RESUMO
Coccidioidomycosis, listed as a priority mycosis by the WHO, is endemic in the United States but often overlooked in Central and South America. Employing a multi-institutional approach, we investigate how disease characteristics, pathogen genetic variation, and environmental factors impact coccidioidomycosis epidemiology and outcomes in South America. We identified 292 cases (1978-2021) and 42 outbreaks in Piauí and Maranhão states, Brazil, the largest series outside the US/Mexico epidemic zone. The male-to-female ratio was 57.4:1 and the most common activity was armadillo hunting (91.1%) 4 to 30 days before symptom onset. Most patients (92.8%) exhibited typical acute pulmonary disease, with cough (93%), fever (90%), and chest pain (77%) as predominant symptoms. The case fatality rate was 8%. Our negative binomial regression model indicates that reduced precipitation levels in the current (p = 0.015) and preceding year (p = 0.001) predict heightened incidence. Unlike other hotspots, acidic soil characterizes this region. Brazilian strains differ genomically from other C. posadasii lineages. Northeastern Brazil presents a distinctive coccidioidomycosis profile, with armadillo hunters facing elevated risks. Low annual rainfall emerges as a key factor in increasing cases. A unique C. posadasii lineage in Brazil suggests potential differences in environmental, virulence, and/or pathogenesis traits compared to other Coccidioides genotypes.
Assuntos
Coccidioidomicose , Humanos , Feminino , Masculino , Animais , Brasil/epidemiologia , Coccidioidomicose/epidemiologia , Tatus , Genômica , GenótipoRESUMO
ABSTRACTHistoplasmosis is an endemic mycosis in North America frequently reported along the Ohio and Mississippi River Valleys, although autochthonous cases occur in non-endemic areas. In the United States, the disease is provoked by two genetically distinct clades of Histoplasma capsulatum sensu lato, Histoplasma mississippiense (Nam1) and H. ohiense (Nam2). To bridge the molecular epidemiological gap, we genotyped 93 Histoplasma isolates (62 novel genomes) including clinical, environmental, and veterinarian samples from a broader geographical range by whole-genome sequencing, followed by evolutionary and species niche modelling analyses. We show that histoplasmosis is caused by two major lineages, H. ohiense and H. mississippiense; with sporadic cases caused by H. suramericanum in California and Texas. While H. ohiense is prevalent in eastern states, H. mississipiense was found to be prevalent in the central and western portions of the United States, but also geographically overlapping in some areas suggesting that these species might co-occur. Species Niche Modelling revealed that H. ohiense thrives in places with warmer and drier conditions, while H. mississippiense is endemic to areas with cooler temperatures and more precipitation. In addition, we predicted multiple areas of secondary contact zones where the two species co-occur, potentially facilitating gene exchange and hybridization. This study provides the most comprehensive understanding of the genomic epidemiology of histoplasmosis in the USA and lays a blueprint for the study of invasive fungal diseases.
Assuntos
Histoplasmose , Histoplasmose/epidemiologia , Histoplasma/genética , Genótipo , Genômica , TexasRESUMO
Feline-transmitted sporotrichosis has garnered attention due to the recent high incidence and the lack of efficient control in the epicenter of the epidemic, Rio de Janeiro, Brazil. Sporothrix brasiliensis is the major pathogen involved in feline-to-human sporotrichosis in Brazil and displays more virulent genotypes than the closely related species S. schenckii. Over the last two decades, several reports of antifungal-resistant strains have emerged. Sequencing and comparison analysis of the outbreak strains allowed us to observe that the azole non-wild-type S. brasiliensis strain CFP 1054 had significant chromosomal variations compared to wild-type strains. One of these variants includes a region of 231 Kb containing 75 duplicated genes, which were overrepresented for lipid and isoprenoid metabolism. We also identified an additional strain (CFP 1055) that was resistant to itraconazole and amphotericin B, which had a single nucleotide polymorphism in the tac1 gene. The patients infected with these two strains showed protracted clinical course and sequelae. Even though our sample size is modest, these results suggest the possibility of identifying specific point mutations and large chromosomal duplications potentially associated with antifungal resistance and clinical outcomes of sporotrichosis.
