Infection of bats with Histoplasma species

Abstract

Histoplasma species infect humans and animals, notably bats. Histoplasma species are thermally dimorphic fungi existing in mycelial form in the natural environment and in yeast form in infected tissues. In this narrative literature review, we summarize the occurrence of Histoplasma spp. in different species of bat tissues (n = 49) and in soil admixed with bat guano where the species of bat dwelling nearby has been identified (an additional 18 species likely infected) to provide an up-to-date summary of data. Most positive isolations are from the Americas and Caribbean, with some studies from Thailand, Malaysia, Nigeria, Slovenia, France, and Australia. We also summarize some of the early experimental work to elucidate pathogenicity, latency, immune response, and faecal excretion in bats. Given the recent recognition of the global extent of histoplasmosis, thermal dimorphism in Histoplasma spp., and global heating, additional work on understanding the complex relationship between Histoplasma and bats is desirable.

Introduction

A genus of pathogenic fungi shared between humans and bats is Histoplasma spp. Initial work on the natural habitat of Histoplasma spp. focused on chicken houses in the 1940’s and 1950’s.^1,2 The first link to bats came from positive cultures from soil in a bat cave in Venezuela in 1956,³ and then from soil in South Africa, Tanzania, and Trinidad.^4–6 The first isolation from a bat (Chilonycterus rubiginosa fusca) came from Panama in 1962.⁷Histoplasma duboisii has only been isolated once from bats in Nigeria.⁸

Histoplasma capsulatum is a thermally dimorphic saprobic fungus that produces microconidia and macroconidia borne on mycelium.^9,10 When suitable microclimatic conditions of temperature (22°C–29°C) and annual rainfall of 35–50 inches are present, and soil is enriched with avian excreta or bat guano, the fungus proliferates abundantly. Birds don't get infected with H. capsulatum, whereas bats can be infected and can disperse the fungus creating new foci of infection.¹¹ Infection is acquired by inhalation of microconidia or hyphal fragments of H. capsulatum from environmental sources such as soil or dried avian or bat excreta. The rapidly changing global environment will inevitably alter some of these interactions.

Following inhalation by a human, the infectious propagules of H. capsulatum are engulfed by pulmonary macrophages, wherein they convert to the yeast form of the fungus and multiply and traverse to hilar and mediastinal lymph nodes.^9,10 The yeast form of the fungus then gets access to the blood circulation system and disseminates swiftly across various organs of the body. After approximately two weeks of exposure, the macrophages become fully fungicidal, and cellular immunity increases, with defense against the fungal particles.¹⁰ This process can lead to necrosis at the sites of infection in the lungs, liver, spleen, lymph nodes, bone marrow, adrenal glands, and mucocutaneous membranes, and acute, sub-acute, or chronic disseminated histoplasmosis, acute pulmonary histoplasmosis, or latency. The human pathogenic life cycle of H. duboisii is less well understood.^12,13 The full life cycle of H. capsulatum has been partially elucidated in experimental bat infections.^14–17

Investigations by several workers have shown that bat guano and bird droppings are the most common sources of Histoplasma capsulatum, the etiological agent of histoplasmosis, which has a worldwide distribution.^11,18–20 The fungus is found either in spaces where bat guano is abundant or in open spaces such as public parks and home yards, where avian droppings are frequently found. Bat and avian excreta provide nutrients necessary for fungal growth and with soil and environmental conditions, humidity, and temperature, constitute the ecologic niche of this microorganism.^1,19,21 Bats are among the few infected mammals that contribute to the maintenance of this fungus in natural foci. Our aim was to review the species of bats that have been reported to be infected by Histoplasma spp. and to link those reports with the bats’ locations. The last time this topic was reviewed was in 1981 by Hoff and Bigler.¹⁸

Materials and Methods

An exhaustive search of the literature, using PubMed, MEDLINE, Med Facts, and LILACS (a database Latin American and Caribbean Health Sciences Literature) was made for all years to September 10^th 2022 using different sets of keywords, viz. histoplasmosis, bats, caves, Histoplasma capsulatum var, capsulatum, Histoplasma capsulatum var. duboisii. The Boolean operator ‘AND’ was used for combining and narrowing the searches. Cross-references were also accessed to extract information relevant for incorporation into the review. Review of papers that were identified in searches also identified references that were not listed online and these were retrieved. No language restriction was applied.

