21 CFR 866.3135 - Coccidioides immitis serological reagents.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Coccidioides immitis serological reagents. 866.3135 Section 866.3135 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3135...

A genetically engineered live attenuated vaccine of Coccidioides posadasii protects BALB/c mice against coccidioidomycosis.

PubMed

Xue, Jianmin; Chen, Xia; Selby, Dale; Hung, Chiung-Yu; Yu, Jieh-Juen; Cole, Garry T

2009-08-01

Coccidioidomycosis (also known as San Joaquin Valley fever) is an occupational disease. Workers exposed to outdoor dust which contains spores of the soil-inhabiting fungus have a significantly increased risk of respiratory infection. In addition, people with compromised T-cell immunity, the elderly, and certain racial groups, particularly African-Americans and Filipinos, who live in regions of endemicity in the southwestern United States have an elevated incidence of symptomatic infection caused by inhalation of spores of Coccidioides posadasii or Coccidioides immitis. Recurring epidemics and escalation of medical costs have helped to motivate production of a vaccine against valley fever. The major focus has been the development of a defined, T-cell-reactive, recombinant protein vaccine. However, none of the products described to date have provided full protection to coccidioidal disease-susceptible BALB/c mice. Here we describe the first genetically engineered, live, attenuated vaccine that protects both BALB/c and C57BL/6 mice against coccidioidomycosis. Two chitinase genes (CTS2 and CTS3) were disrupted to yield the attenuated strain, which was unable to endosporulate and was no longer infectious. Vaccinated survivors mounted an immune response characterized by production of both T-helper-1- and T-helper-2-type cytokines. Histology revealed well-formed granulomas and markedly diminished inflammation. Significantly fewer organisms were observed in the lungs of survivors than in those of nonvaccinated mice. Additional investigations are required to further define the nature of the live, attenuated vaccine-induced immunity against Coccidioides infection.

Coccidioides Exposure and Coccidioidomycosis among Prison Employees, California, United States

PubMed Central

Niemeier, R. Todd; Burr, Gregory A.

2015-01-01

Responding to a request by corrections agency management, we investigated coccidioidomycosis in prison employees in central California, a coccidioidomycosis-endemic area. We identified 103 cases of coccidioidomycosis that occurred over 4.5 years. As a result, we recommended training and other steps to reduce dust exposure among employees and thus potential exposure to Coccidioides. PMID:25989420

Coccidioidomycosis.

PubMed Central

Galgiani, J N

1993-01-01

Coccidioidomycosis is a systemic fungal infection endemic to the southwestern United States and other parts of the western hemisphere. Although producing a wide range of disorders in healthy persons, immunosuppression predisposes to especially severe disease. Thus, a knowledge of the pathogenesis of coccidioidal infections and its relation to the normal immune responses is useful to understand the diversity of problems that Coccidioides immitis may cause. Diagnosis usually requires laboratory studies such as fungal culture or specific serologic testing. Fortunately, many patients do not need to be treated for the infection to resolve. Therapy for the more severe forms of coccidioidal infection was once limited to amphotericin B but now includes azole antifungal agents. These expanded alternatives now require physicians to weigh many factors in determining the best management for specific patients. Images PMID:8212681

Molecular markers in the epidemiology and diagnosis of coccidioidomycosis.

PubMed

Duarte-Escalante, Esperanza; Frías-De-León, María Guadalupe; Zúñiga, Gerardo; Martínez-Herrera, Erick; Acosta-Altamirano, Gustavo; Reyes-Montes, María Del Rocío

2014-01-01

The prevalence of coccidioidomycosis in endemic areas has been observed to increase daily. To understand the causes of the spread of the disease and design strategies for fungal detection in clinical and environmental samples, scientists have resorted to molecular tools that allow fungal detection in a natural environment, reliable identification in clinical cases and the study of biological characteristics, such as reproductive and genetic structure, demographic history and diversification. We conducted a review of the most important molecular markers in the epidemiology of Coccidioides spp. and the diagnosis of coccidioidomycosis. A literature search was performed for scientific publications concerning the application of molecular tools for the epidemiology and diagnosis of coccidioidomycosis. The use of molecular markers in the epidemiological study and diagnosis of coccidioidomycosis has allowed for the typing of Coccidioides spp. isolates, improved understanding of their mode of reproduction, genetic variation and speciation and resulted in the development specific, rapid and sensitive strategies for detecting the fungus in environmental and clinical samples. Molecular markers have revealed genetic variability in Coccidioides spp. This finding influences changes in the epidemiology of coccidioidomycosis, such as the emergence of more virulent or antifungal resistant genotypes. Furthermore, the molecular markers currently used to identify Coccidioides immitis and Coccidioides posadasii are specific and sensitive. However, they must be validated to determine their application in diagnosis. This manuscript is part of the series of works presented at the "V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi" (Oaxaca, Mexico, 2012). Copyright © 2013 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

Urease Produced by Coccidioides posadasii Contributes to the Virulence of This Respiratory Pathogen

PubMed Central

Mirbod-Donovan, Fariba; Schaller, Ruth; Hung, Chiung-Yu; Xue, Jianmin; Reichard, Utz; Cole, Garry T.

2006-01-01

Urease activity during in vitro growth in the saprobic and parasitic phases of Coccidioides spp. is partly responsible for production of intracellular ammonia released into the culture media and contributes to alkalinity of the external microenvironment. Although the amino acid sequence of the urease of Coccidioides posadasii lacks a predicted signal peptide, the protein is transported from the cytosol into vesicles and the central vacuole of parasitic cells (spherules). Enzymatically active urease is released from the contents of mature spherules during the parasitic cycle endosporulation stage. The endospores, together with the urease and additional material which escape from the ruptured parasitic cells, elicit an intense host inflammatory response. Ammonia production by the spherules of C. posadasii is markedly increased by the availability of exogenous urea found in relatively high concentrations at sites of coccidioidal infection in the lungs of mice. Direct measurement of the pH at these infection sites revealed an alkaline microenvironment. Disruption of the urease gene of C. posadasii resulted in a marked reduction in the amount of ammonia secreted in vitro by the fungal cells. BALB/c mice challenged intranasally with the mutant strain showed increased survival, a well-organized granulomatous response to infection, and better clearance of the pathogen than animals challenged with either the parental or the reconstituted (revertant) strain. We conclude that ammonia and enzymatically active urease released from spherules during the parasitic cycle of C. posadasii contribute to host tissue damage, which exacerbates the severity of coccidioidal infection and enhances the virulence of this human respiratory pathogen. PMID:16369007

Use of radiologic modalities in coccidioidal meningitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stadalnik, R.C.; Goldstein, E.; Hoeprich, P.D.

1981-01-01

The diagnostic utility of pentetate indium trisodium CSF studies, technetium Tc 99m brain scans, and computerized tomographic (CT) scans was evaluated in eight patients in whom coccidioidal meningitis developed following a dust storm in the Central Valley of California. The 111In flow studies and the CT scans demonstrated hydrocephalus in five patients with clinical findings suggesting this complication. Ventriculitis has not previously been diagnosed before death in patients with coccidioidal meningitis; however, it was demonstrated in two patients by the technetium Tc 99m brain scan. The finding that communicating hydrocephalus occurs early in meningitis and interferes with CSF flow intomore » infected basilar regions has important therapeutic implications in that antifungal agents injected into the lumbar subarachnoid space may not reach these regions.« less

Emerging Fungal Infections in the Pacific Northwest: The Unrecognized Burden and Geographic Range of Cryptococcus gattii and Coccidioides immitis.

PubMed

Lockhart, Shawn R; McCotter, Orion Z; Chiller, Tom M

2016-06-01

Both Cryptococcus gattii and Coccidioides can cause debilitating diseases if not identified early. It is imperative that clinicians recognize these diseases and begin treatment quickly when necessary. In order to have these two mycoses in their differential diagnosis, clinicians, microbiologists, and public health officials must be aware of the expanding geographic boundary in the case of Coccidioides immitis and the new emergence in the case of C. gattii. Accordingly, there is now mandatory reporting for cases of C. gattii and C. immitis in both Washington and Oregon, and the Centers for Disease Control and Prevention keeps a repository of available isolates. Through the One Health initiative, clinicians, veterinarians, and public health officials are collaborating to better understand the emergence and expanding geographic range of these extremely important fungal diseases.

Valley Fever: Finding New Places for an Old Disease: Coccidioides immitis Found in Washington State Soil Associated With Recent Human Infection

PubMed Central

Litvintseva, Anastasia P.; Marsden-Haug, Nicola; Hurst, Steven; Hill, Heather; Gade, Lalitha; Driebe, Elizabeth M.; Ralston, Cindy; Roe, Chandler; Barker, Bridget M.; Goldoft, Marcia; Keim, Paul; Wohrle, Ron; Thompson, George R.; Engelthaler, David M.; Brandt, Mary E.; Chiller, Tom

2015-01-01

We used real-time polymerase chain reaction and culture to demonstrate persistent colonization of soils by Coccidioides immitis, an agent of valley fever, in Washington State linked to recent human infections and located outside the endemic range. Whole-genome sequencing confirmed genetic identity between isolates from soil and one of the case-patients. PMID:25165087

Delayed Dermal Hypersensitivity in Mice to Spherule and Mycelial Extracts of Coccidioides immitis

PubMed Central

Kong, Yi-Chi M.; Savage, D. C.; Kong, Leighton N. L.

1966-01-01

Kong, Yi-chi M. (University of California, Berkeley), D. C. Savage, and Leighton N. L. Kong. Delayed dermal hypersensitivity in mice to spherule and mycelial extracts of Coccidioides immitis. J. Bacteriol. 91:876–883. 1966.—A delayed hypersensitivity reaction to spherule and mycelial extracts of Coccidioides immitis was elicited in the footpads of mice vaccinated with killed spherules. Emulsification of the spherules with Freund's adjuvants was unnecessary, but a high concentration of antigen was required to elicit the reaction. Injection of the extracts produced, initially, a swelling which subsided within 4 hr, and then induration, which began at 6 to 8 hr and reached a maximum at 24 hr. The time course of the reaction corresponded to that of the tuberculin reaction in BCG-vaccinated mice. The histological response to coccidioidal extracts was characterized by the early infiltration of both polymorphonuclear and mononuclear cells, and the subsequent predominance of mononuclear cells at 24 to 48 hr. By 72 hr, the mononuclear cells comprised >90% of the cellular infiltrate. Animals infected intranasally with arthrospores (1 to 5 ld50) reacted negatively before and during the crisis period; thereafter (by 28 to 31 days after infection), up to 50% of the survivors showed a delayed reaction. Images PMID:5894227

Mycelial forms of Coccidioides spp. in the parasitic phase associated to pulmonary coccidioidomycosis with type 2 diabetes mellitus.

PubMed

Muñoz-Hernández, B; Martínez-Rivera, M A; Palma Cortés, G; Tapia-Díaz, A; Manjarrez Zavala, M E

2008-09-01

Pulmonary coccidioidomycosis shares characteristics with other pulmonary pathologies. In tissue, spherules containing endospores are markers of Coccidioides immitis and C. posadasii infection. Mycelial forms presenting without classical parasitic structures are often misdiagnosed. The study was performed at the National Institute of Respiratory Diseases (INER) of Mexico between September 1991 and June 2005 and analyzed the association between cases, controls, and risk factors, including co-morbidity. A case was defined as any patient who presented mycelial forms and a control as any patient who presented only spherules or no parasitic forms. All patients (n = 44) with pulmonary coccidioidomycosis were diagnosed by culture, histopathology, cytology, and immunology. Type 2 diabetic patients with pulmonary coccidioidomycosis were four times more likely than non-diabetics to develop parasitic mycelial forms (95% confidence interval [CI], 0.85-20.10; P < 0.01). We formulated a comprehensive definition based on the results as follows: patients with pulmonary coccidioidomycosis with an evolution longer than 8 months, cough, hemoptysis, radiological evidence of a cavitary lesion, and type 2 diabetes mellitus, develop parasitic mycelial forms of Coccidioides spp. Based on microscopic images of patient specimens, we propose incorporating mycelial forms into the parasitic phase of Coccidioides spp. in patients with type 2 diabetes mellitus and chronic and cavitary pulmonary coccidioidomycosis.

Coccidioidomycosis among Workers Constructing Solar Power Farms, California, USA, 2011-2014.

PubMed

Wilken, Jason A; Sondermeyer, Gail; Shusterman, Dennis; McNary, Jennifer; Vugia, Duc J; McDowell, Ann; Borenstein, Penny; Gilliss, Debra; Ancock, Benedict; Prudhomme, Janice; Gold, Deborah; Windham, Gayle C; Lee, Lauren; Materna, Barbara L

2015-11-01

Coccidioidomycosis is associated with soil-disruptive work in Coccidioides-endemic areas of the southwestern United States. Among 3,572 workers constructing 2 solar power-generating facilities in San Luis Obispo County, California, USA, we identified 44 patients with symptom onset during October 2011-April 2014 (attack rate 1.2 cases/100 workers). Of these 44 patients, 20 resided in California outside San Luis Obispo County and 10 resided in another state; 9 were hospitalized (median 3 days), 34 missed work (median 22 days), and 2 had disseminated disease. Of the 25 patients who frequently performed soil-disruptive work, 6 reported frequent use of respiratory protection. As solar farm construction in Coccidioides-endemic areas increases, additional workers will probably be exposed and infected unless awareness is emphasized and effective exposure reduction measures implemented, including limiting dust generation and providing respiratory protection. Medical providers, including those in non-Coccidioides-endemic areas, should suspect coccidioidomycosis in workers with compatible illness and report cases to their local health department.

Coccidioidomycosis among Workers Constructing Solar Power Farms, California, USA, 2011–2014

PubMed Central

Sondermeyer, Gail; Shusterman, Dennis; McNary, Jennifer; Vugia, Duc J.; McDowell, Ann; Borenstein, Penny; Gilliss, Debra; Ancock, Benedict; Prudhomme, Janice; Gold, Deborah; Windham, Gayle C.; Lee, Lauren; Materna, Barbara L.

2015-01-01

Coccidioidomycosis is associated with soil-disruptive work in Coccidioides-endemic areas of the southwestern United States. Among 3,572 workers constructing 2 solar power–generating facilities in San Luis Obispo County, California, USA, we identified 44 patients with symptom onset during October 2011–April 2014 (attack rate 1.2 cases/100 workers). Of these 44 patients, 20 resided in California outside San Luis Obispo County and 10 resided in another state; 9 were hospitalized (median 3 days), 34 missed work (median 22 days), and 2 had disseminated disease. Of the 25 patients who frequently performed soil-disruptive work, 6 reported frequent use of respiratory protection. As solar farm construction in Coccidioides-endemic areas increases, additional workers will probably be exposed and infected unless awareness is emphasized and effective exposure reduction measures implemented, including limiting dust generation and providing respiratory protection. Medical providers, including those in non–Coccidioides-endemic areas, should suspect coccidioidomycosis in workers with compatible illness and report cases to their local health department. PMID:26484688

Diagnosis of coccidioidomycosis by culture: safety considerations, traditional methods, and susceptibility testing.

PubMed

Sutton, Deanna A

2007-09-01

The recovery of Coccidioides spp. by culture and confirmation utilizing the AccuProbe nucleic acid hybridization method by GenProbe remain the definitive diagnostic method. Biosafety considerations from specimen collection through culture confirmation in the mycology laboratory are critical, as acquisition of coccidioidomycosis by laboratory workers is well documented. The designation of Coccidioides spp. as select agents of potential bioterrorism has mandated strict regulation of their transport and inventory. The genus appears generally susceptible, in vitro, although no defined breakpoints exist. Susceptibility testing may assist in documenting treatment failures.

Valley fever: finding new places for an old disease: Coccidioides immitis found in Washington State soil associated with recent human infection.

PubMed

Litvintseva, Anastasia P; Marsden-Haug, Nicola; Hurst, Steven; Hill, Heather; Gade, Lalitha; Driebe, Elizabeth M; Ralston, Cindy; Roe, Chandler; Barker, Bridget M; Goldoft, Marcia; Keim, Paul; Wohrle, Ron; Thompson, George R; Engelthaler, David M; Brandt, Mary E; Chiller, Tom

2015-01-01

We used real-time polymerase chain reaction and culture to demonstrate persistent colonization of soils by Coccidioides immitis, an agent of valley fever, in Washington State linked to recent human infections and located outside the endemic range. Whole-genome sequencing confirmed genetic identity between isolates from soil and one of the case-patients. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

First case of mesh infection due to Coccidioides spp. and literature review of fungal mesh infections after hernia repair.

PubMed

Forrester, Joseph D; Gomez, Carlos A; Forrester, Jared A; Nguyen, Mike; Gregg, David; Deresinski, Stan; Banaei, Niaz; Weiser, Thomas G

2015-10-01

Fungal mesh infections are a rare complication of hernia repairs with mesh. The first case of Coccidioides spp. mesh infection is described, and a systematic literature review of all known fungal mesh infections was performed. Nine cases of fungal mesh infection are reviewed. Female and male patients are equally represented, median age is 49.5 years, and critical illness and preinfection antibiotic use were common. Fungal mesh infections are rare, but potentially fatal, complications of hernias repaired with mesh. © 2015 Blackwell Verlag GmbH.

Coccidioidomycosis among persons undergoing lung transplantation in the coccidioidal endemic region.

