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Filarial nematodes infect more than 150 million people worldwide and are responsible for diseases including elephantiasis, river blindness and tropical pulmonary eosinophilia. Antifílarial agents that can kill all the stages in the life cycle of causative filar- iae have yet to be developed. Very little effort has been made towards rational drug design, employing knowledge gained from studies of the biochemistry and physiology of filarial worms and of their interactions with their specific vertebrate hosts. In this review, we highlight the research and development of rational antifílarial agents and we discuss the pitfalls since the discovery of diethylcarbamazine, the only drug of choice for controlling filariasis, despite its adverse side effects.
Onchocerpa lupi was first isolated from a wolf in Russia. Since then, canine ocular onchocercosis has been increasingly reported, particularly in Europe and the United States. It is thought that blackflies and midges are the vectors of transmission, and it is possible that these vectors could transmit the parasite to humans. The first human case of O. lupi in Turkey was reported in 2011. In this report we present the third human case of O. lupi infection in Turkey. Our patient was a 28-year-old male who displayed a painless, immobile mass under the conjunctiva. The mass measured 10 × 12 mm in size. Pathological examination of the surgically excised tissue was suggestive of infection by a filarial nematode. Subsequently, the parasite was identified as O. lupi through molecular analysis. All of the previously reported cases of O. lupi in both humans and dogs were more symptomatic than in our patient, Onchocerca infection should not be ruled out during the differential diagnosis of the subconjunctival and orbital cystic mass in instances where there is little to no inflammation. It is important to consider biopsy and carry out molecular analysis to identify the parasite.
The filarial nematode Dirofilaria repens is currently considered to be one of the most extensively spreading human and animal parasites in Europe. In Ukraine, reporting cases of dirofilariasis has been mandatory since 1975, and the disease was included in the national surveillance system for notifiable diseases. Up until December 31st 2012, a total of 1533 cases have been registered, with 1465 cases occurring within the previous 16 years. Most of the cases of dirofilariasis were registered in 6 regions: Kyiv, and the Donetsk, Zaporizhzhya, Dnipropetrovsk, Kherson and Chernihiv oblasts. In the years 1997–2002 the highest incidence rate was noted in the Kherson oblast in the south of the country (9.79 per 100 000 people), and the lowest in western Ukraine (0.07–1.68 per 100 000 people). D. repens infections were registered in all oblasts. Parasitic lesions were most often located in the head, the subconjunctival tissue and around the eyes. D. repens lesions were also found in the limbs, torso, male sexual organs, and female mammary glands. Dirofilariasis was diagnosed in persons aged from 11 months to 90 years old, most often among people between 21–40 years of age. Most patients had only one parasitic skin lesion; the majority of isolated nematodes were female. The results of our analysis point to a constant increase in D. repens dirofilariasis incidence in humans in Ukraine. Despite educational efforts, infections have become more frequent and the territory in which the disease occurs has enlarged to encompass the whole of Ukraine. Nevertheless, the Ukrainian sanitary-epidemiological services managed to achieve some measure of success, e.g. by creating a registration system for D. repens infections and establishing proper diagnostics for the disease.
ALT-2, a novel antigen belonging to the chromadorea ALT-2 family of the filarial nematode is proved to clear filarial parasites in Jirds. In order to increase the protection efficacy by stimulating the cell mediated immunity, MPLA a detoxified derivative of LPS known to induce the cellular response, was used in this study as an adjuvant on mice models. ALT-2+MPLA formulation elicited a high titer of total IgG antibody, with profoundly increased levels of IgG2b. Reduced splenocyte proliferation was observed in immunized group when compared to control groups which could be attributed to many in vivo factors. The levels of IFN-γ were high in unstimulated MPLA group compared to ALT-2 stimulated MPLA group, suggesting that the ALT-2 antigen suppressed the IFN-γ levels. A high level of IL-10 was induced by the ALT-2+MPLA formulation, which inhibited the production of Th2 cytokines (IL-4, IL-5) and also reduced the Th1 cytokine (IFN-γ, IL-2) levels which are not in vogue with the classical MPLA adjuvant formulation. We propose a mechanism for this immunomodulation which involves a diminished expression of TLR-4, by which the filarial parasites have evolved to evade host immune mechanism.
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