A possible case of mycosis in a post-classical burial from La Selvicciola (Italy).

An examination of an adult male buried from the post-classical necropolis of La Selvicciola (Viterbo, Latium, Italy; 4th-6th centuries AD) revealed a series of skeletal lesions. The lesions, both proliferative and lytic, ranging in size from small (around 0.01 mm) to extensive (up to 16.00 mm) pits, occurred at multiple sites. A holistic approach assessed lesion type, frequency and location in a differential diagnosis, which included myeloma, metastatic carcinoma, tuberculosis, leukemia, osteomyelitis, and mycoses. It was concluded that a mycosis, specifically Cryptococcosis, was the most likely cause of these lesions. Both macroscopic analyses and X-ray scans support our diagnosis. We also provide a methodological scheme as a model for examining unknown lesion patterns.

White-Nose Syndrome Fungus in a 1918 Bat Specimen from France.

White-nose syndrome, first diagnosed in North America in 2006, causes mass deaths among bats in North America. We found the causative fungus, Pseudogymnoascus destructans, in a 1918 sample collected in Europe, where bats have now adapted to the fungus. These results are consistent with a Eurasian origin of the pathogen.

Re-Inventing Infectious Disease: Antibiotic Resistance and Drug Development at the Bayer Company 1945-80.

This paper analyses how research on antibiotic resistance has been a driving force in the development of new antibiotics. Drug resistance, while being a problem for physicians and patients, offers attractive perspectives for those who research and develop new medicines. It imposes limits on the usability of older medicines and simultaneously modifies pathologies in a way that opens markets for new treatments. Studying resistance can thus be an important part of developing and marketing antibiotics. The chosen example is that of the German pharmaceutical company Bayer. Before World War Two, Bayer had pioneered the development of anti-infective chemotherapy, sulpha drugs in particular, but had missed the boat when it came to fungal antibiotics. Exacerbated by the effects of war, Bayer's world market presence, which had been considerable prior to the war, had plummeted. In this critical situation, the company opted for a development strategy that tried to capitalise on the problems created by the use of first-generation antibiotics. Part and parcel of this strategy was monitoring what can be called the structural change of infectious disease. In practice, this meant to focus on pathologies resulting from resistance and hospital infections. In addition, Bayer also focused on lifestyle pathologies such as athlete's foot. This paper will follow drug development and marketing at Bayer from 1945 to about 1980. In this period, Bayer managed to regain some of its previous standing in markets but could not escape from the overall crisis of anti-infective drug development from the 1970s on.

Healthcare-associated outbreaks due to Mucorales and other uncommon fungi.

BACKGROUND: Healthcare-associated outbreaks of fungal infections, especially with uncommon and emerging fungi, have become more frequent in the past decade. MATERIALS AND METHOD: Here, we reviewed the history and definition of healthcare-associated outbreaks of uncommon fungal infections and discussed the principles of investigating, containing and treatment of these outbreaks. RESULTS: In case of these uncommon diseases, occurrence of two or more cases in a short period is considered as an outbreak. Contaminated medical devices and hospital environment are the major sources of these outbreaks. Care must be taken to differentiate a real infection from colonization or contamination. Defining and identifying cases, describing epidemiologic feature of cases, finding and controlling the source of the outbreak, treating patients, and managing asymptomatic exposed patients are main steps for outbreak elimination. These fungal outbreaks are not only difficult to detect but also hard to treat. Early initiation of appropriate antifungal therapy is strongly associated with improved outcomes in infected patients. Choice of antifungal drugs should be made based on spectrum, pharmacodynamic and pharmacokinetic characteristics and adverse effects of available drugs. Combination antifungal therapy and surgical intervention may be also helpful in selected cases. CONCLUSIONS: A multidisciplinary approach and close collaboration between all key partners are necessary for successful control of fungal outbreaks.

Early 1900 s detection of Batrachochytrium dendrobatidis in Korean amphibians.

