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result(s) for
"Gonçalves, Sarah Santos"
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Current Progress on Epidemiology, Diagnosis, and Treatment of Sporotrichosis and Their Future Trends
by
Rozental, Sonia
,
Gonçalves, Sarah Santos
,
de Carvalho, Jamile Ambrósio
in
Acquired immune deficiency syndrome
,
AIDS
,
Animal diseases
2022
Sporotrichosis, a human and animal disease caused by Sporothrix species, is the most important implantation mycosis worldwide. Sporothrix taxonomy has improved in recent years, allowing important advances in diagnosis, epidemiology, and treatment. Molecular epidemiology reveals that S. brasiliensis remains highly prevalent during the cat-transmitted sporotrichosis outbreaks in South America and that the spread of S. brasiliensis occurs through founder effects. Sporothrix globosa and S. schenckii are cosmopolitan on the move, causing major sapronoses in Asia and the Americas, respectively. In this emerging scenario, one-health approaches are required to develop a creative, effective, and sustainable response to tackle the spread of sporotrichosis. In the 21st century, it has become vital to speciate Sporothrix, and PCR is the main pillar of molecular diagnosis, aiming at the detection of the pathogen DNA from clinical samples through multiplex assays, whose sensitivity reaches remarkably three copies of the target. The treatment of sporotrichosis can be challenging, especially after the emergence of resistance to azoles and polyenes. Alternative drugs arising from discoveries or repositioning have entered the radar of basic research over the last decade and point to several molecules with antifungal potential, especially the hydrazone derivatives with great in vitro and in vivo activities. There are many promising developments for the near future, and in this review, we discuss how these trends can be applied to the Sporothrix-sporotrichosis system to mitigate the advance of an emerging and re-emerging disease.
Journal Article
Paracoccidioidomycosis: What We Know and What Is New in Epidemiology, Diagnosis, and Treatment
by
Falqueto, Aloísio
,
Peçanha, Paulo Mendes
,
Gonçalves, Sarah Santos
in
Agriculture
,
Amphotericin B
,
Azoles
2022
Paracoccidioidomycosis (PCM) is a systemic mycosis endemic to Latin America caused by thermodimorphic fungi of the genus Paracoccidioides. In the last two decades, enhanced understanding of the phylogenetic species concept and molecular variations has led to changes in this genus’ taxonomic classification. Although the impact of the new species on clinical presentation and treatment remains unclear, they can influence diagnosis when serological methods are employed. Further, although the infection is usually acquired in rural areas, the symptoms may manifest years or decades later when the patient might be living in the city or even in another country outside the endemic region. Brazil accounts for 80% of PCM cases worldwide, and its incidence is rising in the northern part of the country (Amazon region), owing to new settlements and deforestation, whereas it is decreasing in the south, owing to agriculture mechanization and urbanization. Clusters of the acute/subacute form are also emerging in areas with major human intervention and climate change. Advances in diagnostic methods (molecular and immunological techniques and biomarkers) remain scarce, and even the reference center’s diagnostics are based mainly on direct microscopic examination. Classical imaging findings in the lungs include interstitial bilateral infiltrates, and eventually, enlargement or calcification of adrenals and intraparenchymal central nervous system lesions are also present. Besides itraconazole, cotrimoxazole, and amphotericin B, new azoles may be an alternative when the previous ones are not tolerated, although few studies have investigated their use in treating PCM.
Journal Article
Diagnosis and Treatment of Pulmonary Coccidioidomycosis and Paracoccidioidomycosis
by
Colombo, Arnaldo Lopes
,
Gonçalves, Sarah Santos
,
Bonifaz, Alexandro
in
antifungal treatment
,
Climate change
,
Climatic changes
2023
Coccidioidomycosis (CM) and paracoccidioidomycosis (PCM) are systemic mycoses that are highly endemic in Latin America and have recently been included on the World Health Organization (WHO) Fungal Priority Pathogens List. Coccidioides immitis and Coccidioides posadasii are recognized as etiological agents of CM, with peculiarities in their geographic distribution. The genus Paracoccidioides now includes Paracoccidioides lutzii and the Paracoccidioides brasiliensis complex, which encompasses four phylogenetic species. In both diseases, pulmonary signs and symptoms are the main reasons for patients to seek medical assistance, and they are frequently misdiagnosed as tuberculosis. In this paper, we present a critical view of the strategies for diagnosis and clinical management of CM and PCM. Over the past few decades, there has been an increase in the number of reports of endemic fungal infections in areas previously thought to be “non-endemic” due to climate change and increased travel, among other factors. Learning to recognize their main epidemiological aspects and clinical manifestations is crucial so that clinicians can include them in the differential diagnosis of lung disease and avoid late diagnosis.
