Abstract:Lobomycosis is a chronic disease caused by Lacazia loboi, which is endemic to the Amazon rainforest, where it affects forest dwellers in Brazil. There is no disease control program and no official therapeutic protocol. This situation contributes to an unknown disease prevalence and unmet needs of people disabled by this disease who seek access to treatment. This review provides an update on the subject with an emphasis on therapeutic advances in humans. All relevant studies that addressed epidemiology, diagnos… Show more
“…A major pitfall of our study is the absence of clinical samples from patients with PCM loboi or cetaceans with PCM ceti [ 12 , 26 , 71 ], which is partially justified due to the unculturable nature of the etiological agents and the rarity of these infections compared with classic PCM [ 1 , 8 ]. A BLAST search using the Primer-BLAST tool and the sequences of Paracoco-F and Paracoco-R primers or probes did not retrieve any amplicon related to P. loboi , which could be associated with the scarcity of P. loboi rDNA sequences from public databases [ 7 ].…”
Section: Discussionmentioning
confidence: 99%
“…Paracoccidioides lutzii has an elevated disease burden in the Brazilian Midwest, as well as scattered cases in the Amazon and Peru [ 4 , 9 , 10 , 11 ]. Paracoccidioides cetii from cetaceans is detected through the nearshore zones of the Americas, while P. loboi predominates in riverside populations in the Amazon basin and South America [ 1 , 7 , 12 ].…”
Classic paracoccidioidomycosis (PCM) is a potentially deadly neglected tropical systemic mycosis caused by members of the Paracoccidioides brasiliensis complex (P. brasiliensis s. str., P. americana, P. restrepiensis, and P. venezuelensis) and P. lutzii. The laboratorial diagnosis of PCM relies on observing pathognomonic structures such as the “steering wheel” or “Mickey Mouse” shape in the direct mycological examination, fresh biopsied tissue in 10% KOH, histopathological analysis, and/or the isolation of the fungus in culture. However, these procedures are time-consuming and do not allow for the speciation of Paracoccidioides due to overlapping morphologies. Here, we propose a new one-tube multiplex probe-based qPCR assay to detect and recognize agents of the P. brasiliensis complex and P. lutzii. Primers (Paracoco-F and Paracoco-R) and TaqMan probes (PbraCx-Fam, Plu-Ned, and Paracoco-Vic) were developed to target the rDNA (ITS2/28S) in the Paracoccidioides genome. A panel of 77 Paracoccidioides isolates revealed a 100% specificity (AUC = 1.0, 95% CI 0.964–1.000, p < 0.0001) without cross-reacting with other medically relevant fungi or human and murine DNA. The lower limit of detection was 10 fg of gDNA and three copies of the partial rDNA amplicon. Speciation using qPCR was in perfect agreement with AFLP and TUB1-RFLP markers (kappa = 1.0). As a proof of concept, we assessed a panel of 16 formalin-fixed and paraffin-embedded specimens from histopathologically confirmed PCM patients to reveal a significant sensitivity of 81.25% and specificity of 100% (AUC = 0.906 ± 0.05, 95% CI = 0.756–0.979, p < 0.0001, Youden index J = 0.8125). Our assay achieved maximum sensitivity (100%) and specificity (100%) using fresh clinical samples (n = 9) such as sputum, bronchoalveolar lavage, and tissue fragments from PCM patients (AUC = 1.0, 95% CI 0.872–1.000, p < 0.0001, Youden index J = 1.0). Overall, our qPCR assay simplifies the molecular diagnosis of PCM and can be easily implemented in any routine laboratory, decreasing a critical bottleneck for the early treatment of PCM patients across a vast area of the Americas.
