Details of Disease

General Information of Disease (ID: DISABTW7)

Disease Name	Leishmaniasis
Synonyms	post kala-Azar dermal leishmaniasis; post-kala-azar dermal leishmaniasis; post-kala-azar dermal infectious disease by leishmaniasis; visceral leishmaniasis (subtype); cutaneous leishmaniasis (subtype)
Disease Class	1F54: Leishmaniasis
Definition	Infectious disease that is transmitted through the bite of hematophagous female phlebotomine sand flies. The clinical spectrum ranges from asymptomatic to clinically overt disease which can remain localized to the skin or disseminate to the upper oral and respiratory mucous membranes or throughout the reticulo-endothelial system. Three main clinical syndromes have been described: visceral (or Kala-Azar; with fever, weight loss, hepatosplenomegaly), cutaneous, and mucocutaneous leishmaniasis (cutaneous or mucocutaneous ulceration).
Disease Hierarchy	DIS57EB5: Protozoa infectious disease DISGFCIX: Vector-borne disease DISABTW7: Leishmaniasis
ICD Code	ICD-11 ICD-11: 1F54 ICD-10 ICD-10: B55, B55.9 Expand ICD-11 '1F54 Expand ICD-10 'B55; 'B55.9
Disease Identifiers	MONDO ID MONDO_0011989 MESH ID D007896 UMLS CUI C0023281 MedGen ID 9714 Orphanet ID 507 SNOMED CT ID 80612004

Drug-Interaction Atlas (DIA) of This Disease

Drug-Interaction Atlas (DIA)

This Disease is Treated as An Indication in 2 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Amphotericin B	DMTAJQE	Approved	Small molecular drug	[1]
Miltefosine	DMND304	Approved	Small molecular drug	[2]
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This Disease is Treated as An Indication in 2 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Sodium stibogluconate	DMH5MVE	Phase 2	NA	[3]
GSK3186899	DMJAVN7	Phase 1	Small molecular drug	[4]
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Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 18 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
PABPC1	TTHC8EF	Disputed	Biomarker	[5]
ARG1	TT7ZQEV	Strong	Altered Expression	[6]
CRP	TTWRN6M	Strong	Biomarker	[7]
IFNG	TT93WF5	Strong	Biomarker	[8]
IL18	TTRICUF	Strong	Biomarker	[9]
MCL1	TTL53M6	Strong	Biomarker	[10]
TNF	TTF8CQI	Strong	Altered Expression	[11]
TNFRSF18	TTG6LA7	Strong	Biomarker	[12]
CD160	TTOFEAS	Definitive	Biomarker	[13]
CPB1	TT4UJX5	Definitive	Biomarker	[14]
CYP51A1	TT67TDP	Definitive	Biomarker	[15]
DCLK3	TTMYK4Z	Definitive	Biomarker	[16]
FECH	TTQ6VF4	Definitive	Biomarker	[17]
IL32	TTD4G7L	Definitive	Biomarker	[18]
MAP3K10	TT9FN4J	Definitive	Biomarker	[19]
PDXP	TT9UYG4	Definitive	Biomarker	[20]
SLC1A5	TTF7WRM	Definitive	Altered Expression	[21]
SLC1A7	TTK41DM	Definitive	Altered Expression	[21]
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⏷ Show the Full List of 18 DTT(s)