PubMed

Chaudhary, Sachin; Meinke, Laura; Ateeli, Huthayfa; Knox, Kenneth S; Raz, Yuval; Ampel, Neil M

2017-08-01

Coccidioidomycosis, an endemic fungal infection, is more likely to be symptomatic and severe among those receiving allogeneic transplants. While several case series have been published for various transplanted organs, none has described the incidence and outcomes in those receiving lung transplants within the coccidioidal endemic region. Patients receiving a heart-lung, single-lung, or bilateral-lung transplantation at the University of Arizona between 1985 and 2009 were retrospectively reviewed. Coccidioidomycosis occurred post transplantation in 11 (5.8%) of 189 patients. All but one patient was diagnosed with pulmonary coccidioidomycosis and only one had a history of prior coccidioidomycosis. Two patients received transplants from donors found to have coccidioidomycosis at the time of transplantation and one death was directly attributed to coccidioidomycosis. The risk of developing active coccidioidomycosis was significantly higher if the patient did not receive some type of antifungal therapy post transplantation (P<.001). Within the coccidioidal endemic region, post-transplantation coccidioidomycosis was a definable risk among lung transplant recipients. Use of antifungals appeared to reduce this incidence of disease. Almost all cases resulted in pulmonary disease, suggesting that the lung is the primary site of infection. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Assessing the Habitat of Coccidioides posadasii, the Valley Fever Pathogen: A Study of Environmental Variables and Human Incidence Data in Arizona

NASA Astrophysics Data System (ADS)

Mann, Sarina N.

Coccidioidomycosis, or Valley Fever, is an infectious disease caused by inhalation of soil-dwelling fungus Coccidioides posadasii spores in the Lower Sonoran Life Zone (LSLZ) in Arizona. In the context of climate change, the habitat of environmentally-mediated infectious diseases, such as Valley Fever, are expected to change. Connections have been drawn between climate and Valley Fever infection. The operational scale of the organism is still unknown. Here, we use climatic variables, including precipitation, soil moisture, and temperature. We use PRISM precipitation and temperature data, and Moderate Resolution Imaging Spectroradiometer (MODIS) Normalized Difference Vegetation Index (NDVI) as a measure of soil moisture for the entire state of Arizona, divided into 126 primary care areas (PCA). These data are analyzed and regressed with Valley Fever incidence to determine the effects of climatic variability on disease distribution and timing. This study confirms that Valley Fever occurrence is clustered in the LSLZ. Seasonal Valley Fever outbreak was found to be variable year-to-year based on climatic variability. The inconclusive regression analyses indicate that the operational scale of Coccidioides is smaller than the PCA region. All variables are related to Valley Fever infection, but one variable was not found to hold more predictive power than others.

Coccidioidomycosis Masquerading as Eosinophilic Ascites.

PubMed

Alavi, Kourosh; Atla, Pradeep R; Haq, Tahmina; Sheikh, Muhammad Y

2015-01-01

Endemic to the southwestern parts of the United States, coccidioidomycosis, also known as "Valley Fever," is a common fungal infection that primarily affects the lungs in both acute and chronic forms. Disseminated coccidioidomycosis is the most severe but very uncommon and usually occurs in immunocompromised individuals. It can affect the central nervous system, bones, joints, skin, and, very rarely, the abdomen. This is the first case report of a patient with coccidioidal dissemination to the peritoneum presenting as eosinophilic ascites (EA). A 27-year-old male presented with acute abdominal pain and distention from ascites. He had eosinophilia of 11.1% with negative testing for stool studies, HIV, and tuberculosis infection. Ascitic fluid exam was remarkable for low serum-ascites albumin gradient (SAAG), PMN count >250/mm(3), and eosinophils of 62%. Abdominal imaging showed thickened small bowel and endoscopic testing negative for gastric and small bowel biopsies. He was treated empirically for spontaneous bacterial peritonitis, but no definitive diagnosis could be made until coccidioidal serology returned positive. We noted complete resolution of symptoms with oral fluconazole during outpatient follow-up. Disseminated coccidioidomycosis can present in an atypical fashion and may manifest as peritonitis with low SAAG EA. The finding of EA in an endemic area should raise the suspicion of coccidioidal dissemination.

Coccidioidomycosis Masquerading as Eosinophilic Ascites

PubMed Central

Alavi, Kourosh; Atla, Pradeep R.; Haq, Tahmina; Sheikh, Muhammad Y.

2015-01-01

Endemic to the southwestern parts of the United States, coccidioidomycosis, also known as “Valley Fever,” is a common fungal infection that primarily affects the lungs in both acute and chronic forms. Disseminated coccidioidomycosis is the most severe but very uncommon and usually occurs in immunocompromised individuals. It can affect the central nervous system, bones, joints, skin, and, very rarely, the abdomen. This is the first case report of a patient with coccidioidal dissemination to the peritoneum presenting as eosinophilic ascites (EA). A 27-year-old male presented with acute abdominal pain and distention from ascites. He had eosinophilia of 11.1% with negative testing for stool studies, HIV, and tuberculosis infection. Ascitic fluid exam was remarkable for low serum-ascites albumin gradient (SAAG), PMN count >250/mm3, and eosinophils of 62%. Abdominal imaging showed thickened small bowel and endoscopic testing negative for gastric and small bowel biopsies. He was treated empirically for spontaneous bacterial peritonitis, but no definitive diagnosis could be made until coccidioidal serology returned positive. We noted complete resolution of symptoms with oral fluconazole during outpatient follow-up. Disseminated coccidioidomycosis can present in an atypical fashion and may manifest as peritonitis with low SAAG EA. The finding of EA in an endemic area should raise the suspicion of coccidioidal dissemination. PMID:26266062

Cavitary Lung Disease in an HIV-Positive Patient

DTIC Science & Technology

2009-04-01

Cryptococcus neoformans, and cytomegalovirus. She was treated with anidulafungin for aspergillosis. Discussion Pulmonary cavitation begins with...Histoplasma, Coccidioides, Blastomyces) and opportunistic pathogens (Aspergillus, Cryptococcus , Zygomycetes, Pneumocystis) Parasites: Paragonimus

Next-Generation Sequencing of Coccidioides immitis Isolated during Cluster Investigation

PubMed Central

Engelthaler, David M.; Chiller, Tom; Schupp, James A.; Colvin, Joshua; Beckstrom-Sternberg, Stephen M.; Driebe, Elizabeth M.; Moses, Tracy; Tembe, Waibhav; Sinari, Shripad; Beckstrom-Sternberg, James S.; Christoforides, Alexis; Pearson, John V.; Carpten, John; Keim, Paul; Peterson, Ashley; Terashita, Dawn

2011-01-01

Next-generation sequencing enables use of whole-genome sequence typing (WGST) as a viable and discriminatory tool for genotyping and molecular epidemiologic analysis. We used WGST to confirm the linkage of a cluster of Coccidioides immitis isolates from 3 patients who received organ transplants from a single donor who later had positive test results for coccidioidomycosis. Isolates from the 3 patients were nearly genetically identical (a total of 3 single-nucleotide polymorphisms identified among them), thereby demonstrating direct descent of the 3 isolates from an original isolate. We used WGST to demonstrate the genotypic relatedness of C. immitis isolates that were also epidemiologically linked. Thus, WGST offers unique benefits to public health for investigation of clusters considered to be linked to a single source. PMID:21291593

Valley Fever

MedlinePlus

... mold) called Coccidioides. The fungi live in the soil of dry areas like the southwestern U.S. You ... include Workers in jobs that expose them to soil dust. These include construction workers, agricultural workers, and ...

9 CFR 311.36 - Coccidioidal granuloma.

Code of Federal Regulations, 2011 CFR

2011-01-01

... systemic changes because of such disease shall be condemned. (b) Carcasses affected with localized lesions of this disease may be passed for human food after the affected parts are removed and condemned. ...

CSF coccidioides complement fixation

MedlinePlus

... The name of this infection is coccidioidomycosis, or valley fever. When the infection involves the covering of the ... and the A.D.A.M. Editorial team. Valley Fever Read more NIH MedlinePlus Magazine Read more Health ...

Coccidioidomycosis among cast and crew members at an outdoor television filming event--California, 2012.

PubMed

Wilken, Jason A; Marquez, Patricia; Terashita, Dawn; McNary, Jennifer; Windham, Gayle; Materna, Barbara

2014-04-18

In March 2013, the California Department of Public Health (CDPH) identified two Doctor's First Reports of Occupational Injury or Illness (DFRs) regarding Los Angeles County residents who had worked at the same jobsite in January 2012 and had been evaluated for possible work-associated coccidioidomycosis (valley fever). Occupational exposure to Coccidioides, the causative fungi, typically is associated with soil-disrupting activities. The physicians noted that both workers were cast or crew members filming a television series episode, and the site of possible exposure was an outdoor set in Ventura County, California. On the basis of their job titles, neither would have been expected to have been engaged in soil-disrupting activities. Los Angeles County Department of Public Health (LACDPH) conducted an outbreak investigation by using CDPH-provided occupational surveillance records, traditional infectious disease surveillance, and social media searches. This report describes the results of that investigation, which identified a total of five laboratory-confirmed and five probable cases linked to this filming event. The employer and site manager were interviewed. The site manager stated that they would no longer allow soil-disruptive work at the site and would incorporate information about the potential risk for Coccidioides exposure onsite into work contracts. Public health professionals, clinicians, and the television and film industry should be aware that employees working outdoors in areas where Coccidioides is endemic (e.g., central and southern California), even those not engaged in soil-disruptive work, might be at risk for coccidioidomycosis.

Operational guidelines (version 1.0) for geological fieldwork in areas endemic for Coccidioidomycosis (Valley Fever)

USGS Publications Warehouse

Fisher, Frederick S.; Bultman, Mark W.; Pappagianis, Demosthenes

2000-01-01

Coccidioidomycosis (Valley Fever) is a disease caused by the inhalation of the arthroconidia (spores) of Coccidioides immitis, a fungus that lives in the soils of southwestern United States. Although large numbers of people are exposed to the arthroconidia and are consequently infected, very few individuals contract the more serious forms of the disease. Earth scientists working in field areas where Coccidioides immitis is endemic have an increased risk of becoming infected. Because field operations often disturb the upper surface of the ground, they may inhale large numbers of arthroconidia. This also increases their risk of developing more severe forms of the disease. Any other occupations or activities that create dusty conditions in endemic areas also have increased risk of infection. Risk management strategies can lower the incidence of infection and also reduce the numbers of arthroconidia inhaled thereby decreasing the chances of developing more serious disease. Dust control, by utilizing dust masks, and dust prevention, by limiting ground disturbing activities, are the primary weapons against infection. However, infection risk can also be lowered by conducting fields studies in the winter months; avoiding sites favorable for Coccidioides immitis growth; seeking prompt medical treatment if flu-like or respiratory illness occur during, or within a few weeks following, fieldwork; getting a coccidioidin skin test to determine susceptibility to the disease; and by educating all members of the field party about the possibilities and consequences of infection.

Coccidioides complement fixation

MedlinePlus

... antibodies are detected in the blood sample. Normal value ranges may vary slightly among different laboratories. Some labs use different measurements or test different samples. Talk to your health care provider about the meaning of your specific test results.

Combining Forces - The Use of Landsat TM Satellite Imagery, Soil Parameter Information, and Multiplex PCR to Detect Coccidioides immitis Growth Sites in Kern County, California

PubMed Central

Lauer, Antje; Talamantes, Jorge; Castañón Olivares, Laura Rosío; Medina, Luis Jaime; Baal, Joe Daryl Hugo; Casimiro, Kayla; Shroff, Natasha; Emery, Kirt W.

2014-01-01

Coccidioidomycosis is a fungal disease acquired through the inhalation of spores of Coccidioides spp., which afflicts primarily humans and other mammals. It is endemic to areas in the southwestern United States, including the San Joaquin Valley portion of Kern County, California, our region of interest (ROI). Recently, incidence of coccidioidomycosis, also known as valley fever, has increased significantly, and several factors including climate change have been suggested as possible drivers for this observation. Up to date details about the ecological niche of C. immitis have escaped full characterization. In our project, we chose a three-step approach to investigate this niche: 1) We examined Landsat-5-Thematic-Mapper multispectral images of our ROI by using training pixels at a 750 m×750 m section of Sharktooth Hill, a site confirmed to be a C. immitis growth site, to implement a Maximum Likelihood Classification scheme to map out the locations that could be suitable to support the growth of the pathogen; 2) We used the websoilsurvey database of the US Department of Agriculture to obtain soil parameter data; and 3) We investigated soil samples from 23 sites around Bakersfield, California using a multiplex Polymerase Chain Reaction (PCR) based method to detect the pathogen. Our results indicated that a combination of satellite imagery, soil type information, and multiplex PCR are powerful tools to predict and identify growth sites of C. immitis. This approach can be used as a basis for systematic sampling and investigation of soils to detect Coccidioides spp. PMID:25380290

Local Population Structure and Patterns of Western Hemisphere Dispersal for Coccidioides spp., the Fungal Cause of Valley Fever.

PubMed

Engelthaler, David M; Roe, Chandler C; Hepp, Crystal M; Teixeira, Marcus; Driebe, Elizabeth M; Schupp, James M; Gade, Lalitha; Waddell, Victor; Komatsu, Kenneth; Arathoon, Eduardo; Logemann, Heidi; Thompson, George R; Chiller, Tom; Barker, Bridget; Keim, Paul; Litvintseva, Anastasia P

2016-04-26

Coccidioidomycosis (or valley fever) is a fungal disease with high morbidity and mortality that affects tens of thousands of people each year. This infection is caused by two sibling species, Coccidioides immitis and C. posadasii, which are endemic to specific arid locales throughout the Western Hemisphere, particularly the desert southwest of the United States. Recent epidemiological and population genetic data suggest that the geographic range of coccidioidomycosis is expanding, as new endemic clusters have been identified in the state of Washington, well outside the established endemic range. The genetic mechanisms and epidemiological consequences of this expansion are unknown and require better understanding of the population structure and evolutionary history of these pathogens. Here we performed multiple phylogenetic inference and population genomics analyses of 68 new and 18 previously published genomes. The results provide evidence of substantial population structure in C. posadasii and demonstrate the presence of distinct geographic clades in central and southern Arizona as well as dispersed populations in Texas, Mexico, South America, and Central America. Although a smaller number of C. immitis strains were included in the analyses, some evidence of phylogeographic structure was also detected in this species, which has been historically limited to California and Baja, Mexico. Bayesian analyses indicated that C. posadasii is the more ancient of the two species and that Arizona contains the most diverse subpopulations. We propose a southern Arizona-northern Mexico origin for C. posadasii and describe a pathway for dispersal and distribution out of this region. Coccidioidomycosis, or valley fever, is caused by the pathogenic fungi Coccidioides posadasii and C. immitis The fungal species and disease are primarily found in the American desert southwest, with spotted distribution throughout the Western Hemisphere. Initial molecular studies suggested a likely anthropogenic movement of C. posadasii from North America to South America. Here we comparatively analyze eighty-six genomes of the two Coccidioides species and establish local and species-wide population structures to not only clarify the earlier dispersal hypothesis but also provide evidence of likely ancestral populations and patterns of dispersal for the known subpopulations of C. posadasii. Copyright © 2016 Engelthaler et al.

Extracellular ammonia at sites of pulmonary infection with Coccidioides posadasii contributes to severity of the respiratory disease.

PubMed

Wise, Hua Zhang; Hung, Chiung-Yu; Whiston, Emily; Taylor, John W; Cole, Garry T

2013-01-01

Coccidioides is the causative agent of a potentially life-threatening respiratory disease of humans. A feature of this mycosis is that pH measurements of the microenvironment of pulmonary abscesses are consistently alkaline due to ammonia production during the parasitic cycle. We previously showed that enzymatically active urease is partly responsible for elevated concentrations of extracellular ammonia at sites of lung infection and contributes to both localized host tissue damage and exacerbation of the respiratory disease in BALB/c mice. Disruption of the urease gene (URE) of Coccidioides posadasii only partially reduced the amount of ammonia detected during in vitro growth of the parasitic phase, suggesting that other ammonia-producing pathways exist that may also contribute to the virulence of this pathogen. Ureidoglycolate hydrolase (Ugh) expressed by bacteria, fungi and higher plants catalyzes the hydrolysis of ureidoglycolate to yield glyoxylate and the release CO2 and ammonia. This enzymatic pathway is absent in mice and humans. Ureidoglycolate hydrolase gene deletions were conducted in a wild type (WT) isolate of C. posadasii as well as the previously generated Δure knock-out strain. Restorations of UGH in the mutant stains were performed to generate and evaluate the respective revertants. The double mutant revealed a marked decrease in the amount of extracellular ammonia without loss of reproductive competence in vitro compared to both the WT and Δure parental strains. BALB/c mice challenged intranasally with the Δugh/Δure mutant showed 90% survival after 30 days, decreased fungal burden, and well-organized pulmonary granulomas. We conclude that loss of both Ugh and Ure activity significantly reduced the virulence of this fungal pathogen. Copyright © 2013 Elsevier Ltd. All rights reserved.

Relating coccidioidomycosis (Valley Fever) incidence via to soil moisture conditions

USDA-ARS?s Scientific Manuscript database

Coccidioidomycosis (also called Valley fever) is caused by a soil-borne fungus, Coccidioides spp., in arid regions of the southwestern United States. Though some who develop infections from this fungus remain asymptomatic, others develop respiratory disease as a consequence. Less commonly, severe ...

Systemic fungal infections in patients with human inmunodeficiency virus.