Results

We identified 45 articles describing the isolations of Histoplasma spp. from bats, or detection using histopathology, polymerase chain reaction (PCR) or antigen. A smaller number or articles linked specific bat species to outbreaks in humans, providing inferential evidence of individual bat species infection. The data collected and the important findings found in the survey of literature are described below under different subheadings.

Occurrence of Histoplasma duboisii in bats and environmental sources

The only bat isolation of Histoplasma duboisii is from Nigeria in Nycteris hispida (hairy slit faced bat with long ears) and Tadarida pumila (little free-tailed bat) (Table 1). This was from intestinal contents only of a single bat, but it is not clear which species. Histological examination of the tissue of liver, spleen, and lung from this particular bat and 8 additional bats of Nycteris hispida and Tadarida pumila did not reveal the presence of Histoplasma nor were the cultures from the internal organs of any of the bats examined positive for Histoplasma yeast forms. It is therefore unclear whether this fungus can infect bats.

Table 1.

Association of H. duboisii with bats.

Country	Location	Sample type, No. pos./no. examined	Method of detection	Reference
Nigeria	Ogbunike, Anambra State	Soil admixed with bat guano in a cave. 8/45 were positive.	Culture on mycological media and by intraperitoneal mouse inoculation	Gugnani et al. 19948
Nigeria	Ogbunike, Anambra State	Intestinal contents of bats of the species Nycteris hispida (hairy slit-faced bat) and Tadarida pumila (little free-tailed bat). 1/35 positive from all tested.	Direct plating of serial dilutions of antibiotic treated suspension of soil/bat guano on fungal media supplemented with chloramphenicol and/or cycloheximide. Intraperitoneal inoculation of mice with each suspension. Intestinal contents of 13% of the bats were positive for exoantigen of H. duboisii.	Gugnani et al. 19948

Isolation of Histoplasma capsulatum directly from bats

We have tabulated the species of bats from which H. capsulatum has been directly isolated (Table 2; Supplementary Table 1). We found direct evidence of isolation from bat tissues in 48 species, all but one from the Americas and Caribbean, in studies from 1962 to 2021. Some bat species were sampled and cultures were negative (Supplementary Table 1). Attempts to isolate H. capsulatum from bats in Iran⁴⁴ and Zaire (now Democratic Republic of Congo)⁴⁵ were negative. In some studies, the bat species was not determined.

Table 2.

Bat species and country from which Histoplasma capsulatum has been isolated. This excludes soil and guano samples, even if the roosting bat species was identified.

