Talaromyces marneffei Outside Endemic Regions: An Overlooked Mycosis Under a One-Health Lens

Abstract

Talaromyces marneffei is a zoonotic dimorphic pathogen endemic to Southeast Asia and reported in 33 countries, with an estimated 17,300 human cases and 4900 deaths annually. We aimed to identify the best available evidence regarding the epidemiological and clinical features and the prevalence of T. marneffei reported in companion animals, wildlife, and humans in Europe. A systematic literature review was conducted by searching three databases under PRISMA guidelines for “Talaromyces marneffei” or “talaromycosis” in Europe or the equivalent. References from the obtained publications were also checked to identify additional papers that met the inclusion criteria. The search was not limited by language or year. Studies published until 30 April 2025 were included. Due to the limited number of publications on animals, the geographic scope was expanded to a global level. Of the 915 studies identified, 33 were eligible and categorised according to the subject they addressed: talaromycosis in humans (n = 26), talaromycosis in companion animals (n = 4), and talaromycosis in wildlife (n = 3). Talaromycosis has been reported 28 times in 11 different European countries among humans. Additionally, one case of T. marneffei in wildlife has been documented in Europe. There is a potential liaison host between bamboo rats and humans. Talaromycosis is an emerging planetary neglected disease. Confusion with other diseases and potential misdiagnosis leads to delayed diagnosis and unnecessary risk to lives. Immunocompromised and HIV-positive patients should be screened for talaromycosis. The unexplained worldwide reports in atypical species and locations prompt a call to action for a more proactive search for T. marneffei in other domestic and wild animals, as well as in soil, to fully understand its hosts and transmission, which must incorporate the Stockholm Paradigm and Planetary Health perspectives.

1. Introduction

The Stockholm Paradigm integrates four key ecological concepts—(1) ecological fitting, (2) the geographical mosaic theory of co-evolution, (3) taxon pulses, and (4) the oscillation hypothesis—to explain the emergence, spread, and persistence of infectious diseases. This paradigm underscores how pathogens do not require genetic adaptation to infect new hosts; instead, host jumps occur through exposure to phylogenetically conserved and widespread traits in susceptible species [1,2,3]. The increasing frequency of epidemics and pandemics is driven by climate change, habitat destruction, global trade, and urban expansion, which disrupt ecological barriers and bring humans, companion animals, and wildlife into closer contact, facilitating zoonotic spillover events. The recent SARS-CoV-2 pandemic exemplifies this dynamic [2,3].

Within this framework, Planetary Health expands the traditional One Health concept by recognising human well-being as inseparable from the health of ecosystems and the planet [4,5,6]. It links economic sustainability with environmental and social determinants, emphasising that human civilisation relies on the stability of natural systems [6,7]. Defined by Whitmee et al. [7], Planetary Health is grounded in two principles: “No one is safe until everyone is safe” and “There is no health on a sick planet” [6,8].

Talaromycosis is an infectious disease caused by Talaromyces marneffei (formerly Penicillium marneffei or P. marneffei), the only thermally dimorphic fungal species pathogenic to mammals, including humans [9]. This zoonotic disease is emerging and must be considered within the Stockholm Paradigm and Planetary Health perspectives, as it is primarily reported in tropical and subtropical Asia, yet likely remains underdiagnosed in Europe [10,11], although some authors disagree [12]. The emergence and global expansion of infectious diseases, including talaromycosis, are driven by multiple interconnected factors: (i) population growth, (ii) climate change, (iii) agricultural intensification, (iv) urban expansion, (v) land use and land cover modifications, (vi) desertification, (vii) biodiversity loss, (viii) globalisation, (ix) wildlife trade, (x) wet markets, (xi) unhealthy dietary patterns, (xii) antimicrobial resistance, (xiii) air pollution, (xiv) water stress, (xv) poverty, and (xvi) weak governance [5]. These factors contribute to the planetary scale of diseases, and talaromycosis is no exception. By the end of 2018, 288,000 cases had been reported across 33 countries across Asia, Africa, Europe, and North America, with an estimated 17,300 new cases and 4900 deaths annually in humans [10]. Given its expanding ecological and epidemiological footprint, T. marneffei and talaromycosis are likely more widespread than currently recognised, demanding a renewed scientific perspective that incorporates Planetary Health principles to enhance awareness, early detection, and response (Figure 1).

T. marneffei, formerly known as P. marneffei, was named in honour of Dr. Hubert Marneffe, director of the Pasteur Institute of Indochina in Dalat, South Vietnam, where it was first isolated in 1956 from a bamboo rat (Rhizomys sinensis) as a commensal fungus that has been shown to be pathogenic for various laboratory animals [13]. Identified as P. marneffei in the subgenus Biverticillium, the infection caused by this organism was termed “penicilliosis”. In 2015, the Penicillium subgenus Biverticillium was reclassified into the genus Talaromyces, and the infection is now referred to as talaromycosis [14,15,16,17]. Phylogenetically, T. marneffei is closely related to Thermomyces lanuginosus and Thermomyces dupontii; these species are, in turn, distantly related to Aspergillus and Penicillium [17].

