Paracoccidioidomycosis: Challenges in the Development of a Vaccine Against an Endemic Mycosis in the Americas

Abstract

SUMMARYParacoccidioidomycosis (PCM), caused by Paracoccidioides spp, is an important endemic mycosis in Latin America. There are two recognized Paracoccidioides species, P. brasiliensis and P. lutzii, based on phylogenetic differences; however, the pathogenesis and disease manifestations of both are indistinguishable at present. Approximately 1,853 (~51,2%) of 3,583 confirmed deaths in Brazil due to systemic mycoses from 1996-2006 were caused by PCM. Antifungal treatment is required for patients with PCM. The initial treatment lasts from two to six months and sulfa derivatives, amphotericin B, azoles and terbinafine are used in clinical practice; however, despite prolonged therapy, relapses are still a problem. An effective Th1-biased cellular immune response is essential to control the disease, which can be induced by exogenous antigens or modulated by prophylactic or therapeutic vaccines. Stimulation of B cells or passive transference of monoclonal antibodies are also important means that may be used to improve the efficacy of paracoccidioidomycosis treatment in the future. This review critically details major challenges facing the development of a vaccine to combat PCM.

Brazilian guidelines for the clinical management of paracoccidioidomycosis

“…infection in humans is not available, although promising results have been observed in laboratory animals 109 . Recommendations for the prevention of PCM derive from knowledge of the most obvious infection situations, which occur as a result of aerial exposure to conidia in endemic areas and predisposing risk factors.…”

II Consenso Brasileiro em Paracoccidioidomicose - 2017*

“…Não existe vacina disponível para prevenir a infecção humana por Paracoccidioides spp, embora resultados promissores tenham sido obtidos em animais de laboratório. 109 Recomendações para a prevenção da PCM podem ser propostas a partir do conhecimento das situações mais evidentes de infecção após exposição aérea a conídios em áreas endêmicas, assim como dos fatores predisponentes da doença.…”

Immunotherapy against Systemic Fungal Infections Based on Monoclonal Antibodies

“…PCM presents two major clinical forms: (a) Acute/subacute or juvenile, characterized by fast progress and significant mortality rate; (b) chronic or adult PCM, which represents 90% of cases, and is characterized by gradual progress, typically occurring in male individuals older than 30 years [120,123,125,126,128]. P. brasiliensis and P. lutzii are susceptible to most of the systemic antimycotic medications as well as sulfamthoxazole/trimethoprim [125,126] and the treatment for PCM involves antifungal chemotherapy administered for prolonged periods, varying from patient to patient, depending on the chosen drug, the clinical manifestations and the progress of the disease [111,126,129]. Generally, extended periods of treatment are required-two or even more years-with a considerable chance of relapse [111,129].…”

“…P. brasiliensis and P. lutzii are susceptible to most of the systemic antimycotic medications as well as sulfamthoxazole/trimethoprim [125,126] and the treatment for PCM involves antifungal chemotherapy administered for prolonged periods, varying from patient to patient, depending on the chosen drug, the clinical manifestations and the progress of the disease [111,126,129]. Generally, extended periods of treatment are required-two or even more years-with a considerable chance of relapse [111,129]. Drug options include sulfonamide derivates, amphotericin B, azole derivates and terbinafine, but the most commonly used are itraconazole or sulfamethoxazole/trimethoprim for mild to moderate disease and amphotericin B for severe manifestations [126,129].…”