Aspergillus and Aspergillosis in People with Chronic Diseases

Abstract

Numerous human diseases are caused by Aspergillus species. Mold infections can be more severe in people with weakened immune systems and chronic illnesses. People with underlying chronic conditions are more likely to contract an Aspergillus infection than immunocompromised patients, who are more likely to develop an invasive infection with these opportunistic molds. These disorders include Aspergillus bronchitis, allergic bronchopulmonary aspergillosis, diabetes, cystic fibrosis, severe asthma with fungal sensitivity, and other inflammatory and allergic conditions. The impact of Aspergillus infections in patients with selected chronic infections and the treatment of these infections are discussed in this review along with the most recent research on these topics.

1. Introduction

According to Merad et al. [1], Aspergillus is a form of fungi that is frequently found in a variety of environmental niches, including soil, decaying plant matter, and indoor air. Aspergillus recolonizes indoor areas with high humidity levels, such as air conditioning units and wet carpets [2]. Even though the genus Aspergillus contains more than 300 species, Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, and Aspergillus terreus have a disproportionate amount of pathogenicity. The most well-known and often found pathogenic species is Aspergillus fumigatus, followed by A. flavus; however, A. niger and A. terreus also exhibit virulence. As a saprophyte organism, Aspergillus is capable of colonizing the mucus masses and residual cavities of individuals with chronic obstructive pulmonary disease (COPD) [3].

Although Aspergillus infection often does not harm healthy people, people with chronic conditions are more likely to contract the infection, which could have serious negative effects on their health. Chronic conditions including asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis, and diabetes impair the immune system and make a person more susceptible to infections. Aspergillus bronchitis, Aspergillus pneumonia, and allergic bronchopulmonary aspergillosis (ABPA) are only a few of the respiratory conditions that can develop after inhaling Aspergillus spores [4]. An important consequence of Aspergillus infection in people with chronic medical problems is an increased incidence of morbidity and mortality. These people with chronic illnesses who contract an Aspergillus infection are more likely to endure worsened symptoms, extended hospital stays, and complications such as the potentially fatal invasive aspergillosis. Additionally, Aspergillus infection may worsen preexisting chronic disorders, creating new difficulties in treating them [5]. Aspergillus colonization of the airways is linked to an increased incidence of disease exacerbations and a reduction in lung function, making Aspergillus infection a serious hazard to people with cystic fibrosis. Aspergillus infection can sporadically result in deadly invasive pulmonary aspergillosis (IPA) in cystic fibrosis (CF) patients. Aspergillus infections can harm a person’s health if they already have a chronic illness [6]. To reduce their risk of infection, people with chronic illnesses must take certain precautions. These precautions include avoiding settings with a lot of mold and fungi, practicing excellent hygiene, and seeking immediate medical attention if they feel symptoms of an infection. The clinical progression of chronic disorders can be significantly influenced by Aspergillus and aspergillosis. People who already have respiratory conditions like asthma, COPD, or cystic fibrosis run the risk of having their symptoms worsened by Aspergillus, which could result in progressive lung damage. Long-term Aspergillus exposure, especially in susceptible people, may be a factor in the emergence of chronic lung diseases. The therapy of Aspergillus infection is also significantly complicated by the increased risk of severe forms of aspergillosis in immunocompromised persons [7]. In this body of research, we will look at how Aspergillus infections affect patients with chronic conditions as well as how to avoid and treat them.

