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Epidemiology of systemic mycoses among renal-transplant recipients in India.

BACKGROUND: Systemic mycoses have a high impact on tropical renal-transplant recipients. METHODS: Data from 1,476 primary renal-transplant recipients was prospectively recorded from 1986 to 2000 at a single center. Cumulative incidence of systemic mycoses, its time of occurrence, risk factors, outcome, and postmortem findings in 30 patients with systemic mycoses were analyzed. RESULTS: A total of 110 episodes of systemic mycoses occurred in 98 patients. The fungal genera Aspergillus, Cryptococcus, and Candida constituted 61% of pathogens, 45% localizing to the lungs. Cytomegalovirus (CMV) disease caused a 5-fold and chronic liver disease a 2-fold increase in systemic mycoses. Tuberculosis (TB) with or without nocardiosis was a significant coinfection. Cyclosporine (CsA) was associated with nearly a 4-fold risk of systemic mycoses less than 6 months from the time of transplantation as compared with prednisolone+azathioprine (PRED+AZA) therapy. Overall, the probability of survival with systemic mycoses was 73.4%, 60.8%, 39.5%, and 25.6% and was 92.5%, 87.5%, 80.0%, and 75.5% without systemic mycoses at 1, 2, 5, and 10 years, respectively (P<0.0001). An extended Cox model with time-independent and dependent covariates showed greater than 15 times the risk of death among those who develop systemic mycoses. Similarly, Posttransplantation (postTX) TB+/-Nocardiosis, preTX TB, CMV disease, diabetes mellitus, PTDM, chronic liver disease (>40 months), and Pred+AZA immunosuppression (>2 years) had 3.5, 1.5, 2.9, 1.9, 1.4, 1.6, 2.3 times the risk for death, respectively, as compared with those who did not have those risk factors. CONCLUSIONS: There is a recent predominance of Aspergillus among the transplant recipients. The risk factors for systemic mycoses are CMV disease, chronic liver disease, and hyperglycemia, and TB is an important coinfection. Systemic mycoses increased in the early postTX period with CsA. The risk factors for death are systemic mycoses, CMV disease, chronic liver disease (>40 months), diabetes mellitus, and Pred+AZA immunosuppression (>2 years). Overall, the probability of survival with systemic mycoses was poor; however, survival has recently improved.

Adult↗

Respiratory and systemic mycoses: an overview.

Respiratory and systemic mycoses are globally emerging as a problem of increasing importance in infectious diseases. This is attributed to the growing population of immunocompromised patients due to epidemic outbreak of AIDS or to other factors such as use of immunosuppressive drugs in recipients of organ transplantation. The available evidence has unequivocally established the endemic occurrence of blastomycosis, histoplasmosis and penicilliosis mameffei in India. In fact, pencilliosis marneffei has emerged as a major endemic mycosis of AIDS patients in Southeast Asia. It has manifestations simulating those of histoplasmosis capsulati, and it may spread to other regions with enlarging population of AIDS patients. Comprehensive studies are indicated in order to delineate the endemic areas of the afore-mentioned systemic mycoses. Among the other important systemic mycoses reported from India are aspergillosis, cryptococcosis, candidiasis and zygomycosis. Our current knowledge of the global distribution of systemic mycoses does not depict their true prevalence. It largely reflects the geographic distribution of medical mycologists or other investigators engaged in the study of fungal diseases and their research interests. Invasive aspergillosis has emerged as an important disease in patients with neutropenia and bone narrow transplant recipients, cryptoccosis, penicilliosis marneffei and pneumocystosis in patients with AIDS, fusariosis in patients with leukaemia receiving cytotoxic therapy, zygomycosis in diabetic patients and in patients on defroxamine therapy, and Malasseziafurfur infection in patients on total parenteral nutrition: Opportunistic systemic mycoses due to yeasts and yeast-like fungi have become commoner than those due to filamentous fungi, occupying fourth position in the list of bloodstream pathogens in some centers in USA. Also, their incidence, pattern of clinical presentations and species spectrum have significantly changed, largely due to more frequent and prolonged therapeutic or prophylactic use of antifungal drugs and subsequent development of resistance. Consequently, infections with resistant yeast-like fungi such as C. lusitaniae, C. krusei, C. tropicalis, C. glabrata and Trichosporon ovoides (T. beigelii) have recently been reported with greater frequency. Since respiratory and systemic mycoses have no pathognomonic clinical or radiologic syndrome and mycological diagnostic facilities are restricted to only some of the major metropolitan centres, these diseases may be frequently confused with tuberculosis or other diseases of obscure etiology in India and other developing countries. Greater awareness and a high index of clinical suspicion are important pre-requisites for their diagnosis. Also, active collaboration of internists, pathologists, mycologists and microbiologists is advocated for their expeditous diagnosis and successful management. Further studies should focus on the development of rapid techniques for selective isolation and identification of systemic pathogenic fungi. The problem of antifungal resistance is likely to become more serious in the future as more and more patients with AIDS, bone marrow transplantation and neutropenia will require chemoprophylaxis cover against systemic fungal infections. Thus, it would be of vital importance to intensify search for more potent and less toxic antifungal drugs. It is recognized that an increasing number of people whose life is saved or prolonged due to successful treatment of their underlying diseases fall victim to opportunistic, life threatening systemic mycoses. A great majority of the deaths due to these infections occurs because they remain undiagnosed for want of mycological diagnostic services. In order to cope with the challenge of systemic mycoses, the health authorities of the developing countries are called upon to urgently take necessary measures for establishing a network of diagnostic mycology laboratories.

