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Published in final edited form as: Lancet Microbe. 2024 Aug 24;5(12):100921. doi: 10.1016/S2666-5247(24)00161-7

Geographical distribution of the Cryptococcus gattii species complex: a systematic review

Victoria Poplin 1, Clarissa Smith 2,3, Diego H Caceres 4,5,6, Patricia F Herkert 7, Olujimi Jegede 8, George R Thompson III 9,10, John W Baddley 11, Ilan S Schwartz 12, Ryan Kubat 13, Mark A Deka 14, Mitsuru Toda 15, Shawn R Lockhart 16, Tom Chiller 17, Ferry Hagen 18,19,20, Nathan C Bahr 21,22
PMCID: PMC11995670  NIHMSID: NIHMS2068563  PMID: 39191262

Abstract

The taxonomy of the Cryptococcus gattii species complex continues to evolve, and has been divided into five pathogenic species. The objective of this systematic review was to summarise the geographical distribution of the C gattii species complex and the species within the C gattii species complex. We searched PubMed for articles related to human, animal, ecological, or laboratory-based studies of C gattii species complex isolates with traceable geographical origin published from January, 1970, until September, 2021. Having extracted their geographical origin, we used ArcMap to construct maps according to the highest degree of resolution allowed by their reported taxonomy, to reflect the most likely area of transmission on the basis of published reports of human isolates. 604 such articles were included in the study. This review indicated that although C gattii species complex isolates have been reported globally, understanding their heterogeneous geographical distribution by species can have implications for researchers and clinicians in formulating research questions and considering diagnostic quandaries.

Introduction

The Cryptococcus gattii species complex was initially thought to be confined to tropical and subtropical environments.14 However, the C gattii outbreak in Vancouver Island, British Columbia, Canada in 1999 and subsequent detection in the Pacific Northwest USA led to the questioning of this notion.26 Additional cases have since been diagnosed globally, leading to the current understanding of the widespread geographical range of the C gattii species complex in many regions outside tropical and subtropical areas.3 Refinement in the understanding of the phylogenetic diversity of the C gattii species complex and corresponding taxonomic revisions indicate that some species might pre-dominate in particular regions. Yet, no systematic review has summarised the current knowledge of the geographical distribution of the C gattii species complex and the species within the C gattii species complex on the basis of published reports, which is the aim of this systematic review.

The C gattii species complex was first identified in the 1970s and classified as a subtype of Cryptococcus neoformans (C neoformans var gattii) and Cryptococcus bacillisporus.2,7,8 Cryptococcus species were traditionally classified according to the serotyping of the capsular polysaccharide, with B and C serogroups corresponding to members of the C gattii species complex.2,911 C neoformans var gattii was later renamed as C gattii.2,4,1214 Subsequently, the C gattii species complex has been categorised by molecular types designated VG (var gattii), according to genetic analyses based initially on amplified fragment length polymorphism (AFLP): VGI (AFLP4), VGII (AFLP6), VGIII (AFLP5), VGIV (AFLP7), VGV, and VGVI (AFLP10).9,10 VGII is further divided into VGIIa, VGIIb, and VGIIc.15 VGIII is divided into VGIIIa–c, with VGIIIc similar to VGVI.11 Serotype B typically corresponds to VGI and VGII, whereas serotype C corresponds to VGIII and VGIV.4 However, both serotypes B and C are associated with VGIII.16 These molecular types have been designated as distinct species, collectively referred to as the C gattii species complex.11 Currently, the C gattii species complex includes C gattii sensu stricto (VGI, AFLP4), Cryptococcus deuterogattii (VGII, AFLP6), C bacillisporus (VGIII, AFLP5), Cryptococcus tetragattii (VGIV, AFLP7), and Cryptococcus decagattii (VGVI and VGIIIc, AFLP10).10,11,17

