Treatment
Currently, there is no effective drug or therapeutic protocol for the management of the infections caused by L. loboi in humans or P. brasiliensis var. ceti in dolphins. Surgery in the early stages of the disease remains the treatment of choice in both conditions (Baruzzi et al.
1981; Bossart et al. 2015; Lacaz et al. 1986). In advanced cases, surgery can be also performed, but recurrence rate is high (Lacaz et al. 1986; Opromolla et al. 2000; Rodriguez-Toro 1993; Talhari and Talhari 2012). These two atypical microorganisms were always classified within the fungi, thus treated with antifungal drugs (Bustamante et al. 2013; Cuce et al. 1980; Dudok van Heel 1977; Lawrence and Ajello 1986). The response of infected hosts to antifungal therapy has been unsatisfactory (Cuce et al. 1980; Lacaz et al. 1986; Woods et al. 2010). For instance, amphotericin B, itraconazole, 5-fluorocytosine, ketoconazole, posacon- azole, terbinafine, and others resulted in the reduction of the granuloma size, but cure was achieved only in few instances (Francesconi et al. 2014). On the other hand, antibacterial drugs such as sulfadimethoxine and sulfamethoxypyridazine were found to improve the nodular lesions, but the presence of yeast-like cells persisted in the infected areas (Woods et al. 2010). Because leprosy is the differential diagnosis of lacaziosis, drugs such as clofazimine have been used in patients with dual infection. According to studies conducted in Acre, Brazil (Opromolla et al. 2000; Silva 1972; Talhari and Talhari 2012), the use of dapsone and clofazimine dramatically improved lesion size and itching, usually associate to active lacaziosis, and in some cases the lesions decreased or disappeared (Woods et al. 2010). Moreover, when surgery and these two drugs were combined, no recurrence was reported (Woods et al. 2010).Only a handful of wild infected dolphins have been kept in captivity for treatment; thus there is limited information on the management strategies in animals. Dolphins treated with the strategies used in humans showed similar responses (Minakawa et al. 2016). Surgical removal of small lesions is the best option. However, surgery in large or multicentric lesions is not recommended. In 1977, a dolphin captured in Florida, USA, was successfully treated with miconazole (Dudok van Heel 1977). But, this antifungal drug has not been used ever since. More recently, a dolphin treated with topical itraconazole and ketoconazole did not improve (Esperon et al. 2012). The same animal was then treated with oral 2.5 mg/kg itraconazole and 2.0 mg/kg terbinafine. With this treatment protocol, cutaneous lesions reduced to small nodules that later disappeared, and no relapse was reported. Currently, there is little information on the best antifungal approach to treat dolphins. This is probably in part due to the price of antifungals and the difficulties to keep wild animals for long periods outside their natural ecological habitat.