Fungus Infections

Mycotic keratitis: an overview of diagnosis and therapy

Tue, 22 Apr 2008 14:50:14 GMT

Mycotic keratitis: an overview of diagnosis and therapy

Mycoses. 2008 May

Shukla PK, Kumar M, Keshava GB.

Medical Mycology Lab, Division of Fermentation Technology, Central Drug Research Institute, Lucknow, India. p_kshukla@yahoo.com

The increased incidence of fungal infections in the recent past has been attributed to the increase in the number of human immunodeficiency virus-positive and AIDS patients. Early diagnosis of mycoses in patients is crucial for prompt antifungal therapy. The yield of clinical examination in the diagnosis of keratomycosis is 63-83% and KOH mount is 91%. This still highlights the limitation of routine clinical examination and smear examination, which is not performing 100% efficiently. It is for these 37%, 17% and 9% of cases, every day advanced technologies are called for. Those who deal with patient care are aware of certainties and uncertainties of results of clinical examination. The best reported figures at specialized centres might not translate into clinical practice. Another factor to be kept in mind is that many patients who come after secondary and tertiary referrals are already treated with antibiotics, antivirals, steroids and sometimes even antifungals that distort the clinical picture completely. Further, one has to consider as well the cases caused by yeast-like fungi, which resemble bacterial keratitis. Confirmation of diagnosis, not only in case of mycotic keratitis but also for other diseases, to initiate prompt and accurate therapy would avoid unnecessary and indiscriminate use of steroids/antibacterials/antivirals and antifungals.

Blackwell Synergy

Tags: polymerase chain, Candida spp., Aspergillus spp., Mycotic keratitis, immunodeficiency, AIDS, HIV

Pneumocystis pneumonia

Sat, 29 Mar 2008 02:31:51 GMT

Pneumocystis pneumonia

Semin Respir Crit Care Med. 2008 Apr

D'Avignon LC, Schofield CM, Hospenthal DR.

Infectious Disease Service, San Antonio Military Medical Center, Fort Sam Houston, Texas.

PNEUMOCYSTIS is an opportunistic fungus that is a major cause of morbidity and mortality in immunocompromised hosts. Despite a decline in incidence with the advent of highly active antiretroviral therapy (HAART), PNEUMOCYSTIS remains the most common opportunistic infection in patients with the acquired immunodeficiency syndrome (AIDS) and is an increasing cause of disease in patients with other forms of immunosuppression. Although there have been advances in the prevention and treatment of this infection, the mortality for PNEUMOCYSTIS pneumonia (PCP) in the setting of AIDS remains 10 to 20%. The mortality for patients with other forms of immunosuppression is poorly defined but may actually be higher than that reported in the setting of AIDS. The continued severity of PCP in the AIDS population, its increasing frequency in other immunosuppressed populations, and increasing evidence that normal hosts may serve as a reservoir for the organism merit continued evaluation of the epidemiology, clinical presentation, diagnosis, and treatment of this infection.

Thieme Connect

Tags: Pneumocystis, P. jiroveci, P. carinii, PCP, pneumocystosis, AIDS, antiretroviral therapy, HAART, immunocompromised patient

Pulmonary paracoccidioidomycosis

Sat, 29 Mar 2008 02:27:56 GMT

Pulmonary paracoccidioidomycosis

Semin Respir Crit Care Med. 2008 Apr

Restrepo A, Benard G, de Castro CC, Agudelo CA, Tobón AM.

Medical and Experimental Mycology Unit, Corporación para Investigaciones Biológicas, Medellín, Colombia.

Paracoccidioidomycosis (formerly known as South American blastomycosis) is produced by the thermally dimorphic fungus PARACOCCIDIOIDES BRASILIENSIS . Most often this mycosis runs a chronic progressive course affecting preferentially the lungs followed by the skin, mucous membranes, adrenals, and reticuloendothelial organs. Acute-subacute presentations can be observed in children and immunosuppressed patients.