Developing Countries↗

[Mycoses at Hospital Universitario "Ruiz y Páez", Ciudad Bolívar, Venezuela, 2002].

To estimate the prevalence of mycoses in the Universitary Hospital "Ruiz y Páez" (Bolivar State, Venezuela) during 2002, a retrospective study was carried out. Four hundred and fifty six mycoses were diagnosed in 250,956 patients. The most frequent mycoses, the cutaneous form (94.5%), were produced by dermatophytes, Malassezia furfur and Candida spp. in 90%. Deep mycoses were detected in 4.7% and consisted of histoplasmosis (2.6%), paracoccidioidomycosis (1.7%) and cryptococcosis (0.4%). Several patients with deep mycoses presented HIV infection, tuberculosis and hematological disorders (neoplasias among them). The frequency of mycoses in the general population that attend the Hospital Universitario "Ruiz y Páez" is low, superficial mycoses are predominant, and some conditions seem to predispose to deep mycoses.

Adolescent↗

[General review of maxillofacial mycoses].

It is interesting and useful to review the different mycoses which can affect oral and maxillofacial tissues. In this review, all mycoses which can involve these tissues are described, based on a simple classification into superficial and deep mycoses. The superficial mycoses described are the dermatophytoses, the Tineas, the piedras, but also the candidoses, which are superficial opportunistic infections. The deep mycoses are subdivided into subcutaneous, systemic, and opportunistic mycoses. Subcutaneous fungal infections are sporotrichosis, lobomycosis, rhinosporidiosis, entomophtoromycoses, and chromomycoses. Systemic fungal infections are paracoccidioidomycosis, blastomycosis, cryptococcosis, histoplasmosis, histoplasmosis duboisii, and coccidioidomycosis. Opportunistic mycoses are aspergillosis, mucormycosis, geotrichosis, torulopsosis (considered nowadays as a candidosis), basidiomycosis, cephalosporiomycosis, alternariosis, cercosporomycosis, paecilomycosis, and fusariomycosis. Eumycotic mycetomas are also cited.

Dermatomycoses↗

[General review of mycoses affecting the maxillofacial area].

