Repurposing auranofin as a lead candidate for treatment of lymphatic filariasis and onchocerciasis.

Two major human diseases caused by filariid nematodes are onchocerciasis, or river blindness, and lymphatic filariasis, which can lead to elephantiasis. The drugs ivermectin, diethylcarbamazine (DEC), and albendazole are used in control programs for these diseases, but are mainly effective against the microfilarial stage and have minimal or no effect on adult worms. Adult Onchocerca volvulus and Brugia malayi worms (macrofilariae) can live for up to 15 years, reproducing and allowing the infection to persist in a population. Therefore, to support control or elimination of these two diseases, effective macrofilaricidal drugs are necessary, in addition to current drugs. In an effort to identify macrofilaricidal drugs, we screened an FDA-approved library with adult worms of Brugia spp. and Onchocerca ochengi, third-stage larvae (L3s) of Onchocerca volvulus, and the microfilariae of both O. ochengi and Loa loa. We found that auranofin, a gold-containing drug used for rheumatoid arthritis, was effective in vitro in killing both Brugia spp. and O. ochengi adult worms and in inhibiting the molting of L3s of O. volvulus with IC50 values in the low micromolar to nanomolar range. Auranofin had an approximately 43-fold higher IC50 against the microfilariae of L. loa compared with the IC50 for adult female O. ochengi, which may be beneficial if used in areas where Onchocerca and Brugia are co-endemic with L. loa, to prevent severe adverse reactions to the drug-induced death of L. loa microfilariae. Further testing indicated that auranofin is also effective in reducing Brugia adult worm burden in infected gerbils and that auranofin may be targeting the thioredoxin reductase in this nematode.

Structural and ultrastructural changes in the lungs of cats Felis catus (Linnaeus, 1758) experimentally infected with D. immitis (Leidy, 1856).

Clinical signs are seldom observed in feline heartworm disease, and the pathophysiological changes in the lungs of infected animals remain undefined. The goal of this study was to evaluate the structural and ultrastructural changes in the lungs of cats experimentally infected with Dirofilaria immitis. Six healthy cats were each infected with two adult heartworms by intravenous transplantation (Receptor Group, RG). The control group consisted of two uninfected animals kept under the same conditions as the RG. At 42 days after transplantation, all cats were euthanized and necropsied for worm recovery and collection of lung samples for examination by light microscopy (LM) and transmission electron microscopy. By LM, lung sections from the six infected cats exhibited bronchial and bronchiolar lesions. Alterations in all tissues of the pulmonary arteries were observed in the infected animals. In conclusion, cats infected experimentally with D. immitis developed lesions in their lungs as a consequence of arterial disease and intense interstitial pneumonia.