Conidiobolomycosis with neurological commitment in sheep in Pará, Brazil

Conidiobolomicose com comprometimento neurológico em ovino no Pará, Brasil

ABSTRACT:

The study was conducted on a 3-year-old female Santa Inês sheep from a property located in the municipality of Santo Antônio de Tauá, west of Pará. The affected animal had a history of exophthalmos in the left eye, nasal discharge, and breathing difficulty for more than three months. On physical examination, the animal had a low body score, apathy, unilateral facial asymmetry, moderate unilateral left exophthalmos, mixed dyspnea and unilateral profuse serosanguinous nasal discharge. At necropsy, a large nasal mass was observed, predominantly yellowish-white with blackish-red areas, with an irregular, finely granular, moist, and friable surface. The mass invaded from the mucocutaneous junction of the left nostril to the choanae, infiltrated the frontal sinuses, the cribiform plate, and reached the meninges and the frontal portion of the brain. Microscopy of the surface of the nasal epithelium showed severe destruction of the turbinates and epithelia, evidenced by extensive areas of necrosis with a large amount of cellular debris, ulceration, and secondary bacterial infection. In the central nervous system there was pyogranulomatous meningitis with marked vessel congestion, as well as foci of necrosis and granulomatous inflammation. Immunohistochemistry showed intense staining of numerous intralesional hyphae for antibodies against Conidiobolus lamprauges. The diagnosis of granulomatous rhinitis of mycotic origin associated with the Conidiobolus lamprauges was based on epidemiological, clinical-pathological, and immunohistochemical data.

Key words:
fungus; Conidiobolus lamprauges; central nervous system; Amazon

RESUMO:

O estudo foi realizado em um ovino, fêmea, de três anos de idade, da raça santa inês, procedente de uma propriedade localizada do município de Santo Antônio de Tauá, oeste do Pará. O animal acometido tinha histórico de exoftalmia no olho esquerdo, secreção nasal e dificuldade respiratória há mais de três meses. Ao exame físico o animal apresentava baixo escore corporal, apatia, assimetria facial unilateral, moderada exoftalmia unilateral esquerda, dispneia mista e exsudação nasal serossanguinolenta profusa unilateral. À necropsia, foi observada grande massa nasal, predominantemente branco-amarelada com áreas vermelho enegrecidas, de superfície irregular, finamente granular, úmida e friável. A massa invadia desde a junção mucocutânea do nariz esquerdo até as coanas, se infiltrava pelos seios nasais frontais, placa cribiforme e alcançava as meninges e a porção frontal do cérebro. À microscopia da superfície do epitélio nasal notou-se severa destruição dos cornetos e dos epitélios, evidenciada por extensas áreas de necrose com muitos debris celulares, ulceração e infecção bacteriana secundária. No sistema nervoso central (SNC) havia meningite piogranulomatosa com acentuada congestão de vasos, focos de necrose e inflamação granulomatosa. O diagnóstico de rinite granulomatosa de origem micótica associada ao fungo Conidiobolus lamprauges foi baseado nos achados da imuno-histoquímica.

Palavras-chave:
fungo; Conidiobolus lamprauges; sistema nervoso central; Amazônia

INTRODUCTION

The Amazon biome is characterized by high temperatures, high relative humidity and rainfall, that favor to the appearance of diseases caused by fungi, such as conidiobolomycosis, caused by Conidiobolus spp. This is an opportunistic saprophytic fungus with a predilection for the respiratory tract, but it can also affect the heart, skeletal muscles, kidneys, and brain or promote generalized infections in immunosuppressed patients (RIBES et al., 2000; SILVA et al., 2010; DE PAULA et al., 2010).

Two clinical forms of the disease have been linked to Conidiobolus spp. in sheep. The rhinofacial form is characterized by an increase in volume in the nasal vestibule, mucocutaneous junction of the nose, skin of the anterior region of the face and upper lip, with ulcerated lesions on the nasal mucosa and hard palate (SILVA et al., 2007a; RIET-CORREA et al., 2008). The nasopharyngeal form affects mainly the ethmoid region, pharynx, and paranasal sinuses; the sheep may present with dyspnea, nasal exudation, stridor, craniofacial asymmetry, and unilateral exophthalmos (SILVA et al., 2007a; RIET-CORREA et al., 2008). Clinical manifestations include apathy, anorexia, breathing difficulty, nasal discharge, fever, and stridor (SILVA et al., 2007a; SILVA et al., 2010). Necropsy findings in cases of nasopharyngeal mycosis include the presence of a nodular mass with a granular, yellow or white surface, with necrosis of the ethmoid region. The lesion extends into the sinuses, the cribiform plate, and can invade the ocular orbit and the frontal region of the brain (KETTERER et al., 1992; MORRIS et al., 2001). It is common for animals to have lesions spread to the lungs, and more rarely to the kidneys, lymph nodes, heart, liver, gallbladder, and central nervous system (CNS) (CARRIGAN et al., 1992; SILVA et al., 2007b). Histology showed multifocal chronic granulomatous inflammation, with a necrotic center containing large hyphae surrounded by Splendore-Hoeppli material. Around the area of necrosis there is a proliferation of fibrous tissue with an infiltrate of neutrophils, eosinophils, lymphocytes, epithelioid cells, and numerous multinucleated giant cells (MORRIS et al., 2001; RIET-CORREA et al., 2008). In Brazil, the disease was first reported in sheep in Piauí (SILVA et al., 2007a) and later in Paraíba (RIET-CORREA et al., 2008), Mato Grosso (BOABAID et al., 2008; UBIALI et al., 2013), Rio Grande do Sul (PEDROSO et al., 2009) and Santa Catarina (FURLAN et al., 2010). This is the first confirmed diagnosis of the disease in the state of Pará. Thisof paper reported a case of conidiobolomycosis in sheep, caused by Conidiobolus lamprauges, involving the CNS.

