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.

Background:This review article summarizes and updates the knowledge on paracoccidioidomycosis. P lutzii and the cryptic species of P. brasiliensis and their geographical distribution in Latin America, explaining the difficulties observed in the serological diagnosis.Objectives:Emphasis has been placed on some genetic factors as predisposing condition for paracoccidioidomycosis. Veterinary aspects were focused, showing the wide distribution of infection among animals. The cell-mediated immunity was better characterized, incorporating the recent findings.Methods:Serological methods for diagnosis were also compared for their parameters of accuracy, including the analysis of relapse.Results:Clinical forms have been better classified in order to include the pictures less frequently observesiod.Conclusion:Itraconazole and the trimethoprim-sulfamethoxazole combination was compared regarding efficacy, effectiveness and safety, demonstrating that azole should be the first choice in the treatment of paracoccidioidomycosis.

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.

BackgroundThere are no published reports on studies comparing itraconazole (ITC), sulfamethoxazole-trimethoprim (cotrimoxazole, CMX), and ITC followed by CMX (ITC/CMX) in the treatment of paracoccidiodomycosis. This study aimed to compare the efficacy, effectiveness, safety and time to clinical and serologic cure in paracoccidioidomycosis patients treated with ITC or CMX, the antifungal agents most widely used.MethodologyA quasi-experimental study was performed in 177 patients with a confirmed or probable diagnosis of paracoccidioidomycosis. Treatment was divided into two stages: 1) initial, which was continued until clinical cure was achieved and the erythrocyte sedimentation rate decreased to normal values; 2) complementary, which was continued until serologic cure was achieved. Medians were compared via the Mann-Whitney test, and frequencies were compared via the chi-squared test. The assessment of variables as a function of time was performed using Kaplan-Meier curves and Cox regression. The significance level was established as p≤0.05.Principal FindingsNo difference was found in the efficacy and effectiveness of the initial treatment of 47 individuals given ITC and 130 individuals given CMX; however, the time to clinical cure was shorter in the former compared with the latter group (105 vs. 159 days; p = 0.001), specifically in patients with the chronic form. Efficacy and effectiveness of the three regimens were similar in the complementary treatment; however, the time to serologic cure was shorter when ITC (161 days) or CMX (495 days) was used compared with ITC/CMX (881 days) [p = 0.02]. The independent predictors of a shorter time to serologic cure were treatment with ITC [risk ratio = 6.61 (2.01–21.75)] or with CMX [risk ratio = 5.11 (1.91–13.67)]). The prevalence of side effects was lower with ITC (6.4%) than with CMX (20.0%; p = 0.03).ConclusionsSince ITC induced earlier clinical cure and was better tolerated than CMX, such triazole should be considered the first-choice for PCM treatment.

A review of 400 clinical records of paracoccidioidomycosis (PCM) patients, 93 with the acute/subacute (AF) and 307 with the chronic form (CF), attended from 1977 to 2011, selected as to the schedule of release for study by the Office of Medical Records at the University Hospital of the Faculdade de Medicina de Botucatu – São Paulo State University – UNESP, was performed to detect cases in relapse. The control of cure was performed by clinical and serological evaluation using the double agar gel immunodiffusion test (DID). In the diagnosis of relapse, DID, enzyme-linked immunosorbent assay (ELISA) and immunoblotting assay (IBgp70 and IBgp43) were evaluated. Out of 400 patients, 21 (5.2%) went through relapse, 18 of them were male and 3 were female, 6∶1 male/female ratio. Out of the 21 patients in relapse, 15 (4.8%) showed the CF, and 6 (6.4%) the AF (p>0.05). The sensitivity of DID and ELISA before treatment was the same (76.1%). DID presented higher sensitivity in pre-treatment (80%) than at relapse (45%; p = 0.017), while ELISA showed the same sensitivity (80% vs 65%; p = 0.125). The serological methods for identifying PCM patients in relapse showed low rates of sensitivity, from 12.5% in IBgp70 to 65.0% in IBgp43 identification and 68.8% in ELISA. The sensitivity of ELISA in diagnosing PCM relapse showed a strong tendency to be higher than DID (p = 0.06) and is equal to IBgp43 (p = 0.11). In sum, prevalence of relapse was not high in PCM patients whose treatment duration was based on immunological parameters. However, the used methods for serological diagnosis present low sensitivity. While more accurate serological methods are not available, we pay special attention to the mycological and histopathological diagnosis of PCM relapse. Hence, direct mycological, cytopathological, and histopathological examinations and isolation in culture for P. brasiliensis must be appropriately and routinely performed when the hypothesis of relapse is considered.