title: IgM, lgG and IL-6 profiles in the Trypanosoma brucei brucei monkey model of human African trypanosomiasis.
abstract: Human African trypanosomiasis (HAT) patients manifest immunological profiles, whose variations over time can be used to indicate disease progression. However, monitoring of these biomarkers in human patients is beset by several limitations which can be offset by using chronic animal models. A recent improved monkey model of HAT using a Trypanosoma brucei brucei isolate has been developed but the immunological profile has not been elucidated. The objectives of the current study was to determine the IgM, IgG and IL-6 profiles in blood and cerebrospinal fluid (CSF) in vervet monkeys infected with T. b. brucei. Three vervet monkeys were infected intravenously with 105T. b. brucei, monitored for disease development and subsequently treated 28days post infection (dpi) sub-curatively using diminazene aceturate (DA) to induce late stage disease and curatively treated with melarsoprol (Mel B) at 119 dpi, respectively. Matched serum and cerebrospinal fluid (CSF) samples were obtained at regular intervals and immunospecific IgM, immunoglobulin G (IgG) were quantified by ELISA while IL-6 was assayed using a cytometric bead array (CBA) kit. Results showed that following infection, CSF IgM, IgG, IL-6 and serum IL-6 were significantly (p<0.05) elevated with peak levels coinciding with relapse parasitaemia. The IgG levels increased to reach OD peak levels of 0.442±0.5 at 126 dpi. After curative treatment with MelB, the serum IgM and Ig G levels fell rapidly to attain pre-infection levels within 35 and 49days, respectively. This shows that the profile of these immunoglobulins can be used as an indicator of curative treatment. CSF IL-6 concentrations of infected vervet monkeys showed no significant change (P>0.05) between infection and 35 dpi but levels increased significantly (P<0.05) with the highest level of 55.53pg/ml recorded at112 dpi. IL-6 elevation from 35 dpi may be indicative of parasite neuroinvasion hence can be used as possible candidate marker for late stage disease in the monkey model. Further, the marker can also be used in conjunction with IgG and IgM as markers for development of test of cure for HAT.
authors.affiliation: Jomo Kenyatta University of Agriculture and Technology, College of Health Sciences, Biochemistry Department, P.O. Box 62000-00200, Nairobi, Kenya.
authors.forename: Maxwell W
authors.initials: MW
authors.lastname: Waema
authors.affiliation: Jomo Kenyatta University of Agriculture and Technology, College of Health Sciences, Biochemistry Department, P.O. Box 62000-00200, Nairobi, Kenya.
authors.forename: Naomi W
authors.initials: NW
authors.lastname: Maina
authors.affiliation: Mount Kenya University, Department of Animal Health and Production, P.O. Box 342-01000,Thika, Kenya; Jomo Kenyatta University of Agriculture and Technology, College of Agriculture and Natural Resources, Animal Sciences Department, P.O. Box 62000-00200, Nairobi, Kenya.
authors.forename: Maina
authors.initials: M
authors.lastname: Ngotho
authors.affiliation: Jomo Kenyatta University of Agriculture and Technology, College of Health Sciences(,) Public Health Department, P.O. Box 62000-00200, Nairobi, Kenya.
authors.forename: Simon M
authors.initials: SM
authors.lastname: Karanja
authors.affiliation: Jomo Kenyatta University of Agriculture and Technology, College of Health Sciences, Biochemistry Department, P.O. Box 62000-00200, Nairobi, Kenya.
authors.forename: Beatrice M
authors.initials: BM
authors.lastname: Gachie
authors.affiliation: Institute of Primate Research, Animal Science Department, P.O. Box 24481-00502, Nairobi, Kenya.
authors.forename: Dawn N
authors.initials: DN
authors.lastname: Maranga
authors.affiliation: Jomo Kenyatta University of Agriculture and Technology, College of Agriculture and Natural Resources, Animal Sciences Department, P.O. Box 62000-00200, Nairobi, Kenya. Electronic address: jkagira@yahoo.com.
authors.forename: John M
authors.initials: JM
authors.lastname: Kagira
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology; D002522:Chlorocebus aethiops; D004133:Diminazene / Q000031:analogs & derivatives; D004195:Disease Models, Animal; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D007074:Immunoglobulin G / Q000032:analysis* / Q000276:immunology; D007075:Immunoglobulin M / Q000032:analysis* / Q000276:immunology; D015850:Interleukin-6 / Q000097:blood* / Q000276:immunology; D014346:Trypanosoma brucei brucei / Q000276:immunology; D014353:Trypanosomiasis, African / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology* / Q000469:parasitology*
chemical_list: D000953:Antigens, Protozoan; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D015850:Interleukin-6; C003915:diminazene aceturate; D004133:Diminazene
keywords: Human African trypanosomiasis; IL-6; IgG; IgM; Monkey model; T. b. brucei