Epidemiology of coccidioidomycosis in Argentina, an update.

The National Reference Laboratory in Clinical Mycology of Argentina conducted a retrospective review of human coccidioidomycosis cases diagnosed by the National Mycology Laboratory Network of Argentina between 2010 and 2022 to determine the burden of the disease in the country. A total of 100 human coccidioidomycosis cases were documented, with a higher prevalence in male patients (male-to-female ratio of 1.9:1), with a median age of 41 years. Comparing the number of cases between two 10-year periods (2000-2009 and 2010-2019), the increase was 36.51% (from 63 to 86 cases). Among the 100 recorded cases, 79 tested positive using the double immunodiffusion test. Spherules were observed in 19 cases through histopathology or direct microscopic examination and the fungus was isolated in 39 cases. Thirty-six isolates were identified as Coccidioides posadasii through partial sequencing of the Ag2/PRA gene. Catamarca province had the highest number of cases, comprising 64% of the total, with an incidence rate above 1.0-2.5/100,000 inhabitants until 2018. However, there has been a recent downward trend in the region from 2018 to 2022. It is concerning that more than half of diagnosed cases were chronic pulmonary or disseminated forms, indicating a lack of early disease detection. To rectify this issue, it is imperative to conduct targeted training programs for healthcare personnel and enhance public awareness within the endemic area. This will contribute to a better understanding of the true burden of coccidioidomycosis and enable the implementation of appropriate sanitary control measures.

Cutaneous Coccidiomycosis.

ABSTRACT: Coccidiomycosis is an infectious primary pulmonary disease caused by two highly virulent fungi, Coccidioides immitis and C. Posadasii. Coccidioides spp. are endemic to the southwestern USA, Central America, and South America with infection predominating in the summer and fall seasons. The disease commonly presents with flu-like symptoms. Cutaneous manifestations are rare and are a sign of a more serious infection with poorer outcomes. In this case, a 60-year-old female presented to the dermatology clinic with a 3-month history of a mild, non-pruritic, erythematous rash located on her proximal arms and legs. Two punch biopsies were obtained, and she was found to have a non-endemic case of disseminated coccidiomycosis.

Modeling Chronic Coccidioidomycosis in Mice.

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.

Pulmonary Coccidioidomycosis: A Case Report and Literature Review.

Coccidioidomycosis is an infectious disease caused by Coccidioides immitis or C. posadasii fungus. Humans usually get infected by inhaling spores risen from the soil. Although in 60 percent of cases symptoms are absent, remaining patients can develop various manifestations of the disease, from flu-like symptoms to severe dissemination or meningitis. In endemic regions (California, Arizona, Mexico, Central, and South America), pulmonary coccidioidomycosis causes 25% of community-acquired cases of pneumonia. We present the first registered case of pulmonary coccidioidomycosis in Lithuania. Clinical presentation, pathogenesis, treatment options, and diagnostic alternatives are discussed.

A chromosomal-level reference genome of the widely utilized Coccidioides posadasii laboratory strain "Silveira".

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.

The clinical laboratory evolution in coccidioidomycosis detection: Future perspectives.

Coccidioidomycosis is a systemic disease caused by the fungi Coccidioides immitis and C. posadasii. It is a prevalent disease in arid regions with high temperatures and low precipitations in America. Coccidioidomycosis is a highly endemic disease of US-Mexico border states but commonly underdiagnosed. The diagnosis of coccidiomycosis is not easy due to the lack of specific symptoms; it is usually an integral approach, including clinical laboratory tests as an essential part of the diagnosis. Nevertheless, despite various laboratory tests available, affordability can be a limitation, mainly in developing countries. This review's objectives are 1) to learn the different laboratory approaches that arose and their application for clinical diagnosis; 2) to discuss their advantages and weaknesses, and finally, 3) propose what is on the horizon for future advances in clinical laboratory diagnosis of coccidioidomycosis. It has been a long way in laboratory tests evolution to detect coccidioidomycosis from tissue microscopy to Real-Time PCR. However, there is a delay in technology adoption for Coccidioides spp. detection in the clinical laboratory. The molecular Point of Care Testing (POCT) technology has reached us in our trench while research in PCR variants stills on-going. None of the currently existing scientific literature in coccidioidomycosis research has mentioned it. However, this trend in infectious and non-infectious disease diagnosis will continue in that way in order to offer better options for an easy and fast diagnosis. Undoubtedly, the implementation of molecular POCT for Coccidioides spp. would save resources in health care attention and improve access to diagnostic tools.

