Trend Analysis of Fungal Infections Based on Culture among Inpatients in Henan Province from 2018 to 2023

Globally, the burden of invasive fungal infections has risen sharply in recent decades, driven not only by medical advances but also by emerging environmental and climate-related factors that favor fungal growth and transmission (George et al. 2025). According to the World Health Organization, fungal infections are increasingly recognized as a significant threat to public health, particularly among immunocompromised populations (Giannella et al. 2025). Numerous studies have indicated that significant differences exist in fungal infection status and fungal species composition among patient populations in different countries, regions, and those with comorbid underlying diseases (Liao et al. 2013; Chen et al. 2018; He et al. 2018; Xiao et al. 2018; Yang et al. 2020; Yang et al. 2021; Ding et al. 2023). In Europe, the cases of candidiasis and aspergillosis dominate, followed by mucormycosis. Epidemiological studies have shown an increasing trend in the incidence of all three entities. The recent COVID-19 pandemic has led to a significantly increasing incidence of invasive fungal diseases among hospitalized patients (Lass-Flörl and Steixner 2023). With the evolution of antiretroviral therapy (ART), HIV-associated cases of cryptococcosis and other opportunistic fungal infections have declined in North America, yet diseases caused by health care-associated fungal pathogens, including Candida species, Aspergillus species, and other molds, have increased, largely owing to substantial increases in at-risk populations (Seagle et al. 2021). Therefore, empirical antifungal treatment should be guided by the patient’s clinical condition and local epidemiological patterns.

In China, surveillance data have shown a steady rise in both superficial and invasive fungal infections, with a significant increasing trend in invasive candidiasis (Liao et al. 2013; Chen et al. 2018; Yang et al. 2021; Ding et al. 2023;), while other studies indicated a decreasing trend in the incidence rate of Candida albicans over the past decade (He et al. 2018). However, these data are often derived from general hospitals, and few large-scale analyses focus on specialized infectious disease hospitals or specific provinces. Henan Province, located in central China, has a dense population and a high burden of infectious diseases, yet comprehensive data on fungal infections in this region remain scarce. Most infectious disease patients have a weakened immune system due to prolonged use of antiviral drugs and antibiotics. To date, only a few studies have compared fungal infections among patients with different infectious diseases. Moreover, comparisons of fungal epidemiology between patients with infectious versus non-infectious conditions remain limited, particularly in real-world clinical settings.

To understand the spectrum and epidemiological characteristics of fungal pathogens in patients with infectious diseases, we conducted a retrospective analysis of the fungal distribution and epidemiological features of inpatients at Henan Infectious Diseases Hospital from January 2018 to December 2023. The findings provided important insights to support accurate clinical diagnosis and inform infection control strategies.

Over the past five years, our hospital has demonstrated a steady annual increase in fungal positivity, with marked rises in C. albicans, A. fumigatus, and A. flavus, particularly during the past two years. The annual increase in fungal detection rates, especially after 2020, may reflect both elevated awareness and surveillance of secondary fungal infections during and after the COVID-19 pandemic, as well as increased antifungal usage and immunosuppression in patients with prolonged illness (Bartoletti et al. 2021; Vargas-Espíndola et al. 2023). Notably, pathogens, such as T. marneffei and C. neoformans were detected more frequently in our cohort, especially among immunocompromised individuals, such as those with HIV/AIDS. This contrasts with findings from general hospitals, where C. glabrata and C. parapsilosis may be more prevalent in post-surgical or transplant populations (Xu et al. 2019; Xia et al. 2022; Lou et al. 2023). The absence of pediatric and transplant wards in our hospital may partly explain this deviation in pathogen spectrum. Additionally, the endemicity of T. marneffei in southern and central China, along with the high burden of HIV/AIDS in our center, may contribute to the increased detection rates of this dimorphic fungus.

This study demonstrates significant variations in the prevalence of fungal infections across different departments within our hospital. Among these, HIV/AIDS patients exhibited a notably higher fungal detection rate (19.26%), predominantly caused by C. albicans (14.11%). These infections were primarily confined to the oral cavity/esophagus, resulting in symptoms such as oropharyngeal candidiasis and odynophagia. Additionally, T. marneffei (1.54%) and C. neoformans (1.82%) were predominantly detected in sterile body fluids (such as blood, cerebrospinal fluid, pleural fluid, and ascitic fluid) in this cohort, with detection rates significantly higher than those in patients with other infectious diseases, which is consistent with other studies (Limper et al. 2017). AIDS patients have compromised immune function, making them susceptible to common opportunistic fungal infections that can further exacerbate their condition.

The fungal detection rate in our ICU was 19.04%, which was slightly lower than that in the AIDS department but significantly higher than that in other general departments; the predominant species were C. albicans, C. tropicalis, and A. fumigatus. ICU patients are critically ill and undergo numerous invasive procedures, such as tracheal intubation; mechanical ventilation; and the placement of central venous catheters, arterial catheters, gastric tubes, urinary catheters, and various drainage tubes, thereby increasing the likelihood of fungal infections.

