Ivermectin-facilitated immunity in onchocerciasis; activation of parasite-specific Th1-type responses with subclinical Onchocerca volvulus infection

Author:

SOBOSLAY P T1,LÜDER C G K1,HOFFMANN W H1,MICHAELIS I1,HELLING G1,HEUSCHKEL C1,DREWECK C M1,BLANKE C H1,PRITZE S2,BANLA M3,SCHULZ-KEY H1

Affiliation:

1. Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany

2. Deutsche Gesellschaft für Technische Zusammenarbeit (gtz), Eschborn, Germany

3. Centre Hospitaliér de la Région Centrale, Sokodé, Togo

Abstract

SUMMARY The present study examined the quantitative and qualitative changes registered in the parasite-specific antibody response, cellular reactivity and cytokine production profile in onchocerciasis patients repeatedly treated with ivermectin over a period of 8 years. The densities of Onchocerca volvulus microfilariae (mf) in treated patients remained significantly reduced, whereas the number of permanently amicrofilaridermic patients (subclinical infection) increased with repeated treatments. In vitro cellular responses to O. volvulus antigen (OvAg) were highest (P<0.001) in untreated control individuals exposed to infection, but negative for mf of O. volvulus (endemic normals). Cellular reactivity in repeatedly treated patients was higher at 84 than at 36 months post initial treatment (p.i.t.); furthermore, the proliferative responses to OvAg, mycobacterial purified protein derivative (PPD) and streptococcal SL-O were greater (P<0·05) at 84 months p.i.t. in amicrofilaridermic than in microfilaria-positive onchocerciasis patients. In amicrofilaridermic patients such reactivity approached the magnitude observed in endemic normals. Peripheral blood mononuclear cells (PBMC) from patients and endemic normals produced equivalent amounts of IL-2. IL-4 and interferon-gamma (IFN-γ) in response to mitogenic stimulation with phytohaemagglutinin (PHA); in response to OvAg, however, significantly more IL-2 and IFN-γ were produced by PBMC from subclinical amicrofilaridermic patients or endemic normals than by mf-positive patients OvAg-specific production or IL-4 by PBMC from treated patients was lower at 84 than at 36 months p.i.t. At three months p.i.t. the titres of circulating OvAg-specific IgG1-3 had increased (P<0·05), but they then continuously declined with repeated treatments. Only IgG1 and IgG4 bound to OvAg of mol. wt 2-l2 kD at 1 month p.i.t., while recognition of OvAg of mol. wt 10–200 kD by IgG1, IgG2 and IgG4 reached a maximum intensity at 3–6 months p.i.t., with the overall intensity of binding to OvAg gradually weakening thereafter. These results suggest that onchocerciasis-associated immuno-suppression is reversible following ivermectin-induced permanent clearance of microfilariae from the skin; and that a vigorous parasite-specific cellular reactivity and a sustained production of IL-2 and IFN-γ in amicrofilaridermic individuals may contribute to controlling O. volvulus infection.

Publisher

Oxford University Press (OUP)

Subject

Immunology,Immunology and Allergy

Reference37 articles.

1. Expert committee on onchocerciasis;WHO;Technical Report Series,1987

2. Modern medicine versus an ancient scourge: progress toward control of onchocerciasis;Greene;J Infect Dis,1992

3. Efficacy and tolerance of ivermectin in human onchocerciasis;Aziz;Lancet,1982

4. The predicted and observed decline in onchocorciasis infection during 14 years of successful control of Simulium spp. in West Africa;Remme;Bull WHO,1990

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