Occasionally, self-limited infections have been documented. Two types of clinical presentations are described, the acute-subacute (juvenile) and the chronic (adult) forms of the disease. Paracoccidioidomycosis predominates in adult males (13:1); this gender difference is not observed in children or adolescents. The mycosis is limited geographically to various Latin American countries, with the greatest number of cases originating in Brazil.

The fungus's natural habitat has not been precisely defined, although it is supposed to be a soil-inhabiting microorganism. No outbreaks have been reported. P. BRASILIENSIS is capable of entering into prolonged periods of latency as is demonstrated by its diagnosis in patients who have moved outside the recognized endemic areas. This review updates clinicians and laboratory workers on the characteristics of a mycosis seldom reported outside of the Latin American countries.

Thieme-connect

Tags: Pulmonary paracoccidioidomycosis, p. brasiliensis, South American blastomycosis, immunosuppressed patients, mycosis

Update on azole antifungals

Sat, 29 Mar 2008 02:23:53 GMT

Update on azole antifungals

Semin Respir Crit Care Med. 2008 Apr

Zonios DI, Bennett JE.

Clinical Mycology Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, Maryland.

This is a comprehensive, clinically oriented review of the four commercially available triazoles: fluconazole, itraconazole, voriconazole, and posaconazole. Emphasis is placed in pharmacology, drug interactions, adverse events, antifungal activity, and the evolving perspective of their clinical use. Key clinical trials are briefly discussed, and specific drug indications summarized. Fluconazole remains a valuable low-cost choice for the treatment of various fungal infections, including candidiasis and cryptococcosis. It has relatively few drug interactions and is safe but lacks activity against filamentous fungi. The use of itraconazole is historically plagued by erratic bioavailability of the oral capsule, improved with the oral solution. Drug interactions are numerous. Itraconazole exhibits significant activity against ASPERGILLUS and the endemic fungi. Voriconazole has revolutionized the treatment of aspergillosis in severely immunocompromised patients, but its use is compromised by complicated pharmacokinetics, notable drug interactions, and relatively significant adverse events. Finally, posaconazole is the last addition to the azole armamentarium with extended antifungal spectrum, significant activity against the zygomycetes, and, apparently, optimal safety profile. Posaconazole has a significant role for the prophylaxis of invasive fungal infections in severely immunocompromised patients. Multiple daily dosing, a need for fatty foods for absorption, and absence of an intravenous formulation restrict its use to selected populations.

Thieme-connect

Tags: triazoles, fluconazole, itraconazole, voriconazole, and posaconazole, candidiasis, cryptococcosis

Brewer's/baker's yeast (Saccharomyces cerevisiae) and preventive medicine: Part II

Fri, 14 Mar 2008 13:43:03 GMT

Brewer's/baker's yeast (Saccharomyces cerevisiae) and preventive medicine: Part II

Urol Nurs. 2008 Feb

Moyad MA.

University of Michigan Medical Center, Department of Urology, Ann Arbor, MI, USA.

Yeast is the term generally applied to a unicellular fungus, and there are hundreds of species now identified. One of the most notable and well-known species of yeast in health and wellness is known as Saccharomyces cerevisiae, which is also known by its more common names, brewer's yeast or baker's yeast. Typically, brewer's yeast is used as a protein supplement, energy booster, immune enhancer, or other vehicle where other compounds can be inserted to create a commercialized health product. For example, one of the most notable positive findings was the encouraging results from a large randomized trial of adults recently vaccinated for seasonal influenza who also received an over-the-counter daily adjuvant modified brewer's yeast-based product (EpiCor) to prevent colds and flu symptoms. The modified yeast-based product significantly reduced the incidence and duration of this common condition. Yeast-based technology is also being used as a molecular mechanistic model of caloric restriction (CR) with the goal of improving the human life span. The current and potential impact of yeast-based technology in medicine is encouraging and should receive more attention, but the recent preliminary positive results of CR in humans may be in part due to what has been already learned from brewer's yeast.