PubMed

Rodríguez-Cerdeira, C; Arenas, R; Moreno-Coutiño, G; Vásquez, E; Fernández, R; Chang, P

2014-01-01

Histoplasmosis is a systemic infection caused by the dimorphic fungus Histoplasma capsulatum. In immunocompromised patients, primary pulmonary infection can spread to the skin and meninges. Clinical manifestations appear in patients with a CD4(+) lymphocyte count of less than 150 cells/μL. Coccidioidomycosis is a systemic mycosis caused by Coccidioides immitis and Coccidioides posadasii. It can present as diffuse pulmonary disease or as a disseminated form primarily affecting the central nervous system, the bones, and the skin. Cryptococcosis is caused by Cryptococcus neoformans (var. neoformans and var. grubii) and Cryptococcus gattii, which are members of the Cryptococcus species complex and have 5 serotypes: A, B, C, D, and AD. It is a common opportunistic infection in patients with human immunodeficiency virus (HIV)/AIDS, even those receiving antiretroviral therapy. Histopathologic examination and culture of samples from any suspicious lesions are essential for the correct diagnosis of systemic fungal infections in patients with HIV/AIDS. Copyright © 2011 Elsevier España, S.L. and AEDV. All rights reserved.

Recent Advances in Our Understanding of the Environmental, Epidemiological, Immunological, and Clinical Dimensions of Coccidioidomycosis

PubMed Central

Nguyen, Chinh; Barker, Bridget Marie; Hoover, Susan; Nix, David E.; Ampel, Neil M.; Frelinger, Jeffrey A.; Orbach, Marc J.

2013-01-01

SUMMARY Coccidioidomycosis is the endemic mycosis caused by the fungal pathogens Coccidioides immitis and C. posadasii. This review is a summary of the recent advances that have been made in the understanding of this pathogen, including its mycology, genetics, and niche in the environment. Updates on the epidemiology of the organism emphasize that it is a continuing, significant problem in areas of endemicity. For a variety of reasons, the number of reported coccidioidal infections has increased dramatically over the past decade. While continual improvements in the fields of organ transplantation and management of autoimmune disorders and patients with HIV have led to dilemmas with concurrent infection with coccidioidomycosis, they have also led to advances in the understanding of the human immune response to infection. There have been some advances in therapeutics with the increased use of newer azoles. Lastly, there is an overview of the ongoing search for a preventative vaccine. PMID:23824371

Research and Diagnostic Applications of Monoclonal Antibodies to Coccidioides immitis.

DTIC Science & Technology

1985-01-01

for Human and Animal Mycology , Georgia, May 1985. 17. COSATI CODES 18. SUBJECT TERMS (Co tinue on reverse if necessary and identify by block number...IX Congress of the International Society for Human and Animal Mycology , Atlanta GA, May 1985. ISHAM START ’IResearch and Diagnostic Applications of

Deactivation of the dimorphic fungi Histoplasma capsulatum, Blastomyces dermatitidis and Coccidioides immitis using hydrogen peroxide vapor.

PubMed

Hall, Leslie; Otter, Jonathan A; Chewins, John; Wengenack, Nancy L

2008-03-01

Hydrogen peroxide vapour (HPV) has been proposed as an alternative to formaldehyde fumigation for the decontamination of biosafety level (BSL) III laboratories. The aim of this study was to evaluate the efficacy of HPV against the dimorphic fungi Histoplasma capsulatum, Blastomyces dermatitidis and Coccidioides immitis. Working inside a class II biological safety cabinet (BSC) within a BSL III laboratory, inocula containing approximately 5-log(10) cfu/ml from the mould form of each organism suspended in RPMI medium were deposited on stainless steel discs and allowed to air dry. The organisms were exposed to HPV inside a BSC using a BIOQUELL ClarusS HPV generator. In three replicate experiments, individual discs were transferred into liquid media at timed intervals during a 105 minute HPV exposure period. Control- and HPV-exposed discs were incubated in RPMI media at 30 degrees C for 6 weeks to determine if any viable organisms remained. Positive cultures were confirmed using specific nucleic acid hybridization probes. Results indicate that H. capsulatum, B. dermatitidis and C. immitis were killed within 30 minutes of HPV exposure.

Linear Epitopes of Paracoccidioides brasiliensis and Other Fungal Agents of Human Systemic Mycoses As Vaccine Candidates

PubMed Central

Travassos, Luiz R.; Taborda, Carlos P.

2017-01-01

Dimorphic fungi are agents of systemic mycoses associated with significant morbidity and frequent lethality in the Americas. Among the pathogenic species are Paracoccidioides brasiliensis and Paracoccidioides lutzii, which predominate in South America; Histoplasma capsulatum, Coccidioides posadasii, and Coccidioides immitis, and the Sporothrix spp. complex are other important pathogens. Associated with dimorphic fungi other important infections are caused by yeast such as Candida spp. and Cryptococcus spp. or mold such as Aspergillus spp., which are also fungal agents of deadly infections. Nowadays, the actual tendency of therapy is the development of a pan-fungal vaccine. This is, however, not easy because of the complexity of eukaryotic cells and the particularities of different species and isolates. Albeit there are several experimental vaccines being studied, we will focus mainly on peptide vaccines or epitopes of T-cell receptors inducing protective fungal responses. These peptides can be carried by antibody inducing β-(1,3)-glucan oligo or polysaccharides, or be mixed with them for administration. The present review discusses the efficacy of linear peptide epitopes in the context of antifungal immunization and vaccine proposition. PMID:28344577

[A case of coccidioidomycosis in Turkey imported from the United States of America].

PubMed

Başaran, Seniha; Karabıçak, Nilgün; Şimşek Yavuz, Serap; Wiederhold, Nathan P; Şafak, Seda; Sarıbuğa, Aysun; Sutton, Deanna A; Bingöl, Züleyha; Çağatay, Atahan; Özsüt, Halit; Kılıçaslan, Zeki; Eraksoy, Haluk

2017-04-01

Coccidioidomycosis caused by Coccidioides immitis or Coccidioides posadasii is a rare infectious disease except in endemic regions. In this report the third documented imported case of coccidioidomycosis in Turkey was presented. A thirty-year-old male patient was admitted to our hospital with fever and purulent drainage from his chest tube. He had worked in Arizona, USA, until 4 months before this presentation. While in Arizona, he experienced cough and hemoptysis and was diagnosed as pulmonary coccidioidomycosis. He was treated with itraconazole for two months and he had no symptoms for 3 years. He then returned to Turkey and 2 months after his return to Turkey, he was admitted to another hospital in Istanbul with dyspnea and diagnosed as hydro-pneumothorax, and pleural fluid obtained from the inserted chest tube was found to be purulent. One gram of BID amoxicillin-clavulanate was given. Physical examination on admission revealed a purulent drainage on the right side chest tube, a temperature of 38.5°C and decreased breath sounds on the right lung. Piperacillin-tazobactam 3 x 4.5 g intravenous and fluconazole 400 mg intravenous once daily were started. Human immunodeficiency virus test was negative. Gram-negative diplococci and rods, gram-positive cocci and septate hyphae were seen in the Gram stain of his pleural fluid. Pleural fluid culture revealed Moraxella catarrhalis after 24 hours incubation and a mold after 72 hours of incubation. Anti-coccidioidal antibodies were found positive in a titer of 1/2. Hydro-pneumothorax, atelectasis and a 3 mm nodules in the right lung were seen in his thorax CT. The patient's pleural fluid and the culture plates were sent to the Public Health Institute of Turkey, Mycology Reference Laboratory (PHIT-MRL), with a clinical suspicion of coccidioidomycosis. The specimen and plates were submitted to the PHIT-MRL Bio Safety Level-3 laboratory for mycological evaluation. The microscopic examination of 15% KOH preparations of pleural fluid specimens revealed septate hyphae which appear to be in the early stages of forming arthroconidia. The pleural fluid culture grew buff-white coloured colonies with aerial hyphae, which were suspected of being a Coccidioides spp. The strain was identified as C.immitis/posadasii by direct microscopy and culture, and subsequently confirmed by the FDA-approved DNA probe. DNA sequence analysis of the ITS and D1/D2 rDNA regions confirmed the isolate to be C.posadasii species [ITS 100% match to GenBank Accession No. AB232901 (630/630 base pair match), and D1/D2 100% match to GenBank Accession No. AB232884 (617/617 base pair match)]. ITS1 and ITS2 barcode analysis also confirmed the species to be C.posadasii, which is the species endemic in Arizona. Susceptibility testing was performed according to Clinical and Laboratory Standards Institute M38-A2 guidelines in the Fungus Testing Laboratory of the University of Texas Health Science Center at San Antonio and minimal inhibitory concentration values were; 0.125 µg/ml for amphotericin B, posaconazole and voriconazole, 0.5 µg/ml for itraconazole and 8 µg/ml for fluconazole. He had decortication of the pleura and was discharged from hospital after six weeks treatment with intravenous fluconazole which was continued orally for one year. Anti-coccidioidal antibodies were negative after two months of treatment. The patient is currently asymptomatic. The presented case is the third case reported from Turkey and provides additional contribution to the existing literature with regard to the appearance of arthroconidium, which is the unusual hyphal form, instead of the expected spherules in the infected tissue.

Novel Strategies to Enhance Vaccine Immunity against Coccidioidomycosis

DTIC Science & Technology

2013-12-19

Mexico and Central and South America [1]. Coccidioides is a dimorphic ascomycetous fungus with distinct saprobic and parasitic phases and is classified in...lethal spore inoculum. However, sterile immunity was not achieved and pulmonary tissue damage associated with a persistent host inflammatory response...observation will translate to humans. A recent vector-based vaccine against tuberculosis intended to protect by eliciting strong CMI failed in humans despite

Medical Surveillance Monthly Report (MSMR). Volume 19, Number 12, December 2012

DTIC Science & Technology

2012-12-01

Less com- monly, infection with Coccidioides can dis- seminate outside of the pulmonary system.6 Th e most common sites of extrapulmonary dissemination...soil, and it is impracticable to move all military bases and training sites outside of the endemic region. Available engineering controls to...appendectomy-related Current Procedural Terminology (CPT) codes (outpatient) 44950, 44955, 44960 Open appendectomy 44970, 44979 Laparoscopic appendectomy

Identification Of Protein Vaccine Candidates Using Comprehensive Proteomic Analysis Strategies

DTIC Science & Technology

2007-12-01

urease (URE) gene codes for a urea amidohydrolase protein that catalyzes urea hydrolysis. The protein was first isolated from C. immitis and...the Cu, Zn, Superoxide Dismutase (SOD), the Spherule Outer Wall glycoprotein (SOWgp), the T-Cell Reactive Protein (TCRP), and Urease (URE). It is...et al. 1997. Isolation and characterization of the urease gene (URE) from the pathogenic fungus Coccidioides immitis. Gene 198: 387-391. 54. Li, K

PCR Assays for Identification of Coccidioides posadasii Based on the Nucleotide Sequence of the Antigen 2/Proline-Rich Antigen

PubMed Central

Bialek, Ralf; Kern, Jan; Herrmann, Tanja; Tijerina, Rolando; Ceceñas, Luis; Reischl, Udo; González, Gloria M.

2004-01-01

A conventional nested PCR and a real-time LightCycler PCR assay for detection of Coccidioides posadasii DNA were designed and tested in 120 clinical strains. These had been isolated from 114 patients within 10 years in Monterrey, Nuevo Leon, Mexico, known to be endemic for coccidioidomycosis. The gene encoding the specific antigen 2/proline-rich antigen (Ag2/PRA) was used as a target. All strains were correctly identified, whereas DNA from related members of the family Onygenaceae remained negative. Melting curve analysis by LightCycler and sequencing of the 526-bp product of the first PCR demonstrated either 100% identity to the GenBank sequence of the Silveira strain, now known to be C. posadasii (accession number AF013256), or a single silent mutation at position 1228. Length determination of two microsatellite-containing loci (GAC and 621) identified all 120 isolates as C. posadasii. Specific DNA was amplified by conventional nested PCR from three microscopically spherule-positive paraffin-embedded tissue samples, whereas 20 human tissue samples positive for other dimorphic fungi remained negative. Additionally, the safety of each step of a modified commercially available DNA extraction procedure was evaluated by using 10 strains. At least three steps of the protocol were demonstrated to sufficiently kill arthroconidia. This safe procedure is applicable to cultures and to clinical specimens. PMID:14766853

A Case of Refractory Pulmonary Coccidioidomycosis Successfully Treated with Posaconazole Therapy

PubMed Central

Patel, RH; Pandya, S; Nanjappa, S; Greene, JN

2018-01-01

Coccidioidomycosis is an endemic fungal infection caused by the inhalation of the spores of Coccidioides species. Patients with underlying immunosuppressive illness can contract chronic or disseminated disease which requires prolonged systemic therapy. Pulmonary coccidioidomycosis remains as an illusory and abstruse disease, with increased prevalence that poses as a challenge for clinicians in developing an effective strategy for treatment. Here, we report successful treatment of a refractory case of chronic relapsing pulmonary coccidioidomycosis in a 50-year old woman with a thin-walled cavitary lung lesion who was ultimately treated with posaconazole.

Local Population Structure and Patterns of Western Hemisphere Dispersal for Coccidioides spp., the Fungal Cause of Valley Fever

PubMed Central

Roe, Chandler C.; Hepp, Crystal M.; Teixeira, Marcus; Driebe, Elizabeth M.; Schupp, James M.; Gade, Lalitha; Waddell, Victor; Komatsu, Kenneth; Arathoon, Eduardo; Logemann, Heidi; Thompson, George R.; Chiller, Tom; Keim, Paul; Litvintseva, Anastasia P.

2016-01-01

ABSTRACT Coccidioidomycosis (or valley fever) is a fungal disease with high morbidity and mortality that affects tens of thousands of people each year. This infection is caused by two sibling species, Coccidioides immitis and C. posadasii, which are endemic to specific arid locales throughout the Western Hemisphere, particularly the desert southwest of the United States. Recent epidemiological and population genetic data suggest that the geographic range of coccidioidomycosis is expanding, as new endemic clusters have been identified in the state of Washington, well outside the established endemic range. The genetic mechanisms and epidemiological consequences of this expansion are unknown and require better understanding of the population structure and evolutionary history of these pathogens. Here we performed multiple phylogenetic inference and population genomics analyses of 68 new and 18 previously published genomes. The results provide evidence of substantial population structure in C. posadasii and demonstrate the presence of distinct geographic clades in central and southern Arizona as well as dispersed populations in Texas, Mexico, South America, and Central America. Although a smaller number of C. immitis strains were included in the analyses, some evidence of phylogeographic structure was also detected in this species, which has been historically limited to California and Baja, Mexico. Bayesian analyses indicated that C. posadasii is the more ancient of the two species and that Arizona contains the most diverse subpopulations. We propose a southern Arizona-northern Mexico origin for C. posadasii and describe a pathway for dispersal and distribution out of this region. PMID:27118594

Coccidioidomycosis in travelers returning from Mexico--Pennsylvania, 2000.

PubMed

2000-11-10

Coccidioidomycosis (CM), a fungal disease caused by Coccidioides immitis, is endemic in the southwestern United States and parts of Central and South America. The disease is acquired by inhaling the arthroconidia of C. immitis present in the soil. Outbreaks of CM occur when susceptible persons are exposed to airborne arthroconidia from dust storms, natural disasters, and earth excavation (1,2). Persons who travel to areas where the disease is endemic may become infected and develop symptoms after returning home (3,4). This report describes an outbreak of CM among travelers returning to Pennsylvania from a trip to Mexico.

The influence of current and future climate on the spatial distribution of coccidioidomycosis in the southwestern United States

NASA Astrophysics Data System (ADS)

Gorris, M. E.; Hoffman, F. M.; Zender, C. S.; Treseder, K. K.; Randerson, J. T.

2017-12-01

Coccidioidomycosis, otherwise known as valley fever, is an infectious fungal disease currently endemic to the southwestern U.S. The magnitude, spatial distribution, and seasonality of valley fever incidence is shaped by variations in regional climate. As such, climate change may cause new communities to become at risk for contracting this disease. Humans contract valley fever by inhaling fungal spores of the genus Coccidioides. Coccidioides grow in the soil as a mycelium, and when stressed, autolyze into spores 2-5 µm in length. Spores can become airborne from any natural or anthropogenic soil disturbance, which can be exacerbated by dry soil conditions. Understanding the relationship between climate and valley fever incidence is critical for future disease risk management. We explored several multivariate techniques to create a predictive model of county-level valley fever incidence throughout the southwestern U.S., including Arizona, California, New Mexico, Nevada, and Utah. We incorporated surface air temperature, precipitation, soil moisture, surface dust concentrations, leaf area index, and the amount of agricultural land, all of which influence valley fever incidence. A log-linear regression model that incorporated surface air temperature, soil moisture, surface dust concentration, and the amount of agricultural land explained 34% of the county-level variance in annual average valley fever incidence. We used this model to predict valley fever incidence for the Representative Concentration Pathway 8.5 using simulation output from the Community Earth System Model. In our analysis, we describe how regional hotspots of valley fever incidence may shift with sustained warming and drying in the southwestern U.S. Our predictive model of valley fever incidence may help mitigate future health impacts of valley fever by informing health officials and policy makers of the climate conditions suitable for disease outbreak.