Some studies have shown that tuberculosis patients are coinfected with Candida and Aspergillus species (Liu 2020; Baluku et al. 2021). In our tuberculosis department, the fungal detection rate was 4.41%, with C. albicans, A. fumigatus, and A. flavus being the primary species detected. Patients with pulmonary tuberculosis are prone to pulmonary fungal infections due to poor physical condition, weakened immune function, reduced phagocytic activity of pulmonary macrophages, and decreased ciliary clearance of inhaled pathogens from the bronchial mucosa (Kou et al. 2019; Fan et al. 2020). Accumulating evidence suggests that pulmonary fungal infection should be considered if the patient does not exhibit any significant improvement after antituberculosis treatment, especially if he/she has long-term pulmonary tuberculosis and/or has used broad-spectrum potent antibiotics and/or glucocorticoids for a prolonged period (Infection Group of the Respiratory Diseases Branch and Editorial Committee of the Chinese Journal of Tuberculosis and Respiratory Diseases 2007; Wei et al. 2017; Guo et al. 2019). Consequently, the results emphasize the importance of fungal microbiological diagnosis in patients with high-risk factors for tuberculosis and fungal coinfections.

Studies have indicated that patients with liver disease are susceptible to fungal infections due to reduced leukocyte phagocytosis and chemotaxis, impaired function of mononuclear macrophages, hypoproteinemia, and intestinal flora imbalance, with the infection rate showing an upward trend. Among these, yeast-like fungal infections predominate, with C. albicans accounting for the highest infection rate (Ji et al. 2017). Additional research has indicated that patients with severe liver disease, owing to their compromised immunity, are susceptible to secondary infections. Although fungal infection rates may be low in such patients, the prognosis is poor, and short-term mortality is high (Chen and Chen 2021). This study found that the fungal detection rate in the hepatology department was relatively low, approximately 0.71%, which was lower than that in non-infectious disease patients (1.42%), with C. albicans and A. fumigatus identified as the primary fungal species.

It can be observed that the fungal infection rate among patients in our hospital exhibits seasonal variations. Notably, the positivity rate of C. albicans was relatively high from June to September, with the majority of cases detected from sputum and oral swabs. C. albicans is a common commensal fungus in the human body that widely colonizes mucosal surfaces (e.g., the oral cavity, gastrointestinal tract, and vagina) in both healthy individuals and immunocompromised hosts. Therefore, a positive detection of C. albicans in oral samples does not necessarily indicate active infection. Furthermore, the geographical location of our hospital in central China (Henan Province) features a typical continental monsoon climate, characterized by hot and humid summers. These environmental conditions from June to September may promote fungal growth and colonization on mucosal surfaces, especially for species, such as C. albicans, which thrive in warm, moist environments. This climatic factor likely contributes to the higher detection rates observed during these months. Seasonal variation in fungal infection rates has been similarly reported in other regions with comparable climates, suggesting a possible environmental influence on fungal epidemiology (Zukiewicz-Sobczak 2013). HIV/AIDS patients exhibited the highest detection rate of C. albicans (14.11%), followed by ICU patients (9.53%) and tuberculosis patients (2.05%), which were significantly higher than those in hepatitis virus-infected patients (0.23%) and non-infectious disease patients (0.92%). These findings align with the prevalence of oropharyngeal/esophageal candidiasis symptoms observed in patients from corresponding departments. Therefore, the significance of oral C. albicans positivity in clinical samples should not be overlooked, particularly among HIV/AIDS patients, critically ill patients, and tuberculosis patients.

Additionally, the positivity rates of A. fumigatus and A. flavus among patients in our hospital showed significant increases in January, February, and December. This seasonal pattern contrasts with the conventional understanding that “fungi are more prevalent in the summer environment.” The underlying mechanisms can be analyzed from multiple perspectives. First, although the general population inhales a large number of fungal spores daily, the pathogenicity of fungi is highly dependent on the host immune status, only when the immune function is compromised (e.g., HIV infection) or other susceptible factors are present (e.g., long-term use of glucocorticoid) can spores break through the defense and cause invasive infection (Wang et al. 2018). Second, aspergillosis, a common complication of respiratory infections such as influenza and COVID-19 (Tang et al. 2020; Bartoletti et al. 2021), its epidemic trends are closely related to the seasonal peaks of respiratory infectious diseases. Data from the Chinese Center for Disease Control and Prevention (CDC) show that the incidence of influenza and other respiratory infectious diseases in China significantly increases in January, February, and December; consistent with this, the annual average detection rate of influenza in our hospital also peaks during this period. Notably, after China reclassified COVID-19 as a Category B notifiable infectious disease and adjusted management measures on January 8, 2023, restrictions on population mobility were relaxed, leading to widespread infection with COVID-19 among the general population that year. Consequently, our hospital reported a high proportion of COVID-19 cases before July 2023. The combined prevalence of influenza and COVID-19 may have jointly driven the increased detection rates of A. fumigatus and A. flavus during the same period. Further analysis of data from the control period (early 2020 to the end of 2022) revealed that despite lower infection rates of COVID-19 and influenza due to enhanced Category B control measures (including mobility restrictions), the fungal detection rate showed an upward trend. This paradoxical phenomenon may reveal a positive correlation between disease severity and the risk of fungal infection. When patients seek medical care for severe illnesses, their immune suppression is more pronounced, thereby increasing the risk of fungal colonization/infection. In summary, the seasonal increase in the detection rates of A. fumigatus and A. flavus is the result of the combined effects of respiratory infectious disease epidemics, changes in host immune status, and disease severity, rather than solely due to increased environmental fungal exposure.