MATERIALS AND METHODS

The study was conducted on a 3-year-old female Santa Inês sheep from a property located in the municipality of Santo Antônio de Tauá, west of Pará. Epidemiological data, such as age, gender, breed, and type of management used on the properties, were obtained at the time of the clinical visit. General and specific clinical of the respiratory was performed (NAGY & PUGH, 2012).

The animal died as a result of the severity of its injuries. A necropsy examination was performed and the intensity and location of the lesions were assessed. The specimens of different organs and tissues collected were fixed in 10% buffered formalin and sent to the pathology department of the Universidade Federal Rural do Rio de Janeiro for histopathological examination. The tissue samples were routinely processed, embedded in paraffin, cut into 5 µm sections and stained with hematoxylin and eosin and Grocott’s methenamine silver stain.

Histological 3 µm sections of the mass from the nasopharyngeal and frontal cortex region were submitted to immunohistochemistry (IHC) with anti-Conidiobolus lamprauges and Pythium insidiosum polyclonal antibodies. The antibodies were extracted from purified rabbit serum (UBIALI et al., 2013). The slides were deparaffinized in xylene, immersed in alcohol baths, and washed in phosphate-buffered saline. Subsequently, endogenous peroxidase was blocked using 3% hydrogen peroxide for 20 min, followed by blocking nonspecific reactions with 5% milk (Molico^®). Citrate buffer (10 mM, pH 6.0) at 96 °C for 20 min was used for antigen recovery. Both primary antibody was incubated at 1:1000 at 38 °C for 3 h. The secondary antibody was streptavidin-biotin-peroxidase (LSAB + System HRP, Agilent Technologies, Santa Clara, CA, USA). The reaction occurred with the addition of 3,3′-diaminobenzidine chromogen (DAB + Substrate Chromogen System, DakoCytomation, Carpinteria, California). The slides were counterstained with Mayer’s hematoxylin. A sinus nasal previously PCR positive (conidiobolomycosis from sheep) and negative controls (healthy nasal tissue from sheep) were added simultaneosly in the test (PEREIRA et al., 2023).

RESULTS AND DISCUSSION

The affected sheep, with a history of exophthalmos in the left eye, nasal discharge, and breathing difficulty for more than three months, came from a herd of 70 animals in which, according to the keeper, two animals with similar clinical signs had already died. The herd was kept in pastures of Urochloa humidicola and Urochloa brizantha and had access to flooded areas with a large mass of decaying vegetation. On physical examination, the animal had a low body score, apathy, unilateral facial asymmetry, moderate unilateral left exophthalmos and lacrimation (Figure 1A), mixed dyspnea, unilateral profuse serosanguinous nasal discharge, sneezing, a massive sound on percussion of the frontal sinuses, an extended neck, decreased right pupillary reflex, and congestion of the episcleral vessels.

Figure 1
Conidiobolomycosis with neurological involvement in a sheep in Pará. (A) Rhinofacial swelling and unilateral left exophthalmos and lacrimation; (B-C) greenish-yellow mass, with hemorrhage and necrosis, extending over a large part of the rhinopharyngeal region toward the cribiform plate and invading the frontal cortex; (D) frontal cortex with congestion, hemorrhage, and blackish-red clots (arrow).

At necropsy, after cutting the head sagittally, a large nasal mass was observed, predominantly yellowish-white with blackish-red spots with an irregular, finely granular, moist and friable surface. The mass invaded from the mucocutaneous junction of the left nose to the choanae, infiltrated the frontal sinuses, the cribiform plate, and reached the meninges and the frontal portion of the brain (Figure 1B-D). In addition to the aforementioned structures, the mass invaded the left retrobulbar region, adhered to the eyeball and adjacent structures, and filled a large part of the orbital cavity, projecting the eye out of the orbit.

Microscopy of the surface of the nasal epithelium showed severe destruction of the turbinates and epithelia, evidenced by extensive areas of necrosis with a large amount of cellular debris, ulceration, and secondary bacterial infection, associated with numerous Splendore-Hoeppli formations, congestion/hemorrhage, and neovascularization. In the CNS there was pyogranulomatous meningitis with marked vessel congestion; foci of necrosis and granulomatous inflammation. Negative images of coenocytic hyphae, rarely septated, with irregular branching and thick walls, were observed by hematoxylin and eosin staining and enhanced by Grocott’s methenamine silver staining on the surface of the nasal epithelium and cerebral cortex, in the midst of cell debris (Figure 2A-C). Immunohistochemistry showed intense staining of numerous intralesional hyphae for antibodies against C. lamprauges (Figure 2D) and negative staining to P. insidiosum.

