Neglected Fungal Zoonoses: Hidden Threats to Man and Animals

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Neglected fungal zoonoses: hidden threats to man and animals

S. Seyedmousavi1,2,3, J. Guillot4, A. Tolooe5, P. E. Verweij2 and G. S. de Hoog6,7,8,9,10 1) Department of Medical Microbiology and Infectious Diseases, Erasmus MC, Rotterdam, 2) Department of Medical Microbiology, Radboud University Medical Centre, Nijmegen, The Netherlands, 3) Invasive Fungi Research Center, Mazandaran University of Medical Sciences, Sari, Iran, 4) Department of Parasitology- Mycology, Dynamyic Research Group, EnvA, UPEC, UPE, École Nationale Vétérinaire d’Alfort, Maisons-Alfort, France, 5) Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran, 6) CBS-KNAW Fungal Biodiversity Centre, Utrecht, 7) Institute for Biodiversity and Ecosystem Dynamics, University of Amsterdam, Amsterdam, The Netherlands, 8) Peking University Health Science Center, Research Center for Medical Mycology, Beijing, 9) Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China and 10) King Abdullaziz University, Jeddah, Saudi Arabia

Abstract

Zoonotic fungi can be naturally transmitted between animals and humans, and in some cases cause signiﬁcant public health problems. A number of mycoses associated with zoonotic transmission are among the group of the most common fungal diseases, worldwide. It is, however, notable that some fungal diseases with zoonotic potential have lacked adequate attention in international public health efforts, leading to insufﬁcient attention on their preventive strategies. This review aims to highlight some mycoses whose zoonotic potential received less attention, including infections caused by Talaromyces (Penicillium) marneffei, Lacazia loboi, Emmonsia spp., Basidiobolus ranarum, Conidiobolus spp. and Paracoccidioides brasiliensis. Clinical Microbiology and Infection © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Keywords: Animal, fungi, human, mycoses, neglected, zoonoses Article published online: 11 March 2015

animal populations [4]. Although zoonotic agents can be Corresponding author: Seyedmojtaba Seyedmousavi, Department transmitted from an infected host to others, inter-human of Medical Microbiology and Infectious Diseases, Erasmus MC, P.O.Box. 2040, 3000 CA, Rotterdam, The Netherlands transfer is uncommon. E-mail: [email protected] From a global prospective, zoonotic infections have been recognized for many centuries, and account for the majority of emerging and re-emerging infectious diseases, worldwide [5,6]. It has been shown that zoonoses occur due to increased con- Introduction tact between humans and animals as a by-product of develop- ment, industrialization and encroachment on wildlife habitats, Depending on the source of infections, zoonoses are resulting in a dynamic upward trajectory of these diseases [7]. described as infectious diseases that can be naturally trans- Fungal infections associated with zoonotic and or sapronotic mitted between vertebrate animals and man [1]. The causative transmission are an important public health problem worldwide agent may be a bacterium, a virus, an ectoparasite, a helminth, [8]. A number of these infections are among the group of the most a protozoa, or a fungus [2].Ananimalcanbeeitherreservoir common fungal diseases, such as: dermatophytosis [9],sporotri- or mechanical vector of zoonotic pathogens, therefore the chosis [10,11] and histoplasmosis [12]. Within this context, it is transmission may be direct or indirect [3]. In most cases, many however notable that some fungal diseases with zoonotic potential wild and domesticated animals (including their faeces and soil have lacked adequate attention in international public health ef- ﬁ in their burrows) play an essential role in maintaining the forts, leading to insuf cient attention on their preventive strategies. infection in nature and contribute in varying degrees to the In this paper, we provide an overview of neglected fungal distribution and actual transmission of infection in human and pathogens that could be carried and transmitted between

Clin Microbiol Infect 2015; 21: 416–425 Clinical Microbiology and Infection © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rightsreserved http://dx.doi.org/10.1016/j.cmi.2015.02.031 CMI Seyedmousavi et al. Neglected fungal zoonoses 417

vertebrate animals and people. Their aetiological agents, ecol- marneffei is a dimorphic fungus exhibiting a mycelial form at 25° ogy and geographical distribution, current epidemiology, type of C and a yeast form at 37°C. Upon tissue invasion, P. marneffei diseases in humans and animals, source of infection and mode of undergoes a morphological phase transition from saprobic transmission will be discussed. mould to yeast form that capably evades the host immune system [19]. For phylogenetic reasons the fungus was renamed as Talaromyces marneffei, underlining its remote distance to Fungal zoonoses versus sapronoses saprobic Penicillium species [20,21].

