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1.
Med Mycol ; 62(3)2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38425102

RESUMO

Coccidioides is an endemic fungus that causes infections ranging from mild respiratory illness to life-threatening disease, and immunocompromised hosts such as solid organ transplant recipients are at higher risk for disseminated infection and mortality. Our center administers fluconazole prophylaxis to kidney transplant recipients residing in geographic areas with higher incidences of coccidioidomycosis. However, because drug-drug interactions occur between triazoles and immunosuppressants used in transplant medicine, we undertook a study to ascertain whether fluconazole prophylaxis was associated with any important safety outcomes in kidney transplant recipients. This retrospective study evaluated patients who had undergone kidney transplantation between 2016 and 2019. Data on patient demographics, transplant-related clinical information, use of fluconazole prophylaxis (200 mg daily for 6-12 months post-transplant), and patient outcomes were obtained. The primary outcome was mean estimated glomerular filtration rate (eGFR) at 12 months, comparing those who received fluconazole prophylaxis to those who did not. Secondary outcomes included mean eGFR at 3 months, 6 months, and 9 months post-transplant, patient survival, biopsy-proven graft rejection, graft loss, or a new requirement for post-transplant dialysis, all within 12 months post-transplant. The mean eGFR at 12 months was similar between both groups, with 66.4 ml/min/1.73 m² in the fluconazole prophylaxis group vs. 64.3 ml/min/1.73 m² in the non-fluconazole prophylaxis group (P = 0.55). Secondary outcomes were similar across both groups. Multivariable linear regression found no significant association between fluconazole use and graft function. Fluconazole prophylaxis for prevention of coccidioidomycosis was not associated with adverse graft outcomes in kidney transplant recipients.


Solid organ transplant recipients can be highly immune suppressed, and infection with Coccidioides (valley fever) after transplant can lead to severe infections in these patients. Our study showed that fluconazole was safe and effective for preventing Coccidioides in kidney transplant recipients.


Assuntos
Coccidioidomicose , Transplante de Rim , Humanos , Fluconazol/efeitos adversos , Coccidioidomicose/epidemiologia , Coccidioidomicose/veterinária , Antifúngicos/efeitos adversos , Transplante de Rim/efeitos adversos , Transplante de Rim/veterinária , Estudos Retrospectivos , Transplantados
2.
J Feline Med Surg ; 26(1): 1098612X231220047, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38189264

RESUMO

CLINICAL RELEVANCE: Invasive fungal infections (IFIs) and oomycoses (hereafter termed invasive fungal-like infections [IFLIs]) are characterised by penetration of tissues by fungal elements. The environment is the most common reservoir of infection. IFIs and IFLIs can be frustrating to treat because long treatment times are usually required and, even after attaining clinical cure, there may be a risk of relapse. Owner compliance with medication administration and recheck examinations can also decline over time. In addition, some antifungal drugs are expensive, have variable interpatient pharmacokinetic properties, can only be administered parenterally and/or have common adverse effects (AEs). Despite these limitations, treatment can be very rewarding, especially when an otherwise progressive and fatal disease is cured. AIM: In the second of a two-part article series, the spectrum of activity, mechanisms of action, pharmacokinetic and pharmacodynamic properties, and AEs of antifungal drugs are reviewed, and the treatment and prognosis of specific IFIs/IFLIs - dermatophytic pseudomycetoma, cryptococcosis, sino-orbital aspergillosis, coccidioidomycosis, histoplasmosis, sporotrichosis, phaeohyphomycosis, mucormycosis and oomycosis - are discussed. Part 1 reviewed the diagnostic approach to IFIs and IFLIs. EVIDENCE BASE: Information on antifungal drugs is drawn from pharmacokinetic studies in cats. Where such studies have not been performed, data from 'preclinical' animals (non-human studies) and human studies are reviewed. The review also draws on the wider published evidence and the authors' combined expertise in feline medicine, mycology, dermatology, clinical pathology and anatomical pathology. ABBREVIATIONS FOR ANTIFUNGAL DRUGS: AMB (amphotericin B); FC (flucytosine); FCZ (fluconazole); ISA (isavuconazole); ITZ (itraconazole); KCZ (ketoconazole); PCZ (posaconazole); TRB (terbinafine); VCZ (voriconazole).


