Epidemiological, clinical and laboratory aspects of human visceral leishmaniasis (HVL) associated with human immunodeficiency virus (HIV) coinfection: a systematic review.

Coinfection with human visceral leishmaniasis (HVL) and human immunodeficiency virus (HIV) has become an emerging public health problem in several parts of the world, with high morbidity and mortality rates. A systematic review was carried out in the literature available in PubMed, Scielo and Lilacs related to HVL associated with HIV coinfection, seeking to analyze epidemiological, clinical and laboratory aspects. Of the 265 articles found, 15 articles were included in the qualitative analysis, which referred to the results of HVL treatment in patients coinfected with HIV. In the published articles between 2007 and 2015, 1171 cases of HVL/HIV coinfection were identified, 86% males, average age 34 years, liposomal amphotericin B was the most commonly used drug, cure rates 68 and 20% relapses and 19% deaths, five different countries, bone marrow was used in 10/15 manuscripts. HVL/HIV coinfection is a major challenge for public health, mainly due to the difficulty in establishing an accurate diagnosis, low response to treatment with high relapse rates and evolution to death. In addition, these two pathogens act concomitantly for the depletion of the immune system, contributing to worsening the clinical picture of these diseases, which requires effective surveillance and epidemiological control measures.

Resolvin D1 drives establishment of Leishmania amazonensis infection.

Previous studies have indicated that the balance between different eicosanoids reflect the intensity of the inflammatory profile in patients with tegumentary leishmaniasis. More recently, pro-resolution lipid mediators have been shown to play critical roles in dampening pathological inflammatory processes to reestablish homeostasis in a diverse range of experimental settings. Among these lipid mediator, resolvins from D series have been described as potent anti-inflammatory and immunomodulatory mediators, and its activities include inhibition of leukocyte chemotaxis and blockage production of proinflammatory cytokines, while increasing the expression of regulatory mediators. Whether resolvins play significant roles in establishment and persistence of Leishmania infection is currently unknown. We addressed this question in the current study by assessing circulating levels of D-series resolvins in tegumentary leishmaniasis patients presenting with localized or diffuse disease. We found heightened expression of resolvin D1 in diffuse cutaneous leishmaniasis which was correlated with expression profile of biomarkers associated with disease pathogenesis. Additional in vitro experiments using primary human macrophages indicated that resolvin D1 may promote intracellular Leishmania amazonensis replication through a mechanism associated with induction of heme oxygenase-1. These results suggest that targeting resolvin D1 could serve as potential strategy for host directed therapy in diffuse cutaneous leishmaniasis.

The microbiological signature of human cutaneous leishmaniasis lesions exhibits restricted bacterial diversity compared to healthy skin

Localised cutaneous leishmaniasis (LCL) is the most common form of cutaneous leishmaniasis characterised by single or multiple painless chronic ulcers, which commonly presents with secondary bacterial infection. Previous culture-based studies have found staphylococci, streptococci, and opportunistic pathogenic bacteria in LCL lesions, but there have been no comparisons to normal skin. In addition, this approach has strong bias for determining bacterial composition. The present study tested the hypothesis that bacterial communities in LCL lesions differ from those found on healthy skin (HS). Using a high throughput amplicon sequencing approach, which allows for better populational evaluation due to greater depth coverage and the Quantitative Insights Into Microbial Ecology pipeline, we compared the microbiological signature of LCL lesions with that of contralateral HS from the same individuals.Streptococcus, Staphylococcus,Fusobacterium and other strict or facultative anaerobic bacteria composed the LCL microbiome. Aerobic and facultative anaerobic bacteria found in HS, including environmental bacteria, were significantly decreased in LCL lesions (p < 0.01). This paper presents the first comprehensive microbiome identification from LCL lesions with next generation sequence methodology and shows a marked reduction of bacterial diversity in the lesions.

Repeated praziquantel treatments remodel the genetic and spatial landscape of schistosomiasis risk and transmission.