Journal Article
Genetic diversity and molecular evolution of 3-carboxymuconate cyclase (Gp60-70), the major antigen in pathogenic Sporothrix species
by
Alvarado, Primavera
,
Antonio Pereira, Sandro
,
Gompertz, Olga Fischman
in
3-carboxymuconate cyclase
,
Antigens
,
B-lymphocytes
2025
Sporotrichosis, a neglected tropical disease caused by Sporothrix species, is a growing concern, particularly due to the emergence of highly virulent, cat-transmitted S. brasiliensis. Rapid diagnosis and surveillance are crucial for controlling sporotrichosis. This study investigated the 3-carboxymuconate cyclase (CMC) gene, which encodes the major Sporothrix antigen (Gp60-70), as a molecular marker to understand the genetic diversity and evolution of these fungi. Analysis of 104 isolates (S. brasiliensis, S. schenckii, S. globosa, and S. luriei) revealed 79 unique haplotypes, demonstrating superior discriminatory power over traditional molecular markers. High-CMC polymorphisms, especially in S. brasiliensis and S. schenckii, suggest recent population expansion or positive selection, potentially driven by environmental pressures such as polyaromatic hydrocarbon pollutants. The conserved chromosomal location of CMC in pathogenic Sporothrix and its absence in less virulent species suggest a role in virulence. Identifying conserved residues within predicted B-cell epitopes provides targets for diagnostics and therapeutics. Additionally, we identified N-linked glycosylation sequons (e.g. NGS at 62, NNT at 225, and NGT at 373/374) conserved in pathogenic Sporothrix but absent in environmental Sordariomycetes, possibly contributing to pathogenicity and niche adaptation. This study establishes CMC as a valuable marker for understanding Sporothrix evolution and virulence, aiding in sporotrichosis management.
Journal Article
High-Throughput Microsatellite Markers Development for Genetic Characterization of Emerging Sporothrix Species
by
Spruijtenburg, Bram
,
de Carvalho, Jamile Ambrósio
,
Kano, Rui
in
Capillary electrophoresis
,
Cats
,
Decision making
2023
Sporotrichosis is the main subcutaneous mycosis worldwide transmitted by animal or plant vectors and often escalates to outbreaks or epidemics. The current cat-transmitted sporotrichosis driven by Sporothrix brasiliensis has become a significant public health issue in South America. Transmission dynamics remain enigmatic due to the lack of development of polymorphic markers for molecular epidemiological analysis. This study used a high-throughput mining strategy to characterize simple sequence repeat (SSR) markers from Sporothrix genomes. A total of 118,140–143,912 SSR loci were identified (82,841–98,369 unique markers), with a 3651.55–3804.65 SSR/Mb density and a majority of dinucleotides motifs (GC/CG). We developed a panel of 15 highly polymorphic SSR markers suitable for genotyping S. brasiliensis, S. schenckii, and S. globosa. PCR amplification revealed 240 alleles in 180 Sporothrix isolates with excellent polymorphic information content (PIC = 0.9101), expected heterozygosity (H = 0.9159), and discriminating power (D = 0.7127), supporting the effectiveness of SSR markers in uncovering cryptic genetic diversity. A systematic population genetic study estimated three clusters, corresponding to S. brasiliensis (population 1, n = 97), S. schenckii (population 2, n = 49), and S. globosa (population 3, n = 34), with a weak signature of mixed ancestry between populations 1 and 2 or 3 and 2. Partitioning of genetic variation via AMOVA revealed highly structured populations (ΦPT = 0.539; Nm = 0.213; p < 0.0001), with approximately equivalent genetic variability within (46%) and between (54%) populations. Analysis of SSR diversity supports Rio de Janeiro (RJ) as the center of origin for contemporary S. brasiliensis infections. The recent emergence of cat-transmitted sporotrichosis in northeastern Brazil indicates an RJ-Northeast migration resulting in founder effects during the introduction of diseased animals into sporotrichosis-free areas. Our results demonstrated high cross-species transferability, reproducibility, and informativeness of SSR genetic markers, helping dissect deep and fine-scale genetic structures and guiding decision making to mitigate the harmful effects of the expansion of cat-transmitted sporotrichosis.
