Onchocerca volvulus-specific antibody and cytokine responses in onchocerciasis patients after 16 years of repeated ivermectin therapy

• Published in: Clinical and experimental immunology Vol. 147; no. 3; pp. 504 - 512
• Main Authors: Mai, C.S, Hamm, D.M, Banla, M, Agossou, A, Schulz-Key, H, Heuschkel, C, Soboslay, P.T
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.03.2007; Blackwell Publishing Ltd; Blackwell; Oxford University Press; Blackwell Science Inc
• Subjects: Adult; Aged; Animals; Anthelmintics - therapeutic use; Antibodies, Helminth - biosynthesis; antibody; Biological and medical sciences; Cells, Cultured; Clinical Studies; cytokines; Cytokines - biosynthesis; Drug Administration Schedule; Enzyme-Linked Immunosorbent Assay - methods; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; immune responses; Immunocompetence - drug effects; Immunoglobulin G - biosynthesis; Immunopathology; ivermectin; Ivermectin - therapeutic use; Male; Mansonelliasis - complications; Mansonelliasis - immunology; Medical sciences; Middle Aged; Necatoriasis - complications; Necatoriasis - immunology; Onchocerca volvulus; Onchocerca volvulus - immunology; Onchocerciasis - complications; Onchocerciasis - drug therapy; Onchocerciasis - immunology; Skin disease; Onchocerciasis; Macrocycle; immune responses; Immunology; cytokines; Nematoda; Humoral immunity; Human; Immunopathology; Immune response; Antibody; Cytokine; Onchocerca volvulus; Lactone; Parasitosis; Helminthiasis; Infection; Eye disease; Treatment; Nematode disease; Helmintha; Nemathelminthia; Filariosis; Invertebrata; Ivermectin
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.2006.03312.x

The recommended control option against onchocerciasis is repeated ivermectin treatment, which will need to be implemented for decades, and it remains unknown how repeated ivermectin therapy might affect immunity against Onchocerca volvulus in the long term. O. volvulus-specific antibody reactivity and cellular cytokine production were investigated in onchocerciasis patients receiving ivermectin (150 μg/kg) annually for 16 years. In treated patients, the T helper type 2 (Th2) cytokine interleukin (IL)-5 and T regulatory IL-10 in response to O. volvulus antigen (OvAg) and bacteria-derived Streptolysin O (SL-O) diminished to levels found in infection-free endemic controls; also, cellular release of Th1-type interferon (IFN)-γ at 16 years post initial ivermectin treatment (p.i.t.) approached control levels. In ivermectin-treated onchocerciasis patients, IL-5 production in responses to the mitogen phytohaemagglutinin (PHA) decreased, but IL-10 in response PHA increased, and neither attained the cytokine production levels of endemic controls. At 16 years p.i.t., O. volvulus-specific IgG1 and IgG4 subclass reactivity still persisted at higher levels in onchocerciasis patients than in O. volvulus exposed but microfilariae-free endemic controls. In addition, cytokine responses remained depressed in onchocerciasis patients infected concurrently with Mansonella perstans and Necator americanus or Entamoeba histolytica/dispar. Thus, long-term ivermectin therapy of onchocerciasis may not suffice to re-establish fully a balanced Th1 and Th2 immune responsiveness in O. volvulus microfilariae-negative individuals. Such deficient reconstitution of immune competence may be due to an as yet continuing and uncontrolled reinfection with O. volvulus, but parasite co-infections can also bias and may prevent the development of such immunity.