Outcomes and factors influencing prognosis in patients with vascular pythiosis

Sermsathanasawadi, Nuttawut; Praditsuktavorn, Banjerd; Hongku, Kiattisak; Wongwanit, Chumpol; Chinsakchai, Khamin; Ruangsetakit, Chanean; Hahtapornsawan, Suteekhanit; Mutirangura, Pramook

doi:10.1016/j.jvs.2015.12.024

Cited by 25 publications

(52 citation statements)

References 14 publications

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“…In our study, definitive surgery was performed in 49 of 50 (98%) patients. This is likely the reason why the mortality rate in our study decreased to 10% from 36.4% to 44.4% in the previous studies (13,14,29). As expected, patients who survived had a significant shorter mean duration from the onset of disease to their first medical encounters as well as a shorter mean waiting time for their definitive surgeries.…”

Section: Discussionsupporting

confidence: 56%

Monitoring Anti-Pythium insidiosum IgG Antibodies and (1→3)-β-d-Glucan in Vascular Pythiosis

et al. 2018

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Despite aggressive treatment, vascular pythiosis has a mortality rate of 40%. This is due to delays in diagnosis and a lack of effective monitoring tools. To overcome this drawback, serum beta-d-glucan (BG) and -specific antibody (-Ab) were examined as potential monitoring markers in vascular pythiosis. A prospective cohort study of vascular pythiosis patients was carried out from January 2010 to July 2016. Clinical information and blood samples were collected and evaluated by the BG and -Ab assays. Linear mixed-effect models were used to compare BG and-Ab levels. The susceptibility test was performed with all isolates from culture-positive cases. A total of 50 patients were enrolled: 45 survived and 5 died during follow-up. The survivors had a significantly shorter time to medical care ( < 0.0001) and a significantly shorter waiting time to the first surgery ( < 0.0001). There were no differences in BG levels among the groups at diagnosis ( = 0.33); however, BG levels among survivors were significantly lower than those of the deceased group at 0.5 months ( < 0.0001) and became undetectable after 3 months. Survivors were able to maintain an enzyme-linked immunosorbent assay (ELISA) value (EV) of -Ab above 8, whereas the EV among deceased patients was less than 4. susceptibility results revealed no synergistic effects between itraconazole and terbinafine. This study showed that BG and -Ab are potentially valuable markers to monitor the disease after treatment initiation. An unchanged BG level at 2 weeks after surgery should prompt an evaluation for residual disease.

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Section: Discussionsupporting

confidence: 56%

Monitoring Anti-Pythium insidiosum IgG Antibodies and (1→3)-β-d-Glucan in Vascular Pythiosis

et al. 2018

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“…Previous data support claims that PiV proteins have the ability to modulate the Th2 response in cases of pythiosis to a Th1 response after successful immunotherapy [2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 23]. Using the mouse Leishmania model, we demonstrated that the Th2 response in place during experimental L. major mice experimental infection of BALB/c mice, switched to a polarized Th1 response.…”

Section: Discussionsupporting

confidence: 79%

“…However, few immunotherapeutic proteins of microbial origin are presently being considered for immunotherapy; one of them is PiV, while the rest represent antigenic epitopes harvested from cancer patients [33, 37]. So far, PiV antigenic preparation has shown minimal or no side effects in experimental animals (1,2,10,13, this study), and in cured humans and animals with pythiosis [3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 14, 23]. Based on these results, we anticipate further interest in PiV immunomodulatory capabilities applied to other infectious and non-infectious processes that otherwise involve a non-curative Th2 response.…”

Section: Discussionmentioning

confidence: 99%

“…These authors linked the curative properties of P. insidiosum ’ s extracts to a change from an eosinophilic granuloma to a lymphocytic mononuclear cell response, which they proposed was key in the killing of P. insidiosum ’ s hyphae in infected tissues [3, 4]. Since then, PiV immunogens have been successful in humans [5, 6, 7, 8], cattle [2], dogs [9, 10, 11] and horses [12, 13, 14] with pythiosis. It was later found in successfully treated mammals that in addition to the switching from an eosinophilic to a mononuclear cell response, a shift from a Th2 to a Th1 cytokine profile occurred [2].…”

Section: Introductionmentioning

confidence: 99%

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A Leishmania murine model to evaluate the immunomodulatory properties of Pythium insidiosum proteins