It is interesting and useful to review the different mycoses which can affect oral and maxillofacial tissues. In this review, all mycoses which can involve these tissues are described, based on a simple classification into superficial and deep mycoses. The superficial mycoses described are the dermatophytoses, Tinea, the piedra, but also the candidiasis, which are superficial opportunistic infections. The deep mycoses are subdivided into subcutaneous, systemic, and opportunistic mycoses. Subcutaneous fungal infections are sporotrichosis, lobomycosis, rhinosporidiosis, entomophthoromycosis, and chromomycosis. Systemic fungal infections are paracoccidioidomycosis, blastomycosis, cryptococcosis, histoplasmosis, histoplasmosis duboisii, and coccidioidomycosis. Opportunistic mycoses are aspergillosis, mucormycosis, geotrichosis, torulopsosis (considered nowadays as a candidiasis), basidiomycosis, cephalosporiomycosis, alternariosis, cercosporomycosis, paecilomycosis, and fusariomycosis. Eumycotic mycetomas are also cited.

Dermatomycoses↗

A study of 3891 cases of mycoses in the tropics.

4103 cases suspected of mycoses were analysed as to sex, age and site of disease and 3891 were proved cases. This group formed 50% of total mycoses or 13-93% of all dermatoses recorded in the Government General Hospital, Madras, during the period of study. There were 66-26% adult female, 27-6% adult male and 6-14% were below 13 years. Dermatophytoses were found in 73-5%; the other common diseases were tinea versicolor (17-68%) and candidiasis (12-43%). Multiple sites of involvement or more than 1 disease in the same individual were mostly observed. The incidence of piedra (0-1%) and deep mycoses (0-156%) was very low. Mycetoma was the common disease (5/6) in deep mycoses. In dermatophytoses, tinea corporis (49-71%) and tinea cruris (47-85%) commonest; tinea axillaris (3-42%), tinea capitis (1-72%) and tinea barbae (1-29%) were less common. The incidence of tinea manuum, tinea pedis and tinea unguium was similar (4-97%-6-38%). High temperature and humidity were related to the higher incidence of tinea corporis, tinea cruris and tinea versicolor. Mainly children suffered from tinea capitis. All other mycoses were commonly found in adults between 2nd and 3rd decades. In all mycoses but candidiasis, female predominated. Cutaneous candidiasis was mainly a problem of housewives. Among the dermatophytes Trichophyton violaceum was predominant (33-7%) followed by T. rubrum (32-6%). Trichophyton schoenleinii and M. gypseum were rarely isolated. From mycetoma, Madurella mycetomii, Nocardia braziliensis, N. asteroides and Actinomadura spp. were isolated. Demonstration of Cryptococcus laurentii in 1 case is reported in this area for the first time.

Adolescent↗

[A study of postmortem infectious lesions of bacteremia and fungemia patients--relationship between fungemia and deep mycoses].

Postmortem infectious lesions were analyzed in 63 patients with bacteremia and fungemia. Bacterial infection was found in 36 patients, deep mycoses in 27 and cytomegalovirus infection in 7. Among deep mycoses patients, yeast was noticed in 17, Aspergillus in 13 and Mucor in one. Infectious lesions were not observed in 10 cases. Fifteen cases of 23 leukopenic patients were complicated with deep mycoses. Deep mycoses was noticed in 43% of bacteremia and fungemia patients, but not in candicemia patients. Fungemia due to Candida was related to blood access, however, not to deep mycoses. On the other hand, disseminated mycoses was found in 4 of 5 cases with Trichosporon beigelii fungemia. T. beigelii infection is noticeably life-threatening to the immunocompromised host.

Adolescent↗

[Paranasal sinus mycoses].

