Human Lobomycosis Caused by Paracoccidioides (Lacazia) loboi, Panama, 2022.

We report a patient from Panama who had lobomycosis caused by Paracoccidioides (Lacazia) loboi. We used combined clinical-epidemiologic and phylogenetic data, including a new gene sequence dataset on this fungus in Panama, for analysis. Findings contribute useful insights to limited knowledge of this fungal infection in the Mesoamerican Biologic Corridor.

Epidemiologic and Clinical Progression of Lobomycosis among Kaiabi Indians, Brazil, 1965-2019.

Lobomycosis is a rare granulomatous skin disease with a high prevalence in the Amazon region. The Kaiabi Indians are an especially affected group. We studied the current epidemiologic and clinical progression of lobomycosis among the Kaiabi in Brazil, from initial case reports in 1965 through 2019. A total of 60 lobomycosis cases had been reported among the Kaiabi, and we identified 3 new cases in our review. Of 550 cases of lobomycosis ever reported worldwide, 11.5% were among the Kaiabi. We note a high incidence among female Kaiabi and a precocious onset of disease in this indigenous population. Male Kaiabi frequently are infected with the multicentric form and women more frequently exhibit the localized form. Ulcerated lesions are observed more often in the multicentric form. The prevalence among this indigenous group could be explained by genetic susceptibility and lifestyle, which exposes them to a particular agent in the habitats in which they live.

Lobomycosis in Soldiers, Colombia.

Lobomycosis is a disease that is endemic to the Amazon rainforest and is caused by the still uncultured fungus Lacazia loboi. This disease occurs in loggers, farmers, miners, fishermen, and persons living near coastal rivers of this region. We report 6 soldiers in Colombia in whom lobomycosis developed after military service in the Amazon area. The patients had nodular and keloid-like lesions on the face, neck, trunk, and limbs. The duration of illness ranged from 2 years to 15 years. The initial diagnosis was leishmaniasis on the basis of clinical manifestations and direct smear results, but biopsies confirmed the final diagnosis of lobomycosis. Treatment with surgical excision, itraconazole and clofazimine was satisfactory. However, the follow-up time was short. Healthcare professionals responsible for the diagnosis and treatment of skin diseases need to be able to recognize the clinical signs of lobomycosis and differentiate them from those of cutaneous leishmaniasis.

Cutaneous Granulomas in Dolphins Caused by Novel Uncultivated Paracoccidioides brasiliensis.

Cutaneous granulomas in dolphins were believed to be caused by Lacazia loboi, which also causes a similar disease in humans. This hypothesis was recently challenged by reports that fungal DNA sequences from dolphins grouped this pathogen with Paracoccidioides brasiliensis. We conducted phylogenetic analysis of fungi from 6 bottlenose dolphins (Tursiops truncatus) with cutaneous granulomas and chains of yeast cells in infected tissues. Kex gene sequences of P. brasiliensis from dolphins showed 100% homology with sequences from cultivated P. brasiliensis, 73% with those of L. loboi, and 93% with those of P. lutzii. Parsimony analysis placed DNA sequences from dolphins within a cluster with human P. brasiliensis strains. This cluster was the sister taxon to P. lutzii and L. loboi. Our molecular data support previous findings and suggest that a novel uncultivated strain of P. brasiliensis restricted to cutaneous lesions in dolphins is probably the cause of lacaziosis/lobomycosis, herein referred to as paracoccidioidomycosis ceti.

Toward the identification, characterization and experimental culture of Lacazia loboi from Atlantic bottlenose dolphin (Tursiops truncatus).

Lobomycosis (lacaziosis) is a chronic, granulomatous, fungal infection of the skin and subcutaneous tissues of humans and dolphins. To date, the causative agent, the yeast-like organism Lacazia loboi, has not been grown in the laboratory, and there have been no recent reports describing attempts to culture the organism. As a result, studies on the efficacy of therapeutics and potential environmental reservoirs have not been conducted. Therefore, the objective of the current study was to utilize both classical and novel microbiological methods in order to stimulate growth of Lacazia cells collected from dolphin lesions. This included the experimental inoculation of novel media, cell culture, and the use of artificial skin matrices. Although unsuccessful, the methods and results of this study provide important insight into new approaches that could be utilized in future investigations of this elusive organism.