From an evolutionary viewpoint, mycotic infectious agents can Ecology and source of infection be either true pathogens or opportunists [13], and from the same The fungus may have a natural habitat in soil in areas of perspective pathogens can be divided into environmental path- southern China and South-East Asia where it is endemic ogens (having a saprobic but infectious phase in the environment) [18,22]. Talaromyces marneffei was originally isolated from the and obligatory pathogens (having host-to-host transmission). bamboo rat, Rhizomys sinensis, in 1956 [19]. Since then, addi- Systemic environmental pathogenic fungi may produce invasive tional studies demonstrated that three other bamboo rat spe- forms in infected tissue, such as the spherule in Coccidioides or cies may act as reservoirs: Rhizomys pruinosus, Rhizomys intracellular yeast in Histoplasma [12]. Nearly all fungi are able to sumatrensis and the reddish-brown subspecies of Cannomys thrive in the environment for extended periods, but pathogens badius. Within these rodent species, the prevalence of infection have an evolutionary advantage of the use of a vertebrate vector varies widely across South-East Asia [23,24]. In addition, more during a part of their life cycle. Often an animal other than recently, dogs have been suggested as a possible reservoir for humans is the prime target of the fungus, with humans as non- T. marneffei [25]. optimal hosts. Infections originating from an animal are termed zoonoses [1]. The clinical course of systemic pathogens can be Epidemiology in humans fi fatal in hosts with severe impairment of acquired immunity, but in The infection is recognized as an AIDS-de ning opportunistic healthy hosts the infection is often relatively mild. infection [26,27] in regions where the fungus is endemic. In In contrast, opportunistic fungi have a preferred habitat in- Thailand Chiang Mai province, it is the third most common dependent from the living hosts [13]. Factors enabling survival HIV-related opportunistic infection (after tuberculosis and in human tissue are purely coincidental. Infections may never- cryptococcosis) [18,27,28]. Penicilliosis affects all ages and both theless occur repeatedly from a single source, and we then sexes, although 90% of the cases reported in the literature are speak of sapronoses [14]. Infection of the non-preferred human male [29]. Notably, the risk of infection is not restricted to host decreases fitness of the fungus. The fungus is poorly those living in areas where it is endemic. HIV-infected in- adapted to this unexpected habitat and therefore may provoke dividuals who travelled to areas of endemicity have also become a strongly inflammatory response, which in patients with severe infected by T. marneffei [30]. Of note, the mortality rate of impairment of their innate cellular immunity may be fatal. untreated T. marneffei infections in HIV-infected patients is Table 1 shows the list of clinically significant fungi with 100% [31]. zoonotic potential that can cause considerable medical, veterinary and/or public health problems. Some of these fungi and Disease in humans corresponding infections have been extensively investigated in In patients who are not immunocompromised, most cases of the literature [8–12,15–17]. Here we discuss the fungal path- penicilliosis show generalized lymphadenopathy, fever, weight ogens whose zoonotic potential is neglected, including: Talar- loss, anaemia and a non-productive cough, which may strongly omyces (Penicillium) marneffei, Lacazia loboi, Emmonsia spp., resemble histoplasmosis, cryptococcosis and tuberculosis [32]. Conidiobolus spp., Basidiobolus ranarum and Paracoccidioides In HIV-infected patients, the disease is usually disseminated, brasiliensis. affecting skin, reticuloendothelial system, lung and gut. Other tissues can be involved in the disease such as liver, spleen, skin and mucosa, which are the most commonly affected tissues. In Penicilliosis contrast to histoplasmosis and tuberculosis, adrenal involvement and central nervous system infections are uncommon. The molluscum contagiosum-like lesions of skin and mucosa Penicilliosis is caused by the emerging pathogenic fungus Peni- indicate disseminated disease [29]. Most patients acquire skin cillium marneffei that usually causes a fatal disseminated disease lesions on the face and neck. Chest radiographs show patchy in immunocompromised individuals, especially those with hu- infiltration and sometimes abscess formation. man immunodeficiency virus (HIV) infection [18]. Penicillium