This Disease Is Related to 2 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC11A1	DT650XW	Strong	Genetic Variation	[22]
SLC7A6	DTTBSQG	Definitive	Biomarker	[23]
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This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
ALDH1A2	DEKN1H4	Definitive	Biomarker	[24]
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This Disease Is Related to 29 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
FCN2	OTTHJBKZ	Limited	Biomarker	[25]
GTF3C1	OT7JK0RG	Limited	Altered Expression	[26]
HM13	OTGEO1LP	Limited	Biomarker	[27]
IL12RB1	OTM1IJO2	Limited	Biomarker	[28]
LMLN	OTQF0JPY	Limited	Biomarker	[29]
ATP2A3	OTFYDEES	Disputed	Biomarker	[30]
ATP2B4	OTMWFDAC	Disputed	Biomarker	[30]
DDT	OTF5HTYL	Disputed	Biomarker	[31]
DPAGT1	OTYEJAGZ	Disputed	Biomarker	[32]
HSPA4	OT5HR0AR	Disputed	Biomarker	[33]
MAPK4	OTVWWUYS	Disputed	Biomarker	[34]
PNOC	OTJEAADN	Disputed	Genetic Variation	[35]
POLR1A	OTDWI0TG	Disputed	Biomarker	[36]
RPA1	OT76POLP	Disputed	Biomarker	[36]
TOLLIP	OTYEO4NR	Disputed	Genetic Variation	[37]
CD244	OTSMR85N	Definitive	Biomarker	[13]
DUSP4	OT6WAO12	Definitive	Biomarker	[38]
EEF2	OTZ7SZ39	Definitive	Biomarker	[39]
EIF2B1	OT4NCVY1	Definitive	Biomarker	[40]
EIF2B2	OTQQMHM1	Definitive	Biomarker	[40]
EIF2B4	OTTM5SX1	Definitive	Biomarker	[40]
EIF2S2	OTXF0B09	Definitive	Biomarker	[40]
H6PD	OTO7TNDD	Definitive	Altered Expression	[41]
LRBA	OTOUZN9G	Definitive	Biomarker	[42]
MPG	OTAHW80B	Definitive	Biomarker	[43]
MPST	OTCDPH5D	Definitive	Biomarker	[19]
MSTO1	OT37XCNP	Definitive	Biomarker	[19]
PLP1	OT8CM9CX	Definitive	Biomarker	[20]
PSG5	OTHTU98X	Definitive	Biomarker	[44]
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⏷ Show the Full List of 29 DOT(s)