Detection of Multiple Budding Yeast Cells and a Partial Sequence of 43-kDa Glycoprotein Coding Gene of Paracoccidioides brasiliensis from a Case of Lacaziosis in a Female Pacific White-Sided Dolphin (Lagenorhynchus obliquidens).

Lacaziosis, formerly called as lobomycosis, is a zoonotic mycosis, caused by Lacazia loboi, found in humans and dolphins, and is endemic in the countries on the Atlantic Ocean, Indian Ocean and Pacific Ocean of Japanese coast. Susceptible Cetacean species include the bottlenose dolphin (Tursiops truncatus), the Indian Ocean bottlenose dolphin (T. aduncus), and the estuarine dolphin (Sotalia guianensis); however, no cases have been recorded in other Cetacean species. We diagnosed a case of Lacaziosis in a Pacific white-sided dolphin (Lagenorhynchus obliquidens) nursing in an aquarium in Japan. The dolphin was a female estimated to be more than 14 years old at the end of June 2015 and was captured in a coast of Japan Sea in 2001. Multiple, lobose, and solid granulomatous lesions with or without ulcers appeared on her jaw, back, flipper and fluke skin, in July 2014. The granulomatous skin lesions from the present case were similar to those of our previous cases. Multiple budding and chains of round yeast cells were detected in the biopsied samples. The partial sequence of 43-kDa glycoprotein coding gene confirmed by a nested PCR and sequencing, which revealed a different genotype from both Amazonian and Japanese lacaziosis in bottlenose dolphins, and was 99 % identical to those derived from Paracoccidioides brasiliensis; a sister fungal species to L. loboi. This is the first case of lacaziosis in Pacific white-sided dolphin.

Nutritional status and immune response in murine experimental Jorge Lobo's disease.

There are no studies investigating the role of nutritional status and immunity associated with Jorge Lobo's disease. The objective of this study was to evaluate the effects of protein-calorie malnutrition on the immune response of BALB/c mice inoculated with Lacazia loboi. In this study,the animals were divided into four groups: G1: inoculated with restricted diet, G2: not inoculated with restricted diet, G3: inoculated with regular diet, G4: not inoculated with regular diet. The animals of groups G1 and G2 were submitted to malnutrition for 20 days and once installed the animals were inoculated intradermally into the footpad. After 4 months, they were euthanised for the isolation of peritoneal lavage cells and removal of the footpad. The production of IL-2, IL-4, IL-10, IL-12, IFN-γ, TNF-α, H2 O2 and nitric oxide (NO) was evaluated in the peritoneal lavage cells. The footpad was evaluated regarding the size of macroscopic lesions, number of fungi and viability index. The results showed that the infection did not exert great influence on the body weight of the mice and previous malnutrition was an unfavourable factor for viability index, number of fungi, macroscopic lesion size in the footpad and production of H2 O2 , NO, IL-12, IL-10 and IFN-γ, suggesting that malnutrition significantly altered fungal activity and peritoneal cells. The results suggest considerable interaction between nutrition and immunity in Jorge Lobo's disease.

Comparative effect of osmium tetroxide and ruthenium tetroxide on Lacazia loboi ultrastructure.

Lobomycosis is a skin infection produced by the fungus Lacazia loboi, which mainly affects some indigenous and afro-descendant populations in Tropical America. We previously reported the comparative effect of osmium tetroxide (OsO4 ) and ruthenium tetroxide (RuO4 ) in the electron microscopy (EM) of other related microorganisms. The objective of this study is to compare the effect of postfixation with OsO4 and RuO4 in the ultrastructure of L. loboi yeasts. Skin biopsies on patients diagnosed with lobomycosis were fixed in glutaraldehyde at 3% and postfixed in the following solutions: (a) 1% OsO4 , (b) 0.2% RuO4 , and (c) OsO4 at 1% followed by RuO4 at 0.2%. They were then processed using the conventional method for EM. Unlike OsO4, the treatment with RuO4 revealed different shades of gray and electron dense bands in the cell wall and other cell components of L. loboi. The most notable finding was the presence of radial filamentous structures around the yeast, which made the image look like the sun. Postfixation with RuO4 revealed ultrastructural details that had not been previously reported for L loboi. The combined use of OsO4 and RuO4 in EM of microorganisms with cell walls can be useful to evaluate the effect of microbicide substances.