To summarize, the seasonal peak in the positivity rate of C. albicans during summer (June-September) may be associated with local climatic conditions (conducive to excessive fungal growth), while the detection peak of Aspergillus species in winter may be linked to respiratory virus epidemics and increased glucocorticoid use.

Additionally, this study revealed a significantly greater fungal positivity rate in rural patients than in urban patients. Among them, C. albicans, A. flavus, T. marneffei, and C. neoformans showed statistically significant differences in detection rates. These trends may be associated with increased occupational exposure to fungi through agricultural activities and environmental contact in farming populations. Furthermore, the lower HIV screening rates and suboptimal antiretroviral therapy adherence in rural areas might contribute to the high prevalence of T. marneffei and C. neoformans infections. The significantly higher fungal positivity among rural patients may reflect increased environmental exposure and disparities in healthcare access, leading to delayed diagnosis and treatment.

The predominance of C. albicans across nearly all departments, contrasted with the department-specific peaks of T. marneffei and C. neoformans in AIDS patients, highlights the influence of underlying disease profiles on fungal epidemiology. The particularly high fungal positivity rates observed in the AIDS and ICU departments (19.26% and 19.04%, respectively) support the important role of immune suppression and invasive procedures in fungal colonization and infection, consistent with the higher susceptibility observed in these units. In the present study, patients in departments treating chronic infectious conditions, such as AIDS and tuberculosis, had markedly higher fungal detection rates, underscoring the need for targeted surveillance and empiric antifungal strategies in these high-risk populations. These findings suggest that the fungal pathogens in infectious disease hospitals may diverge significantly from that in general hospitals due to differences in patient populations, comorbidities, immune status, and environmental exposures.

As this analysis was based on fungal detection rather than confirmed clinical infections, it is possible that some of the isolates, particularly C. albicans from non-sterile sites, reflect colonization rather than true infection. Nevertheless, their distribution provides important clues for empirical antifungal strategies. We acknowledge that relying solely on fungal culture and MALDI-TOF MS may miss certain cases due to the potential for false-negative results, particularly in patients who had received prior antifungal or broad-spectrum antimicrobial treatment. However, culture-based methods combined with MALDI-TOF remain standard, widely used, and cost-effective techniques for large-scale retrospective analyses in real-world hospital settings, especially where molecular diagnostics are not routinely available. Although this may result in underestimation of the true infection burden, our findings still provide a valuable reflection of the clinical caseload and detection patterns of fungal pathogens across a large and diverse patient population. The upward trend observed is thus likely a conservative estimate and may in fact reflect a more substantial underlying epidemiological burden.

In summary, the fungal positivity rate among infectious disease patients at our hospital has shown a steady increase from 2018 to 2023, with C. albicans, A. fumigatus, and A. flavus being the most commonly detected pathogens. The distribution of fungal species varies substantially across different clinical populations. HIV/AIDS patients showed the highest fungal detection rate (19.26%), primarily presenting with oropharyngeal or esophageal candidiasis, and also had disproportionately higher rates of opportunistic pathogens, such as T. marneffei and C. neoformans in sterile body fluids. ICU patients, who undergo frequent invasive procedures, had similarly high detection rates, with C. tropicalis and A. flavus being more prominent. Patients with tuberculosis also demonstrated notable coinfection with Candida and Aspergillus species, often mimicking or compounding their respiratory symptoms. Furthermore, patients from rural areas exhibited significantly higher fungal detection rates, possibly due to environmental exposure and lower access to timely HIV diagnosis and treatment. These findings highlight the need for fungal screening strategies based on patient profiles, especially among immunocompromised individuals, critically ill patients, and those with chronic respiratory diseases, to enable early identification and targeted antifungal therapy. Clinicians should integrate both epidemiological patterns and clinical risk factors when interpreting positive fungal results, especially in departments where fungal infections contribute significantly to morbidity.