C gattii species complex infections are frequently complicated by neurological sequelae and clinical relapses and are slow to respond to therapy, thus resulting in high morbidity.1826 C gattii species complex infections also have a higher incidence of both pulmonary and cerebral cryptococcoma than C neoformans infections.19,23,27,28 C gattii species complex infections most commonly present themselves as pulmonary and CNS manifestations with different frequencies based on the geography and the predominant species.2,20,22,2932 For example, C gattii sensu stricto has been associated with higher rates of CNS infection and cryptococcoma, as compared with other species within the C gattii species complex.23,30 C deuterogattii infection is more common in immunocompetent patients and often presents as a respiratory infection.11,22 The C gattii species complex occurs more frequently than the C neoformans species complex in immunocompetent patients.2,3,5,14,20,27,33,34 However, over time, such cases have been reported in immunocompromised patients as well.3555 In addition, patients presumed to be immunocompetent could have unrecognised immunodeficiencies, for example, due to anti-granulocyte macrophage colony stimulating factor autoantibodies.56,57 Moreover, some species within the C gattii species complex could have predilection for immunocompetent hosts over immunocompromised hosts.3,58 C deuterogattii and C gattii sensu stricto infections are more frequently seen in immunocompetent patients, whereas C bacillisporus, C decagattii, and C tetragattii infections appear to occur more often in immunocompromised hosts.3,11,22,5962 These differences in clinical syndromes highlight the crucial need for understanding the geographical distribution of species within the C gattii species complex for proper diagnosis and treatment of the infections caused by them. The information summarised herein can help clinicians to consider the species in the C gattii species complex in the treatment of individuals under their care, with better knowledge of which species are most likely to be of concern in their geographical region.

Methods

Search strategy and selection criteria

In this study, reports with the taxonomy that did not use the names of the species were categorised as the Cryptococcus gattii species complex. Specific species names were used everywhere else. PubMed was searched for articles from January, 1970, until September, 2021, using the search terms “Cryptococcus gattii”, “Cryptococcus gattii complex”, “VGI”, “AFLP4”, “Cryptococcus bacillisporus”, “VGIII”, “AFLP5”, “Cryptococcus deuterogattii”, “VGII”, “AFLP6”, “Cryptococcus tetragattii”, “AFLP7”, “Cryptococcus decagattii”, “VGIIIc”, “AFLP10”, “VGVI”, “VGV”, and “VGIV”.

Published case reports, case series, and epidemiological reports were included. Human, non-human animal, and ecological isolate studies were included. Article languages included were English, Spanish, Portuguese, French, Chinese, and Japanese. Laboratory studies were included if C gattii species complex isolates were reported and the origin provided. Interspecies hybrids were also included. All studies considered were required to specify the basic geographical location (at least the country of origin). The study was conducted according to PRISMA guidelines.

Articles were excluded when they failed to identify Cryptococcus at the species level or to differentiate the C gattii species complex from the C neoformans species complex when utilising the earlier taxonomy. Other exclusion criteria were no mention of geographical location, laboratory reports using reference strains, isolates from culture collections, or isolates from a clearly cited study that had already been included.

Three authors (VP, CS, OJ) independently screened articles published in English using different search terms (appendix p 22), reviewed them, and extracted information from them. Four additional authors (DHC, PFH, TC, FH) reviewed, translated, and extracted information from non-English articles. For all the articles recovered in each search, the PubMed identification numbers, individual species of the C gattii species complex, type of report (human, animal, ecologic, or unknown), number of isolates or cases, geographical locations and, wherever applicable, the reason for exclusion were recorded. After completion of the search, the excluded articles were separated, and the remaining articles organised in terms of the species within the C gattii species complex and type of isolate. An additional 51 unpublished reports were added from the US Centers for Disease Control and Prevention database.

Map construction

Maps were constructed using ArcMap (ArcGIS desktop: release 10⋅8⋅2, Environmental Systems Research Institute), to reflect the most likely area of geographical distribution on the basis of published reports of human isolates of the C gattii species complex and the species within the same. Isolates from human cases associated with travel were not included in the construction of the map. To account for over-attribution to specific cities (eg, some countries have this type of testing only at a single centre), whole countries were labelled as areas of most likely transmission whenever there were any cases found within the country. Strength of evidence, based on the number of isolates reported, was assigned to each location and divided into very high, high, medium, and low groups. These groups were created using the natural breaks classification, which creates maximum variance between the individual classes and least variance within each class. The specific areas in which the isolates were reported were shaded and labelled as areas of evidence of locally acquired cases on each map.

