The nocardiae are bacteria belonging to the aerobic actinomycetes. They are an important part of the normal soil microflora worldwide. The type species, Nocardia asteroides, and N. brasiliensis, N. farcinica, N. otitidiscaviarum, N. nova, and N. transvalensis cause a variety of diseases in both normal and immunocompromised humans and animals. The mechanisms of pathogenesis are complex, not fully understood, and include the capacity to evade or neutralize the myriad microbicidal activities of the host. The relative virulence of N. asteroides correlates with the ability to inhibit phagosome-lysosome fusion in phagocytes; to neutralize phagosomal acidification; to detoxify the microbicidal products of oxidative metabolism; to modify phagocyte function; to grow within phagocytic cells; and to attach to, penetrate, and grow within host cells. Both activated macrophages and immunologically specific T lymphocytes constitute the major mechanisms for host resistance to nocardial infection, whereas B lymphocytes and humoral immunity do not appear to be as important in protecting the host. Thus, the nocardiae are facultative intracellular pathogens that can persist within the host, probably in a cryptic form (L-form), for life. Silent invasion of brain cells by some Nocardia strains can induce neurodegeneration in experimental animals; however, the role of nocardiae in neurodegenerative diseases in humans needs to be investigated.

Nocardia species: host-parasite relationships.

African horse sickness (AHSV) 246, 350, 353-55, 373, 401 African swine fever virus (ASFV) 246, 350, 352, 373, 401 Agriculture Agents 343, 352 Agriculture pathogen biosafety 343 Akabane virus 350, 354, 401 Allergic reactions 192 animal biosafety levels 61 Animal Biosafety Levels (ABSL) 60 Animal Biosafety Level 1 61 Animal Biosafety Level 2 67 Animal Biosafety Level 3 61, 75 Animal Biosafety Level 4 85 Animal facilities 27, 60, 91, 173, 243, 361-63, 372 Anthrax iii, 104, 123-24, 161, 273 Arboviruses 2, 5, 233, 236, 238-40, 246, 265-267 arenaviruses 234, 237 armadillos 144-45, 166 Arthropod containment 61, 160, 169, 377-78, 401 Ascaris 192-93

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Biosafety in microbiological and biomedical laboratories

Summary: Melanized or dematiaceous fungi are associated with a wide variety of infectious syndromes Many are soil organisms and are generally distributed worldwide, though certain species appear to have restricted geographic ranges Though they are uncommon causes of disease, melanized fungi have been increasingly recognized as important pathogens, with most reports occurring in the past 20 years The spectrum of diseases with which they are associated has also broadened and includes allergic disease, superficial and deep local infections, pneumonia, brain abscess, and disseminated infection For some infections in immunocompetent individuals, such as allergic fungal sinusitis and brain abscess, they are among the most common etiologic fungi Melanin is a likely virulence factor for these fungi Diagnosis relies on careful microscopic and pathological examination, as well as clinical assessment of the patient, as these fungi are often considered contaminants Therapy varies depending upon the clinical syndrome Local infection may be cured with excision alone, while systemic disease is often refractory to therapy Triazoles such as voriconazole, posaconazole, and itraconazole have the most consistent in vitro activity Further studies are needed to better understand the pathogenesis and optimal treatment of these uncommon infections

