Climate controls on valley fever incidence in Kern County, California

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.     

Review of human and animal cases of coccidioidomycosis diagnosed in Canada

The first Canadian case of coccidioidomycosis in a human was reported in 1952 and 11 more cases since then. This study provides details of other cases of coccidioidomycosis that have been diagnosed in Canada. Based on clinical details, isolation of Coccidioides immitis, detection of a specific antibody (F band) for coccidioidomycosis by macro- or microimmunodiffusion tests, concurrently used with the complement fixation procedure, and histopathological findings, 116 more cases of this disease were verified. The great majority (94%) of these cases were diagnosed in the western Canadian provinces of British Columbia, Alberta, Saskatchewan and Manitoba, and the others in Quebec, Ontario and Nova Scotia (5,1, and 1 cases, respectively). Available information indicates that the C. immitis infections were contracted during visits to endemic areas in the United States (Arizona, California and New Mexico), Mexico, and Bolivia. Pulmonary infections were the most common type of coccidioidomycosis (93%) followed by the disseminated or meningeal types C. immitis infections occurred in individuals with or without predisposing factor(s) and were more common in males than in females. The exoantigen procedure was very useful and reliable in the accurate and rapid identification of suspected C. immitis isolates. Two cases of coccidioidomycosis were reported in animals in Ontario, Canada.     

Investigation of an outbreak of endemic coccidioidomycosis in Brazil's Northeastern State of Piauí with a review of the occurrence and distribution of Coccidioides immitis in three other Brazilian states

An outbreak of coccidioidomycosis is described that involved three individuals and eight of their dogs, who had engaged in a successful hunt for nine-banded armadillos (Dasypus novemcinctus) in the environs of Oeiras, a community in Brazil's north eastern state of Piauí.Diagnosis was based on clinical, serological and cultural findings. Four of 24 soil samples collected in and around the burrow of an armadillo yielded cultures of Coccidioides immitis, thus establishing the endemicity of that mould in the state of Piauí. A literature review revealed that C. immitis, aside from that state, is endemic in three other Brazilian states — Bahia, Ceará and Maranhão. These four contiguous states have semi-arid regions where climatic conditions and their flora are similar to those that exist in C. immitis's endemic regions in North, Central and South America.This revised version was published online in October 2005 with corrections to the Cover Date.     

Investigating the Relationship Between Climate and Valley Fever (Coccidioidomycosis)

Valley fever (coccidioidomycosis) is a disease caused by inhalation of spores from the soil-dwelling Coccidioides fungal species. The disease is endemic to semiarid areas in the western USA and parts of Central and South America. The region of interest for this study, Kern County, California, accounts for approximately 14% of the reported valley fever cases in the USA each year. It is hypothesized that the weather conditions that foster the growth and dispersal of the fungus influence the number of cases in the endemic area. This study uses regression-based analysis to model and assess the seasonal relationships between valley fever incidence and climatic variables including concurrent and lagged precipitation, temperature, Palmer Drought Severity Index, wind speed, and PM₁₀ using data from 2000 to 2015. We find statistically significant links between disease incidence and climate conditions in Kern County, California. The best performing seasonal model explains up to 76% of the variability in fall valley fever incidence based on concurrent and antecedent climate conditions. Findings are consistent with previous studies, suggesting that antecedent precipitation is an important predictor of disease. The significant relationships found support the “grow and blow” hypothesis for climate-related coccidioidomycosis incidence risk that was originally developed for Arizona.     

Coccidioides immitis isolated from armadillos (Dasypus novemcinctus) in the state of Piauí, northeast Brazil

Natural infection of armadillos with Coccidioides immitis was studied in the state of Piauí, northeast of Brazil, endemic for coccidioidomycosis. In 1998, 26 nine-banded armadillos (Dasypus novemcinctus) were captured in 4 different counties. The animals were sacrificed under deep anesthesia with ether. At necropsy fragments of spleen, liver, lungs and heart were homogenized and seeded onto Sabouraud dextrose agar with and without cycloheximide (BBL, USA). Part of each organ was also processed for histological examination. Suspected colonies of filamentous fungi observed after the second week of incubation at room temperature, exhibiting barrel-shaped arthroconidia alternating with empty spaces, were inoculated intraperitoneally into mice. Three armadillos proved to be infected with C. immitis. Mice inoculated with suspected colonies obtained from homogenized spleen of three and liver of two armadillos developed disseminated coccidioidomycosis and immature and mature spherules of C. immitis were disclosed in several organs. For the first time armadillos (D. novemcinctus) were found naturally infected with C. immitis, adding new data on the ecology and on a possible role of these ancestral mammals in the evolutionary life cycle of this fungus. This revised version was published online in July 2006 with corrections to the Cover Date.     