Repeated treatments with praziquantel reduce schistosomiasis prevalence and morbidity, but transmission persists and populations often recover within a few years. To identify factors associated with persistence, we surveyed and treated all identified Schistosoma mansoni infections in two rural Brazilian communities (Jenipapo and Volta do Rio) in 2009, 2012 and 2013. Eggs were collected from all infected individuals and genotyped with 11 microsatellite markers to evaluate parasite differentiation and diversity. After successive rounds of community-wide treatment, prevalence decreased from 45% to 24% then 16%. Intensity of infection decreased by 57% over this period, and the number of eggs transmitted to the environment decreased by 92%. During all time periods the majority of eggs were excreted by those >15years of age. The incidence was 23% in 2012 and 15% in 2013, consistent with a decrease in transmission. There was little immigration or gene flow over a distance of 6km. On reinfection, infrapopulations were moderately differentiated indicating that pretreatment multilocus genotypes were not fully reacquired. The effective population size responded to census population decline more rapidly than differentiation. Reinfection was concentrated in the downstream portion of Jenipapo, consistent with the observed increased human fecal contamination. At this scale and in this area S. mansoni infections exist on a fragmented landscape with a highly focal pattern of transmission that may facilitate future elimination.

Differential Expression of the Eicosanoid Pathway in Patients With Localized or Mucosal Cutaneous Leishmaniasis.

Unfettered inflammation is thought to play critical role in the development of different clinical forms of tegumentary leishmaniasis. Eicosanoids are potent mediators of inflammation and tightly associated with modulation of immune responses. In this cross-sectional exploratory study, we addressed whether targets from the eicosanoid biosynthetic pathway, assessed by multiplexed expression assays in lesion biopsy and plasma specimens, could highlight a distinct biosignature in patients with mucocutaneous leishmaniasis (MCL) or localized cutaneous leishmaniasis (LCL). Differences in immunopathogenesis between MCL and LCL may result from an imbalance between prostaglandins and leukotrienes, which may serve as targets for future host-directed therapies.

Arginase I, polyamine, and prostaglandin E2 pathways suppress the inflammatory response and contribute to diffuse cutaneous leishmaniasis.

Diffuse cutaneous leishmaniasis (DCL) is a rare clinical manifestation of tegumentary leishmaniasis. The molecular mechanisms underlying DCL pathogenesis remain unclear, and there is no efficient treatment available. This study investigated the systemic and in situ expression of the inflammatory response that might contribute to suppression in DCL. The plasma levels of arginase I, ornithine decarboxylase (ODC), transforming growth factor ß (TGF-ß), and prostaglandin E2 (PGE2) were higher in patients with DCL, compared with patients with localized cutaneous leishmaniasis (LCL) or with controls from an area of endemicity. In situ transcriptomic analyses reinforced the association between arginase I expression and enzymes involved in prostaglandin and polyamine synthesis. Immunohistochemistry confirmed that arginase I, ODC, and cyclooxygenase2 expression was higher in lesion biopsy specimens from patients with DCL than in those from patients with LCL. Inhibition of arginase I or ODC abrogates L. amazonensis replication in infected human macrophages. Our data implicate arginase I, ODC, PGE2, and TGF-ß in the failure to mount an efficient immune response and suggest perspectives in the development of new strategies for therapeutic intervention for patients with DCL.

Exposure of phosphatidylserine on Leishmania amazonensis isolates is associated with diffuse cutaneous leishmaniasis and parasite infectivity.

Diffuse cutaneous leishmaniasis (DCL) is a rare clinical manifestation of leishmaniasis, characterized by an inefficient parasite-specific cellular response and heavily parasitized macrophages. In Brazil, Leishmania (Leishmania) amazonensis is the main species involved in DCL cases. In the experimental model, recognition of phosphatidylserine (PS) molecules exposed on the surface of amastigotes forms of L. amazonensis inhibits the inflammatory response of infected macrophages as a strategy to evade the host immune surveillance. In this study, we examined whether PS exposure on L. amazonensis isolates from DCL patients operated as a parasite pathogenic factor and as a putative suppression mechanism of immune response during the infection. Peritoneal macrophages from F1 mice (BALB/c×C57BL/6) were infected with different L. amazonensis isolates from patients with localized cutaneous leishmaniasis (LCL) or DCL. DCL isolates showed higher PS exposure than their counterparts from LCL patients. In addition, PS exposure was positively correlated with clinical parameters of the human infection (number of lesions and time of disease) and with characteristics of the experimental infection (macrophage infection and anti-inflammatory cytokine induction). Furthermore, parasites isolated from DCL patients displayed an increased area in parasitophorous vacuoles (PV) when compared to those isolated from LCL patients. Thus, this study shows for the first time that a parasite factor (exposed PS) might be associated with parasite survival/persistence in macrophages and lesion exacerbation during the course of DCL, providing new insights regarding pathogenic mechanism in this rare chronic disease.

