Multiple myeloma and Chagas disease: qPCR as a marker for preemptive antiparasitic therapy: a case reports series and review

ABSTRACT Multiple myeloma (MM) associated with Chagas disease is rarely described. This disease and its therapy suppress T cell and macrophage functions and increase regulatory T cell function, allowing the increase of parasitemia and the risk of Chagas Disease Reactivation (CDR). We aimed to analyze the role of conventional (cPCR) and quantitative Polymerase Chain Reaction (qPCR) for prospective monitoring of T. cruzi parasitemia, searching for markers of preemptive antiparasitic therapy in MM patients with Chagas disease. Moreover, we investigated the incidence and management of hematological diseases and CDR both inside and outside the transplant setting in the MEDLINE database. We found 293 studies and included 31 of them. Around 1.9-2.0% of patients with Chagas disease were reported in patients undergoing Stem Cell Transplantation. One case of CDR was described in eight cases of MM and Chagas disease. We monitored nine MM and Chagas disease patients, seven under Autologous Stem Cell Transplantation (ASCT), during 44.56±32.10 months (mean±SD) using parasitological methods, cPCR, and qPCR. From these patients, three had parasitemia. In the first, up to 256 par Eq/mL were detected, starting from 28 months after ASCT. The second patient dropped out and died soon after the detection of 161.0 par Eq/mL. The third patient had a positive blood culture. Benznidazole induced fast negativity in two cases; followed by notably lower levels in one of them. Increased T. cruzi parasitemia was related to the severity of the underlying disease. We recommend parasitemia monitoring by qPCR for early introduction of preemptive antiparasitic therapy to avoid CDR.

Genetic diversity of Trypanosoma cruzi strains isolated from chronic chagasic patients and non-human hosts in the state of São Paulo, Brazil

BACKGROUND Trypanosoma cruzi shows an exuberant genetic diversity. Currently, seven phylogenetic lineages, called discrete typing units (DTUs), are recognised: TcI-TcVI and Tcbat. Despite advances in studies on T. cruzi and its populations, there is no consensus regarding its heterogeneity. OBJECTIVES This study aimed to perform molecular characterisation of T. cruzi strains, isolated in the state of São Paulo, to identify the DTUs involved and evaluate their genetic diversity. METHODS T. cruzi strains were isolated from biological samples of chronic chagasic patients, marsupials and triatomines through culture techniques and subjected to molecular characterisation using the fluorescent fragment length barcoding (FFLB) technique. Subsequently, the results were correlated with complementary information to enable better discrimination between the identified DTUs. FINDINGS It was possible to identify TcI in two humans and two triatomines; TcII/VI in 19 humans, two marsupials and one triatomine; and TcIII in one human host, an individual that also presented a result for TcI, which indicated the possibility of a mixed infection. Regarding the strains characterised by the TcII/VI profile, the correlation with complementary information allowed to suggest that, in general, these parasite populations indeed correspond to the TcII genotype. MAIN CONCLUSIONS The TcII/VI profile, associated with domestic cycles and patients with chronic Chagas disease, was the most prevalent among the identified DTUs. Furthermore, the correlation of the study results with complementary information made it possible to suggest that TcII is the predominant lineage of this work.

Emerging and reemerging forms of Trypanosoma cruzi transmission

This review aims to update and discuss the main challenges in controlling emergent and reemergent forms of Trypanosoma cruzi transmission through organ transplantation, blood products and vertical transmission in endemic and non-endemic areas as well as emergent forms of transmission in endemic countries through contaminated food, currently representing the major cause of acute illness in several countries. As a neglected tropical disease potentially controllable with a major impact on morbimortality and socioeconomic aspects, Chagas disease (CD) was approved at the WHO global plan to interrupt four transmission routes by 2030 (vector/blood transfusion/organ transplant/congenital). Implementation of universal or target screening for CD are highly recommended in blood banks of non-endemic regions; in organ transplants donors in endemic/non-endemic areas as well as in women at risk from endemic areas (reproductive age women/pregnant women-respective babies). Moreover, main challenges for surveillance are the application of molecular methods for identification of infected babies, donor transmitted infection and of live parasites in the food. In addition, the systematic recording of acute/non-acute cases and transmission sources is crucial to establish databases for control and surveillance purposes. Remarkably, antiparasitic treatment of infected reproductive age women and infected babies is essential for the elimination of congenital CD by 2030.