Assuntos
Doenças do Gato , Coccidioidomicose , Infecções Fúngicas Invasivas , Gatos , Animais , Antifúngicos/uso terapêutico , Infecções Fúngicas Invasivas/veterinária , Itraconazol , Terbinafina , Coccidioidomicose/veterinária , Doenças do Gato/tratamento farmacológico
3.
J Feline Med Surg ; 26(1): 1098612X231219696, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38189288

RESUMO

CLINICAL RELEVANCE: In contrast to superficial fungal infections, such as dermatophytosis, invasive fungal infections (IFIs) are characterised by penetration of tissues by fungal elements. Disease can spread locally within a region or can disseminate haematogenously or via the lymphatics. The environment is the most common reservoir of infection. Since fungal spores are airborne, indoor cats are also susceptible to IFIs. Some environmental fungi are ubiquitous and present globally, while others are endemic or hyperendemic within specific geographic regions. Zoonotic pathogens include Microsporum canis, Sporothrix schenckii and Sporothrix brasiliensis. AIM: In the first of a two-part article series, the approach to the investigation of feline IFIs and oomycoses is reviewed. As well as tips for diagnosis, and information on the ecological niche and distribution of fungal pathogens, the review covers clinical presentation of the most common IFIs, including cryptococcosis, histoplasmosis, blastomycosis, coccidioidomycosis, sporotrichosis, phaeohyphomycosis, aspergillosis and dermatophytic pseudomycetoma, as well as the oomycoses pythiosis, lagenidiosis and paralagenidiosis. In Part 2, the spectrum of activity, mechanisms of action, pharmacokinetic and pharmacodynamic properties and adverse effects of antifungal drugs are reviewed, and the treatment and prognosis for specific IFIs and oomycoses are discussed. EVIDENCE BASE: The review draws on published evidence and the authors' combined expertise in feline medicine, mycology, dermatology, clinical pathology and anatomical pathology.


Assuntos
Doenças do Gato , Coccidioidomicose , Dermatomicoses , Histoplasmose , Infecções Fúngicas Invasivas , Gatos , Animais , Infecções Fúngicas Invasivas/veterinária , Antifúngicos/uso terapêutico , Coccidioidomicose/veterinária , Dermatomicoses/veterinária , Histoplasmose/veterinária , Doenças do Gato/diagnóstico , Doenças do Gato/tratamento farmacológico
4.
Surg Today ; 54(4): 325-330, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37555929

RESUMO

PURPOSE: Coccidioidomycosis, caused by the Coccidioides species, is a well-known disease in the Southwestern United States and North Mexico, with scattered reports in Latin America countries. While this disease is still rare in Japan and other Asian countries, its incidence has been increasing over the last two decades. Coccidioides species are highly infectious and require caution when encountered. This study presents a case series of chronic pulmonary coccidioidomycosis surgically treated at a single institution. METHODS: We conducted a retrospective chart review of six patients who underwent lung resection for pulmonary coccidioidomycosis at Chiba University Hospital between January 2007 and December 2021. RESULTS: All six patients had travelled to the Southwestern United States. Preoperative serology was negative for the anti-Coccidioides antibody in four patients and positive in two. Chest computed tomography revealed a single, well-defined round nodule in all patients. Preoperative biopsy taken from three patients failed to obtain a definitive diagnosis. Histopathological examination of the resected pulmonary nodules revealed granulomas that contained numerous spherules with many endospores, thereby confirming the diagnosis of pulmonary coccidioidomycosis. CONCLUSIONS: Pulmonary coccidioidomycosis should be suspected based on travel history and radiological findings. Meticulous care should be taken during specimen processing to prevent cross infection.