T. marneffei is a dimorphic pathogen whose virulence is primarily attributed to its ability to transition between a saprophytic mycelial form at 25 °C and a pathogenic yeast form at 37 °C (Figure 2) [9,18]. Although its capacity to remain latent has not been fully elucidated, it is suggested that T. marneffei may persist in the environment or within hosts at lower temperatures, potentially remaining dormant for months to years before reactivating in immunocompromised individuals. The pathogen is mainly saprophytic in the environment and may exhibit this behaviour across various species, although this has not been confirmed in all species, particularly those beyond the endemic region.

Talaromyces marneffei is endemic to Southeast Asia (Thailand, Burma, Cambodia, Hong Kong, India, Indonesia, Korea, Laos, Myanmar, Malaysia, Southern China, Taiwan, and Vietnam), where it is a major cause of opportunistic fungal infections in HIV-infected and other immunosuppressed individuals [18,19,20,21,22,23,24,25,26,27,28,29]. In certain regions of Southeast Asia, talaromycosis ranks as the third most common opportunistic infection, following tuberculosis and cryptococcosis, and was the primary defining illness in 10% of AIDS patients before the advent of highly active antiretroviral therapy [18,19,22,30].

However, talaromycosis is not confined to HIV-positive patients; it also affects individuals with immunocompromised conditions, including primary immunodeficiencies caused by interferon-gamma autoantibodies, autoimmune diseases, and malignancies, and those undergoing solid organ or bone marrow transplants. Furthermore, even HIV-negative patients can be impacted, although clinical manifestations can vary significantly between individuals with or without HIV infection [31,32,33,34].

Although endemic to Southeast Asia, there are reports of patients with no connection or relation to those geographical locations: a Ghanaian man in Germany, a Congolese man in France, and natives from Burkina Faso and Brazil [35,36,37,38]. Furthermore, imported cases of individuals who have lived in or visited endemic areas have also been reported in Australia, the USA, Canada, Argentina, and Oman, which may pose a diagnostic challenge for advanced HIV patients outside the endemic regions [39,40,41,42,43].

Traveller cases suggest that talaromycosis can be acquired following relatively short-term exposure. However, the latency period between infection and disease development may range from months to years, underscoring the importance of obtaining an accurate and comprehensive travel history from all immunocompromised patients presenting with potential opportunistic infections [44,45].

In Southeast Asia, the known carriers consist of four species of bamboo rats: R. sinensis, Rhizomys pruinosus, Rhizomys sumatrensis, and Cannomys badius [18,46].

Although the exact duration of T. marneffei’s contagiousness in soil remains unclear, its saprophytic nature suggests it may persist in the environment for extended periods. Talaromyces marneffei is typically found in soil, and the rainy season, characterised by high humidity, could increase the risk of human contact in endemic countries. This is supported by the consistent seasonal rise in talaromycosis during the rainy season in Thailand, from May to October [47,48]. This situation implies that infection might be acutely acquired [49]. Another factor to consider is temperature, as conditions between 25 °C and 30 °C favour the inhalation of spores (conidia) and subsequent pulmonary involvement [18,37].

The transmission of T. marneffei remains unclear, as no definitive environmental source or transmission route has been identified. Bamboo rats are considered natural reservoirs since infected individuals of these species do not exhibit significant clinical signs [50]. They occupy the ecological niche for T. marneffei, yet they are not typically in contact with humans [9,51]. Anecdotal evidence suggests that bamboo rats and HIV-positive patients share genetically similar strains of T. marneffei, indicating either direct transmission or a common source of infection, although firm evidence is lacking [52]. It has been proposed that the death of bamboo rats could lead to large-scale spore production, contributing to an amplifying host process for human infections or a potential indirect transmission pathway involving intermediary hosts between bamboo rats and humans (Figure 3) [52,53,54]. However, host-to-host transmission is not known to occur [19].

Conidia are inhaled; they transition to yeast form and are rapidly ingested by lung phagocytes; however, T. marneffei can survive inside macrophages. Its dimorphic behaviour and capacity to evade immunity by producing oxidative bursts and lysosomal enzymes are crucial elements of the virulence mechanism of T. marneffei. This mechanism has a significant impact on immunocompromised patients, particularly those with HIV and a CD4+ count of <100/μL in the endemic areas of Southeast Asia, as they face an increased risk of talaromycosis [9,20]. T. marneffei is a primary lung pathogen, and subsequent hematogenous or lymphatic spread results in fungal invasion across multiple organs, especially the blood, bone marrow, skin, mucous membranes of the mouth, digestive system, and reticuloendothelial tissues, which have high fatality rates, particularly in cases of delayed diagnosis and treatment [18,20,55,56]. Recently, an experimental infection was established in a consistent murine model, revealing clinical features that were coherent with those presented in human talaromycosis [57].

Yet rare invasive talaromycosis has been described as involving the CNS [18,19,36,38,58,59,60]. There are also reports of acute abdomen and one case of visceral leishmaniosis [27,39,61].

