Changming Lu

Molecular diversity of Fonsecaea (Chaetothyriales) causing chromoblastomycosis in southern China

Chromoblastomycosis is a chronic, cutaneous and subcutaneous infection caused by members of the order Chaetothyriales and commonly found in China. Among the etiologic agents, members of the genus Cladophialophora are predominant in northern China. Alternatively, Fonsecaea spp. are particularly common in southern China. However, the identification of Fonsecaea isolates recovered in China is difficult due to the fact that different species lack distinctive morphological characters. Therefore, the identification of 24 Fonsecaea isolates from symptomatic patients were re-evaluated by using morphology, ITS rDNA sequence diversity and partly through the use of randomly amplified polymorphic DNA (RAPD) typing. Twenty strains, including a morphological mutant were found to be Fonsecaea monophora, while four strains corresponded to F. pedrosoi. We have demonstrated that Fonsecaea monophora is the predominant etiologic agent of chromoblastomycosis in southern China and populations showed marked geographic structuring.

Successful treatment for chromoblastomycosis caused by Fonsecaea monophora: a report of three cases in Guangdong, China

Fonsecaea pedrosoi is the most prevalent aetiological agent of chromoblastomycosis. Fonsecaea monophora is a new species segregated from Fonsecaea pedrosoi. Herein, we report on three cases of chromoblastomycosis caused by F. monophora that were successfully treated with terbinafine and/or itraconazole. Clinical characteristics and mycological parameters are described. Two of the three patients underwent combination therapy with itraconazole and terbinafine during early stages of treatment and were completely healed in a relatively short course of treatment.

Chromoblastomycosis in Mainland China: A Systematic Review on Clinical Characteristics

Chromoblastomycosis is one of the most frequent chronic infections caused by melanized fungi. In order to evaluate the clinical characteristics of chromoblastomycosis in Mainland China, we performed an evidence-based review of published literature. PubMed and Chinese-language database of CNKI, VIP and Wanfang data during January 1990–August 2011 were searched. Epidemiology, clinical features, laboratory findings, therapy and prognosis were analyzed. Cladophialophora carrionii was the most common causative agent in the north of the Mainland China, and Fonsecaea monophora and F. pedrosoi were the most common agents in the southern part of the Mainland China. Infection commonly initiated after the etiologic agents gain entrance through puncture wounds and more common involved extremities of the males. Skin lesions were found in different sites, like the extremities, buttocks, trunk and face, and presented diversity morphology. There were about seven different clinical types found in Mainland China: plaque type, tumoral type, cicatricial type, verrucous type, pseudo-vacuole type, eczymatous type and mixed type of lesions. The success of treatment for chromoblastomycosis was related to the causative agent, the clinical form and severity of the lesions. Most of the patients could be treated successfully with the physical treatment, chemotherapy and/or combination therapy. The itraconazole, terbinafine or a combination of both were commonly medication for these mycosis patients. Physical methods were usually indicated to support chemotherapy with some severe forms and long-lasting cases. Photodynamic therapy has been extended from the oncological field to that of antimicrobial chemotherapy in these years. We applied it on some recalcitrant cases of chromoblastomycosis and found its good clinical response, and hopeful it could be a promising therapy in near future.

A refractory case of chromoblastomycosis due to Fonsecaea monophora with improvement by photodynamic therapy

Chromoblastomycosis is one of the most frequently encountered mycoses in tropical and temperate regions caused by the implantation of the infectious structures and one which is associated with low cure and high relapse rates. The etiologic agents play a critical role affecting clinical outcome and in southern China, Fonsecaea pedrosoi and F. monophora are the main causative agents of chromoblastomycosis. We treated, for two years, a 55-year-old male patient with chromoblastomycosis caused by F. monophora with itraconazole and terbinafine, two antifungals recommend in earlier papers in the literature but without any positive response. As a result we introduced the photodynamic therapy (PDT) employing 5-aminolevulinic acid (ALA) irradiation. The lesions were improved after two periods of ALA-PDT treatment, each consisting of exposures at weekly intervals for 5 weeks but new lesions developed with the cessation of ALA-PDT treatment. Thereafter, positive clinical improvement was obtained when voriconazole at 200 mg was combined with terbinafine at 250 mg in treating the patient. The in vitro susceptibility of the F. monophora isolate to terbinafine, itraconazole, and voriconazole was assessed and the fungus was found to be sensitive to all three, with the minimal inhibitory concentrations of 0.125, 1, 0.0625 μg/ml, respectively. However, the determination of in vitro susceptibility profiles may not predict clinical response.

Chromoblastomycosis caused by a meristematic mutant of Fonsecaea monophora

We report the first case of chromoblastomycosis caused by a meristematic mutant of Fonsecaea monophora in an 81-year-old Cantonese male. The patient had a seven-month history of a red plaque with thick yellow crust and purulent exudates on the back of his right hand. Microscopic examination of direct smears revealed brown sclerotic cells and black colonies were recovered in culture from samples of the purulent exudantes. The microscopic appearance of this isolate was quite different from that of other Fonsecaea species, exhibiting mere meristematic growth. The rDNA ITS sequence data confirmed that this isolate was a mutant of Fonsecaea monophora. The patient showed good response to treatment with itraconazole and complete healing was achieved without relapse after long-term follow-up.