Gene exchange between two divergent species of the fungal human pathogen,Coccidioides

The fungal genus Coccidioides is composed of two species, Coccidioides immitis and Coccidioides posadasii. These two species are the causal agents of coccidioidomycosis, a pulmonary disease also known as valley fever. The two species are thought to have shared genetic material due to gene exchange in spite of their long divergence. To quantify the magnitude of shared ancestry between them, we analyzed the genomes of a population sample from each species. Next, we inferred what is the expected size of shared haplotypes that might be inherited from the last common ancestor of the two species and find a cutoff to find what haplotypes have conclusively been exchanged between species. Finally, we precisely identified the breakpoints of the haplotypes that have crossed the species boundary and measure the allele frequency of each introgression in this sample. We find that introgressions are not uniformly distributed across the genome. Most, but not all, of the introgressions segregate at low frequency. Our results show that divergent species can share alleles, that species boundaries can be porous, and highlight the need for a systematic exploration of gene exchange in fungal species.     

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

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.     

Statistical modeling of valley fever data in Kern County,California

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.     

Serology of coccidioidomycosis

Summary We believe there is strong evidence to support a continuing search for coccidioidomycosis in new areas, in the Old World as well as in the New World, and in places with a climate and ecology different from the semi-arid conditions of the known endemic areas. Such an investigation would be justified in any population group where there is a high incidence of respiratory disease of unknown etiology. Very satisfactory and practical immunological techniques are available, but the present evidence indicates that the antigens used in these tests should be prepared from strains ofC. immitis recovered from the area to be investigated. Obviously this cannot be done at present, so such a program should be preceeded by an extensive survey of soil samples in the area in order to recover any existing native strains ofC. immitis. Whereas this would be the ideal situation, one could consider initiating the proposed study with coccidioidins prepared from selected strains of this fungus, incorporating as complete a spectrum of known antigens as is possible with our present knowledge, and keeping in mind that even this may not be adequate. We would welcome the opportunity to assist any investigator preparing to undertake a survey for coccidioidomycosis in his country.Paper read at the Eighth International Congresses for Tropical Medicine and Malaria, September 1968, Teheran (Iran).     

Inhibition of the mold phase of Coccidioides immitis by beta-ionine and dimethoxane

The mold phase ofCoccidioides immitis was exposed to varying concentrations of beta-ionone and dimethoxane in Sabouraud'sl Glucose Agar and the inhibitory concentration of each compound was determined. Beta-ionone demonstrated an inhibitory effect at 0.2 % or less, but completely inhibited the growth ofC. immitis above 0.2 %. Its mouse LD₅₀ was 4.4 × 10⁴ mg. Because of its great toxicity for mice, it could not be considered a possible candidate for chemotherapy. However, results suggested its use as a selective additive for an isolation medium. Dimethoxane demonstrated complete inhibition ofC. immitis at concentrations of 0.55 % and higher and some fungistatic effects at lower concentrations. Because the mouse IP toxicity dose was found to be rather low (0.65 mg/kg), it may have potential as a chemotherapeutic agent for coccidioidomycosis.     

Elastase activity of fungi with anamorphs similar to Coccidioides immitis

The elastin digestion assay was examined to determine if it would facilitate the identification of Coccidioides immitis when non-pathogenic fungi resembling C. immitis are encountered. Fungal isolants tested have anamorphs that closely resemble the macroscopic or microscopic morphology of C. immitis. Elastin hydrolysis was measured by elastin-agar plate assays. Approximately 80% of the isolants hydrolyzed elastin; thus, the elastin digestion assay as a differential test appears to have little value.     

Murine models of blastomycosis,coccidioidomycosis, and histoplasmosis

Animal models have contributed much to the knowledge of fungal infections and their corresponding therapeutic treatments. This is true for animal models of the primary fungal pathogens, Blastomyces dermatitidis, Coccidioides immitis, and Histoplasma capsulatum. This review gives a brief background of human diseases associated with these organisms and describes the development, details, and utility of murine models of blastomycosis, as well as coccidioidomycosis and histoplasmosis. This revised version was published online in June 2006 with corrections to the Cover Date.     

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

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.     

Strategies to Combat Coccidioidomycosis: Are We Making Any Progress?

Coccidioidomycosis is caused by the dimorphic fungi Coccidioides immitis and Coccidioides posadasii. One of the endemic mycoses, this organism has been found solely in the semiarid to arid life zones of the southwestern United States, Mexico, and parts of Central America and South America. Clinical manifestations of disease vary greatly between patients and are largely dependent upon both the extent of exposure and the immune status of the host. The incidence of coccidioidomycosis continues to rise within the United States. Primary coccidioidal pneumonia accounts for close to 25% of all community-acquired pneumonia within endemic regions, reflecting the substantial burden of disease and health care costs associated with this infection. Although most patients with coccidioidomycosis resolve their initial infection without long-term complications, a minority of patients develop complications of disease ranging from asymptomatic pulmonary nodules to life-threatening disease such as meningitis. This review focuses on the epidemiology, clinical manifestations, spectrum of disease, and treatment options currently available for coccidioidomycosis.     