Assuntos
Coccidioidomicose , Humanos , Coccidioidomicose/diagnóstico , Coccidioidomicose/cirurgia , Coccidioidomicose/epidemiologia , Estudos Retrospectivos , Coccidioides , Biópsia , Tomografia Computadorizada por Raios X
5.
J Investig Med High Impact Case Rep ; 11: 23247096231197863, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37700666

RESUMO

Cavitary pulmonary coccidioidomycosis is rare diagnosis with an incidence of 13% to 15% of pulmonary coccidioidomycosis cases. High clinical suspicion is necessary in the setting of geographical location endemicity. We present a 49-year-old male who has lived in the Coachella Valley of California for several years, with a medical history of uncontrolled type 2 diabetes who noted 1 week of right-sided chest pain with shortness of breath, fever, chills, night sweats, and weight loss. A chest X-ray revealed a 4- to 5-cm mass in the right lung. Initial workup revealed negative sputum cultures (aerobic/anaerobic, acid-fast bacilli). However, dedicated fungal cultures (samples from sputum, lymph nodes, lung right lower lobe bronchial swabs), bronchial washings, and surgical tissue biopsy of the right lower lobe revealed mold. The patient underwent right thoracotomy with right lower lobectomy and right mediastinal lymph node dissection for both diagnostic (lung specimen) and therapeutic (removing necrotic lung tissue, source control) purposes. Finally, serum Coccidioides antigens were positive and antibody titers were positive at 1:8; surgical biopsy of the right lower lobe grew mold that came back positive for Coccidioides posadasii. Targeted pharmacotherapy was commenced using intravenous fluconazole and then oral fluconazole for 3 months was prescribed upon discharge. The patient had gradual improvement of his shortness of breath and was instructed to follow-up at an infectious disease clinic.


Assuntos
Coccidioidomicose , Diabetes Mellitus Tipo 2 , Masculino , Humanos , Pessoa de Meia-Idade , Coccidioidomicose/complicações , Coccidioidomicose/diagnóstico , Coccidioidomicose/tratamento farmacológico , Fluconazol/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Pulmão/diagnóstico por imagem , Pulmão/patologia , Dispneia , Bactérias
6.
J Investig Med High Impact Case Rep ; 11: 23247096231191872, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37559378

RESUMO

We present the case of a 30-year-old man with no prior medical history who presented to the hospital with a myriad of symptoms such as shortness of breath, generalized weakness, lower limb weakness, and urinary retention. He was recently diagnosed with "disseminated coccidioidomycosis" by an outside provider on an outpatient basis and started on fluconazole orally. However, due to a lack of improvement and significant symptoms, he was sent to the hospital to initiate liposomal amphotericin B treatment. After a comprehensive workup, an alternative diagnosis was suspected and eventually confirmed as metastatic germ cell carcinoma. Due to the vast dissemination and his poor functional status despite chemotherapy initiation, the patient elected for palliative care and expired shortly after at hospice. This case demonstrates the similarity of clinical findings between disseminated infections and malignancies.


Assuntos
Coccidioidomicose , Masculino , Humanos , Adulto , Coccidioidomicose/diagnóstico , Coccidioidomicose/tratamento farmacológico , Coccidioidomicose/patologia , Antifúngicos/uso terapêutico , Fluconazol/uso terapêutico
7.
J Am Vet Med Assoc ; 261(11): 1-7, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37481255

RESUMO

OBJECTIVE: To determine associations between antibody serologic tests and tracheobronchial lymphadenopathy (TBL) in dogs with pulmonary coccidioidomycosis and identify variables associated with time to resolution of TBL. ANIMALS: 32 client owned dogs with newly diagnosed pulmonary coccidioidomycosis from October 2020 to February 2021. METHODS: Prospective cohort study. Thoracic radiographs and anti-Coccidioides spp antibody serology were performed at baseline and once every 3 months until remission or for a maximum of 12 months. Radiographic tracheobronchial lymph node height, length, and area were measured and recorded as ratios via comparison with the length of the T4 vertebral body (LT4) and length of the manubrium. Severity of TBL was also subjectively categorized as mild, moderate, or severe. RESULTS: Tracheobronchial lymphadenopathy was identified in 81% (26/32; 95% CI, 64% to 93%) of dogs. There was no relevant association between TBL presence or severity and antibody serology results. Tracheobronchial lymphadenopathy resolved in 72% (n = 18) of dogs at the 3-month evaluation. The median time to resolution of TBL after initiation of fluconazole was 96 days (range, 72 to 386 days). Univariate analysis identified increasing TBL severity (hazard ratio, 0.40; 95% CI, 0.19 to 0.84; P = .02) and length:LT4 ratio (hazard ratio, 0.41; 95% CI, 0.20 to 0.82; P = .01) as variables associated with reduced probability of resolution of TBL. CLINICAL RELEVANCE: Antibody serologic test results are not clinically useful to predict TBL presence or severity in dogs with pulmonary coccidioidomycosis, and larger tracheobronchial lymph nodes are more likely to take longer to resolve. Resolution of TBL occurs in most dogs within 3 to 6 months after fluconazole administration.