Figure 2
Conidiobolomycosis with neurological involvement in sheep in Pará. (A) Nasal tissue with foci of necrosis, inflammatory reaction rich in macrophages and unstained hyphae (H&E x20); (B) nasal tissue with coenocytic hyphae with thick, irregular branching enhanced by Grocott’s methenamine silver staining (x40); (C) cerebral cortex with coenocytic hyphae with thick, irregular branching enhanced by Grocott’s methenamine silver staining (x40); (D) Intense immunolabeling of hyphae inside multinucleated giant cells with antibodies against Conidiobolus lamprauges (immunohistochemistry, counterstaining with Mayer’s hematoxylin, x40).

The diagnosis of granulomatous rhinitis of mycotic origin associated with the C. lamprauges was based on epidemiological, clinical-pathological, and immunohistochemical data; this disease is often associated with this genus (CARRIGAN et al., 1992; KETTERER et al., 1992; MORRIS et al., 2001; SILVA et al., 2007a; SILVA et al., 2007b; BOABAID et al., 2008). The diagnosis was made in September in the northeast region of Pará, in flooded areas with a large mass of decomposing vegetation. In this region, the period between November and September is characterized by high rainfall, high temperatures, and high relative humidity. These environmental conditions are favorable to the development of this fungi, and similar conditions have been reported in other regions of Brazil where the disease has occurred (SILVA et al., 2007a; SILVA et al., 2007b; BOABAID et al., 2008; RIET-CORREA et al., 2008).

The low grazing habit of sheep have been described as a predisposing factor for conidiobolomycosis, as it favors contamination through the inhalation of spores because conidia can be ejected at a height of more than 2 cm from the ground (HUMBER et al., 1989; SILVA et al., 2007b). Alternatively, contamination can occur through wounds in the mucosa caused by pointy-leaved plants containing these conidia (KETTERER et al., 1992).

The clinical signs were related to upper airway involvement, which led to the animal having difficulty in breathing, an extended neck, mixed dyspnea, stridor, mucosanguinous nasal discharge, and exophthalmos. In this study, the clinical findings were similar to those already described in the literature (KETTERER et al., 1992; SILVA et al., 2007a; BOABAID et al., 2008; RIET-CORREA et al., 2008; UBIALI et al., 2013; AGUIAR et al., 2014; CARMO et al., 2020). Those authors also reported the predominance of respiratory manifestations in sheep with conidiobolomycosis. Clinical signs related to the nervous system, such as decreased alertness and loss of visual acuity, occurred as a result of the invasive lesions in the CNS. The involvement of brain structures in sheep with conidiobolomycosis has been described previously (PEIXOTO et al., 2017). However, the authors did not mention the lesions caused by the fungus in the CNS, nor did they mention the presence of hyphae. At necropsy, the main alteration was the proliferation of a yellowish mass in the region of the ethmoid bones and adjacent areas. These lesions are characteristic of rhinitis caused by Conidiobolus spp. (KETTERER et al., 1992; SILVA et al., 2007a; BOABAID et al., 2008; RIET-CORREA et al., 2008). Extranasal lesions occurring in the brain, eyeballs, lymph nodes, and lungs are frequently described in these cases (KETTERER et al., 1992; MORRIS et al., 2001; SILVA et al., 2007a; BOABAID et al., 2008; RIET-CORREA et al., 2008). The differential diagnosis of conidiobolomycosis should be made with the enzootic nasal tumor of sheep and goats (YONEMICHI et al., 1978; DE LAS HERAS et al., 1991). Differentiation between the two diseases must be made with the aid of histological examination. Oestrosis must be ruled out when there are mild rhinophyma deformities, which are often responsive to treatment (MUSTAFA et al., 2015).

Rhinofacial necrosis in sheep must be differentiated from P. insidiosum (CARMO et al., 2020). In these cases, the histological findings are similar and complementary tests are necessary to aid in the etiological diagnosis.

Involvement in this case was due to the chronic evolution of the disease. Conidiobolomycosis should be included in the differential diagnosis of nerve diseases, and we emphasized the importance of diagnosing suspected cases using histology and immunohistochemistry.

ACKNOWLEDGEMENTS

The authors are grateful to Pró-Reitoria de Pesquisa e Pós-graduação da Universidade Federal do Pará (PROPESP-UFPA) for the qualified publication support program and was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brasil - Finance code 001.

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• CR-2024-0016.R2

Edited by

Editor: Rudi Weiblen (0000-0002-1737-9817)

Publication Dates

• Publication in this collection
  28 Oct 2024
• Date of issue
  2025

History

• Received
  14 Jan 2024
• Accepted
  26 June 2024
• Reviewed
  26 Aug 2024