References

1	Amphotericin B FDA Label
2	2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
3	Leishmaniasis in Norway. Tidsskr Nor Laegeforen. 2021 Feb 22;141(3).
4	ClinicalTrials.gov (NCT03874234) Safety, Tolerability and Pharmacokinetics (PKs) Investigation of GSK3186899 in Healthy Subjects. U.S. National Institutes of Health.
5	Coadministration of the Three Antigenic Leishmania infantum Poly (A) Binding Proteins as a DNA Vaccine Induces Protection against Leishmania major Infection in BALB/c Mice.PLoS Negl Trop Dis. 2015 May 8;9(5):e0003751. doi: 10.1371/journal.pntd.0003751. eCollection 2015 May.
6	Leishmania infection activates host mTOR for its survival by M2macrophage polarization.Parasite Immunol. 2018 Nov;40(11):e12586. doi: 10.1111/pim.12586.
7	Circulating nitric oxide and C-reactive protein levels in Indian kala azar patients: correlation with clinical outcome.Clin Immunol. 2007 Mar;122(3):343-8. doi: 10.1016/j.clim.2006.11.008. Epub 2007 Jan 9.
8	Total serum IgD from healthy and sick dogs with leishmaniosis.Parasit Vectors. 2019 Mar 26;12(1):119. doi: 10.1186/s13071-019-3384-0.
9	Effects of trans-stilbene and terphenyl compounds on different strains of Leishmania and on cytokines production from infected macrophages.Exp Parasitol. 2018 Jan;184:31-38. doi: 10.1016/j.exppara.2017.11.004. Epub 2017 Nov 14.
10	Leishmania donovani Exploits Myeloid Cell Leukemia 1 (MCL-1) Protein to Prevent Mitochondria-dependent Host Cell Apoptosis.J Biol Chem. 2016 Feb 12;291(7):3496-507. doi: 10.1074/jbc.M115.672873. Epub 2015 Dec 15.
11	Leishmaniasis and tumor necrosis factor alpha antagonists in the Mediterranean basin. A switch in clinical expression.PLoS Negl Trop Dis. 2019 Aug 30;13(8):e0007708. doi: 10.1371/journal.pntd.0007708. eCollection 2019 Aug.
12	Therapeutic glucocorticoid-induced TNF receptor-mediated amplification of CD4+ T cell responses enhances antiparasitic immunity.J Immunol. 2010 Mar 1;184(5):2583-92. doi: 10.4049/jimmunol.0903080. Epub 2010 Feb 5.
13	Phenotypic and Functional Profiles of Antigen-Specific CD4(+) and CD8(+) T Cells Associated With Infection Control in Patients With Cutaneous Leishmaniasis.Front Cell Infect Microbiol. 2018 Nov 19;8:393. doi: 10.3389/fcimb.2018.00393. eCollection 2018.
14	Recombinant Cysteine Proteinase B from Leishmania braziliensis and Its Domains: Promising Antigens for Serodiagnosis of Cutaneous and Visceral Leishmaniasis in Dogs.J Clin Microbiol. 2019 Oct 23;57(11):e00819-19. doi: 10.1128/JCM.00819-19. Print 2019 Nov.
15	Synthesis and Biological Activity of Sterol 14-Demethylase and Sterol C24-Methyltransferase Inhibitors.Molecules. 2018 Jul 17;23(7):1753. doi: 10.3390/molecules23071753.
16	Dectin-1 Positive Dendritic Cells Expand after Infection with Leishmania major Parasites and Represent Promising Targets for Vaccine Development.Front Immunol. 2018 Feb 26;9:263. doi: 10.3389/fimmu.2018.00263. eCollection 2018.
17	Heme synthesis through the life cycle of the heme auxotrophic parasite Leishmania major.FASEB J. 2019 Dec;33(12):13367-13385. doi: 10.1096/fj.201901274RR. Epub 2019 Sep 25.
18	-Glucan-Induced Trained Immunity Protects against Leishmania braziliensis Infection: a Crucial Role for IL-32.Cell Rep. 2019 Sep 3;28(10):2659-2672.e6. doi: 10.1016/j.celrep.2019.08.004.
19	Effectiveness of an immunohistochemical protocol for Leishmania detection in different clinical forms of American tegumentary leishmaniasis.Parasitol Int. 2017 Feb;66(1):884-888. doi: 10.1016/j.parint.2016.10.003. Epub 2016 Oct 8.
20	Ornithine Decarboxylase Inhibition: A Strategy to Combat Various Diseases.Mini Rev Med Chem. 2018;18(12):1008-1021. doi: 10.2174/1389557517666170927130526.
21	The alkylaminoalkanethiosulfuric acids exhibit in-vitro antileishmanial activity against Leishmania (Viannia) braziliensis: a new perspective for use of these schistosomicidal agents.J Pharm Pharmacol. 2019 Dec;71(12):1784-1791. doi: 10.1111/jphp.13163. Epub 2019 Oct 3.
22	Susceptibility to leishmaniasis is affected by host SLC11A1 gene polymorphisms: a systematic review and meta-analysis.Parasitol Res. 2019 Aug;118(8):2329-2342. doi: 10.1007/s00436-019-06374-y. Epub 2019 Jun 23.
23	Amino acid permease 3 (aap3) coding sequence as a target for Leishmania identification and diagnosis of leishmaniases using high resolution melting analysis.Parasit Vectors. 2018 Jul 16;11(1):421. doi: 10.1186/s13071-018-2989-z.
24	Leishmania donovani reduces the levels of retinoic acid-synthesizing enzymes in infected macrophages and favoring its own survival.Parasitol Res. 2019 Jan;118(1):63-71. doi: 10.1007/s00436-018-6115-0. Epub 2018 Oct 18.