Clinical Microbiology and Infection © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved, CMI, 21,416–425 418 lnclMcoilg n neto 05Erpa oit fCiia irbooyadIfciu iess ulse yEsve t.Alright All Ltd. Elsevier by Published Diseases. Infectious and Microbiology Clinical of Society European 2015 © Infection and Microbiology Clinical TABLE 1. Medically important fungi with the potential of zoonotic transmission to humans

Probable means of

transmission to Clinical signs of disease in Infection and Microbiology Clinical Aetiological agent Disease Known distribution humans Target animals animals Clinical signs of disease in human

Microsporum spp., Dermatophytosis Worldwide Direct contact with All domesticated Classical ring lesion with central Tinea capitis, Tinea barbae, Tinea faciei, Tinea Trichophyton spp. infected animals or mammals and healing and crusts at the corporis, Tinea cruris, Tinea ungium, Tinea material sometimes wildlife peripheral area, some degree pedis, Tinea manum, Tinea of folliculitis Sporothrix schenckii Sporotrichosis Worldwide Work-related trauma, Cats; occasionally Localized cutaneous, Fixed cutaneous, lymphocutaneous, Sporothix brasiliensis scratches or bites dogs, horse, cow, lymphocutaneous and osteoarticular and disseminated infection from animals camel, dolphin, goat, disseminated infection mule, bird, pig, rat, armadillo Mallasezia spp. Malassezia infection Worldwide Malassezia yeasts are Domestic animals such Dermatitis, alopecia, stenosis, Chronic superficial disease of the skin (pityriasis) commensal of as dogs, cats, cows, otitis externa (pityriasis versicolor), folliculitis, human skin (part of sheep, pig, horse, seborrhoeic dermatitis and dandruff, the normal wild animals held in fungaemia microbiota) captivity, and 2015 May 5, Number 21 Volume , animals from wildlife Cryptococcus neoformans, Cryptococcosis Worldwide Mainly by inhalation od Wide variety of Focal or disseminated infection, Cutaneous, ocular, pulmonary and central Cryptococcus gattii fungus, occasionally mammals, birds, affecting a single organ system nervous system involvement through breaks in reptiles and or many, central nervous the skin amphibians system involvement Penicillium (Talaromyces) Penicilliosis Southern China Unknown Bamboo rats, domestic Skin dermatitidis, rhinitis, otitis Non-specific clinical signs (generalized marneffei and South-East Asia animals such as externa and disseminated lymphadenopathy, molluscum contagiosum- dogs, cats infection like lesions of the skin and mucosa) and disseminated infection Lacazia loboi Lobomycosis South and Central Trauma Dolphins Granulomatous dermatitis Granulomatous dermatitis America, United States, Canada, Europe, South Africa Emmonsia spp. Adiaspiromycosis Case reports from Asia, Inhalation of the fungus Wild rodents Deep mycoses Lung and disseminated disease Australia, Europe, North America Conidiobolus coronatus, Entomophthoromycosis Tropical countries of Africa, Traumatic Horses, dogs, sheep Cutaneous and disseminated Chronic subcutaneous and invasive infection Conidiobolus incongruus, Asia, United States implantation or infection Basidiobolus ranarum and Europe inhalation of the fungus Histoplasma capsulatum Histoplasmosis Worldwide (endemic in Inhalation of the fungus Cattle, sheep, horses Non-specific signs (chronic Chronic progressive lung disease, chronic Mississippi and Ohio gastrointestinal infection) and cutaneous or systemic disease or an acute River valleys in USA) disseminated infection fulminating fatal systemic disease Coccidioides immitis, Coccidioidomycosis Southwestern USA, Inhalation of Dogs, llamas, non- Asymptomatic to severe and Cutaneous, pulmonary, disseminated infection Coccidioides posadasii northern Mexico, arthroconidia and human primates, fatal infection Central and South America skin trauma cats, horses, domesticated or wild mammals, snakes Paracoccidioides brasiliensis, Paracoccidioidomycosis South America Inhalation of the Dogs, domesticated Non-specific clinical signs Mucocutaneous, pulmonary or disseminated Paracoccidioides lutzii fungus, injuries of and wild animals depending on the organ infection the skin and mucosal (armadillos and involved (lymphadenomegaly, reserved, s membranes monkeys) apathy, and hepatosplenomegaly) Blastomyces dermatitidis Blastomycosis Worldwide (endemic in Inhalation of airborne Dogs, cats, horses, Cutaneous, pulmonary, systemic Cutaneous, pulmonary, disseminated infection North American continent, conidia marine mammals infection (granulomatous and suppurative lesions in