Case Report: Severe Craniofacial Coccidioidomycosis in a Pregnant Woman.

Coccidioidomycosis is a systemic fungal disease caused by Coccidioides immitis and Coccidioides posadasii. The lungs are the most common and often the initial site of involvement, and the non-pulmonary presentation is infrequent. We describe an unusual case of primary craniocutaneous coccidioidomycosis in a pregnant woman with infected bilateral periorbital nodules, intense pain at paranasal sinuses, and several osteolytic skull lesions. The analysis of 54 cases available in the literature makes us suggest that the area between the United States and Mexico is a risk zone for primary cutaneous coccidioidomycosis.

Systemic coccidioidomycosis in a dog in Northeastern Brazil / Coccidioidomicose sistêmica em um cão no Nordeste do Brasil

We described a case of systemic infection by Coccidioides sp. in a dog. An adult, mixed breed, free-ranging male dog presented with clinical signs that included apathy, cachexia, anorexia, limited mobility with sternal recumbency, bilateral mucopurulent ocular discharge, dyspnoea, pulmonary crepitation, erosive and nodular lesions on the skin, and swelling and stiffness of the left tibiotarsal joint. The dog was submitted to a postmortem examination. Grossly, there were multiple yellow to white nodules in various organs. Histologically, the lesions were characterized as pyogranulomatous inflammation associated with fungal spherules morphologically consistent with Coccidioides sp. The dog was concomitantly diagnosed with undifferentiated sarcoma affecting the skin, lymph nodes, liver, and testicles. The diagnosis of coccidioidomycosis was made based on the histologic changes associated with morphotintorial features and positive immunolabeling of organisms with anti-Coccidioides immunohistochemistry. This case demonstrated that Coccidioides sp. can infect dogs that inhabit urban centers in the semiarid region of Northeastern Brazil, likely due to exposure to dust from contaminated environments.

Descreve-se um caso de infecção sistêmica por Coccidioides em um cão. Um cão adulto, sem raça definida e errante, atendido com sinais clínicos que incluíram apatia, caquexia, anorexia, dificuldade de locomoção com decúbito esternal, secreção ocular bilateral mucopurulenta, dispneia, crepitação pulmonar, lesões erosivas e nodulares na pele, aumento de volume e rigidez na articulação tibiotársica do membro pélvico esquerdo. O cão foi submetido a um exame post-mortem. Macroscopicamente, haviam múltiplos nódulos amarelo-brancacentos em vários órgãos. Histologicamente, as lesões foram caracterizadas por inflamação piogranulomatosa associada a esférulas fúngicas morfologicamente consistentes com Coccidioides sp. O cão foi diagnosticado concomitantemente com sarcoma indiferenciado afetando a pele, linfonodos, fígado e testículos. O diagnóstico de coccidioidomicose foi realizado com base nas alterações histológicas associadas as características morfotintoriais e imunomarcação positiva dos organismos com anti-Coccidioides na imuno-histoquímica. Esse caso demonstra que Coccidioides sp. pode infectar cães que habitam centros urbanos no semiárido do Nordeste do Brasil, provavelmente devido à exposição a poeira de ambientes contaminados.

