Details of Disease

General Information of Disease (ID: DIS3Q9KF)

• Disease Name: Plasmodium falciparum malaria
• Synonyms: falciparum malaria; malignant tertian fever; falciparum malaria [malignant tertian]; malaria fever, subtertian; malignant tertian fever (finding); Plasmodium falciparum malaria, unspecified
• Disease Class: 1F40-1F45: Malaria
• Definition: Malaria resulting from infection by Plasmodium falciparum.
• Disease Hierarchy:
  DISQ9Y50: Malaria
  DIS3Q9KF: Plasmodium falciparum malaria
• ICD Code:
  ICD-11: ICD-11: 1F40
  ICD-10: ICD-10: B50
  Expand ICD-11: '1F40
  Expand ICD-10: 'B50
• Disease Identifiers:
  MONDO ID: MONDO_0005920
  MESH ID: D016778
  UMLS CUI: C0024535
  MedGen ID: 6185
  SNOMED CT ID: 248441000

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 4 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Artesunate	DMR27C8	Approved	Small molecular drug	[1]
Chloroquine	DMSI5CB	Approved	Small molecular drug	[2]
Hydroxychloroquine	DMSIVND	Approved	Small molecular drug	[3]
Sulfisoxazole	DMXLT8C	Approved	Small molecular drug	[4]

This Disease is Treated as An Indication in 1 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
PfSPZ-GA1	DMG2IBZ	Phase 2	NA	[5]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 14 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
ADAMTS13	TTUREBK	moderate	Altered Expression	[6]
FCGR2B	TT5RWKQ	moderate	Genetic Variation	[7]
MSMB	TTYH1ZK	moderate	Biomarker	[8]
ACKR1	TTKY2NS	Strong	Genetic Variation	[9]
CD36	TTPJMCU	Strong	Genetic Variation	[10]
DCPS	TTLSW9V	Strong	Biomarker	[11]
DHFR	TTYZVDJ	Strong	Genetic Variation	[12]
DNAJB1	TTPXAWS	Strong	Biomarker	[13]
FAS	TT7LTUJ	Strong	Biomarker	[14]
FCGR2A	TTXT21W	Strong	Genetic Variation	[15]
FDPS	TTIKWV4	Strong	Altered Expression	[16]
GRK5	TTTCXO0	Strong	Genetic Variation	[17]
PDXK	TTXI3KF	Strong	Altered Expression	[18]
TIRAP	TTKU0LS	Strong	Genetic Variation	[19]

This Disease Is Related to 4 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
ABO	DESIA7R	moderate	Biomarker	[20]
CYP2C8	DES5XRU	Strong	Genetic Variation	[21]
PGM1	DEA3VM1	Strong	Biomarker	[22]
UGT1A9	DE85D2P	Strong	Genetic Variation	[23]

This Disease Is Related to 22 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ATAD1	OTJ02XFL	moderate	Genetic Variation	[24]
DNAH8	OTGES2OU	moderate	Genetic Variation	[25]
FCGR2C	OTNLMNYB	moderate	Genetic Variation	[7]
HDGFL2	OTWX2GHS	moderate	Altered Expression	[26]
KCNG1	OTZ9ZRG8	moderate	Genetic Variation	[27]
KRT13	OTTYSKGX	moderate	Genetic Variation	[27]
LMLN	OTQF0JPY	moderate	Biomarker	[8]
TMPRSS13	OTMAOAP3	moderate	Biomarker	[8]
CD1E	OT4F3AKI	Strong	Genetic Variation	[28]
CLEC11A	OT9KBH7C	Strong	Biomarker	[29]
CNTNAP1	OT5Y03EU	Strong	Biomarker	[30]
ENOSF1	OT65D3ZK	Strong	Biomarker	[31]
FAM53B	OTVD7OU6	Strong	Biomarker	[32]
GGPS1	OTVEHG28	Strong	Altered Expression	[16]
GNLY	OTZJKA8C	Strong	Biomarker	[33]
HBE1	OTJPKMX4	Strong	Biomarker	[34]
HPX	OT14T7Q1	Strong	Biomarker	[35]
IFNGR1	OTCTQBWW	Strong	Genetic Variation	[36]
MCCC1	OTLOHEQE	Strong	Biomarker	[37]
RECQL4	OT59LSW7	Strong	Biomarker	[31]
SLURP1	OT89YD2E	Strong	Biomarker	[11]
TIMD4	OTGGC20G	Strong	Genetic Variation	[38]