Assuntos
Coccidioidomicose , Doenças do Cão , Linfadenopatia , Humanos , Cães , Animais , Coccidioidomicose/diagnóstico , Coccidioidomicose/veterinária , Fluconazol/uso terapêutico , Estudos Prospectivos , Coccidioides , Linfadenopatia/veterinária , Doenças do Cão/patologia
8.
BMJ Case Rep ; 16(7)2023 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-37463776

RESUMO

Coccidioidomycosis is known to occur around the western hemisphere. In tropical countries, the clinical presentation is atypical presenting with a superficial abscess preceded by respiratory tract involvement often mimicking tuberculosis. Eliciting a history of exposure and high suspicion is imperative for early diagnosis.In the present case report, a man in his early 30s presented with complaints of swelling over the neck for the past 2 months with a recent travel history. With a provisional clinical diagnosis of tuberculosis, a biopsy of the swelling revealed features of granulomas with non-caseating necrosis with Coccidioidomycosis organisms demonstrated by fungal stains. Fungal culture and serology reiterated Coccidioides and he recovered after a course of fluconazole.The case report concludes with a statement that Coccidioidomycosis is known to manifest with lymphadenitis mimicking tuberculosis and must be taken into account as one of the differentials. The current report is presented for its rarity in India with atypical presentation.


Assuntos
Coccidioidomicose , Linfadenopatia , Masculino , Humanos , Coccidioidomicose/diagnóstico , Coccidioidomicose/tratamento farmacológico , Coccidioidomicose/microbiologia , Antifúngicos/uso terapêutico , Fluconazol/uso terapêutico , Coccidioides , Linfadenopatia/tratamento farmacológico
9.
Mycopathologia ; 188(4): 307-334, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37294504

RESUMO

Endemic systemic mycoses such as blastomycosis, coccidioidomycosis, histoplasmosis, talaromycosis, paracoccidioidomycosis are emerging as an important cause of morbidity and mortality worldwide. We conducted a systematic review on endemic systemic mycoses reported in Italy from 1914 to nowadays. We found out: 105 cases of histoplasmosis, 15 of paracoccidioidomycosis, 10 of coccidioidomycosis, 10 of blastomycosis and 3 of talaromycosis. Most cases have been reported in returning travelers and expatriates or immigrants. Thirtytwo patients did not have a story of traveling to an endemic area. Fortysix subjects had HIV/AIDS. Immunosuppression was the major risk factor for getting these infections and for severe outcomes. We provided an overview on microbiological characteristics and clinical management principles of systemic endemic mycoses with a focus on the cases reported in Italy.


Assuntos
Blastomicose , Coccidioidomicose , Histoplasmose , Micoses , Paracoccidioidomicose , Humanos , Histoplasmose/diagnóstico , Histoplasmose/tratamento farmacológico , Histoplasmose/epidemiologia , Coccidioidomicose/epidemiologia , Blastomicose/epidemiologia , Paracoccidioidomicose/diagnóstico , Paracoccidioidomicose/tratamento farmacológico , Paracoccidioidomicose/epidemiologia , Micoses/tratamento farmacológico , Micoses/epidemiologia
10.
Methods Mol Biol ; 2667: 139-158, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37145282

RESUMO

Coccidioidomycosis, caused by the dimorphic pathogens Coccidioides posadasii and C. immitis, is a fungal disease endemic to the southwestern United States, Mexico, and some regions of Central and South America. The mouse is the primary model for studying pathology and immunology of disease. Mice in general are extremely susceptible to Coccidioides spp., which creates challenges in studying the adaptive immune responses that are required for host control of coccidioidomycosis. Here, we describe how to infect mice to model asymptomatic infection with controlled, chronic granulomas and a slowly progressive but ultimately fatal infection that has kinetics more similar to the human disease.