CMI autochthonous in Africa, lung, skin and bones) South America and Asia ,

21 Pneumocystis carinii (mammals), Pneumocystosis Worldwide Inhalation of airborne Rodents, dogs, cats, Lethal pneumonia in immune Asymptomatic, interstitial pneumonia,

,416 Pneumocystis jirovecii (Human) conidia cattle debilitated animals progressive pneumonia (in immunocompromised hosts) – 425 CMI CMI Seyedmousavi et al. Neglected fungal zoonoses 419

Disease in animals than 75% [41]. The calculated prevalence of lobomycosis is Penicilliosis is a rare infection in domestic animals such as dogs 3.05/10 000 inhabitants in the Amazon region of Brazil [42,43]. and cats [25]. Clinical signs of infection include skin dermatitis, Most patients diagnosed have been in the Amazon basin and rhinitis and otitis externa [33]. Symptomatic animals have nasal countries of South and Central America [44]. There have also discharge and ulceration of external nares and epistaxis. How- been imported cases in the USA, Canada, Europe and South ever, up to 40% of seemingly normal dogs will have a nasal swab Africa [38]. positive for T. marneffei on culture [25]. In addition, disseminated infections have been reported in dogs, with peripheral lymph- Disease in humans adenopathy [34] and bronchopneumonia [35]. No clinical signs Lobomycosis does not affect the general health of the patient have been reported in naturally infected bamboo rats [20]. The [43]. Patients often report a bite or sting from an arthropod, prevalence of infection varies widely across South-East Asia, snake or stingray, or trauma from a cutting instrument. The suggesting that there are regional variations in the endemicity of clinical manifestations of lobomycosis are pleomorphic lesions, infection or there are geographical variations in the predisposi- dermal nodules, either lenticular or in plaques, which can be tion to infection within different species of bamboo rats [18]. either hyperpigmented or hypopigmented (Fig. 1). The lesions are generally painless, although pruritus and dysaesthesia have Mode of transmission been occasionally described. The cheloid-like lesions can A lot is still unknown about the natural reservoir and route of resemble nodular leprosy or leishmaniasis, or other subcu- transmission of T. marneffei. While bamboo rats are a natural taneous mycoses (sporotrichosis, chromomycosis, para- reservoir, they are generally not in close contact with humans coccidioidomycosis), cheloids and malignant tumours [37]. and there is no evidence of direct transmission from rats to humans [25]. However, bamboo rats and HIV-positive patients Disease in animals have been found to share genetically similar strains of Lobomycoses have been described in two species of dolphins T. marneffei, suggesting that rat-to-human transmission might be (Delphinidae): the common bottlenose dolphin (Tursiops trun- possible or co-infection from a common but still unidentiﬁed catus) from the Atlantic coast of the USA and Europe, and the source [36]. Infected rats appear healthy [24]. In addition, Guyana dolphin (Sotalia guianensis) from the Surinam River es- recent studies suggested that domestic animals such as dogs tuary [45]. The lesions are characterized by greyish, white to might be another possible reservoir for T. marneffei in the re- pink verrucous lesions that may ulcerate and form large plaques gions where it is endemic [25]. To date T. marneffei has never (Fig. 2) [46]. The disease progresses over years and may been recovered from environments other than those that are disﬁgure large areas of the body [38]. The prevalence of intimately associated with bamboo rats. lobomycosis in bottlenose dolphins of Florida is reported to be 6.8% [47].