Lesion size correlates with Leishmania antigen-stimulated TNF-levels in human cutaneous leishmaniasis.

Cutaneous leishmaniasis (CL) is a worldwide disease endemic in several regions of the globe. The hallmark of CL is skin ulcers likely driven by efforts of the immune system to control Leishmania growth. Cytokines, such as tumor necrosis factor (TNF) and interferon-gamma can control disease progression in animal models. Nevertheless, the impact of these cytokines in CL ulcer outcome is not well established in humans. In this study, 96 CL patients from an endemic area of Leishmania braziliensis were enrolled for a follow-up study that consisted of clinical and immunological evaluations in a 2-year period. Statistical analysis revealed that healing time (P = 0.029), age (P = 0.002), and TNF levels (P = 0.0002) positively correlate with ulcer size at the time of the first clinical evaluation. Our findings suggest that ulcer size correlates with healing time and TNF levels support the use of TNF inhibitors combined with standard therapy to improve healing in CL patients with severe lesions.

Schistosoma mansoni population structure and persistence after praziquantel treatment in two villages of Bahia, Brazil.

Praziquantel has been used to treat schistosome infections since 1979 and currently is the only chemotherapeutic agent in production for this purpose, raising concerns about the potential for the emergence of drug resistance. In practice, 10-20% of infected patients will continue to excrete eggs after treatment. It is not understood to what degree this represents selection of a resistant population or incomplete elimination due to the presence of immature worms at the time of treatment. We used a population genetics approach to test whether or not persistent Schistosomamansoni parasites were drawn from the same population as susceptible parasites. In this study, stool samples were collected from 96% of individuals in two small Brazilian communities (populations 482 and 367) and examined for S.mansoni eggs. The combined prevalence of S.mansoni infections in the villages was 41%. Total egg DNA was extracted from each sample and was genotyped at 15 microsatellite markers. Day-to-day variation of the infrapopulation from an individual human host was low (median differentiation using Jost's D=0.010), so that a single stool was representative of the genotypes present in stool eggs, at least in the short term. Average pairwise analysis of D among all pre-treatment infrapopulations suggested moderate differentiation (mean D=0.082 and 0.122 for the two villages), whereas the pre-treatment component population differentiation between the two communities was 0.047. The differentiation of the component population remaining after treatment from the fully susceptible component population was low (mean D=0.007 and 0.020 for the two villages), suggesting that the persistent parasites were not selected by praziquantel treatment. We will continue to follow these communities for evidence of selection or changes in population structure.

Immune and inflammatory responses to Leishmania amazonensis isolated from different clinical forms of human leishmaniasis in CBA mice.

Leishmania amazonensis causes different diseases depending on the host and parasitic virulence factors. In this study, CBA mice were infected with L. amazonensis isolates from patients with localized (Ba125), diffuse cutaneous (Ba276) or visceral leishmaniasis (Ba109). Mice infected with Ba125 and Ba276 progressed rapidly and lesions displayed an infiltrate rich in parasitized macrophages and were necrotic and ulcerated. Ba109 induced smaller lesions and a mixed inflammatory infiltrate without necrosis or ulceration. Ba109 induced an insidious disease with lower parasite load in CBA mice, similar to human disease. Levels of IFN-γ, IL-4 and IL-10 did not differ among the groups. Because all groups were unable to control the infection, expression of IL-4 associated with low production of IFN-γ in the early phase of infection may account for susceptibility, but others factors may contribute to the differences observed in inflammatory responses and infection progression. Evaluation of some parasitic virulence factors revealed that Ba276 exhibits higher ecto-ADPase and 5'-nucleotidase activities compared to the Ba109 and Ba125 strains. Both Ba276 and Ba125 had higher arginase activity in comparison to Ba109. Finally, these data suggest that the differences in enzyme activities among parasites can account for differences in host inflammatory responses and infection progression.

