North American Blastomycosis in California—Diagnosis of a Case and a Survey with 28 California Observed Cases

North American blastomycosis is not seen often in California. An exhaustive survey uncovered records of only 28 cases. It is believed that this disease does not occur naturally in California and that a careful study of the history will reveal that a residence or visit to a known endemic area can be found.A chart summarizing the results of complement fixation and skin tests for coccidioidomycosis, North American blastomycosis, and histoplasmosis in the 28 cases is included. Use of all three antigens is recommended in cases where there is a difficult diagnostic pulmonary problem, even though there is occasional occurrence of cross-reactions between the three antigens. Finally, an appeal is made to be aware of other mycotic diseases non-edemic to this state.     

Epidemiology of 46 wisconsin cases of north american blastomycosis, 1960–1964

Summary In an attempt to find the source of infection 45 Wisconsin North American blastomycosis patients or their immediate relatives were interviewed and the records studied. B. dermatitidis was considered to have been proved to be endemic in Wisconsin, since infection took place in several parts of the state, and a large proportion of the patients were shown to have been infected while living in the state.A study of the yearly occurrence of cases of blastomycosis in Wisconsin, 1960–1964, revealed an unequal distribution. A noticeably small number of cases occurred in 1963. Since this was the driest year in Milwaukee and many other parts of the state in 30 years, further work on a possible relationship between the disease and annual precipitation was suggested.The seasonal distributions of both onset and diagnosis were found to differ significantly from an even distribution among the seasons. The distributions were found to be compatible with the hypothesis that infection took place toward the end of the growing season.Evidence was presented that the American Indian in Wisconsin may have a racial susceptibility or an environmental relationship favoring infection byB. dermatitidis.When compared with other published series of blastomycosis cases, an unusually large number of women patients was found resulting in a 3.5 : 1 male to female ratio.The study failed to show an occupational connection with the disease.This investigation was supported in part by Public Health Service Research Grant AI-02211 (03–07) from the National Institute of Allergy and Infectious Diseases.     

Immunologic studies on the etiologic agents of North and South American blastomycosis

Summary This study presents an antigenic comparison of the fungi,B. brasiliensis andB. dermatitidis, by intradermal reactions in animals and humans.Guinea pigs, hypersensitive to the homologous infecting fungus, reacted when skin tested with standardized broth filtrates and yeast-phase vaccines of the heterologous organism. Similar results were obtained in the limited number of human cases of North American blastomycosis when the yeast-phase vaccines were employed.A statistical method, the 50 per cent end-point, was utilized for standardizing broth filtrates of fungi to be employed as skin test antigens.A part of this investigation was used in partial fulfillment of the requirements for the degree of Doctor of Philosophy.     

Pulmonary mycotic infections; allergic and immunologic factors

The mechanisms of immunity and allergy, at play in every infectious disease, must be comprehended before the pathogenesis of an infection can be appreciated.Immunity, allergy and serology are concerned with specific antigen-antibody reactions. In immunity the principal concern is with the final disposition of antigen (agglutination, lysis, and phagocytosis). In allergy attention is focused upon tissue damage resulting from antigen-antibody union. In serology interest is devoted to the presence of antibody as evaluated by certain visible in vitro reactions-precipitin, agglutination, opsonization and complement fixation tests. There are two types of allergic reaction-the immediate or anaphylactic type and the delayed type or the allergic disease of infection. Neither kind takes part in the mechanism of immunity. At this time the allergic antibody and the immune antibody must be considered as two different and distinct antibodies. Skin and serologic tests are important diagnostic aids in certain pulmonary mycotic infections-for example, coccidioidomycosis, blastomycosis, histoplasmosis and moniliasis. Clinical expressions of allergy may appear in coccidioidomycosis, histoplasmosis and moniliasis. Pulmonary mycoses are divided into three groups, that is, the endogenous mycoses (actinomycosis, moniliasis, geotrichosis), the endogenous-exogenous mycoses (cryptococcosis, aspergillosis, mucormycosis) and the exogenous mycoses (nocardiosis, coccidioidomycosis, histoplasmosis, North American blastomycosis). The diagnosis and treatment of the important mycotic infections that invade lung tissue are discussed.     