Systemic coccidioidomycosis in a dog in Northeastern Brazil / Coccidioidomicose sistêmica em um cão no Nordeste do Brasil

We described a case of systemic infection by Coccidioides sp. in a dog. An adult, mixed breed, free-ranging male dog presented with clinical signs that included apathy, cachexia, anorexia, limited mobility with sternal recumbency, bilateral mucopurulent ocular discharge, dyspnoea, pulmonary crepitation, erosive and nodular lesions on the skin, and swelling and stiffness of the left tibiotarsal joint. The dog was submitted to a postmortem examination. Grossly, there were multiple yellow to white nodules in various organs. Histologically, the lesions were characterized as pyogranulomatous inflammation associated with fungal spherules morphologically consistent with Coccidioides sp. The dog was concomitantly diagnosed with undifferentiated sarcoma affecting the skin, lymph nodes, liver, and testicles. The diagnosis of coccidioidomycosis was made based on the histologic changes associated with morphotintorial features and positive immunolabeling of organisms with anti-Coccidioides immunohistochemistry. This case demonstrated that Coccidioides sp. can infect dogs that inhabit urban centers in the semiarid region of Northeastern Brazil, likely due to exposure to dust from contaminated environments.(AU)

Descreve-se um caso de infecção sistêmica por Coccidioides em um cão. Um cão adulto, sem raça definida e errante, atendido com sinais clínicos que incluíram apatia, caquexia, anorexia, dificuldade de locomoção com decúbito esternal, secreção ocular bilateral mucopurulenta, dispneia, crepitação pulmonar, lesões erosivas e nodulares na pele, aumento de volume e rigidez na articulação tibiotársica do membro pélvico esquerdo. O cão foi submetido a um exame post-mortem. Macroscopicamente, haviam múltiplos nódulos amarelo-brancacentos em vários órgãos. Histologicamente, as lesões foram caracterizadas por inflamação piogranulomatosa associada a esférulas fúngicas morfologicamente consistentes com Coccidioides sp. O cão foi diagnosticado concomitantemente com sarcoma indiferenciado afetando a pele, linfonodos, fígado e testículos. O diagnóstico de coccidioidomicose foi realizado com base nas alterações histológicas associadas as características morfotintoriais e imunomarcação positiva dos organismos com anti-Coccidioides na imuno-histoquímica. Esse caso demonstra que Coccidioides sp. pode infectar cães que habitam centros urbanos no semiárido do Nordeste do Brasil, provavelmente devido à exposição a poeira de ambientes contaminados.(AU)

Coccidioidomycosis in a reference center in Northeast Brazil: clinical/epidemiological profile and most common radiological findings.

INTRODUCTION: Coccidioidomycosis, a disease caused by Coccidioides immitis or Coccidioides posadasii, is endemic in arid climatic regions in Northeast Brazil. Its prevalence is higher among young adult males living in rural areas. Existing literature about this disease in Ceará, a Northeast Brazilian state, are scarce. Here, we aimed to outline the clinical and epidemiological profiles, radiological patterns, and therapeutic responses of patients with coccidioidomycosis in a reference center in Ceará, Brazil. METHODS: This is a descriptive study with quantitative analysis. Patients who underwent medical follow-up in São José Hospital of Infectious Diseases and received confirmed mycological diagnosis of coccidioidomycosis between January, 2007 and December 2017 were included. Epidemiological, clinical, radiological, and therapeutic response data were collected from medical charts. RESULTS: Thirty patients were included. The patients were males with median age of 30 years, and 73% were considered to have high-risk exposure to Coccidioides owing to professional activities. Cough (96.7%), dyspnea (63.3%), fever (86.7%), and pleuritic pain (60%) were the most prevalent clinical manifestations. Interstitial pattern (91.3%) was the most frequent pulmonary radiological finding. Fluconazole, amphotericin B, and itraconazole were administered for treatment (in 82.1%, 42.8%, and 21.4% of cases, respectively). A favorable outcome was observed in 83.8% of patients. CONCLUSIONS: Coccidioidomycosis was more prevalent in the central and southern regions of the State of Ceará. Understanding the local epidemiology and clinical manifestations of the disease, in addition to the pulmonary radiologic findings, may aid the early detection of coccidioidomycosis and facilitate early diagnosis.

Risk for Coccidioidomycosis among Hispanic Farm Workers, California, USA, 2018.