Species	Common name and additional data	Countries	References
Artibeus hirsutus	Hairy fruit-eating bat only known in Ecuador and Peru	Mexico	Taylor, 199922; Taylor, 201223
Artibeus fimbriatus	Fringed fruit-eating bat	Brazil	Veloso, 201424
Artibeus jamaicensis parvipes	Hairy fruit-eating bat endemic in Mexico	Cuba	D'Escoubet, 197625
Artibeus literatus	Great fruit-eating bat	Brazil	Veloso, 2014,24 Dos Santos, 201826
Brachyphylla nana	Cuban fruit-eating bat found in Cayman Islands and Hispabiola. Prefers to live in deep caves that are often hot and humid	Cuba	D'Escoubet, 197624
Carollia perspicillata	Short-tailed bat found in Central America	Colombia, Panama, Brazil	Klite, 196527; Diercks, 196528; Tesh, 196829; Shacklette, 196930; Hasenclever, 197231 da Silva 202032
Chilonycterus rubiginosa fusca Pteronotus parnellii Pteronotus rubiginosa	Found in flowering trees including purple coral tree Parnell's mustached bat Wagner's Common Mustached Bat	Panama, Belize, Mexico	Shacklette, 19627; Klite, 196527; Diercks, 196528; Shacklette, 196733; Shacklette, 196930; Hasenclever, 197231; Quinones, 197834; Taylor, 199922
Desmodus rotundus	Small leaf-nosed vampire bat native to neotropics	Colombia, Brazil	Diercks, 196528; Tesh, 196829; Shacklette, 196930; Taylor, 201223 Veloso, 201424
Eptescicus brasiliensis	Brazilian brown bat found in neotrpics	Colombia, USA	Tesh, 196829; Emmons, 196635
Eptesicus fuscus dutertreus	Big brown bat commonly found in in heavily forested regions	Cuba	D'Escoubet, 197625
Eumops bonariensis	Dwarf bonneted bat, or Peters' mastiff bat found in leaved dry grasslands.	Brazil	Taylor, 201223
Eumpos glaucinus	Wagner's bonneted bat, found in subtropical forests	Brazil	Veloso, 201424; Dos Santos, 201826
Eumops perotis	Western mastiff bat	Brazil	Dos Santos, 201826
Glossophaga soricina	House bat Pallas's long-tongued bat	Panama, Brazil	Klite, 196527; Diercks, 196528; Shacklette, 196930; Hasenclever, 197231 Veloso, 201424
Histiotus velatus	Tropical big-eared brown bat	Brazil	Velosos, 201424
Lasiurus blossevillii	Southern red bat	Brazil	Velosos, 201424
Leptonycteris curasoae	Southern long-nosed bat found in semiarid and dry forests	?	Taylor, 201223
Leptonycteris nivalis	Greater long-nosed bat living in desert scrub areas	Mexico	Taylor, 199922; Taylor, 201223; Vite-Garin, 202136
Leptonycteris sanborni	Sanborn's long-nosed bat found in caves, rock crevices, old buildings, bridges, mines and trees	USA (Arizona)	Di Salvo, 196937
Lonchophylla aurita	Tomes's or common sword-nosed bat found in forested and sometimes in agricultural area	Panama	Diercks, 196528; Shacklette, 196930
Lonchophylla robusta	Orange nectar bat found in some South American counties	Panama	Shacklette, 196930
Micronycteris megalotis	Little big-eared bat found in wet and dry areas, evergreen forests, and swamps throughout South America	Panama	Klite, 196527
Molussus sp.r	Mastiff bat species	Panama	Shacklette, 196930
Mollosus major	Velvety free-tailed batthat occurs in Central and South America. Also found roosting in houses in urban areas	Panama	Klite, 196527; Hasenclever, 197231
