Claudio Guedes Salgado

Chromoblastomycosis: an overview of clinical manifestations, diagnosis and treatment

Chromoblastomycosis is one of the most frequent infections caused by melanized fungi. It is a subcutaneous fungal infection, usually an occupational related disease, mainly affecting individuals in tropical and temperate regions. Although several species are etiologic agents, Fonsecaea pedrosoi and Cladophialophora carrionii are prevalent in the endemic areas. Chromoblastomycosis lesions are polymorphic and must be differentiated from those associated with many clinical conditions. Diagnosis is confirmed by the observation of muriform cells in tissue and the isolation and the identification of the causal agent in culture. Chromoblastomycosis still is a therapeutic challenge for clinicians due to the recalcitrant nature of the disease, especially in the severe clinical forms. There are three treatment modalities, i.e., physical treatment, chemotherapy and combination therapy but their success is related to the causative agent, the clinical form and severity of the chromoblastomycosis lesions. There is no treatment of choice for this neglected mycosis, but rather several treatment options. Most of the patients can be treated with itraconazole, terbinafine or a combination of both. It is also important to evaluate the patients individual tolerance of the drugs and whether the antifungal will be provided for free or purchased, since antifungal therapy must be maintained in long-term regimens. In general, treatment should be guided according to clinical, mycological and histopathological criteria.

Isolation of Fonsecaea pedrosoi from thorns of Mimosa pudica, a probable natural source of chromoblastomycosis

We report the isolation of Fonsecaea pedrosoi from thorns of the plant Mimosa pudica L. at the place of infection identified by one of our patients. Clinical diagnosis of chromoblastomycosis was established by direct microscopic examination and cultures from the patients lesion. The same species was isolated from the patient and from the plant. Scanning electron microscopy of the surface of the thorns showed the characteristic conidial arrangement of F. pedrosoi. These data indicate that M. pudica could be a natural source of infection for the fungus F. pedrosoi.

Spatial analysis spotlighting early childhood leprosy transmission in a hyperendemic municipality of the Brazilian Amazon region.

Background More than 200,000 new cases of leprosy were reported by 105 countries in 2011. The disease is a public health problem in Brazil, particularly within high-burden pockets in the Amazon region where leprosy is hyperendemic among children. Methodology We applied geographic information systems and spatial analysis to determine the spatio-temporal pattern of leprosy cases in a hyperendemic municipality of the Brazilian Amazon region (Castanhal). Moreover, we performed active surveillance to collect clinical, epidemiological and serological data of the household contacts of people affected by leprosy and school children in the general population. The occurrence of subclinical infection and overt disease among the evaluated individuals was correlated with the spatio-temporal pattern of leprosy. Principal Findings The pattern of leprosy cases showed significant spatio-temporal heterogeneity (p<0.01). Considering 499 mapped cases, we found spatial clusters of high and low detection rates and spatial autocorrelation of individual cases at fine spatio-temporal scales. The relative risk of contracting leprosy in one specific cluster with a high detection rate is almost four times the risk in the areas of low detection rate (RR = 3.86; 95% CI = 2.26–6.59; p<0.0001). Eight new cases were detected among 302 evaluated household contacts: two living in areas of clusters of high detection rate and six in hyperendemic census tracts. Of 188 examined students, 134 (71.3%) lived in hyperendemic areas, 120 (63.8%) were dwelling less than 100 meters of at least one reported leprosy case, 125 (66.5%) showed immunological evidence (positive anti-PGL-I IgM titer) of subclinical infection, and 9 (4.8%) were diagnosed with leprosy (8 within 200 meters of a case living in the same area). Conclusions/Significance Spatial analysis provided a better understanding of the high rate of early childhood leprosy transmission in this region. These findings can be applied to guide leprosy control programs to target intervention to high risk areas.