Immune and inflammatory responses to Leishmania amazonensis isolated from different clinical forms of human leishmaniasis in CBA mice

Leishmania amazonensis causes different diseases depending on the host and parasitic virulence factors. In this study, CBA mice were infected with L. amazonensis isolates from patients with localized (Ba125), diffuse cutaneous (Ba276) or visceral leishmaniasis (Ba109). Mice infected with Ba125 and Ba276 progressed rapidly and lesions displayed an infiltrate rich in parasitized macrophages and were necrotic and ulcerated. Ba109 induced smaller lesions and a mixed inflammatory infiltrate without necrosis or ulceration. Ba109 induced an insidious disease with lower parasite load in CBA mice, similar to human disease. Levels of IFN-γ, IL-4 and IL-10 did not differ among the groups. Because all groups were unable to control the infection, expression of IL-4 associated with low production of IFN-γ in the early phase of infection may account for susceptibility, but others factors may contribute to the differences observed in inflammatory responses and infection progression. Evaluation of some parasitic virulence factors revealed that Ba276 exhibits higher ecto-ADPase and 5'-nucleotidase activities compared to the Ba109 and Ba125 strains. Both Ba276 and Ba125 had higher arginase activity in comparison to Ba109. Finally, these data suggest that the differences in enzyme activities among parasites can account for differences in host inflammatory responses and infection progression.

Infecção bacteriana na leishmaniose cutânea: padrão bacteriano e sensibilidade a antibióticos / Bacterial infection in cutaneous leishmaniasis: bacterial pattern and sensitivity to antibiotics

Foi estudada a flora bacteriana em úlceras leishmanióticas, destacando-se o encontro das espécies aeróbicas Staphylococus aureus e Pseudomonas aeruginosa. O estudo da sensibilidade destas espécies a antibióticos mostrou sensibilidade à vancomicina, à amicacina e ao cloranfenicol em 100 por cento dos isolados testados de Staphylococus aureus e à amicacina, à gentamicina e à tobramicina em 100 por cento dos isolados testados de Pseudomonas aeruginosa. Estas espécies foram, em geral, resistentes às penicilinas e à tetraciclina.

The bacterial flora from leishmanial ulcers was studied. The aerobic species Staphylococcus aureus and Pseudomonas aeruginosa were found most frequently. Evaluation of the sensitivity of these species to antibiotics showed that 100 percent of these isolates of Staphylococcus aureus were sensitive to vancomycin, amikacin and chloramphenicol, while 100 percent of the isolates of Pseudomonas aeruginosa were sensitive to amikacin, gentamicin and tobramycin. These species were generally resistant to penicillins and tetracycline.

Efeito leishmanicida in vitro de Stachytarpheta cayennensis (Rich. ) Vahl (Verbenaceae) / In vitro leishmanicidal effect of Stachytarpheta cayennensis (Rich. ) Vahl (Verbenaceae)

A atividade anti-Leishmania do extrato hidroalcoólico de Stachytarpheta cayennensis, espécie utilizada popularmente no tratamento de lesões cutâneas causadas por Leishmania sp, foi testado em ensaios in vitro utilizando formas promastigotas de Leishmania braziliensis e L. amazonensis. O extrato hidroalcoólico foi preparado a partir das folhas secas e utilizado em culturas de L. amazonensis e L. braziliensis nas concentrações de 500 a 32,5 æg/mL. Após 24 horas as formas promastigotas foram quantificadas para o cálculo da CI50. A citotoxicidade do extrato foi avaliada também em culturas de macrófagos peritoneais. O extrato apresentou efeito leishmanicida dose e espécie-dependente para promastigotas de Leishmania sendo mais eficaz para L. braziliensis. O extrato não apresentou efeito citotóxico quando utilizado nas culturas de macrófagos. Concluiu-se que o extrato hidroalcoólico de S. cayennensis inibe formas promastigotas de Leishmania in vitro o que poderia justificar, pelo menos parcialmente, o uso popular dessa espécie no tratamento de úlceras causadas por Leishmania.

Leishmanicidal activity of the hydroalcoholic extract of Stachytarpheta cayennensis, species that is usually employed in ulcers caused by Leishmania, was evaluated in vitro using Leishmania braziliensis and L. amazonensis promastigotes forms. The hydroalcoholic extract was prepared from dried leaves and used in L. amazonensis and L. braziliensis promastigotes cultures at concentrations of 500 to 32.5 æg/mL. After 24 hours the promastigotes forms were quantified and the IC50 was calculated. The cytotoxicity of the extract was evaluated using peritoneal macrophages. The extract presented a dose and specie-dependent leishmanicidal effect to Leishmania promastigotes, mainly to the L. braziliensis ones. The cytotoxic effect was not observed in macrophage cultures. In conclusion, the hydroalcoholic extract of S. cayennensis inhibits the growing of Leishmania promastigotes forms in vitro accounting for the folk use of this vegetal in skin ulcers caused by Leishmania.