The pathogenic fungus Batrachochytrium dendrobatidis (Bd) is a major conservation concern because of its role in decimating amphibian populations worldwide. We used quantitative PCR to screen 244 museum specimens from the Korean Peninsula, collected between 1911 and 2004, for the presence of Bd to gain insight into its history in Asia. Three specimens of Rugosa emeljanovi (previously Rana or Glandirana rugosa), collected in 1911 from Wonsan, North Korea, tested positive for Bd. Histology of these positive specimens revealed mild hyperkeratosis - a non-specific host response commonly found in Bd-infected frogs - but no Bd zoospores or zoosporangia. Our results indicate that Bd was present in Korea more than 100 years ago, consistent with hypotheses suggesting that Korean amphibians may be infected by endemic Asian Bd strains.

Retrospective survey of museum specimens reveals historically widespread presence of Batrachochytrium dendrobatidis in China.

Chytridiomycosis, caused by the chytrid fungus Batrachochytrium dendrobatidis (Bd), has been implicated in amphibian population declines worldwide. However, no amphibian declines or extinctions associated with Bd have been reported in Asia. To investigate the history of this pathogen in China, we examined 1,007 museum-preserved amphibian specimens of 80 species collected between 1933 and 2009. Bd was detected in 60 individuals (6.0%), with the earliest case of Bd infection occurring in one specimen of Bufo gargarizans and two Fejervarya limnocharis, all collected in 1933 from Chongqing, southwest China. Although mainly detected in non-threatened native amphibians, Bd was also found in four endangered species. We report the first evidence of Bd for Taiwan and the first detection of Bd in the critically endangered Chinese giant salamander (Andrias davidianus). Bd appears to have been present at a low rate of infection since at least the 1930s in China, and no significant differences in prevalence were detected between decades or provinces, suggesting that a historical steady endemic relationship between Bd and Chinese amphibians has occurred. Our results add new insights on the global emergence of Bd and suggest that this pathogen has been more widely distributed in the last century than previously believed.

Host innate immune responses to microbial pathogens.

Sepsis is among the leading causes of death worldwide and its incidence is increasing. Defined as the host response to infection, sepsis is a clinical syndrome considered to be the expression of a dysregulated immune reaction induced by danger signals that may lead to organ failure and death. Remarkable progresses have been made in our understanding of the molecular basis of host defenses in recent years. The host defense response is initiated by innate immune sensors of danger signals designated under the collective name of pattern-recognition receptors. Members of the family of microbial sensors include the complement system, the Toll-like receptors, the nucleotide-binding oligomerization domainlike receptors, the RIG-I-like helicases and the C-type lectin receptors. Ligand-activated pattern-recognition receptors kick off a cascade of intracellular events resulting in the expression of co-stimulatory molecules and release of effector molecules playing a fundamental role in the initiation of the innate and adaptive immune responses. Fine tuning of proinflammatory and anti-inflammatory reactions is critical for keeping the innate immune response in check. Overwhelming or dysregulated responses induced by infectious stimuli may have dramatic consequences for the host as shown by the profound derangements observed in sepsis. Unfortunately, translational research approaches aimed at the development of therapies targeting newly identified innate immune pathways have not held their promises. Indeed, all recent clinical investigations of adjunctive anti-sepsis treatments had little, if any, impact on morbidity and all-cause mortality of sepsis. Dissecting the mechanisms underlying the transition from infection to sepsis is essential for solving the sepsis enigma. Important components of the puzzle have already been identified, but the hunt must go on in the laboratory and at the bedside.

Prevalence of Batrachochytrium dendrobatidis in 120 archived specimens of Lithobates catesbeianus (American bullfrog) collected in California, 1924-2007.

The chytrid fungus, Batrachochytrium dendrobatidis (Bd), has been identified as a major cause of the recent worldwide amphibian decline. Numerous species in North America alone are under threat or have succumbed to Bd-driven population extinctions. The American bullfrog (Lithobates catesbeianus) has been reported as a tolerant carrier of Bd. In this report, we used a qPCR assay to test 120 archived American bullfrog specimens collected between 1924 and 2007 in California, USA and Baja California, Mexico. The overall prevalence of Bd infection in this archived population of L. catesbeianus was 19.2%. The earliest positive specimen was collected in Sacramento County, California, USA in 1928 and is to date the earliest positive archived Bd specimen reported globally. These data demonstrate that Bd-infected wild amphibians have been present in California longer than previously known.