“…A major pitfall of our study is the absence of clinical samples from patients with PCM loboi or cetaceans with PCM ceti [ 12 , 26 , 71 ], which is partially justified due to the unculturable nature of the etiological agents and the rarity of these infections compared with classic PCM [ 1 , 8 ]. A BLAST search using the Primer-BLAST tool and the sequences of Paracoco-F and Paracoco-R primers or probes did not retrieve any amplicon related to P. loboi , which could be associated with the scarcity of P. loboi rDNA sequences from public databases [ 7 ].…”
Section: Discussionmentioning
confidence: 99%
“…Paracoccidioides lutzii has an elevated disease burden in the Brazilian Midwest, as well as scattered cases in the Amazon and Peru [ 4 , 9 , 10 , 11 ]. Paracoccidioides cetii from cetaceans is detected through the nearshore zones of the Americas, while P. loboi predominates in riverside populations in the Amazon basin and South America [ 1 , 7 , 12 ].…”
Classic paracoccidioidomycosis (PCM) is a potentially deadly neglected tropical systemic mycosis caused by members of the Paracoccidioides brasiliensis complex (P. brasiliensis s. str., P. americana, P. restrepiensis, and P. venezuelensis) and P. lutzii. The laboratorial diagnosis of PCM relies on observing pathognomonic structures such as the “steering wheel” or “Mickey Mouse” shape in the direct mycological examination, fresh biopsied tissue in 10% KOH, histopathological analysis, and/or the isolation of the fungus in culture. However, these procedures are time-consuming and do not allow for the speciation of Paracoccidioides due to overlapping morphologies. Here, we propose a new one-tube multiplex probe-based qPCR assay to detect and recognize agents of the P. brasiliensis complex and P. lutzii. Primers (Paracoco-F and Paracoco-R) and TaqMan probes (PbraCx-Fam, Plu-Ned, and Paracoco-Vic) were developed to target the rDNA (ITS2/28S) in the Paracoccidioides genome. A panel of 77 Paracoccidioides isolates revealed a 100% specificity (AUC = 1.0, 95% CI 0.964–1.000, p < 0.0001) without cross-reacting with other medically relevant fungi or human and murine DNA. The lower limit of detection was 10 fg of gDNA and three copies of the partial rDNA amplicon. Speciation using qPCR was in perfect agreement with AFLP and TUB1-RFLP markers (kappa = 1.0). As a proof of concept, we assessed a panel of 16 formalin-fixed and paraffin-embedded specimens from histopathologically confirmed PCM patients to reveal a significant sensitivity of 81.25% and specificity of 100% (AUC = 0.906 ± 0.05, 95% CI = 0.756–0.979, p < 0.0001, Youden index J = 0.8125). Our assay achieved maximum sensitivity (100%) and specificity (100%) using fresh clinical samples (n = 9) such as sputum, bronchoalveolar lavage, and tissue fragments from PCM patients (AUC = 1.0, 95% CI 0.872–1.000, p < 0.0001, Youden index J = 1.0). Overall, our qPCR assay simplifies the molecular diagnosis of PCM and can be easily implemented in any routine laboratory, decreasing a critical bottleneck for the early treatment of PCM patients across a vast area of the Americas.
“…En Colombia, el primer reporte fue hecho en 1958, con posterior reporte de más casos que han predominado en las regiones de la Amazonía, Orinoquía y Pacífico Colombiano, con afectación de agricultores, mineros y pescadores, mestizos, mulatos, así como indígenas y población afrodescendiente residentes en estas áreas geográficas indicadas; también han sido reportados casos en soldados colombianos, en quienes la lobomicosis se desarrolló después del servicio militar prestado en la zona amazónica del país (3)(4)(5)(6) . En una revisión publicada recientemente se mencionan los casos reportados en diferentes países del mundo hasta el año 2006, donde se contabiliza un total de 490 casos de lobomicosis, de los cuales, el 65% eran de Brasil, con 318 casos, y, en segundo lugar, el 10% eran de Colombia, lo que equivalían a 50 casos hasta ese momento (7) . En esta publicación reportamos cuatro casos, dos hombres y dos mujeres, diagnosticados en brigadas de salud realizadas con la Patrulla Aérea Civil Colombiana en los departamentos del Vichada y Chocó, entre los años 2017 y 2020.…”
La lobomicosis es una enfermedad micótica poco frecuente, afecta personas que viven en áreas tropicales con características ambientales y ocupacionales que facilitan su aparición. Los pacientes en su mayoría son hombres trabajadores o habitantes en áreas selváticas, pueden presentar traumas con posterior aparición de lesiones en piel, generalmente polimorfas, con evolución lenta y progresiva a través de los años. En estos casos se presentan demoras para el diagnóstico y tratamiento, este último con varias opciones terapéuticas de respuesta variable y efectividad parcial, siendo frecuente la recurrencia o avance de las lesiones. Presentamos el reporte de 4 casos de lobomicosis en pacientes de la orinoquía y el pacífico colombiano, vistos en brigadas de salud con la patrulla aérea civil colombiana, en áreas de difícil acceso del país. Es una enfermedad rara, que no debe ser olvidada.
“…The true incidence of emergomycosis is unknown, but after the introduction of molecular techniques, many cases initially classified as histoplasmosis on the basis of histopathology have been demonstrated to be emergomycosis, indicating that its prevalence may be more frequent than previously thought [ 17 ]. Lobomycosis prevalence is unknown but an increase in new cases has been observed in recent years [ 18 ].…”
Diagnosis of endemic mycoses is still challenging. The moderated availability of reliable diagnostic methods, the lack of clinical suspicion out of endemic areas and the limitations of conventional techniques result in a late diagnosis that, in turn, delays the implementation of the correct antifungal therapy. In recent years, molecular methods have emerged as promising tools for the rapid diagnosis of endemic mycoses. However, the absence of a consensus among laboratories and the reduced availability of commercial tests compromises the diagnostic effectiveness of these methods. In this review, we summarize the advantages and limitations of molecular methods for the diagnosis of endemic mycoses.
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