In recent years there has been a marked increase in mycosis infections of the paranasal sinuses, attributed both to an increase in the survival of subjects at risk and improved diagnostic techniques (endoscopy, CT, MR) able to identify cases which had previously gone unrecognized and treated as aspecific chronic sinusitis. The present study involves 45 cases (4.3%) out of a total of 1050 patients who had undergone endoscopic surgery for sinusopathy between April 1994 and December 1998. Following the Katzenstein classification, the cases were broken down into non-invasive chronic mycoses or fungus ball (34 cases), allergic mycoses (7), chronic indolent invasive mycoses (3) and fulminating invasive mycosis (1 case). The mycetes most often involved was Aspergillus Fumigatus (76.9%). The recurrent symptom was facial algia, followed by nasal obstruction. Paranasal sinuses endoscopy did not modify the specific picture. CT presented such indicative signs as focal areas with non-homogeneous intensity, images of metal-like foreign bodies and endosinus calcifications in 84.4% of the cases. MR--performed in only 6 cases--always presented T2 images showing the typical signal void area corresponding to pathological lesions. All patients underwent endoscopic surgery of the paranasal sinus. The effectiveness of this treatment differed according to the clinical form. In the fungus balls surgery always resolved the pathology without requiring subsequent pharmacological treatment. In allergic mycosis, surgery improved the symptom of nasal respiratory obstruction but local drug treatment was required. With the aid of drug treatment, surgery resolved chronic indolent invasive mycoses and prevented the endocranial progression of complications. In the cases of fulminating invasive mycosis, timely surgery prevented the onset of endocranial complications and made it possible to perform antimycotic polychemotherapy to control the disease. This experience shows how important a protocol involving several different tests is in diagnosing the many clinical forms of paranasal sinus mycoses and distinguishing them from sinusopathies. Endoscopic surgery is indicated for all forms of paranasal sinus mycoses although the realistic objectives differ according to type.

Adolescent↗

[Mycoses--a broad spectrum multi-faceted disease complex].

This article gives a survey of the most important general aspects of mycoses. This comprises their spectrum of organisms, their pathogenicity and their nosologic features. In a more detailed way, the following topical forms of infections will be discussed: Mycoses favoured by factors of civilization, survival mycoses, mycoses resulting from progress of medicine, opportunistic mycoses and mycoses associated with AIDS.

Acquired Immunodeficiency Syndrome↗

The trend of imported mycoses in Japan.

Pathogenic fungi that are non-native in Japan are highly virulent and present a significant health hazard to persons in the environment into which they are introduced. Little is known, however, about the precise trend of infection by imported mycoses in Japan. To clarify this issue, all available cases were collected through a search of MEDLINE and Japana Centra Revuo Medicine and analyzed. Also included in this analysis were cases not reported in the literature for which the authors provided identification of the fungi, diagnosis, or treatment. The analysis revealed that, for three diseases, the number of imported mycoses cases in Japan is much higher than previously reported: 31 cases of coccidioidomycosis, 34 cases of histoplasmosis, and 17 cases of paracoccidioidomycosis. Additionally, one case of penicilliosis marneffei was found. The most rapid increase in the incidence of these mycoses occurred from 1991 to 1995. Analysis of the patients' profiles provided the following information: (1) coccidioidomycosis infection in Japan is increasing very rapidly, (2) Japan might be an endemic area of histoplasmosis infection, (3) histoplasmosis is a potentially fatal disease; and (4) reliable serodiagnostic methods have been used only infrequently. Because of the increase of international travel and immigration, the incidence of imported mycoses in Japan is expected to continue rising, and mycoses that have never been reported in Japan, such as blastomycosis, might also be encountered in the near future. To cope with this newly emerging health problem to residents of Japan, the Japanese medical system must train its members to identify and treat mycoses.

Adolescent↗

Therapeutic approaches to subcutaneous mycoses.

Subcutaneous mycoses, which are much less common than superficial fungal infections, are characterized by a heterogeneous group of infections that often result from direct penetration of the fungus into the dermis and subcutaneous tissue through traumatic injury. The fungus spreads by local deep tissue invasion from the inoculation site. The disease usually remains localized and then slowly spreads to adjacent tissue and eventually to the lymphatics. More rarely, hematogenous dissemination is observed. There are usually various clinical features and thus a broad range of differential diagnoses. The common subcutaneous mycoses are sporotrichosis, chromoblastomycosis, phaeohyphomycosis, eumycotic mycetoma, and hyalohyphomycosis. Many subcutaneous mycoses are confined to the tropical and subtropical regions, but some, such as sporotrichosis, are also prevalent in temperate regions. Subcutaneous mycoses can occur in healthy individuals. In immunocompromised individuals, these infections can disseminate widely. Treatment usually involves use of antifungal agents and/or surgical excision. Treatment of some serious subcutaneous mycoses remains unresolved, and there have been reports of relapses or progression during therapy and problems with lack of tolerability of antifungal drugs. Identification of the etiologic agent by culture is essential for prognostic and management considerations, since some fungi are more frequently associated with dissemination. Results of antifungal susceptibility tests may provide valuable information for deciding the appropriate method of treatment. Development of new antifungal agents and combination therapies may result in improvement in the management of subcutaneous mycoses in the future.