Mollosus mollosus	Pallas’ mastiff bat found in subtropical forests and fields throughout Central and South America	Argentina, Brazil	Taylor, 201223 dos Santos, 201826 Veloso, 201424
Mollosus rufus (Molussus afer)	Black mastiff bat found throughout Central and South America. Can be found in dark places like rock fissures, in caves, roofs and cracks of buildings	Mexico, Brazil	Taylor, 201223 Veloso, 201424
Mormoops blainvillei	Antillean ghost-faced bat found in caves throughout the world	Cuba	D'Escoubet, 197625
Mormoops megalophylla	Ghost-faced bat typically found near desert shrubs in Central and South America	Mexico	Taylor, 199922
Myotis austroriparius	Southeastern myotis feeds on a variety of insects, living close to water sources	Florida, USA	Tesh, 196738; Hoff, 198118
Myotis californicus	Californian myotis found in caves, mines, rocky hill sides, under tree bark, on the ground, and in buildings	Mexico	Taylor, 199922
Myotis grisescens	Gray bat that occurs in a limited range in limestone areas of Southeastern USA	USA	Tesh, 196738
Myotis levis	Yellowish myotis	Brazil	Veloso, 201424
Myotis lucifugus*	Little brown bat often uses human made structures, typically roots in caves and mines in winter, and under rocks and piles of wood in summer	USA	Bell cit Emmons, 1966)35
Myotis nigricans	Black myotis	Brazil	Veloso, 201424
Myotis sodalis	Indiana bat occurs in arid habitats, but can use a wide range of roosts	USA	Tesh, 196738
Natalus stramineus	Gray funnel-eared bat, native to the Nearctic and the Neotropics	Mexico	Taylor, 199922
Noctilio labialis	Lesser long-nosed bat, roosts externally on tree trunks or in the branches of trees	Panama	Shacklette, 196930
Nyctalus noctula	Common noctule generally resides in forests, most often found in lowland areas and those with old forests and rivers	France	Gonzalez-Gonzalez, 201339
Nyctinomops laticaudatus	Broad-eared bat or broad-tailed bat	Brazil	Veloso, 201424
Nyctinomops macrotis	Big free-tailed bat	Brazil	Veloso, 201424
Phyllostomus discolour	Pale spear-nosed bat found in mature and secondary rain forest, dry forest, gardens and plantations	Panama, El Salvador	Shacklette, 196930; Klite, 196540
Phyllostomus hastatus	Greater spear-nosed bat occurs in tropical regions of America	Panama	Klite, 196527; Shacklette, 196930; Hasenclever, 197231
Platyrrhinus lineatus	White-lined broad-nosed bat	Brazil	Dos Santos, 201826
Pteronotus suratensis	Taxonomy changed. Mustached bat	Panama	Shacklette, 196930
Tadarida brasiliensis T. brasilensis cynocephala	Mexican free-tailed bat occurs in caves, mine tunnels, old wells, hollow of trees	USA, Mexico, Argentina, Brazil	Ajello, 196741; Bryles, 196942; Emmons, 196635; Gonzalez-Gonzalez, 201243; Taylor, 201223; Veloso, 201424; Vite-Garin, 202136
Tadarida yucatanica	Broad-eared bat occurs in tropical and subtroical forests from coastal Mexico to southern Brazil	Panama	Shacklette, 196930; Hasenclever, 197231
Tonatia biden	Northern long-eared bat	Panama	Shacklette, 196930
Vampyriscus bidens	Bidentate yellow-eared bat	Brazil	Da Silva, 202032