Assuntos
Sporothrix , Esporotricose , Animais , Gatos , Humanos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Brasil/epidemiologia , Variações do Número de Cópias de DNA , Polimorfismo de Nucleotídeo Único , Sporothrix/genética , Esporotricose/epidemiologia , Esporotricose/microbiologia , Farmacorresistência Fúngica/genéticaRESUMO
Coccidioidomycosis is a common fungal disease that is endemic to arid and semi-arid regions of both American continents. Coccidioides immitis and Coccidioides posadasii are the etiological agents of the disease, also known as Valley Fever. For several decades, the C. posadasii strain Silveira has been used widely in vaccine studies, is the source strain for production of diagnostic antigens, and is a widely used experimental strain for functional studies. In 2009, the genome was sequenced using Sanger sequencing technology, and a draft assembly and annotation were made available. In this study, the genome of the Silveira strain was sequenced using single molecule real-time sequencing PacBio technology, assembled into chromosomal-level contigs, genotyped, and the genome was reannotated using sophisticated and curated in silico tools. This high-quality genome sequencing effort has improved our understanding of chromosomal structure, gene set annotation, and lays the groundwork for identification of structural variants (e.g. transversions, translocations, and copy number variants), assessment of gene gain and loss, and comparison of transposable elements in future phylogenetic and population genomics studies.
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Coccidioides , Coccidioidomicose , Sequência de Bases , Coccidioides/genética , Coccidioidomicose/diagnóstico , Coccidioidomicose/epidemiologia , Coccidioidomicose/genética , Humanos , FilogeniaRESUMO
Histoplasmosis is a severe mycotic disease affecting thousands of immunocompetent and immunocompromised individuals with high incidence in Latin America, where the disease agents are Histoplasma capsulatum and Histoplasma suramericanum. In this work, we used whole-genome sequencing to infer the species diversity and the population structure of H. suramericanum in South America. We find evidence for strong population structure and little admixture within the species. Genome-level phylogenetic trees indicate the existence of at least three different discrete populations. We recovered the existence of a previously identified population, LAmB, and confirm that it is highly differentiated along the whole genome. We also find that H. suramericanum is composed of two populations, one in Northern South America, and another in the southern portion of the continent. Moreover, one of the lineages from the southern population is endemic to Rio de Janeiro and there was no association with clinical data and species isolated from patients with histoplasmosis. Our results point out the need to characterize the symptomatology of histoplasmosis caused by different species and lineages of Histoplasma spp.
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Sporotrichosis is a subcutaneous infection caused by fungi from the genus Sporothrix. It is transmitted by inoculation of infective particles found in plant-contaminated material or diseased animals, characterizing the classic sapronotic and emerging zoonotic transmission, respectively. Since 1998, southeastern Brazil has experienced a zoonotic sporotrichosis epidemic caused by S. brasiliensis, centred in the state of Rio de Janeiro. Our observation of feline sporotrichosis cases in Brasília (Midwestern Brazil), around 900â km away from Rio de Janeiro, led us to question whether the epidemic caused by S. brasiliensis has spread from the epicentre in Rio de Janeiro, emerged independently in the two locations, or if the disease has been present and unrecognized in Midwestern Brazil. A retrospective analysis of 91 human and 4 animal cases from Brasília, ranging from 1993 to 2018, suggests the occurrence of both sapronotic and zoonotic transmission. Molecular typing of the calmodulin locus identified S. schenckii as the agent in two animals and all seven human patients from which we were able to recover clinical isolates. In two other animals, the disease was caused by S. brasiliensis. Whole-genome sequence typing of seven Sporothrix spp. strains from Brasília and Rio de Janeiro suggests that S. brasiliensis isolates from Brasília are genetically distinct from those obtained at the epicentre of the outbreak in Rio de Janeiro, both in phylogenomic and population genomic analyses. The two S. brasiliensis populations seem to have separated between 2.2 and 3.1 million years ago, indicating independent outbreaks or that the zoonotic S. brasiliensis outbreak might have started earlier and be more widespread in South America than previously recognized.
Assuntos
Calmodulina/genética , Sporothrix/classificação , Esporotricose/epidemiologia , Sequenciamento Completo do Genoma/métodos , Zoonoses/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Brasil/epidemiologia , Gatos , Criança , Pré-Escolar , Estudos Transversais , Cães , Evolução Molecular , Feminino , Genoma Fúngico , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Tipagem Molecular , Filogenia , Sporothrix/genética , Sporothrix/isolamento & purificação , Esporotricose/microbiologia , Adulto Jovem , Zoonoses/epidemiologiaRESUMO
Modern genome analysis and phylogenomic methods have increased the number of fungal species, as well as enhanced appreciation of the degree of diversity within the fungal kingdom. In this context, we describe a new Parengyodontium species, P. americanum, which is phylogenetically related to the opportunistic human fungal pathogen P. album. Five unusual fungal isolates were recovered from five unique and confirmed coccidioidomycosis patients, and these isolates were subsequently submitted to detailed molecular and morphological identification procedures to determine identity. Molecular and morphological diagnostic analyses showed that the isolates belong to the Cordycipitaceae. Subsequently, three representative genomes were sequenced and annotated, and a new species, P. americanum, was identified. Using various genomic analyses, gene family expansions related to novel compounds and potential for ability to grow in diverse habitats are predicted. A general description of the genomic composition of this newly described species and comparison of genome content with Beauveria bassiana, Isaria fumosorosea and Cordyceps militaris shows a shared core genome of 6371 genes, and 148 genes that appear to be specific for P. americanum. This work provides the framework for future investigations of this interesting fungal species.