Antifungal Agents↗

[Histopathological diagnosis of mycoses in veterinary pathology].

Histopathological analysis demonstrates the morphology of the fungi and shows their relationship with tissue lesions, which is a valuable information in the diagnosis of veterinary mycoses, especially in superficial infections where reservoirs make difficult the diagnosis using other techniques. On the other hand, histopathological analysis should be complementary to other methods such as culture, immunohistochemistry, serology, PCR, etc. In this work, the most relevant histopathological features of some of the most common mycoses of domestic animals, some of which have zoonotic potential, are described and their differential diagnosis is discussed. To facilitate the discussion of the differential diagnoses, mycoses have been grouped by the sites of the infections and by the nature of the fungi (dimorphic and filamentous). Mycoses included in the study were 1) Superficial and deep infections: dermatophytosis, dermatophytic pseudomycetoma, eumycotic mycetoma, phaeohyphomycosis and malasezziasis. 2) Systemic mycoses: aspergillosis and zygomycosis. 3) Mycoses due to dimorphic fungi: candidiasis, cryptococcosis, blastomycosis, sporotrichosis, coccidioidomycosis and histoplasmosis. 4) Infections by algae and other fungi: protothecosis and pneumocystosis.

English Abstract↗

Rabbit as an animal model of paranasal sinus mycoses.

Paranasal sinus mycoses are endemic in rural populations of northern India. To study host-parasite interactions, we developed an animal model of paranasal sinus mycoses. After failure in small animals such as mice and rats, we used New Zealand white rabbits weighing 2.5-3 kg. Inoculum sizes consisted of 0.75-1.0 x 10(8), 0.75-1.0 x 10(7), 0.75-1.0 x 10(6) conidia of a clinical isolate of Aspergillus flavus. The inoculum was injected at a spot 0.5 cm in front of the alveolar process of the maxilla and 0.5 cm below the maxillary process of frontal bone and vertically to a depth of 0.5 cm across the bone directly into the nasal sinus. Paranasal sinus mycoses proven by culture and histopathology developed in 67% of animals injected with 0.75-1.0 x 10(8) conidia and 17% of animals with 0.75 x 10(7) conidia. No lesions were found in the group injected with 0.75-1.0 x 10(6) conidia. Precipitating antibody against culture filtrate antigen was found in rabbits with paranasal sinus mycoses. Therefore, rabbits can be used as an animal model to study paranasal sinus mycoses.

Animals↗

Oral lesions in the systemic mycoses.

Oral lesions have rarely been reported in systemic mycoses, though over the past few years they have been recorded particularly in immunocompromised individuals. The dramatic increase in numbers of immunocompromised persons, especially those infected with human immunodeficiency virus, has almost certainly been responsible for the increase in reports of oral disease caused by systemic mycoses, particularly aspergillosis, cryptococcosis, and histoplasmosis. However, reports of coccidioidomycosis, blastomycosis, and paracoccidioidomycosis have, as yet, increased little in this population. Dentists, when they observe chronic oral ulceration, chronic maxillary sinus infection, or bizarre mouth lesions (particularly in immunocompromised patients) should be aware of the possibility of a systemic mycosis. Amphotericin remains the standard therapy for most deep mycoses, while the newer azoles are the first-line agents for superficial mycoses, such as candidiasis, and are increasingly used in the deep mycoses.

Antifungal Agents↗