An outbreak of blastomycosis in Eastern Tennessee

Most cases of blastomycosis are sporadic and only nine outbreaks representing a total of 112 cases have previously been reported. Less than half of these have been culture proven cases. Outbreaks have previously occurred in North Carolina, Minnesota, Illinois, Wisconsin and Virginia. We report three culturally confirmed cases of blastomycosis from Elizabethton, Tennessee, who had onset of illness within a one-week span of time. The patients presented with fever, chest pain, weight loss, poor appetite and myalgia. Each initially had a dry cough which became productive of purulent sputum as the illness progressed. Mild hemoptysis occurred during each patient's course. Serologic testing by immunodiffusion and enzyme immunoassay were positive and testing by complement fixation was negative in each case. The diagnosis was made by histopathology on transbronchial biopsy or transthoracic needle aspiration material. Each patient improved on ketoconazole therapy.     

The action of bacillary inhibitory substances on human-pathogenic, phytopathogenic and saprotrophic fungi]

The study has shown that the growth of many soil fungi is inhibited by the effect of substances which are produced into the environment by some bacilli-saprotrophs. Besides, these substances can bring about a dimorphism of the Trichoderma, Blastomyces, Emmonsia, Alternaria and Verticillium fungi from the mycelial form into the yeast form, which results in the death of the fungi. The existence of bacilli capable of producing the inhibitory substances, in the soil in the territory of the USSR may explain, to a certain extent, the absence of the coccidioidomycosis and North American blastomycosis agents pathogenic for people and many animals.     

Secondary Intracerebral Blastomycosis with Giant Yeast Forms

Secondary central nervous system (CNS) blastomycosis is an unusual manifestation of blastomycosis. We report a case of recurrent intracerebral blastomycosis that presented histopathologically with giant yeast-like cells and multinucleation that mimicked Coccidioides immitis. The yeast forms of Blastomyces dermatitidis usually range in size from 8 to 20 μm in diameter. Large or giant yeast forms (20–40 μm) are rare. The four cases previously reported in the literature involving giant yeast cell forms of B. dermatitidis are reviewed here. Intracerebral blastomycosis should be suspected in patients with signs and symptoms of CNS lesions and histories of primary blastomycosis, or treatment with corticosteroids, or comprised immune systems. The diagnosis should be confirmed by culture which presents typical biphasic microbiologic features.     

Blastomycosis in Africa

The known African cases of blastomycosis to 1987 are presented, including thirteen previously undescribed cases. This brings to 81 the total number of cases known to have occurred in Africa. The question of whether the disease in Africa is the same in all respects as that in North America is addressed; the age and sex distributions of patients are similar. Minor differences in the clinical features relate particularly to the type of skin lesion, the more frequent bone involvement and the less frequent central nervous system involvement in the African patient. Little is known about the epidemiology of blastomycosis in Africa; one noteworthy feature is the apparent absence of the disease in dogs. Isolates of Blastomyces dermatitidis from the two continents, although closely related, differ in some respects.     

Geographic Distribution of Human Blastomycosis Cases in Milwaukee, Wisconsin, USA: Association with Urban Watersheds

Most studies of endemic blastomycosis and outbreaks have involved rural areas. Case homesites in rural Northern Wisconsin have been associated with waterways and sand soils. ARC-GIS was used to geocode addresses and to observe geographic features of homesites from 45 State-mandated reports of human blastomycosis in urban Milwaukee County, Southeastern Wisconsin 2000–2004. Each case property was directly observed, and houses and duplexes (N = 38) were compared with 151 same-street control homesites. Categorical data was analyzed using a chi-square or Fisher’s exact test; continuous variables by Kruskal–Wallis test. One case cluster was seen on Milwaukee’s North side where the estimated annual incidence was 2.8/100,000 compared to 0.96/100,000 for the entire county. Cases were less common in the most urbanized watersheds (0.49/100,000/yr) versus Lake Michigan shores (0.85) versus remaining three open watersheds (1.4) [P<0.01]. Case homesites averaged 1067 m to waterways and none were on sand soils. (Comparison is made to a Northern Wisconsin community where case homesites averaged 354 m to waterways, 24/25 were on sand soils and annual incidence was 74/100,000.) No unique features of case homesites were identified in Milwaukee County. In this urban area of Wisconsin, relatively low incidence rates may be explained, in part, by lower density of inland waterways and lack of sand soils, however, blastomycosis cases appear to be associated with open watersheds.     