Experimental model of chronic osteomyelitis caused by Leishmania (L) amazonensis.

Experimental animal models have been used for the study of the physiopathogenesis of leishmaniasis, on some occasions with success, while in other situations such as bone alterations that accompany tegumentary leishmaniasis, especially in diffuse cutaneous form (DCL), the mechanisms are still unknown. In the present study, we determined these alterations in an animal model susceptible to Leishmania (L) amazonensis. Amastigotes of L. (L) amazonensis isolated from patients with diffuse cutaneous leishmaniasis (DCL) were inoculated into the hind paws of eight BALB/c mice, macroscopic and histopathological aspects were analyzed. After 90 and 120 days of evolution, histopathological analysis demonstrated a mononuclear cell infiltrate rich in plasma cells and intense parasitism of intra- and extra-medullary macrophages, with areas of bone necrosis and discrete involvement of cartilaginous tissue. The results show that the inflammatory process developed during L. (L) amazonensis infection might cause bone tissue destruction and secondarily affect the joints.

CD16+ monocytes in human cutaneous leishmaniasis: increased ex vivo levels and correlation with clinical data.

Peripheral blood CD16 (Fc receptor for immunoglobulin G III)-positive monocytes have been shown to expand in different pathological conditions, such as cancer, asthma, sepsis, human immunodeficiency virus infection, and AIDS progression, but data in leishmaniasis are lacking. We found that cutaneous leishmaniasis patients (n = 15) displayed a significant increase in the percentage (3.5 vs. 10.1) as well as mean fluorescent intensity (13.5 vs. 29.2) of ex vivo CD16 expression in monocytes as compared with healthy controls. We observed a significant positive correlation between the percentage of ex vivo CD16+ monocytes and lesion size (P = 0.0052, r = 0.75) or active transforming growth factor-beta plasma levels (P = 0.0017, r = 0.78). In addition, two patients with nonhealing lesions during a 3-year follow-up had high (9.1-19.4%) CD16 levels at diagnosis. Our data suggest a deleterious role for CD16 in human leishmaniasis, as well as its possible use as a marker for disease severity and/or adverse disease outcome.

Microbiological analyses of water from hemodialysis services in São Luís, Maranhão, Brazil

A necessidade de um controle rigoroso no servico de hemodiálise tornou-se algo de extrema importância para garantir uma melhor qualidade de vida aos pacientes submetidos a este tratamento, uma vez que, a falta de controle de qualidade da água, tem levado a óbito vários pacientes. Este estudo teve como objetivo avaliar as características físico-químicas e bacteriológicas da água utilizada pelos servicos de hemodiálise em hospitais da cidade de São Luís. A metodologia utilizada para as análises bacteriológicas foi: método da membrana filtrante para determinacão de coliformes totais, método Cult-Dipcombi-ttc-ágar para bactérias heterotróficas e método limulus amebocyte lysate para endotoxinas. Foram analisadas dezoito amostras de água em três unidades hospitalares, sendo seis amostras provenientes de cada servico de hemodiálise, colhidas diretamente dos pontos pré e pós-tratamento. Quanto à presenca de microrganismos na água utilizada pelos servicos de hemodiálise, observou-se positividade nas unidades hospitalares B e C. Não foi encontrada contaminacão por bactérias heterotróficas nas amostras examinadas no pré-tratamento, entretanto a contaminacão por endotoxinas foi em 100 per center das amostras. Nas amostras pós-tratamento encontrou-se para bactérias heterotróficas 66,6 per center e endotoxinas 33,3 per center. Os microrganismos identificados na unidade hospitalar B foram: Burkholderia cepacia, Alcalígenes xilosoxidans, Pseudomonas aeruginosa e Stenotrophomonas maltophilia. Na unidade C, foram identificados: Flavimonas oryzihabitans, Ralstônia pickettii e Burkholderia cepacia. Houve uma correlacão significativa entre a presenca de endotoxinas e características físico-químicas da água tais como: turbidez e condutividade. Estes dados revelaram que duas das três unidades hospitalares avaliadas necessitam rever o controle do sistema de água de hemodiálise.

Polymerase chain reaction (PCR) is highly sensitive for diagnosis of mucosal leishmaniasis.