In humans, the non-specific clinical signs of talaromycosis may be confused with those of tuberculosis, histoplasmosis, cryptococcosis, toxoplasmosis, leishmaniasis, or other systemic fungal infections [21,36,38,45,55,60,61,62,63,64,65,66,67,68,69,70,71,72]. A common misperception about other diseases, stemming from the assumption that T. marneffei is not found outside endemic areas, leads to a lack of screening, diagnosis, and eventual treatment of talaromycosis, resulting in the neglect of this emerging zoonotic disease [10]. This contrasts with a comprehensive understanding of talaromycosis features in endemic areas, which enhances clinical suspicion and diagnosis [9,72,73,74,75].

In humans, European reports of T. marneffei infections are based on imported cases from Asia, suggesting that this pathogen is predominantly found in South-eastern Asia and mainly affects HIV/AIDS patients. Its global transmission is thought to result from migration and travel patterns among the population [20,21].

Amphotericin B and itraconazole are frequently utilised for the treatment of T. marneffei infections, with voriconazole presenting an effective option, particularly for HIV-associated disseminated talaromycosis [20,21,76]. Early diagnosis and prompt initiation of antifungal therapy are essential for enhancing patient outcomes, especially in immunocompromised individuals.

As planetary mobility becomes a reality, unusual microorganisms should be included in the differential diagnosis outside endemic areas, and detailed travel history is critical [20]. Immunocompromised patients from Southeast Asia may suffer from opportunistic infections caused by T. marneffei, and immunocompromised travellers to endemic areas face an increased risk of infection. In patients with this geographical background and who are immunocompromised, especially those with HIV/AIDS, talaromycosis must be considered if invasive or cutaneous mycosis is suspected [20,62,65,66,77]. Short-term prophylaxis for T. marneffei in HIV-positive individuals with a CD4 count of <100 cells/µL should be considered [66,78]. Likewise, immunocompromised patients should be more vigilant regarding their exposure to risk factors in endemic areas [26]. Following a global call to recognise talaromycosis as a neglected tropical disease [10], T. marneffei was subsequently included in the “WHO fungal priority pathogens list to guide research, development and public health action” [79]. Although some systematic reviews focused on humans in Asia, they complemented case reports rather than serving the study’s primary objective. It is important to note that these reviews only addressed specific issues, such as T. marneffei infections associated with intestinal involvement [80,81], T. marneffei infections linked to published immunodeficiency-related gene mutations [82], T. marneffei infections in HIV-infected populations in Asia [83], Talaromyces-related intestinal infections [84], a systematic review of the literature regarding fungal cerebral vasculitis caused by T. marneffei and Aspergillus niger in an HIV-positive patient in 2022 [85], T. marneffei infections following transplants [86,87], and T. marneffei infections in Japan [88]. However, no study has sought to aggregate cases in humans, companion animals, wild animals, and those outside endemic geographies.

Given the increasing reports of human and animal infections outside endemic regions, a systematic analysis of talaromycosis cases in Europe and beyond is essential to understand its true epidemiological footprint. To address this gap, this systematic review aims to identify the best available evidence concerning the epidemic, clinical features, and prevalence of T. marneffei reported in companion animals, wildlife, and humans in Europe.

2. Materials and Methods

2.1. Study Design

This systematic review, registered under the number INPLASY202480010 and with DOI 10.37766/inplasy2024.8.0010, was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [89]. Its aim was to synthesise the best available evidence regarding the epidemiological and clinical features of Talaromyces marneffei in Europe and beyond. The INPLASY record was formally updated to reflect an extended literature search covering studies published up to 30 April 2025.

2.2. Eligibility Criteria

This current study included case reports or cross-sectional studies that described clinical and epidemiological characteristics or from which the prevalence of infection or disease could be calculated using available data, in accordance with PRISMA guidelines [89].

Short communications and case reports were included, focusing on (i) the clinical presentation of T. marneffei-caused talaromycosis in animals and humans and (ii) the prevalence of the disease in both animals and humans. Review articles, case–control studies, conference proceedings, and book chapters were excluded. Case–control studies were excluded because our objective was to synthesise descriptive data from individual cases across humans and animals, focusing on clinical features and geographical occurrence. Given the rarity and heterogeneity of reported cases outside endemic areas, we prioritised study types that offer detailed clinical and epidemiological descriptions at the individual level, rather than analytical designs aimed at assessing associations or risk factors.

Research notes, editorials, experimental assays, proceedings, articles without primary data, and dissertations/theses with unpublished data were also excluded.

2.3. Information Sources and Search Strategy

Articles were retrieved from the PubMed, ScienceDirect, and Web of Science databases. The search terms comprised a combination of Europe AND (Talaromyces marneffei OR Talaromycosis OR Penicillium marneffei OR penicilliosis). The publications’ references were also reviewed to identify additional papers that met the inclusion criteria.

The initial search was conducted between February and September 2022 and was updated in April 2025 to ensure inclusion of the most recent studies. The same search strategy and eligibility criteria were applied in both rounds. However, due to the limited number of publications reporting T. marneffei, talaromycosis, P. marneffei, or penicilliosis in animals, the geographical scope was expanded globally.

2.4. Screening and Data Extraction

Two independent reviewers selected publications based on their titles or abstracts. Using a bibliographic management tool (Mendeley© Reference Manager version 2.70.0), duplicate records were excluded. Publications meeting the inclusion criteria, as well as those with titles or abstracts deemed questionable for exclusion, were read in full. Any differing opinions were discussed, and a consensus was reached.