High rates of undiagnosed leprosy and subclinical infection amongst school children in the Amazon Region

Leprosy in children is correlated with community-level factors, including the recent presence of disease and active foci of transmission in the community. We performed clinical and serological examinations of 1,592 randomly selected school children (SC) in a cross-sectional study of eight hyperendemic municipalities in the Brazilian Amazon Region. Sixty-three (4%) SC, with a mean age of 13.3 years (standard deviation = 2.6), were diagnosed with leprosy and 777 (48.8%) were seropositive for anti-phenolic glycolipid-I (PGL-I). Additionally, we evaluated 256 house-hold contacts (HHCs) of the students diagnosed with leprosy; 24 (9.4%) HHC were also diagnosed with leprosy and 107 (41.8%) were seropositive. The seroprevalence of anti-PGL-I was significantly higher amongst girls, students from urban areas and students from public schools (p < 0.0001). Forty-five (71.4%) new cases detected amongst SC were classified as paucibacillary and 59 (93.6%) patients did not demonstrate any degree of physical disability at diagnosis. The results of this study suggest that there is a high rate of undiagnosed leprosy and subclinical infection amongst children in the Amazon Region. The advantages of school surveys in hyperendemic areas include identifying leprosy patients at an early stage when they show no physical disabilities, preventing the spread of the infection in the community and breaking the chain of transmission.

Drug and Multidrug Resistance among Mycobacterium leprae Isolates from Brazilian Relapsed Leprosy Patients

ABSTRACT Skin biopsy samples from 145 relapse leprosy cases and from five different regions in Brazil were submitted for sequence analysis of part of the genes associated with Mycobacterium leprae drug resistance. Single nucleotide polymorphisms (SNPs) in these genes were observed in M. leprae from 4 out of 92 cases with positive amplification (4.3%) and included a case with a mutation in rpoB only, another sample with SNPs in both folP1 and rpoB, and two cases showing mutations in folP1, rpoB, and gyrA, suggesting the existence of multidrug resistance (MDR). The nature of the mutations was as reported in earlier studies, being CCC to CGC in codon 55 in folP (Pro to Arg), while in the case of rpoB, all mutations occurred at codon 531, with two being a transition of TCG to ATG (Ser to Met), one TCG to TTC (Ser to Phe), and one TCG to TTG (Ser to Leu). The two cases with mutations in gyrA changed from GCA to GTA (Ala to Val) in codon 91. The median time from cure to relapse diagnosis was 9.45 years but was significantly shorter in patients with mutations (3.26 years; P = 0.0038). More than 70% of the relapses were multibacillary, including three of the mutation-carrying cases; one MDR relapse patient was paucibacillary.

Cutaneous diffuse chromoblastomycosis.

A 43-year-old man presented with a 2-year history of nodules on the skin, which first appeared on the left leg and then disseminated to other regions of his skin. On examination, he had widespread nodular lesions, which were hard, elongated, violaceous, with a rough surface and well-delineated borders. In some places, such as his left buttock, the lesions became confluent, forming plaques where normal skin almost disappeared (figure, A). As well as the lesions on his limbs, the patient had lesions on his genital area, including the pubic region and the scrotum. In addition, infiltrated plaques with exulceration were found in both ear lobules. Chromoblastomycosis was confirmed by the presence of round, brown, thick-walled sclerotic bodies, which are pathognomonic for this disease (figure, B). The culture grew black filamentous fungi with a velvet surface (figure, C), and microscopic examination demonstrated cylindrical, terminal conidiophores, slackly branched, originating 3·0 1·5 m subhyaline conidia, characteristic of Fonsecaea pedrosoi (figure, D). In 1975, 25 years before his first visit to us, the patient was diagnosed with lepromatous leprosy and sent to a leprosy colony, 150 km from Belem, the state capital of Para, in the northeast of Brazil. He was treated with dapsone for many years. In 1996, he was diagnosed again with lepromatous leprosy, and he received the WHO-recommended multidrug therapy (dapsone, rifampicin, and clofazimine) for 24 months. Chromoblastomycosis is a subcutaneous mycosis with a worldwide distribution. The state of Para has the second highest prevalence rate, behind Madagascar. Usually, patients have nodular verrucous—slow growing lesions—which can appear on one of the legs and spread to neighbouring tissues through the lymphatic vessels. In this case, the lesions disseminated very rapidly, in less then 2 years, with no treatment. 5 years after the appearance of the first signs of chromoblastomycosis, the patient died of unknown causes. Cutaneous diffuse chromoblastomycosis