We evaluated the use of polymerase chain reaction (PCR) for diagnosis of mucosal leishmaniasis (ML) in an endemic area in Acre, Brazil, where Leishmania braziliensis is present. Leishmania DNA was detected 34 of 35 cases, yielding a positivity rate of 97.1%, which was higher than the positivity rates for all of the other diagnostic methods studied, namely Montenegro skin test (MST), anti-Leishmania serological testing and microscopic examination of lesion biopsy specimens. These findings have led us to propose guidelines for the diagnosis of ML that use PCR as the principal method of parasitological confirmation of cases.

Role of costimulatory molecules in immune response of patients with cutaneous leishmaniasis.

T cell-mediated immunity is critical in resistance against Leishmania parasites, and T cell activation requires signals provided by costimulatory molecules. Herein we evaluated the role of costimulatory molecules on cytokine production and T cell surface molecule expression by peripheral blood mononuclear cells (PBMC) from cutaneous leishmaniasis (CL) patients. PBMC from CL patients were stimulated with soluble Leishmania antigen (SLA, 10 microg/ml), in the presence or absence of soluble CTLA4-Ig to block CD28-B7 interaction or in the presence or absence of anti-human CD40L to block CD40-CD40L interaction. Supernatants were harvested to evaluate tumor necrosis factor alpha (TNF-alpha), interleukin 10 (IL-10), transforming growth factor beta (TGF-beta) and interferon gamma (IFN-gamma) production by ELISA. Cells were harvested after 48 h of culture, stained for specific activation markers and analyzed by flow cytometry. Results show that the blockade of CD28-B7 interaction by CTLA4-Ig downmodulated IFN-gamma, IL-10, and TNF-alpha secretion by PBMC from CL patients. No alteration was detected on either TGF-beta production or the expression of CTLA44 or CD25 on CD4+ and CD8+ T cells. When the CD40-CD40L interaction was blockade using anti-CD40L, we did not observe changes in cytokine production or in surface molecule expression. The blockade of the CD28-B7 interactions by CTLA4-Ig also did not alter cytokine production in volunteers immunized against tetanus toxoid (TT). Taken together, these data suggest that the interaction of CTLA4 and CD28-B7 is a TGF-beta-independent mechanism that specifically downmodulates the immune response in cutaneous leishmaniasis patients.

Subclinical form of the American visceral leishmaniasis

The subclinical form of visceral leishmaniasis (VL) shows nonspecific clinical manifestations, with difficulties being frequently met in its clinical characterization and diagnostic confirmation. Thus, the objective of the present study was to define the clinical-laboratory profile of this clinical form. A cohort study was conducted in the state of Maranhão, Brazil, from January/1998 to December/2000, with monthly follow-up of 784 children aged 0-5 years. Based on the clinical-laboratory parameters reported in the literature, four categories were established, with the children being classified (according to their clinical-evolutive behavior) as asymptomatic (N = 144), as having the subclinical form (N = 33) or the acute form (N = 12) or as subjects "without VL" (N = 595). Multiple discriminant analysis demonstrated that the combination of fever, hepatomegaly, hyperglobulinemia, and increased blood sedimentation rate (BSR) can predict the subclinical form of VL as long as it is not associated with splenomegaly or leukopenia. Subjects with the subclinical form did not show prolonged or intermittent evolution or progression to the acute form of VL. Subclinical cases have a profile differing from the remaining clinical forms of VL, being best characterized by the combination of fever, hepatomegaly, hyperglobulinemia, and increased BSR.

Uso de Cetoconazol® no tratamento da entomoftoromicose cutâneo-mucosa: relato de caso / Use of Ketoconazole for treating mucocutaneous Entomophthoromycosis: a case report

As entomoftoromicoses constituem entidade clínica pertencente ao grupo das zigomicoses, cujos agentes etiológicos são o Conidiobolus coronatus, Conidiobolos incongruus e o Basidiobolos ranarum. Um caso de entomoftoromicose cutâneo-mucosa é descrito em homem de 51 anos de idade, lavrador, procedente da região amazônica do Estado do Maranhão, Brasil. Teve diagnóstico esclarecido por exame anatomopatológico, um ano após as manifestações clínicas iniciais. Como tratamento utilizou-se um dos derivados imidazólicos (cetoconazol®) 400mg/dia divididos em duas tomadas, por 12 meses), mostrando boa tolerância, com resposta favorável. Na última avaliação, 24 meses após início do tratamento, encontrava-se clinicamente curado.