Two authors organised data in an electronic spreadsheet into three groups: (i) companion animals, (ii) wildlife, and (iii) humans. For classification purposes, animals were grouped into companion animals, wildlife, and humans. Companion animals included dogs, cats, and ferrets, as defined under European Animal Health Law (Regulation (EU) 2016/429). Wildlife referred to non-domesticated species living in natural environments. Humans comprised patients diagnosed with talaromycosis.

When multiple cases were reported within a single study, each individual case was considered separately in the analysis but presented collectively under the same study in the summary tables.

Equivalent information was obtained from all included studies. This qualitative data encompasses details regarding the country, authors, year of publication, species, breed, age, gender, geography, lifestyle, number of infected animals, and clinical features.

2.5. Quality Assessment

Due to the descriptive nature and heterogeneity of the included studies—mostly case reports, short communications, and cross-sectional surveys—the commonly used appraisal tools such as the Newcastle–Ottawa Scale or JBI checklists were not fully applicable.

Instead, we developed a structured and transparent assessment grid based on adapted criteria from the CARE (Case Report) guidelines and previous systematic reviews dealing with similar study types. Each study was independently assessed by two reviewers across six domains: (i) clarity of objectives, (ii) case definition, (iii) diagnostic confirmation, (iv) clinical description, (v) contextual epidemiological information, and (vi) limitations acknowledged.

Each domain was scored as 1 (fulfilled) or 0 (not fulfilled/unclear), with a total possible score of 0–6. Studies were then classified as low (0–2), moderate (3–4), or high (5–6) quality. Discrepancies were resolved through discussion with a third reviewer.

Full details of the scoring system and individual assessments are provided in Supplementary Table S1.

2.6. Data Analysis

Data were analysed using JMP© Statistical Discovery Version 16.2.0. The results were presented in a structured format, categorising cases into three groups: companion animals, wildlife, and humans. This classification was deliberate as it facilitates a nuanced understanding of the epidemiology of T. marneffei across different hosts and environments.

2.7. Risk of Bias Assessment

Two independent reviewers assessed the risk of bias in the included studies. Each study was critically evaluated based on its methodology, sample size, study design, clarity of the presented data, and potential biases. Any disagreements were discussed to reach a consensus.

3. Results

Record identification and selection are depicted in Figure 4. Articles that did not meet the inclusion criteria, duplicates, incomplete articles, or studies unavailable online or on other platforms were excluded. Consequently, out of 914 results, 33 were eligible and were categorised according to the subject they addressed: talaromycosis in humans (n = 26), talaromycosis in companion animals (n = 4), and talaromycosis in wildlife (n = 3).

In addition to identifying 32 eligible studies grouped by species and context, we also analysed the main epidemiological and clinical characteristics reported. In humans, talaromycosis was most frequently associated with immunocompromised patients, primarily those with HIV, showing predominant clinical manifestations of fever, skin/mucosal lesions, weight loss, and systemic involvement of organs such as the liver and spleen. In companion animals, all the reported cases involved dogs, with respiratory manifestations being the most common. In wildlife, cases were found in an Egyptian mongoose and a Cynomolgus macaque, showing splenomegaly and skin lesions. These findings reinforce the suspicion of potential intermediary hosts and suggest that this zoonotic disease may be underdiagnosed outside endemic areas.

3.1. Qualitative Analysis of the Epidemiological and Clinical Features of T. marneffei Infection in Humans in Europe

The 26 records included in the qualitative synthesis of talaromycosis in humans reported 29 cases in 11 different countries (

Table 1. Epidemiological and clinical features of the studies included in the qualitative analysis regarding Talaromyces marneffei infection in humans in Europe.