References

• [1] Artesunate FDA Label
• [2] Chloroquine FDA Label
• [3] Hydroxychloroquine FDA Label
• [4] Sulfisoxazole FDA Label
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] Reduced ADAMTS13 activity is associated with an ADAMTS13 SNP, fever and microparticles in a malaria-like model.Malar J. 2014 Jan 3;13:3. doi: 10.1186/1475-2875-13-3.
• [7] FcgammaRIIa (CD32) polymorphism and anti-malarial IgG subclass pattern among Fulani and sympatric ethnic groups living in eastern Sudan.Malar J. 2009 Mar 13;8:43. doi: 10.1186/1475-2875-8-43.
• [8] Variant-specific antibodies to merozoite surface protein 2 and clinical expression of Plasmodium falciparum malaria in rural Amazonians.Am J Trop Med Hyg. 2007 Jun;76(6):1084-91.
• [9] Fy(a)/Fy(b) antigen polymorphism in human erythrocyte Duffy antigen affects susceptibility to Plasmodium vivax malaria.Proc Natl Acad Sci U S A. 2011 Dec 13;108(50):20113-8. doi: 10.1073/pnas.1109621108. Epub 2011 Nov 28.
• [10] CD36 T188G gene polymorphism and severe falciparum malaria in India.Trans R Soc Trop Med Hyg. 2009 Jul;103(7):687-90. doi: 10.1016/j.trstmh.2008.11.015. Epub 2009 Jan 10.
• [11] Comparison of the Pharmacokinetics and Ex Vivo Antimalarial Activities of Artesunate-Amodiaquine and Artemisinin-Piperaquine in Healthy Volunteers for Preselection Malaria Therapy.Am J Trop Med Hyg. 2018 Jul;99(1):65-72. doi: 10.4269/ajtmh.17-0434. Epub 2018 May 3.
• [12] Sustained efficacy of artesunate-sulfadoxine-pyrimethamine against Plasmodium falciparum in Yemen and a renewed call for an adjunct single dose primaquine to clear gametocytes.Malar J. 2016 May 27;15(1):295. doi: 10.1186/s12936-016-1344-0.
• [13] Artemisinin-resistant Leishmania parasite modulates host cell defense mechanism and exhibits altered expression of unfolded protein response genes.Parasitol Res. 2019 Sep;118(9):2705-2713. doi: 10.1007/s00436-019-06404-9. Epub 2019 Jul 29.
• [14] A -436C>A polymorphism in the human FAS gene promoter associated with severe childhood malaria.PLoS Genet. 2011 May;7(5):e1002066. doi: 10.1371/journal.pgen.1002066. Epub 2011 May 19.
• [15] Association between Fc receptor IIA, IIIA and IIIB genetic polymorphisms and susceptibility to severe malaria anemia in children in western Kenya.BMC Infect Dis. 2017 Apr 20;17(1):289. doi: 10.1186/s12879-017-2390-0.
• [16] Specific Inhibition of the Bifunctional Farnesyl/Geranylgeranyl Diphosphate Synthase in Malaria Parasites via a New Small-Molecule Binding Site.Cell Chem Biol. 2018 Feb 15;25(2):185-193.e5. doi: 10.1016/j.chembiol.2017.11.010. Epub 2017 Dec 21.
• [17] Categorical complexities of Plasmodium falciparum malaria in individuals is associated with genetic variations in ADORA2A and GRK5 genes.Infect Genet Evol. 2015 Aug;34:188-99. doi: 10.1016/j.meegid.2015.06.010. Epub 2015 Jun 9.
• [18] Low erythrocyte pyridoxal-kinase activity in Blacks: Its possible relation to falciparum malaria.Lancet. 1978 Mar 4;1(8062):466-8. doi: 10.1016/s0140-6736(78)90133-2.
• [19] Heterozygous mutants of TIRAP (S180L) polymorphism protect adult patients with Plasmodium falciparum infection against severe disease and mortality.Infect Genet Evol. 2016 Sep;43:146-50. doi: 10.1016/j.meegid.2016.04.035. Epub 2016 May 7.
• [20] Increased susceptibility of blood type O individuals to develop anemia in Plasmodium vivax infection.Infect Genet Evol. 2017 Jun;50:87-92. doi: 10.1016/j.meegid.2017.03.001. Epub 2017 Mar 6.
• [21] Distribution of the cytochrome P450 CYP2C8*2 allele in Brazzaville, Republic of Congo.Int J Infect Dis. 2019 Aug;85:49-53. doi: 10.1016/j.ijid.2019.04.035. Epub 2019 May 9.
