Chromoblastomycosis in an Endemic Area of Brazil: A Clinical-Epidemiological Analysis and a Worldwide Haplotype Network

Abstract

Chromoblastomycosis (CBM) is a neglected implantation mycosis prevalent in tropical climate zones, considered an occupational disease that affects impoverished rural populations. This retrospective study described clinical aspects of CBM in a hyperendemic area in Brazil and constructed a worldwide haplotype network of Fonsecaea spp. strains. The variables were collected from medical records using a standard report form, reporting 191 patients with CBM from Maranhão, Brazil. The mean age was 56.1 years, 168 (88%) patients were male and predominantly farmers (85.8%). The mean time of evolution of the disease until diagnosis was 9.4 years. Lower limbs (81.2%) and upper limbs (14.2%) were the main sites affected. Most patients exhibited verrucous (55%) and infiltrative plaque (48.2%). Fonsecaea spp. were identified in 136 cases and a haplotype network constructed with ITS sequences of 185 global strains revealed a total of 59 haplotypes exhibiting high haplotypic and low nucleotide diversities. No correlation was observed between the different haplotypes of Fonsecaea species and dermatological patterns, severity of disease or geographic distribution inside Maranhão. Data from this area contributed to better understanding the epidemiology of CBM. For the first time, a robust haplotype network with Fonsecaea strains reveals an evolutionary history with a recent population expansion.

The global burden of chromoblastomycosis

“…A total of 51 articles described 2,619 patients that were reported in Venezuela (1,167 cases) [ 43 – 49 ], Brazil (1,143 cases) [ 50 – 70 ], Colombia (167 cases) [ 71 – 76 ], Paraguay (82 cases) [ 77 – 81 ], Ecuador (34 cases) [ 82 , 83 ], French Guiana (11 cases) [ 84 – 86 ], Peru (7 cases) [ 87 – 89 ], Argentina (4 cases) [ 90 , 91 ], Bolivia (3 cases) [ 92 ], and Uruguay (1 case) [ 93 ]. In Brazil, most cases came from the Amazon region (states of Pará, Rondonia, and Amazon), Maranhão state (northeast region), in addition to the Central-West Region (Mato Grosso) and South Regions (states of Paraná and Rio Grande do Sul) [ 50 – 54 , 56 – 58 , 62 , 68 – 70 ]. Venezuela is an important endemic area in South America, and the disease is found throughout the country, with the states of Falcón, Lara, and Zulia standing out [ 44 , 45 , 48 ].…”

“…The presence of immunosuppressive diseases at the time of diagnosis of CBM was reported in only 16 (0.2%) cases, with solid organ transplantation the most common condition (kidney, heart transplantation), followed by HIV infection, rheumatoid arthritis, systemic lupus erythematosus, bladder neoplasia, celiac disease, pernicious anemia, and non-Hodgkin lymphoma [ 66 , 68 , 92 , 148 , 170 , 229 ]. Concomitant infection diseases were reported in 19 cases of CBM, including mycetoma (5 cases), leprosy (5 cases), cutaneous filariasis (3 cases), paracoccidioidomycosis (2 cases), cutaneous histoplasmosis (1 case), syphilis (1 case), actinomycosis (1 case) and visceral leishmaniasis (1 case) [ 19 , 50 , 54 , 56 , 60 , 65 , 68 , 108 , 121 , 157 , 158 , 170 ].…”

“…Surgical debridement as adjuvant therapy was described in additional 191 cases [ 35 , 37 , 39 , 47 , 50 , 100 , 110 , 113 , 165 , 170 , 182 , 204 , 212 ]. Itraconazole was the antifungal therapy mostly used in all continents, being reported in 318 patients, followed by treatment with terbinafine that was used by 87 patients, especially in India, China, and Madagascar [ 18 , 65 , 67 , 68 , 70 , 77 , 99 , 165 , 170 ]. The use of fluconazole, ketoconazole, flucytosine, and systemic or intralesional amphotericin were only sporadically reported.…”

“…A total and partial cure were described in 302 and 188 cases, respectively. Amputation of the affected limb was observed in 14 cases [ 56 , 67 , 68 , 76 , 99 , 103 , 116 , 119 , 167 , 181 ].…”

“…Although the diagnosis of CBM does not rely on expensive and sophisticated laboratory tools, the disease remains neglected by all health systems, making the time of diagnosis too long (mean of 9 years). This aspect certainly impacts in morbidity, including disease progression, risk of superinfection and malignant transformation [ 8 , 56 , 68 , 99 , 167 , 175 , 240 , 241 , 242 ]. Considering the insidious progression of the fungal disease, patients continue their labor and social activities for many years before having the diagnosis made [ 1 , 3 , 5 , 48 , 176 ].…”