Daniel Wagner de Castro Lima Santos

Challenges in the therapy of chromoblastomycosis.

Chromoblastomycosis (CBM) is an implantation mycosis mainly occurring in tropical and subtropical zones worldwide. If not diagnosed at early stages, patients with CBM require long-term therapy with systemic antifungals flanked by various physical treatment regimens. As in other neglected endemic mycoses, comparative clinical trials have not been performed for this disease; nowadays, therapy is mainly based on a few open trials and on expert opinions. Itraconazole, either as monotherapy or associated with other drugs, or with physical methods, is widely used. Recently, photodynamic therapy has been employed successfully in combination with antifungals in patients presenting with CBM. In the present paper, the most used therapeutic options against CBM are reviewed as well as the several factors that may have impact on the patient’s outcome.

Molecular Identification of Melanised Non-Sporulating Moulds: A Useful Tool for Studying the Epidemiology of Phaeohyphomycosis

Subcutaneous infections caused by melanised fungi have been increasingly reported among transplant patients, and these infections have the potential for blood and visceral dissemination. Some moulds, such as Mycelia sterilia, cannot grow and sporulate on different media, making their identification impossible by conventional methods. The fast and accurate identification of melanised fungi at the species level is important because species may have tropism to different organs and different susceptibilities to antifungal agents. Molecular tools have been reported to be helpful for the species identification of non-sporulating moulds. Our goal was to identify the species of M. sterilia isolates obtained from clinical samples of transplant patients using sequences of ITS and the D1/D2 regions of rDNA. Clinical samples were obtained from eight kidney transplant recipients who developed subcutaneous fungal infections. The diagnosis was confirmed by histopathology and conventional culture. Histopathology showed septated, melanised hyphae, and the cultures identified non-sporulating fungi. Therefore, the DNA from the M. sterilia isolates was subjected to PCR amplification and sequencing of the ITS and D1/D2 regions. Genus/species identification was obtained by comparison with gene banks. We obtained the following identifications: Alternaria sp. (2), Cochliobolus lunatus/Curvularia lunata (2), Cochliobolus hawaiiensis/Bipolaris hawaiiensis (1), Ochroconis sp. (1), Medicocopsis romeroi/Pyrenochaeta romeroi (1) and Nigrograna mackinnonii/Pyrenochaeta mackinnonii (1).

Molecular Epidemiology of Agents of Human Chromoblastomycosis in Brazil with the Description of Two Novel Species

The human mutilating disease chromoblastomycosis is caused by melanized members of the order Chaetothyriales. To assess population diversity among 123 clinical strains of agents of the disease in Brazil we applied sequencing of the rDNA internal transcribed spacer region, and partial cell division cycle and β-tubulin genes. Strains studied were limited to three clusters divided over the single family Herpotrichiellaceae known to comprise agents of the disease. A Fonsecaea cluster contained the most important agents, among which F. pedrosoi was prevalent with 80% of the total set of strains, followed by 13% for F. monophora, 3% for F. nubica, and a single isolate of F. pugnacius. Additional agents, among which two novel species, were located among members of the genus Rhinocladiella and Cyphellophora, with frequencies of 3% and 1%, respectively.

Early Invasive Pulmonary Aspergillosis in a Kidney Transplant Recipient Caused by Aspergillus lentulus : First Brazilian Report

AbstractWe report the first Brazilian case of pulmonary invasive aspergillosis caused by Aspergillus lentulus, a new opportunistic Aspergillus species included in the section fumigati that is usually resistant to amphotericin B and azoles.

Chromoblastomycosis in the Clinical Practice

Chromoblastomycosis is one of the most important implantation (subcutaneous) mycoses in the world. In recent years, the most significant advances against this disease have been made on the molecular taxonomy of the etiologic agents with an increase of the reported cases from Mainland China and South America. This article outlines the actual microbiologic, eco-epidemiologic and clinico-pathologic aspects of the disease, as well as recent therapeutic tolls to treat patients with different severity of chromoblasomycosis lesions.

Melanized fungal infections in kidney transplant recipients: contributions to optimize clinical management

OBJECTIVES This is a retrospective and observational study addressing clinical and therapeutic aspects of melanized fungal infections in kidney transplant recipients. METHODS We retrospectively reviewed medical records of all patients admitted between January 1996 and December 2013 in a single institution who developed infections by melanized fungi. RESULTS We reported on 56 patients aged between 30 and 74 years with phaeohyphomycosis or chromoblastomycosis (0.54 cases per 100 kidney transplants). The median time to diagnosis post-transplant was 31.2 months. Thirty-four (60.8%) infections were reported in deceased donor recipients. Fifty-one cases of phaeohyphomycosis were restricted to subcutaneous tissues, followed by two cases with pneumonia and one with brain involvement. Most dermatological lesions were represented by cysts (23/51; 45.1%) or nodules (9/51; 17.9%). Exophiala spp. (34.2%) followed by Alternaria spp. (7.9%) were the most frequent pathogens. Graft loss and death occurred in two patients and one patient, respectively. Regarding episodes of subcutaneous phaeohyphomycosis, a complete surgical excision without antifungal therapy was possible in 21 of 51 (41.2%) patients. Long periods of itraconazole were required to treat the other 30 (58.8%) episodes of subcutaneous disease. All four cases of chromoblastomycosis were treated only with antifungal therapy. CONCLUSIONS Melanized fungal infections should be considered in the differential diagnosis of all chronic skin lesions in transplant recipients. It is suggested that the impact of these infections on graft function and mortality is low. The reduction in immunosuppression should be limited to severely ill patients.

The influence of mTOR inhibitors on the incidence of CMV infection in high-risk donor positive-recipient negative (D+/R−) kidney transplant recipients

Several studies and meta‐analysis suggest the mTOR inhibitors are associated with reduced incidence of CMV infection after kidney transplantation, although their effects on the high‐risk population have not been investigated thoroughly.

Fungal Infections of Implantation (Chromoblastomycosis, Mycetoma, Entomophthoramycosis, and Lacaziosis)

Implantation mycoses include a heterogeneous group of fungal diseases that develop at the site of transcutaneous trauma. They are also known as “subcutaneous mycoses,” but this term seems to be imprecise because some of implantation mycoses may also involve muscles, fascia, cartilage, and bones, beyond the skin and the subcutaneous tissues. These diseases are a frequent health problem in Latin American countries and other tropical and subtropical areas of the world. Although these infections rarely cause disseminated or invasive disease, they have an important impact on public health, may be difficult to control, and often recur.The implantation mycoses covered in this chapter include chromoblastomycoses, eumycetoma, lacaziosis, and entomophthoramycoses.

Sexual acquisition of HIV infection after solid organ transplantation: Late presentation and potentially fatal complications

While the growing knowledge on HIV among solid organ transplant recipients (SOT) is limited to either pretransplant infection or allograft transmission, there are only sparse reports describing HIV‐infection after transplantation through sexual route, the primary mode of transmission in the general population.

The effect of anti-thymocyte globulin and everolimus on the kinetics of cytomegalovirus viral load in seropositive kidney transplant recipients without prophylaxis

The use of mTOR inhibitors is associated with lower incidence of CMV infections but its effect on viral load has not been investigated.