2. Clinical manifestations, diagnosis, and epidemiology of the spectrum of Aspergillus diseases

Lung infections brought on by Ammophilus fumigatus are produced by airborne conidia, which are present in both indoor and outdoor settings at concentrations ranging between 1 and 100 conidia per m³, but which can reach up to 108 conidia per m³ in some circumstances [8]. Because of this, Aspergillus spp. are regularly found in the respiratory tract cultures of asymptomatic patients who do not exhibit any symptoms of an invasive or allergic illness [9], and Aspergillus DNA has been found in 37% of lung biopsy samples from healthy persons. Additionally, Aspergillus colonization in up to 30% of people with chronic obstructive pulmonary disease (COPD) has been confirmed by culture [10]. Inadequate expression of the transcriptional factor ZNF77 in bronchial epithelia leads to defective epithelial cell integrity and upregulation of extracellular matrix (ECM) proteins that support conidial adhesion, which is the genetic basis of Aspergillus colonization, according to recent research [8]. Although Aspergillus colonization does not always result in infection, it increases the risk of invasive infection in several immunocompromised individuals. However, because invasive pulmonary aspergillosis arises from breathing Aspergillus conidia, environmental exposures affect the epidemiology of the disease. There have been several nosocomial clusters of invasive pulmonary aspergillosis (IPA) reported over the past three decades, which are typically associated with issues with hospital architecture and air-handling equipment [11].

Aspergillus species are responsible for a wide range of human ailments. Based on the underlying immunological status of the host, Aspergillus illnesses can be roughly categorized into three classes [8]. These three categories have various pathogenetic routes, clinical manifestations, and overlapping traits. These three groups are depicted in Figure 1 based on their respective clinical importance. The sections that follow will discuss a few chronic illnesses and their connections to the Aspergillus species.

Figure 1.

Syndromes related to aspergillosis patients with various immune statuses.

Among the syndromes related to aspergillosis patients with various immune statuses are allergy-related bronchial pulmonary aspergillosis (ABPA), chronic pulmonary aspergillosis (CPA), invasive pulmonary aspergillosis (IPA), and invasive bronchial aspergillosis (IBA) as shown in Figure 1 [8].

3. Effect of Aspergillus infections on people with lung chronic disease

3.1 Asthma

The increased incidence and prevalence of asthma in the industrialized world have generated significant concerns and coordinated research efforts. Numerous theories to explain this significant change in public health have emerged as a result of the lack of clarity surrounding the etiopathogenesis of asthma. One of the most well-liked theories, the hygiene hypothesis, makes use of the fascinating interaction between the innate and acquired immune systems. According to this theory, the developed world’s increased hygiene is a direct cause of the growth in asthma [12]. Even while this advancement has all but eliminated many infectious diseases like cholera, the lack of pathogen exposure in early children seems to cause allergies and asthma later in life. The hygiene hypothesis states that any bacterium that triggers a sizable type 1 cytokine response may prevent the onset of asthma later in life even if no established list of illnesses that are “protective” has been created [13]. The emergence of Th1-type autoimmune illnesses and the anti-allergic benefits of robust Th2-cytokine-mediated parasite infections cannot exclusively be attributed to insufficient environmental pathogen exposure. The same cannot be stated for the growth of allergies and asthma. Many studies are currently devoted to figuring out how genetics affects allergies and asthma [14].

Inhalant allergens have a key role in triggering the airway inflammation seen in patients with allergic asthma. It is becoming increasingly clear that fungi are important inhalant allergens [13]. Numerous studies have linked asthma to the vast genus of spore-forming fungus known as Aspergillus. The “aspergillum” brush used to dispense holy water is referenced in the name of this fungus. All people inhale its spores, although a healthy, normal person is rarely affected by them [15]. However, the fungus spores get stuck in the thick, viscous secretions that are frequently present in the airways of asthmatics. To maintain this state, which commonly develops in atopic people and produces asthma, Aspergillus antigens are continuously breathed [3].

It is significant to mention that allergic broncho-pulmonary aspergillosis (ABPA) and chronic pulmonary aspergillosis (CPA) can confuse asthmatic patients’ symptoms [16]. The primary cause of allergic bronchopulmonary aspergillosis, which is primarily linked to Aspergillus fumigatus, is hypersensitivity illness. The threatening type of aspergillosis is usually present in people with allergic bronchopulmonary aspergillosis [8]. Asthma sufferers are prone to respiratory infections brought on by the common mold genus Aspergillus. According to Seyedmousavi et al. [17], exposure to Aspergillus can cause allergic reactions in people with asthma, resulting in airway inflammation and constriction and making it harder to breathe.