Clinical Characteristics and Outcomes in Patients with Pulmonary Blastomycosis

Background  Blastomycosis is an uncommon granulomatous infection caused by the thermally dimorphic fungus Blastomyces dermatitidis. The most frequent clinical infections involve the lung, skin, and bone. Pulmonary manifestations range from asymptomatic self-limited infection to severe diffuse pneumonia causing respiratory failure. Objectives  To establish the clinical characteristics and outcomes of patients with pulmonary blastomycosis diagnosed at hospitals in Manitoba and northwestern Ontario, Canada. Methods  A retrospective review of medical records was done for 318 patients with blastomycosis in these regions. Results  The majority of patients were Caucasian (198 (62.5%) patients), male (193 (61%) patients), and residents of Ontario (209 (65.7%) patients). Most patients were treated in an inpatient hospital ward (266 (84%) patients) and survived (294 (92%) patients). Pulmonary involvement, either alone or associated with other sites, was present in 296 (93%) of the 318 patients; 22 (7%) patients had no evidence of pulmonary blastomycosis. The majority of patients had localized lung disease (1–3 quadrants on chest radiograph involved; 225 (82%) patients). Of 294 (92%) patients requiring hospitalization, 266 (90%) patients received all inpatient care on a general medical ward; 28 (10%) patients received some care in the intensive care unit (ICU). Factors associated with ICU admission included diffuse pulmonary disease (four quadrants involved on chest radiograph), diabetes, and prior use of antimicrobial therapy. Twenty-four (8%) patients died, and multivariate analysis showed that older age and Aboriginal ethnicity were the significant risk factors for death from blastomycosis. Conclusion  Blastomycosis is a cause of serious, potentially life-threatening pulmonary infection in this geographic region. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Blastomycosis in a Papanicolaou Smear. Report of a case with possible venereal transmission

An incidental case of cervical blastomycosis discovered by examination of a Papanicolaou smear is reported. Examinations revealed no other focus of blastomycosis in the patient. Since her husband was undergoing treatment for disseminated blastomycosis involving the lungs and prostate at the time the fungus was found, this case may represent venereally transmitted blastomycosis.     

Specific Immunodiffusion Test for Blastomycosis

A specific immunodiffusion test for blastomycosis has been developed. The test permitted the detection of approximately 80% of 113 proven cases of blastomycosis. Two diagnostically important precipitins designated A and B were frequently recognized in patients with blastomycosis. Routine use of reference sera containing the A and B precipitins in immunodiffusion tests would permit the specific diagnosis of blastomycosis without the need for parallel tests with coccidioidin and histoplasmin.     

Epidemiologic and Ecologic Features of Blastomycosis: A Review

Blastomycosis is a potentially fatal infection caused by Blastomyces dermatitidis, a fungus endemic to North America in areas surrounding the Ohio and Mississippi River valleys and the Great Lakes. The clinical manifestations, diagnostic techniques, and treatment strategies for blastomycosis are relatively well-described in the literature; however, the epidemiologic features of disease are not as clearly defined as those of other endemic mycoses, such as histoplasmosis and coccidioidomycosis. We review the ecologic and epidemiologic aspects of B. dermatitidis and blastomycosis, including geographic distribution, environmental niche, seasonality, and possible risk factors.     