PMID: 18335702 [PubMed - in process]

Tags: brewer's yeast, baker's yeast, Saccharomyces cerevisiae, preventive medicine, protein supplement, energy booster, immune enhancer

Fungal Sinusitis

Mon, 03 Mar 2008 04:10:33 GMT

Fungal Sinusitis

What Is A Fungus? Fungi are plant-like organisms that lack chlorophyll. Since they do not have chlorophyll, fungi must absorb food from dead organic matter. Fungi share with bacteria the important ability to break down complex organic substances of almost every type (cellulose) and are essential to the recycling of carbon and other elements in the cycle of life. Fungi are supposed to "eat" only dead things, but sometimes they start eating when the organism is still alive. This is the cause of fungal infections; the treatment selected has to eradicate the fungus to be effective.

In the past 30 years, there has been a significant increase in the number of recorded fungal infections. This can be attributed to increased public awareness, new immunosuppressive therapies (medications such as cyclosporine that "fool" the body's immune system to prevent organ rejection) and overuse of antibiotics (anti-infectives).

When the body's immune system is suppressed, fungi find an opportunity to invade the body and a number of side effects occur. Because these organisms do not require light for food production, they can live in a damp and dark environment. The sinuses, consisting of moist, dark cavities, are a natural home to the invading fungi. When this occurs, fungal sinusitis results.

There Are Four Types Of Fungal Sinusitis:

Mycetoma Fungal Sinusitis produces clumps of spores, a "fungal ball," within a sinus cavity, most frequently the maxillary sinuses. The patient usually maintains an effective immune system, but may have experienced trauma or injury to the affected sinus(es). Generally, the fungus does not cause a significant inflammatory response, but sinus discomfort occurs. The noninvasive nature of this disorder requires a treatment consisting of simple scraping of the infected sinus. An anti-fungal therapy is generally not prescribed.

Allergic Fungal Sinusitis (AFS) is now believed to be an allergic reaction to environmental fungi that is finely dispersed into the air. This condition usually occurs in patients with an immunocompetent host (possessing the ability to mount a normal immune response). Patients diagnosed with AFS have a history of allergic rhinitis, and the onset of AFS development is difficult to determine. Thick fungal debris and mucin (a secretion containing carbohydrate-rich glycoproteins) are developed in the sinus cavities and must be surgically removed so that the inciting allergen is no longer present. Recurrence is not uncommon once the disease is removed. Anti-inflammatory medical therapy and immunotherapy are typically prescribed to prevent AFS recurrence.

Note: A 1999 study published in the Mayo Clinic Proceedings asserts that allergic fungal sinusitis is present in a significant majority of patients diagnosed with chronic rhinosinusitis. The study found 96 percent of the study subjects with chronic rhinosinusitis to have a fungus in cultures of their nasal secretions. In sensitive individuals, the presence of fungus results in a disease process in which the body's immune system sends eosinophils (white blood cells distinguished by their lobulated nuclei and the presence of large granules that attract the reddish-orange eosin stain) to attack fungi, and the eosinophils irritate the membranes in the nose. As long as fungi remain, so will the irritation.

Chronic Indolent Sinusitis is an invasive form of fungal sinusitis in patients without an identifiable immune deficiency. This form is generally found outside the US, most commonly in the Sudan and northern India. The disease progresses from months to years and presents symptoms that include chronic headache and progressive facial swelling that can cause visual impairment.

Microscopically, chronic indolent sinusitis is characterized by a granulomatous inflammatory infiltrate (nodular shaped inflammatory lesions). A decreased immune system can place patients at risk for this invasive disease.

Fulminant Sinusitis is usually seen in the immunocompromised patient (an individual whose immunologic mechanism is deficient either because of an immunodeficiency disorder or because it has been rendered so by immunosuppressive agents). The disease leads to progressive destruction of the sinuses and can invade the bony cavities containing the eyeball and brain.