Assuntos
Coccidioidomicose/microbiologia , Hypocreales , Beauveria/genética , Cordyceps/genética , Proteínas Fúngicas/genética , Genoma Fúngico , Humanos , Hypocreales/classificação , Hypocreales/citologia , Hypocreales/genética , Hypocreales/isolamento & purificação , Infecções Oportunistas/microbiologia , Filogenia , ProteômicaRESUMO
Coccidioides posadasii is a pathogenic fungus that causes coccidioidomycosis in many arid regions of the Americas. One of these regions is bordered by the Caribbean Sea, and the surrounding landscape may play an important role in the dispersion of C. posadasii across South America through southeastern Mexico, Honduras, Guatemala, and Venezuela. Comparative phylogenomic analyses of C. posadasii reveal that clinical strains from Venezuela are genetically distinct from the North American populations found in (i) Arizona and (ii) Texas, Mexico, and the rest of South America (TX/MX/SA). We find evidence for admixture between the Venezuela and the North American populations of C. posadasii in Central America. Additionally, the proportion of Venezuelan alleles in the admixed population decreases as latitude (and distance from Venezuela) increases. Our results indicate that the population in Venezuela may have been subjected to a recent bottleneck and shows a strong population structure. This analysis provides insight into potential for Coccidioides spp. to invade new regions.IMPORTANCE Valley Fever is a fungal disease caused by two species of fungi: Coccidioides immitis and C. posadasii These fungi are found throughout the arid regions of North and South America; however, our understanding of genetic diversity and disease in South America is limited. In this report, we analyze 10 new genomes of Coccidioides posadasii from regions bordering the Caribbean Sea. We show that these populations are distinct and that isolates from Venezuela are likely a result of a recent bottleneck. These data point to patterns that might be observed when investigating recently established populations.
Assuntos
Coccidioides/genética , Coccidioidomicose/microbiologia , Variação Genética , Coccidioides/classificação , Coccidioides/isolamento & purificação , Coccidioidomicose/epidemiologia , Humanos , América do Norte/epidemiologia , Filogenia , América do Sul/epidemiologia , Venezuela/epidemiologiaRESUMO
INTRODUCTION: The agents of paracoccidioidomycosis, historically identified as Paracoccidioides brasiliensis, are in fact different phylogenetic species. This study aims to evaluate associations between Paracoccidioides phylogenetic species and corresponding clinical data. METHODS: Paracoccidioides strains from INI/Fiocruz patients (1998-2016) were recovered. Socio-demographic, epidemiological, clinical, serological, therapeutic and prognostic data of the patients were collected to evaluate possible associations of these variables with the fungal species identified through partial sequencing of the ADP-ribosylation factor (arf) and the 43-kDa-glycoprotein (gp43) genes. RESULTS: Fifty-four fungal strains were recovered from 47 patients, most (72.3%) infected in Rio de Janeiro state, Brazil. Forty-one cases were caused by Paracoccidioides brasiliensis and six by Paracoccidioides americana (former PS2). P. brasiliensis was responsible for severe lymph abdominal forms, whereas patients infected with P. americana presented a high rate of adrenal involvement. However, no statistically significant associations were found for all variables studied. P. americana presented 100% reactivity to immunodiffusion, even when tested against antigens from other species, while negative results were observed in 9 (20%) cases caused by P. brasiliensis, despite being tested against a homologous antigen. CONCLUSIONS: P. brasiliensis and P. americana are sympatric and share similar clinical features and habitat, where they may compete for similar hosts.