Assuntos
Coccidioidomicose , Humanos , Animais , Camundongos , Coccidioides , América do Sul/epidemiologia , México
11.
Immunohorizons ; 7(5): 333-352, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-37195872

RESUMO

Links between repeated microbial infections and B cell chronic lymphocytic leukemia (B-CLL) have been proposed but not tested directly. This study examines how prolonged exposure to a human fungal pathogen impacts B-CLL development in Eµ-hTCL1-transgenic mice. Monthly lung exposure to inactivated Coccidioides arthroconidia, agents of Valley fever, altered leukemia development in a species-specific manner, with Coccidioides posadasii hastening B-CLL diagnosis/progression in a fraction of mice and Coccidioides immitis delaying aggressive B-CLL development, despite fostering more rapid monoclonal B cell lymphocytosis. Overall survival did not differ significantly between control and C. posadasii-treated cohorts but was significantly extended in C. immitis-exposed mice. In vivo doubling time analyses of pooled B-CLL showed no difference in growth rates of early and late leukemias. However, within C. immitis-treated mice, B-CLL manifests longer doubling times, as compared with B-CLL in control or C. posadasii-treated mice, and/or evidence of clonal contraction over time. Through linear regression, positive relationships were noted between circulating levels of CD5+/B220low B cells and hematopoietic cells previously linked to B-CLL growth, albeit in a cohort-specific manner. Neutrophils were positively linked to accelerated growth in mice exposed to either Coccidioides species, but not in control mice. Conversely, only C. posadasii-exposed and control cohorts displayed positive links between CD5+/B220low B cell frequency and abundance of M2 anti-inflammatory monocytes and T cells. The current study provides evidence that chronic lung exposure to fungal arthroconidia affects B-CLL development in a manner dependent on fungal genotype. Correlative studies suggest that fungal species differences in the modulation of nonleukemic hematopoietic cells are involved.


Assuntos
Coccidioidomicose , Leucemia Linfocítica Crônica de Células B , Animais , Camundongos , Humanos , Coccidioides/genética , Pulmão , Camundongos Transgênicos
12.
J Neurosurg Spine ; 39(3): 419-426, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37243554

RESUMO

OBJECTIVE: Vertebral osteomyelitis is a rare complication of coccidioidomycosis infection. Surgical intervention is indicated when there is failure of medical management or presence of neurological deficit, epidural abscess, or spinal instability. The relationship between timing of surgical intervention and recovery of neurological function has not been previously described. The purpose of this study was to investigate if the duration of neurological deficits at presentation affects neurological recovery after surgical intervention. METHODS: This was a retrospective study of all patients diagnosed with coccidioidomycosis involving the spine at a single tertiary care center between 2012 and 2021. Data collected included patient demographics, clinical presentation, radiographic information, and surgical intervention. The primary outcome was change in neurological examination after surgical intervention, quantified according to the American Spinal Injury Association Impairment Scale. The secondary outcome was the complication rate. Logistic regression was used to test if the duration of neurological deficits was associated with improvement in the neurological examination after surgery. RESULTS: Twenty-seven patients presented with spinal coccidioidomycosis between 2012 and 2021; 20 of these patients had vertebral involvement on spinal imaging with a median follow-up of 8.7 months (IQR 1.7-71.2 months). Of the 20 patients with vertebral involvement, 12 (60.0%) presented with a neurological deficit with a median duration of 20 days (range 1-61 days). Most patients presenting with neurological deficit (11/12, 91.7%) underwent surgical intervention. Nine (81.2%) of these 11 patients had an improved neurological examination after surgery and the other 2 had stable deficits. Seven patients had improved recovery sufficient to improve by 1 grade according to the AIS. The duration of neurological deficits on presentation was not significantly associated with neurological improvement after surgery (p = 0.49, Fisher's exact test). CONCLUSIONS: The duration of neurological deficits on presentation should not deter surgeons from operative intervention in cases of spinal coccidioidomycosis.


