Lymph nodes of onchocerciasis patients after treatment with ivermectin: reaction of eosinophil granulocytes and their cationic granule proteins.

Abstract

Lymph node and skin biopsies from Liberian patients with generalized and localized (sowda) onchocerciasis were studied 12-68 hours after oral administration of ivermectin at a single dose of 150 micrograms/kg body weight. Electron microscopic examination and immunohistochemical staining with antibodies against two different forms of eosinophil cationic protein (ECP EG1, ECP EG2), eosinophil peroxidase (EPO) and cationic leukocyte antigen (CLA) were performed. Following their disappearance from the skin, a large number of microfilariae was found in the regional lymph nodes. The lymph nodes from treated patients had over ten times more eosinophils compared to those from untreated persons with a peak of eosinophil density at 40-48 hours after treatment. Degenerating microfilariae in the lymph nodes were encircled by eosinophils, which showed positive immunostaining for ECP, EPO or CLA. Intra- and extracellular eosinophil granules revealed a great variation in their condition. In some specific granules a variety of structural alterations in the crystalloid cores occurred while in others different stages of deficiency in the matrix electron density were observed. The frequent necrosis of eosinophils in the immediate vicinity and at some distance from the microfilariae, with subsequent release of granules and the deposition of toxic cationic granule proteins onto the microfilarial cuticle during the eosinophil-parasite adherence reaction, demonstrated the function of these proteins in the ivermectin-reinforced killing of microfilariae in lymph nodes.