Clinic-epidemiological evaluation of ulcers in patients with leprosy sequelae and the effect of low level laser therapy on wound healing: a randomized clinical trial

BackgroundMycobacterium leprae is the only pathogenic bacteria able to infect peripheral nerves. Neural impairment results in a set of sensitive, motor and autonomic disturbances, with ulcers originating primarily on the hands and feet. The study objectives were to analyze the clinic-epidemiological characteristics of patients attended at one specialized dressing service from a leprosy-endemic region of the Brazilian Amazon and to evaluate the effect of low level laser therapy (LLLT) on wound healing of these patients.MethodsClinic-epidemiological evaluation of patients with leprosy sequelae was performed at the reference unit in sanitary dermatology of the state of Pará in Brazil. We conducted anamnesis, identification of the regions affected by the lesions and measurement of ulcer depth and surface area. After that, we performed a randomized clinical trial. Fifty-one patients with ulcers related to leprosy were evaluated, twenty-five of them were randomly assigned to a low level laser therapy group or a control group. Patients were treated 3 times per week for 12 weeks. Outcome measures were ulcer surface area, ulcer depth and the pressure ulcer scale for healing score (PUSH).ResultsNinety-seven ulcers were identified, with a mean (SD) duration of 97.6 (111.7) months, surface area of 7.3 (11.5) cm2, and depth of 6.0 (6.2) mm. Statistical analysis of the data determined that there were no significant differences in the variables analyzed before and after treatment with low level laser therapy.ConclusionsUlcers in patients with leprosy remain a major source of economic and social losses, even many years after they have been cured of M. leprae infection. Our results indicate that it is necessary to develop new and more effective therapeutic tools, as low level laser therapy did not demonstrate any additional benefits to ulcer healing with the parameters used in this study.Trial RegistrationThe trial was registered at ClinicalTrials.gov as NCT00860717.

Development of Natural Culture Media for Rapid Induction of Fonsecaea pedrosoi Sclerotic Cells In Vitro

ABSTRACT Fonsecaea pedrosoi is the main agent of chromoblastomycosis, a skin disease presenting verrucous lesions, in which round, thick-walled sclerotic cells are found. In vitro induction of sclerotic cells is time-consuming (20 to 45 days) and temperature dependent. We present two new natural media that reduce the sclerotic-cell induction time to only 2 days.

Cutaneous localized annular chromoblastomycosis

Chromoblastomycosis (CBM) is a difficult‐to‐treat dermal mycosis characterized by the presence of round, pigmented, sclerotic bodies formed by black fungi found in polymorphic lesions. According to the morphology of a lesion, different clinical types of the disease have been described. We present three patients who each developed a single, 10‐cm diameter, 8 to 15‐year‐old, well‐circumscribed, slow‐growing, annular, papulosquamous or papulosquamous‐verrucous lesion, with no regression despite the use of topical antifungals. Skin scrapings and biopsies confirmed CBM and microculture defined the agent as Fonsecaea pedrosoi. The patients were treated with 200 mg/day of itraconazole for 6–9 months and were discharged after complete regression of the lesions. All were examined after the first and second year of the end of treatment and there were no signs of recurrence. A new clinical type of CBM is described, and itraconazole appears to be effective and safe in curing these patients after no more than 9 months of therapy.

What do we actually know about leprosy worldwide

778 www.thelancet.com/infection Vol 16 July 2016 with leprosy varies from 1·2% to 39·8% (or why grade 2 disability ranges from 0·0% to 28·0%) in different, but all equally poor, countries? The answers will only be possible when we understand that absence of diagnosis of leprosy is not the same as the absence of leprosy. The elimination target has become the mantra everywhere, but it is now meaningless. Although the zero-transmission strategy is highly desirable, comprehension and acknowledgment of the real worldwide leprosy situation is imperative fi rst.