Acesso e direito à saúde para migrantes bolivianos em uma metrópole brasileira / Access and right to health for Bolivian migrants in a Brazilian metropolis

Resumo Este artigo analisa as condições de acesso do imigrante boliviano ao sistema de saúde brasileiro e a percepção do direito à saúde. É um estudo transversal de metodologia quantitativa e qualitativa, realizado de 2013 a 2015. Foi elaborado um questionário com perguntas fechadas respondidas por 633 bolivianos, e em relação ao acesso à saúde por 472 indivíduos bolivianos maiores de 18 anos. A abordagem qualitativa foi feita por meio da análise de conteúdo de entrevistas semiestruturadas com 55 sujeitos (bolivianos, profissionais de saúde, representantes de Secretarias de Saúde, Consulado da Bolívia, Defensoria Pública da União, Ministério Público Federal e Organizações Não Governamentais). Os bolivianos conhecem o Sistema Único de Saúde (SUS) e utilizam com frequência a Atenção Primária à Saúde (APS). Todavia, barreiras de acesso são descritas, como falta de documentação, condições de trabalho, procedimentos de média e/ou alta complexidades, dificuldades para entenderem o que é dito assim como para serem compreendidos, entre outras. Sobressai-se a obtenção do Cartão Nacional de Saúde (CNS) como porta de entrada para o acesso à saúde, desempenhando papel de integração social. O reconhecimento da Saúde como direito social destaca-se entre os entrevistados, apontado como valor humano e solidário. A garantia desse reconhecimento fica ameaçada quando não se apoia na consolidação de políticas sociais que visem o fortalecimento da proteção social universal.

Abstract This paper analyzes the health care accessibility conditions afforded to Bolivian immigrants in the Brazilian health system and their perception of the right to health. This was a cross-sectional, quantitative and qualitative study carried out from 2013 to 2015. Data were collected by a questionnaire with closed questions answered by 633 Bolivian individuals; questions regarding access to health were answered by 472 immigrants over 18 years old. Semi-structured interviews conducted with 55 subjects (Bolivians, health professionals, representatives of Health Departments, Consulate of Bolivia, Public Defender's Office, Federal Public Prosecutor's Office and Non-Governmental Organizations) underwent content analysis. Most Bolivian immigrants know the Brazilian National Health System (SUS) and often use Primary Health Care; however, they described structural and systemic barriers to health accessibility, such as lack of documentation, working conditions, medium and high complexity procedures, language barriers, among others. The National Health Card (CNS) is an important gateway to access health care, playing a role of social integration. Interviewees recognize health as a social right, pointing it out as a human and solidary value. Ensuring this recognition, when not based on the consolidation of social policies aimed at strengthening universal social protection, is threatened.

Role of T. cruzi exposure in the pattern of T cell cytokines among chronically infected HIV and Chagas disease patients

OBJECTIVES: The impact of Chagas disease (CD) in HIV-infected patients is relevant throughout the world. In fact, the characterization of the adaptive immune response in the context of co-infection is important for predicting the need for interventions in areas in which HIV and Chagas disease co-exist. METHODS: We described and compared the frequency of cytokine-producing T cells stimulated with soluble antigen of Trypanosoma cruzi (T. cruzi) using a cytometric assay for the following groups: individuals with chronic Chagas disease (CHR, n=10), those with Chagas disease and HIV infection (CO, n=11), those with only HIV (HIV, n=14) and healthy individuals (C, n=15). RESULTS: We found 1) a constitutively lower frequency of IL-2+ and IFN-γ+ T cells in the CHR group compared with the HIV, CO and healthy groups; 2) a suppressive activity of soluble T. cruzi antigen, which down-regulated IL-2+CD4+ and IFN-γ+CD4+ phenotypes, notably in the healthy group; 3) a down-regulation of inflammatory cytokines on CD8+ T cells in the indeterminate form of Chagas disease; and 4) a significant increase in IL-10+CD8+ cells distinguishing the indeterminate form from the cardiac/digestive form of Chagas disease, even in the presence of HIV infection. CONCLUSIONS: Taken together, our data suggest the presence of an immunoregulatory response in chronic Chagas disease, which seems to be driven by T. cruzi antigens. Our findings provide new insights into immunotherapeutic strategies for people living with HIV/AIDS and Chagas disease.