* presumptive identification

These mostly culture-based studies have almost always included analysis of liver and spleen, usually lungs and sometimes intestines and/or intestinal contents. One study of 122 bats randomly captured in Argentina, French Guyana, Mexico found 77% positive by PCR of the lungs only,⁴⁶ and a single Nyctalus noctule bat in France was also positive by PCR from lungs.³⁸ The assumption is that if bat tissues are positive, then the bat is infected. Given the pathology of the intestine showing clumps of yeast and concurrent positive cultures from the intestine demonstrated in Pteronotus (Chilonycteris) rubiginosa,^28,47 this seems a reasonable assumption given the diets of bats. Some bats have histological evidence of infection in various tissues, with negative cultures, others positive cultures, without evidence of fungi histologically.⁴⁴ Such studies have only been done in a limited number of bat species. The relative proportion of organs that were culture positive in several species of bats captured in SE USA (primarily Myotis austroriparius and Myotis grisescens) were lungs (88%), spleen (73%), liver (72%), and faeces (36%).³⁸ Recent studies from Brazil have limited sampling to the lungs and only used PCR for detection.^24,26,32

Experimental infections using intraperitoneal inoculation demonstrated mice to be infectable with very few or a single spore^14,48 and bats were experimentally infected via both intranasal and intraperitoneal routes with inocula as low as 10 infective units intraperitoneally and 100 intranasally.^15–17,46 Experimental infection found differences between species. So Tadarida brasiliensis had an 80% mortality whereas Artibeus lituratus and Pteronotus suapurensis were infectable, but without any mortality.¹⁸ Experimental intranasal infection of the lungs of A. lituratus was possible with fewer than 100 viable spores,⁴⁹ and led to disseminated infection, antibody production, and temporary cutaneous delayed hypersensitivity. Subsequently yeasts were shed via the intestinal villi into the faeces. Naturally infected bats of the species have 10–2000 viable Histoplasma cells in their faeces, when the total faecal contents were sampled.²⁷

Further supportive evidence of past infection using Histoplasma antibody detection in bats was sought in several studies and negative in all samples.^25,27,50 The immune response to natural infection by Histoplasma spp. in bats seems muted.⁴⁴

Isolation of Histoplasma capsulatum from soil and guano linked to bats

Indirect evidence of bat infection by Histoplasma spp. was sought by sampling and culturing guano from bat caves and roosts, and soil from these locations. In 10 studies, guano from the same bat species were found to be infected as from the bats themselves (Table 3). An additional 18 species of bats were presumptively infected, including four species of Hipposideros, based on guano alone (Table 3). Isolations of H. capsulatum were reported from multiple countries, including Puerto Rica, Thailand, Trinidad, Panama, Malaysia, Australia, Slovenia and the USA.

Table 3.

Histoplasma-positive guano and soil from bat roosts implicating a particular species of bat as infected.

Species	Common name and additional data	Country	References
Artibeus jamaicensis parvipes	Jamaican fruit-bat prefers humid and tropical habitats but is also adapted to cloud forests and drier tropical areas	Puerto Rica	Torres-Blasini, 196651
Aselliscus stoliczkanus	Stoliczka's trident bat found across SE Asia	Changmai, Thailand	Norkaew, 201352
Carollia perspicillata	Seba's short-tailed bat found in moist evergreen and dry forests usually below 1 000 m elevation	Trinidad	Emmons, 196353
Chaetura brachyura	Short-tailed swift bat found in a range of habitats including savanna and open woodland	Trinidad	Emmons, 196353
Chilonycterus rubiginosa fusca	Horseshoe bat with a paleo-tropic distribution	Panama	Shacklette, 19627; Klite, 196527
Desmodus rotundus	Small leaf-nosed vampire bat native to the neotropics	Trinidad	Emmons, 196353
Eonycteris spleaea	Cave nectar bat also called common nectar bat or lesser dawn bat. It is found in Bangladesh, Brunei, and in several small islands in Indonesia and SE Asia	Malaysia	Ponnampalam, 196354
Eptesicus fuscus dutertreus	Big brown bat inhabiting cities, towns, and rural areas, but is least commonly found in heavily forested regions	USA	Emmons, 195855
Glossophaga soricina	Pallas's long-tongued bat found in forest and rainforest	Trinidad	Emmons, 196353
Hipposideros armiger	Great roundleaf bat found in South Asia, Southeast Asia, and China	Malaysia, Changmai, Thailand	Ponnampalam, 196354; Norkaew, 201352
Hipposideros biclor	Bicolored rounded leaf bat. It is found in Indonesia, Malaysia, the Philippines, Thailand, Timor-Leste. It inhabits caves rock crevices and tunnels among lowland forests	Malaysia	Ponnampalam, 196354
Hipposideros diaderma	Diadem leaf-nosed or diadem roundleaf bat occurs in lowland rainforest and open woodland	Malaysia	Ponnampalam, 196354
Hipposideros lylei	Shield-faced roundleaf bat found in China, Laos, Malaysia, Myanmar, Thailand and Vietnam	Changmai, Thailand	Norkaew, 201352
Micronycteris megalotis	Little big-eared bat widely distributed in many habitats including wet and dry areas, evergreen and deciduous forests, and swamps	Panama	Klite, 196556
Miniopterus schreibersii	Long fingered bat roosts in caves, rock clefts, culverts and caverns	New South Wales, Australia and Slovenia	Hunt, 198457; Mulec, 202058
Mollosus ater (Molossus rufus)	Black mastiff bat.	Trinidad	Emmons, 196353
Mollosus major	Velvety free-tailed bat that occurs in Central and South America. Also found roosting in houses in urban areas	Trinidad	Emmons, 196353
Myotis chinensis	Vesper bat found in China, Hong, Kong, Myanmar, Thailand and Northern Vietnam	Changmai, Thailand	Norkaew, 201352
Myotis muricola	Wall-roosting mouse-eared bat, or Nepalese whiskered myotis roosts in many sites including curled-up banana leaves, limestone forests, hollow trees, rock shelters, artificial caves, mines and tunnels, and old buildings	Malaysia	Ponnampalam, 196354
Phyllostictus roostus	Unknown	Panama	Taylor, 196259
Phyllostomus hastatus	This species inhabits tropical regions of the Americas, and Trinidad and Tobago	Trinidad, Panama	Taylor, 196259; Emmons, 196353; Hasenclever, 197231
Pteronotus suapurensis	Taxonomy changed. Mustached bat	Panama	Taylor, 196259
Rhinolphus luctus	Great woolly horseshoe bat lives in large caves in forests, rocky outcrops, and semi evergreen forests	Malaysia	Ponnampalam, 196354
Saccopteryx bilineata	Greater sac-winged bat native to the Central and South America	Trinidad, Panama	Emmons, 196353; Klite, 196556
Taphozous melanopogon	Black-bearded tomb bat found in caves in Guangxi and Guangdong, sometimes in large numbers. Also roosts in temples, ruins and other old buildings in India	Changmai, Thailand	Norkaew, 201352
Tadarida brasiliensis	Mexican free-tailed bat	USA	McMurray 198250