Results

Appendix p 2 shows the PRISMA flow diagram. The initial search returned 3787 records. After the duplicates were discarded, 1801 records remained, of which 1087 were assessed in full text format after excluding abstracts. Of these, 604 records were included. 4758 reported isolates (eg, individual isolates obtained from human, animal, or environmental sources) were identified at the species complex level; 2424 were human isolates. Species-level information was available for 5303 reported isolates, including 1854 C gattii sensu stricto (660 human), 2449 C deuterogattii (1437 human), 679 C bacillisporus (412 human), 290 C tetragattii (185 human), 18 C decagattii (16 human), and six C gattii lineage VGV (all ecological) isolates. Seven isolates from interspecies hybrids were reported. 54 reports had potential travel-associated acquisition. Travel-related cases were excluded from map-making but included in the tables for reference. The details of all reports, including organisation by way of geographical location, category of isolate and the species within the C gattii species complex, and interspecies hybrids reported with citations are in appendix pp 2351.

C gattii species complex

Many reports identified C gattii isolates to the species complex level only. Figure 1 shows the likely area of geographical distribution based on the published human reports of all species within C gattii species complex and reports that describe C gattii species complex broadly. C gattii species complex reports were predominantly from the USA, Canada, Africa, South America, Australia, and India. In North America, the majority of C gattii species complex reports were within the USA (California, Washington, and Oregon) and Canada (British Columbia). In South America, the C gattii species complex was found predominantly in Brazil and Colombia. Reports on the C gattii species complex were scattered throughout sub-Saharan Africa, most often from southern Africa. Many reports on the C gattii species complex were from Australia, primarily from New South Wales. The C gattii species complex has also been reported in India, China, Taiwan, Japan, and several countries in Southeast Asia. In Europe, most C gattii species complex cases were reported from animals in Spain.

Figure 1: Most likely areas of geographical distribution of the Cryptococcus gattii species complex.

Figure 1:

This map incorporates human reports of all C gattii species members and specifically those of the C gattii species complex. Number of reports per category: very high (≥233), high (115–232), medium (33–114), and low (≤32).

C gattii sensu stricto (AFLP4, VGI)

Figure 2 shows the likely geographical distribution of C gattii sensu stricto (VGI, AFLP4) based on human reports. Most reports were from Australia, India, the USA, and Europe, with fewer reports from Africa, South America, Canada, China, Taiwan, and Papua New Guinea. Fewer than 15 reports each were noted from Mexico, Viet Nam, Thailand, Malaysia, Cambodia, and New Zealand. One report each was noted from Cuba (in a South African Cheetah), Honduras, and Japan.

Figure 2: Most likely areas of transmission of Cryptococcus gattii sensu stricto (AFLP4/VGI).

Figure 2:

Number of reports per category: very high (≥47), high (18–46), medium (5–17), and low (≤4).

In Australia, the primary types of C gattii sensu stricto reports were ecological and animal cases, and most reports of human cases did not provide a specific location within the country. Papua New Guinea had reports of human cases. India (particularly Delhi) had the most frequent reports of C gattii sensu stricto, primarily involving ecological cases. Although most human reports in India only mentioned the country, some specified particular regions, including Tamil Nadu, Bengal, Bihar, and Karnataka. Other reports did not specify a particular region. Most reports from China were human cases and did not specify the subnational location; however, some reports specified Shanghai, Fujian, East China, Guangxi, Sichuan, Beijing, Hong Kong, Hainan, and Neimeng as the specific regions. Reports from Taiwan were predominantly about ecological cases.

In the USA, C gattii sensu stricto has most often been documented in California, including reports of human, animal, and ecological cases, with additional reports scattered around the country. C gattii sensu stricto was occasionally reported in Canada, particularly British Columbia, and the reports were primarily about humans. Reports of C gattii sensu stricto from South America were most commonly from Brazil (mostly human) and Argentina (mostly ecological). Reports from Colombia and Peru were rare.

In Europe, C gattii sensu stricto were predominantly noted in Italy and Spain, with some additional reports scattered across the continent.

In Africa, the majority of C gattii sensu stricto reports were from southern Africa, including South Africa, Zimbabwe, Zambia, and Mozambique. In eastern Africa, most reports were from Kenya. Reports in the remainder of Africa were scattered and uncommon (Ivory Coast, Senegal, the Democratic Republic of the Congo [formerly Zaire, as reported by some older reports], and Republic of the Congo).

