Jorge Lobo’s disease: experimental inoculation in Swiss mice

Abstract

SUMMARYSixty-four isogenic Swiss mice were intradermically inoculated in both hind foot pads. The inocula, consisting of fungal suspensions from biopsies obtained from Jorge Lobo's Disease patients, had the total number of fungi and the viability index determined using a Neubauer chamber and the fluorescein diacetate-ethidium bromide technique (FD-EB), respectively. The animals were sacrificed at times ranging from ten days to eighteen months after inoculation. The cellular infiltrate, mainly consisting of macrophages containing fungi, increased progressively up to end of the study; however, no macroscopic alterations were observed in the inoculated feet. After nine months, small numbers of Langhans' giant cells started to appear in the infiltrate. A considerable number of fungi was observed at the end of the experimental period, but only a few were viable when stained by the FD-EB technique. This fact suggests that there is a multiplication of fungal cells, which are destroyed by the macrophages but remain in the tissue for a long time due perhaps to the difficulties in their elimination. These findings led us to conclude that in spite of the maintenance of the infection in these animals, Swiss mice cannot be considered an ideal model to study Jorge Lobo's Disease. However, the authors call attention to the possibility of other mouse strains being more susceptible to Paracoccidioides loboi.

Macrophage and TGF-β immunohistochemical expression in Jorge Lobo's disease

“…Jorge Lobo's disease is a chronic deep mycosis whose prognosis in terms of survival is good, although treatment does not lead to complete cure of the infection [4,5]. Most patients present with long disease progression.…”

“…Trauma and injuries or sites of insect bites facilitate penetration of the fungus. Lesion progression is slow, with new lesions arising contiguous to other lesions or through the lymphatic route [4,5].…”

“…The lesions are most frequently located in the auricle and on the upper and www.elsevier.com/locate/humpath lower limbs and consist of atrophic epidermis, with rectification of the interpapillary crests. In the dermis, a grenz zone, dilated and newly formed vessels, fibrosis, and a dense infiltrate consisting of lymphocytes, foamy histiocytes rich in parasites, epithelioid cells, numerous giant cells (especially Langhans cells), some eosinophils, and plasma cells are observed [4][5][6].…”

Modeling lacaziosis lesion progression in common bottlenose dolphins Tursiops truncatus using long-term photographic records

“…As a result, very little is understood about the conditions under which the pathogen grows and thrives, as well as its source and transmission route (Wiersema & Niemel 1965, Pang et al 2004, Lupi et al 2005, Paniz-Mondolfi et al 2007). Experimental inoculation attempts have been made using guinea pigs (Wiersema & Niemel 1965), hamsters (Wiersema & Niemel 1965, Opromolla & Noguiera 2000, tortoises (Geochelone denticulate, G. carbonaria and Kinosternon scorpioides; Sampaio et al 1971), monkeys (Macacca mulatta, M. nemestrina and M. fascicularis; Caldwell et al 1975), armadillos Euphractus sexcinctus (Sampaio & Braga-Dias 1977) and mice (Wiersema & Niemel 1965, Caldwell et al 1975, Opromolla et al 1999, Madeira et al 2000, 2003, Belone et al 2003, but many of those attempts yielded only short-term data on the development of the disease. Opromolla et al (1999) were able to successfully inoculate a Swiss strain of mice with lacaziosis and follow disease progression up to 18 mo post-inoculation; however, clinical presentation of the disease did not occur, and very few fungal cells were active by the end of the study.…”

“…Experimental inoculation attempts have been made using guinea pigs (Wiersema & Niemel 1965), hamsters (Wiersema & Niemel 1965, Opromolla & Noguiera 2000, tortoises (Geochelone denticulate, G. carbonaria and Kinosternon scorpioides; Sampaio et al 1971), monkeys (Macacca mulatta, M. nemestrina and M. fascicularis; Caldwell et al 1975), armadillos Euphractus sexcinctus (Sampaio & Braga-Dias 1977) and mice (Wiersema & Niemel 1965, Caldwell et al 1975, Opromolla et al 1999, Madeira et al 2000, 2003, Belone et al 2003, but many of those attempts yielded only short-term data on the development of the disease. Opromolla et al (1999) were able to successfully inoculate a Swiss strain of mice with lacaziosis and follow disease progression up to 18 mo post-inoculation; however, clinical presentation of the disease did not occur, and very few fungal cells were active by the end of the study. Other studies have demonstrated that BALB/c mice may be a suitable animal model for studying the infectivity and aggression of the lacaziosis pathogen, as infection was sustained and lesions developed post-inoculation; however, all of the BALB/c inoculation studies maintained infection for a maximum of 18 mo before the animals were sacrificed, thereby supplying limited short-term data on the progression of lacaziosis (Madeira et al 2000, 2003, Belone et al 2003.…”