The effects of Aspergillus infections on people with asthma can vary depending on the infection’s intensity and the person’s general health. Aspergillus infections may sporadically result in the development of allergic bronchopulmonary aspergillosis (ABPA), a chronic respiratory illness marked by symptoms like coughing, wheezing, and dyspnea, according to Chotirmall et al. [7]. When Aspergillus infections are severe, they can result in invasive aspergillosis, a condition that can be fatal and seriously harm the lungs. Kosmidis and Denning [18] claim that those with weakened immune systems, such as those undergoing chemotherapy or organ transplantation, are more likely to contract this condition.

Epithelial cells or alveolar macrophages cause inflammation as part of innate immunity’s protective mechanisms. Toll-like receptors (TLRs), C-type lectin receptors (CLRs), and nucleic-binding oligomerization domain (NOD)-like receptors (NLRs) are examples of pattern recognition receptors that are used by innate immunity to identify fungi. Aspergillus stimulates these receptors, which activates cytokines and results in cellular and humoral immune responses. Aspergillus is protected and eliminated by T-helper cell type 1, while T-helper cell type 2 reacts by preventing its elimination. The severe inflammation seen in allergic bronchopulmonary aspergillosis, which results in eosinophilia, increased mucus formation, and IgE antibody production is caused by an excessive T-helper cell type 2 response. This inflammation leads to airway hypersensitivity, which aggravates asthma by causing bronchial obstruction [19, 20]. The clinical spectrum of Aspergillus-associated hypersensitivity respiratory diseases includes Aspergillus-induced asthma, allergic bronchopulmonary aspergillosis (ABPA), and allergy Aspergillus sinusitis (AAS). Hypersensitivity pneumonitis can also be brought on by Aspergillus, albeit this is often only seen in non-atopic persons. Aspergillus-caused asthma has not yet received the attention it merits. Given the association between the mold Aspergillus and asthma, it is imperative to understand the frequency of Aspergillus sensitivity in asthmatic participants in each geographical area [21].

3.2 Arthritis

Gamaletsou et al. [22] found that Aspergillus infection can elevate inflammatory levels in the body, which can aggravate arthritic symptoms. Infections with Aspergillus can affect the respiratory system and result in symptoms, including coughing, wheezing, and shortness of breath. This may be particularly difficult for people with arthritis who already experience breathing issues due to joint pain and stiffness [23]. Furthermore, those with impaired immune systems who have arthritis are more likely to develop Aspergillus infections. For those who take immunosuppressive medicines to address their arthritic symptoms, this may be very challenging. Furthermore, Aspergillus infections can increase pain, stiffness, and mobility issues in those who already have arthritis by damaging their joints [22]. Due to the infection’s potential to hinder the body’s capacity to absorb medication, Aspergillus infections can also undermine the efficacy of arthritis treatments [24].

3.3 Cystic fibrosis

Cystic fibrosis (CF), the most common fatal genetically inherited disease that is caused by a mutation in a gene that encodes the CFTR protein, affects one in every 2400 live births in Caucasian cultures [25]. Two thousand different CFTR variations have so far been identified, with the most frequent being F508del, a single amino acid loss that accounts for about 70% of disorders [26]. Infants born today are expected to live into their fifth decade with CF, which has improved throughout a generation from a condition that often killed infants in their early years to one with a median lifespan of 28 years.

Ion fluxes and intracellular calcium homeostasis are compromised when the CFTR protein is absent from the cell membrane, where it acts as an ATP-driven chloride channel. Through a cycle of infection and exaggerated inflammation, thickened mucus forms in the airway epithelial cells, impeding the mucociliary clearance of inhaled pathogens and ultimately leading to respiratory failure [27, 28]. Continual lung infections and airway inflammation are the primary causes of mortality and morbidity in CF patients. To end this destructive cycle, the prevention and treatment of airway infection have been the cornerstones of clinical management; yet, respiratory failure brought on by chronic or recurrent infection still accounts for over 90% of fatalities [29]. The pathogenesis of respiratory decline has typically been studied through the role of bacterial pathogens like Staphylococcus aureus, Pseudomonas aeruginosa, Haemophilus influenzae, and the Burkholderia cepacia complex. The significance of Aspergillus species and other filamentous fungi in the pathogenesis of non-ABPA (allergic bronchopulmonary aspergillosis) respiratory illness in CF has received little attention, despite their frequent isolation in respiratory samples. However, it has become clearer that Aspergillus fumigatus may also be crucial for the CF lung [30]. People with CF are susceptible to respiratory infections brought on by the fungus Aspergillus [31].