C deuterogattii (AFLP6, VGII)

Figure 3 shows the likely geographical distribution of C deuterogattii based on human reports. C deuterogattii has been recognised as the species within the C gattii species complex that caused the outbreak in Vancouver Island, British Columbia, Canada, with many reports coming from this region.59,60 Most reports from British Columbia, Canada, were of human or ecological isolates, although the first reports were of animal isolates.63 C deuterogattii has also been reported in Quebec and Nova Scotia, Canada.64,65 In the USA, C deuterogattii has most commonly been reported in Oregon and Washington, with some other scattered reports across the country.

Figure 3: Most likely areas of geographical distribution of Cryptococcus deuterogattii.

Figure 3:

Number of reports per category: very high (≥46), high (12–45), medium (4–11), and low (≤3).

Within South America, reports on C deuterogattii have mostly been of human isolates from Brazil, in the states of Piauí, São Paulo, Amazonas, Minas Gerais, Mato Grosso, Paraná, and Rio de Janeiro. C deuterogattii was also reported frequently from Colombia and more rarely from Uruguay, Argentina, and French Guiana. Reports were uncommon in Mexico and the Caribbean.

In Africa, the majority of C deuterogattii reports were human isolates from Ivory Coast, with a few reports from Senegal. Reports of ecological isolates were also rare. In Europe, most reports were human cases from Greece, followed by reports from France. A few other countries had rare reports as well. Human and animal reports were most common in Australia. In Asia, most reports of human cases were from China.

C bacillisporus (AFLP5, VGIII)

The known distribution of C bacillisporus is much more restricted—predominantly in the USA and South America. Although there have been scattered reports from elsewhere, they are comparatively fewer than those for some other species. Figure 4 outlines the likely geographical distribution of C bacillisporus based on human reports.

Figure 4: Most likely areas of geographical distribution of Cryptococcus bacillisporus.

Figure 4:

Number of reports per category: very high (≥25), high (9–24), medium (4–8), and low (≤3).

Within the USA, most reports of C bacillisporus were from California (predominantly human or animal cases); fewer reports were from Oregon, New Mexico, Georgia, Washington, Alabama, and Michigan; and rare reports originated from other states. Mexico had a substantial number of reports on human isolates, whereas Canada had three C bacillisporus reports. Reports were also found from Cuba (a single report with travel to Honduras and Guatemala) and Guatemala.66 Reports were common in South America, particularly in Colombia, where all reports were either of ecological or human isolates. Brazil had the second highest number of reports (all human cases) within South America and a few additional reports were from Argentina, Venezuela, Bolivia, and Paraguay. A few reports originated in Europe, Australia, a small number of Asian countries, and South Africa.

C decagattii (AFLP10, VGVI, and VGIIIc)

Figure 5 describes the likely area of geographical distribution for C decagatti, C tetragattii, and lineage VGV. C decagattii is a rare species. To date, most reports on C decagattii are in humans, with only one report each on ecological and animal cases. C decagattii has been reported in Argentina, Colombia, Mexico, and the USA. One report came from Spain, but the infected individual had immigrated from Mexico.58

Figure 5: Most likely areas of geographical distribution of Cryptococcus decagattii, Cryptococcus tetragattii, and the VGV lineage.

Figure 5:

Both C tetragattii and C decagattii have been reported in Mexico. An inset map of Mexico is included to depict the reported distribution of C decagattii and area with locally acquired cases. Number of reports per C tetragattii category: very high (≥36), high (16–35), medium (2–15), and low (≤1). Number of reports per C decagattii category: medium (≥4) and low (1–3); only two categories were used because there were only a few reports of C decagattii. The VGV lineage was not subcategorised given that there were very few reports of VGV.

C tetragattii (AFLP7)

C tetragattii (AFLP7) is more common than C decagattii, but is still quite rare. Reports of human, animal, and ecological isolates of C tetragattii have all been documented, predominantly within India and sub-Saharan Africa. Most reports from India were in humans and did not specify a location, although some reports did give the detailed location. The sub-Saharan African reports came from South Africa, Botswana, Zimbabwe, Malawi, Mozambique, and the Miombo Woodlands (which span multiple countries).67 Additional reports came from Spain, Puerto Rico, Mexico, and Colombia.