Pulmonary blastomycosis masquerading as metastatic disease in the lung: a case report

We report a case of pulmonary blastomycosis appearing as metastatic laryngeal squamous cell carcinoma. Pulmonary blastomycosis was discovered as right lower lobe subpleural activity consistent with metastatic disease on a positron emission tomographic (PET) scan following total laryngectomy and bilateral neck dissection for locally invasive laryngeal squamous cell carcinoma. A computed tomographic (CT) scan of the chest showed a right lower lobe, subpleural pulmonary nodule. CT-guided fine-needle aspiration of the nodule revealed broad-based budding yeast consistent with blastomycosis. To our knowledge, this is the first case of a PET-positive pulmonary blastomycosis lesion mimicking pulmonary malignancy reported in the literature.     

Allelopathic inhibition of germination by Alliaria petiolata (Brassicaceae)

Garlic mustard (Alliaria petiolata, Brassicaceae) is an invasive, nonindigenous species currently invading the understory of North American woodlands where it is a serious threat to the native flora. Part of this success might be due to allelopathic interference by garlic mustard. Two congeneric species, the European Geum urbanum and the North American Geum laciniatum, were tested for allelopathic inhibition of germination by garlic mustard. Seeds were germinated either on substrate contaminated by garlic mustard or on substrate with contamination neutralized by activated carbon. Allelopathic effects of native European and invasive North American garlic mustard populations were also compared. Activated carbon increased germination by 14%, indicating that garlic mustard contaminated the substrate through root exudates. Activated carbon in turn counteracted this effect. The two test species differed in their sensitivity to allelopathic interference. North American G. laciniatum had a much stronger increase in germination when activated carbon was added to the substrate, independent of the origin of garlic mustard. In contrast, the European G. urbanum germinated better in substrate precultivated with North American garlic mustard, whereas activated carbon increased its germination only in substrate precultivated with European garlic mustard.     

Structural and nonstructural protein genome regions of eastern equine encephalitis virus are determinants of interferon sensitivity and murine virulence

Eastern equine encephalitis virus (EEEV) causes sporadic epidemics of human and equine disease in North America, but South American strains have seldom been associated with human neurologic disease or mortality, despite serological evidence of infection. In mice, most North American and South American strains of EEEV produce neurologic disease that resembles that associated with human and equine infections. We identified a South American strain that is unable to replicate efficiently in the brain or cause fatal disease in mice yet produces 10-fold higher viremia than virulent EEEV strains. The avirulent South American strain was also sensitive to human interferon (IFN)-alpha, -beta, and -gamma, like most South American strains, in contrast to North American strains that were highly resistant. To identify genes associated with IFN sensitivity and virulence, infectious cDNA clones of a virulent North American strain and the avirulent South American strain were constructed. Two reciprocal chimeric viruses containing swapped structural and nonstructural protein gene regions of the North American and South American strains were also constructed and found to replicate efficiently in vitro. Both chimeras produced fatal disease in mice, similar to that caused by the virulent North American strain. Both chimeric viruses also exhibited intermediate sensitivity to human IFN-alpha, -beta, and -gamma compared to that of the North American and South American strains. Virulence 50% lethal dose assays and serial sacrifice experiments further demonstrated that both structural and nonstructural proteins are important contributors to neurovirulence and viral tissue tropism. Together, the results of this study emphasize the complex and important influences of structural and nonstructural protein gene regions on EEEV virulence.     

Phylogenetic relationships of North American nymphophiline gastropods based on mitochondrial DNA sequences

Phylogenetic relationships of 36 nymphophiline species representing 10 genera were inferred from mtCOI sequence data and compared to recent morphology-based classifications of this group. Parsimony and maximum likelihood analyses of the molecular data set suggested monophyly of the North American nymphophilines and a sister or otherwise close relationship between this fauna and a European species assigned to the subfamily. Results also supported a previously hypothesized close relationship between the predominantly freshwater nymphophilines and the brackish-water genus Hydrobia . Our analyses resolved a North American nymphophiline subclade composed of Floridobia , Nymphophilus , and Pyrgulopsis , and depicted the remaining North American genera ( Cincinnatia , Marstonia , Notogillia , Rhapinema , Spilochlamys , Stiobia ) as either a monophyletic or paraphyletic group. Two of the large North American genera ( Floridobia , Marstonia ) were supported as monophyletic groups while monophyly of Pyrgulopsis , a western North American group containing > 100 species, was equivocal. North American nymphophiline phylogeny implies that vicariance of eastern and western North American groups was followed by a secondary invasion of eastern coastal areas from the west. We attribute this to dispersal of salt-tolerant progenitors along the Gulf of Mexico coast     

