Endemic Mycoses Research Articles

Invasive fungal infections in liver diseases.

Patients with liver diseases, including decompensated cirrhosis, alcohol-associated hepatitis, and liver transplant recipients are at increased risk of acquiring invasive fungal infections (IFIs). These infections carry high morbidity and mortality. Multiple factors, including host immune dysfunction, barrier failures, malnutrition, and microbiome alterations, increase the risk of developing IFI. Candida remains the most common fungal pathogen causing IFI. However, other pathogens, including Aspergillus, Cryptococcus, Pneumocystis, and endemic mycoses, are being increasingly recognized. The diagnosis of IFIs can be ascertained by the direct observation or isolation of the pathogen (culture, histopathology, and cytopathology) or by detecting antigens, antibodies, or nucleic acid. Here, we provide an update on the epidemiology, pathogenesis, diagnosis, and management of IFI in patients with liver disease and liver transplantation.

South Asian Transplant Infectious Disease Guidelines for Solid Organ Transplant Candidates, Recipients, and Donors.

These guidelines discuss the epidemiology, screening, diagnosis, posttransplant prophylaxis, monitoring, and management of endemic infections in solid organ transplant (SOT) candidates, recipients, and donors in South Asia. The guidelines also provide recommendations for SOT recipients traveling to this region. These guidelines are based on literature review and expert opinion by transplant physicians, surgeons, and infectious diseases specialists, mostly from South Asian countries (India, Pakistan, Bangladesh, Nepal, and Sri Lanka) as well as transplant experts from other countries. These guidelines cover relevant endemic bacterial infections (tuberculosis, leptospirosis, melioidosis, typhoid, scrub typhus), viral infections (hepatitis A, B, C, D, and E; rabies; and the arboviruses including dengue, chikungunya, Zika, Japanese encephalitis), endemic fungal infections (mucormycosis, histoplasmosis, talaromycosis, sporotrichosis), and endemic parasitic infections (malaria, leishmaniasis, toxoplasmosis, cryptosporidiosis, strongyloidiasis, and filariasis) as well as travelers' diarrhea and vaccination for SOT candidates and recipients including travelers visiting this region. These guidelines are intended to be an overview of each topic; more detailed reviews are being published as a special supplement in the Indian Journal of Transplantation .

Factors associated with pulmonary infection in kidney and kidney-pancreas transplant recipients: a case-control study.

To evaluate the etiology of and factors associated with pulmonary infection in kidney and kidney-pancreas transplant recipients. This was a single-center case-control study conducted between December of 2017 and March of 2020 at a referral center for kidney transplantation in the city of Belo Horizonte, Brazil. The case:control ratio was 1:1.8. Cases included kidney or kidney-pancreas transplant recipients hospitalized with pulmonary infection. Controls included kidney or kidney-pancreas transplant recipients without pulmonary infection and matched to cases for sex, age group, and donor type (living or deceased). A total of 197 patients were included in the study. Of those, 70 were cases and 127 were controls. The mean age was 55 years (for cases) and 53 years (for controls), with a predominance of males. Corticosteroid use, bronchiectasis, and being overweight were associated with pulmonary infection risk in the multivariate logistic regression model. The most common etiologic agent of infection was cytomegalovirus (in 14.3% of the cases), followed by Mycobacterium tuberculosis (in 10%), Histoplasma capsulatum (in 7.1%), and Pseudomonas aeruginosa (in 7.1%). Corticosteroid use, bronchiectasis, and being overweight appear to be risk factors for pulmonary infection in kidney/kidney-pancreas transplant recipients, endemic mycoses being prevalent in this population. Appropriate planning and follow-up play an important role in identifying kidney and kidney-pancreas transplant recipients at risk of pulmonary infection.