Aspergillus infections can have a variety of impacts on CF patients, depending on the infection’s severity and overall health. The following are a few of the implications of Aspergillus infections in people with CF: Aspergillus infections can cause a variety of respiratory symptoms, including coughing, wheezing, shortness of breath, chest pain, and fever. These symptoms can be extremely severe in CF patients because the underlying illness of CF already damages a person’s lungs [18]. Again, Aspergillus infections can damage the lungs and impede their ability to function, leading to greater breathing issues and a worsening of CF symptoms. Lung damage caused by Aspergillus infections can occasionally be permanent [32]. Furthermore, Aspergillus infections can reduce the quality of life of CF patients by limiting their ability to perform routine tasks, attend school or work, and participate in social activities [33]. Infections with Aspergillus can also weaken immunity, raising the possibility of further respiratory infections in CF patients [34]. Additionally, treating Aspergillus infections in CF patients can be difficult and typically requires lengthy courses of antifungal medication. The infection may occasionally come back even after treatment [35].

3.4 Chronic obstructive pulmonary disease

People who have Aspergillus spp. growing in their airways and having chronic obstructive pulmonary disease (COPD) are often regarded as contaminants. Although it is unclear how common invasive pulmonary aspergillosis (IPA) is in this community, accumulating evidence suggests that individuals with severe COPD have an increased risk of contracting the condition [10]. According to certain estimates, COPD is the underlying illness in 1% of individuals with IPA. Given that tissue samples are infrequently taken before death in COPD patients, it may be difficult to make a definitive diagnosis of IPA. To make a diagnosis, a combination of clinical traits, radiographic findings—often from thoracic computed tomography scans—microbiological results, and occasionally serological data is used [36].

Chronic obstructive pulmonary disease (COPD), a progressive lung disorder that makes breathing challenging, can be brought on by several factors, including extended exposure to irritants like cigarette smoke [37]. A reaction to Aspergillus called allergic bronchopulmonary aspergillosis (ABPA) can occasionally strike patients with COPD. Wheezing, coughing, and shortness of breath are some of the symptoms of ABPA, which can worsen if left untreated [38].

4. Effects of Aspergillus infections on people living with other chronic infections

4.1 Hepatitis B and C viruses

Co-infection with Aspergillus may increase the pathogenicity of the hepatitis B and C viruses, leading to increased hepatocellular damage in those who are infected. There has been a hepatitis outbreak in some parts of Western India, which is characterized by jaundice, rapidly developing ascites, portal hypertension, and a high fatality rate. The illness was associated with eating maize that had been heavily contaminated with Aspergillus flavus. According to an analysis of contaminated samples, victims may have consumed 2–6 mg of aflatoxin per day over a month. Massive cells and bile duct development were found in a liver sample obtained during a necropsy. The sickness appears to be brought on by toxicosis [39]. Infections with Aspergillus can worsen preexisting liver damage and cause hepatic impairment, especially in those who also have hepatitis B or C viruses [40]. The detoxification and elimination of xenobiotics, such as the mycotoxins Aspergillus generates, depends on the liver [41]. Fungal infections like aspergillosis might worsen the immunosuppressive effects of the hepatitis B and C viruses. Aspergillus infection considerably raises the risk of severe or widespread infection in people with hepatitis B or C viruses, thereby exacerbating the immune impairment already present in these individuals. As a result, an Aspergillus co-infection may result in more severe symptoms and a longer time to recover [42]. A prominent therapeutic strategy for treating patients with hepatitis B and C viral infections is the use of antiviral medications. Antifungal medications used to treat Aspergillus infection may interact unfavorably or induce drug interactions in this case with some antiviral medications [43]. Furthermore, those with hepatitis B or C virus infections may have a higher chance of dying if they also have an Aspergillus infection. Due to a complex interplay of impaired liver function, immunosuppression, potential drug interactions, and increased disease severity, people who have concurrent hepatitis B or C virus and Aspergillus co-infection may have higher mortality rates than those who only have one disease [8].