C gattii lineage VGV

Lineage VGV is the most recently identified genotype of the C gattii species complex and seems to be non-pathogenic. Reports of ecological isolates have come from Zambia.67

Interspecies hybrids

Isolates from interspecies hybrids (C gattii species complex with C neoformans or C deneoformans) have also been reported in humans from Kenya, Denmark, the Netherlands, the USA, and Canada.6870 There was one human case from Montreal, Quebec, Canada with travel to Mexico 15 months earlier.71 So far, no interspecies hybrids between members of the C gattii species complex have been reported.

Discussion

This systematic review provides up-to-date evaluation of the current understanding of the geographical distribution of the C gattii species complex, and the respective species therein. The C gattii species complex has been reported in many parts of the world, with most cases and isolates in North America, South America, Africa, and Australia, and less frequent ones in Asia and Europe. In North America, most reports were from British Columbia, Canada, and northwestern USA (where C deuterogattii is the predominant species) or California, USA (most commonly C bacillisporus and C gattii sensu stricto). In South America, Brazil and Colombia were the most common origins of the reports and C deuterogattii and C bacillisporus were the most frequently identified species. C bacillisporus appears to be more geographically restricted than C gattii sensu stricto and C deuterogattii. In Africa, particularly the sub-Saharan region, many reports of the C gattii species complex were present, although most of them did not identify the species. In Australia, C gattii sensu stricto was the most common. Reports of C decagattii, C tetragattii, and C gattii VGV lineage were much rarer, with C decagattii primarily found in the western hemisphere, C tetragattii in India and sub-Saharan Africa, and lineage VGV only in Zambia.

A study by Hitchcock and colleagues characterised the geographical distribution of C gattii using multilocus sequence typing rather than on the basis of species and did not construct maps.72 In terms of distribution, some similarities were noted between our study and the study by Hitchcock and colleagues, with most of their reports being of VGI (correlating to C gattii sensu stricto), VGII (correlating to C deuterogattii), and VGIV. Notably, differences were found in terms of distributions between our study and theirs—although we found numerous reports of C deuterogattii in South America and reports of C bacillisporus in Africa and Asia, their study did not. Further, their text (though conflicting with their tables) noted VGI as the most common in Europe. C gattii sensu stricto was found in Europe in our study, but it was less common than in Australia, the USA, and India.

All reports summarised herein have been previously published (but not summarised in this way) aside from some data from the US Centers for Disease Control and Prevention. In most cases, the species from these data had already been reported in published literature. However, C gattii sensu stricto had not previously been reported in Nebraska or Louisiana, USA; C bacillisporus had not been previously reported in Florida, USA; and C deuterogattii had not been previously reported in Alabama, USA. These are first-time reports from this publication.

The geographical distribution is important as the various species within C gattii species complex might cause clinically distinct disease or affect different immunocompromised individuals. For example, C gattii sensu stricto appears to be associated with higher rates of CNS infection, CNS cryptococcoma, and infection in immunocompetent patients, compared with other members within the C gattii species complex.23,30,60 C deuterogattii also predominantly affects immunocompetent patients, but respiratory infections are more common than CNS infections in the case of C deuterogattii.11,22 One study found that the VGIIb subtype of C deuterogattii occurs more often in older individuals (> 50 years of age) and could be more likely to be associated with fatal outcomes than the VGIIa subtype or C gattii sensu stricto (VGI).29 C bacillisporus, C tetragattii, and C decagattii occur primarily in people living with HIV or individuals with other immunocompromising conditions; there was one report of C decagattii in an immunocompetent child in Argentina.3,11,16,5962,73 Efficacy of antifungal treatments can also vary by species. The mean minimum inhibitory concentrations for antifungal azole drugs vary by species. One study of the C gattii species complex in the Pacific Northwest USA found that the VGI and VGIII isolates had comparatively low fluconazole minimum inhibitory concentrations than the VGIIc isolate (which included a majority of isolates with fluconazole minimum inhibitory concentrations of 16–32 μg/mL).15 Similarly, in another study of antifungal susceptibilities in C gattii species complex strains, Pacific Northwest USA strains had approximately two-fold higher minimum inhibitory concentrations than USA non-Pacific Northwest C gattii species complex and C neoformans species complex strains.74 However, no standard breakpoints for Cryptococcus species exist and in-vitro data might not relate to clinical outcomes, owing to which the importance of elevated minimum inhibitory concentrations is not clear.11,15,17,75

