Keynote Message

The history of bacterial endosymbiosis in Dirofilaria worms begins more than 30 years ago, when the presence of dense bodies within the reproductive organs and microfilariae of D. immitis was observed. Later, they were identified as intracellular, gram-negative microorganisms,and it was found that such microorganisms were transovarially transmitted in adult worms. In 1995, these microorganisms were identified as bacteria belonging to the genus Wolbachia and subsequently, Wolbachia was observed in representatives of several filarial pathogenic genera and species (Onchocerca, Brugia, Wuchereria). These endosymbiont bacteria are phylogenetically close to rickettsiae and are transovarially transmitted to microfilariae. Because of the bacterial nature of the symbiont, antibiotic treatment is able to deplete bacteria from the worms leading to sterility of females, death of microfilariae, and eventually of adult worms. Furthermore, the discovery of Wolbachia endosymbiosis on filarial worms has opened the way to a new understanding of pathogenesis and immune response of filarial diseases, both in humans and animals. The immunopathology of filarial disease is extremely complex and the clinical manifestations of infection are strongly dependent, not only on the type of immune response elicited by the parasite, but also on the presence of Wolbachia in the infected host. Furthermore, the fact that adult parasites can survive for years in otherwise immune-competent hosts is likely a consequence of the Wolbachia-mediated parasite's ability to avoid/modulate the immune response. Current field and experimental studies have demonstrated that treating with antibiotic drugs in association with a macrocyclic lactone effective against heartworms is able to decrease the risk of thromboembolism caused by the inflammatory reaction mediated by the endosymbiont bacteria released by dying worms and that such a regimen is highly effective in eliminating adult worms.

Key References

1.  Casiraghi M., Anderson TJC, Bandi C, Bazzocchi C, Genchi C. A phylogenetic analysis of filarial nematodes: comparison with the phylogeny of Wolbachia endosymbionts. Parasitology. 2001;122:93–103. DOI:10.1017/S0031182000007149.

2.  Kramer L, Genchi C. Where are we with Wolbachia and doxycycline: an in-depth review of the current state of our knowledge. Vet Parasitol. 2014;206:1–4. DOI: 10.1016/j.vetpar.2014.03.028.

3.  McCall JW, Genchi C, Kramer LH, et al. Heartworm disease in animals and humans. Adv Parasitol. 2008;66:193–285. DOI: 10.1016/S0065-308X(08)00204-2.

4.  Sironi M, Bandi C, Sacchi L, Di Sacco B, Damiani G, Genchi C. Molecular evidence for a close relative of the arthropod endosymbiont Wolbachia in a filarial worm. Mol Biochem Parasitol. 1995;74:223–227.