Increasing Incidence and Severity of Coccidioidomycosis at a Naval Air Station

PubMed Central

Lee, Rachel U; Crum-Cianflone, Nancy F

2009-01-01

Background Increasing rates of coccidioidomycosis among the general population are being described. Given the large number of military personnel stationed and training in endemic areas, data regarding infection trends among military members would be informative. Methods We performed a retrospective epidemiologic study concerning the incidence and severity of clinical cases of coccidioidomycosis at a Naval base located in an endemic area in California. Results Eighty-two military beneficiaries at the base were diagnosed with coccidioidomycosis from January 2002 to December 2006. Among active duty personnel, the rate of coccidioidomycosis rose 10-fold during the five-year study period: 29.88 to 313.71 cases per 100,000 person-years. The incidence of coccidioidal infections occurring in active duty members was higher than other military beneficiaries at the base. The median age of patients with a coccidioidal infection was 28 years, and 73% were male. Sixty-six had primary pulmonary disease, and 14 had disseminated disease; data were unavailable for two cases. The number of disseminated cases increased significantly over time; by 2006, 30% of the diagnosed cases were disseminated disease. Among cases of dissemination, 43% occurred among white/non-Hispanics. Disseminated disease was associated with high complement fixation titers and a more recent year of diagnosis. Although the sample size was small, we found no differences in rates of disseminated disease by race, likely due to the large number of cases among Caucasians. Conclusions Coccidioidomycosis incidence rates have significantly increased during the last five years among military beneficiaries. Active duty members were more likely to develop coccidioidomycosis than dependents or retirees, perhaps related to the number and intensity of exposures in this group. PMID:18751595

Preventing and treating biologic-associated opportunistic infections.

PubMed

Winthrop, Kevin L; Chiller, Tom

2009-07-01

A variety of opportunistic pathogens have been reported to infect patients receiving tumor necrosis factor (TNF) antagonists for the treatment of autoimmune diseases. These pathogens are numerous, and include coccidioides, histoplasma, nontuberculous mycobacteria, Mycobacteria tuberculosis, and others of public health concern. Accordingly, TNF antagonists should be used with caution in patients at risk for tuberculosis, and screening for latent tuberculosis infection should be undertaken before anti-TNF therapy is initiated. Although screening and prevention efforts have decreased the risk of tuberculosis in this setting, optimal screening methods represent an area of evolving controversy. This article discusses the latest developments in screening methodologies for latent tuberculosis infection, as well as potential preventive and therapeutic considerations for opportunistic infections associated with anti-TNF agents and other biologic therapies.

Coccidioidomycosis in southern sea otters

USGS Publications Warehouse

Thomas, Nancy J.; Pappagianis, Demosthenes; Creekmore, Lynn H.; Duncan, Ruth M.

1994-01-01

Disseminated coccidioidomycosis was diagnosed postmortem in six southern sea otters (Enhydra lutris nereis) found dying or dead along the Pacific Coast of California at San Luis Obispo County.  These otters were found during winter or summer 1992, 1993, and 1994.  Coccidioides immitis was identified by its morphology in tissue impression smears and by histopathology, and was confirmed by culture.  Positive serologic results were obtained from four of five sea otters tested.  The lungs, pleura, tracheobronchial lymph nodes, liver, and spleen were involved in each case.  There was meningeal involvement in half of the affected animals.  Coccidioidomycosis has been reported in a wild sea otter only once previously, in 1976, and that otter was also found on the coast of San Luis Obispo County.

Case of coccidioidomycosis in Ireland.

PubMed

Duggan, Patrick Thomas; Deegan, Alexander P; McDonnell, Timothy J

2016-08-11

Coccidioidal infection is a well-recognised cause of pulmonary disease in certain parts of the south-western USA, Central and South America; however, it is rarely encountered elsewhere in the world. We describe the case of a previously healthy man presenting to a Dublin hospital with fever, dry cough and chest pain, following a visit to the western USA. Despite treatment with broad-spectrum antimicrobials, the patient developed progressive bilateral pulmonary infiltrates and a large pleural effusion. After extensive investigations including CT, bronchoscopy and pleural fluid analysis, a diagnosis of pulmonary coccidioidomycosis was made. Following the initiation of appropriate antifungal therapy, the patient made a full recovery. This case was of interest due to the rarity of the disease outside its areas of endemicity and the unusual findings associated with its diagnosis. 2016 BMJ Publishing Group Ltd.

Coccidioidomycosis in Biopsies with Presumptive Diagnosis of Malignancy in Dogs: Report of Three Cases and Comparative Discussion of Published Reports.

PubMed

Ramírez-Romero, Rafael; Silva-Pérez, Rolando Antonio; Lara-Arias, Jorge; Ramírez-Hernández, Cecilia; Marino-Martínez, Iván Alberto; Barbosa-Quintana, Álvaro; López-Mayagoitia, Alfonso

2016-02-01

Coccidioidomycosis is a respiratory fungal infection with occasional systemic dissemination. The disseminated coccidioidomycosis is considered a multifaceted disease. In medicine, disseminated coccidioidomycosis is included within a group of infectious diseases that have been referred as the great imitators. In many cases, malignancies are included in the presumptive diagnosis. In veterinary medicine, disseminated coccidioidomycosis is common in dogs. Nonetheless, despite of being a diagnostic dilemma, disseminated coccidioidomycosis is underestimated and frequently not included into differentials, even in endemic zones. Herein, we describe three cases of granulomatous inflammation caused by Coccidioides spp. which were masquerading malignancies in dogs (0.39 %). The presumptive diagnoses in these cases were osteosarcoma, lymphoma and neurofibroma, respectively. A PCR assay employing tissues in paraffin blocks resulted positive for C. posadasii in one of these cases. A comparative discussion on the ambiguous clinic-pathological presentation of disseminated coccidioidomycosis in dogs and humans is included.

Coccidioidomycosis in the llama: case report and epidemiologic survey.

PubMed

Muir, S; Pappagianis, D

1982-12-01

An 8-year-old nongravid female llama with a 1-month history of progressive posterior paresis was referred because of suspected degenerative myelopathy secondary to copper deficiency or plant poisoning. Neurologic examination revealed loss of conscious proprioception and slightly depressed bilateral patellar reflexes. Electromyographic examination of hindlimb flexors and extensors did not elicit evidence of lower motor neuron disease. Possible fragmentation and mottling of the 10th thoracic vertebral body were noted radiographically. Results of a lumbar CSF tap, complete blood count, and fecal flotation were not diagnostic. In the face of poor prognosis, the llama was euthanatized. Postmortem and histologic evaluation revealed, in addition to disseminated visceral granulomas, an extradural pyogranulomatous mass compressing the cord laterally at the level of T-10. Large numbers of Coccidioides immitis were dispersed throughout the granulomas. Complement fixing antibody tests in 11 other herd members showed evidence of C immitis infection in three.

Coccidioidomycosis as a Common Cause of Community-acquired Pneumonia

PubMed Central

Valdivia, Lisa; Nix, David; Wright, Mark; Lindberg, Elizabeth; Fagan, Timothy; Lieberman, Donald; Stoffer, T'Prien; Ampel, Neil M.

2006-01-01

The early manifestations of coccidioidomycosis (valley fever) are similar to those of other causes of community-acquired pneumonia (CAP). Without specific etiologic testing, the true frequency of valley fever may be underestimated by public health statistics. Therefore, we conducted a prospective observational study of adults with recent onset of a lower respiratory tract syndrome. Valley fever was serologically confirmed in 16 (29%) of 55 persons (95% confidence interval 16%–44%). Antimicrobial medications were used in 81% of persons with valley fever. Symptomatic differences at the time of enrollment had insufficient predictive value for valley fever to guide clinicians without specific laboratory tests. Thus, valley fever is a common cause of CAP after exposure in a disease-endemic region. If CAP develops in persons who travel or reside in Coccidioides-endemic regions, diagnostic evaluation should routinely include laboratory evaluation for this organism. PMID:16707052

Travel and transplantation: travel-related diseases in transplant recipients.

PubMed

Kotton, Camille N

2012-12-01

Travel-related diseases may be seen in transplant recipients after travel, after transplant tourism, and via transmission from blood and organ donors, augmented by recent increases in travel, migration, and globalization. Such infections include tuberculosis, Plasmodium (malaria), Babesia, Trypanosoma cruzi (Chagas disease), Strongyloides, Coccidioides, Histoplasma, Leishmania, Brucella, HTLV, dengue, among numerous others. Review of cohorts of transplant recipients show that they tend to have minimal or suboptimal preparation prior to travel, with limited pretravel vaccination, medications, and education, which poses a greatly increased risk of travel-related infections and complications. The epidemiology of such travel-related infections in transplant recipients, along with methods for prevention, including vaccines, chemoprophylaxis, and education may help SOT recipients avoid travel-related infections, and are discussed in this review. Optimizing the understanding of the risk of tropical, geographically restricted, and other unusual or unexpected, travel-related infections will enhance the safety of vulnerable transplant recipients from potentially life-threatening infections.

Coccidioidomycosis Outbreaks, United States and Worldwide, 1940-2015.

PubMed

Freedman, Michael; Jackson, Brendan R; McCotter, Orion; Benedict, Kaitlin

2018-03-01

Coccidioidomycosis causes substantial illness and death in the United States each year. Although most cases are sporadic, outbreaks provide insight into the clinical and environmental features of coccidioidomycosis, high-risk activities, and the geographic range of Coccidioides fungi. We identified reports published in English of 47 coccidioidomycosis outbreaks worldwide that resulted in 1,464 cases during 1940-2015. Most (85%) outbreaks were associated with environmental exposures; the 2 largest outbreaks resulted from an earthquake and a large dust storm. More than one third of outbreaks occurred in areas where the fungus was not previously known to be endemic, and more than half of outbreaks involved occupational exposures. Coccidioidomycosis outbreaks can be difficult to detect and challenging to prevent given the unknown effectiveness of environmental control methods and personal protective equipment; therefore, increased awareness of coccidioidomycosis outbreaks is needed among public health professionals, healthcare providers, and the public.

Airborne Dust Models in Valley Fever Research

NASA Astrophysics Data System (ADS)

Sprigg, W. A.; Galgiani, J. N.; Vujadinovic, M.; Pejanovic, G.; Vukovic, A. J.; Prasad, A. K.; Djurdjevic, V.; Nickovic, S.

2011-12-01

Dust storms (haboobs) struck Phoenix, Arizona, in 2011 on July 5th and again on July 18th. One potential consequence: an estimated 3,600 new cases of Valley Fever in Maricopa County from the first storm alone. The fungi, Coccidioides immitis, the cause of the respiratory infection, Valley Fever, lives in the dry desert soils of the American southwest and southward through Mexico, Central America and South America. The fungi become part of the dust storm and, a few weeks after inhalation, symptoms of Valley Fever may appear, including pneumonia-like illness, rashes, and severe fatigue. Some fatalities occur. Our airborne dust forecast system predicted the timing and extent of the storm, as it has done with other, often different, dust events. Atmosphere/land surface models can be part of public health services to reduce risk of Valley Fever and exacerbation of other respiratory and cardiovascular illness.

Coccidioidomycosis Outbreaks, United States and Worldwide, 1940–2015

PubMed Central

Freedman, Michael; Jackson, Brendan R.; McCotter, Orion

2018-01-01

Coccidioidomycosis causes substantial illness and death in the United States each year. Although most cases are sporadic, outbreaks provide insight into the clinical and environmental features of coccidioidomycosis, high-risk activities, and the geographic range of Coccidioides fungi. We identified reports published in English of 47 coccidioidomycosis outbreaks worldwide that resulted in 1,464 cases during 1940–2015. Most (85%) outbreaks were associated with environmental exposures; the 2 largest outbreaks resulted from an earthquake and a large dust storm. More than one third of outbreaks occurred in areas where the fungus was not previously known to be endemic, and more than half of outbreaks involved occupational exposures. Coccidioidomycosis outbreaks can be difficult to detect and challenging to prevent given the unknown effectiveness of environmental control methods and personal protective equipment; therefore, increased awareness of coccidioidomycosis outbreaks is needed among public health professionals, healthcare providers, and the public. PMID:29460741

Seroincidence of Coccidioidomycosis during Military Desert Training Exercises

PubMed Central

Crum, Nancy F.; Potter, Mark; Pappagianis, Demosthenes

2004-01-01

Coccidioidomycosis is a common fungal infection acquired in the southwestern United States. This is the first study in over 2 decades to determine the seroincidence of Coccidioides immitis infections among U.S. military members performing training exercises in an area of endemicity. Only 8% of participants were aware of coccidioidomycosis, despite the majority having visited or lived previously in an area of endemicity. One (0.6%) of the 178 participants developed “definite” serologic evidence of infection over a 5-week training period; four (2.3%) additional patients developed “possible” coccidioidomycosis infections. None had complicated disease. The calculated annual incidence ranged from 6 to 32%. This study suggests that the risk of serious coccidioidomycosis is low among military personnel during desert training exercises; however, disease incidence may vary depending on specific activities and geographic factors. Due to the potential morbidity and mortality of this infection, preventative strategies, including vaccine development, are advocated. PMID:15472308

Defining Responses to Therapy and Study Outcomes in Clinical Trials of Invasive Fungal Diseases: Mycoses Study Group and European Organization for Research and Treatment of Cancer Consensus Criteria

PubMed Central

Segal, Brahm H.; Herbrecht, Raoul; Stevens, David A.; Ostrosky-Zeichner, Luis; Sobel, Jack; Viscoli, Claudio; Walsh, Thomas J.; Maertens, Johan; Patterson, Thomas F.; Perfect, John R.; Dupont, Bertrand; Wingard, John R.; Calandra, Thierry; Kauffman, Carol A.; Graybill, John R.; Baden, Lindsey R.; Pappas, Peter G.; Bennett, John E.; Kontoyiannis, Dimitrios P.; Cordonnier, Catherine; Viviani, Maria Anna; Bille, Jacques; Almyroudis, Nikolaos G.; Wheat, L. Joseph; Graninger, Wolfgang; Bow, Eric J.; Holland, Steven M.; Kullberg, Bart-Jan; Dismukes, William E.; De Pauw, Ben E.

2009-01-01

Invasive fungal diseases (IFDs) have become major causes of morbidity and mortality among highly immunocompromised patients. Authoritative consensus criteria to diagnose IFD have been useful in establishing eligibility criteria for antifungal trials. There is an important need for generation of consensus definitions of outcomes of IFD that will form a standard for evaluating treatment success and failure in clinical trials. Therefore, an expert international panel consisting of the Mycoses Study Group and the European Organization for Research and Treatment of Cancer was convened to propose guidelines for assessing treatment responses in clinical trials of IFDs and for defining study outcomes. Major fungal diseases that are discussed include invasive disease due to Candida species, Aspergillus species and other molds, Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis. We also discuss potential pitfalls in assessing outcome, such as conflicting clinical, radiological, and/or mycological data and gaps in knowledge. PMID:18637757

Rates and Risk Factors for Coccidioidomycosis among Prison Inmates, California, USA, 2011

PubMed Central

Lucas, Kimberley D.; Mohle-Boetani, Janet C.

2015-01-01

In California, coccidioidomycosis is a disease acquired by inhaling spores of Coccidioides immitis, a fungus found in certain arid regions, including the San Joaquin Valley, California, USA, where 8 state prisons are located. During 2011, we reviewed coccidioidomycosis rates at 2 of the prisons that consistently report >80% of California’s inmate cases and determined inmate risk factors for primary, severe (defined as pulmonary coccidioidomycosis requiring >10 hospital days), and disseminated coccidioidomycosis (defined by hospital discharge International Classification of Disease, Ninth Revision code). Inmates of African American ethnicity who were >40 years of age were at significantly higher risk for primary coccidioidomycosis than their white counterparts (odds ratio = 2.0, 95% CI 1.5–2.8). Diabetes was a risk factor for severe pulmonary coccidioidomycosis, and black race a risk factor for disseminated disease. These findings contributed to a court decision mandating exclusion of black inmates and inmates with diabetes from the 2 California prisons with the highest rates of coccidioidomycosis. PMID:25533149

Insights from paleomicrobiology into the indigenous peoples of pre-colonial America - a review.

PubMed

Darling, Millie I; Donoghue, Helen D

2014-04-01

This review investigates ancient infectious diseases in the Americas dated to the pre-colonial period and considers what these findings can tell us about the history of the indigenous peoples of the Americas. It gives an overview, but focuses on four microbial pathogens from this period: Helicobacter pylori, Mycobacterium tuberculosis, Trypanosoma cruzi and Coccidioides immitis, which cause stomach ulceration and gastric cancer, tuberculosis, Chagas disease and valley fever, respectively. These pathogens were selected as H. pylori can give insight into ancient human migrations into the Americas, M. tuberculosis is associated with population density and urban development, T. cruzi can elucidate human living conditions and C. immitis can indicate agricultural development. A range of methods are used to diagnose infectious disease in ancient human remains, with DNA analysis by polymerase chain reaction one of the most reliable, provided strict precautions are taken against cross contamination. The review concludes with a brief summary of the changes that took place after European exploration and colonisation.

Insights from paleomicrobiology into the indigenous peoples of pre-colonial America - A Review

PubMed Central

Darling, Millie I; Donoghue, Helen D

2014-01-01

This review investigates ancient infectious diseases in the Americas dated to the pre-colonial period and considers what these findings can tell us about the history of the indigenous peoples of the Americas. It gives an overview, but focuses on four microbial pathogens from this period: Helicobacter pylori, Mycobacterium tuberculosis, Trypanosoma cruzi and Coccidioides immitis, which cause stomach ulceration and gastric cancer, tuberculosis, Chagas disease and valley fever, respectively. These pathogens were selected as H. pylori can give insight into ancient human migrations into the Americas, M. tuberculosis is associated with population density and urban development, T. cruzi can elucidate human living conditions and C. immitis can indicate agricultural development. A range of methods are used to diagnose infectious disease in ancient human remains, with DNA analysis by polymerase chain reaction one of the most reliable, provided strict precautions are taken against cross contamination. The review concludes with a brief summary of the changes that took place after European exploration and colonisation. PMID:24714964

Disseminated coccidioidomycosis in a captive Indochinese tiger (Panthera tigris corbetti) with chronic renal disease.