Melanized Fungi in Human Disease

Acquired immune deficiency syndrome (AIDS) has become a worldwide epidemic1–6, so the development of vaccines and antiviral agents effective against the causative agent, human T-lymphotropic virus type III (HTLV-III), is vital. This work would be greatly simplified if a suitable animal model could be developed. Here we report the isolation of an HTLV-III-related retrovirus, STLV-III/Delta, from rhesus macaques (Macaca mulatta) with transmissible simian AIDS (SAIDS) and from asymptomatic sooty mangabeys (Cercocebus atys). SAIDS was initially diagnosed in several macaques previously inoculated with tissue homogenates of mangabey origin. Western blot analysis of both the mangabey and macaque sera demonstrated the presence of antibody cross-reactive primarily with the HTLV-III proteins p24 and p61. In a related experiment, analysis of these same sera revealed simian antibody to STLV-III/Delta proteins similar, but not identical, to those of HTLV-III with estimated relative molecular masses (Mrs) of 16,000 (16K), 26K, 35K, 45K, 60K and 110K. Infection of the mangabey, an African primate, with an HTLV-III-related virus may provide a clue to the origin of HTLV-III in humans. The apparent difference in susceptibility to SAIDS-like disease between infected macaques and mangabeys suggests that these species may respond differently to STLV-III infection.

Isolation of an HTLV-III-related retrovirus from macaques with simian AIDS and its possible origin in asymptomatic mangabeys

Phaeohyphomycosis refers to infections caused by darkly pigmented fungi. These fungi rarely cause life-threatening disease. We reviewed 101 cases of culture-proven primary central nervous system phaeohyphomycosis reported in the English-language literature from 1966 to 2002. The most frequently isolated species was Cladophialophora bantiana. The next most frequent isolate was Ramichloridium mackenziei, seen exclusively in patients from the Middle East. More than one-half of the cases occurred in patients with no known underlying immunodeficiency. Mortality rates were high regardless of immune status. Therapy is not standardized, although the combination of amphotericin B, flucytosine, and itraconazole may improve survival rates. Newer azoles, such as voriconazole, also have a broad spectrum of activity against these fungi, although clinical experience is limited. Complete excision of brain lesions may provide better results than simple aspiration. An aggressive medical and surgical approach is warranted in treating these infections to optimize outcomes.

Primary Central Nervous System Phaeohyphomycosis: A Review of 101 Cases

Histoplasmosis: tissue reactions and morphologic variations of the fungus.

Leprosy-like disease occurring naturally in armadillos.

Mycotic Brain Abscess Due to Cladosporium Trichoides, a New Species

Eight of twenty armadillos (Dasypus novemcinctus L.) developed severe lepromatous leprosy 3 to 3.5 years after inoculation with viable Mycobacterium leprae. A total of 988 grams of lepromas containing an estimated 15 to 20 grams of leprosy bacilli has been harvested from these animals. The large amounts of material now available will permit in-depth studies of the biochemistry and metabolism of the leprosy bacillus, and the animal model should make possible definitive studies on the immunology, chemotherapy, and epidemiology of the disease.

https://science.sciencemag.org/content/sci/183/4127/851.full.pdf

Leprosy in the Armadillo: New Model for Biomedical Research

Naturally acquired leprosy was detected in an otherwise normal "sooty" mangabey monkey (Cercocebus atys). This animal was imported from West Africa in 1975 and developed clinical symptoms of leprosy in 1979. Histopathologic findings were those of subpolar-lepromatous to borderline-lepromatous leprosy in the Ridley-Jopling classification. The disease was progressive, with crippling neuropathic deformities of the hands and feet. The disease regressed under specific therapy. The etiologic agent was identified as Mycobacterium leprae by the following criteria: invasion of nerves of host, staining properties, electron microscopic findings, noncultivable on mycobacteriologic media, DOPA-oxidase positive, lepromin reactivity, infection patterns in mice and armadillos, sensitivity to sulfone, and DNA homology. We believe the animal acquired the disease from a patient with active leprosy. The mangabey monkey offers promise as a primate model for leprosy, and adds a third reported species to animals with naturally acquired leprosy.

Chapman H. Binford

Papers

Histoplasmosis: tissue reactions and morphologic variations of the fungus.

Leprosy-like disease occurring naturally in armadillos.

Mycotic Brain Abscess Due to Cladosporium Trichoides, a New Species

Leprosy in the Armadillo: New Model for Biomedical Research

Leprosy in a mangabey monkey--naturally acquired infection.