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Sarcocystis calchasi has recently been identified as the cause of pigeon protozoal encephalitis, PPE, a lethal brain disease in pigeons and parrots. While only avian species have been identified so far to be susceptible to this pathogen as definitive or intermediate hosts, we speculated whether mammals may be susceptible as well, as in Sarcocystis neurona and other related apicomplexan parasites. Specifically, we hypothesized its involvement in mammalian meningoencephalitis of unknown origin, MUO. A total of 143 archived formalin fixed, paraffin embedded brain samples with MUO from dogs, cats, pigs, cattle, sheep, guinea pigs, horses, goats, mice, raccoon, ferret, hamster, mink and maned wolf were examined pathohistologically and by PCR for parasitic stages or DNA, respectively, of Sarcocystis calchasi or other apicomplexan parasites. All samples had non-suppurative, lymphoplasmacytic and/or granulomatous encephalitis or meningoencephalitis typical of MUO with many similarities to PPE in pigeons. However, neither parasitic structures nor DNA of Sarcocystis calchasi or other apicomplexan parasites were detected. It thus appears that, despite histological similarities between mammalian MUO and pigeon PPE and despite seemingly high prevalence of PPE and a persistent threat by Sarcocystis calchasi in pigeons, based on histopathology and PCR there is no evidence for a role of this parasite in MUO in mammals as intermediate or aberrant hosts.