Outbreaks of histoplasmosis associated with bat guano, implicating species of bats

An outbreak of histoplasmosis is defined as the occurrence of at least two cases of the disease. Numerous reports of epidemics or outbreaks of histoplasmosis in the Americas have been described over the years, dating back to the late 1930s.^19,60,61 To our knowledge, only one of these reports identified the species of bats linked to exposure—in Costa Rica. In this report, 15 students entered a cave in Santa Rosa National Park, Guanacaste Province inhabited by about 500 bats.⁶² Twelve of the students subsequently developed persistent illness, with abnormal chest radiographs and serologic evidence of acute pulmonary histoplasmosis. The cave housed three species of fruit bats (Glossophaga soricina, Carollia perspicillata, and Carollia subrufra) and one species of vampire bats (Desmodus rotundus).

Staffolani et al. (2018) in an exhaustive review of literature identified 814 persons who acquired acute or disseminated histoplasmosis amongst the travellers to bat caves in different countries in the Caribbean, South America, some parts of North America, Europe, and Africa.⁶³ These authors also mentioned details of exposure to bats, cases occurring in clusters, and types of antifungal therapy if given. They also provided a timeline distribution of the studies reporting cases of acute histoplasmosis in immunocompetent travellers.

Discussion

In 1981, Hoff and Bigler counted 24 species of bats with documented Histoplasma infection recorded (two not confirmed).¹⁸ We identified an additional 25 bat species infected, with indirect evidence of infection of another 18 species (total of 67). There are over 1400 species of bats present worldwide. The vast majority of studies of Histoplasma infection in bats are from the Americas, including the Caribbean, with a few others from Thailand, Malaysia, Australia, Slovenia, France, Iran, DRC, South Africa, Tanzania, and for Histoplasma duboisii in Nigeria. Additional hyperendemic areas of histoplasmosis (based on histoplasmin skin testing population frequency) include Myanmar, southern Thailand, parts of Java Island in Indonesia, Luzon in northern Philippines, and probably other areas of SE Asia.⁶⁴ It is highly likely that these and other areas have resident and migratory bat populations with histoplasmosis. Not only are bat and environmental data on Histoplasma missing from these and other areas, but reports of outbreaks of acute pulmonary histoplasmosis from most of these areas are also absent, the exceptions being New Caledonia, Indonesia, and South Africa.⁶³