[Cancer and mycoses and literature review]. / Cancer et mycoses et revue de la littérature.

Various infectious agents are classical risk factors for cancer including bacteria, viruses and parasites. There is less evidence concerning the implication of fungal infection in carcinogenesis. The role of chronic Candida infection in the development of squamous cell carcinoma has been suspected for years. Candida sp are more prevalent in potentially malignant disorder and cancer of the oral mucosa. Other epidemiological evidence of a link between Candida infection and cancer is what is observed in patients with Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED). Oral and oesophagal carcinoma are frequent in these patients with chronic mucocutaneous candidiasis. Production of nitrosamine and metabolism of procarcinogen are mecanisms in which Candida sp may be involved in oral cancer development. In chromomycosis and lobomycosis chronic lesions may have a risk of malignant transformation. A diagnosis of paracoccidioidomycosis appears to increase the risk of lung cancer.

DNA damage in BALB/c mice infected with Lacazia loboi and its relation to nutritional status.

BACKGROUND: Jorge Lobo's disease, also known as lacaziosis, is a cutaneous-subcutaneous mycosis with chronic evolution. It is caused by the fungus Lacazia loboi. Herein we report a study that relates the genotoxicity caused by L. loboi in isogenic mice with nutritional status, through a normal or restricted diet. METHODS: DNA damage was assessed in the peripheral blood by the comet assay (tail intensity). RESULTS: The results for leukocytes showed increases in the mean tail intensity in mice under dietary restriction, in infected mice under dietary restriction and in infected mice ingesting a normal diet. CONCLUSION: These results indicate that dietary restriction and L. loboi infection may increase DNA damage levels in mice, as detected by the comet assay.

Lobomycosis: epidemiology, clinical presentation, and management options.

Lobomycosis is a subcutaneous mycosis of chronic evolution caused by the Lacazia loboi fungus. Its distribution is almost exclusive in the Americas, and it has a particularly high prevalence in the Amazon basin. Cases of lobomycosis have been reported only in dolphins and humans. Its prevalence is higher among men who are active in the forest, such as rubber tappers, bushmen, miners, and Indian men. It is recognized that the traumatic implantation of the fungus on the skin is the route by which humans acquire this infection. The lesions affect mainly exposed areas such as the auricles and upper and lower limbs and are typically presented as keloid-like lesions. Currently, surgical removal is the therapeutic procedure of choice in initial cases. Despite the existing data and studies to date, the active immune mechanisms in this infection and its involvement in the control or development of lacaziosis have not been fully clarified. In recent years, little progress has been made in the appraisal of the epidemiologic aspects of the disease. So far, we have neither a population-based study nor any evaluation directed to the forest workers.

Lobomycosis: A case from Southeastern Europe and review of the literature.

BACKGROUND: Lobomycosis, also known as Jorge Lobo's disease, represents a rare chronic subcutaneous mycosis caused by the fungus Lacazia loboi, an organism that is found within lesions but has not been cultured to date. The natural reservoir of L. loboi is unknown but it is believed to be aquatic, or associated with soil and vegetation. More than 550 human cases have been reported, especially in patients with a history of travel or residence in endemic areas (Central and South America, particularly Brazil) or in communities along rivers. MAIN OBSERVATIONS: We describe a 64-year-old Greek female farmer living in a coastal region, who presented with an erythematous plaque on her left inner thigh resembling a keloid. The diagnosis was based on the triad: 1) absence of fungal growth in cultures, 2) positive direct microscopic examination of the lesion and 3) histopathology, all consistent with lobomycosis. Particularly, skin biopsy showed deep cutaneous fungal infection with granulomatous reaction. Fungal cells were found inside giant cells. The fungi were thick-walled with some budding, isolated or in short chains. Dermal fibrosis was present. Our patient had a medical history of common variable immunodeficiency but no history of travel to South or Central America. She probably acquired this rare infection by injury during her agricultural works. CONCLUSION: Our case represents probably the first documented case of human lobomycosis in Southeastern Europe. This case is unusual due to the rarity of lobomycosis in Mediterranean countries, particularly in Southeastern Europe.

