Neoplastic change in Onchocerca volvulus and its relation to ivermectin treatment

Abstract

A pleomorphic neoplasm (PN) is described from sections of Onchocerca volvulus worms in nodules excised from Cameroonian patients. PN is confined to older, non-fecund, female worms, and those classed as moribund/dead. It is mainly composed of small, roundish, basophilic cells of diverse sizes, often forming a 'rosette' pattern around amorphous eosinophilic centres. The cells have a high nuclear/cytoplasmic ratio and up to 2-3 mitoses/high-power field; some become grossly enlarged, highly polymorphic and contain large, irregular blocks of chromatin. The eukaryotic PN cells first appear posteriorly in the pseudocoelom, probably from ovarian cells; they spread anteriorly, invading or compressing the uteri. Ivermectin treatment increased the prevalence PN from 3.7% of 1422 female worms in 637 patients before treatment to 17.5% of 1134 worms in 511 patients after 3 years treatment. Ivermectin at 400-800 microg/kg annually, or at 150 microg/kg or 400-800 microg/kg 3-monthly, over 3 years, did not increase the PN prevalence significantly, as compared with standard doses of 150 microg/kg annually. In other small series of African patients, PN prevalence increased in worms 2, 4, 6 and 10 months after ivermectin treatment; but there was no increase after treatment with amocarzine, albendazole or diethylcarbamazine and suramin. PN may partly account for the increased macrofilaricidal action of ivermectin on female O. volvulus in patients treated for 3 years at 3-monthly intervals.

Efficacy of 5-week doxycycline treatment on adult Onchocerca volvulus

“…2 Signs of certain death are entirely calcified worm portions (arrowhead) or small cuticular fragments of nearly absorbed filariae (arrows) Fig. 3 Moribund worms with pleomorphic neoplasms as described by Duke et al (2002) (arrowhead) will definitely die even when the APR-positive posterior ends appear undamaged (arrows). Untreated patient Fig.…”

“…Nodules from untreated patients contained 16% dead female and 5% dead male worms. Four moribund female worms with pleomorphic neoplasms, as described by Duke et al (2002) and Gardon et al (2002), were included in the category 'dead'. The proportions of dead worms are in accordance to those from other studies in West Africa (Table 6).…”

Evidence for macrofilaricidal activity of ivermectin against female Onchocerca volvulus: further analysis of a clinical trial in the Republic of Cameroon indicating two distinct killing mechanisms

“…Numbers (and nos./nodule) of uncalcified and calcified M and D female worms found at each round of nodulectomy, and the presumed reasons for their deaths Constant no./nodule based on no./nodule at Round 1 ofTable 1ofDuke et al (2002). (B) (iii) Based on pre-treatment findings, i.e.…”

The nematode parasite Onchocerca volvulus generates the transforming growth factor-beta (TGF-beta)

“…1 (7)). Duke et al (2002) described pleomorphic neoplasms in the uterus and pseudocoeloma cavity of moribund or already dead O. volvulus. Neoplasms in dead worms were TGF-β-negative but living worms presented strongly stained large cells ( Fig.…”

“…7 An untreated immature female shows labeling of median and lateral hypodermal (hy) chords, uterus (ut) epithelium and adjacent to a nucleus of a body wall muscle (arrow). 8 The large cells (arrows) of a pleomorphic neoplasm as described by Duke et al (2002) and the thin hypodermis (hy) are well labeled in an untreated female. The cuticle (cu) is negative.…”