Genetic evidence suggests a widespread distribution of native North American populations of reed canarygrass

Reed canarygrass is an important agricultural crop thought to be native to Europe, Asia, and North America. However, it is one of the worst wetland invaders in North American wetlands. The native North American status has been supported by the circumstantial evidence of early botanical records and the dating and location of herbarium specimens. The lack of empirical evidence has left the North American native status of the species in doubt and prevented comparisons between native North American and Eurasian populations of the species. We utilized genetic markers to compare a wide range of European and Asian collections to DNA extracted from 38 early North American herbarium specimens. The genetic data confirm the presence of a distinct population present throughout North America in the early twentieth century, but not present in Europe or Asia, ranging from Alaska, USA to New Brunswick, Canada. These native North American populations of reed canarygrass are likely present throughout Alaska today, as one specimen was collected as recently as 1996, and may still be present in other regions of North America. Future research can utilize this dataset to determine the origin of present-day invasive populations in North American wetlands.     

Population genetic structure of clinical and environmental isolates of Blastomyces dermatitidis, based on 27 polymorphic microsatellite markers

Blastomyces dermatitidis, a thermally dimorphic fungus, is the etiologic agent of North American blastomycosis. Clinical presentation is varied, ranging from silent infections to fulminant respiratory disease and dissemination to skin and other sites. Exploration of the population genetic structure of B. dermatitidis would improve our knowledge regarding variation in virulence phenotypes, geographic distribution, and difference in host specificity. The objective of this study was to develop and test a panel of microsatellite markers to delineate the population genetic structure within a group of clinical and environmental isolates of B. dermatitidis. We developed 27 microsatellite markers and genotyped B. dermatitidis isolates from various hosts and environmental sources (n=112). Assembly of a neighbor-joining tree of allele-sharing distance revealed two genetically distinct groups, separated by a deep node. Bayesian admixture analysis showed that two populations were statistically supported. Principal coordinate analysis also reinforced support for two genetic groups, with the primary axis explaining 61.41% of the genetic variability. Group 1 isolates average 1.8 alleles/locus, whereas group 2 isolates are highly polymorphic, averaging 8.2 alleles/locus. In this data set, alleles at three loci are unshared between the two groups and appear diagnostic. The mating type of individual isolates was determined by PCR. Both mating type-specific genes, the HMG and α-box domains, were represented in each of the genetic groups, with slightly more isolates having the HMG allele. One interpretation of this study is that the species currently designated B. dermatitidis includes a cryptic subspecies or perhaps a separate species.     

High migration rates shape the postglacial history of amphi‐Atlantic bryophytes

Paleontological evidence and current patterns of angiosperm species richness suggest that European biota experienced more severe bottlenecks than North American ones during the last glacial maximum. How well this pattern fits other plant species is less clear. Bryophytes offer a unique opportunity to contrast the impact of the last glacial maximum in North America and Europe because about 60% of the European bryoflora is shared with North America. Here, we use population genetic analyses based on approximate Bayesian computation on eight amphi‐Atlantic species to test the hypothesis that North American populations were less impacted by the last glacial maximum, exhibiting higher levels of genetic diversity than European ones and ultimately serving as a refugium for the postglacial recolonization of Europe. In contrast with this hypothesis, the best‐fit demographic model involved similar patterns of population size contractions, comparable levels of genetic diversity and balanced migration rates between European and North American populations. Our results thus suggest that bryophytes have experienced comparable demographic glacial histories on both sides of the Atlantic. Although a weak, but significant genetic structure was systematically recovered between European and North American populations, evidence for migration from and towards both continents suggests that amphi‐Atlantic bryophyte population may function as a metapopulation network. Reconstructing the biogeographic history of either North American or European bryophyte populations therefore requires a large, trans‐Atlantic geographic framework.