Taxonomy of the Histoplasma genus has recently undergone a revision with H. capsulatum var capsulatum being split into four species: H. capsulatum sensu stricto (also known as the Panama or H81 lineage), Histoplasma ohiense, H. mississippiense, and H. suramericanum.⁶⁵ This taxonomic revision has yet to be fully accepted. It will take some time to ascertain if certain bat species are more or less likely to harbour any of these species/varieties/taxonomic groups preferentially. One bat from Sao Paolo state in Brazil was infected with H. suramericanum, assuming this is a valid species name.⁶⁶ Recently sequence data from a small number of H. capsulatum isolates from bats in Mexico and migratory bats has started to unravel these relationships.³⁶

While bats may have Histoplasma spp. isolated from deep tissues, notably lungs, liver and spleen, and may be experimentally infected with low inocula, it is not clear to what extent they suffer from disease, or whether they have latent infection, with gastrointestinal colonization or excretion. Pathologic lesions were seen a few examined specimens of Pteronotus (Chilonycteris) rubiginosa, but not many. It is probably unwise to generalize from one species to all others, especially where attempts to isolate Histoplasma spp. from multiple other bats was unsuccessful (Supplementary Table 1). Likewise given the variable manifestations and yield from these prior experiments (which often used mouse inoculation to improve culture sensitivity), it would be unwise to assume that some species of bat were intrinsically immune to infection with Histoplasma spp. A complicating factor in understanding Histoplasma infection in bats is their variable temperature over time. There is probably some variation in temperature in different species, but body temperature during flight is typically 40°C, and it falls to lower than 10°C when in torpor.⁶⁷ These temperatures bracket the dimorphism temperature sensitivity of Histoplasma spp, typically around 32°C, when filamentous forms at the lower temperature shift to a yeast form. To add further complexity, some strains of H. capsulatum grow more slowly at higher temperature, notably above 39°C.⁶⁸ To our knowledge the biological implications of the temperature dynamics of bats on the physiology of Histoplasma spp. have yet to be fully addressed. Changing weather patterns, extremes of temperature and possibly altered migratory patterns of bats in response to these climatic pressures, could alter the ‘status quo’ between bats and Histoplasma spp..

The recent outbreak of the lethal fungal infection of bats in N. America of White Nose Syndrome,^69–71 has led to a resurgence of interest in bat disease. Further attempts are underway to immunize bats to prevent mass die-offs and potentially species extinctions.⁷² It is conceivable that Histoplasma infection of bats could evolve and become problematic for bats, humans and the other mammals that can be infected. Infection due to H. capsulatum in cats and dogs is reported to be frequent in Midwest and southern United States.⁷³ A recent survey of Histoplasma in mammals in Europe indicates a much wider endemic area than previously appreciated.⁷⁴

Conclusion

This study provides an update on the occurrence of Histoplasma spp. in bats and soil mixed with bat guano. Fifty four of the approximately 1400 species of bat have been documented to be infected by Histoplasma spp. There has been slow progress in this area in recent decades. There is a need to explore the occurrence of histoplasmosis in human populations around caves that harbour bats in areas of endemicity of histoplasmosis. Only one bat species has been reported to be infected with H. duboisii (in Nigeria), yet this fungus is present throughout the African continent. A better understanding of the pathogenicity, latency, and intestinal excretion of Histoplasma in bats is called for.

Author contributions

Harish C. Gugnani (Conceptualization, Data curation, Writing – review & editing), and David W. Denning (Conceptualization, Data curation, Formal analysis, Project administration, Writing – original draft, Writing – review & editing)

Funding

No external funds were used in preparation of the manuscript

Conflict of Interest

There are no conflicts of interest to declare.