II Consenso Brasileiro em Doença de Chagas, 2015 / Brazilian Consensus on Chagas Disease, 2015

A doença de Chagas é uma condição crônica negligenciada com elevada carga de morbimortalidade e impacto dos pontos de vista psicológico, social e econômico. Representa um importante problema de saúde pública no Brasil, com diferentes cenários regionais. Este documento traduz a sistematização das evidências que compõe o Consenso Brasileiro de Doença de Chagas. O objetivo foi sistematizar estratégias de diagnóstico, tratamento, prevenção e controle da doença de Chagas no país, de modo a refletir as evidências científicas disponíveis. Sua construção fundamentou-se na articulação e contribuição estratégica de especialistas brasileiros com conhecimento, experiência e atualização sobre diferentes aspectos da doença. Representa o resultado da estreita colaboração entre a Sociedade Brasileira de Medicina Tropical e o Ministério da Saúde. Espera-se com este documento fortalecer o desenvolvimento de ações integradas para enfrentamento da doença no país com foco em epidemiologia, gestão, atenção integral (incluindo famílias e comunidades), comunicação, informação, educação e pesquisas.

Chagas disease is a neglected chronic condition that presents high morbidity and mortality burden, with considerable psychological, social, and economic impact. The disease represents a significant public health issue in Brazil, with different regional patterns. This document presents the evidence that resulted in the Brazilian Consensus on Chagas Disease. The objective was to review and standardize strategies for diagnosis, treatment, prevention, and control of Chagas disease in the country, based on the available scientific evidence. The consensus is based on collaboration and contribution of renowned Brazilian experts with vast knowledge and experience on various aspects of the disease. It is the result of close collaboration between the Brazilian Society of Tropical Medicine and the Ministry of Health. This document shall strengthen the development of integrated control measures against Chagas disease in the country, focusing on epidemiology, management, comprehensive care (including families and communities), communication, information, education, and research.

CHAGASIC MENINGOENCEPHALITIS IN AN HIV INFECTED PATIENT WITH MODERATE IMMUNOSUPPRESSION: PROLONGED SURVIVAL AND CHALLENGES IN THE HAART ERA / Meningoencefalite chagásica em paciente infectada pelo HIV com imunodepressão moderada: desafios na era HAART e sobrevida prolongada

The reactivation of Chagas disease in HIV infected patients presents high mortality and morbidity. We present the case of a female patient with confirmed Chagasic meningoencephalitis as AIDS-defining illness. Interestingly, her TCD4+ lymphocyte cell count was 318 cells/mm3. After two months of induction therapy, one year of maintenance with benznidazol, and early introduction of highly active antiretroviral therapy (HAART), the patient had good clinical, parasitological and radiological evolution. We used a qualitative polymerase chain reaction for the monitoring of T. cruzi parasitemia during and after the treatment. We emphasize the potential value of molecular techniques along with clinical and radiological parameters in the follow-up of patients with Chagas disease and HIV infection. Early introduction of HAART, prolonged induction and maintenance of antiparasitic therapy, and its discontinuation are feasible, in the current management of reactivation of Chagas disease.

A reativação da doença de Chagas em pacientes com a infecção pelo HIV apresenta uma alta morbidade e mortalidade. Neste relato, apresentamos caso confirmado de meningoencefalite chagásica, como doença definidora de aids, em paciente com 318 linfócitos T-CD4+/mm3. Após 2 meses de tratamento seguido de um ano de profilaxia secundária com benzonidazol e início precoce de terapia antirretroviral (HAART), a paciente apresentou boa evolução clínica, parasitológica e radiológica. Utilizamos a reação em cadeia da polimerase qualitativa do T. cruzi, para monitorização da parasitemia por T. cruzi durante e após o tratamento. Ressaltamos o valor potencial das técnicas moleculares associadas aos parâmetros clínicos e radiológicos nos pacientes com doença de Chagas e infecção pelo HIV. A introdução precoce da terapia antirretroviral, a terapia antiparasitária prolongada, manutenção e descontinuação da mesma, são desafios atuais, embora possíveis, no manejo da reativação da doença de Chagas na era das terapias antirretrovirais de alta eficácia.

