E4094-103
TACI deficiency leads to alternatively activated macrophage phenotype and susceptibility to Leishmania infection.
Allman WR, Dey R, Liu L, Siddiqui S, Coleman AS, Bhattacharya P, Yano M, Uslu K, Takeda K, Nakhasi HL, Akkoyunlu M

Vaccine 2015 Jan 3;33(2):280-8
Vaccination using live attenuated Leishmania donovani centrin deleted parasites induces protection in dogs against Leishmania infantum.
Fiuza JA, Gannavaram S, Santiago HD, Selvapandiyan A, Souza DM, Passos LS, Mendonca LZ, Lemos-Giunchetti DD, Ricci ND, Bartholomeu DC, Giunchetti RC, Bueno LL, Correa-Oliveira R, Nakhasi HL, Fujiwara RT

Lancet Glob Health 2014 Dec;2(12):e683-4
Research priorities for elimination of visceral leishmaniasis.
Matlashewski G, Arana B, Kroeger A, Be-Nazir A, Mondal D, Nabi SG, Banjara MR, Das ML, Marasini B, Das P, Medley G, Satoskar A, Nakhasi H, Argaw D, Reeder J, Olliaro P

Front Immunol 2014 Dec 19;5:660
Targeted immunology for prevention and cure of VL.
Ali N, Nakhasi HL, Valenzuela JG, Reis AB

J Immunol 2014 Oct 1;193(7):3513-27
Characterization of cross-protection by genetically modified live-attenuated Leishmania donovani parasites against Leishmania mexicana.
Dey R, Natarajan G, Bhattacharya P, Cummings H, Dagur PK, Terrazas C, Selvapandiyan A, McCoy JP Jr, Duncan R, Satoskar AR, Nakhasi HL

Vaccine 2014 Jun 30;32(31):3895-901
Generation of growth arrested Leishmania amastigotes: a tool to develop live attenuated vaccine candidates against visceral leishmaniasis.
Selvapandiyan A, Dey R, Gannavaram S, Solanki S, Salotra P, Nakhasi HL

Front Immunol 2014 May 23;5:241
Biomarkers of Safety and Immune Protection for Genetically Modified Live Attenuated Vaccines Against Visceral Leishmaniasis - Discovery and Implications.
Gannavaram S, Dey R, Avishek K, Selvapandiyan A, Salotra P, Nakhasi HL

PLoS Negl Trop Dis 2014 Feb 20;8(2):e2707
Deletion of ubiquitin fold modifier protein Ufm1 processing peptidase Ufsp in L. donovani abolishes Ufm1 processing and alters pathogenesis.
Gannavaram S, Davey S, Lakhal-Naouar I, Duncan R, Nakhasi HL

J Mol Diagn 2014 Jan;16(1):136-44
Multiplex screening for blood-borne viral, bacterial, and protozoan parasites using an OpenArray platform.
Grigorenko E, Fisher C, Patel S, Chancey C, Rios M, Nakhasi HL, Duncan RC

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