P21 Facial papules in an immunocompromised patient

Abstract A 29-year-old man presented with a 6-week history of clustered facial papules. Of note, he had a diagnosis of HIV 5 months previously and was on maintenance antiretroviral treatment. His initial CD4 count was 5, which increased to 38, and his viral load was now no longer detectable. He had also been treated for cytomegalovirus reactivation, pneumocystis pneumonia and suspected mycobacterium infection for the previous 3 months. He had ongoing symptoms of malaise, fevers, weight loss and nausea, along with abnormal liver function tests and a raised C-reactive protein. A bone marrow trephine showed noncaseating discrete small granulomas; Grocott and periodic acid–Schiff (PAS) stains were negative. Prior to his dermatology review, the papules were initially perioral and he had been treated with empiric valaciclovir for suspected herpes simplex virus (HSV) but with no resolution. Testing for HSV DNA and syphilis was negative. On examination, there were clusters of small nontender, well-circumscribed papules (some umbilicated), distributed on the forehead, cheeks, and cutaneous and mucosal lips. A diagnostic punch biopsy was taken of one of the characteristic papules. Histological examination demonstrated a dense dermal infiltrate of histiocytes with focal non-necrotizing granuloma formation. Interspersed neutrophilic microabscesses and occasional eosinophils were present. PAS stain for fungi confirmed the presence of numerous thick-walled spherules, many with a single distinct nucleus, with some showing binucleation, consistent with fungal organisms located within the histiocytes in the dermis. Differential diagnosis included histoplasmosis, cryptococcosis, blastomycosis and coccidiomycosis. He was commenced on intravenous liposomal amphotericin B for disseminated endemic mycosis while awaiting definitive diagnosis. Formal identification by panfungal polymerase chain reaction of skin tissue was positive for Histoplasma capsulatum and itraconazole was added. The diagnosis was consistent with disseminated histoplasmosis with cutaneous involvement. The lesions resolved completely over 4 weeks, with some residual hyperpigmentation remaining. Histoplasma capsulatum is a dimorphic fungus found in soil and the droppings of bats and birds. Infection is through spore inhalation, with most patients being asymptomatic. It is more prevalent in temperate and tropical climates. Disseminated histoplasmosis occurs mostly in immunocompromised individuals and can be fatal if left untreated. Although endemic to specific world regions, disseminated histoplasmosis should be considered in immunocompromised patients presenting with atypical cutaneous findings, even in regions of low prevalence.

Seasonality of sporotrichosis in Brazil: A modelled analysis of the epidemic in São Paulo, 2011-2020.

Sporotrichosis is an endemic subcutaneous mycosis classically caused by the Sporothrix schenckii species complex. Recently, sporotrichosis has emerged in Brazil as a cat-transmitted epidemic caused by a new species, Sporothrix brasiliensis. To survey the clinical-epidemiological profile of all sporotrichosis cases diagnosed between 2011 and 2020 at a reference hospital in São Paulo metropolitan area and evaluate the annual distribution of cases in relation to seasonality. Patients' demographic and clinical-epidemiological data were surveyed. A generalized linear model was fitted to relate the quarterly number of sporotrichosis cases detected between 2015 and 2019 with precipitation and temperature series. Prediction of the number of cases from 2011 to 2014 was attempted based on the fitted model without the trend component that appears from 2015. Among 271 suspected cases admitted during 2011-2020, 254 were confirmed by fungal isolation and/or clinical-epidemiological criteria. We observed that 2015 onwards the number of cases regularly increased during Autumn and Winter, the driest and coldest stations of the year. We verified that temperature series affected the number of cases (p = .005) because an increase of 1°C in the temperature series was associated with a 14.24% decrease in the average cases number, with the average number of cases increasing by 10.96% (p < .0001) every quarter, corresponding to an annual increase of 52%. Between 2011 and 2014, the predicted number of sporotrichosis cases averaged 10-12 per year, with 33%-38% occurring in the winter. We hypothesize that sporotrichosis seasonality is associated with the felines' oestrus cycle, which may provide alternative, cat-directed approaches to the sporotrichosis epidemic control.

Genetic and Other Determinants for the Severity of Coccidioidomycosis: A Clinician's Perspective.

The endemic fungal infection, coccidioidomycosis, occurs after inhalation of one or very few Coccidioides spp. spores. Infections produce diverse clinical manifestations, ranging from insignificant to extremely destructive, even fatal. Approaches to understanding this range of consequences have traditionally categorized patients into a small number of groups (asymptomatic, uncomplicated self-limited, fibro-cavitary, and extra-thoracic disseminated) and then looked for immunologic differences among them. Recently, variants within genes of innate pathways have been found to account, in part, for infections that result in disseminated disease. This discovery raises the very attractive theory that, in patients without severe immunosuppression, much of the disease spectrum can be accounted for by various combinations of such deleterious variants in innate pathways. In this review, we summarize what is known about genetic determinants that are responsible for the severity of coccidioidal infections and how complex innate genetic differences among different people might account for the spectrum of disease observed clinically.