Lobomycosis Mode of transmission The possibility of zoonotic transmission of this disease is still Lobomycosis is a rare chronic, granulomatous, fungal infection of under investigation. However, it is highly probable that the the skin and subcutaneous tissues [37,38]. Despite important transmission occurs by direct contact with infected animals advances having been made through the use of updated molecular following abrasion or trauma of the skin [40]. Lobomycosis biology techniques, the aetiological agent of lobomycosis has never can be transmitted directly from human-to-human under been cultured and grown in vitro. In 1999, Taborda et al. proposed accidental circumstances [48]. Dolphin-to-human transmission the agent in a new genus, Lacazia,callingitLacazia loboi [39]. of lobomycosis has also been reported in an aquarium attendant who had had close physical contact with an affected Ecology and source of infection dolphin [49]. Soil and vegetation are believed to be the chief habitat of the fungus. However, increasing reports of the disease in aquatic Adiaspiromycosis mammals such as the dolphin has shifted attention to water and the aquatic environment [38,40]. Adiaspiromycosis is a rare chronic pulmonary infection caused Epidemiology in humans by dimorphic fungi from the genus Emmonsia within the family The disease has been diagnosed generally in tropical areas with Ajellomycetaceae [50–52]. The infection is characterized by an average temperature of 24°C and relative humidity higher the presence of very large adiaspores in the lungs [53]. Inhaled

FIG. 1. Clinical manifestations and laboratory features of lobomycosis in humans. Reproduced from reference Paniz-Mondolfi et al. 2012 [38] with permission of the publisher. Keloid-like lesions over the upper limb of a patient with lobomycosis (a); multiple confluent papules, plaques and nodule lesions admixed with small verrucous areas on the foot of a patient with lobomycosis (b, c); Grocott methamine silver-stained section showing multiple isolated and chained yeasts (magnification × 40) (d). conidia of Emmonsia produced from the mycelial phase growing Currently, two species of Emmonsia are known as main at ambient temperatures fail to germinate in the lung, and agents of pulmonary diseases in human and animals: instead simply increase in volume to form thick-walled, non- Emmonsia crescens and Emmonsia parva [51].However,anew replicating adiaspores [54]. species, ‘Emmonsia pasteuriana’, has been recently described

FIG. 2. Clinical manifestations and laboratory features of lobomycosis in a dolphin. Reproduced from reference Paniz-Mondolfi et al. 2012 [38] with permission of the publisher. Extensive white greyish proliferating lesions with keloidal and verrucous aspect forming rosettes on the dorsal (a), flanks (b) and fin (c) of a dolphin; Grocott methamine silver-stained section from a skin biopsy specimen of a dolphin showing abundant yeast cells individually and in chains connected by thin tubular bridges (magnification ×400) (d).

causing disseminated cutaneous infection in HIV-infected Entomophthoromycosis patients [55].