Journal Article
Human and Feline Sporotrichosis in a Reference Center of Southeastern Brazil: Genetic Differentiation, Diversity, and Antifungal Susceptibility of Sporothrix Species
by
Kruschewsky, Wdson Luis Lima
,
Falqueto, Aloísio
,
Rediguieri, Bruno Carneiro
in
Amplified fragment length polymorphism
,
Animals
,
Cats
2023
Sporotrichosis is a neglected subcutaneous fungal infection that affects humans and animals worldwide caused by species belonging to the genus Sporothrix. This study aims to examine the range of genetic variations, assess molecular epidemiology significance, and explore potential modes of transmission of the Sporothrix species associated with the current sporotrichosis outbreaks in Espírito Santo, Brazil. In this investigation, 262 samples were evaluated, including 142 from humans and 120 from felines, collected between 2016 and 2021. The isolates were identified based on morphological and molecular characteristics. Sexual idiomorphs were determined by mating-type PCR using primers specific to the MAT1-1 and MAT1-2 loci. Amplified fragment length polymorphism (AFLP) was employed to assess the genetic variability of Sporothrix spp. Finally, antifungal susceptibility testing was performed following the CLSI M38-A2 protocol. Of the 142 human samples, 125 were identified as S. brasiliensis and 17 as S. schenckii s. str. The presence of S. brasiliensis was overwhelming (100%) during outbreaks, highlighting the significant role of domestic cats in the emergence of this species. Heterothallism was the only observed mating strategy. However, the MAT1-2 idiomorph was predominant in cases of cat-transmitted sporotrichosis (χ2 = 202.976; p < 0.0001). Our AFLP results show significant intraspecific variability observed among S. brasiliensis isolates in Espírito Santo. Different genotypes forming subgroups within the same population suggest that these isolates do not originate from a single ancestor, indicating multiple emergences. Furthermore, terbinafine was the antifungal with the best results in vitro. However, in clinical practice, itraconazole remains the primary treatment choice. Sporotrichosis continues to advance in the state; therefore, the health system must outline one-health strategies to contain the disease to prevent future epidemics.
Journal Article
Global Aspects of Triazole Resistance in Aspergillus fumigatus with Focus on Latin American Countries
2017
Azole resistance in Aspergillus has emerged as an escalating problem in health care, and it has been detected in patients exposed, or not, to these drugs. It is known that azole antifungals are widely applied not only in clinical treatments for fungal infections, but also as agricultural fungicides, resulting in a significant threat for human health. Although the number of cases of azole-resistant aspergillosis is still limited, various resistance mechanisms are described from clinical and environmental isolates. These mechanisms consist mainly of alterations in the target of azole action (CYP51A gene)—specifically on TR34/L98H and TR46/Y121F/T289A, which are responsible for over 90% of resistance cases. This review summarizes the epidemiology, management, and extension of azole resistance in A. fumigatus worldwide and its potential impact in Latin American countries, emphasizing its relevance to clinical practice.
