Abstract
Trypanosoma brucei (T.b.) rhodesiense is the cause of the acute form of human African trypanosomiasis (HAT) in eastern and southern African countries. There is some evidence that there is diversity in the disease progression of T.b. rhodesiense in different countries. HAT in Malawi is associated with a chronic haemo-lymphatic stage infection compared to other countries, such as Uganda, where the disease is acute with more marked neurological impairment. This has raised the question of the role of host genetic factors in infection outcomes. A candidate gene association study was conducted in the northern region of Malawi. This was a case-control study involving 202 subjects, 70 cases and 132 controls. All individuals were from one area; born in the area and had been exposed to the risk of infection since birth. Ninety-six markers were genotyped from 17 genes: IL10, IL8, IL4, HLA-G, TNFA, IL6, IFNG, MIF, APOL, HLA-A, IL1B, IL4R, IL12B, IL12R, HP, HPR, and CFH. There was a strong significant association with APOL1 G2 allele (p = 0.0000105, OR = 0.14, CI95 = [0.05–0.41], BONF = 0.00068) indicating that carriers of the G2 allele were protected against T.b. rhodesiense HAT. SNP rs2069845 in IL6 had raw p < 0.05, but did not remain significant after Bonferroni correction. There were no associations found with the other 15 candidate genes. Our finding confirms results from other studies that the G2 variant of APOL1 is associated with protection against T.b. rhodesiense HAT.
Highlights
Human African trypanosomiasis (HAT), known as sleeping sickness, is one of the major neglected infectious diseases
Though some work has been done on the genetics of trypanosome infections in animals, relatively little is known about the genetics of human African trypanosomiasis (HAT)
It is caused by two subspecies of the single-celled parasite Trypanosoma brucei: T.b. rhodesiense found in eastern and southern Africa, with reservoirs in livestock and wildlife, and T.b. gambiense found in central and western Africa, which causes the majority of human cases with the main reservoir being humans [2,3]
Summary
Human African trypanosomiasis (HAT), known as sleeping sickness, is one of the major neglected infectious diseases. Sleeping sickness is endemic in 36 African countries and over 60 million people are at risk of being infected [1]. HAT is a vector-borne parasitic disease transmitted by tsetse flies of the genus Glossina. It is caused by two subspecies of the single-celled parasite Trypanosoma brucei: T.b. rhodesiense found in eastern and southern Africa, with reservoirs in livestock and wildlife, and T.b. gambiense found in central and western Africa, which causes the majority of human cases with the main reservoir being humans [2,3]. The two subspecies have different rates of disease progression; T.b. rhodesiense infection is typically described as an acute disease with rapid progression to late stage and T.b. gambiense progresses more slowly [3]
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