To determine occupational risk factors for coccidioidomycosis among adult Hispanic outdoor agricultural workers in California, USA, we conducted a case-control study of workers seen at the Kern County medical facility and referred to the public health laboratory for coccidioidomycosis serologic testing. Participants completed an interviewer-administered health and work questionnaire. Among 203 participants (110 case-patients with positive and 93 controls with negative serologic results), approximately half were women, and more than three quarters were born in Mexico. Associated with coccidioidomycosis were self-reported dust exposure and work with root and bulb vegetable crops. A protective factor was leaf removal, an activity associated with grape cultivation. We conclude that subjective dust exposure and work with root and bulb vegetable crops are associated with increased risk for coccidioidomycosis among Hispanic farm workers. The agricultural industry should evaluate and promote dust-reduction measures, including wetting soil and freshly harvested products.

Coccidioidal meningitis in non-AIDS patients. A case series at a Mexican neurological referral center.

BACKGROUND: Coccidioidal meningitis is a life-threatening condition and a diagnostic challenge in cases of chronic meningitis. It is associated to severe complications, like basal arachnoiditis, hydrocephalus, and secondary vasculitis. OBJECTIVE: To present a 20-year retrospective clinical series of coccidioidal meningitis cases at a Mexican neurological referral center. RESULTS: The clinical records of 11 patients, predominantly males, were retrieved. Weight loss and night sweats were observed in 64 % of cases. Neurological signs included intracranial hypertension in 91 % of cases, altered alertness and meningeal syndrome in 72 %, and neuropsychiatric symptoms in 64 %. Mean CSF glucose levels were 30 ± 25 mg/dL, and pleocytosis ranged from 0 to 2218 cells/mm3. The diagnosis was confirmed by coccidioidal antigen latex agglutination in 91 % of cases. Radiological findings were hepatomegaly in 55 % of cases and pneumonia in 45 %. Neuroimaging findings included leptomeningitis in 73 % of cases, pachymeningitis in 45 %, and vascular involvement in 91 %. Less common findings included spinal cord lesion and mycotic aneurism, found in 18 % of cases. A molecular coccidioidal DNA test confirmed the predominance of Coccidioides immitis, detected in 64 % of cases. With respect to the clinical outcome, 46 % of patients died. The survivors suffered from sequels like chronic headache, cognitive alterations, and depression. CONCLUSIONS: Coccidioidal meningitis is an entity with high mortality rates. More than one half of patients suffered disseminated disease. Although meningeal signs are not frequent in chronic meningitis, more than two-thirds of our patients showed mild nuchal rigidity. In addition, cerebral and cerebellar volume loss, associated with cognitive impairment and depression, was often observed in surviving patients during the clinical-radiological follow-up.

Primary Cutaneous Coccidioidomycosis: An Update.

Coccidioidomycosis is an endemic mycosis of the southern United States, Northern Mexico, and South America. Primary cutaneous coccidioidomycosis, despite being a very rare clinical presentation, has shown an increasing incidence. An extensive literature search for cutaneous coccidioidomycosis cases was performed using the OLDMEDLINE, PubMed, Cochrane, LILACS and Google Scholar databases for studies published from January 1927 through December 21, 2019. Forty-two observational studies were included totaling 82 cases of primary cutaneous coccidioidomycosis. Narrative reviews, systematic reviews, and meta-analyses were also included. Additionally, an original case was included. Patients with primary cutaneous coccidioidomycosis share the same geographical and epidemiological characteristics as those with pulmonary or disseminated coccidioidomycosis. Most of the imported cases came from endemic areas. A large portion of cases had prior local skin trauma. Tissue culture is still the leading diagnostic method; nevertheless, molecular techniques such as polymerase chain reaction (PCR) are currently relevant to differentiate between species. First-line treatment consists of azoles; however, it has an excellent prognosis even without treatment. Primary cutaneous coccidioidomycosis should be considered a differential diagnosis of unusual infections or neoformations in any part of the body in resident populations of endemic areas or in patients with a previous history of travel to these areas.