Ecology and source of infection Entomophthoromycosis is a chronic subcutaneous infection Emmonsia species are commonly found in soil but also occur in caused by zygomycetes of the order Entomophthorales: Con- mammalian species living in close association with soils such as idiobolus coronatus, Conidiobolus incongruus and Basidiobolus rodents, insectivores, otters, stoats, weasels, moles and ground ranarum [58]. squirrels [56]. Among species in this genus, E. crescens is Ecology and source of infection widespread in continental Europe and UK, whereas E. parva is Both Conidiobolus spp. and B. ranarum are generally considered found mainly in some xerothermic regions, including parts of as saprobe distributed in plant debris and soil of tropical areas the Americas, Central Asia and Africa [56]. [59]. In addition, these fungi are present as a commensals in the fi Epidemiology in humans gastrointestinal tract of amphibians, sh, reptiles and insectiv- In humans, adiaspiromycosis is a rare pulmonary infection. orous bats [60]. Disseminated pulmonary adiaspiromycosis can progress to Epidemiology in humans respiratory failure and death; however, mortality rates are low The disease occurs sporadically as a result of traumatic im- [53]. There are nearly 200 reports of Emmonsia infections in plantation or inhalation of the fungus that is present in plant human lungs and less than 20 (sub)cutaneous infections in the debris in tropical environments. Both types of entomophthor- literature [53]. omycosis are reported in tropical countries of Africa, Asia, USA Disease in humans and Europe [58]. Gastrointestinal basidiobolomycosis has a 20% Cases of human infection are rare and primarily pulmonary mortality rate despite all of the therapeutic measures [61,62]. conditions similar to that observed in animals, with only a few Disease in humans cases of infection at other sites [53]. The disease is usually Typically, B. ranarum causes subcutaneous infection in immu- localized, asymptomatic and self-limited; however, disseminated nocompetent young adults and rarely involves the gastrointes- fatal cases have been reported [54]. The severity of the adias- tinal tract [61]. Human infection with Conidiobolus species piromycosis in humans depends on the amount of the airborne occurs predominately as chronic rhinofacial mycosis in other- conidial burden inhaled and host immunocompetence, and wise healthy hosts [59]. In addition, invasive con- range from asymptomatic infection through necrogranuloma- idiobolomycosis has been reported in immunocompromised tous pneumonia and even death [54]. patients that can cause endocarditis and widespread fatal Disease in animals dissemination [63]. Emmonsia species have an extremely broad host range and Disease in animals infections have been reported in many species of small Conidiobolomycosis is reported mainly in horses [64], sheep mammals, worldwide [56,57]. Histopathological examination [65,66] and dogs [67]. Ulcerative pyogranulomatous lesions of of the infected animals generally reveals a multifocal extensive the mucosa of the nasopharyngeal tissue, mouth or nodular granulomatous reaction containing oval adiaspores scattered growths of the nasal mucosa and the lips may be seen with irregularly throughout the lungs [57]. The frequency of conidiobolomycosis, similar to those caused by pythiosis and infected animals varies according to geographic area, altitude, lagenidiosis. Disseminated basidiobolomycosis is rare but has habitat, and season. Several studies clearly indicated that been described in dogs and mandrills [68]. almost 30% of all small wild mammals examined in the UK and parts of central and eastern Europe where it is endemic, Mode of transmission had evidence of infection [57], raising the possibility that The transmission dynamics of these fungi is still under investi- sporadic infections might also occur in domestic animals and gation. However, the isolation of Conidiobolus spp. and humans [56]. B. ranarum from reptiles, amphibians and fish, and infection in various animals, strongly suggest interspecific transmission [8]. Mode of transmission Infection due to B. ranarum is thought to occur following Similar to other dimorphic onygenalean fungi, Emmonsia species traumatic implantation of the fungus into the subcutaneous are environmental pathogens, having a life cycle involving soil tissues. Infections with Conidiobolus spp. occur following and vectoring by the animals [50].

inhalation of the fungal spores, which then germinate and continent, and the highest incidence of the disease was regis- induce the invasion of nasal cavity, paranasal sinuses and facial tered in South American countries including Brazil, Argentina, soft tissues. Colombia and Venezuela [72]. However, cases outside of the areas of endemicity continue to be described, in general with long periods of latency, representing endogenous reactivations Paracoccidioidomycosis of the infectious focus previously acquired in endemic regions [73]. The annual prevalence of the disease in areas where it is Paracoccidioidomycosis is an acute to chronic systemic infec- endemic ranges from three or four new cases/1 000 000 pop- tion caused by a thermally dimorphic fungus, Paracoccidioides ulation to one to three new cases/100 000 population. Most brasiliensis [12,69] and its relative Paracoccidioides lutzii. patients are males (>90%), agricultural workers, often malnourished, and usually 30–60 years of age [12,72]. Ecology and source of infection The natural habitat of P. brasiliensis, its environmental niche and Disease in humans life cycle in nature remain unknown, but it is presumed that the Following inhalation, P. brasiliensis typically causes asymptomatic fungus is able to survive and proliferate in the soil [69]. The chronic pulmonary infection that disseminates as ulcerative fungus generally enters via the respiratory tract or injuries of granulomata in the mucosal surfaces of the nose, mouth and the skin and mucosal membranes [70]. gastrointestinal tract [69]. In addition to the skin and lymph nodes, the infection may spread to internal organs [12,72]. Epidemiology in humans Symptomatic cases may develop an acute and or sub-acute or Paracoccidioidomycosis is considered to be the third leading chronic pneumonia with clinical features resembling tubercu- cause of death from chronic infectious disease in South America, losis (Fig. 3) [12]. This form of infection is almost always and the mortality rate for paracoccidioidomycosis is 1.65 cases/ observed in children, adolescents, and adults <30 years of age, 1 000 000 population [71]. It is endemic in the American and represents <10% of the cases [69,72,74].