PubMed

Helmick, Kelly E; Koplos, Peter; Raymond, James

2006-12-01

A 19-yr-old, 78.2-kg captive female Indochinese tiger (Panthera tigris corbetti) from the El Paso Zoo (El Paso, Texas, USA) with chronic renal disease was euthanized after a 10-day course of anorexia, depression, progressive rear limb weakness, muscle fasciculations, and head tremors. Postmortem findings included pericardial effusion, generalized lymphadenopathy, glomerulosclerosis, glomerular atrophy with membranous glomerulonephropathy, and pancreatic adenocarcinoma. Pyogranulomatous pneumonia, pericarditis, and lymphadenitis were associated with fungal spherules histomorphologically consistent with Coccidioides immitis. Rising antibodies to C. immitis were detected on samples obtained perimortem and 2 mo before euthanasia. Retrospective serology was negative for two additional Indochinese tigers, two Iranian leopards (Panthera pardus saxicolor), two jaguars (Panthera onca), two bobcats (Lynx rufus texensis), two ocelots (Leopardus pardalis), and three Amur leopards (Panthera pardus orientalis) housed at the zoo over an 8-yr period. Despite being located within the endemic region for C. immitis, this is only the second case of coccidioidomycosis reported from this institution.

A point-source outbreak of Coccidioidomycosis among a highway construction crew.

PubMed

Nicas, Mark

2018-01-01

Coccidioidomycosis is an infection caused by inhaling spores of the soil fungus Coccidioides immitis (hereafter termed Cocci). Cocci is endemic in certain areas of California. When soil containing the fungus is disturbed, as during earth-moving activities, respirable Cocci spores can become airborne and be inhaled by persons in the vicinity. This article describes a cluster of seven Cocciodioidomycosis cases among a highway construction crew that occurred in June/July 2008 in Kern County, CA, which is among the most highly endemic regions for Cocci in California. The exposures spanned no more than seven work days, and illness developed within two to three weeks of the exposures. Given the common source of exposure (soil dust generated at the work site) and the multiple cases occurring close in time, the cluster can also be termed a "point-source outbreak." The contractor was not informed of the infection risk and did not take adequate precautions against dust exposure. Appropriate engineering/administrative controls and respiratory protection are discussed.

Fungal dimorphism: the switch from hyphae to yeast is a specialized morphogenetic adaptation allowing colonization of a host.

PubMed

Boyce, Kylie J; Andrianopoulos, Alex

2015-11-01

The ability of pathogenic fungi to switch between a multicellular hyphal and unicellular yeast growth form is a tightly regulated process known as dimorphic switching. Dimorphic switching requires the fungus to sense and respond to the host environment and is essential for pathogenicity. This review will focus on the role of dimorphism in fungi commonly called thermally dimorphic fungi, which switch to a yeast growth form during infection. This group of phylogenetically diverse ascomycetes includes Talaromyces marneffei (recently renamed from Penicillium marneffei), Blastomyces dermatitidis (teleomorph Ajellomyces dermatitidis), Coccidioides species (C. immitis and C. posadasii), Histoplasma capsulatum (teleomorph Ajellomyces capsulatum), Paracoccidioides species (P. brasiliensis and P. lutzii) and Sporothrix schenckii (teleomorph Ophiostoma schenckii). This review will explore both the signalling pathways regulating the morphological transition and the transcriptional responses necessary for intracellular growth. The physiological requirements of yeast cells during infection will also be discussed, highlighting recent advances in the understanding of the role of iron and calcium acquisition during infection. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

High-throughput label-free microcontact printing graphene-based biosensor for valley fever.

PubMed

Tsai, Shih-Ming; Goshia, Tyler; Chen, Yen-Chang; Kagiri, Agnes; Sibal, Angelo; Chiu, Meng-Hsuen; Gadre, Anand; Tung, Vincent; Chin, Wei-Chun

2018-06-18

The highly prevalent and virulent disease in the Western Hemisphere Coccidioidomycosis, also known as Valley Fever, can cause serious illness such as severe pneumonia with respiratory failure. It can also take on a disseminated form where the infection spreads throughout the body. Thus, a serious impetus exists to develop effective detection of the disease that can also operate in a rapid and high-throughput fashion. Here, we report the assembly of a highly sensitive biosensor using reduced graphene oxide (rGO) with Coccidioides(cocci) antibodies as the target analytes. The facile design made possible by the scalable microcontact printing (μCP) surface patterning technique which enables rapid, ultrasensitive detection. It provides a wide linear range and sub picomolar (2.5 pg/ml) detection, while also delivering high selectivity and reproducibility. This work demonstrates an important advancement in the development of a sensitive label-free rGO biosensor for Coccidioidomycosis detection. This result also provides the potential application of direct pathogen diagnosis for the future biosensor development. Copyright © 2018 Elsevier B.V. All rights reserved.

Statistical modeling of valley fever data in Kern County, California

NASA Astrophysics Data System (ADS)

Talamantes, Jorge; Behseta, Sam; Zender, Charles S.

2007-03-01

Coccidioidomycosis (valley fever) is a fungal infection found in the southwestern US, northern Mexico, and some places in Central and South America. The fungus that causes it ( Coccidioides immitis) is normally soil-dwelling but, if disturbed, becomes air-borne and infects the host when its spores are inhaled. It is thus natural to surmise that weather conditions that foster the growth and dispersal of the fungus must have an effect on the number of cases in the endemic areas. We present here an attempt at the modeling of valley fever incidence in Kern County, California, by the implementation of a generalized auto regressive moving average (GARMA) model. We show that the number of valley fever cases can be predicted mainly by considering only the previous history of incidence rates in the county. The inclusion of weather-related time sequences improves the model only to a relatively minor extent. This suggests that fluctuations of incidence rates (about a seasonally varying background value) are related to biological and/or anthropogenic reasons, and not so much to weather anomalies.

[Clinical problems in medical mycology: Problem number 52].

PubMed

Messina, Fernando; Depardo, Roxana; Negroni, Ricardo; Romero, Mercedes; Walker, Laura; Arechavala, Alicia; Marín, Emmanuel; Canteros, Cristina; Santiso, Gabriela

The case of a 60 year old woman with hemoptysis and a thin-walled cavitary lesion at the upper lobe of the right lung is presented. The woman presented at the Mycology Unit of the Muñiz Hospital in Buenos Aires City 3 months after the beginning of her clinical manifestations. A hyaline micelial fungus with chlamido-arthroconidias was isolated from the bronchoalveolar lavage. Immunodiffusion and counter-immnunoelectrophoresis with coccidioidin and histoplasmin rendered positive results against both antigents, and skin tests with coccidioidin and histoplasmin were also positive with strong reactions. The isolated fungus was identified as Coccidioides posadasii at the National Microbiology Institute Carlos Malbrán, by means of a molecular technique. The patient was treated with itraconazole by oral route at a daily dose of 200mg with good clinical response, but due to the persistence of the lung cavity, a surgical removal of the upper lobe of the right lung had to be scheduled. Copyright © 2017 Asociación Española de Micología. Publicado por Elsevier España, S.L.U. All rights reserved.

Agent-Based Modeling of Physical Factors That May Control the Growth of Coccidioides immitis (Valley Fever Fungus) in Soils

NASA Astrophysics Data System (ADS)

Gettings, M. E.; Fisher, F. S.

2003-12-01

A model of the spread and survival of the fungus Coccidioides immitis in soil via wind-borne spore transport has been completed using public domain agent-based modeling software. The hypothetical model posits that for a successful new site to become established, four factors must be simultaneously satisfied. 1) There must be transport of spores from a source site to sites with favorable soil geology, texture, topographic aspect, and lack of biomass competition. 2) There must be sufficient moisture for fungal growth. 3) Temperature of the surface and soil must be favorable for growth. Finally, 4) the temperature and moisture must remain in favorable ranges for a long enough time interval for the fungus to grow down to depths at which spores will survive subsequent heat, aridity, and ultraviolet radiation of the hot, dry season typical of the Southwest U.S. climate. Using agent-based modeling software, a model was built so that the effects of combinations of these controlling factors could be evaluated using realistic temperature, rain and wind models. The rain probability and amount, temperature annual and diurnal variation, and wind direction and intensity were based on the weather records at Tucson, Arizona for the 107-year period from 1894 to 2001. Favorable ground was defined using a fractal tree algorithm that emulates a drainage network in accordance with observations that favorable sites are often adjacent to drainage channels. Numerous model runs produced the following five conclusions. 1) If any property is not isotropic, for example wind direction or narrow paths of rainstorms, parts of the favorable areas will never become colonized no matter how long the model runs. 2)The spread of sites is extremely sensitive to moisture duration. The amount of wind and temperature after a rain control the length of time before a site becomes too dry. 3) The distribution of wind and rainstorm direction relative to that of the favorable sites is a strong control on the spread of colonization. East-west winds across an area that has mostly north-south favorable sites restricts spread strongly. 4) Soil temperature was the least sensitive control in the model, although it does control the ultimate dormancy of a site. Fifth, the model results cover the spectrum of complete colonization of all favorable sites from a few source sites to none, one, or two new sites in three years of model simulation. This implies the probability of new sites depends on the four factors in a Bayesian way. These results indicate that the complexity introduced in the model from site favorableness, temperature, moisture, and duration of favorable temperature and moisture conditions is adequate to explain observed distributions of real sites.

In vitro interactions between amphotericin B and hydrocortisone: potential implications for intrathecal therapy.

PubMed

Hodge, Greg; Cohen, Stuart H; Thompson, George R

2015-09-01

Fungal meningitis remains a severe and often lethal infection requiring aggressive antifungal therapy and in refractory cases the use of intrathecal amphotericin B (AmB). Administration of amphotericin B by this method may result in clinically apparent adverse reactions such as paresthesias, radiculitis, or myelopathy. Coadministration of hydrocortisone is therefore often given in an attempt to avoid these effects; however, the potential consequences of this approach on fungal growth or on drug synergy/antagonism had not previously been assessed. We used the checkerboard titration broth microdilution method to analyze interactions by fractional inhibitory concentration indices (FICIs). The combination of amphotericin B and hydrocortisone resulted in synergy or indifference against all isolates (Candida, Cryptococcus, and Coccidioides) during in vitro testing at low concentrations. Antagonism was observed using higher hydrocortisone concentrations (those not observed in vivo) suggesting possible steric hindrance or binding to AmB may occur at doses unlikely to be present during clinical care. Concurrent hydrocortisone and AmB administration should not be avoided due to in vitro antagonism concerns. © The Author 2015. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Polyketides, toxins and pigments in Penicillium marneffei.

PubMed

Tam, Emily W T; Tsang, Chi-Ching; Lau, Susanna K P; Woo, Patrick C Y

2015-10-30

Penicillium marneffei (synonym: Talaromyces marneffei) is the most important pathogenic thermally dimorphic fungus in China and Southeastern Asia. The HIV/AIDS pandemic, particularly in China and other Southeast Asian countries, has led to the emergence of P. marneffei infection as an important AIDS-defining condition. Recently, we published the genome sequence of P. marneffei. In the P. marneffei genome, 23 polyketide synthase genes and two polyketide synthase-non-ribosomal peptide synthase hybrid genes were identified. This number is much higher than those of Coccidioides immitis and Histoplasma capsulatum, important pathogenic thermally dimorphic fungi in the Western world. Phylogenetically, these polyketide synthase genes were distributed evenly with their counterparts found in Aspergillus species and other fungi, suggesting that polyketide synthases in P. marneffei did not diverge from lineage-specific gene duplication through a recent expansion. Gene knockdown experiments and ultra-high performance liquid chromatography-photodiode array detector/electrospray ionization-quadruple time of flight-mass spectrometry analysis confirmed that at least four of the polyketide synthase genes were involved in the biosynthesis of various pigments in P. marneffei, including melanin, mitorubrinic acid, mitorubrinol, monascorubrin, rubropunctatin, citrinin and ankaflavin, some of which were mycotoxins and virulence factors of the fungus.

Fungal infections of the spine.

PubMed

Kim, Choll W; Perry, Andrew; Currier, Brad; Yaszemski, Michael; Garfin, Steven R

2006-03-01

Fungal infections of the spine are relatively uncommon. Fungi such as Coccidioides immitis and Blastomyces dermatitidis are limited to specific geographical areas whereas cryptococcus, candida, and aspergillus are found worldwide. Candida and aspergillus are normal commensals of the body and produce disease in susceptible organisms when they gain access to the vascular system through intravenous lines, during implantation of prosthetic devices, or during surgery. For the other fungi, spinal involvement usually is the result of hematogenous or direct spread of organisms from an initial pulmonary source of infection. Involvement of the vertebral bodies can lead to vertebral compression fractures and gross deformity of the spine. Spread of infection along the anterior longitudinal ligament can lead to psoas or paravertebral abscesses. Early recognition of the disease requires a high index of suspicion, proper travel history, and a detailed physical examination. Treatment relies on the prompt institution of appropriate pharmacotherapy and constant monitoring of clinical progress. Resistance to medical therapy, spinal instability, and neurologic deficits are indications for débridement and stabilization with spinal fusion. Prognosis depends on the premorbid state of the patient, the type of fungal organism, and the timing of treatment. Level V (expert opinion). Please see the Guidelines for Authors for a complete description of levels of evidence.

Proteomic Analysis of Pathogenic Fungi Reveals Highly Expressed Conserved Cell Wall Proteins

PubMed Central

Champer, Jackson; Ito, James I.; Clemons, Karl V.; Stevens, David A.; Kalkum, Markus

2016-01-01

We are presenting a quantitative proteomics tally of the most commonly expressed conserved fungal proteins of the cytosol, the cell wall, and the secretome. It was our goal to identify fungi-typical proteins that do not share significant homology with human proteins. Such fungal proteins are of interest to the development of vaccines or drug targets. Protein samples were derived from 13 fungal species, cultured in rich or in minimal media; these included clinical isolates of Aspergillus, Candida, Mucor, Cryptococcus, and Coccidioides species. Proteomes were analyzed by quantitative MSE (Mass Spectrometry—Elevated Collision Energy). Several thousand proteins were identified and quantified in total across all fractions and culture conditions. The 42 most abundant proteins identified in fungal cell walls or supernatants shared no to very little homology with human proteins. In contrast, all but five of the 50 most abundant cytosolic proteins had human homologs with sequence identity averaging 59%. Proteomic comparisons of the secreted or surface localized fungal proteins highlighted conserved homologs of the Aspergillus fumigatus proteins 1,3-β-glucanosyltransferases (Bgt1, Gel1-4), Crf1, Ecm33, EglC, and others. The fact that Crf1 and Gel1 were previously shown to be promising vaccine candidates, underlines the value of the proteomics data presented here. PMID:26878023

Relating coccidioidomycosis (valley fever) incidence to soil moisture conditions.

PubMed

Coopersmith, E J; Bell, J E; Benedict, K; Shriber, J; McCotter, O; Cosh, M H

2017-04-17

Coccidioidomycosis (also called Valley fever) is caused by a soilborne fungus, Coccidioides spp. , in arid regions of the southwestern United States. Though some who develop infections from this fungus remain asymptomatic, others develop respiratory disease as a consequence. Less commonly, severe illness and death can occur when the infection spreads to other regions of the body. Previous analyses have attempted to connect the incidence of coccidioidomycosis to broadly available climatic measurements, such as precipitation or temperature. However, with the limited availability of long-term, in situ soil moisture data sets, it has not been feasible to perform a direct analysis of the relationships between soil moisture levels and coccidioidomycosis incidence on a larger temporal and spatial scale. Utilizing in situ soil moisture gauges throughout the southwest from the U.S. Climate Reference Network and a model with which to extend those estimates, this work connects periods of higher and lower soil moisture in Arizona and California between 2002 and 2014 to the reported incidence of coccidioidomycosis. The results indicate that in both states, coccidioidomycosis incidence is related to soil moisture levels from previous summers and falls. Stated differently, a higher number of coccidioidomycosis cases are likely to be reported if previous bands of months have been atypically wet or dry, depending on the location.

Intensified dust storm activity and Valley fever infection in the southwestern United States

NASA Astrophysics Data System (ADS)

Tong, Daniel Q.; Wang, Julian X. L.; Gill, Thomas E.; Lei, Hang; Wang, Binyu

2017-05-01

Climate models have consistently projected a drying trend in the southwestern United States, aiding speculation of increasing dust storms in this region. Long-term climatology is essential to documenting the dust trend and its response to climate variability. We have reconstructed long-term dust climatology in the western United States, based on a comprehensive dust identification method and continuous aerosol observations from the Interagency Monitoring of Protected Visual Environments (IMPROVE) network. We report here direct evidence of rapid intensification of dust storm activity over American deserts in the past decades (1988-2011), in contrast to reported decreasing trends in Asia and Africa. The frequency of windblown dust storms has increased 240% from 1990s to 2000s. This dust trend is associated with large-scale variations of sea surface temperature in the Pacific Ocean, with the strongest correlation with the Pacific Decadal Oscillation. We further investigate the relationship between dust and Valley fever, a fast-rising infectious disease caused by inhaling soil-dwelling fungus (Coccidioides immitis and C. posadasii) in the southwestern United States. The frequency of dust storms is found to be correlated with Valley fever incidences, with a coefficient (r) comparable to or stronger than that with other factors believed to control the disease in two endemic centers (Maricopa and Pima County, Arizona).