The recommended therapies for both chronic indolent and fulminant sinusitis are aggressive surgical removal of the fungal material and intravenous anti-fungal therapy.

AAO-HNS

Tags: Fungal Sinusitis. Mycetoma Fungal Sinusitis, Allergic Fungal Sinusitis (AFS), Chronic Indolent Sinusitis, Fulminant Sinusitis

Prevalence of allergic sensitization to indoor fungi in West Virginia

Sun, 02 Mar 2008 13:00:00 GMT

Prevalence of allergic sensitization to indoor fungi in West Virginia

Allergy Asthma Proc. 2008 Jan-Feb

Beezhold DH, Green BJ, Blachere FM, Schmechel D, Weissman DN, Velickoff D, Hogan MB, Wilson NW.

Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, West Virginia.

Exposure to indoor fungi is of growing concern in residential and occupational environments in the United States. The purpose of this study was to determine the prevalence of sensitization to common indoor fungal species in an atopic population. We evaluated 102 patients (73 female and 29 male patients) for immunoglobulin E (IgE) reactivity to a panel of skin-prick test (SPT) reagents used for routine allergy testing. Patients also were tested for six additional fungi that are common indoor contaminants. All patients had symptoms consistent with allergic rhinitis or asthma. The presence of specific IgE against the fungal species was determined using immunoblotting. Of the 102 eligible patients, 68% had at least one positive skin test. The most prevalent positive SPTs were to dust mites, cats, vernal grass, and short ragweed. Overall, 21/102 (21%) patients with asthma or allergic rhinitis were skin test positive to at least one fungal extract. Of the patients with a positive SPT to fungi, 12/21 (58%) showed sensitivity to one or more of the newly tested species; most notably Trichoderma viride (8%), Chaetomium globosum (7%), Paecilomyces variotii (7%), and Acremonium strictum (6%). Immunoblotting revealed specific IgE against a number of protein bands belonging to these fungal species. The prevalence of fungal sensitization was common, particularly for indoor fungal contaminants that are not routinely included in SPT panels. Cross-reactivity with other fungi may partially explain our results; however, skin testing for these indoor fungi may provide useful diagnostic information.

PMID: 18302835 [PubMed - in process]

Tags: , allergic sensitization, indoor fungi, allergic rhinitis, asthma, Chaetomium globosum, Trichoderma viride, Paecilomyces variotii, Acremonium strictum

Late-phase allergic reaction in nasal provocation with fungal allergens

Sun, 02 Mar 2008 12:56:14 GMT

Late-phase allergic reaction in nasal provocation with fungal allergens

Allergy Asthma Proc. 2008 Jan-Feb

Niedoszytko M, Chełmińska M, Chełmiński K, Knopińska-Posłuszny W, Gruchała-Niedoszytko M, Jassem E.

Department of Allergology, Medical University of Gdansk, Gdansk, Poland.

Differentiation between asymptomatic sensitization to fungi and clinically relevant allergy is difficult. The aim of this study was to assess the value of nasal provocation with fungal allergens in the diagnosis of allergic rhinitis with special attention to the late phase of monitoring. Eighteen patients with allergic rhinitis and confirmed sensitivity to molds were included in the study. In 16 patients with allergic rhinitis, nasal provocation with fungal allergens was positive. The provocation tests were performed in the asymptomatic period. Stallergenes nasal provocation extracts were used. Extracts were blinded and patients were not informed whether allergen or control solution was tested. The results of both allergen and control solution challenge were compared. Results of the challenge were assessed with symptoms score (after 5 and 30 minutes and 6 and 24 hours), mast cell tryptase level (before and 30 minutes after), and cytological examination of the nasal fluid (before and 6 hours after), and an early and a late-phase of the allergic response was evaluated. Clinical reaction was noted in 16 patients, with significantly marked late phase of the allergic reaction in 14 subjects. The late phase was the only reaction to the challenge in 6 subjects. Tryptase level rose in 2 subjects, whereas significant increase in eosinophils count was observed in 11 patients (Wilcoxon test, p = 0.001). The nasal allergen challenge with fungal allergen seems to be a promising diagnostic method of allergic rhinitis. Late phase of the allergic reaction seems to be an important part of the assessment.