Targeting the P10 Peptide in Maturing Dendritic Cells via the DEC205 Receptor In Vivo: A New Therapeutic Strategy against Paracoccidioidomycosis

Paracoccidioidomycosis (PCM) is a systemic mycosis caused by Paracoccidioides brasiliensis, a thermally dimorphic fungus, which is the most frequent endemic systemic mycosis in many Latin American countries, where ~10 million people are believed to be infected. In Brazil, it is ranked as the tenth most common cause of death among chronic infectious diseases. Hence, vaccines are in development to combat this insidious pathogen. It is likely that effective vaccines will need to elicit strong T cell-mediated immune responses composed of IFNγ secreting CD4+ helper and CD8+ cytolytic T lymphocytes. To induce such responses, it would be valuable to harness the dendritic cell (DC) system of antigen-presenting cells. To assess the potential of targeting P10, which is a peptide derived from gp43 secreted by the fungus, directly to DCs, we cloned the P10 sequence in fusion with a monoclonal antibody to the DEC205 receptor, an endocytic receptor that is abundant on DCs in lymphoid tissues. We verified that a single injection of the αDEC/P10 antibody caused DCs to produce a large amount of IFNγ. Administration of the chimeric antibody to mice resulted in a significant increase in the levels of IFN-γ and IL-4 in lung tissue relative to control animals. In therapeutic assays, mice pretreated with αDEC/P10 had significantly lower fungal burdens compared to control infected mice, and the architecture of the pulmonary tissues of αDEC/P10 chimera-treated mice was largely normal. Altogether, the results obtained so far indicate that targeting P10 through a αDEC/P10 chimeric antibody in the presence of polyriboinosinic: polyribocytidylic acid is a promising strategy in vaccination and therapeutic protocols to combat PCM.

Fever in the returning traveler

Evaluation of febrile illness in a returning traveler is challenging as it requires careful history taking and knowledge of local epidemiology of endemic and epidemic diseases. Incorporating information of host characteristics for susceptibility of infections is also important for endemic mycosis apart from history of tick bites and animal exposures. Laboratory tests directed by clinical and laboratory parameters will help to reach final diagnosis.

In silico-chemogenomic repurposing of new chemical scaffolds for histoplasmosis treatment.

Histoplasmosis is a systemic form of endemic mycosis to the American continent and may be lethal to people living with HIV/AIDS. The drugs available for treating histoplasmosis are limited, costly, and highly toxic. New drug development is time-consuming and costly; hence, drug repositioning is an advantageous strategy for discovering new therapeutic options. This study was conducted to identify drugs that can be repositioned for treating histoplasmosis in immunocompromised patients. Homologous proteins among Histoplasma capsulatum strains were selected and used to search for homologous targets in the DrugBank and Therapeutic Target Database. Essential genes were selected using Saccharomyces cerevisiae as a model, and functional regions of the therapeutic targets were analyzed. The antifungal activity of the selected drugs was verified, and homology modeling and molecular docking were performed to verify the interactions between the drugs with low inhibitory concentration values and their corresponding targets. We selected 149 approved drugs with potential activity against histoplasmosis, among which eight were selected for evaluating their in vitro activity. For drugs with low minimum inhibitory concentration values, such as mebendazole, everolimus, butenafine, and bifonazole, molecular docking studies were performed. A chemogenomic framework revealed lanosterol 14-α-demethylase, squalene monooxygenase, serine/threonine-protein kinase mTOR, and the β-4B tubulin chain of H. capsulatum, respectively, as the protein targets of the drugs. Our strategy can be used to identify promising antifungal targets, and drugs with repositioning potential for treating H. capsulatum.

Endemic mycoses in children in North America: a review of radiologic findings.

Clinically significant endemic mycoses (fungal infections) in the United States (U.S.) include Blastomyces dermatitidis, Histoplasma capsulatum, and Coccidioides immitis/posadasii. While the majority of infections go clinically unnoticed, symptomatic disease can occur in immunocompromised or hospitalized patients, and occasionally in immune-competent individuals. Clinical manifestations vary widely and their diagnosis may require fungal culture, making the rapid diagnosis a challenge. Imaging can be helpful in making a clinical diagnosis prior to laboratory confirmation, as well as assist in characterizing disease extent and severity. In this review, we discuss the three major endemic fungal infections that occur in the U.S., including mycology, epidemiology, clinical presentations, and typical imaging features with an emphasis on the pediatric population.

