Resumo A paracoccidioidomicose (PCM) é uma micose sistêmica, relacionada às atividades agrícolas, com incidência e prevalência subestimadas, pela ausência de notificação em várias Unidades da Federação (UFs). A evolução insidiosa do quadro clínico pode ter como consequência sequelas graves se o diagnóstico e o tratamento não forem instituídos precoce e adequadamente. Ao lado do complexo Paracoccidioides brasiliensis (P. brasiliensis), a descrição de nova espécie, Paracoccidioides lutzii (P. lutzii), em Rondônia, onde a doença alcançou níveis epidêmicos, bem como na região Centro-Oeste e no Pará, constituem-se em desafios para a instituição do diagnóstico e a urgente disponibilização de antígenos que tenham reatividade com os soros dos pacientes. Este consenso visa atualizar o primeiro consenso brasileiro em PCM, estabelecendo recomendações para o manejo clínico do paciente, com base nas evidências conhecidas. São apresentados dados de etiologia, epidemiologia, imunopatogenia, diagnóstico, terapêutica e sequelas, enfatizando-se o diagnóstico e a terapêutica, bem como recomendações e desafios atuais nessa área do conhecimento.

Abstract Paracoccidioidomycosis is a systemic fungal disease associated with agricultural activities. Its incidence and prevalence are underestimated because of the lack of reporting in several Brazilian states. If paracoccidiodomycosis is not diagnosed and treated early and adequately, endemic fungal infection may result in serious sequelae. In addition to the Paracoccidioides brasiliensis (P. brasiliensis) complex, the appearance of a new species, Paracoccidioides lutzii (P. lutzii), in Rondônia state, where the disease has reached epidemic levels, and in the country’s Midwest region and Pará state, are challenges to diagnosis and to the urgent availability of antigens that are reactive with patients’ sera. These guidelines aim to update the first Brazilian consensus on paracoccidioidomycosis by providing evidence-based recommendations for bedside patient management. The guidelines provide data on etiology, epidemiology, immunopathogenesis, diagnosis, treatment and sequelae, with emphasis on diagnosis and treatment, as well as current recommendations and challenges in this field of knowledge.

Resumen La paracoccidioidomicosis es una micosis sistémica, relacionada con las actividades agrícolas, con incidencia y prevalencia subestimadas por la ausencia de notificación en varios estados. La evolución insidiosa del cuadro clínico puede tener como consecuencia secuelas graves si el diagnóstico y el tratamiento no se establecen precoz y adecuadamente. Al lado del complejo Paracoccidioides brasiliensis (P. brasiliensis), la descripción de nueva especie, Paracoccidioides lutzii (P. lutzii) en Rondonia, donde la enfermedad alcanzó niveles epidémicos, y en la región Centro Oeste y en Pará, se constituyen en desafíos para la institución del diagnóstico y la urgente puesta a disposición de antígenos que tengan reactividad con los sueros de los pacientes. El presente consenso tiene por objeto actualizar el primer consenso brasileño en paracoccidioidomicosis, estableciendo recomendaciones para el manejo del paciente al borde del lecho, con base en las evidencias conocidas. Se presentan datos de etiología, epidemiología, inmunopatogenia, diagnóstico, terapéutica y secuelas, enfatizando el diagnóstico y terapéutica, así como recomendaciones desafíos y actuales en esta área del conocimiento.

Resumo A paracoccidioidomicose (PCM) é uma micose sistêmica, relacionada às atividades agrícolas, com incidência e prevalência subestimadas, pela ausência de notificação em várias Unidades da Federação (UFs). A evolução insidiosa do quadro clínico pode ter como consequência sequelas graves se o diagnóstico e o tratamento não forem instituídos precoce e adequadamente. Ao lado do complexo Paracoccidioides brasiliensis (P. brasiliensis), a descrição de nova espécie, Paracoccidioides lutzii (P. lutzii), em Rondônia, onde a doença alcançou níveis epidêmicos, bem como na região Centro-Oeste e no Pará, constituem-se em desafios para a instituição do diagnóstico e a urgente disponibilização de antígenos que tenham reatividade com os soros dos pacientes. Este consenso visa atualizar o primeiro consenso brasileiro em PCM, estabelecendo recomendações para o manejo clínico do paciente, com base nas evidências conhecidas. São apresentados dados de etiologia, epidemiologia, imunopatogenia, diagnóstico, terapêutica e sequelas, enfatizando-se o diagnóstico e a terapêutica, bem como recomendações e desafios atuais nessa área do conhecimento.

Abstract Paracoccidioidomycosis is a systemic fungal disease associated with agricultural activities. Its incidence and prevalence are underestimated because of the lack of reporting in several Brazilian states. If paracoccidiodomycosis is not diagnosed and treated early and adequately, endemic fungal infection may result in serious sequelae. In addition to the Paracoccidioides brasiliensis (P. brasiliensis) complex, the appearance of a new species, Paracoccidioides lutzii (P. lutzii), in Rondônia state, where the disease has reached epidemic levels, and in the country’s Midwest region and Pará state, are challenges to diagnosis and to the urgent availability of antigens that are reactive with patients’ sera. These guidelines aim to update the first Brazilian consensus on paracoccidioidomycosis by providing evidence-based recommendations for bedside patient management. The guidelines provide data on etiology, epidemiology, immunopathogenesis, diagnosis, treatment and sequelae, with emphasis on diagnosis and treatment, as well as current recommendations and challenges in this field of knowledge.