Coccidioidomycosis in a reference center in Northeast Brazil: clinical/epidemiological profile and most common radiological findings

Abstract INTRODUCTION: Coccidioidomycosis, a disease caused by Coccidioides immitis or Coccidioides posadasii, is endemic in arid climatic regions in Northeast Brazil. Its prevalence is higher among young adult males living in rural areas. Existing literature about this disease in Ceará, a Northeast Brazilian state, are scarce. Here, we aimed to outline the clinical and epidemiological profiles, radiological patterns, and therapeutic responses of patients with coccidioidomycosis in a reference center in Ceará, Brazil. METHODS This is a descriptive study with quantitative analysis. Patients who underwent medical follow-up in São José Hospital of Infectious Diseases and received confirmed mycological diagnosis of coccidioidomycosis between January, 2007 and December 2017 were included. Epidemiological, clinical, radiological, and therapeutic response data were collected from medical charts. RESULTS Thirty patients were included. The patients were males with median age of 30 years, and 73% were considered to have high-risk exposure to Coccidioides owing to professional activities. Cough (96.7%), dyspnea (63.3%), fever (86.7%), and pleuritic pain (60%) were the most prevalent clinical manifestations. Interstitial pattern (91.3%) was the most frequent pulmonary radiological finding. Fluconazole, amphotericin B, and itraconazole were administered for treatment (in 82.1%, 42.8%, and 21.4% of cases, respectively). A favorable outcome was observed in 83.8% of patients. CONCLUSIONS Coccidioidomycosis was more prevalent in the central and southern regions of the State of Ceará. Understanding the local epidemiology and clinical manifestations of the disease, in addition to the pulmonary radiologic findings, may aid the early detection of coccidioidomycosis and facilitate early diagnosis.

Population Structure and Genetic Diversity among Isolates of Coccidioides posadasii in Venezuela and Surrounding Regions.

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.

Design and evaluation of an AFLP molecular marker for the detection of Coccidioides spp. in biological samples.

At present, there is no standardized marker that is routinely used in clinical laboratories to diagnose coccidioidomycosis. Thus, the goals of this study were to obtain a sequence characterized amplified region (SCAR) marker for the identification of Coccidioides spp., evaluate its specificity and sensitivity in fungal DNA-spiked blood and sputum samples, and compare it with previously described molecular markers. Specific amplified fragment length polymorphism (AFLP) amplicons for Coccidioides immitis and Coccidioides posadasii were cloned into the vector pGEM® -T Easy vector and sequenced to develop a SCAR marker. Oligonucleotides were designed to identify Coccidioides spp. by polymerase chain reaction (PCR), and the specificity and sensitivity of these oligonucleotides were tested with the DNA from related pathogens. The specificity and sensitivity of the SCAR marker was evaluated with blood and sputum samples spiked with Coccidioides DNA and compared with other previously described markers (621, GAC2, and Ag2/PRA). In addition, the conditions for its use were established using biological samples. A specific marker named SCAR300 was obtained to identify Coccidioides spp. that exhibited good sensitivity and specificity. The results showed that all of the markers tested in this study can identify Coccidioides spp. However, the SCAR300 and 621 markers were the most sensitive, whereas the SCAR300 marker was the most specific. Thus, the SCAR300 marker is a useful tool to identify Coccidioides spp.

The mysterious desert dwellers: Coccidioides immitis and Coccidioides posadasii, causative fungal agents of coccidioidomycosis.

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.

Laboratory exposure to Coccidioides: lessons learnt in a non-endemic country.

Coccidioides is a primary pathogenic fungus, which infects humans through highly infectious arthroconidia, causing substantial morbidity including life-threatening disseminated infections. Due to the low infectious dose, laboratory personnel might become infected during diagnostic procedures. Accordingly, coccidioidomycosis is reported as the most frequent laboratory-acquired systemic mycosis worldwide. This risk is aggravated in non-endemic countries, where the diagnosis may not be suspected. We report on an inadvertent exposure of 44 persons to Coccidioides posadasii in a clinical microbiology laboratory in Chile, the measures of containment after rapid diagnosis with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and the lessons learnt in a non-endemic setting.

Coccidioides ecology and genomics.

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.