Inêz-Ferreira

Mendoza

Vilela

et al. 2017

Heliyon

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Pythium insidiosum immunomodulatory vaccine (PiV) has been tested in clinical and experimental pythiosis. Previous data showed that P. insidiosum immunogens have the ability to switch the Th2 immune response, normally in place during pythiosis, to a curative Th1 response. Pythiosis cannot be reproduced in experimental rodents with the exception of rabbits, and thus thorough evaluation of PiV´s immunomodulatory properties has been limited by the lack of a compatible inbred mouse model. In this study, we took advantage of the murine BALB/c Leishmania infection model, where infected mice produce a Th2 response, to evaluate the PiV Th2 to Th1 immunomodulatory potential. Twenty-one days following challenge with L. major, large cutaneous granulomas developed in control mice, consistent with the expected Th2 response. In contrast, Leishmania-induced cutaneous lesions in PiV-immunized mice were minimal or absent. Flow cytometry analysis of spleen cells from mice immunized with PiV and subsequently challenged with L. major displayed more CD4+ and CD8+ cells than the control group. Moreover, spleen cells from mice that were immunized with PiV then challenged with L. major secreted high levels of IFN-γ, with a moderate IL-2, IL-4, and IL-10 mixed cytokine profile upon in vitro re-stimulation with PiV. Anti-P. insidiosum IgG1 in immunized animals was present at low titers suggesting a minor immunological role for this Ig isotype in this model. Our preliminary data showed that BALB/c mice challenged with L. major represent an attractive model in which to study PiV´s immunomodulatory properties.

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“…In our study, definitive surgery was performed in 49/50 (98%) patients. This is likely the reason why the mortality rate in our study decreased to 10% from 36.4%-44.4% in the previous studies (2, 3, 17). As expected, patients who survived had a significant shorter mean duration from the onset of disease to their first medical encounters as well as a shorter mean waiting time for their definitive surgeries.…”

Section: Discussioncontrasting

confidence: 57%

Monitoring Anti-Pythium insidiosum IgG Antibodies and (1->3)-β-D-Glucan in Vascular Pythiosis

Worasilchai¹,

Permpalung

Chongsathidkiet

et al. 2018

Preprint

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41Background: Despite aggressive treatment, vascular pythiosis has a mortality rate of 40%. This 42 is due to the delay in diagnosis and lack of effective monitoring tools. To overcome this 43 drawback, serum beta-D-glucan (BG) and P. insidiosum specific antibody (Pi-Ab) were 44 examined as potential monitoring markers in vascular pythiosis. 45 Methods: A prospective cohort study of vascular pythiosis patients was carried on during 46 January 2010-July 2016. Clinical information and blood samples were collected and evaluated by 47 the BG and Pi-Ab assays. Linear mixed effect models were used to compare BG and Pi-Ab 48 levels. The in vitro susceptibility test was performed in all P. insidiosum isolates from culture 49 positive cases.50Results: A total of 50 patients were enrolled; 45 survived and 5 died during follow-up. The 51 survivors had a significantly shorter time to medical care (p<0.0001) and a significantly shorter 52 waiting time to the first surgery (p<0.0001). There were no differences in BG levels among the 53 groups at diagnosis (p=0.17); however, BG levels among survivors were significantly lower than 54 the deceased group at 0.5 months (p<0.0001) and became undetectable after 3 months. Survivors 55 were able to maintain ELISA value (EV) of Pi-Ab above 8, whereas EV among deceased 56 patients was less than 4. In vitro susceptibility results revealed no synergistic effects between 57 itraconazole and terbinafine. 58Conclusions: This study showed that BG and Pi-Ab were potentially valuable markers to 59 monitor the disease after treatment initiation. An unchanged BG level at 2 weeks after surgery 60 should prompt an evaluation for residual disease. 61Pythium insidiosum (P. insidiosum). Vascular pythiosis almost always occurs in patients with 64 underlying hemoglobinopathy complicated by hemochromatosis (1-4). Despite state-of-the-art 65 treatments, the mortality rate of vascular pythiosis is still at 40% (1) and its morbidity, among 66 survivors, is severe due to the need for aggressive amputation to remove all infected tissues (2). 67Currently, the following diagnostic criteria are used (1, 2). Presence of typical 68 pathological features, successful isolation of P. insidiosum (2), positivity for P. insidiosum 69 specific antibody (Pi-Ab) by western blot (5) or enzyme-linked immunosorbent assay (ELISA) 70 (6), and positive PCR using internal transcribed spacer and cytochrome oxidase II (PCR-71 ITS/COX2) primers (7-9). Positive culture in conjunction with zoospore production remains the 72 gold standard (10). 73 Treatment practices vary across different institutions (2, 6). At King Chulalongkorn 74 Memorial Hospital (KCMH), aggressive surgery, systemic antifungal therapy with a combination 75 of itraconazole and terbinafine (ITC/TRB) as well as the adjunctive use of P. insidiosum 76 immunotherapy (PIAI) have been recommended in all vascular pythiosis patients under our 77 institutional research protocols (2). A year course of ITC/TRB has been recommended based on 78 a case report of P. insidiosum peri...

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Outcomes and factors influencing prognosis in patients with vascular pythiosis

Cited by 25 publications

References 14 publications

Monitoring Anti-Pythium insidiosum IgG Antibodies and (1→3)-β-d-Glucan in Vascular Pythiosis

Monitoring Anti-Pythium insidiosum IgG Antibodies and (1→3)-β-d-Glucan in Vascular Pythiosis

A Leishmania murine model to evaluate the immunomodulatory properties of Pythium insidiosum proteins

Monitoring Anti-Pythium insidiosum IgG Antibodies and (1->3)-β-D-Glucan in Vascular Pythiosis

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