Country	Authors/Year	n	Age/Sex	Epidemiology	CD4+/µL/AIDS	Clinical Signs
Belgium	Depraetere et al., (1998) [90]	2	34/F	Thai living in Belgium travelled to Thailand	10/Yes	Fever, weakness, lymphadenopathy, hepatomegaly, splenomegaly, skin/mucous lesions (extremities)
			34/F	Thai living in Belgium travelled to Thailand	40/Yes	Fever, weakness, lymphadenopathy, skin/mucous lesion
Denmark	Nørredam et al., (2017) [21]	1	25/F	Thai traveling from Northern Thailand	21/Yes	Fever, weight loss, cough
Denmark	Mens et al., (2004) [63]	1	31/F	Thai on vacation in Denmark	<1/Yes	Fever, weight loss, cough
France	de Monte et al., (2014) [45]	1	79/M	French, several years before travelled to Thailand and China	Normal/No	Sixty-pack-year smoking history complicated by chronic obstructive pulmonary disease (COPD)
France	Rosenthal et al., (2000) [61]	1	51/M	French travelled to Southeast Asia	10/Yes	Fever, weight loss, hepatomegaly, splenomegaly
France	Botterel et al., (1999) [91]	1	NA/NA	Thai lived in Thailand	NA/Yes	Fever, weight loss, lymphadenopathy
France	Valeyrie et al., (1999) [92]	1	39/M	French living in rural northern Thailand travelled back to France	40/Yes	Fever, weight loss, weakness, anaemia, lymphadenopathy
France	Hilmarsdottir et al., (1994) [36]	1	32/M	Congolese that had never visited Asia; 4-month course in tropical microbiology at the Institute Pasteur (Paris)	<1 /Yes	Fever, weakness, anaemia, cough, skin/mucous lesions (face, trunk, and extremities)
France	Stern et al., (1989) [93]	1	40/M	Travelled to Thailand, Myanmar	60/Yes	Fever, weight loss, cough
France	Ancelle et al., (1988) [94]	1	30/M	Travelled to Indonesia, Southeast Asia	NA/Yes	Fever
Germany	Lo et al., (2000) [35]	1	38/M	Ghanaian that never travelled to Asia	27/Yes	Fever, weight loss, anaemia, hepatomegaly, splenomegaly, skin/mucous lesions
Germany	Rimek et al., (1999) [95]	1	33/F	Thai living in Germany frequent traveller to Thailand	18/Yes	Fever, lymphadenopathy, skin/mucous lesions
Germany	Sobottka et al., (1996) [71]	1	33/M	German who had been on vacation in Thailand	20/Yes	Fever, weight loss, weakness, lymphadenopathy, hepatomegaly, splenomegaly, skin/mucous lesion (face, trunk)
Greece	Filiotou et al., (2006) [96]	1	45/M	Greek frequent traveller to Southeast Asia and China	50/Yes	Fever, weight loss, weakness, anaemia, cough, skin/mucous lesions (face, trunk)
Italy	Antinori et al., (2006) [44]	1	36/M	Italian lived 4 years in Thailand	6/Yes	Fever, weight loss, anaemia, skin/mucous lesions (face, trunk, extremities)
Italy	Viviani et al., (1993) [64]	1	33/M	Italian that had visited Thailand several times	12/Yes	Fever, anaemia, lymphadenopathy, hepatomegaly, cough, skin/mucous lesions (face, extremities)
Italy	Basile et al., (2022) [97]	1	<30/M	Chinese with frequent travels to China	4/Yes	Fever, weight loss, weakness, anaemia, skin/mucous lesions (trunk, extremities)
Netherlands	Kok et al., (1994) [98]	2	33/M	Travelled to Sumatra	NA/Yes	Fever, weight loss, splenomegaly, cough, skin/mucous lesions
			28/M	Surinamese travelled to Thailand	NA/Yes	Fever, lymphadenopathy, skin/mucous lesions
Netherlands	Hulshof et al., (1990) [69]	1	47/M	Travelled to Thailand	NA/Yes	Fever, hepatomegaly, splenomegaly
Spain	Prim et al., (2013) [62]	1	33/M	Spanish travelled to Vietnam and to the Dominican Republic	25/Yes	Fever, weight loss, lymphadenopathy, cough
Sweden	Julander & Petrini, (1997) [65]	1	38/M	Swedish had visited Northern Thailand	60 Yes	Fever, anaemia, lymphadenopathy, hepatomegaly, splenomegaly, skin/mucous lesions
Switzerland	Garbino et al., (2001) [99]	2	NA/NA	Travelled to Asia	NA/Yes	NA
			NA/NA	Travelled to Asia	NA/Yes	NA
Switzerland	Kronauer et al., (1993) [77]	1	35/M	Swiss visited Thailand	90/Yes	Fever, weight loss, splenomegaly, cough, skin/mucous lesions (face)
United Kingdom	Hall et al., (2013) [66]	1	62/M	British visited Thailand	29/Yes	Fever, weight loss, weakness, lymphadenopathy, hepatomegaly, splenomegaly, cough, skin/mucous lesions (trunk, extremities)
United Kingdom	Bateman et al., (2002) [70]	1	29/F	Thai moved to UK lived in Thailand	NA/Yes	Weakness, anaemia, lymphadenopathy, hepatomegaly, splenomegaly, cough, skin/mucous lesions (face)
United Kingdom	Peto et al., (1988) [67]	1	46/M	Visited Hong Kong, Western China, Nepal, India (bat caves)	NA/Yes	Fever, weight loss, cough, skin/mucous lesions (face, trunk)

F = female; M = male; NA = not available.

): Belgium (n = 2), Denmark (n = 2), France (n = 7), Germany (n = 3), Greece (n = 1), Italy (n = 3), the Netherlands (n = 3), Spain (n = 1), Sweden (n = 1), Switzerland (n = 3), and the United Kingdom (n = 3).

The 29 cases are distributed over the decades of 1981–1990 (n = 3), 1991–2000 (n = 13), 2001–2010 (n = 8), 2011–2020 (n = 4), and 2021–2025 (n = 1).

Of the 29 cases, 20 were male (69.0%) and 6 were female (20.7%), and there was no information available about the sex of 3 patients (10.3%). The cases were aged between 25 and 79 years, averaging 39 years (n = 25).

Of the 29 cases reported, 28 (96.6%) patients were HIV positive, and 1 (3.4%) patient was negative, but presented a severe chronic obstructive pulmonary disease (COPD); 19 (65.5%) patients had a CD4+ count below 100/µL, 1 (3.4%) had normal values, and for 9 (31.0%) there was no information available.

