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Series Fungal Infections 4 Neglected Endemic Mycoses Series Fungal infections 4 Neglected endemic mycoses Flavio Queiroz-Telles, Ahmed Hassan Fahal, Diego R Falci, Diego H Caceres, Tom Chiller, Alessandro C Pasqualotto Fungi often infect mammalian hosts via the respiratory route, but traumatic transcutaneous implantation is also an Lancet Infect Dis 2017 important source of infections. Environmental exposure to spores of pathogenic fungi can result in subclinical and Published Online unrecognised syndromes, allergic manifestations, and even overt disease. After traumatic cutaneous inoculation, July 31, 2017 several fungi can cause neglected mycoses such as sporotrichosis, chromoblastomycosis, mycetoma, http://dx.doi.org/10.1016/ S1473-3099(17)30306-7 entomophthoramycosis, and lacaziosis. Most of these diseases have a subacute to chronic course and they can become See Online/Series recalcitrant to therapy and lead to physical disabilities, including inability to work, physical deformities, http://dx.doi.org/10.1016/ and amputations. For many years, paracoccidioidomycosis was considered the most prevalent endemic systemic S1473-3099(17)30303-1, mycosis in the Americas, but this situation might be changing with recognition of the worldwide presence of http://dx.doi.org/10.1016/ Histoplasma capsulatum. Both paracoccidioidomycosis and histoplasmosis can mimic several infectious and non- S1473-3099(17)30304-3, http://dx.doi.org/10.1016/ infectious medical conditions and lead to death if not recognised early and treated. Cutaneous implantation and S1473-3099(17)30309-2, systemic mycoses are neglected diseases that affect millions of individuals worldwide, especially in low-income http://dx.doi.org/10.1016/ countries where their management is suboptimum because challenges in diagnosis and therapeutic options are S1473-3099(17)30316-X, substantial issues. http://dx.doi.org/10.1016/ S1473-3099(17)30442-5, http://dx.doi.org/10.1016/ Introduction Cutaneous implantation mycoses S1473-3099(17)30443-7, and Neglected tropical diseases (NTDs) are a diverse series Implantation mycoses are a heterogeneous group http://dx.doi.org/10.1016 of endemic diseases that prevail in tropical or of fungal diseases, which present months or years after S1473-3099(17)30308-0 subtropical climates worldwide. They are infectious initial infection.5 This group includes sporotrichosis, See Online/Comment http://dx.doi.org/10.1016/ diseases usually affecting people living in low-income chromoblastomycosis (chromomycosis), mycetoma, S1473-3099(17)30319-5 countries in Asia, Africa, and Latin America. NTDs lacaziosis (lobomycosis), and entomophthoramycosis This is the fourth in a Series of usually affect populations that do not travel abroad, (subcutaneous zygomycosis). These diseases primarily eight papers about fungal with little political voice and low visibility. According to affect the cutaneous and subcutaneous tissues, but in infections WHO, a high prevalence of NTDs is associated with most cases they also involve adjacent structures such as Hospital de Clínicas, Federal poverty and other disadvantageous conditions.1 the lymphatics, cartilage, fascia, joints, and bones.5–8 University of Paraná, Curitiba, Individuals affected by NTDs are often the world’s Most implantation mycoses occur in tropical and Brazil (F Queiroz-Telles MD); Mycetoma Research Centre, poorest populations, often living in remote rural areas, subtropical regions of the world and usually affect University of Khartoum, urban slums, or conflict zones. Although progress has individuals involved in outdoor activities such as Khartoum, Sudan been made for some NTDs, many of these diseases are agriculture, hunting, mining, and lumbering. Less (Prof A H Fahal); Infectious Diseases Service, Hospital de not on the public health radar, by contrast with other commonly, children, travellers, and visiting workers Clínicas de Porto Alegre, Porto 1 5–9 high-profile global diseases. WHO and other develop implantation mycoses. These diseases mimic Alegre, Brazil (D R Falci PhD); organisations such as the G-FINDER project recognise several infectious and non-infectious disorders and their Centro Universitário La Salle, several helmintic, protozoan, bacterial, and viral burden is underestimated because of a lack of diagnosis Canoas, Brazil (D R Falci); Mycotic Diseases Branch, infections as NTDs, but most fungal infections have in the areas where they occur (table 1). Centers for Disease Control and not yet reached such status. However, in 2016, Prevention, Atlanta, GA, USA mycetoma was included as the only fungal disease in Sporotrichosis (D H Caceres PhD, T Chiller MD); the WHO list of NTDs, and chromoblastomycosis was Sporotrichosis is the most prevalent and widespread Santa Casa de Misericórdia de 1–4 Porto Alegre, Porto