Abstract
The fungus-like microorganism Pythium insidiosum causes pythiosis, a life-threatening infectious disease increasingly reported worldwide. Antimicrobial drugs are ineffective. Radical surgery is an essential treatment. Pythiosis can resume post-surgically. Immunotherapy using P. insidiosum antigens (PIA) has emerged as an alternative treatment. This review aims at providing up-to-date information of the immunotherapeutic PIA, with the focus on its history, preparation, clinical application, outcome, mechanism, and recent advances, in order to promote the proper use and future development of this treatment modality. P. insidiosum crude extract is the primary source of immunotherapeutic antigens. Based on 967 documented human and animal (mainly horses) pythiosis cases, PIA immunotherapy reduced disease morbidity and mortality. Concerning clinical outcomes, 19.4% of PIA-immunized human patients succumbed to vascular pythiosis instead of 41.0% in unimmunized cases. PIA immunotherapy may not provide an advantage in a local P. insidiosum infection of the eye. Both PIA-immunized and unimmunized horses with pythiosis showed a similar survival rate of ~70%; however, demands for surgical intervention were much lesser in the immunized cases (22.8% vs. 75.2%). The proposed PIA action involves switching the non-protective T-helper-2 to protective T-helper-1 mediated immunity. By exploring the available P. insidiosum genome data, synthetic peptides, recombinant proteins, and nucleic acids are potential sources of the immunotherapeutic antigens worth investigating. The PIA therapeutic property needs improvement for a better prognosis of pythiosis patients.
Highlights
The P. insidiosum antigens (PIA) immunotherapy may not provide an advantage in a local P. insidiosum infection of the eye
The PIA formulation containing the crude antigenic extracts of P. insidiosum has been clinically used over the past decades
As the final clinical outcomes, 19.4% of PIA-immunized human patients succumbed to vascular pythiosis instead of 41.0% in unimmunized cases
Summary
Pythiosis is a life-threatening infectious disease [1,2,3,4,5,6,7] that has been increasingly reported in humans [8,9,10,11,12,13], horses [14,15,16,17,18,19], dogs [20,21,22,23], cats [24,25,26,27], camels [28,29], and some other animals [30,31,32,33,34] living in tropical and subtropical areas worldwide. In 1986, Mendoza et al reported a different PIA formulation for treating five horses with cutaneous pythiosis in Costa Rica [120] Their formulation contains culture filtrate antigens (CFA; representing exoantigens or extracellular proteins) prepared by ether precipitation of P. insidiosum hyphae-removed culture broth [120]. It cured three out of five horses with pythiosis (60%), exhibited a relatively long shelf life (~8 months), and demonstrated minimal skin reaction with no sterile abscess at the injection site. Lyophilization can preserve the extracted antigens at room temperature for at least one year [122]
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