THE RELEVANCE OF NUTRITIONAL STATUS AND HISTOPATHOLOGICAL FINDINGS ON THE INFECTIOUS PROCESS OF BALB/C MICE INOCULATED WITH Lacazia loboi / A relevância do estado nutricional e alterações histopatológicas no processo infeccioso de camundongos BALB/c inoculados com Lacazia loboi

SUMMARY The aim of this study was to evaluate the effects of the protein-calorie malnutrition in BALB/c isogenic mice infected with Lacazia loboi, employing nutritional and histopathological parameters. Four groups were composed: G1: inoculated with restricted diet, G2: not inoculated with restricted diet, G3: inoculated with regular diet, G4: not inoculated with regular diet. Once malnutrition had been imposed, the animals were inoculated intradermally in the footpad and after four months, were sacrificed for the excision of the footpad, liver and spleen. The infection did not exert great influence on the body weight of the mice. The weight of the liver and spleen showed reduction in the undernourished groups when compared to the nourished groups. The macroscopic lesions, viability index and total number of fungi found in the footpads of the infected mice were increased in G3 when compared to G1. Regarding the histopathological analysis of the footpad, a global cellularity increase in the composition of the granuloma was observed in G3 when compared to G1, with large numbers of macrophages and multinucleated giant cells, discrete numbers of lymphocytes were present in G3 and an increase was observed in G1. The results suggest that there is considerable interaction between Jorge Lobo's disease and nutrition.

RESUMO O objetivo do estudo foi avaliar os efeitos da desnutrição protéico-calórica em camundongos isogênicos da linhagem BALB/c inoculados com Lacazia loboi, empregando parâmetros nutricionais e histopatológicos. Foram constituídos quatro grupos: G1- inoculados com restrição dietética; G2- não inoculados com restrição dietética; G3- inoculados sem restrição dietética; G4- não inoculados sem restrição dietética. Após instalada a desnutrição, os animais foram inoculados via intradérmica no coxim plantar e após quatro meses foram sacrificados para remoção do coxim plantar, fígado e baço. A infecção não exerceu grande influência no peso corporal dos camundongos. O peso do fígado e baço apresentou redução nos grupos desnutridos em comparação aos grupos nutridos. A lesão macroscópica, a viabilidade e o número total de fungos dos coxins plantares dos camundongos inoculados revelaram aumento no G3 quando comparado com o G1. Em relação à análise histopatológica dos coxins plantares observou-se aumento da celularidade global na composição do granuloma no G3 em relação ao G1, com grande número de macrófagos e células gigantes multinucleadas, discretos números de linfócitos estavam presentes em G3 e aumentados no G1. Os resultados sugerem que existe grande interação entre nutrição e doença de Jorge Lobo.

DNA damage in BALB/c mice infected with Lacazia loboi and its relation to nutritional status

Background Jorge Lobo's disease, also known as lacaziosis, is a cutaneous-subcutaneous mycosis with chronic evolution. It is caused by the fungus Lacazia loboi. Herein we report a study that relates the genotoxicity caused by L. loboi in isogenic mice with nutritional status, through a normal or restricted diet.Methods DNA damage was assessed in the peripheral blood by the comet assay (tail intensity).Results The results for leukocytes showed increases in the mean tail intensity in mice under dietary restriction, in infected mice under dietary restriction and in infected mice ingesting a normal diet.Conclusion These results indicate that dietary restriction and L. loboi infection may increase DNA damage levels in mice, as detected by the comet assay.(AU)

DNA damage in BALB/c mice infected with Lacazia loboi and its relation to nutritional status

AbstractBackground Jorge Lobos disease, also known as lacaziosis, is a cutaneous-subcutaneous mycosis with chronic evolution. It is caused by the fungus Lacazia loboi. Herein we report a study that relates the genotoxicity caused by L. loboi in isogenic mice with nutritional status, through a normal or restricted diet.Methods DNA damage was assessed in the peripheral blood by the comet assay (tail intensity).Results The results for leukocytes showed increases in the mean tail intensity in mice under dietary restriction, in infected mice under dietary restriction and in infected mice ingesting a normal diet.Conclusion These results indicate that dietary restriction and L. loboi infection may increase DNA damage levels in mice, as detected by the comet assay.