The Celecoxib Derivative AR-12 Has Broad-Spectrum Antifungal Activity In Vitro and Improves the Activity of Fluconazole in a Murine Model of Cryptococcosis

PubMed Central

Koselny, Kristy; Green, Julianne; DiDone, Louis; Halterman, Justin P.; Fothergill, Annette W.; Wiederhold, Nathan P.; Patterson, Thomas F.; Cushion, Melanie T.; Rappelye, Chad; Wellington, Melanie

2016-01-01

Only one new class of antifungal drugs has been introduced into clinical practice in the last 30 years, and thus the identification of small molecules with novel mechanisms of action is an important goal of current anti-infective research. Here, we describe the characterization of the spectrum of in vitro activity and in vivo activity of AR-12, a celecoxib derivative which has been tested in a phase I clinical trial as an anticancer agent. AR-12 inhibits fungal acetyl coenzyme A (acetyl-CoA) synthetase in vitro and is fungicidal at concentrations similar to those achieved in human plasma. AR-12 has a broad spectrum of activity, including activity against yeasts (e.g., Candida albicans, non-albicans Candida spp., Cryptococcus neoformans), molds (e.g., Fusarium, Mucor), and dimorphic fungi (Blastomyces, Histoplasma, and Coccidioides) with MICs of 2 to 4 μg/ml. AR-12 is also active against azole- and echinocandin-resistant Candida isolates, and subinhibitory AR-12 concentrations increase the susceptibility of fluconazole- and echinocandin-resistant Candida isolates. Finally, AR-12 also increases the activity of fluconazole in a murine model of cryptococcosis. Taken together, these data indicate that AR-12 represents a promising class of small molecules with broad-spectrum antifungal activity. PMID:27645246

Relating coccidioidomycosis (valley fever) incidence to soil moisture conditions

PubMed Central

Coopersmith, E. J.; Bell, J. E.; Benedict, K.; Shriber, J.; McCotter, O.; Cosh, M. H.

2017-01-01

Coccidioidomycosis (also called Valley fever) is caused by a soilborne fungus, Coccidioides spp., in arid regions of the southwestern United States. Though some who develop infections from this fungus remain asymptomatic, others develop respiratory disease as a consequence. Less commonly, severe illness and death can occur when the infection spreads to other regions of the body. Previous analyses have attempted to connect the incidence of coccidioidomycosis to broadly available climatic measurements, such as precipitation or temperature. However, with the limited availability of long-term, in situ soil moisture data sets, it has not been feasible to perform a direct analysis of the relationships between soil moisture levels and coccidioidomycosis incidence on a larger temporal and spatial scale. Utilizing in situ soil moisture gauges throughout the southwest from the U.S. Climate Reference Network and a model with which to extend those estimates, this work connects periods of higher and lower soil moisture in Arizona and California between 2002 and 2014 to the reported incidence of coccidioidomycosis. The results indicate that in both states, coccidioidomycosis incidence is related to soil moisture levels from previous summers and falls. Stated differently, a higher number of coccidioidomycosis cases are likely to be reported if previous bands of months have been atypically wet or dry, depending on the location. PMID:29124249

Occurrence of dermatophytes in fresh bat guano.

PubMed

Kajihiro, E S

1965-09-01

Evidence is presented in support of the hypothesis that fresh bat guano serves as a means of pathogenic fungi dissemination in caves. A total of 371 guano samples were collected from caves in southeastern New Mexico. Each sample was agitated in sterile saline and sand. The supernatant fluid was treated with an antibiotic and streaked on differential media. Cultures were incubated at 25 and 37 C and examined at intervals over a 4-week period. For animal inoculation, highly concentrated inoculum was injected intraperitoneally into white Swiss mice. Animals were sacrificed 4 weeks later, and portions of their lung, liver, and spleen were cultured on selective media, incubated at 25 C, and examined at intervals over a 4-week period. Microsporum gypseum was isolated at all 10 collecting stations with an incidence of 22.4%, Trichophyton mentagrophytes at 7 stations with an incidence of 5%, T. rubrum at 3 stations with an incidence of 3%, and T. terrestre at 1 station with an incidence of 0.5%. From a total of 60 pools of liver-spleen-lung suspensions, 6 pools yielded positive cultures of Histoplasma capsulatum and 1 pool yielded T. mentagrophytes. No significant difference was found among the different selective media with respect to recovery of dermatophytes. Among the human pathogenic fungi isolated were Candida sp., Cladosporium sp., Coccidioides immitis, Cryptococcus neoformans, H. capsulatum, M. gypseum, T. mentagrophytes, T. rubrum, T. terrestre, and Sporotrichum sp.

[Osteoarticular coccidioidomicosis. Clinical and pathological study of 36 Mexican patients].

PubMed

Torres-Nájera, Manuel; de la Garza-Galván, Sergio; Cerda-Flores, Ricardo M; Nocedal-Rustrián, Fausto C; Calderón-Garcidueñas, Ana Laura

2006-01-01

Coccidioidomycosis (CM) is primarily a lung disease. Systemic spread occurs in 1% of cases and one of its manifestation is osteoarthritis. To describe the clinical and pathological characteristics of 36 patients with osteoarthritis by Coccidioides immitis (COA). The surgical pathology records of two medical institutions were reviewed; patients with clinical diagnosis of osteoarthritis and definitive histopathological diagnosis of COA were included in the study. Results were analyzed by contingence tables (RXC) and chi2 test. Twenty six adults (19 men, seven women) and 10 children (seven males, three females) were studied. The chi2 analysis demonstrated a predominance of disease in men (72.2%, p = 0.008). There was no difference between males and females in relation to history of mycotic disease or diagnosis of lung disease after the diagnosis of COA. Bone involvement (76% of cases) was more frequent that pure joint lesions and the predominant radiological lesion was of lytic type. 30.5% of patients (11 cases) had multiple bone lesions and eight of them were men with multiple vertebral bone lesions. The COA was the only manifestation of disease in 83% of the patients. Therefore is important to consider this etiology in patients of endemic area. The clinical and radiological spectrum of COA is wide and may include a dentigerous and synovial cyst or simulates metastatic disease. The recognition of the clinical manifestations of COA may contribute to an opportune diagnosis and treatment.

Diagnosis of coccidioidomycosis in a non-endemic area: Inference of the probable geographic area of an infection.

PubMed

Fernández, Ramón; Arenas, Roberto; Duarte-Escalante, Esperanza; Frías-De León, María Guadalupe; Vega Memige, María Elisa; Acosta Altamirano, Gustavo; Reyes-Montes, María Del Rocío

Coccidioidomycosis is one of the most important endemic mycoses in Northern Mexico. However, diagnosing this disease can be challenging, particularly in patients who do not reside in endemic areas. The case of a Mexican HIV+ patient who developed fever, general malaise, a severe cough, and dyspnea during a stay in Acapulco, Guerrero, Mexico, is presented. Since various diseases are endemic to the state of Guerrero, the doctors originally suspected that the patient had contracted influenza A (H1N1), Q fever, or tuberculosis. All the diagnostic tests for those diseases were negative. The patient had received numerous mosquito bites while staying in Acapulco, and a nodule had appeared on his right cheek. Therefore, malaria, cryptococcosis, and histoplasmosis were also suspected, but those infections were also ruled out through diagnostic tests. A direct microscopic examination was performed using KOH on a sample taken from the cheek nodule. The observation of spherules suggested the presence of a species of Coccidioides. The fungus was isolated, and its identity was confirmed by phenotypic and molecular methods. The geographic area in which the infection was likely acquired was identified by random amplified polymorphic DNA (RAPD) analysis. The results suggested a probable endogenous reactivation. This clinical case illustrates the difficulties associated with diagnosing coccidioidomycosis in non-endemic areas. Copyright © 2017. Publicado por Elsevier España, S.L.U.

Structural prediction of a novel chitinase from the psychrophilic Glaciozyma antarctica PI12 and an analysis of its structural properties and function

NASA Astrophysics Data System (ADS)

Ramli, Aizi Nor Mazila; Mahadi, Nor Muhammad; Shamsir, Mohd Shahir; Rabu, Amir; Joyce-Tan, Kwee Hong; Murad, Abdul Munir Abdul; Illias, Rosli Md.

2012-08-01

The structure of psychrophilic chitinase (CHI II) from Glaciozyma antarctica PI12 has yet to be studied in detail. Due to its low sequence identity (<30 %), the structural prediction of CHI II is a challenge. A 3D model of CHI II was built by first using a threading approach to search for a suitable template and to generate an optimum target-template alignment, followed by model building using MODELLER9v7. Analysis of the catalytic insertion domain structure in CHI II revealed an increase in the number of aromatic residues and longer loops compared to mesophilic and thermophilic chitinases. A molecular dynamics simulation was used to examine the stability of the CHI II structure at 273, 288 and 300 K. Structural analysis of the substrate-binding cleft revealed a few exposed aromatic residues. Substitutions of certain amino acids in the surface and loop regions of CHI II conferred an increased flexibility to the enzyme, allowing for an adaptation to cold temperatures. A substrate binding comparison of CHI II with the mesophilic chitinase from Coccidioides immitis, 1D2K, suggested that the psychrophilic adaptation and catalytic activity at low temperatures were achieved through a reduction in the number of salt bridges, fewer hydrogen bonds and an increase in the exposure of the hydrophobic side chains to the solvent.

Coccidioidomycosis and other endemic mycoses in Mexico.

PubMed

Laniado-Laborín, Rafael

2007-12-31

The endemic mycoses traditionally include coccidioidomycosis, histoplasmosis, blastomycosis and paracoccidioidomycosis. Although sporotrichosis and chromomycosis are technically not included among the endemic mycoses, they are frequently diagnosed in Mexico. Most systemic endemic mycoses are a consequence of inhaling the fungi, while subcutaneous mycoses are acquired through the inoculation of vegetable matter or soil containing the organism. Coccidioidomycosis is caused by Coccidioides spp., a dimorphic pathogenic fungus. Approximately 60% of exposures result in asymptomatic infection; in the rest there are protean manifestations that range from a benign syndrome also known as "Valley Fever" to progressive pulmonary or extrapulmonary disease. Histoplasmosis, caused by the dimorphic fungus Histoplasma capsulatum, is endemic to the Americas. Pulmonary histoplasmosis manifestations are protean, ranging from a brief period of malaise to a severe, prolonged illness. The spectrum of illness in disseminated histoplasmosis ranges from a chronic, intermittent course to an acute and rapidly fatal infection. Paracoccidioidomycosis is a chronic, granulomatous systemic disease caused by Paracoccidioides brasiliensis that characteristically produces a primary pulmonary infection, often asymptomatic, and then disseminates to form ulcerative granulomata of the oral, nasal and occasionally the gastrointestinal mucosa. Sporotrichosis, caused by Sporothrix schenckii, has diverse clinical manifestations; the most frequent is the lymphocutaneous form. Generally, infection results from inoculation of the fungus through thorns, splinters, scratches and small traumas. Chromomycosis (Chromoblastomycosis) is a slowly progressive cutaneous and subcutaneous mycosis attributed to various saprophyte Hypomycetes fungi. The primary lesion is also thought to develop as a result of percutaneous traumatic inoculation.

Fungi that Infect Humans.

PubMed

Köhler, Julia R; Hube, Bernhard; Puccia, Rosana; Casadevall, Arturo; Perfect, John R

2017-06-01

Fungi must meet four criteria to infect humans: growth at human body temperatures, circumvention or penetration of surface barriers, lysis and absorption of tissue, and resistance to immune defenses, including elevated body temperatures. Morphogenesis between small round, detachable cells and long, connected cells is the mechanism by which fungi solve problems of locomotion around or through host barriers. Secretion of lytic enzymes, and uptake systems for the released nutrients, are necessary if a fungus is to nutritionally utilize human tissue. Last, the potent human immune system evolved in the interaction with potential fungal pathogens, so few fungi meet all four conditions for a healthy human host. Paradoxically, the advances of modern medicine have made millions of people newly susceptible to fungal infections by disrupting immune defenses. This article explores how different members of four fungal phyla use different strategies to fulfill the four criteria to infect humans: the Entomophthorales, the Mucorales, the Ascomycota, and the Basidiomycota. Unique traits confer human pathogenic potential on various important members of these phyla: pathogenic Onygenales comprising thermal dimorphs such as Histoplasma and Coccidioides ; the Cryptococcus spp. that infect immunocompromised as well as healthy humans; and important pathogens of immunocompromised patients- Candida , Pneumocystis , and Aspergillus spp. Also discussed are agents of neglected tropical diseases important in global health such as mycetoma and paracoccidiomycosis and common pathogens rarely implicated in serious illness such as dermatophytes. Commensalism is considered, as well as parasitism, in shaping genomes and physiological systems of hosts and fungi during evolution.

Occurrence of Dermatophytes in Fresh Bat Guano1

PubMed Central

Kajihiro, Edwin S.

1965-01-01

Evidence is presented in support of the hypothesis that fresh bat guano serves as a means of pathogenic fungi dissemination in caves. A total of 371 guano samples were collected from caves in southeastern New Mexico. Each sample was agitated in sterile saline and sand. The supernatant fluid was treated with an antibiotic and streaked on differential media. Cultures were incubated at 25 and 37 C and examined at intervals over a 4-week period. For animal inoculation, highly concentrated inoculum was injected intraperitoneally into white Swiss mice. Animals were sacrificed 4 weeks later, and portions of their lung, liver, and spleen were cultured on selective media, incubated at 25 C, and examined at intervals over a 4-week period. Microsporum gypseum was isolated at all 10 collecting stations with an incidence of 22.4%, Trichophyton mentagrophytes at 7 stations with an incidence of 5%, T. rubrum at 3 stations with an incidence of 3%, and T. terrestre at 1 station with an incidence of 0.5%. From a total of 60 pools of liver-spleen-lung suspensions, 6 pools yielded positive cultures of Histoplasma capsulatum and 1 pool yielded T. mentagrophytes. No significant difference was found among the different selective media with respect to recovery of dermatophytes. Among the human pathogenic fungi isolated were Candida sp., Cladosporium sp., Coccidioides immitis, Cryptococcus neoformans, H. capsulatum, M. gypseum, T. mentagrophytes, T. rubrum, T. terrestre, and Sporotrichum sp. Images Fig. 1 PMID:5867652

[Acute encephalitis. Neuropsychiatric manifestations as expression of influenza virus infection].

PubMed

Moreno-Flagge, Noris; Bayard, Vicente; Quirós, Evelia; Alonso, Tomás

2009-01-01

The aim is to review the encephalitis in infants and adolescents as well as its etiology, clinical manifestation, epidemiology, physiopathology, diagnostic methods and treatment, and the neuropsyquiatric signs appearing an influenza epidemy. Encephalitis is an inflammation of the central nervous system (CNS) which involves the brain. The clinical manifestations usually are: headache, fever and confusional stage. It could also be manifested as seizures, personality changes, or psiqyiatric symptoms. The clinical manifestations are related to the virus and the cell type affected in the brain. A meningitis or encephalopathy need to be ruled out. It could be present as an epidemic or isolated form, beeing this the most frequent form. It could be produced by a great variety of infections agents including virus, bacterias, fungal and parasitic. Viral causes are herpesvirus, arbovirus, rabies and enterovirus. Bacterias such as Borrelia burgdorferi, Rickettsia and Mycoplasma neumoniae. Some fungal causes are: Coccidioides immitis and Histoplasma capsulatum. More than 100 agents are related to encephalitis. The diagnosis of encephalitis is a challenge for the clinician and its infectious etiology is clear in only 40 to 70% of all cases. The diagnosis of encephalitis can be established with absolute certainty only by the microscopic examination of brain tissue. Epidemiology is related to age of the patients, geographic area, season, weather or the host immune system. Early intervention can reduce the mortality rate and sequels. We describe four patients with encephalitis and neuropsychiatric symptoms during an influenza epidemic.

Climate controls on valley fever incidence in Kern County, California

NASA Astrophysics Data System (ADS)

Zender, Charles S.; Talamantes, Jorge

2006-01-01

Coccidiodomycosis (valley fever) is a systemic infection caused by inhalation of airborne spores from Coccidioides immitis, a soil-dwelling fungus found in the southwestern United States, parts of Mexico, and Central and South America. Dust storms help disperse C. immitis so risk factors for valley fever include conditions favorable for fungal growth (moist, warm soil) and for aeolian soil erosion (dry soil and strong winds). Here, we analyze and inter-compare the seasonal and inter-annual behavior of valley fever incidence and climate risk factors for the period 1980-2002 in Kern County, California, the US county with highest reported incidence. We find weak but statistically significant links between disease incidence and antecedent climate conditions. Precipitation anomalies 8 and 20 months antecedent explain only up to 4% of monthly variability in subsequent valley fever incidence during the 23 year period tested. This is consistent with previous studies suggesting that C. immitis tolerates hot, dry periods better than competing soil organisms and, as a result, thrives during wet periods following droughts. Furthermore, the relatively small correlation with climate suggests that the causes of valley fever in Kern County could be largely anthropogenic. Seasonal climate predictors of valley fever in Kern County are similar to, but much weaker than, those in Arizona, where previous studies find precipitation explains up to 75% of incidence. Causes for this discrepancy are not yet understood. Higher resolution temporal and spatial monitoring of soil conditions could improve our understanding of climatic antecedents of severe epidemics.