Clinical features were available in 27 (93.1%) cases, and in 2 (6.9%), they were not. The clinical features reported in 27 cases included (Figure 5) fever (n = 26; 96.3%), skin/mucous lesions (n = 17; 63.0%), weight loss (n = 16; 59.3%), cough (n = 12; 44.4%), lymphadenopathy (n = 12; 44.4%), splenomegaly (n = 10; 37.0%), hepatomegaly (n = 9; 33.3%), anaemia (n = 9; 33.3%), and weakness (n = 9; 33.3%). Out of the 17 cases exhibiting skin/mucous lesions, 10 (58·8%) specified the localisation: on the face and trunk (n = 3; 30.0%); on the face, trunk, and extremities (n = 3; 30.0%); on the face (n = 2; 20.0%); on the trunk and extremities (n = 1; 10.0%); on the face and extremities (n = 1; 10.0%); and on the extremities (n = 1; 10.0%).

One patient did not present typical clinical features related to talaromycosis. However, he presented a severe COPD associated with a 60-year smoking history, which resulted in immunocompromised lungs, either by corticotherapy or age-related condition [45].

Interestingly, a recent study by Matos et al. [11] identified T. marneffei colonisation in the nasal swabs of three asymptomatic individuals in Portugal. Although not representing active infection, this is the first documented detection of T. marneffei in healthy carriers outside endemic regions. This finding suggests the possibility of environmental exposure or transient colonisation in non-endemic areas, warranting further epidemiological investigation [11].

3.2. Occurrence of T. marneffei in Companion Animals Worldwide

The four studies reporting talaromycosis in companion animals focus exclusively on dogs (

Table 2. Epidemiological and clinical features of the studies included in the qualitative analysis regarding Talaromyces marneffei infection in companion animals worldwide.

Country	Author(s)/Year	Species	n	Age/Sex	Epidemiology	Clinical Signs
Thailand	Chaiwun et al., (2011) [53]	Dog	11/83	NA	Outdoor dogs Chiang Mai	Apparently healthy dogs—investigation
Brazil	Headley et al., (2017) [100]	Dog	1	adult/female	Londrina, Paraná	Cough; fever; cachectic and dyspnoeic with bilateral pulmonary crepitation
United States of America	Harvey et al., (1981) [101]	Dog	6	NA	NA	Nasal talaromycosis
United States of America	Harvey, (1984) [102]	Dog	NA	NA	NA	Nasal talaromycosis

NA = not available.

), encompassing a total of 18 cases across three countries: Thailand (n = 11), the United States of America (n = 6), and Brazil (n = 1). However, one study failed to specify the number of dogs affected by talaromycosis (Table 2).

Concerning the clinical features of the 18 reported cases, 11 (61.1%) were apparently healthy, 1 (5.6%) exhibited fever and cough, while 6 (33.3%) did not demonstrate specific clinical features associated with diagnosed nasal talaromycosis.

Pneumonia caused by T. marneffei was reported in a dog from southern Brazil, which had a concurrent infection with the canine distemper virus [100].

3.3. Occurrence of T. marneffei in Wildlife Worldwide

There are only three reported cases of T. marneffei detection in wildlife. The studies included in the qualitative analysis of talaromycosis in wildlife were conducted in Portugal and the United States of America (

Table 3. Epidemiological and clinical features of the studies included in the qualitative analysis regarding Talaromyces marneffei in wildlife worldwide.

Country	Authors/Year	Species	n	Age/Sex	Epidemiology	Clinical Signs
Portugal	Matos et al., (2023) [54]	Beech marten a	1	Adult/male		No clinical aspects—death due to car trauma; T. marneffei found in fur and skin culture
Portugal	Matos et al., (2019) [103]	Egyptian mongoose b	1	Adult/male		No clinical aspects—death due to vehicular trauma; T. marneffei found due to fur and skin culture
United States of America	Iverson et al., (2018) [104]	Cynomolgus macaque c	1	Female	From Yunnan province in Southern China	Splenomegaly. Terminal necropsy occurred as scheduled on study day 192. Lesions at necropsy: skin abrasion with several crusts on the mandibula, an adhesion between the parietal peritoneum and viscera, and severe splenomegaly

^a Martes foina, found dead due to a car collision; ^b Herpestes ichneumon, L. 1758, found dead due to vehicular trauma; ^c Macaca fascicularis assigned to the high-dose group in a 26-week toxicology study with an experimental immunomodulatory therapeutic antibody, euthanised at the scheduled terminal sacrifice on study day 192.

). They documented the occurrence of T. marneffei infection in a beech marten (Martes foina) (n = 1) and an Egyptian mongoose (H. ichneumon) (n = 1) and a Cynomolgus macaque (Macaca fascicularis) (n = 1). The cases involving the beech marten and the Egyptian mongoose exhibited no clinical features, as the animals succumbed to traffic accidents. Talaromycosis in the Cynomolgus macaque was linked to splenomegaly and skin lesions.

Cases of T. marneffei in humans, companion animals, and wildlife retrieved from the systematic review are represented per country on the world map (Figure 6).

4. Discussion

To the best of our knowledge, this study is the first systematic review of T. marneffei in humans, companion animals, and wildlife in Europe. It is the first systematic review to encompass humans and non-human animals affected by T. marneffei, regardless of the affected system or apparatus, and it is the first systematic review about T. marneffei outside endemic areas of talaromycosis.