Resumen La paracoccidioidomicosis es una micosis sistémica, relacionada con las actividades agrícolas, con incidencia y prevalencia subestimadas por la ausencia de notificación en varios estados. La evolución insidiosa del cuadro clínico puede tener como consecuencia secuelas graves si el diagnóstico y el tratamiento no se establecen precoz y adecuadamente. Al lado del complejo Paracoccidioides brasiliensis (P. brasiliensis), la descripción de nueva especie, Paracoccidioides lutzii (P. lutzii) en Rondonia, donde la enfermedad alcanzó niveles epidémicos, y en la región Centro Oeste y en Pará, se constituyen en desafíos para la institución del diagnóstico y la urgente puesta a disposición de antígenos que tengan reactividad con los sueros de los pacientes. El presente consenso tiene por objeto actualizar el primer consenso brasileño en paracoccidioidomicosis, estableciendo recomendaciones para el manejo del paciente al borde del lecho, con base en las evidencias conocidas. Se presentan datos de etiología, epidemiología, inmunopatogenia, diagnóstico, terapéutica y secuelas, enfatizando el diagnóstico y terapéutica, así como recomendaciones desafíos y actuales en esta área del conocimiento.

Abstract Paracoccidioidomycosis is a systemic fungal disease occurring in Latin America that is associated with rural environments and agricultural activities. However, the incidence and prevalence of paracoccidiodomycosis is underestimated because of the lack of compulsory notification. If paracoccidiodomycosis is not diagnosed and treated early and adequately, the endemic fungal infection could result in serious sequelae. While the Paracoccidioides brasiliensis ( P. brasiliensis ) complex has been known to be the causal agent of paracoccidiodomycosis, a new species, Paracoccidioides lutzii ( P. lutzii ), has been reported in Rondônia, where the disease has reached epidemic levels, and in the Central West and Pará. Accurate diagnoses and availability of antigens that are reactive with the patients’ sera remain significant challenges. Therefore, the present guidelines aims to update the first Brazilian consensus on paracoccidioidomycosis by providing evidence-based recommendations for bedside patient management. This consensus summarizes etiological, ecoepidemiological, molecular epidemiological, and immunopathological data, with emphasis on clinical, microbiological, and serological diagnosis and management of clinical forms and sequelae, as well as in patients with comorbidities and immunosuppression. The consensus also includes discussion of outpatient treatments, severe disease forms, disease prevalence among special populations and resource-poor settings, a brief review of prevention and control measures, current challenges and recommendations.

One hundred and thirty cases of diarrhea and 43 age-matched controls, 0 to 5 years old, were studied in a pediatric outpatient unit from a poor peri urban area of Porto Velho, Rondônia. Eighty percent of diarrheal cases were observed in the groups under 2 years of age. Rotavirus (19.2%) was the most frequent enteropathogen associated with diarrhea, followed by Shigella flexneri (6.15%) and S. sonnei (1.5%) and Salmonella sp. (6.9%). Four cases of E. coli enterotoxigenic infections (3.1%), E. coli enteropathogenic (EPEC)(2.3%) one case of E. coli enteroinvasive infection (0.8%) and one case of Yersinia enterocolitica (0.8%) were also identified. Mixed infections were frequent, associating rotavirus, EPEC and Salmonella sp. with Entamoeba histolytica and Giardia lamblia.

From March 1996 to August 1997, a study was carried out in a malaria endemic area of the Brazilian Amazon region. In vivo sensitivity evaluation to antimalarial drugs was performed in 129 patients. Blood samples (0.5 ml) were drawn from each patient and cryopreserved to proceed to in vitro studies. In vitro sensitivity evaluation performed using a radioisotope method was carried out with the cryopreserved samples from September to December 1997. Thirty-one samples were tested for chloroquine, mefloquine, halofantrine, quinine, arteether and atovaquone. Resistance was evidenced in 96.6% (29/30) of the samples tested for chloroquine, 3.3% (1/30) for quinine, none (0/30) for mefloquine and none for halofantrine (0/30). Overall low sensitivity was evidenced in 10% of the samples tested for quinine, 22.5% tested for halofantrine and in 20% tested for mefloquine. Means of IC 50 values were 132.2 (SD: 46.5) ng/ml for chloroquine, 130.6 (SD: 49.6) ng/ml for quinine, 3.4 (SD: 1.3) ng/ml for mefloquine, 0.7 (SD: 0.3) ng/ml for halofantrine, 1 (SD: 0.6) ng/ml for arteether and 0.4 (SD: 0.2) ng/ml for atovaquone. Means of chloroquine IC 50 of the tested samples were comparable to that of the chloroquine-resistant strain W2 (137.57 ng/ml) and nearly nine times higher than that of the chloroquine-sensitive strain D6 (15.09 ng/ml). Means of quinine IC 50 of the tested samples were 1.7 times higher than that of the low sensitivity strain W2 (74.84 ng/ml) and nearly five times higher than that of the quinine-sensitive strain D6 (27.53 ng/ml). These results disclose in vitro high resistance levels to chloroquine, low sensitivity to quinine and evidence of decreasing sensitivity to mefloquine and halofantrine in the area under evaluation.