Comparative and functional genomics provide insights into the pathogenicity of dermatophytic fungi

PubMed Central

2011-01-01

Background Millions of humans and animals suffer from superficial infections caused by a group of highly specialized filamentous fungi, the dermatophytes, which exclusively infect keratinized host structures. To provide broad insights into the molecular basis of the pathogenicity-associated traits, we report the first genome sequences of two closely phylogenetically related dermatophytes, Arthroderma benhamiae and Trichophyton verrucosum, both of which induce highly inflammatory infections in humans. Results 97% of the 22.5 megabase genome sequences of A. benhamiae and T. verrucosum are unambiguously alignable and collinear. To unravel dermatophyte-specific virulence-associated traits, we compared sets of potentially pathogenicity-associated proteins, such as secreted proteases and enzymes involved in secondary metabolite production, with those of closely related onygenales (Coccidioides species) and the mould Aspergillus fumigatus. The comparisons revealed expansion of several gene families in dermatophytes and disclosed the peculiarities of the dermatophyte secondary metabolite gene sets. Secretion of proteases and other hydrolytic enzymes by A. benhamiae was proven experimentally by a global secretome analysis during keratin degradation. Molecular insights into the interaction of A. benhamiae with human keratinocytes were obtained for the first time by global transcriptome profiling. Given that A. benhamiae is able to undergo mating, a detailed comparison of the genomes further unraveled the genetic basis of sexual reproduction in this species. Conclusions Our results enlighten the genetic basis of fundamental and putatively virulence-related traits of dermatophytes, advancing future research on these medically important pathogens. PMID:21247460

Cellular and Molecular Defects Underlying Invasive Fungal Infections—Revelations from Endemic Mycoses

PubMed Central

Lee, Pamela P.; Lau, Yu-Lung

2017-01-01

The global burden of fungal diseases has been increasing, as a result of the expanding number of susceptible individuals including people living with human immunodeficiency virus (HIV), hematopoietic stem cell or organ transplant recipients, patients with malignancies or immunological conditions receiving immunosuppressive treatment, premature neonates, and the elderly. Opportunistic fungal pathogens such as Aspergillus, Candida, Cryptococcus, Rhizopus, and Pneumocystis jiroveci are distributed worldwide and constitute the majority of invasive fungal infections (IFIs). Dimorphic fungi such as Histoplasma capsulatum, Coccidioides spp., Paracoccidioides spp., Blastomyces dermatiditis, Sporothrix schenckii, Talaromyces (Penicillium) marneffei, and Emmonsia spp. are geographically restricted to their respective habitats and cause endemic mycoses. Disseminated histoplasmosis, coccidioidomycosis, and T. marneffei infection are recognized as acquired immunodeficiency syndrome (AIDS)-defining conditions, while the rest also cause high rate of morbidities and mortalities in patients with HIV infection and other immunocompromised conditions. In the past decade, a growing number of monogenic immunodeficiency disorders causing increased susceptibility to fungal infections have been discovered. In particular, defects of the IL-12/IFN-γ pathway and T-helper 17-mediated response are associated with increased susceptibility to endemic mycoses. In this review, we put together the various forms of endemic mycoses on the map and take a journey around the world to examine how cellular and molecular defects of the immune system predispose to invasive endemic fungal infections, including primary immunodeficiencies, individuals with autoantibodies against interferon-γ, and those receiving biologic response modifiers. Though rare, these conditions provide importance insights to host defense mechanisms against endemic fungi, which can only be appreciated in unique climatic and geographical regions. PMID:28702025

Application of Immunosignatures for Diagnosis of Valley Fever

PubMed Central

Navalkar, Krupa Arun; Johnston, Stephen Albert; Woodbury, Neal; Galgiani, John N.; Magee, D. Mitchell; Chicacz, Zbigniew

2014-01-01

Valley fever (VF) is difficult to diagnose, partly because the symptoms of VF are confounded with those of other community-acquired pneumonias. Confirmatory diagnostics detect IgM and IgG antibodies against coccidioidal antigens via immunodiffusion (ID). The false-negative rate can be as high as 50% to 70%, with 5% of symptomatic patients never showing detectable antibody levels. In this study, we tested whether the immunosignature diagnostic can resolve VF false negatives. An immunosignature is the pattern of antibody binding to random-sequence peptides on a peptide microarray. A 10,000-peptide microarray was first used to determine whether valley fever patients can be distinguished from 3 other cohorts with similar infections. After determining the VF-specific peptides, a small 96-peptide diagnostic array was created and tested. The performances of the 10,000-peptide array and the 96-peptide diagnostic array were compared to that of the ID diagnostic standard. The 10,000-peptide microarray classified the VF samples from the other 3 infections with 98% accuracy. It also classified VF false-negative patients with 100% sensitivity in a blinded test set versus 28% sensitivity for ID. The immunosignature microarray has potential for simultaneously distinguishing valley fever patients from those with other fungal or bacterial infections. The same 10,000-peptide array can diagnose VF false-negative patients with 100% sensitivity. The smaller 96-peptide diagnostic array was less specific for diagnosing false negatives. We conclude that the performance of the immunosignature diagnostic exceeds that of the existing standard, and the immunosignature can distinguish related infections and might be used in lieu of existing diagnostics. PMID:24964807

Isavuconazole Treatment of Cryptococcosis and Dimorphic Mycoses.

PubMed

Thompson, George R; Rendon, Adrian; Ribeiro Dos Santos, Rodrigo; Queiroz-Telles, Flavio; Ostrosky-Zeichner, Luis; Azie, Nkechi; Maher, Rochelle; Lee, Misun; Kovanda, Laura; Engelhardt, Marc; Vazquez, Jose A; Cornely, Oliver A; Perfect, John R

2016-08-01

Invasive fungal diseases (IFD) caused by Cryptococcus and dimorphic fungi are associated with significant morbidity and mortality. Isavuconazole (ISAV) is a novel, broad-spectrum, triazole antifungal agent (IV and by mouth [PO]) developed for the treatment of IFD. It displays potent activity in vitro against these pathogens and in this report we examine outcomes of patients with cryptococcosis or dimorphic fungal infections treated with ISAV. The VITAL study was an open-label nonrandomized phase 3 trial conducted to evaluate the efficacy and safety of ISAV treatment in management of rare IFD. Patients received ISAV 200 mg 3 times daily for 2 days followed by 200 mg once-daily (IV or PO). Proven IFD and overall response at end of treatment (EOT) were determined by an independent, data-review committee. Mortality and safety were also assessed. Thirty-eight patients received ISAV for IFD caused by Cryptococcus spp. (n = 9), Paracoccidioides spp. (n = 10), Coccidioides spp. (n = 9), Histoplasma spp. (n = 7) and Blastomyces spp. (n = 3). The median length of therapy was 180 days (range 2-331 days). At EOT 24/38 (63%) patients exhibited a successful overall response. Furthermore, 8 of 38 (21%) had stable IFD at the end of therapy without progression of disease, and 6 (16%) patients had progressive IFD despite this antifungal therapy. Thirty-three (87%) patients experienced adverse events. ISAV was well tolerated and demonstrated clinical activity against these endemic fungi with a safety profile similar to that observed in larger studies, validating its broad-spectrum in vitro activity and suggesting it may be a valuable alternative to currently available agents. NCT00634049. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

Heat-Killed Yeast as a Pan-Fungal Vaccine.

PubMed

Martinez, Marife; Clemons, Karl V; Stevens, David A

2017-01-01

Fungal infections continue to rise worldwide. Antifungal therapy has long been a mainstay for the treatment of these infections, but often can fail for a number of reasons. These include acquired or innate drug resistance of the causative agent, poor drug penetration into the affected tissues, lack of cidal activity of the drug and drug toxicities that limit therapy. In some instances, such as coccidioidal meningitis, therapy is life-long. In addition, few new antifungal drugs are under development. In light of this information a preventative vaccine is highly desirable. Although numerous investigators have worked toward the development of fungal vaccines, none have become commercially available for use in humans. In the course of our studies, we have discovered that heat-killed yeast (HKY) of Saccharomyces cerevisiae can be used as a vaccine and have shown that it has efficacy in the prevention and reduction of five different fungal infections when used experimentally in mice, which raises the possibility of a pan-fungal vaccine preparation. In our studies we grow S. cerevisiae in broth and heat-kill the organism at 70 ° C for 3 h. The number of dead yeast cells is adjusted and mice are vaccinated subcutaneously beginning 3-7 weeks prior to infection. After infection, efficacy is assessed on the basis of survival and residual burden of the fungus in the target organs. Alternatively, efficacy can be assessed solely on fungal burden at a predetermined time postinfection. Although itself it is unlikely to be moved toward commercialization, HKY can be used a positive control vaccine for studies on specific molecular entities as vaccines, and as a guidepost for the key elements of potential, more purified, pan-fungal vaccine preparations.

Large-Scale Land Development, Fugitive Dust, and Increased Coccidioidomycosis Incidence in the Antelope Valley of California, 1999-2014.

PubMed

Colson, Aaron J; Vredenburgh, Larry; Guevara, Ramon E; Rangel, Natalia P; Kloock, Carl T; Lauer, Antje

2017-06-01

Ongoing large-scale land development for renewable energy projects in the Antelope Valley, located in the Western Mojave Desert, has been blamed for increased fugitive dust emissions and coccidioidomycosis incidence among the general public in recent years. Soil samples were collected at six sites that were destined for solar farm construction and were analyzed for the presence of the soil-borne fungal pathogen Coccidioides immitis which is endemic to many areas of central and southern California. We used a modified culture-independent nested PCR approach to identify the pathogen in all soil samples and also compared the sampling sites in regard to soil physical and chemical parameters, degree of disturbance, and vegetation. Our results indicated the presence of C. immitis at four of the six sites, predominantly in non-disturbed soils of the Pond-Oban complex, which are characterized by an elevated pH and salt bush communities, but also in grassland characterized by different soil parameters and covered with native and non-native annuals. Overall, we were able to detect the pathogen in 40% of the soil samples (n = 42). Incidence of coccidioidomycosis in the Antelope Valley was positively correlated with land use and particulate matter in the air (PM10) (Pearson correlation coefficient >0.5). With the predicted population growth and ongoing large-scale disturbance of soil in the Antelope Valley in coming years, incidence of coccidioidomycosis will likely further increase if policy makers and land developers continue to ignore the risk of grading land without implementing long-term dust mitigation plans in Environmental Impact Reports.

Evaluation of the Specificity of Two Enzyme Immunoassays for Coccidioidomycosis by Using Sera from a Region of Endemicity and a Region of Nonendemicity

PubMed Central

Ahn, YoonJi; McCotter, Orion; Gade, Lalitha; Hurst, Steven F.; Brandt, Mary E.; Park, Benjamin J.; Litvintseva, Anastasia P.

2015-01-01

Coccidioidomycosis (CM), a serious life-threatening fungal infection endemic to arid regions of the western United States and Mexico, can be challenging to diagnose in a timely manner. Commercially developed enzyme immunoassays (EIAs) (from Meridian Biosciences and Immuno-Mycologics [IMMY]) have provided faster, simpler means for serodiagnosis; however, independent evaluations have questioned EIA specificity, particularly IgM-positive/IgG-negative results. This study was conducted to evaluate EIA specificity among persons residing in Puerto Rico (n = 534), where CM is not endemic (who were not likely to have been exposed to Coccidioides spp.), compared to blood bank donors residing in Arizona (n = 1,218), where CM is endemic. Upon comparing serum reactivity between Puerto Rico and Arizona, the Meridian EIA showed a significant difference in IgG reactivity (0.37% versus 3.6%; P < 0.001) but not IgM reactivity (3.4% versus 2.4%; P = 0.31). No IgM-/IgG-reactive sera were detected among sera from Puerto Rico, compared to 7 (0.57%) sera from Arizona. Similar results were observed using the IMMY EIA, although significantly (P = 0.03) fewer IgM-reactive sera from Arizona were observed, compared to the Meridian EIA. EIA-reactive sera were also evaluated by immunodiffusion before and after 3- to 4-fold concentration of the sera. These results demonstrate that elevated IgG EIA reactivity is present in sera from healthy individuals in regions of endemicity and that IgM EIA reactivity observed in sera from individuals residing outside regions of endemicity is most likely nonspecific. Other criteria, including clinical and microbiological evaluations, should be taken into account when interpreting results from surveillance studies and other reporting measures. PMID:26245352

Development of a Quantitative TaqMan{trademark}-PCR Assay and Feasibility of Atmosphoric Collection for Coccidioides Immits for Ecological Studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Daniels, J I; Wilson, W J; DeSantis, T Z

2002-02-01

Understanding and then modeling the complex relationships between environmental, climatological, and biological systems can present great opportunities for developing effective strategies to prevent outbreaks of environmentally linked infectious disease. For example, a report from the American Academy of Microbiology (Rose et al., 2001) points out that including climatic signals and ecological triggers into the decision making process for disease management, is going to be essential for developing a proactive approach for protecting public health, and circumventing the practice of having to wait for clinical cases to appear before any action is taken. To meet this grand challenge, specific and sensitivemore » analytical techniques and effective collection devices are required for finding the microorganisms of concern in environmentally relevant media (air, soil, water, vegetation, etc.), and a multidisciplinary approach is needed for evaluating all of the environmental and biological data and building the applicable predictive models. In this study, the unique capabilities in biotechnology and environmental science available at Lawrence Livermore National Laboratory (LLNL) are combined with the distinguished and highly regarded expertise for clinically investigating and treating infectious disease at the Department of Microbiology and Immunology in the School of Medicine of the University of California, Davis, in order to develop, standardize, validate, and test safely the feasibility of applying advanced polymerase chain reaction (PCR) technology and new air-sample collection media that would be appropriate for addressing comprehensively the environmentally linked, medically important infectious disease Valley Fever (coccidioidomycosis). The responsible agent for this disease is the airborne spore (arthroconidia) of the pathogenic fungus Coccidioides immitis, which is a microorganism that is endemic to California, Arizona, and the southwestern United States, and also is identified as a select (biological) agent in the federal Anti-Terrorist and Effective Death Penalty Act. Successful demonstration of these tools in this study will place this multidisciplinary team in a credible position to proceed with additional research designed to determine the climatic signals and ecological triggers that would be associated with the presence of this microorganism environmentally and that would correlate with subsequent outbreaks of Valley Fever clinically. Results from such future research would then provide the information needed for environmental intervention of the disease occurrence, well before clinical cases appear. The technology and modeling developed for such a study also could be used for determining the ecology of other environmentally linked, medically important infectious diseases that occur naturally or that might be introduced deliberately into environmental media indoors or outside. The following approach was taken to achieve the technological objectives of this study. First, the protocols for the TaqMan{trademark}-PCR assay were enhanced to achieve the superior specificity and sensitivity required for quantifying, from a DNA signature, those C. immitis spores that are present in calibration samples (consisting of known quantities of pure culture inoculated onto air-filter concentrate, and then removed, and the DNA extracted) and those that are present within the calibration range on air filters obtained from the field and handled similarly. Second, the feasibility of using advanced nuclepore air-filter media to collect the spores from ambient air in C immitis endemic areas in the Central Valley of California was evaluated. These membranes permit the physics of high-volume air sampling to be used to filter larger amounts of air than previously possible for detecting airborne microorganisms. Thus, the higher volume of air flow improves the likelihood of capturing on the filter any C. immitis spores resuspended from nearby soil, where this microorganism grows prior to sporulation, and where its exact location can be elusive under any environmental conditions. Finally, experiments were conducted in the Department of Microbiology and Immunology at the School of Medicine of the University of California, Davis (UCD), to demonstrate that C. immitis spores can be killed, whether in pure culture or on air-filter media, to ensure safe handling during laboratory processing and analyses.« less

The Changing Epidemiology of Coccidioidomycosis in Los Angeles (LA) County, California, 1973–2011

PubMed Central

2015-01-01

Coccidioidomycosis, also known as Valley Fever, is often thought of as an endemic disease of central California exclusive of Los Angeles County. The fungus that causes Valley Fever, Coccidioides spp., grows in previously undisturbed soil of semi-arid and arid environments of certain areas of the Americas. LA County has a few large areas with such environments, particularly the Antelope Valley which has been having substantial land development. Coccidioidomycosis that is both clinically- and laboratory-confirmed is a mandated reportable disease in LA County. Population surveillance data for 1973–2011 reveals an annual rate increase from 0.87 to 3.2 cases per 100,000 population (n = 61 to 306 annual cases). In 2004, case frequency started substantially increasing with notable epidemiologic changes such as a rising 2.1 to 5.7 male-to-female case ratio stabilizing to 1.4–2.2. Additionally, new building construction in Antelope Valley greatly rose in 2003 and displayed a strong correlation (R = 0.92, Pearson p<0.0001) with overall LA County incidence rates for 1996–2007. Of the 24 LA County health districts, 19 had a 100%-1500% increase in cases when comparing 2000–2003 to 2008–2011. Case residents of endemic areas had stronger odds of local exposures, but cases from areas not known to be endemic had greater mortality (14% versus 9%) with notably more deaths during 2008–2011. Compared to the 57 other California counties during 2001–2011, LA County had the third highest average annual number of cases and Antelope Valley had a higher incidence rate than all but six counties. With the large number of reported coccidioidomycosis cases, multi-agency and community partnering is recommended to develop effective education and prevention strategies to protect residents and travelers. PMID:26313151

A new class of fatty acid allene oxide formed by the DOX-P450 fusion proteins of human and plant pathogenic fungi, C. immitis and Z. tritici[S

PubMed Central

Oliw, Ernst H.; Aragó, Marc; Chen, Yang; Jernerén, Fredrik

2016-01-01

Linoleate dioxygenase-cytochrome P450 (DOX-CYP) fusion enzymes are common in pathogenic fungi. The DOX domains form hydroperoxy metabolites of 18:2n-6, which can be transformed by the CYP domains to 1,2- or 1,4-diols, epoxy alcohols, or to allene oxides. We have characterized two novel allene oxide synthases (AOSs), namely, recombinant 8R-DOX-AOS of Coccidioides immitis (causing valley fever) and 8S-DOX-AOS of Zymoseptoria tritici (causing septoria tritici blotch of wheat). The 8R-DOX-AOS oxidized 18:2n-6 sequentially to 8R-hydroperoxy-9Z,12Z-octadecadienoic acid (8R-HPODE) and to an allene oxide, 8R(9)-epoxy-9,12Z-octadecadienoic acid, as judged from the accumulation of the α-ketol, 8S-hydroxy-9-oxo-12Z-octadecenoic acid. The 8S-DOX-AOS of Z. tritici transformed 18:2n-6 sequentially to 8S-HPODE and to an α-ketol, 8R-hydroxy-9-oxo-12Z-octadecenoic acid, likely formed by hydrolysis of 8S(9)-epoxy-9,12Z-octadecadienoic acid. The 8S-DOX-AOS oxidized [8R-2H]18:2n-6 to 8S-HPODE with retention of the 2H-label, suggesting suprafacial hydrogen abstraction and oxygenation in contrast to 8R-DOX-AOS. Both enzymes oxidized 18:1n-9 and 18:3n-3 to α-ketols, but the catalysis of the 8R- and 8S-AOS domains differed. 8R-DOX-AOS transformed 9R-HPODE to epoxy alcohols, but 8S-DOX-AOS converted 9S-HPODE to an α-ketol (9-hydroxy-10-oxo-12Z-octadecenoic acid) and epoxy alcohols in a ratio of ∼1:2. Whereas all fatty acid allene oxides described so far have a conjugated diene impinging on the epoxide, the allene oxides formed by 8-DOX-AOS are unconjugated. PMID:27282156

Estimating sources of Valley Fever pathogen propagation in southern Arizona: A remote sensing approach

NASA Astrophysics Data System (ADS)

Pianalto, Frederick S.

