Intradermal injection of Pythium insidiosum protein antigens for improved diagnosis and treatment of pythiosis in an experimental model

Abstract

The oomycetous pathogen Pythium insidiosum is the causative agent of pythiosis, a life-threatening disease that affects animals and humans. This infectious disease is difficult to treat, and early and accurate diagnosis is critical for effective treatment. In this sense, this study aimed to evaluate the intradermal (ID) injection of P. insidiosum protein antigens (PiPA) for the diagnosis and treatment of pythiosis using an experimental model. For diagnostic purposes, PiPA were injected by the ID route in the following groups of rabbits: (a) control; (b) previously immunized with PiPA injected by the subcutaneous (SC) route; and (c) infected with P. insidiosum zoospores. For treatment purposes, rabbits with pythiosis were also treated with PiPA by the ID or SC routes. Mean induration sizes were different at 24 h and 72 h readings when compared to the control group. Sensitivity of the protocol was 100% at 24 h and 80% at 72 h, with 100% specificity in both readings. PiPA treatment using ID or SC routes did not result in significant differences in lesion sizes and cure rates; however, serum levels of interferon-gamma were higher in SC route. This study demonstrates the applicability of PiPA ID for diagnosis and treatment of pythiosis in an experimental model.

History and Perspective of Immunotherapy for Pythiosis

“…An APC should process an immunomodulating antigen of P. insidiosum, such as (1,3)(1,6)-β-glucan, which is a main cell wall component [251,253,254], before priming a resulting antigenic epitope to a naïve T cell (via MHC-TCR complex) [242,243]. This cellular interaction might trigger the release of IFNγ and IL-2 for enhancing the differentiation of Th0 to Th1 cell and Th0 to regulatory T (Treg) cell, respectively [242,246,251,252,255,256]. The Th1 cell produces IFN-γ to activate the macrophages and cytotoxic T lymphocytes [131,142,242,244,246,251,253,256].…”

“…Therefore, a multicentric prospective clinical study should be performed to gain insights into the pharmacologic properties of PIA, such as efficacy, adverse effect, optimal dose, and antigen administration. The rabbit model of pythiosis has been established to investigate PIA immunotherapeutic properties [122,250,255,261]. Such an animal model shows atypical manifestations (i.e., cutaneous nodules) compared with pythiosis in the natural hosts (i.e., humans and various animals) [50,97,122,216,224,[262][263][264].…”