4.2 Cancers

Infections account for the majority of deaths in patients with acute leukemia and lymphoma [44]. Host defenses have been breached [45]. The most prevalent condition in these patient populations is candidiasis, which is followed by Aspergillus spp.-related fungal infections [46]. For patients using immunosuppressive medications for illnesses including collagen vascular disorders, kidney transplants, and cardiac transplants, Aspergillus infections, which are the primary factors in their mortality when they exist, are extremely deadly [47].

Aspergillus infections in cancer patients can have a variety of effects depending on the infection’s intensity and the patient’s overall health. One of the most common types of Aspergillus infections in people with cancer is invasive aspergillosis, which occurs when the fungus enters the bloodstream and spreads to other parts of the body [48]. Other signs of this kind of virus include coughing, fever, chest pain, and shortness of breath. In extreme cases, invasive aspergillosis can result in organ failure and death [5]. Infections with Aspergillus can also cause additional conditions in cancer patients, including sinusitis, pneumonia, and skin infections. These infections can be difficult to recognize and treat, especially in people with weakened immune systems [49]. Chemotherapy or other cancer treatments raise the incidence of Aspergillus infections in cancer patients. To prevent these disorders, healthcare providers may advise antifungal medications or take other precautions, such as limiting mold exposure and preserving good hygiene practices [48].

4.3 HIV/AIDS

A study of 35,252 HIV patients in a national database estimated the incidence of invasive aspergillosis in AIDS to be 3.5 cases per 1000 person-years [50]. Aspergillosis was discovered in 0.43% of HIV patients, according to the findings of another database study of 38 million hospital diagnoses [50]. People with HIV/AIDS may be more susceptible to infections, such as aspergillosis, as a result of their suppressed immune systems [50]. Symptoms after exposure to Aspergillus might vary depending on how serious the illness becomes. Patients with weakened immune systems, such as those with HIV/AIDS, may experience more severe infection symptoms, including fever, coughing, shortness of breath, chest discomfort, and other respiratory symptoms. According to Wang et al. [51], it may result in high mortality or serious lung injury. Neutropenia, which can arise as a result of HIV treatment, is a recognized risk factor for invasive aspergillosis [50]. Neutropenia or corticosteroid use is associated with nearly half of aspergillosis infections in HIV patients [51]. Additional risk factors for aspergillosis infection in HIV patients include concurrent Pneumocystis jirovecii (PCP) infection and a CD4 count of less than 50–100 cells/mm³ [52].

Skin infections and infections of other organs, notably the brain, can arise from exposure to Aspergillus in addition to lung infections [51]. It wasn’t until 2017 that researchers learned that HIV-positive patients might also get CPA and that their infection patterns were similar to those of HIV-negative people. Usually, CPA makes other respiratory conditions worse. Many people who have unexplained pulmonary tuberculosis (PTB), sometimes referred to as a smear or GeneXpert negative TB, actually have CPA instead of PTB [53], yet they are mistreated, and some of them will die as a result. According to Adams et al. [54], there is a considerable clinical and radiological overlap between CPA and subacute invasive aspergillosis.

Compared to other invasive fungal infections (IFIs), less is known, especially about the incidence and prognosis of aspergillosis in patients with HIV/AIDS [50]. This is thought to be the result of the difficulty in making a clinical diagnosis, which causes many aspergillosis patients to go untreated for the bulk of their lives. After death, aspergillosis is usually discovered [55]. The overall impact of this fungus on patients with HIV/AIDS is unknown as a result [50]. Patients with HIV/AIDS should make an effort to lower their risk of acquiring Aspergillus and other fungus-related illnesses. This requires practicing excellent cleanliness, avoiding areas with a lot of molds, and seeking immediate medical attention if any signs of infection emerge [56].