Coccidioidomycosis (Valley Fever) is an environmentally-mediated respiratory disease caused by the inhalation of airborne spores from the fungi Coccidioides spp. The fungi reside in arid and semi-arid soils of the Americas. The disease has increased epidemically in Arizona and other areas within the last two decades. Despite this increase, the ecology of the fungi remains obscure, and environmental antecedents of the disease are largely unstudied. Two sources of soil disturbance, hypothesized to affect soil ecology and initiate spore dissemination, are investigated. Nocturnal desert rodents interact substantially with the soil substrate. Rodents are hypothesized to act as a reservoir of coccidioidomycosis, a mediator of soil properties, and a disseminator of fungal spores. Rodent distributions are poorly mapped for the study area. We build automated multi-linear regression models and decision tree models for ten rodent species using rodent trapping data from the Organ Pipe Cactus National Monument (ORPI) in southwest Arizona with a combination of surface temperature, a vegetation index and its texture, and a suite of topographic rasters. Surface temperature, derived from Landsat TM thermal images, is the most widely selected predictive variable in both automated methods. Construction-related soil disturbance (e.g. road construction, trenching, land stripping, and earthmoving) is a significant source of fugitive dust, which decreases air quality and may carry soil pathogens. Annual differencing of Landsat Thematic Mapper (TM) mid-infrared images is used to create change images, and thresholded change areas are associated with coordinates of local dust inspections. The output metric identifies source areas of soil disturbance, and it estimates the annual amount of dust-producing surface area for eastern Pima County spanning 1994 through 2009. Spatially explicit construction-related soil disturbance and rodent abundance data are compared with coccidioidomycosis incidence data using rank order correlation and regression methods. Construction-related soil disturbance correlates strongly with annual county-wide incidence. It also correlates with Tucson periphery incidence aggregated to zip codes. Abundance values for the desert pocket mouse (Chaetodipus penicillatus), derived from a soil-adjusted vegetation index, aspect (northing) and thermal radiance, correlate with total study period incidence aggregated to zip code.

[Tropical and travel-related dermatomycoses : Part 2: cutaneous infections due to yeasts, moulds, and dimorphic fungi].

PubMed

Nenoff, P; Reinel, D; Krüger, C; Grob, H; Mugisha, P; Süß, A; Mayser, P

2015-07-01

Besides dermatophytoses, a broad range of cutaneous infections due to yeasts and moulds may occur in subtropical and tropical countries where they can affect travellers. Not to be forgotten are endemic occurring dimorphic or biphasic fungi in countries with hot climate, which cause systemic and secondary cutaneous infections in immunosuppressed and immunocompetent people. In the tropics, the prevalence of pityriasis versicolor, caused by the lipophilic yeast Malassezia spp., is about 30-40 %, in distinct areas even 50 %. Increased hyperhidrosis under tropical conditions and simultaneously humidity congestion have to be considered as significant disposing factors for pityriasis versicolor. In tropical countries, therefore, an exacerbation of a preexisting pityriasis versicolor in travellers is not rare. Today, mostly genital yeast infections due to the new species Candida africana can be found worldwide. Due to migration from Africa this yeast pathogen has reached Germany and Europe. Eumycetomas due to mould fungi are rarely diagnosed in Europe. These deep cutaneous mould infections are only found in immigrants from African countries. The therapy of eumycetoma is protracted and often not successful. Cutaneous cryptococcoses due to the yeast species Cryptococcus neoformans and Cryptococcus gattii occur worldwide; however, they are found more frequently in the tropics. Immunosuppressed patients, especially those with HIV/AIDS, are affected by cryptococcoses. Furthermore, Cryptococcus gattii also causes infections in immunocompetent hosts in Central Africa, Australia, California, and Central America.Rarely found are infections due to dimorphic fungi after travel to countries where these fungal pathogens are endemic. In individual cases, cutaneous or lymphogenic transferred sporotrichosis due to Sporothrix schenkii can occur. Furthermore, scarcely known is secondary cutaneous coccidioidomycosis due to Coccidioides immitis after travelling to desert-like endemic regions in southwestern states of the United States and in Latin America, where primary respiratory infection due to this biphasic fungus can be acquired. The antifungal agent itraconazole is the treatment of choice for sporotrichosis and coccidioidomycosis. Talaromyces marneffei-until recently known as Penicillium marneffei-is only found in Southeastern Asia. Mycosis due to this dimorphic fungus has to be considered as an AIDS-defining opportunistic infection. After hematogeneous spread, Talaromyces marneffei affects the skin and mucous membranes of the mouth. Amphotericin B and itraconazole can be used for therapy.

Microbial Disease Spectrum Linked to a Novel IL-12Rβ1 N-Terminal Signal Peptide Stop-Gain Homozygous Mutation with Paradoxical Receptor Cell-Surface Expression

PubMed Central

Louvain de Souza, Thais; de Souza Campos Fernandes, Regina C.; Azevedo da Silva, Juliana; Gomes Alves Júnior, Vladimir; Gomes Coelho, Adelia; Souza Faria, Afonso C.; Moreira Salomão Simão, Nabia M.; Souto Filho, João T.; Deswarte, Caroline; Boisson-Dupuis, Stéphanie; Torgerson, Dara; Casanova, Jean-Laurent; Bustamante, Jacinta; Medina-Acosta, Enrique

2017-01-01

Patients with Mendelian Susceptibility to Mycobacterial Diseases (MSMD) exhibit variable vulnerability to infections by mycobacteria and other intramacrophagic bacteria (e.g., Salmonella and Klebsiella) and fungi (e.g., Histoplasma, Candida, Paracoccidioides, Coccidioides, and Cryptococcus). The hallmark of MSMD is the inherited impaired production of interferon gamma (IFN-γ) or the lack of response to it. Mutations in the interleukin (IL)-12 receptor subunit beta 1 (IL12RB1) gene accounts for 38% of cases of MSMD. Most IL12RB1 pathogenic allele mutations, including ten known stop-gain variants, cause IL-12Rβ1 complete deficiency (immunodeficiency-30, IMD30) by knocking out receptor cell-surface expression. IL12RB1 loss-of-function genotypes impair both IL-12 and IL-23 responses. Here, we assess the health effects of a rare, novel IL12RB1 stop-gain homozygous genotype with paradoxical IL-12Rβ1 cell-surface expression. We appraise four MSMD children from three unrelated Brazilian kindreds by clinical consultation, medical records, and genetic and immunologic studies. The clinical spectrum narrowed down to Bacillus Calmette-Guerin (BCG) vaccine-related suppurative adenitis in all patients with one death, and recrudescence in two, histoplasmosis, and recurrence in one patient, extraintestinal salmonellosis in one child, and cutaneous vasculitis in another. In three patients, we established the homozygous Trp7Ter predicted loss-of-function inherited genotype and inferred it from the heterozygote parents of the fourth case. The Trp7Ter mutation maps to the predicted IL-12Rβ1 N-terminal signal peptide sequence. BCG- or phytohemagglutinin-blasts from the three patients have reduced cell-surface expression of IL-12Rβ1 with impaired production of IFN-γ and IL-17A. Screening of 227 unrelated healthy subjects from the same geographic region revealed one heterozygous genotype (allele frequency 0.0022) vs. one in over 841,883 public genome/exomes. We also show that the carriers bear European ancestry-informative alleles and share the extended CACCAGTCCGG IL12RB1 haplotype that occurs worldwide with a frequency of 8.4%. We conclude that the novel IL12RB1 N-terminal signal peptide stop-gain loss-of-function homozygous genotype confers IL-12Rβ1 deficiency with varying severity and early-onset age through diminished cell-surface expression of an impaired IL-12Rβ1 polypeptide. We firmly recommend attending to warning signs of IMD30 in children who are HIV-1 negative with a history of adverse effects to the BCG vaccine and presenting with recurrent Histoplasma spp. and extraintestinal Salmonella spp. infections. PMID:28450854

Neuroinfections caused by fungi.

PubMed

Góralska, Katarzyna; Blaszkowska, Joanna; Dzikowiec, Magdalena

2018-05-21

Fungal infections of the central nervous system (FIs-CNS) have become significantly more common over the past 2 decades. Invasion of the CNS largely depends on the immune status of the host and the virulence of the fungal strain. Infections with fungi cause a significant morbidity in immunocompromised hosts, and the involvement of the CNS may lead to fatal consequences. One hundred and thirty-five articles on fungal neuroinfection in PubMed, Google Scholar, and Cochrane databases were selected for review using the following search words: "fungi and CNS mycoses", CNS fungal infections", "fungal brain infections", " fungal cerebritis", fungal meningitis", "diagnostics of fungal infections", and "treatment of CNS fungal infections". All were published in English with the majority in the period 2000-2018. This review focuses on the current knowledge of the epidemiology, clinical presentations, diagnosis, and treatment of selected FIs-CNS. The FIs-CNS can have various clinical presentations, mainly meningitis, encephalitis, hydrocephalus, cerebral abscesses, and stroke syndromes. The etiologic factors of neuroinfections are yeasts (Cryptococcus neoformans, Candida spp., Trichosporon spp.), moniliaceous moulds (Aspergillus spp., Fusarium spp.), Mucoromycetes (Mucor spp., Rhizopus spp.), dimorphic fungi (Blastomyces dermatitidis, Coccidioides spp., Histoplasma capsulatum), and dematiaceous fungi (Cladophialophora bantiana, Exophiala dermatitidis). Their common route of transmission is inhalation or inoculation from trauma or surgery, with subsequent hematogenous or contiguous spread. As the manifestations of FIs-CNS are often non-specific, their diagnosis is very difficult. A fast identification of the etiological factor of neuroinfection and the application of appropriate therapy are crucial in preventing an often fatal outcome. The choice of effective drug depends on its extent of CNS penetration and spectrum of activity. Pharmaceutical formulations of amphotericin B (AmB) (among others, deoxycholate-AmBd and liposomal L-AmB) have relatively limited distribution in the cerebrospinal fluid (CSF); however, their detectable therapeutic concentrations in the CNS makes them recommended drugs for the treatment of cryptococcal meningoencephalitis (AmBd with flucytosine) and CNS candidiasis (L-AmB) and mucormycosis (L-AmB). Voriconazole, a moderately lipophilic molecule with good CNS penetration, is recommended in the first-line therapy of CNS aspergillosis. Other triazoles, such as posaconazole and itraconazole, with negligible concentrations in the CSF are not considered effective drugs for therapy of CNS fungal neuroinfections. In contrast, clinical data have shown that a novel triazole, isavuconazole, achieved considerable efficacy for the treatment of some fungal neuroinfections. Echinocandins with relatively low or undetectable concentrations in the CSF do not play meaningful role in the treatment of FIs-CNS. Although the number of fungal species causing CNS mycosis is increasing, only some possess well-defined treatment standards (e.g., cryptococcal meningitis and CNS aspergillosis). The early diagnosis of fungal infection, accompanied by identification of the etiological factor, is needed to allow the selection of effective therapy in patients with FIs-CNS and limit their high mortality.

Environmental Variability and Fluctuation of Coccidioidomycosis (Valley Fever) In California: Based on a New Framework Involving Fungal Life Cycle

NASA Astrophysics Data System (ADS)

Jia, S.; Okin, G. S.; Shafir, S. C.

2013-12-01

Coccidioidomycosis (valley fever), caused by inhalation of spores from pathogenic fungus includingCoccidiodes immitis (C. immitis) and Coccidioides posadasii (C. posadasii), is a disease endemic to arid regions in the southwest US, as well as parts of Central and South America. With a projected increase of drought in this region, an improved understanding of environmental factors behind the outbreaks of coccidioidomycosis will enable the prediction of coccidioidomycosis in a changing climate regime. Previous research shows the infections correlate with climate conditions including precipitation, temperature, and dust. However, most studies focus only on the environmental conditions of fungus growth, which is the first stage in the fungal life cycle. In contrast, we extend the analysis to the following two stages in the life cycle, arthrospore formation and dispersal, to form a better model to predict the disease outbreaks. Besides climate conditions, we use relative spectral mixture analysis (RSMA) based on MODIS MOD43 nadir BRDF adjusted reflectance (NBAR) data to derive the relative dynamics of green vegetation, non-photosynthetic vegetation and bare soil coverage as better indicators of soil moisture, which is important for arthospore formation and dispersal. After detecting the hotspots of disease outbreaks, we correlate seasonal incidence from 2000 to 2010 with the environmental variables zero to eight seasons before to obtain candidates for stepwise regression. Regression result shows a seasonal difference in the leading explanatory variables. Such difference indicates the different seasonal main influential process from fungal life cycle. C. immitis (fungus responsible for coccidioidomycosis outbreaks in California) growth explains outbreaks in winter and fall better than other two stages in the life cycle, while arthospore formation is more responsible for spring and summer outbreaks. As the driest season, summer has the largest area related with arthospore dispersal. The seasonal difference of main influential process relates to the length of lags between the outbreaks and stages in fungal life cycle. During wet seasons of California including winter and fall, outbreaks are less correlated with the short-lag process such as dispersal of arthospores because of high soil moisture. In contrast, the long-lag process like C.immitis growth is influential on outbreaks in wet seasons. The arthospore formation, especially during the latest dry season (with a lag less than one year), is more responsible for outbreaks in spring and summer, when the influence of C. immitis growth is dampened by time. However, arthospores formed and preserved years ago may introduce uncertainty to the seasonal lag patterns. The long lags also exist in outbreaks related to arthospore formation. By including all three stages of fungal life cycle, we formed a more comprehensive framework in explaining the relationship between environmental conditions and disease outbreaks. Such analysis can be extended to a finer temporal resolution (e.g. per month) to obtain a clearer picture between environmental variability and coccidioidomycosis fluctuation.

Combining disparate data for decision making

NASA Astrophysics Data System (ADS)

Gettings, M. E.

2010-12-01

Combining information of disparate types from multiple data or model sources is a fundamental task in decision making theory. Procedures for combining and utilizing quantitative data with uncertainties are well-developed in several approaches, but methods for including qualitative and semi-quantitative data are much less so. Possibility theory offers an approach to treating all three data types in an objective and repeatable way. In decision making, biases are frequently present in several forms, including those arising from data quality, data spatial and temporal distribution, and the analyst's knowledge and beliefs as to which data or models are most important. The latter bias is particularly evident in the case of qualitative data and there are numerous examples of analysts feeling that a qualitative dataset is more relevant than a quantified one. Possibility theory and fuzzy logic now provide fairly general rules for quantifying qualitative and semi-quantitative data in ways that are repeatable and minimally biased. Once a set of quantified data and/or model layers is obtained, there are several methods of combining them to obtain insight useful in decision making. These include: various combinations of layers using formal fuzzy logic (for example, layer A and (layer B or layer C) but not layer D); connecting the layers with varying influence links in a Fuzzy Cognitive Map; and using the set of layers for the universe of discourse for agent based model simulations. One example of logical combinations that have proven useful is the definition of possible habitat for valley fever fungus (Coccidioides sp.) using variables such as soil type, altitude, aspect, moisture and temperature. A second example is the delineation of the lithology and possible mineralization of several areas beneath basin fill in southern Arizona. A Fuzzy Cognitive Map example is the impacts of development and operation of a hypothetical mine in an area adjacent to a city. In this model variables such as water use, environmental quality measures (visual and geochemical), deposit quality, rate of development, and commodity price combine in complex ways to yield frequently counter-intuitive results. By varying the interaction strengths linking the variables, insight into the complex interactions of the system can be gained. An example using agent-based modeling is a model designed to test the hypothesis that new valley fever fungus sites could be established from existing sites by wind transport of fungal spores. The variables include layers simulating precipitation, temperature, soil moisture, and soil chemistry based on historical climate records and studies of known valley fever habitat. Numerous agent-based model runs show that the system is self organizing to the extent that there will be new sites established by wind transport over decadal scales. Possibility theory provides a framework for gaining insight into the interaction of known or suspected variables in a complex system. Once the data layers are quantified into possibility functions, varying hypotheses of the relative importance of variables and processes can be obtained by repeated combinations with varying weights. This permits an evaluation of the effects of various data layers, their uncertainties, and biases from the layers, all of which improve the objectivity of decision making.