Assuntos
Patrimônio Genético , Paracoccidioides/classificação , Paracoccidioides/genética , Paracoccidioidomicose/microbiologia , Paracoccidioidomicose/patologia , Simpatria , Fatores de Ribosilação do ADP/genética , Adulto , Antígenos de Fungos/genética , Brasil , Feminino , Proteínas Fúngicas/genética , Glicoproteínas/genética , Humanos , Masculino , Pessoa de Meia-Idade , Paracoccidioides/isolamento & purificação , Análise de Sequência de DNARESUMO
The genus Coccidioides consists of two species: C. immitis and C. posadasii. Prior to 2000, all disease was thought to be caused by a single species, C. immitis. The organism grows in arid to semiarid alkaline soils throughout western North America and into Central and South America. Regions in the United States, with highest prevalence of disease, include California, Arizona, and Texas. The Mexican states of Baja California, Coahuila, Sonora, and Neuvo Leon currently have the highest skin test positive results. Central America contains isolated endemic areas in Guatemala and Honduras. South America has isolated regions of high endemicity including areas of Colombia, Venezuela, Argentina, Paraguay, and Brazil. Although approximately 15,000 cases per year are reported in the United States, actual disease burden is estimated to be in the hundreds of thousands, as only California and Arizona have dedicated public health outreach, and report and track disease reliably. In this review, we survey genomics, epidemiology, ecology, and summarize aspects of disease, diagnosis, prevention, and treatment.
Assuntos
Coccidioides/patogenicidade , Coccidioidomicose/epidemiologia , Clima Desértico , Animais , América Central/epidemiologia , Coccidioides/genética , Coccidioides/isolamento & purificação , Coccidioidomicose/diagnóstico , Coccidioidomicose/tratamento farmacológico , Ecologia , Genômica , Humanos , América do Norte/epidemiologia , América do Sul/epidemiologiaRESUMO
Although the natural history and ecology of Coccidioides spp. have been studied for over 100 years, many fundamental questions about this fungus remain unanswered. Two of the most challenging aspects of the study of Coccidioides have been the undefined ecological niche and the outdated geographic distribution maps dating from midcentury. This review details the history of Coccidioides ecological research, and discusses current strategies and advances in understanding Coccidioides genetics and ecology.
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Coccidioides/genética , Ecossistema , Genômica , Animais , California/epidemiologia , Coccidioidomicose/epidemiologia , Coccidioidomicose/microbiologia , Genética Populacional , Geografia , História do Século XX , História do Século XXI , Humanos , México/epidemiologia , Camundongos , Pesquisa/história , Microbiologia do Solo , Sequenciamento Completo do GenomaRESUMO
Coccidioides posadasii is a pathogenic fungus that causes coccidioidomycosis in many arid regions of the Americas. One of these regions is bordered by the Caribbean Sea, and the surrounding landscape may play an important role in the dispersion of C. posadasii across South America through southeastern Mexico, Honduras, Guatemala, and Venezuela. Comparative phylogenomic analyses of C. posadasii reveal that clinical strains from Venezuela are genetically distinct from the North American populations found in (i) Arizona and (ii) Texas, Mexico, and the rest of South America (TX/MX/SA). We find evidence for admixture between the Venezuela and the North American populations of C. posadasii in Central America. Additionally, the proportion of Venezuelan alleles in the admixed population decreases as latitude (and distance from Venezuela) increases. Our results indicate that the population in Venezuela may have been subjected to a recent bottleneck and shows a strong population structure. This analysis provides insight into potential for Coccidioides spp. to invade new regions. IMPORTANCE Valley Fever is a fungal disease caused by two species of fungi: Coccidioides immitis and C. posadasii. These fungi are found throughout the arid regions of North and South America; however, our understanding of genetic diversity and disease in South America is limited. In this report, we analyze 10 new genomes of Coccidioides posadasii from regions bordering the Caribbean Sea. We show that these populations are distinct and that isolates from Venezuela are likely a result of a recent bottleneck. These data point to patterns that might be observed when investigating recently established populations.
RESUMO
During the past 20 years, a general picture of the genetic diversity and population structure of Coccidioides, the causal agent of coccidioidomycosis (Valley fever), has emerged. The genus consists of 2 genetically diverse species, C. immitis and C. posadasii, each of which contains 1 or more distinct populations with limited gene flow. Genotypic data indicate that C. immitis is divided into 2 subpopulations (central and southern California populations) and C. posadasii is divided into 3 subpopulations (Arizona, Mexico, and Texas/South America populations). However, admixture within and among these populations and the current paucity of environmental isolates limit our understanding of the population genetics of Coccidioides. We assessed population structure of Coccidioides in Arizona by analyzing 495 clinical and environmental isolates. Our findings confirm the population structure as previously described and indicate a finer scale population structure in Arizona. Environmental isolates appear to have higher genetic diversity than isolates from human patients.