Paracoccidioidomycosis treatment / Tratamento da paracoccidioidomicose

SUMMARYConsidered to be an emerging endemic mycosis in Latin America, paracoccidioidomycosis is characterized by a chronic course and involvement of multiple organs in immunocompromised hosts. Infection sequelae are mainly related to pulmonary and adrenal insufficiency. The host-parasite interaction results in different expressions of the immune response depending on parasite pathogenicity, fungal load and genetic characteristics of the host. A few controlled and case series reports have shown that azoles and fast-acting sulfa derivatives are useful treatment alternatives in milder forms of the disease. For moderate/severe cases, more prolonged treatments or even parenteral routes are required especially when there is involvement of the digestive tract mucosa, resulting in poor drug absorption. Although comparative studies have reported that shorter treatment regimens with itraconazole are able to induce cure in chronically-infected patients, there are still treatment challenges such as the need for more controlled studies involving acute cases, the search for new drugs and combinations, and the search for compounds capable of modulating the immune response in severe cases as well as the paradoxical reactions.

RESUMOConsiderada micose endêmica emergente na América Latina, a paracoccidioidomicose é caracterizada por uma evolução crônica e envolvimento de múltiplos órgãos em pacientes com comprometimento imunológico. Sequelas da infecção estão relacionadas principalmente à insuficiência pulmonar e adrenal. A interação hospedeiro-parasito resulta em diferentes expressões da resposta imune dependendo da patogenicidade do parasito, carga fúngica e características genéticas do hospedeiro. Alguns estudos controlados e séries de casos têm demonstrado que azóis de ação rápida e derivados de sulfa constituem alternativas terapêuticas úteis nas formas mais leves da doença. Para casos moderados/graves, tratamentos mais prolongados ou mesmo por via parenteral são necessários especialmente quando há envolvimento de mucosa do trato digestivo, resultando em absorção deficiente de drogas. Embora estudos comparativos tenham relatado que esquemas terapêuticos mais curtos com itraconazol sejam capazes de induzir cura em pacientes cronicamente infectados, ainda existem desafios no tratamento, tais como a necessidade de maior número de estudos controlados envolvendo casos agudos, busca por novas drogas e combinações, compostos capazes de modular a resposta imune nos casos graves, e reações paradoxais.

Management of post-transplant Epstein-Barr virus-related lymphoproliferative disease in solid organ and hematopoietic stem cell recipients

Epstein-Barr virus (EBV)-related post-transplant lymphoproliferative disease (PTLD) is one of the most serious complications associated with solid organ and hematopoietic stem cell transplantation. PTLD is most frequently seen with primary EBV infection post-transplant, a common scenario for pediatric solid organ recipients. Risk factors for infection or reactivation of EBV following solid organ transplant are stronger immunosuppressive therapy regimens, and being seronegative for receptor. For hematopoietic stem cell transplantation, the risk factors relate to the type of transplant, human leukocyte antigen disparity, the use of stronger immunosuppressants, T-cell depletion, and severe graft-versus-host disease. Mortality is high, and most frequent in patients who develop PTLD in the first six months post-transplant. The primary goal of this article is to provide an overview of the clinical manifestations, diagnosis, accepted therapies, and management of EBV infection in transplant recipients, and to suggest that the adoption of monitoring protocols could contribute to a reduction in related complications.

The lung in paracoccidioidomycosis: new insights into old problems

OBJECTIVES: Chronic paracoccidioidomycosis can diffusely affect the lungs. Even after antifungal therapy, patients may present with residual respiratory abnormalities due to fungus-induced lung fibrosis. METHODS: A cross-sectional analysis of 50 consecutive inactive, chronic paracoccidioidomycosis patients was performed using high resolution computed tomography, pulmonary function tests, ergospirometry, the six-minute walk test and health-related quality of life questionnaires. RESULTS: Radiological abnormalities were present in 98% of cases, the most frequent of which were architectural distortion (90%), reticulate and septal thickening (88%), centrilobular and paraseptal emphysema (84%) and parenchymal bands (74%). Patients typically presented with a mild obstructive disorder and a mild reduction in diffusion capacity with preserved exercise capacity, including VO2max and six-minute walking distance. Patient evaluation with the Saint-George Respiratory Questionnaire showed low impairment in the health-related quality of life, and the Medical Research Council questionnaire indicated a low dyspnea index. There were, however, patients with significant oxygen desaturation upon exercise that was associated with respiratory distress compared with the non-desaturated patients. The initial counterimmunoelectrophoresis of these patients was higher and lung emphysema was more prominent; however, there were no differences in the interstitial fibrotic tomographic abnormalities, tobacco exposure, functional responses, exercise capacity or quality of life. CONCLUSIONS: Inactive, chronic paracoccidioidomycosis patients show persistent and disseminated radiological abnormalities by high resolution computed tomography, short impairments in pulmonary function and low impacts on aerobic capacity and quality of life. However, there was a subset of individuals whose functional impairment was more severe. These patients present with higher initial ...