Museums and disease: using tissue archive and museum samples to study pathogens.

Molecular studies of archival and fossil samples have traditionally focused on the nucleic acids derived from the host species. However, there has recently been an increase in ancient DNA research on the identification and characterization of infectious agents within the hosts. The study of pathogens from the past provides great opportunities for discovering the causes of historical infection events, characterizing host-microorganism co-evolution and directly investigating the evolution of specific pathogens. Several research teams have been able to isolate and characterize a variety of different bacterial, parasite and viral microorganisms. However, this emerging field is not without obstacles. The diagenetic processes that make ancient DNA research generally difficult are also impediments to ancient pathogen research and perhaps more so given that their DNA may represent an even rarer proportion of the remaining nucleic acids in a fossil sample than host DNA. However, studies performed under controlled conditions and following stringent ancient DNA protocols can and have yielded reliable and often surprising results. This article reviews the advantages, problems, and failures of ancient microbiological research.

[History of Polish botanical and mycological researches on sheets of land of Antarctic and Sub-Antarctic in the years 1977-2009]. / Dzieje polskich badan botanicznych i mykologicznych mykologicznych ladowych obszarów Antarktyki i subantarktyki.

The work includes a description of the period from the moment of setting up Polish Polar Station on King George Island (1977) to the end of International Polar Year IV in 2009. Researches on flower plants focused, among others, on plants' morphology, morphological composition of the pollen and anatomical ultra-structure of the leaves. There were also carried out biochemical and other searches for the internal mutability. Within physiological studies one concentrated on the problem of reaction to temperature stress. Biological researches focused mainly on solving taxonomic and bio-geographic problems. Finally, were published several monographs and, among others, the first in history complete description of moss' flora of the whole of Antarctic (2008). Research works over algae included also such issues as floristics, bio-geography, taxonomy and ecology (for instance, the rookery's impact on distribution of algae, or the influence of inanimate factors on dynamics of condensing the Diatoma in different water and soil-bound tanks). Up till now, within mycological investigations has been identified a variety of lichen fungi that for the most part of Antarctic are a novelty. There were scientifically described new for science genera and species of Western Antarctic. Lichenological studies were made in the field of taxonomy, geography, lichenometry, biochemistry of lichens, lichenoindication, ecophysiology and from the point of analysis of base metals' content. There were also described new for science species. Since 1991, were published the results of searches for the base metals' content and vestigial chemical elements in lichens' thallus. Ecophysiological researches concerned both micro-climatic conditions' impact on primary production and lichens' adaptation to a very cold climate. One discovered a mechanism of two-phase hydratization/dehydratization of lichens' thallus. On the ground of palaeobotanical analyzes was reconstructed a development of flora in Western Antarctic from the late Cretaceous period to the beginning of Melville's continental glaciation. One singled out three floristic stages and were reconstructed their peculiarities in the development of flora. There was also described an early Jurassic flora of Hope Bay (Pólwysep Antarktyczny - Antarctic Peninsula) that turned out to be the richest Jurassic flora in the world. From that point of view were analyzed new species of mineral plants. Ecological researches concentrated on the problems connected with several issues and, among others, with the processes of settlement and succession, distribution and ecology of land biotopes, changes in their spatial structure, and state of biotopes' biological mass. The second group of issues concerned the anthropogenous impacts. One also analyzed early stages of synanthropization of flora. Another important issue was recognizing an extent of the pollution of the environment, particularly with base metals. In the years 1977-2009 were published, at least, 426 notes, articles and monographs that were a result of botanical and mycological researches on sheets of land of Antarctic and Sub-Antarctic.

Specialization and medical mycology in the US, Britain and Japan.