Since its first identification in eucalyptus trees, the C gattii species complex has been isolated from numerous types of trees, particularly from decaying wood within tree hollows.12,7697 Environmental sampling in the Pacific Northwest USA indicates that the C gattii species complex possibly spreads by means of anthropogenic distribution via mechanical vectors such as vehicles, foot-wear, or wooden pallets and crates.98 Animal migration could also contribute to the spread of the C gattii species complex.6,98 Warmer average global temperatures have been shown to increase the susceptibility of trees to fungal colonisation; thus, climate change could have facilitated the expansion of the C gattii species complex.99 In the Pacific Northwest, marine coastlines were thought to be contaminated with C gattii species complex through ballast water-dumping events, with the coastal forests subsequently contaminated by tsunami water surges.100 These factors, combined with the growing knowledge of the various species within the C gattii species complex, underscore the importance of delineating the geographical distribution of the various species within the C gattii species complex.

The limitations of this study stem from its passive surveillance and reliance on published data. The study design precludes estimating the prevalence of the C gattii species complex in specific locations. Moreover, other locations where these fungi cause disease might have been missed. Publication bias surely influences our findings and most likely overemphasises particular locations or species, or both, and is potentially stronger because the period for this study ended in September, 2021 and we only used one search database (PubMed). Similarly, some areas are most likely to be under-represented (or not represented at all) as species can only be identified in areas where samples are obtained, tested, and reported. Many laboratories cannot test for the specific species or differentiate the C gattii species complex from the C neoformans species complex; older studies would not have had the ability to do so either. Because of this, we chose to label our maps as most likely geographical distribution and included entire countries; for additional clarity, we also highlighted the location of the reported human isolates. We excluded cases with known travel, but unknown travel history cannot be excluded and would have affected our results. Our goal was to bring attention to information within the realm of the known so that clinicians can consider this disease in an appropriate situation and location. In addition, because speciation of the C gattii species complex is not routine in clinical settings, studies were most likely either published as C gattii species complex (rather than a specific species) or deferred publication, assuming they had a C gattii species complex case without information about the species involved. In addition, since we only used PubMed, other published reports, particularly environmental studies, could have been missed out. Further, using natural breaks for classification could simply reflect the abovementioned biases and further project these biases as additional certainty. We advocate using maps as indicators of the most likely areas of geographical distribution, rather than as firm measures of endemic concentration. The maps should not be seen as a final complete distribution as there are most likely areas missed because of a lack of reporting and areas of endemicity will most likely change over time. Similar studies should be taken up in future using multiple databases to increase the rigour of research. Laboratory studies were included in this systematic review to ensure that most C gattii species complex reports get covered, but this could have led to duplication of the isolates reported, over-emphasising particular locations or species, or both. Given that this study aims to serve as a first step towards mapping the origin of these fungi, we favoured inclusiveness, which could have resulted in some duplication. Lastly, we did not perform statistical analysis because of the substantial heterogeneity in the study. If possible, such a statistical analysis would have been helpful, but with the available data, the analysis could have been misleading.

Yet, the overall goal of this study was to summarise the current knowledge of the geographical distribution of the C gattii species complex and species therein so that clinicians can appropriately consider these infections in individuals under their care. C gattii species complex was scarcely reported in numerous areas. We hope this report will bring additional attention to the presence of the C gattii species complex in these regions and result in improved care for individuals.

Improved public health funding for advanced molecular techniques that can be used in surveillance would add to the knowledge of the geographical locations where species within the C gattii species complex exist and cause disease. Public health resource allocation is always a concern, but increased resources directed towards this area would improve the knowledge of the geographical distribution of species and translate into improved clinical care. Additional data on clinical presentations of the various species is warranted, but early reports point to varied presentations by species. Improved surveillance could lead to more rapid diagnosis and better outcomes.