Diagnosis and Treatment of Pulmonary Coccidioidomycosis and Paracoccidioidomycosis.

Coccidioidomycosis (CM) and paracoccidioidomycosis (PCM) are systemic mycoses that are highly endemic in Latin America and have recently been included on the World Health Organization (WHO) Fungal Priority Pathogens List. Coccidioides immitis and Coccidioides posadasii are recognized as etiological agents of CM, with peculiarities in their geographic distribution. The genus Paracoccidioides now includes Paracoccidioides lutzii and the Paracoccidioides brasiliensis complex, which encompasses four phylogenetic species. In both diseases, pulmonary signs and symptoms are the main reasons for patients to seek medical assistance, and they are frequently misdiagnosed as tuberculosis. In this paper, we present a critical view of the strategies for diagnosis and clinical management of CM and PCM. Over the past few decades, there has been an increase in the number of reports of endemic fungal infections in areas previously thought to be "non-endemic" due to climate change and increased travel, among other factors. Learning to recognize their main epidemiological aspects and clinical manifestations is crucial so that clinicians can include them in the differential diagnosis of lung disease and avoid late diagnosis.

Nanotechnology-Based Approaches for Voriconazole Delivery Applied to Invasive Fungal Infections.

Invasive fungal infections increase mortality and morbidity rates worldwide. The treatment of these infections is still limited due to the low bioavailability and toxicity, requiring therapeutic monitoring, especially in the most severe cases. Voriconazole is an azole widely used to treat invasive aspergillosis, other hyaline molds, many dematiaceous molds, Candida spp., including those resistant to fluconazole, and for infections caused by endemic mycoses, in addition to those that occur in the central nervous system. However, despite its broad activity, using voriconazole has limitations related to its non-linear pharmacokinetics, leading to supratherapeutic doses and increased toxicity according to individual polymorphisms during its metabolism. In this sense, nanotechnology-based drug delivery systems have successfully improved the physicochemical and biological aspects of different classes of drugs, including antifungals. In this review, we highlighted recent work that has applied nanotechnology to deliver voriconazole. These systems allowed increased permeation and deposition of voriconazole in target tissues from a controlled and sustained release in different routes of administration such as ocular, pulmonary, oral, topical, and parenteral. Thus, nanotechnology application aiming to delivery voriconazole becomes a more effective and safer therapeutic alternative in the treatment of fungal infections.

Reactivation Histoplasmosis Manifested by Lymphocutaneous Fistula with Cervical Drainage of Stones

Histoplasmosis, the most common endemic fungal infection in the United States, is usually self-limiting but can cause a myriad of unusual manifestations, including lithiasis. Despite more than a century of clinical experience with the disease, controversy persists regarding the potential for latent infection with subsequent reactivation. We report a case of an apparently immunocompetent young woman who developed recurrent histoplasmosis after eight years. The presumed secondary reactivation was complicated by a lymphocutaneous fistula with the drainage of stones from her neck after the initiation of antifungal therapy. This case supports the concept of reactivation histoplasmosis. Patients with histoplasmosis are at risk for paradoxical transiently worsening local inflammation while receiving effective antifungal therapy.