Doença de Jorge Lobo: relato de caso e revisão de literatura / Jorge Lobo's disease: case report and literature review

Introdução e objetivos: A doença de Jorge Lobo é uma enfermidade crônica rara causada pelo fungo Lacazia loboi, caracterizada por lesões queloideanas na pele. Objetivou-se realizar revisão de literatura referente ao tema e relatar o primeiro caso de doença de Jorge Lobo atendido no Hospital Universitário Cassiano Antônio Moraes (HUCAM). Materiais e métodos: Os dados do estudo foram obtidos retrospectivamente mediante a análise e revisão sistemática do prontuário de paciente com doença de Jorge Lobo identificado no HUCAM. Relato do caso: Paciente masculino, 37 anos, encaminhado ao HUCAM em abril de 2010 apresentando lesões queloideanas e com diagnóstico prévio de lobomicose por exame anátomo-patológico. Em dezembro de 2011, foi realizada exérese parcial das lesões com enxertia; três meses depois, foi observada recidiva da lobomicose no tecido enxertado. Em junho de 2012, instituiu-se tratamento medicamentoso com clofazimina associada a fluconazol. A ausência de resposta clínica satisfatória dois meses após fez com que a doença fosse considerada fora de possibilidades terapêuticas. Discussão e revisão de literatura: A lobomicose é uma afecção endêmica na Amazônia brasileira e em outras zonas tropicais úmidas das Américas Central e do Sul. Sua transmissão ocorre pela inoculação do fungo através de soluções de continuidade na pele. O diagnóstico é feito por meio do exame clínico e do exame histopatológico ou citológico. A escolha do tipo de terapêutica varia de acordo com a extensão das lesões cutâneas. No entanto, nenhuma das terapias descritas na literatura é totalmente eficaz. Conclusão: No presente caso, falharam as duas principais propostas terapêuticas, sendo a doença considerada incurável...

Ten years experience with Jorge Lobo's disease in the state of Acre, Amazon region, Brazil / Dez anos de experiência com a Doença de Jorge Lobo no estado do Acre, região amazônica, Brasil

Jorge Lobo's disease is a cutaneous and subcutaneous mycosis that affects patients in the Amazon region. The number of patients is relatively small, but the real situation of the disease as public health problem is not known, because Jorge Lobo's disease is not a notifiable disease. This study aims to report the clinical evolution in patients affected and to determine the prevalence and areas of occurrence of the disease. A retrospective study was carried out based on the analysis of the clinical records, which included a collection of photographs of patients in the Department of Sanitary Dermatology, in Rio Branco, and patients seen in the interior of the state. In a decade, in Rio Branco, 249 cases of the disease were reported, 30 were females and 219 males. Of these patients, 153 had localized lesions, 94 of them were on one ear, 55 had multifocal lesions and 41 had disseminated lesions. The average time between the onset of symptoms and diagnosis was 19 years. The average age at the time of diagnosis was 53 years, and ages ranged from 14 to 96 years.

A doença de Jorge Lobo é micose cutânea e subcutânea que afeta pessoas na região Amazônica. O número de pacientes é relativamente pequeno, no entanto, a real prevalência da doença como problema de saúde pública é pouco conhecida. A doença de Jorge Lobo não é de notificação compulsória. Este estudo teve como objetivo determinar a prevalência, as áreas de ocorrência da doença de Jorge Lobo, além de sua evolução clínica. Um estudo retrospectivo foi desenvolvido com base na análise de prontuários de pacientes, incluindo documentação fotográfica dos mesmos, que foram atendidos no Departamento de Dermatologia Sanitária em Rio Branco e no interior do Estado. Foram registrados 249 casos em uma década em Rio Branco, 30 mulheres e 219 homens. Do total 153 apresentavam lesões localizadas, 94 lesões em apenas uma orelha, 55 lesões multifocais e 41 lesões disseminadas. A média de tempo entre o início dos sintomas e o diagnóstico foi de 19 anos. A média de idade no momento do diagnóstico foi de 53 anos, e as idades variaram de 14 a 96 anos.