PMID: 18302836 [PubMed - in process]

Tags: fungal allergens, allergic reaction, allergic rhinitis, Clinical reaction, Tryptase level, cytological examination

Evolution of host resistance in a toxin-producing bacterial-fungal alliance

Sun, 02 Mar 2008 12:50:55 GMT

Evolution of host resistance in a toxin-producing bacterial-fungal alliance

ISME J. 2008 Feb 28

Schmitt I, Partida-Martinez LP, Winkler R, Voigt K, Einax E, Dölz F, Telle S, Wöstemeyer J, Hertweck C.

[1] 1Department of Biomolecular Chemistry, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Jena, Germany [2] 2Department of Plant Biology, University of Minnesota, Saint Paul, MN, USA.

The rice seedling blight fungus Rhizopus microsporus harbors endosymbiotic Burkholderia sp. for the production of the virulence factor, the antimitotic agent rhizoxin. Since the toxin highly efficiently blocks mitosis in most eukaryotes, it remained elusive how self-resistance emerged in the fungal host. In this study, rhizoxin sensitivity was systematically correlated with the nature of beta-tubulin sequences in the kingdom Fungi. A total of 49 new beta-tubulin sequences were generated for representative species of Ascomycota, Basidiomycota and Zygomycota. Rhizoxin sensitivity assays revealed two further amino acids at position 100 (Ser-100 and Ala-100), in addition to the known Ile-100 and Val-100, which convey rhizoxin resistance. All sensitive strains feature Asn-100. This hot spot was verified by modeling studies, which support the finding that rhizoxin preferentially interacts with the tubulin molecule in a cavity near position 100. Ancestral character state reconstructions conducted in a Bayesian framework suggest that rhizoxin sensitivity represents the ancestral character state in fungi, and that evolution of rhizoxin resistance took place in the ancestor of extant resistant Zygomycota. These findings support a model according to which endosymbiosis became possible through a parasitism-mutualism shift in insensitive fungi.

The ISME Journal advance online publication, 28 February 2008; doi:10.1038/ismej.2008.19.

ISME Journal

Tags: bacterial-fungal alliance, host resistance, Rhizopus microsporus, rhizoxin resistance, fungal host, Ascomycota, Basidiomycota, Zygomycota, mitosis, eukaryotes, evolution, fungi, symbiosis, tubulin

Programmed cell death in pathogenic fungi

Wed, 27 Feb 2008 12:04:43 GMT

Programmed cell death in pathogenic fungi

Biochim Biophys Acta. 2008 Feb 11

Ramsdale M.

School of Biosciences, University of Exeter, Geoffrey Pope Building, Stocker Road, Exeter EX4 4QD, United Kingdom.

Greater understanding of programmed cell death (PCD) responses in pathogenic fungi may offer a chance of exploiting the fungal molecular death machinery to control fungal infections. Clearly identifiable differences between the death machineries of pathogens and their hosts, make this a feasible target. Evidence for PCD in a range of pathogenic fungi is discussed alongside an evaluation of the capacity of existing antifungal agents to promote apoptosis and other forms of cell death. Information about death related signalling pathways that have been examined in pathogens as diverse as Candida albicans, Aspergillus fumigatus, Magnaporthe grisea and Colletotrichum trifolii are discussed.

Elsevier

Candida albicans, Aspergillus fumigatus, Magnaporthe grisea, Colletotrichum trifolii, cell death, fungal infections, pathogenic fungi, Apoptosis; Necrosis, Antifungal drug