480. Redefining the Epidemiologic Profile of Histoplasmosis from 2011 to 2021 in Central Ohio

Abstract Background Histoplasma is a common endemic mycosis in multiple Midwestern states. Most of the data defining epidemiologic risk are from 20th century outbreak investigations. A known exacerbating factor is immune suppression; but use of biologics, immunosuppressants (ISP), and chemotherapy has advanced since these investigations were conducted. This study sought to use clinical data from a tertiary care facility to address these gaps to define the evolving epidemiology of histoplasmosis in Ohio. Methods In a single-center retrospective cohort study, we identified adult patients with a histoplasmosis-specific diagnosis, a positive diagnostic test, and an itraconazole/amphotericin B prescription between 1/1/2012 and 10/1/2021. Prisoners were excluded. A random sample of 100 patients underwent in-depth chart review. Comorbidities, environmental risk factors, and ISP use data were collected. Cases were classified by the CDC 2017 Histoplasmosis case definition. “Confirmed” cases had culture growth, a confirmatory lab result, or histopathology plus signs and symptoms of disease, and “probable” cases had a non-confirmatory lab result plus signs and symptoms. Associations between variables were assessed using Fisher’s exact test, p &amp;lt; 0.05. Results Of 100 patients, 56 had confirmed and 22 had probable histoplasmosis (Table 1). Three had confirmed blastomycosis, 15 met definitions for both histoplasmosis and blastomycosis, and 4 met neither definition. These were excluded from analysis. No environmental exposure history was documented for 23 of 78 (29.4%) patients. Of those with documented history, 15 (27.1%) had recent renovation or construction exposure; 14 (25.4%) to soil, gardening, or outdoors; 12 (21.8%) to birds, bats, and farm animals; and 25 (45.4%) had no known exposure. There were 51 (65.4%) exposed to at least one dose of ISP in the year prior to diagnosis, including 41 (52.5%) to corticosteroids. Table 1Characteristics of patient cohort Conclusion In this cohort, more patients with confirmed or probable histoplasmosis were exposed to ISP than had a documented traditional environmental risk factor. This study shows reliance on traditional environmental exposure history might not accurately gauge risk. Further work is needed using ISP exposure to drive appropriate diagnostic testing. Disclosures All Authors: No reported disclosures.

Osteoarticular Mycoses.

Osteoarticular mycoses are chronic debilitating infections that require extended courses of antifungal therapy and may warrant expert surgical intervention. As there has been no comprehensive review of these diseases, the International Consortium for Osteoarticular Mycoses prepared a definitive treatise for this important class of infections. Among the etiologies of osteoarticular mycoses are Candida spp., Aspergillus spp., Mucorales, dematiaceous fungi, non-Aspergillus hyaline molds, and endemic mycoses, including those caused by Histoplasma capsulatum, Blastomyces dermatitidis, and Coccidioides species. This review analyzes the history, epidemiology, pathogenesis, clinical manifestations, diagnostic approaches, inflammatory biomarkers, diagnostic imaging modalities, treatments, and outcomes of osteomyelitis and septic arthritis caused by these organisms. Candida osteomyelitis and Candida arthritis are associated with greater events of hematogenous dissemination than those of most other osteoarticular mycoses. Traumatic inoculation is more commonly associated with osteoarticular mycoses caused by Aspergillus and non-Aspergillus molds. Synovial fluid cultures are highly sensitive in the detection of Candida and Aspergillus arthritis. Relapsed infection, particularly in Candida arthritis, may develop in relation to an inadequate duration of therapy. Overall mortality reflects survival from disseminated infection and underlying host factors.

Effects of fungal infections associated with COVID-19 in pandemic era

Fungal infections such as endemic mycoses, pneumocystosis, candidiasis, aspergillosis, mucormycosis and cryptococcosis associated with COVID-19 are becoming complicated in management and diagnosis of critical ill COVID-19 patients. However, mortality rates due to fungal infections are significantly high. The purpose of this study is to evaluate the effect of fungal infections associated with COVID-19 during the pandemic era. A systemic literature review was carried out to evaluate the effect of fungal infections associated with COVID-19 incidence from relevant published articles. Invasive Fungal Infections (IFIs) had the highest incidence of 26.7% from 137 intensive care unit patients screened for IFIs in 2020. Currently, drugs that are commonly used in the treatment of COVID-19 patients such as casirivimab and imdevimab, bamlanivimab and etesevimab, sotrovimab, and remdesivir had no any effects on fungal infections. In India, 53% of mortality rate which caused by 60% of Candida auris and in Brazil, 72.7% following corticosteroids use were reported. Recently, no any reports related to mortality rate due to Candida infections associated with COVID-19 in Spain and USA. Numerous current advances in management and diagnosis of these fungal infections associated with COVID-19 have not been much potentially significant. It is predicted and possible that the development of new and potent antifungal drugs, antimicrobial peptides and nanotechnology based approaches for drug delivery would help to reduce or eliminate these fungal infections associated with COVID-19 and restraint its spread across the globe.

Chest Imaging in Systemic Endemic Mycoses.

Endemic fungal infections are responsible for high rates of morbidity and mortality in certain regions of the world. The diagnosis and management remain a challenge, and the reason could be explained by the lack of disease awareness, variability of symptoms, and insidious and often overlooked clinical presentation. Imaging findings are nonspecific and frequently misinterpreted as other more common infectious or malignant diseases. Patient demographics and clinical and travel history are important clues that may lead to a proper diagnosis. The purpose of this paper is to review the presentation and differential diagnosis of endemic mycoses based on the most common chest imaging findings.