Co-infection Trypanosoma cruzi/HIV: systematic review (1980 - 2010) / Coinfecção Trypanosoma cruzi/HIV: revisão sistemática (1980 - 2010)

INTRODUCTION: The co-infection Trypanosoma cruzi/HIV has been described as a clinical event of great relevance. The objective of this study wasto describe clinical and epidemiological aspects published in literature. METHODS: It is a systematic review of a descriptive nature from the databases Medline, Lilacs, SciELO, Scopus, from 1980 to 2010. RESULTS: There were 83 articles (2.8 articles/year) with a total of 291 cases. The co-infection was described in 1980 and this situation has become the defining AIDS clinical event in Brazil. This is the country with the highest number of publication (51.8 percent) followed by Argentina (27.7 percent). The majority of cases are amongst adult men (65.3 percent) native or from endemic regions with serological diagnosis in the chronic stage (97.9 percent) and indeterminate form (50.8 percent). Both diseases follow the normal course, but in 41 percent the reactivation of the Chagas disease occurs. The most severe form is the meningoencephalitis, with 100 percent of mortality without specific and early treatment of the T. cruzi. The medication of choice was the benznidazole on doses and duration normally used for the acute phase. The high parasitemia detected by direct or indirect quantitative methods indicated reactivation and its elevation is the most important predictive factor. The lower survival rate was related to the reactivation of the Chagas disease and the natural complications of both diseases. The role of the antiretroviral treatment on the co-infection cannot yet be defined by the knowledge currently existent. CONCLUSIONS: Despite the relevance of this clinical event there are still gaps to be filled.

INTRODUÇÃO: A coinfecção Trypanosoma cruzi/HIV vem sendo sistematicamente descrita como um evento clínico de grande relevância. O objetivo deste estudo foi descrever aspectos clínicos e epidemiológicos publicados na literatura científica. MÉTODOS: Trata-se de revisão sistemática, de natureza descritiva, a partir da busca nas bases Medline, Lilacs, SciELO, Scopus, de 1980 a 2010. RESULTADOS: Identificou-se 83 artigos (2,8 artigos/ano), com um total de 291 casos registrados. A coinfecção foi descrita em 1980 e, no Brasil, tornou-se evento clínico definidor de AIDS. Este é o país com maior número de publicações (51,8 por cento), seguido pela Argentina (27,7 por cento). A maioria dos casos é de homens adultos (65,3 por cento), naturais ou procedentes de regiões endêmicas, com diagnóstico sorológico, na fase crônica (97,9 por cento) e na forma indeterminada (50,8 por cento). As duas doenças evoluem naturalmente, mas em 41 por cento dos casos ocorreu reativação da doença de Chagas. A forma mais grave é a meningoencefalite, com 100 por cento de letalidade nos casos sem tratamento específico e precoce do T. cruzi. O medicamento indicado foi benznidazole, nas doses e duração utilizadas na fase aguda em imunocompetentes. O diagnóstico da reativação foi comprovado por alta parasitemia, detectada por métodos diretos ou indiretos quantitativos, sendo a sua elevação considerada fator preditivo para reativação. A menor sobrevida nacoinfecção esteve relacionada à reativação da doença de Chagas e às complicações naturais de ambas as doenças. O papel do tratamento antirretroviral sobre a evolução da coinfecção ainda não pode ser definido pelo conhecimento existente. CONCLUSÕES: Apesar da relevância deste evento clínico, ainda persistem lacunas a serem preenchidas.

Acute Chagas disease outbreak associated with oral transmission / Surto de doença de Chagas aguda associada à transmissão oral

Seven individuals living in a town in the Southwest of Bahia developed sudden signs of cardiac and systemic impairment, with lethality of 28.6 percent. Serological tests were positive at least in one test in the five patients examined. Forty percent of the Triatoma sordida mynphs found inside or around Trypanosoma cruzi were found by blood culturig in there out five cases the homes of these cases were positive for Trypanosoma cruzi. Transmission probably occurred through consumption of water contaminated with triatomine feces. These findings emphasize the necessity to evaluation the importance of vectors like Triatoma sordida in maintaining the endemicity of this disease.