Alegre, added in 2017. implantation mycosis in the world. For more than a Brazil (A C Pasqualotto MD); and The burden and medical impact of fungal diseases century, this disease was believed to be caused by a single Universidade Federal de are largely unknown and often underestimated, species, Sporothrix schenckii, but more recent molecular Ciências da Saúde de Porto especially for endemic fungal infections. Endemic phylogenetic methods have shown that this fungus has a Alegre, Porto Alegre, Brazil (A C Pasqualotto) mycoses can be divided into two groups: implantation wide spectrum of biodiversity with several sibling species. Correspondence to: (subcutaneous) mycoses in which the fungal agents These species vary by virulence, mode of transmission, Dr Flavio Queiroz-Telles, generally infect transcutaneous wounds; and systemic clinical manifestations, and response to therapy. The Department of Public Health, mycoses, in which thermodimorphic fungi are inhaled taxonomy of the Sporothrix genus has recently been Federal University of Paraná, causing infection and can disseminate. Fungal revised and is now classified according to its phenotypic Curitiba, Paraná 80060-240, Brazil [email protected] (mycotic) keratitis is an implantation mycosis and and biochemical characteristics together with its fulfils criteria for an NTD, although it is a global molecular profile. The original S schenckii sensu lato problem with occasional cases in high-income non- contains clinically relevant cryptic species with diverse tropical countries; this disease will not be addressed in geographical distribution: S schenckii sensu stricto and this paper. Sporothrix globosa cause sapronotic sporotrichosis www.thelancet.com/infection Published online July 31, 2017 http://dx.doi.org/10.1016/S1473-3099(17)30306-7 1 Series epidemiological pattern of transmission. The highest Key messages estimated prevalence rates of infection range from 0·1% 5,31 • The burden and medical importance of endemic mycoses remain underestimated. to 0·5% in some Latin American countries. A few • Most of the serious endemic fungal infections have not yet reached the status of hyperendemic areas of sporotrichosis have been 31,37–40 neglected diseases as defined by WHO. identified—namely, in Mexico, Peru, and China. • The most relevant implantation mycoses are sporotrichosis, chromoblastomycosis, Case reports from several countries have been published, and mycetoma. Most of these infections occur in underdeveloped tropical and but outbreaks and clusters of cases can occur. The largest subtropical regions of the world. reported sporotrichosis outbreak involved more than 41 • Sporotrichosis caused by Sporothrix schenckii sensu lato is a sapronosis and occurs 3000 miners in South Africa during the 1940s. However, worldwide, whereas sporotrichosis caused by Sporothrix brasiliensis is an a larger outbreak of cat-transmitted sporotrichosis is anthropozoonosis affecting human beings, cats, and dogs. The disease can occur as currently occurring in Brazil. In the state of Rio de outbreaks that might affect thousands of people. Janeiro, the number of human cases jumped • Chromoblastomycosis is a potentially debilitating disease caused by several melanised from 759 between 1998 and 2004 to more than 4000 in 2014, fungi found in plants or soil. It has an occupational risk and diagnosis relies on mostly resulting from feline transmission. This outbreak 34,42,43 visualisation of the typical muriform (sclerotic) cells by direct microscopy. is expanding to neighbouring Brazilian regions • Mycetoma causes high morbidity and affects poor populations living in remote areas (figure 1). of the world. This disease causes painless subcutaneous masses, sinus formation, and occasional discharge of grains. Clinical presentation • Entomophthoramycosis, also known as subcutaneous zygomycosis, causes chronic Most patients present with cutaneous forms of destructive lesions that can be diagnosed by a combination of microscopy, culture, sporotrichosis that include fixed cutaneous (25%) and 6 and histopathology. lymphocutaneous (55%) involvement. Cutaneous dis- • Lacaziosis, also known as lobomycosis, is an exotic and mysterious disease. Most seminated forms are reported in immunocompetent and 44 affected individuals are from the Amazon region. Lacazia loboi, which infects human immunosuppressed individuals. Extracutaneous involve- beings and dolphins, has never been cultivated in vitro. It is recalcitrant to antifungal ment has rarely been described, notably pulmonary, therapy. osteoarticular, ophthalmic, and CNS infection. Meningitis • Histoplasmosis and paracoccidioidomycosis are the most relevant neglected endemic is more frequently seen in immunocompromised systemic mycoses in Latin American countries. These diseases
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