Conclusions

The C gattii species complex is reported frequently in the USA (Oregon, Washington, and California), Canada (British Columbia), Australia, Brazil, Colombia, and sub-Saharan Africa, albeit with considerable variation in the reporting by species. C gattii sensu stricto has been predominantly reported in Australia, the USA (California and southeast USA), India, southern Africa, and Europe; C deuterogattii in the Pacific Northwest USA, British Columbia (Canada), and Brazil; and C bacillisporus in the USA (California), Brazil, and Colombia. C tetragattii and lineage VGV have only been rarely reported, mainly in Africa, although C tetragattii has also been found in India. C decagattii has also been rarely reported, mostly in the western hemisphere. These differences are most likely to influence clinical presentations and outcomes and clinicians, which should be considered. Although the understanding of the taxonomy of the C gattii species complex has grown over the years in the scientific community, the ability to identify these infections at the species level is still low in many clinical settings. To fully understand the areas where species within the C gattii species complex occur, more widespread availability of species identification techniques is needed.

We urge the global public health community to facilitate improved identification of C gattii species complex and infections caused by them. Improved knowledge of the geographical locations where these infections occur is key to early diagnosis; thus, more ecological and epidemiological studies are warranted. In areas where the C gattii species complex is newly recognised, public health stakeholders should work to inform clinicians and adjust public health policy and planning accordingly.

Supplementary Material

Supplementary Material

Acknowledgments

The authors would like to acknowledge Kosuke Yasukawa for assistance in article translations and the AR Dykes Library of the University of Kansas for their assistance in retrieving many of the articles. NCB receives research support from the National Institutes of Health (National Institute of Neurological Disorders and Stroke): K23NS110470. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the US Centers for Disease Control and Prevention and should not be considered as an endorsement by the Federal Government.

Footnotes

Declaration of interests

FH is the Vice President of the International Society for Human and Animal Mycology, treasurer of the Netherlands Society for Medical Mycology, chair of the Royal Netherlands Society for Microbiology, Microbial Genomic Division, and received molecular diagnostic kits from Bruker Molecular Diagnostics. NCB was the Data and Safety Monitoring Board chair for NCT04335123. All other authors declare no conflicts of interest.

Contributor Information

Victoria Poplin, Division of Infectious Diseases, Department of Medicine, University of Kansas, Kansas City, KS, USA.

Clarissa Smith, Section of Pulmonary/Critical Care, Department of Medicine, University of Chicago, Chicago, IL, USA; Department of Internal Medicine, University of Kansas, Kansas City, KS, USA.

Diego H Caceres, Studies in Translational Microbiology and Emerging Diseases (MICROS) Research Group, School of Medicine and Health Sciences, Universidad del Rosario, Bogota, Colombia; Center of Expertise in Mycology Radboudumc/CWZ, Nijmegen, Netherlands; Immuno-Mycologics (IMMY), Norman, OK, USA.

Patricia F Herkert, Faculty of Medicine, Centro Universitário de Pato Branco, UNIDEP, Pato Branco, Brazil.

Olujimi Jegede, Division of Infectious Diseases, Department of Medicine, University of Kansas, Kansas City, KS, USA.

George R Thompson, III, Division of Infectious Diseases, Department of Internal Medicine, University of California Davis Medical Center, Sacramento, CA, USA; Department of Medical Microbiology and Immunology, University of California Davis Medical Center, Sacramento, CA, USA.

John W Baddley, Division of Infectious Diseases, Department of Medicine, University of Maryland, Baltimore, MD, USA.

Ilan S Schwartz, Division of Infectious Diseases, Department of Medicine, Duke University, Durham, NC, USA.

Ryan Kubat, Division of Infectious Diseases, Department of Medicine, University of Kansas, Kansas City, KS, USA.

Mark A Deka, Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, GA, USA.

Mitsuru Toda, Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, GA, USA.

Shawn R Lockhart, Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, GA, USA.

Tom Chiller, Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, GA, USA.

Ferry Hagen, Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, Netherlands; Institute for Biodiversity and Ecosystem Dynamics, University of Amsterdam, Amsterdam, Netherlands; Department of Medical Mycology, Westerdijk Fungal Biodiversity Institute, Utrecht, Netherlands.

Nathan C Bahr, Division of Infectious Diseases and International Medicine, Department of Internal Medicine, University of Minnesota, Minneapolis, MN, USA; Division of Infectious Diseases, Department of Medicine, University of Kansas, Kansas City, KS, USA.

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