Sete indivíduos que viviam em uma cidade do sudoeste da Bahia desenvolveram sinais súbitos de envolvimento cardíaco e sistêmico com letalidade de 28,6 por cento Trypanosoma cruzi foi isolado por hemocultura em três de cinco casos examinados. Testes sorológicos foram positivos em mais de um teste nos cinco pacientes, que os realizaram. Qinquenta por cento dos Triatoma sordida encontrados na residência ou no peridomicilio dos casos estavam positivos para Trypanosoma cruzi. A transmissão provavelmente foi devido à ingestão de água contaminada por fezes de triatomíneos. Estes achados enfatizam a necessidade de se avaliar a importância de vetores como Triatoma sordida na manutenção da endemicidade da doença.

Kinetics of IFN-gamma, TNF-alpha, IL-10 and IL-4 production by mononuclear cells stimulated with gp43 peptides, in patients cured of paracoccidioidomycosis

We analyzed the kinetics of cytokine production by mononuclear cells from 17 patients who had been treated for paracoccidioidomycosis, using the stimulus of gp43 peptide groups (43kDa glycoprotein of Paracoccidioides brasiliensis) at 0.1 and 1µM, gp43 (1µg/ml) and crude Paracoccidioides brasiliensis antigen (PbAg; 75µg/ml). IFN-gamma production was a maximum at 144 hours in relation to the G2 and G8 peptide groups at 1µM and was greatest at 144 hours when stimulated by gp43 and by PbAg. The maximum TNF-alpha production was at 144 hours for the G2 group (0.1µM) and for gp43. IL-10 production was highest after 48 and 72 hours for G7 and G6 at 1µM, respectively. We also suggest the best time for analysis of IL4 production. These results may contribute towards future studies with gp43 peptides and encourage further investigations with the aim of understanding the influence of these peptides on the production of inflammatory and regulatory cytokines.

Analisamos a cinética da produção de citocinas de células mononucleares de 17 pacientes com paracoccidioidomicose tratada, usando como estímulo: grupos de peptídeos da gp43 (glicoproteina de 43kDa de Paracoccidioides brasiliensis) a 0,1 e 1µM, gp43 (1µg/mL) e antígeno bruto de Paracoccidioides brasiliensis - AgPb (75µg/mL). A produção de IFN-gama foi máxima em 144 horas frente aos grupos de peptídeos G2 e G8 a 1µM e maior em 144 horas quando estimuladas por gp43 e por AgPb. A produção de TNF-alfa foi máxima em 144 horas para G2 (0,1µM) e para gp43. A produção de IL-10 foi maior após 48 e 72 horas para G7 e G6 a 1µM, respectivamente. Sugerimos também o melhor período para a análise da produção de IL4. Tais resultados podem contribuir para estudos com peptídeos da gp43, estimulando investigações posteriores visando entender a influência de tais peptídeos na produção de citocinas inflamatórias e regulatórias.

Posaconazole treatment of refractory eumycetoma and chromoblastomycosis

Eumicetoma e cromoblastomicose são infecções fúngicas crônicas do tecido subcutâneo que evoluem com aspecto desfigurado, raramente involuindo espontaneamente. A maioria dos pacientes não apresenta melhora sustentada por longo tempo com os tratamentos disponíveis, sendo de grande importância as novas opções terapêuticas. A eficácia do posaconazol, um novo agente antifúngico de amplo espectro do grupo dos triazóis, foi estudada em 12 pacientes com eumicetoma ou cromoblastomicose refratária às terapêuticas antifúngicas disponíveis. Os pacientes receberam por no máximo 34 meses, doses divididas de 800 mg/dia de posaconazol. Resposta clínica parcial ou completa foi considerada como sucesso; doença estável ou falha terapêutica foi considerada como insucesso. Todos os 12 pacientes tinham infecções comprovadas ou prováveis, refratárias à terapêutica padrão preconizada. Sucesso clínico foi registrado em cinco de seis pacientes com eumicetoma e cinco de seis pacientes com cromoblastomicose. Em dois pacientes observou-se doença estável. Como parte do protocolo de extensão do tratamento, dois pacientes com eumicetoma que inicialmente tinham tido sucesso terapêutico e que após um intervalo maior de 10 meses apresentaram recidiva da micose, foram retratados com sucesso com posaconazol. Posaconazol foi bem tolerado durante o longo período de administração (até 1015 dias). A terapêutica com posaconazol foi seguida de sucesso na maioria dos pacientes com eumicetoma ou cromoblastomicose refratária à terapêutica padrão, sugerindo que tal droga possa ser uma importante opção no tratamento de tais doenças.