This paper attempts to bring new insights to a long-standing historical debate over medical specialization by analyzing the formation of medical mycology, a somewhat marginal biomedical discipline that emerged in the mid-twentieth century around studies of fungal disease in humans. The study of fungi predates that of bacteria and viruses, but from the 1880s it became eclipsed by bacteriology. However, in the postwar period, there were moves to establish medical mycology as an independent speciality. I trace the processes that led to the launch of professional societies in the United States, Britain and Japan, three major players in medical mycology, and more broadly in biomedicine. The analysis of the three different national contexts illustrates how geographical, medico-technological, epidemiological, political and social conditions gave the specialty a distinctive character in each country; this was further complicated by the different and changing medical fields in which fungal diseases were studied and treated. The three case studies show medical specialization as a process that is not simply cumulative but responds to specific historical events and developments.

Medical history and progress in infectious diseases, especially systemic fungal infections in Japan.

This paper reports on medical history from the end of the Edo period to the present and development of studies on infectious diseases, especially medical mycology including systemic fungal diseases. With the inflow of Dutch studies at the end of the Edo period and the adoption of European, mainly German, medicine in the Meiji Restoration, Japanese medical studies gradually developed. However, evolution in the medical field as well as other scientific fields was prevented during the 2nd World War. After the War, there was marked progress in scientific fields and medical research made strong advances. In the past 20 years, basic fungal studies and clinical fungal diseases, especially clinical analysis, clinical diagnosis and treatment of systemic fungal infections have progressed. The level in this field is now equivalent to or higher than that in European countries. Further development is necessary, however, to relieve patients suffering from systemic fungal infections. Members of the Japanese Association of Medical Mycology must be leaders among international medical mycologists.

Aspergilosis invasiva: reporte de un caso y revisión de literatura / Invasive aspergillosis: a case report and literature review

La aspergilosis invasiva es una enfermedad infecciosa producida por un hongo del género Aspergillus. La infección se adquiere generalmente por vía respiratoria al inhalar las esporas que se encuentran en altas concentraciones en el aire, el suelo y sobre todo en la materia orgánica en descomposición. El diagnóstico es difícil realizarlo, por tanto el tratamiento muchas veces se instaura de manera tardía; una vez instaurada la infección el pronóstico es muy malo. Se presenta el caso de un paciente masculino de 9 años de edad, con desnutrición severa y pancitopenia, atendido en el Hospital Materno Infantil de Tegucigalpa, a quien en la autopsia se le demostró aspergilosis invasiva. No se encontró publicaciones locales sobre este tema...

Mold hysteria: origin of the hoax.

The topic of building related illness came into the public's eye as a major health issue in the mid 1970s, when several cases of pneumonia were found to be associated with an infectious agent in Philadelphia. This agent was subsequently found to be a gram-positive bacterium known as Legionella pneumoniae. During the ensuing 30 years, a myriad of symptom constellations, disorders, clinical syndromes and illnesses have been attributed to indoor living or working environments. Over time, there appeared to be no limit to claims of building related illness, and it was "reported" that almost any kind of clinical symptom, real or imaginary, could be blamed on indoor environments. As society became more and more litigious, many of these disorders were erroneously played out in courtrooms rather than medical offices, creating a circus atmosphere surrounding this class of disorders. With the advent of the internet, as well as other advances in telecommunications, these issues eventually became part of a media frenzy, and all truths could be thrown out the window as issues became more and more decided upon by emotions and unfounded beliefs, rather than scientific data and logical thinking.

Mold: "tsara'at," Leviticus, and the history of a confusion.

The noun tsara'at appears about two dozen times in the Hebrew Bible, almost exclusively in Leviticus, where it is used to describe a state of ritual defilement manifested as a scaly condition of the skin, a condition of cloth, leather, and the walls of houses. In the Septuagint, the Greek translation of the Hebrew Bible, negac tsara'at was translated as aphe lepras; in the Latin Vulgate, this became plega leprae. These words in Greek and Latin implied a condition that spread over the body, not a term of ritual impurity. Tsara'at has continued to be translated as "leprosy," even though this term is not appropriate, as there was no leprosy as we know it in the Middle East during the time period the Hebrew Bible was written. Others have suggested that the proper translation of tsara'at is "mold." The recent identification of a specific mold (Stachybotrys sp.) that contaminates buildings and causes respiratory distress, memory loss, and rash, and the fact that mold has been present for millennia, lend support to the translation of tsara'at as "mold."