Assuntos
Coccidioidomicose , Abscesso Epidural , Doenças da Coluna Vertebral , Humanos , Coccidioidomicose/diagnóstico por imagem , Coccidioidomicose/cirurgia , Estudos Retrospectivos , Coluna Vertebral/cirurgia , Abscesso Epidural/diagnóstico , Abscesso Epidural/cirurgia
13.
Oral Maxillofac Surg Clin North Am ; 35(2): 271-281, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36805904

RESUMO

Oral fungal infections are opportunistic and due to impaired host resistance. The increasing number of immunosuppressed individuals contributes to rising numbers of mycoses worldwide, and the ease of global migration has allowed the geographic range of endemic mycoses to expand. Deep fungal infections can clinically mimic other pathologic conditions including malignancy. This review highlights the pathogenesis, clinical features, diagnosis, and treatment recommendations of eight fungal infections that can be encountered in the dental setting.


Assuntos
Actinomicose , Aspergilose , Blastomicose , Coccidioidomicose , Criptococose , Histoplasmose , Mucormicose , Micoses , Esporotricose , Humanos , Mucosa Bucal
15.
Cutis ; 110(2): E32-E34, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36219649

RESUMO

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare nodular mass that has not commonly been reported in the literature in association with coccidioidomycosis (CM). Coccidioidomycosis has other known skin manifestations including erythema nodosum and interstitial granulomatous dermatitis. Pulmonary CM is the most common form of the disease and the most common cause of CM-associated rash. This is an important clinical consideration for patients with ALHE who reside in CM-endemic areas, which notably include the southwestern region of the United States, Mexico, and South America. We report the case of an ALHE lesion that resolved following treatment for CM.


Assuntos
Hiperplasia Angiolinfoide com Eosinofilia , Coccidioidomicose , Hemangioma , Hiperplasia Angiolinfoide com Eosinofilia/complicações , Hiperplasia Angiolinfoide com Eosinofilia/diagnóstico , Hiperplasia Angiolinfoide com Eosinofilia/patologia , Coccidioidomicose/complicações , Coccidioidomicose/diagnóstico , Hemangioma/complicações , Humanos , México
16.
BMJ Case Rep ; 15(9)2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36127036

RESUMO

An elderly man without history of travel presented with complaints of intermittent fever for 2 months, cough with scanty expectoration for 15 days and history of weight loss of 5 kg in 1 year. The chest X-ray and CT scan of the thorax showed dispersed centrilobular nodules and patchy subpleural consolidation in both lungs with mediastinal lymphadenopathy. He underwent bronchoscopy and bronchoalveolar lavage culture grew Pseudomonas aeruginosa He was prescribed antibiotics based on culture sensitivity; however, patient continued to have symptoms. All relevant blood investigations were within normal limits. He underwent CT-guided biopsy of the right lung lesion during which clearing of the radio-opacities present in the initial CT scan and appearance of fresh lesions in different locations were observed. Migratory shadows were suspected. Fine-needle aspiration cytology showed features suggestive of coccidioidomycosis for which antifungals were started. After 1 month, he improved symptomatically and chest X-ray showed clearance of shadows.