Determinação dos níveis séricos de lectina ligada a manose e citocinas em pacientes de lacaziose e a associação destes com as formas clínicas da doença / Determination of serum levels of mannose binding lectin and cytokines in lacaziosis patients and the association of them with the clinical forms of disease

A lacaziose é uma micose cutânea – subcutânea de evolução crônica, cujo agente etiológico é a Lacazia loboi (L. loboi). A suscetibilidade a infecção e desenvolvimento da doença pode se manifestar diferentemente de um indivíduo para outro. Isto pode ser atribuído a inúmeros fatores como a deficiência de lectina ligada a manose – MBL (mannose binding lectin) e distúrbios no equilíbrio da produção e liberação das citocinas. No entanto, entre MBL e doenças fúngicas poucos estudos são encontrados na literatura, assim como para algumas determinações séricas de citocinas. Diante disso, a análise da associação entre as manifestações clínicas e níveis séricos destes mediadores é de fundamental importância para avaliar o padrão de resposta imune inata e adaptativa nos portadores de lacaziose da região de Rio branco (AC). Assim, o objetivo deste estudo foi avaliar os níveis séricos de MBL e das citocinas (IL-4, IL-6, IL-10, IL-17, IL-22, TGF-Beta1 e IFN-Gama) em pacientes com a doença nas suas distintas formas clínicas...

Lacaziosis is a cutaneous – subcutaneous mycosis of chronic evolution, whose etiologic agent is Lacazia loboi (L. loboi). The infection susceptibility and disease development can manifest differently in one individual to another. It can be due to many factors, like the deficiency of mannose binding lectin - MBL and disturb the balance of the production and release of cytokines. However, few studies are found in the literature of MBL and fungal diseases and likewise some on serum cytokines determinations. The analysis of the association between clinical manifestations and serum levels of these mediators is of fundamental importance in evaluating the standard of innate and adaptive immune response of the Jorge Lobo’s disease patients the of Rio Branco (AC) region. Through carrying out this type of analysis, the objective of this study was to evaluate serum levels of MBL and cytokines (IL-4, IL-6, IL-10, IL-17, IL-22, TGF-Beta1 and IFN-Gamma) in patients with disease in their distinct clinical form...

THE RELEVANCE OF NUTRITIONAL STATUS AND HISTOPATHOLOGICAL FINDINGS ON THE INFECTIOUS PROCESS OF BALB/C MICE INOCULATED WITH Lacazia loboi / A relevância do estado nutricional e alterações histopatológicas no processo infeccioso de camundongos BALB/c inoculados com Lacazia loboi

The aim of this study was to evaluate the effects of the protein-calorie malnutrition in BALB/c isogenic mice infected with Lacazia loboi, employing nutritional and histopathological parameters. Four groups were composed: G1: inoculated with restricted diet, G2: not inoculated with restricted diet, G3: inoculated with regular diet, G4: not inoculated with regular diet. Once malnutrition had been imposed, the animals were inoculated intradermally in the footpad and after four months, were sacrificed for the excision of the footpad, liver and spleen. The infection did not exert great influence on the body weight of the mice. The weight of the liver and spleen showed reduction in the undernourished groups when compared to the nourished groups. The macroscopic lesions, viability index and total number of fungi found in the footpads of the infected mice were increased in G3 when compared to G1. Regarding the histopathological analysis of the footpad, a global cellularity increase in the composition of the granuloma was observed in G3 when compared to G1, with large numbers of macrophages and multinucleated giant cells, discrete numbers of lymphocytes were present in G3 and an increase was observed in G1. The results suggest that there is considerable interaction between Jorge Lobo's disease and nutrition

O objetivo do estudo foi avaliar os efeitos da desnutrição protéico-calórica em camundongos isogênicos da linhagem BALB/c inoculados com Lacazia loboi, empregando parâmetros nutricionais e histopatológicos. Foram constituídos quatro grupos: G1- inoculados com restrição dietética; G2- não inoculados com restrição dietética; G3- inoculados sem restrição dietética; G4- não inoculados sem restrição dietética. Após instalada a desnutrição, os animais foram inoculados via intradérmica no coxim plantar e após quatro meses foram sacrificados para remoção do coxim plantar, fígado e baço. A infecção não exerceu grande influência no peso corporal dos camundongos. O peso do fígado e baço apresentou redução nos grupos desnutridos em comparação aos grupos nutridos. A lesão macroscópica, a viabilidade e o número total de fungos dos coxins plantares dos camundongos inoculados revelaram aumento no G3 quando comparado com o G1. Em relação à análise histopatológica dos coxins plantares observou-se aumento da celularidade global na composição do granuloma no G3 em relação ao G1, com grande número de macrófagos e células gigantes multinucleadas, discretos números de linfócitos estavam presentes em G3 e aumentados no G1. Os resultados sugerem que existe grande interação entre nutrição e doença de Jorge Lobo