25	IL12 p35 and p40 subunit genes administered as pPAL plasmid constructs do not improve protection of pPAL-LACK vaccine against canine leishmaniasis.PLoS One. 2019 Feb 22;14(2):e0212136. doi: 10.1371/journal.pone.0212136. eCollection 2019.
26	Mechanism of down-regulation of RNA polymerase III-transcribed non-coding RNA genes in macrophages by Leishmania.J Biol Chem. 2011 Feb 25;286(8):6614-26. doi: 10.1074/jbc.M110.181735. Epub 2010 Dec 13.
27	Understanding serine proteases implications on Leishmania spp lifecycle.Exp Parasitol. 2018 Jan;184:67-81. doi: 10.1016/j.exppara.2017.11.008. Epub 2017 Nov 22.
28	A case of interleukin-12 receptor beta-1 deficiency with recurrent leishmaniasis.Pediatr Infect Dis J. 2007 Apr;26(4):366-8. doi: 10.1097/01.inf.0000258696.64507.0f.
29	Extracellular release of virulence factor major surface protease via exosomes in Leishmania infantum promastigotes.Parasit Vectors. 2018 Jun 19;11(1):355. doi: 10.1186/s13071-018-2937-y.
30	Regulation of PKC mediated signaling by calcium during visceral leishmaniasis.PLoS One. 2014 Oct 17;9(10):e110843. doi: 10.1371/journal.pone.0110843. eCollection 2014.
31	Global trends in the production and use of DDT for control of malaria and other vector-borne diseases.Malar J. 2017 Oct 5;16(1):401. doi: 10.1186/s12936-017-2050-2.
32	Identification and phylogenetic relationship of Iranian strains of various Leishmania species isolated from cutaneous and visceral cases of leishmaniasis based on N-acetylglucosamine-1-phosphate transferase gene.Infect Genet Evol. 2014 Aug;26:203-12. doi: 10.1016/j.meegid.2014.05.026. Epub 2014 Jun 7.
33	Identification of Leishmania (Viannia) species and clinical isolates of Leishmania (Leishmania) amazonensis from Brazil using PCR-RFLP of the heat-shock protein 70 gene reveals some unexpected observations.Diagn Microbiol Infect Dis. 2018 Aug;91(4):312-318. doi: 10.1016/j.diagmicrobio.2018.03.004. Epub 2018 Mar 12.
34	Linear B-cell epitope mapping of MAPK3 and MAPK4 from Leishmania braziliensis: implications for the serodiagnosis of human and canine leishmaniasis.Appl Microbiol Biotechnol. 2015 Feb;99(3):1323-36. doi: 10.1007/s00253-014-6168-7. Epub 2014 Oct 31.
35	Molecular detection of the blood meal source of sand flies (Diptera: Psychodidae) in a transmission area of American cutaneous leishmaniasis, Paran State, Brazil.Acta Trop. 2015 Mar;143:8-12. doi: 10.1016/j.actatropica.2014.11.006. Epub 2014 Dec 18.
36	Leishmania braziliensis replication protein A subunit 1: molecular modelling, protein expression and analysis of its affinity for both DNA and RNA.Parasit Vectors. 2014 Dec 12;7:573. doi: 10.1186/s13071-014-0573-8.
37	Polymorphisms in the TOLLIP Gene Influence Susceptibility to Cutaneous Leishmaniasis Caused by Leishmania guyanensis in the Amazonas State of Brazil.PLoS Negl Trop Dis. 2015 Jun 24;9(6):e0003875. doi: 10.1371/journal.pntd.0003875. eCollection 2015.
38	Immunomodulation of dual specificity phosphatase 4 during visceral leishmaniasis.Microbes Infect. 2018 Feb;20(2):111-121. doi: 10.1016/j.micinf.2017.10.009. Epub 2017 Nov 10.
39	Induction of protective cellular immune responses against experimental visceral leishmaniasis mediated by dendritic cells pulsed with the N-terminal domain of Leishmania infantum elongation factor-2 and CpG oligodeoxynucleotides.Mol Immunol. 2018 Nov;103:7-20. doi: 10.1016/j.molimm.2018.08.004. Epub 2018 Aug 30.
40	Analysis of the Antigenic and Prophylactic Properties of the Leishmania Translation Initiation Factors eIF2 and eIF2B in Natural and Experimental Leishmaniasis.Front Cell Infect Microbiol. 2018 Apr 5;8:112. doi: 10.3389/fcimb.2018.00112. eCollection 2018.
41	Glucose-6-phosphate dehydrogenase (G6PD) activity can modulate macrophage response to Leishmania major infection.Int Immunopharmacol. 2019 Apr;69:178-183. doi: 10.1016/j.intimp.2019.01.028. Epub 2019 Feb 1.
42	Leishmaniasis and Autoimmunity in Patient with LPS-Responsive Beige-Like Anchor Protein (LRBA) Deficiency.Endocr Metab Immune Disord Drug Targets. 2020;20(3):479-484. doi: 10.2174/1871530319666190807161546.
43	Encapsulation of the HSP-90 Chaperone Inhibitor 17-AAG in Stable Liposome Allow Increasing the Therapeutic Index as Assessed, in vitro, on Leishmania (L) amazonensis Amastigotes-Hosted in Mouse CBA Macrophages.Front Cell Infect Microbiol. 2018 Aug 30;8:303. doi: 10.3389/fcimb.2018.00303. eCollection 2018.
44	Promastigote secretory gel from natural and unnatural sand fly vectors exacerbate Leishmania major and Leishmania tropica cutaneous leishmaniasis in mice.Parasitology. 2019 Dec;146(14):1796-1802. doi: 10.1017/S0031182019001069. Epub 2019 Aug 29.