Assuntos
Coccidioidomicose , Idoso , Antibacterianos/uso terapêutico , Antifúngicos/uso terapêutico , Broncoscopia , Coccidioidomicose/diagnóstico por imagem , Coccidioidomicose/tratamento farmacológico , Humanos , Pulmão/patologia , Masculino
17.
Microbiol Spectr ; 10(5): e0257322, 2022 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-36121238

RESUMO

Coccidioidomycosis, also called valley fever (VF), is a fungal infection with endemicity in desert regions of the western United States as well as certain arid regions of Central and South America. Laboratory-based diagnosis of VF often relies on the composite results from three serologic-based diagnostics, complement fixation, immunodiffusion, and enzyme immunoassay (EIA). EIA is commonly performed in clinical laboratories because results can be obtained in a few hours. Two commercially available EIAs, IMMY clarus Coccidioides antibody and Meridian Premier Coccidioides, look for the presence of anticoccidioidal IgG and IgM in patient sera that are diluted 1:441. Per regulatory requirements, this dilution step must be verified with a dilution step control despite not being provided as a reagent in either FDA-approved EIA kit. Therefore, clinical laboratories collect and reuse patient sera in subsequent tests that had a positive result in a previous test. This is a nonstandard process, reinforcing the need for a consistent and reliable dilution control. Here, we evaluate the performance of a humanized IgG and IgM antibody as a dilution control in both EIA kits. Both humanized IgG and IgM work well in each EIA and meet the appropriate threshold for positivity. IMPORTANCE In southwestern and western regions of the United States, at least half a million diagnostic tests for coccidioidomycosis (valley fever) are run annually. Enzyme immunoassays (EIAs) are blood tests which require precise dilution of patient serum prior to testing. To ensure patient serum is properly diluted, there is a regulatory requirement to ensure the dilution step is accurate. Two FDA-approved EIAs used to aid in the diagnosis of coccidioidomycosis do not contain controls for this dilution step, leaving clinical laboratories with the only option of using previously positive patient sera, which may not react in a reliable or predictable manner. Here, we evaluate a humanized monoclonal antibody against a coccidioidal antigen and its utility as a dilution control in both available commercial EIAs. The use of a humanized monoclonal antibody provides a standardized and well-characterized dilution control for use in serological assays that aid in diagnosis of coccidioidomycosis.


Assuntos
Coccidioidomicose , Humanos , Coccidioidomicose/diagnóstico , Anticorpos Antifúngicos , Laboratórios Clínicos , Imunoglobulina G , Sensibilidade e Especificidade , Coccidioides , Técnicas Imunoenzimáticas , Imunoglobulina M , Anticorpos Monoclonais
18.
JCI Insight ; 7(22)2022 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-36166305

RESUMO

Disseminated coccidioidomycosis (DCM) is caused by Coccidioides, pathogenic fungi endemic to the southwestern United States and Mexico. Illness occurs in approximately 30% of those infected, less than 1% of whom develop disseminated disease. To address why some individuals allow dissemination, we enrolled patients with DCM and performed whole-exome sequencing. In an exploratory set of 67 patients with DCM, 2 had haploinsufficient STAT3 mutations, and defects in ß-glucan sensing and response were seen in 34 of 67 cases. Damaging CLEC7A and PLCG2 variants were associated with impaired production of ß-glucan-stimulated TNF-α from PBMCs compared with healthy controls. Using ancestry-matched controls, damaging CLEC7A and PLCG2 variants were overrepresented in DCM, including CLEC7A Y238* and PLCG2 R268W. A validation cohort of 111 patients with DCM confirmed the PLCG2 R268W, CLEC7A I223S, and CLEC7A Y238* variants. Stimulation with a DECTIN-1 agonist induced DUOX1/DUOXA1-derived hydrogen peroxide [H2O2] in transfected cells. Heterozygous DUOX1 or DUOXA1 variants that impaired H2O2 production were overrepresented in discovery and validation cohorts. Patients with DCM have impaired ß-glucan sensing or response affecting TNF-α and H2O2 production. Impaired Coccidioides recognition and decreased cellular response are associated with disseminated coccidioidomycosis.