Despite several systematic reviews conducted in humans in Asia, alongside case reports related to specific issues such as T. marneffei infection with intestinal involvement [80,81], T. marneffei infections linked to published immunodeficiency-related gene mutations [82], T. marneffei infection in HIV-infected populations in Asia [83], Talaromyces-related intestinal infections [84], and a systematic review of the literature on fungal cerebral vasculitis caused by T. marneffei and Aspergillus niger in an HIV-positive patient in 2022 [85], as well as T. marneffei infections following transplants [86,87] and T. marneffei infections in Japan [88], this study contributes to understanding the epidemiology of T. marneffei from the perspective of Planetary Health and the Stockholm Paradigm, extending beyond the usual geographies and areas of study.

The Stockholm Paradigm has established a new standard wherein pathogens rely more on their characteristics (capacity) and opportunities (exposure) to colonise than on evolution. This scenario, linked to climate change, overpopulation, the migratory movements of humans and animals, and the close proximity between nature and civilisation, contributes to the emergence of infectious diseases [2,3]. Furthermore, fungal diseases typically associated with animals are appearing in humans due to increasing pressure from human activities on their habitats and the crossing of host barriers, necessitating active surveillance [11,54,103]. This new paradigm demands a fresh perspective on health—Planetary Health—even though it arises from a complex, multidimensional, and multifactorial framework (social, economic, environmental, technological, political, and health) and is grounded in the fundamental principle that there is no health on a sick planet [4,5,7,8]. Collectively, these factors can help explain some of the gaps identified in the epidemiology of T. marneffei, particularly its geographic dispersion beyond endemic borders and its emergence in new hosts [35,36,53,100,101,102,103,104].

However, while talaromycosis is believed to be an imported condition primarily found outside Southeast Asia, instances of infections in humans and animals unrelated to those locations have also been reported [11,35,36,53,54,100,101,102,103,104].

Despite the transmission mechanisms remaining insufficiently understood and bamboo rats being considered natural reservoirs, T. marneffei has been identified in dogs, beech martens, Egyptian mongooses, and Cynomolgus macaques [53,54,100,101,102,103,104]. These reports strengthen the hypothesis regarding the involvement of “mediator” animals between rats and humans, addressing the lack of proximity between the two that could explain direct transmission. A significant finding of this review is the emergence of T. marneffei in humans and animals with no direct link to the endemic regions of Southeast Asia. However, it is important to note that indigenous human cases outside of Southeast Asia remain rare, and these occurrences should be interpreted cautiously until further evidence supports a broader transmission scenario. A plausible hypothesis, as indicated by some studies [50,51,96,97,98,99,100], involves the role of intermediary or ‘liaison hosts’, which may act as a bridge for the pathogen between bamboo rats and humans. These hosts could facilitate the spread of the fungus beyond its traditional geographic boundaries. Furthermore, the saprophytic nature of T. marneffei in soil environments suggests that it may persist in non-endemic regions, potentially infecting individuals who come into contact with contaminated soil or animals. This highlights the need for more extensive research into the environmental reservoirs and transmission pathways of T. marneffei, particularly in areas where it has not been previously reported. Moreover, dogs tested positive for T. marneffei on nasal swabs in Thailand, suggesting they may acquire the organism through nasal contact with soil and could also serve as a potential reservoir [53]. The suggestion that dogs might acquire T. marneffei through nasal contact with soil raises questions for other animals exhibiting similar behaviours or those in contact with humans, such as elephants [53].

Furthermore, the detection of T. marneffei in nasal swabs from healthy volunteers in Portugal introduces new questions regarding its environmental presence and potential asymptomatic carriage in humans [11]. This finding could indicate environmental exposure or transient colonisation, which might have implications for immunocompromised individuals residing in non-endemic regions. Future studies should explore the role of asymptomatic carriers in the epidemiological cycle of T. marneffei, particularly in relation to sporadic cases observed in Europe.

Further supporting the notion of T. marneffei presence outside endemic regions, a recent retrospective analysis of hospital records in Spain documented cases of imported systemic endemic mycoses, including talaromycosis, over a period of 24 years [105]. Although this study was based on aggregate hospital data and did not provide detailed clinical descriptions, its findings underscore the clinical relevance of T. marneffei in non-endemic European countries. These data suggest that talaromycosis, although considered rare in Europe, may be underreported and should be included in the differential diagnosis of disseminated fungal infections in travellers or immigrants from endemic regions. Further research is warranted to explore its epidemiology, clinical management, and potential environmental reservoirs in these settings. All reported cases of talaromycosis in humans in Europe involved immunocompromised patients; only one was HIV-negative but had COPD related to 60 years of smoking history, which led to immunocompromised lungs due to corticotherapy and age. This finding supports the opportunistic nature of the infection and could help explain the observed latency of a few years between infection and disease in some cases and also raises suspicions regarding a saprophytic behaviour in immunocompetent individuals, which may explain its global emergence in animals and humans outside endemic areas. Additionally, the recent detection of T. marneffei in nasal swabs of asymptomatic individuals in Portugal introduces new questions about its ecological presence and potential environmental reservoirs outside Southeast Asia [11]. Unlike previous reports that focused on clinical cases, this study identified T. marneffei colonisation in healthy carriers, raising the possibility of silent carriage in human populations. Although the clinical significance of this colonisation remains unclear, its identification suggests that the fungus may persist in the environment in ways that were previously unrecognised. This observation underscores the need for further studies to explore environmental exposure pathways and the epidemiological relevance of asymptomatic carriers in non-endemic regions.