Journal Article
Endophytic Fungi of Calea pinnatifida (Asteraceae): Dereplication of Crude Extracts, Antimicrobial Properties, and Identification of New Tetronic Acid Derivative Produced by Hypomontagnella barbarensis
by
dos Santos, Glaucia Queiroz
,
de Carvalho, Jamile Ambrósio
,
Caldas, Lhaís Araújo
in
Antimicrobial activity
,
Antimicrobial agents
,
Bacterial infections
2025
Endophytic fungi are increasingly being recognized for their diverse metabolites that may exhibit antimicrobial properties. In our study, we isolated seven endophytic fungal strains from Calea pinnatifida, which were identified as Hypomontagnella barbarensis, Neopestalotiopsis clavispora, Nigrospora sacchari-officinarum, Annulohypoxylon moriforme, Colletotrichum siamense, and Colletotrichum karstii (with two isolates from the same species). Furthermore, the antimicrobial activity of the extracts was assessed, revealing that the extract from Hypomontagnella barbarensis demonstrated activity against Staphylococcus aureus. Further investigation of secondary metabolites, employing UHPLC-HR-ESI-MS/MS in combination with molecular networking, facilitated annotation of the nine compounds. Of these, five were identified based on matches with the GNPS spectral library, and four were predicted based on the molecular network. Notably, from the extract of Hypomontagnella barbarensis, two pairs of diastereoisomeric acyl-tetronic acid derivatives were isolated and characterized using MS and NMR spectroscopy. This study highlights the potential of endophytic fungi as a valuable source of novel antimicrobial agents.
Journal Article
Respiratory Tract Infection Caused by Fonsecaea monophora After Kidney Transplantation
by
Akiti, Tiyomi
,
Nucci, Marcio
,
Cleinman, Isabella Barbosa
in
Alveoli
,
Amphotericin B
,
Amphotericin B - therapeutic use
2017
Fonsecaea
spp. are melanized fungi which cause most cases of chromoblastomycosis. The taxonomy of this genus has been revised, now encompassing four species, with different pathogenic potential:
F. pedrosoi, F. nubica, F. pugnacius
,
and F. monophora
. The latter two species present wider clinical spectrum and have been associated with cases of visceral infection, most often affecting the brain. To our knowledge, this is the first report of proven case of
F. monophora
respiratory tract infection. A Brazilian 57-year-old-female patient underwent kidney transplantation on January 12, 2013. On the fourth postoperative month, the patient presented with fever, productive cough, and pleuritic pain in the right hemithorax. A thoracic CT scan showed a subpleural 2.2-cm nodular lesion in the right lung lower lobe, with other smaller nodules (0.5–0.7 cm) scattered in both lungs. Bronchoscopy revealed a grayish plaque on the right bronchus which was biopsied. Microscopic examination demonstrated invasion of bronchial mucosa by pigmented hyphae. Culture from the bronchial biopsy and bronchoalveolar lavage samples yielded a melanized mold, which was eventually identified as
F. monophora
. She started treatment with voriconazole (400 mg q.12h on the first day, followed by 200 mg q.12h). After 4 weeks of therapy, voriconazole dose was escalated to 200 mg q.8h and associated with amphotericin B (deoxycolate 1 mg/kg/day) because of a suspected dissemination to the brain. The patient eventually died of sepsis 8 weeks after the start of antifungal therapy. In conclusion,
F. monophora
may cause respiratory tract infection in solid organ transplant recipients.
Journal Article
Trichosporon asahii causing subcutaneous mycoses in an immunocompetent patient: case report and a minireview
by
Massaroni-Peçanha, Pedro
,
Leite, Marcelo Santos
,
Kruschewsky, Wdson Luis Lima
in
Antifungal agents
,
Antifungal Agents - therapeutic use
,
Azoles
2022
Trichosporon
spp. are a constituent of the normal flora of humans that can cause both superficial and invasive infections, mainly in immunocompromised and immunocompetent hosts, respectively. Herein, we a report of
Trichosporon asahii
causing subcutaneous fungal infection (SFI) in an immunocompetent patient after carpal tunnel surgery. Although susceptible to fluconazole, the treatment of SFI failed even using high doses of this azole. The skin lesion improved following the administration of voriconazole. We conducted a literature minireview searching reports on SFI in immunocompetent patients to check for epidemiological, diagnostic, therapeutic, and outcome characteristics. A total of 32 cases were reported. Despite being uncommon, the clinical suspicion and early diagnosis of SFI in immunocompetent patients undergoing previous surgery are important. Our study indicated that the azoles are the most active antifungal agents against
Trichosporon
spp., except for fluconazole, and voriconazole can be considered the first therapeutic option.
Journal Article