Assuntos
Coccidioidomicose , beta-Glucanas , Humanos , Fator de Necrose Tumoral alfa/genética , Peróxido de Hidrogênio , Coccidioidomicose/genética , Coccidioidomicose/epidemiologia , Coccidioidomicose/microbiologia , Coccidioides/genética
19.
BMC Infect Dis ; 22(1): 623, 2022 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-35843935

RESUMO

BACKGROUND: Pericardial disease can be a manifestation of infection and imaging can have a role in its diagnosis. coccidioidomycosis endemic fungal infection has been more frequently reported over the past few decades. Other than case reports or series, there has been no systemic study evaluating pericardial imaging findings in patients with coccidioidomycosis to the best of our knowledge. The purpose of this study was to evaluate intrathoracic computed tomographic (CT) imaging abnormalities in patients with coccidioidal infection with specific emphasis on the pericardium. METHODS: Retrospective review of radiology reports and clinical chart review was performed to identify patients with coccidioidomycosis between January 2000 and September 2021 at our medical center. Diagnosis of infection was confirmed predominately with serology. Patients were excluded if a CT was not performed within 3 months of confirmed diagnosis date and if there was concomitant additional granulomatous or fungal infection. Chest CT was reviewed for pericardial and additional intrathoracic findings. RESULTS: The final retrospective cohort consisted of 37 patients. Imaging findings included lung nodules (N = 33/37), consolidation (N = 25/37), mediastinal or hilar lymphadenopathy (N = 20/37) and pleural effusions (N = 13/37). Eleven of 37 patients (30%) had either trace pericardial fluid (N = 3/37) or small pericardial effusions (N = 8/37). One patient had pericardial enhancement/thickening and history of pericardial tamponade. No other patient had clinical pericarditis or pericardial tamponade. Pericardial calcifications were not seen in any patient. Pericardial effusion was statistically associated with presence of pleural effusion as 9/13 patients with pleural effusion had pericardial effusion versus 2/26 patients without pleural effusion had pericardial effusion (p < 0.001). Otherwise patients with and without pericardial imaging findings were similar in terms of demographics, comorbidities and other imaging findings. CONCLUSION: Pulmonary parenchymal pathology is a common manifestation of coccidioidal infection. Most patients with coccidioidomycosis do not have pericardial imaging abnormalities on CT.


Assuntos
Tamponamento Cardíaco , Coccidioidomicose , Derrame Pericárdico , Derrame Pleural , Coccidioidomicose/diagnóstico por imagem , Coccidioidomicose/microbiologia , Humanos , Derrame Pericárdico/diagnóstico por imagem , Derrame Pleural/microbiologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
20.
J Vet Diagn Invest ; 34(6): 995-999, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35879871

RESUMO

Coccidioidomycosis is a fungal disease caused by Coccidioides immitis or Coccidioides posadasii. We searched the records of the California Animal Health and Food Safety Laboratory from 1990 through 2020 for cases of coccidioidomycosis in horses. The selection criteria for these cases were: 1) live-born horses submitted for autopsy, and 2) a diagnosis of coccidioidomycosis was established, regardless of cause of death. During that time, 19,054 horses were received, and 26 cases (0.14%) of coccidioidomycosis were diagnosed in horses, of which 19 (73%) cases had pneumonia and/or pleuritis with or without lesions in other organs, and 7 (27%) cases had lesions only in organs other than the lungs (nasal mucosa, spleen, thoracic lymph nodes, heart, pericardial sac, liver, kidney, mediastinum, and/or mesentery). Pneumonia was diagnosed as the cause of death in 1,838 (9.64%) of the horses received; Coccidioides spp. was the cause of pneumonia in 19 (1.0%) of these animals. Horses have been reported to have low susceptibility to coccidioidomycosis, and the severity and chronicity of the disease can be variable. Lesions in our cases consisted of multifocal-to-coalescing pyogranulomas with intralesional fungal spherules. Coccidioidomycosis must be considered a differential diagnosis in cases of persistent cough, chronic weight loss, fever, and cases with a travel history to, or living in, a region considered endemic for coccidioidomycosis. Coccidioides spp. infection should also be considered when pyogranulomatous inflammation is found within lung, spleen, nasal mucosa, and lymph nodes of horses.


Assuntos
Coccidioidomicose , Doenças dos Cavalos , Cavalos , Animais , Coccidioidomicose/diagnóstico , Coccidioidomicose/epidemiologia , Coccidioidomicose/veterinária , Pulmão/patologia , Granuloma/veterinária , California/epidemiologia , Doenças dos Cavalos/patologia
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