Clinical performance of metagenomic next-generation sequencing for the rapid diagnosis of talaromycosis in HIV-infected patients.

Talaromycosis is an invasive endemic mycosis caused by the dimorphic fungus Talaromyces marneffei (T. marneffei, TM). It mainly affects immunodeficient patients, especially HIV-infected individuals, which causes significant morbidity and mortality. Culture-based diagnosis takes a long turnaround time with low sensitivity, leading to treatment delay. In this study, we aimed to evaluate the performance of Metagenomic Next-Generation Sequencing (mNGS) for the rapid diagnosis of talaromycosis in HIV-infected patients. Retrospectively analysis was conducted in HIV-infected cases at Changsha First Hospital (China) from January 2021 to March 2022. Patients who underwent routine microbiological examination and mNGS testing in parallel were enrolled. The clinical final diagnosis was used as a reference standard, and cases were classified into the TM group (60 cases) and the non-TM group (148 cases). The clinical performances of mNGS were compared with culture and serum Galactomannan (GM). The mixed infections detected by mNGS were analyzed. The impact of mNGS detection on treatment was also investigated. The sensitivity of mNGS test reached 98.3% (95% CI, 89.8-99.9), which was significantly higher than culture (66.7% [95% CI, 53.2-77.9], P < 0.001) and serum GM (83.3% [95% CI, 71.0-91.2], P < 0.05). The specificity of 98.6% (95% CI, 94.7-99.7) was similar to culture (100.0% [95% CI, 96.8-100.0], P = 0.156), and superior to serum GM (91.9% [95% CI, 85.9-95.5], P < 0.05). In bronchoalveolar lavage fluid (BALF) samples, the positive rate of mNGS was 97.6%, which was significantly higher than culture (28.6%, P <0.001). mNGS has excellent performance in the identification of mixed infection in TM group patients. Cytomegalovirus, Epstein-Barr virus and Pneumocystis jirovecii were the most common concurrent pathogens. In summary, 60.0% (36/60) patients were added or adjusted to antimicrobial therapy after mNGS test. mNGS is a powerful technique with high specificity and sensitivity for the rapid diagnosis of talaromycosis. mNGS of BALF samples may be a good option for early identification of T. marneffei in HIV-infected individuals with manifestations of infection. Moreover, mNGS shows excellent performance in mixed infection, which benefits timely treatment and potential mortality reduction.

SEVERE ARDS DUE TO BLASTOMYCOSIS IN AN ERA OF COVID-19

SEVERE ARDS DUE TO BLASTOMYCOSIS IN AN ERA OF COVID-19

Expert Group Opinion for Diagnosis and Management of Fungal Infections in Solid Organ Transplant Recipients in South Asia

Fungal infections, are common in solid organ transplant (SOT) récipients in South Asia. Invasive fungal infections (IFI) are the third-most common cause of infections in SOT recipients in South Asia after urinary tract infection and tuberculosis and are a significant cause of morbidity and mortality in this population. There are multiple factors, which lead to poor outcomes of these patients, i.e., lack of awareness, inadequate training of physicians, poor laboratory support to diagnose these infections, and sometimes nonavailability of appropriate antifungal agents to treat these infections. Among the IFI in India, invasive candidiasis is the most common followed by mucormycosis, invasive aspergillosis, and cryptococcosis. There is an increasing prevalence of azole resistance and multi-drug resistance among candida infections in South Asia. There are drug interactions of azoles with tacrolimus, cyclosporine, and everolimus and this must be kept in mind when treating various fungal infections. Another challenge is, how to screen and treat the donors and recipients before accepting them for transplant and subsequent management of transplant recipients. The most common endemic mycoses in the Asia-Pacific region are histoplasmosis caused by Histoplasma capsulatum, talaromycosis caused by Talaromyces marneffei and sporotrichosis caused by Sporothrix schenckii. The endemic fungal infections should be kept in the differential diagnosis of pyrexia of unknown origin in transplant recipients. Finally, the outcomes of these patients can be improved by increasing awareness among transplant physicians, better and wider availability of diagnostic facilities, and appropriate use of antifungal agents to treat these infections.