The clinical features observed in humans in Europe correspond to those reported in the literature [18,20,29,55].

Among the 29 cases reported in Europe, 28 (96.6%) patients were HIV positive, and 19 (65.5%) had a CD4+ count below 100/µL. This underscores that T. marneffei is more frequently associated with immunocompromised individuals, particularly those with HIV, thereby reinforcing the necessity for T. marneffei screening in HIV patients with CD4 counts under 100/µL. Furthermore, bone marrow studies are vital to confirm the diagnosis, as delays in diagnosis increase morbidity and mortality, even with antifungal therapy [106].

Cytological and histological examinations can provide presumptive diagnoses, but microbiology culture remains the gold standard. The most reliable samples for fungal cultures include bone marrow (100%), a skin biopsy (90%), and a blood culture (76%). While bone marrow culture is predominantly used in immunocompromised individuals, a broader application of this method could potentially unveil more latent or asymptomatic cases, particularly in immunocompetent patients. Although available serological and genetic diagnostic methods show promise, they have yet to be routinely implemented [29,88,107]. In animals, due to the low number of diagnosed cases and the conditions under which identification occurred (post-mortem examination or screening), a clear clinical pattern of talaromycosis has not been fully established, and infection may be overlooked, as it is in humans [10,53,103]. However, in the few animals where clinical features were documented, signs such as splenomegaly, skin lesions, cough, fever, cachexia, and respiratory signs resembling human clinical features were observed [100,104]. Diagnostic confirmation in animals, including dogs, has primarily been achieved through microbiological cultures, such as nasal swabs; this underscores the significance of companion animals in the potential epidemiology of the disease. The role of companion animals and wildlife in the spread of this pathogen should be closely monitored, particularly in light of increasing human pressure, which seems to be a key factor in the emergence of new epidemics [108]. Surprisingly, the WHO places T. marneffei on its list of priority pathogens for research, development, and public health action, yet it entirely disregards the Planetary Health perspective and the Stockholm Paradigm [79].

Based on our results, cases of T. marneffei are not restricted to imports from endemic areas or bamboo rats. Therefore, this agent must be given greater attention outside endemic areas, in humans, companion animals, and wildlife. This requires coordinated, interdisciplinary strategies that operationalise the One Health framework, including (i) integration of environmental sampling—particularly of soil and air dust from areas with human or animal contact; (ii) routine screening of immunocompromised patients in non-endemic regions, especially those with compatible clinical signs; and (iii) strengthening of veterinary surveillance systems for emerging fungal infections in domestic and wild animal populations. Such practical measures will support early identification of cases and potential environmental sources, in line with the principles of the Planetary Health and Stockholm Paradigm approaches.

The updated literature search confirmed the ongoing scarcity of published reports on T. marneffei infection in humans in Europe and in companion and wildlife animals outside endemic regions.

This study has limitations linked to the databases used—PubMed, ScienceDirect, and Web of Science—as well as the search terms employed. Future systematic reviews should expand their search bases to incorporate studies that are not included in this systematic review.

5. Conclusions

This systematic review identified and summarised reported cases of talaromycosis in humans, companion animals, and wildlife, with a specific focus on human cases in Europe. This review identified a total of 29 cases in humans and animals outside endemic regions. While most of these were associated with travel or residence in Southeast Asia, a few cases may represent autochthonous infections. These findings support the hypothesis that T. marneffei might be more widespread than previously assumed. Non-specific clinical manifestations, diagnostic delays, and the risk of misidentification contribute to the continued underdiagnosis of talaromycosis, particularly in non-endemic regions. All confirmed human cases in Europe involved immunocompromised patients, most of them HIV-positive with CD4 counts below 100/μL, reinforcing the need for targeted screening in high-risk populations.

This raises the possibility of intermediary hosts facilitating transmission, though further evidence is needed. Clinical data in animals remain sparse, and diagnosis has often been incidental.

In animals, although cases are rare, T. marneffei has been identified in species beyond its known reservoirs, such as dogs, beech martens, and monkeys.

The main limitations of this review include the small number of studies, especially in non-human hosts, and the limited size of the available datasets. Moreover, variations in study design and quality pose challenges to standardised interpretation.

Given the pathogen’s emergence in unexpected species and settings, we recommend implementing systematic One Health surveillance protocols that integrate environmental sampling (e.g., soil or dust) and animal monitoring. Additionally, socioeconomic vulnerability—especially poverty—appears to be a significant determinant of disease risk.

Finally, the emergence of T. marneffei in non-endemic regions aligns with the broader framework of Planetary Health and the Stockholm Paradigm, which highlight the interplay between human activity, ecological disruption, and infectious disease emergence. Addressing talaromycosis as a neglected fungal disease demands a transdisciplinary approach, proactive clinical vigilance, and improved diagnostic accessibility to reduce its global burden.