• [22] Resistance to falciparum malaria among adults in central Sudan.Am J Trop Med Hyg. 1986 Jan;35(1):45-55. doi: 10.4269/ajtmh.1986.35.45.
• [23] Preliminary investigation of the contribution of CYP2A6, CYP2B6, and UGT1A9 polymorphisms on artesunate-mefloquine treatment response in Burmese patients with Plasmodium falciparum malaria.Am J Trop Med Hyg. 2014 Aug;91(2):361-6. doi: 10.4269/ajtmh.13-0531. Epub 2014 Jun 2.
• [24] MAD 20 alleles of merozoite surface protein-1 (msp-1) are associated with severe Plasmodium falciparum malaria in Pakistan.J Microbiol Immunol Infect. 2015 Apr;48(2):213-8. doi: 10.1016/j.jmii.2014.01.004. Epub 2014 Mar 27.
• [25] Therapeutic efficacy of artesunate in the treatment of uncomplicated Plasmodium falciparum malaria and anti-malarial, drug-resistance marker polymorphisms in populations near the China-Myanmar border.Malar J. 2012 Aug 16;11:278. doi: 10.1186/1475-2875-11-278.
• [26] Clearance dynamics of lactate dehydrogenase and aldolase following antimalarial treatment for Plasmodium falciparum infection.Parasit Vectors. 2019 Jun 10;12(1):293. doi: 10.1186/s13071-019-3549-x.
• [27] Genetic association between the Pfk13 gene mutation and artemisinin resistance phenotype in Plasmodium falciparum isolates from Yunnan Province, China.Malar J. 2018 Dec 18;17(1):478. doi: 10.1186/s12936-018-2619-4.
• [28] Homozygosity for the CD1E*02 allele is associated with a resistance to Plasmodium falciparum malaria infection in Gabonese school children.Asian Pac J Trop Med. 2017 Feb;10(2):204-207. doi: 10.1016/j.apjtm.2017.01.017. Epub 2017 Jan 20.
• [29] A novel functional variant in the stem cell growth factor promoter protects against severe malarial anemia.Infect Immun. 2010 Jan;78(1):453-60. doi: 10.1128/IAI.00895-09. Epub 2009 Nov 2.
• [30] Major surface antigen gene of a human malaria parasite cloned and expressed in bacteria.Nature. 1984 Sep 27-Oct 3;311(5984):379-82. doi: 10.1038/311379a0.
• [31] Immune response to the hepatitis B antigen in the RTS,S/AS01 malaria vaccine, and co-administration with pneumococcal conjugate and rotavirus vaccines in African children: A randomized controlled trial.Hum Vaccin Immunother. 2018 Jun 3;14(6):1489-1500. doi: 10.1080/21645515.2018.1442996. Epub 2018 Apr 13.
• [32] A fixed-dose 24-hour regimen of artesunate plus sulfamethoxypyrazine-pyrimethamine for the treatment of uncomplicated Plasmodium falciparum malaria in eastern Sudan.Ann Clin Microbiol Antimicrob. 2006 Aug 26;5:18. doi: 10.1186/1476-0711-5-18.
• [33] Control of Plasmodium falciparum erythrocytic cycle: T cells target the red blood cell-invasive merozoites.Blood. 2011 Dec 22;118(26):6952-62. doi: 10.1182/blood-2011-08-376111. Epub 2011 Nov 1.
• [34] Extended linkage disequilibrium surrounding the hemoglobin E variant due to malarial selection.Am J Hum Genet. 2004 Jun;74(6):1198-208. doi: 10.1086/421330. Epub 2004 Apr 27.
• [35] Prolonged neutrophil dysfunction after Plasmodium falciparum malaria is related to hemolysis and heme oxygenase-1 induction.J Immunol. 2012 Dec 1;189(11):5336-46. doi: 10.4049/jimmunol.1201028. Epub 2012 Oct 24.
• [36] IFNGR1 polymorphisms in Thai malaria patients.Infect Genet Evol. 2009 Dec;9(6):1406-9. doi: 10.1016/j.meegid.2009.08.004. Epub 2009 Aug 25.
• [37] CR1 Knops blood group alleles are not associated with severe malaria in the Gambia.Genes Immun. 2003 Jul;4(5):368-73. doi: 10.1038/sj.gene.6363980.
• [38] Significant association between TIM1 promoter polymorphisms and protection against cerebral malaria in Thailand.Ann Hum Genet. 2008 May;72(Pt 3):327-36. doi: 10.1111/j.1469-1809.2007.00424.x. Epub 2008 Feb 19.