Phenotypic and molecular identification of Coccidioides posadasii in a patient evaluated for bilateral lung transplantation

BackgroundCoccidioidomycosis is an endemic fungal infection caused by Coccidioides immitis and Coccidioides posadasii. It can be particularly severe in transplant recipients that have a current or a previous coccidioidal infection. Fatal case of coccidioidomycosis has been described in this group of patients.AimsWe report a severe case of pneumonia caused by C. posadassi in a 29 year-old white woman that had been admitted to hospital as part of the evaluation for bilateral lung transplantation. The patient was a native and resident of Catamarca, Argentina. Molecular methodologies contributed to the species identification.MethodsClinical, laboratory records and microbiological tests were carried out to diagnose the infection and to identify C. posadasii.ResultsA fungus was isolated from BAL culture. Phenotypic characterization, specific PCR and experimental animal inoculation demonstrated the presence of C. posadasii. The patient responded well to amphotericin B deoxycholate. Lung transplantation was postponed.ConclusionsSpecific PCR can be an important alternative for the correct identification of C. immitis or C. posadasii in laboratories with implemented molecular biology tools. This case emphasizes the need for a systematic assessment in organ transplant units of patients inhabiting endemic areas of coccidioidomycosis.     

Coccidioidomycosis of the male reproductive tract

Coccidioides immitis infection of the male reproductive tract is a rare entity that can evade diagnosis and pose a dilemma in management. Initially, patients are often evaluated for malignancy or other infections such as tuberculosis. In the past, surgery was the only management option for C. immitis infection of the male reproductive tract, but azole therapy now provides an adjunct or an alternative. We describe two patients who received azole therapy for C. immitis infection of the male reproductive tract. One received fluconazole for prostatic disease, while one received surgery followed by itraconazole for testicular disease. After 12 months of therapy, both remain asymptomatic and have decreased antibody titers against C. immitis.Disclaimer: The Views expressed herein are those of the authors do not reflect the official policy or position of the Department of the Air Force, Department of the Army, Department of Defence, or the U.S. Government.     

Real-time PCR assay for detection and differentiation of Coccidioides immitis and Coccidioides posadasii from culture and clinical specimens

Coccidioidomycosis (Valley fever) is a pulmonary and systemic fungal disease with increasing incidence and expanding endemic areas. The differentiation of etiologic agents Coccidioides immitis and C. posadasii remains problematic in the clinical laboratories as conventional PCR and satellite typing schemes are not facile. Therefore, we developed Cy5- and FAM-labeled TaqMan-probes for duplex real-time PCR assay for rapid differentiation of C. immitis and C. posadasii from culture and clinical specimens. The RRA2 gene encoding proline-rich antigen 2, specific for Coccidioides genus, was the source for the first set of primers and probe. Coccidioides immitis contig 2.2 (GenBank: AAEC02000002.1) was used to design the second set of primers and probe. The second primers/probe did not amplify the corresponding C. posadasii DNA, because of an 86-bp deletion in the contig. The assay was highly sensitive with limit of detection of 0.1 pg gDNA/PCR reaction, which was equivalent to approximately ten genome copies of C. immitis or C. posadasii. The assay was highly specific with no cross-reactivity to the wide range of fungal and bacterial pathogens. Retrospective analysis of fungal isolates and primary specimens submitted from 1995 to 2020 confirmed 168 isolates and four primary specimens as C. posadasii and 30 isolates as C. immitis from human coccidioidomycosis cases, while all eight primary samples from two animals (rhesus monkey and rhinoceros) were confirmed as C. posadasii. A preliminary analysis of cerebrospinal fluid (CSF) and pleural fluid samples showed positive correlation between serology tests and real-time PCR for two of the 15 samples. The Coccidioides spp. duplex real-time PCR will allow rapid differentiation of C. immitis and C. posadasii from clinical specimens and further augment the treatment and surveillance of coccidioidomycosis.     

Ubiquinone system,GC contents and cellular fatty acid composition of species of the form-genusMalbranchea andCoccidioides immitis for chemotaxonomic study

Ubiquinone system, GC contents and cellular fatty acid (CFA) composition were analyzed as criteria for chemotaxonomy ofMalbranchea species andCoccidioides immitis, which are suggested to be phylogenetically related. Based on the major ubiquinone,Malbranchea spp. were divided into two groups, of which one group possessed the same major ubiquinone asC. immitis. Similar GC contents and CFA profiles were obtained for the species ofMalbranchea andC. immitis. On the basis of these criteria the relationships between the fungi are discussed.