FIG. 3. Clinical manifestations and laboratory features of paracoccidioidomycosis in humans. Reproduced from reference Ameen et al. 2010 [72] with permission of the publisher. Ulcerative lesion with punctate haemorrhagic dots (a); dissemination to the skin, presenting as erythematous papules and plaques, some of which are beginning to ulcerate (b); centrofacial cutaneous and mucosal ulcerative lesions (c); chest radiograph depicting diffuse bilateral nodular opacities in pulmonary Paracoccidioidomycosis (d); direct microscopy of a skin scraping detects fungal cells of paracoccidioidomycosis with thick bi-refringent walls (magniﬁcation × 40) (e); splenic tissue showing the characteristic ‘ship-pilot’s wheel’ (magniﬁcation × 40) (f).

FIG. 4. Clinical manifestations and laboratory features of paracoccidioidomycosis in a dog. Reproduced from reference de Farias et al. 2011 [75] with permission of the publisher. Generalized lymphadenomegaly in submandibular lymph node (a); prescapular lymph node (b); inguinal lymph node (c); popliteal lymph node (d); histological fragment of popliteal lymph node stained with haematoxylin & eosin showing oval structures (e) and stained with periodic acid–Schiff showing the same poorly stained oval structure surround by neutrophils, macrophages and giant cells (f).

Disease in animals critical component of prevention. From a global public health The disease has been demonstrated in domestic [75] and wild prospective, clearly more efforts are needed to raise aware- (armadillos and monkeys) [76,77] animals. Experimental infec- ness of the scale of the problem for neglected zoonotic or tion can be obtained in dogs [78,79]. Naturally acquired infec- sapronotic fungi in order to better define the burden, distri- tion is also reported in dogs with emaciation, bution, mortality and socio-economic consequences, and also lymphadenomegaly and hepatosplenomegaly (Fig. 4) [75,80]. provide an integrated platform of prevention and control strategies. Mode of transmission The epidemiology of the disease indicates a rural predilection, consistent with most zoonotic infections [34]. The infection, in Transparency declaration both humans and other animals, is transmitted in an airborne manner by inhalation of conidia present in the environment SS has received travel grants from Astellas Pharma B.V. and [75]. Given that armadillos can harbour the fungus at high Gilead Sciences. JG has served as consultant to Lilly Elanco, frequencies, this suggests their role as a wild host in the Merial, MSD, Novartis, and Bayer. AT and GSdH have no epidemiological cycle of the disease [76]. In addition, in areas of conflict of interests. PEV has served as consultant and has endemicity, it has been shown that infected armadillos and received research grants from Astellas, Basilea, Gilead Sciences, humans share genetically similar strains of P. brasiliensis [81], Merck, and Pfizer. which also suggests a zoonotic role for this infection.

Acknowledgements Conclusions

This publication was prepared as a collaborative study between The importance of fungal zoonotic or sapronotic infections the Department of Medical Microbiology, Radboud University has been demonstrated. There is no doubt that these types of Medical Centre, Nijmegen, the Netherlands, the Dynamyc fungi need to be controlled. Control of human exposure to Research Group, Maisons-Alfort, Créteil, France, and the Vet- animal reservoirs can protect susceptible populations and is a erinary Mycology and Black Yeast Working groups of the

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