First Case of Arthrographis kalrae Ethmoid Sinusitis and Ophthalmitis in the People's Republic of China

ABSTRACT We present here the first case in the Peoples Republic of China of human disease caused by the fungus Arthrographis kalrae. The male patient had fungal panophthalmitis and invasive sinusitis involving the maxillary and ethmoid sinuses. He was an apparently healthy man before receiving trauma to his left eye. He complained of pain and loss of visual acuity in the injured eye, which displayed redness and edema and eventually discharged pus. His symptoms became more severe after he was treated with steroids and several antibacterial agents. A computed tomography scan of the left eye revealed that the maxillary and ethmoid sinuses were involved. A smear of purulent material from the left eye orbit revealed fungal elements, and cultures of the material grew a fungus. The isolate was identified as A. kalrae based on gross and microscopic morphologies, biochemical assays, and DNA sequence analysis. The patient received amphotericin B intravenously, itraconazole orally, and atomized allitridum by nebulizing allitridum therapy. The patients wound healed following surgical intervention, but the patient lost the use of his left eye. This case should remind ophthalmologists and other clinicians to consider the possibility of infections being fungal when antibacterial agents have no effect and the patients condition worsens.

Cutaneous protothecosis: two new cases in China and literature review

Protothecosis is a rare infection caused by Prototheca spp., which are achlorophyllous algae found in trees, various aquatic sources such as lakes and rivers, sewage treatment plants, soil, and household garbage. They can infect both humans and animals. Human protothecosis is rare, and most cases are found in immunocompromised patients. In mainland China, only four cases caused by Prototheca spp. have been reported. In general, clinical manifestations of reported cases can be classified into three clinical forms: cutaneous (66%); olecranon bursitis (15%); and disseminated or systemic infections (19%). Currently, Prototheca zopfii, P. wickerhamii, P. stagnora, P. ulmea, and P. blaschkeae are classified to the genus. Among these, only the former two have been reported to cause infections in humans, with P. wickerhamii being most common. In this article, two cases of cutaneous protothecosis caused by P. wickerhamii will be presented. Both patients responded well to treatment with intravenous voriconazole (VRC), although one died later from other complications.

A chronic chromoblastomycosis model by Fonsecaea monophora in Wistar rat

Chromoblastomycosis is a chronic, cutaneous and subcutaneous infection characterized by verrucose lesions. It is primarily caused by Fonsecaea monophora in southern China and responds poorly to available therapies. In order to investigate the pathogenicity of Fonsecaea monophora, we established a chronic chromoblastomycosis animal model in Wistar rats. Suspensions of 2x10(6) cfu conidia and hyphal fragments were intracutaneous (ic) and subcutaneous (sc) on either side of the backs of the rats. Small nodules were formed at the inoculation sites within the first week after inoculation. By the second week, the nodules had enlarged and become soft, and pus could be aspirated from them. In the fourth week, the nodules in the ic inoculated group had ulcerated and sclerotic bodies were observed in smears prepared from all animals. In the 3rd month after inoculation, the nodules at the sites of the ic inoculation had become flat, with a thin black crust on the surface. For the ic inoculated group, sequential biopsy studies revealed extensive necrosis with neutrophil infiltration and sclerotic bodies and some debris of fungi in the 1st month, sclerotic bodies inside multinucleated giant cells by the 2nd month and widespread granulomatous inflammations in the 3rd month.

Isolation of Penicillium marneffei From Soil and Wild Rodents in Guangdong, SE China

Infection by Penicillium marneffei is an important emerging public health problem, especially among travelers and inhabitants in SE China and SE Asia infected with human immunodeficiency virus (HIV). In recent years, the number of patients with penicilliosis marneffei (PM) has increased rapidly in Guangdong province, SE China. However, the natural habitat and transmission mode of the etiologic agent remains unclear. In this study, wild rats (Microtus, focus Rattus and Rhizomys pruinosus) and soil samples were collected from rat burrows, populated and rural areas from November 2007 to December 2008 for fungus cultures. All isolates, suspected of being P. marneffei, were identified by gross and microscopic morphology and ITS analysis. Sixteen of 23 (about 70%) bamboo rats were P. marneffei positive, whereas none was recovered from hamsters, loirs or soil. This suggests that as of today the bamboo rat is the exclusive natural reservoir for P. marneffei. Definite evidence that rodents are a part of the infectious cycle is still lacking.

In vitro susceptibility testing of amorolfine in pathogenic fungi isolated from dermatomycosis patients in China

The antifungal susceptibility of isolates from Chinese dermatomycosis patients to amorolfine was investigated following National Committee for Clinical Laboratory Standards (NCCLS) protocols. In total, 383 isolates were tested, including 132 strains from tinea pedis, 148 strains from tinea corporis/cruris, and 103 strains from onychomycosis. The minimum inhibitory concentration (MIC) of amorolfine against dermatophytes ranged from 0.01 to 0.08 μg ml−1. The MIC50 and MIC90 of amorolfine for Trichophyton rubrum were both equal to 0.04 μg ml−1; for T. mentagrophytes these MICs were 0.04 μg ml−1 and 0.08 μg ml−1 respectively; and for Epidermophyton floccosum they were 0.02 μg ml−1 and 0.04 μg ml−1 respectively. The MIC range of amorolfine against Candida parapsilosis was 0.5–16 μg ml−1. MIC50 and MIC90 for C. parapsilosis were 0.5 and 2 μg ml−1. MIC ranges of amorolfine against Scopulariopsis spp. and Acremonium spp. were 0.5–4 and 2–8 μg ml−1, respectively. Candida albicans, Fusarium solani and Aspergillus flavus required relatively higher concentrations of amorolfine to inhibit their growth (MIC 0.125–64 μg ml−1, MIC50 and MIC90 were 4 and 64 μg ml−1). The results demonstrated that amorolfine is the only topical agent that has such a potent antifungal activity and a broad spectrum against a wide range of pathogenic fungi.