4.4 Diabetes

Diabetes patients experience more severe illnesses, a higher risk of infection, and a higher death rate when compared to the general population [57]. Aspergillus fumigatus (A. fumigatus) is the most common opportunistic airborne fungal infection that results in fatal invasive pulmonary aspergillosis (IPA) in immunocompromised individuals [8]. According to research by Ghanaat and Tayek [58], non-immunocompromised diabetic patients are more likely to acquire invasive aspergillosis. What makes diabetics more susceptible to an A. fumigatus infection is still a mystery, though. According to a study, people with diabetes had a poorer prognosis for fungal pneumonia since diabetes is an independent risk factor for long-term hospitalization for the condition [59]. Research on the effects of diabetes on pulmonary A. fumigatus infection uses a streptozotocin-induced mice model of diabetes as an example. A study revealed a more severe course of the pulmonary A. fumigatus infection in diabetic mice as demonstrated by a considerably poorer survival rate and clearance of A. fumigatus [60], in addition to the observed increased fungal burden 24 hours post-pulmonary A. fumigatus infection. Both the inflammatory and immunological responses are necessary for the host to be protected from pulmonary A. fumigatus infection. A good inflammatory response is necessary for the fungal infection to be eradicated. The overactive immune response that produces cytokines abruptly and in enormous numbers is known as hypercytokinemia, commonly referred to as a cytokine storm, and it can be even more destructive than the diseases that are invading the body [61]. When diabetic mice were infected with A. fumigatus in the lungs, the inflammatory response was hyperactive, as seen by notably extended and increased lung leukocyte infiltration as well as noticeably greater plasma cytokine expression. The abnormal reaction was strongest in the early phases of infection. The inflammatory and immune responses, including cytokine-cytokine receptor interaction, tumor necrosis factor (TNF) signaling pathway, nucleotide-binding oligomerization domain-like (NOD-like) receptor, and toll-like receptor (TLR) signaling pathways, were the biological processes most enriched in diabetes. On the second day after infection, a transcriptome analysis of the lung tissue indicated this. Together, these results show that pulmonary A. fumigatus infection in diabetes results in a rapid, exaggerated inflammatory response that raises mortality. For diabetics, aspergillosis can be very problematic. Immunity can be weakened by diabetes, making it more challenging for the body to fight infections. Some diabetes medications may potentially increase the susceptibility of the immune system. Because of this, individuals with diabetes who are exposed to Aspergillus may get aspergillosis more frequently and with a more serious illness [60]. To lower their risk of aspergillosis and other fungal illnesses, diabetics must take precautions. This may require controlling blood sugar levels, keeping an impeccable standard of cleanliness, avoiding contact with mold and other fungi, and seeking medical attention as soon as any signs of aspergillosis or other illnesses appear. People with diabetes should work closely with their healthcare professionals to manage their condition and watch out for any complications, such as infections [62].

4.5 Obesity

Aspergillus infections are caused by a fungus of that name. These diseases can affect several parts of the body, including the skin, sinuses, and lungs. There is not any evidence yet that Aspergillus infections have a direct impact on weight. However, several studies suggest that several environmental factors, such as exposure to toxins and diseases, may have an impact on the development of obesity. For instance, exposure to endocrine-disrupting chemicals (EDCs) and other pollutants has been linked to increased adiposity in both human and animal models. Aspergillus infections may indirectly cause obesity by impairing the immune system and increasing susceptibility to other infections or variables in the environment that promote obesity [63]. It is critical to realize that obesity is a complex condition with a variety of underlying causes, including genetics, lifestyle, and environmental factors. Although Aspergillus infections may not directly contribute to obesity, they can nevertheless have major health consequences and must be treated effectively to prevent issues.

4.6 Alzheimer’s disease

Alzheimer’s disease is a neurological ailment that typically affects the elderly and gets worse with time. The hallmarks of this disease in the brain are amyloid plaques and neurofibrillary tangles, which result in neuronal cell death, vascular dysfunction, and inflammatory processes. In a study, researchers looked at whether people with Alzheimer’s disease had fungal infections. Proteomic research provides substantial evidence that brain samples from Alzheimer’s disease patients contain fungus-related proteins. Additionally, PCR analysis of these samples revealed a variety of fungal species, depending on the patient and the tissue investigated. Brain tissues included a variety of fungi, according to DNA research. Together, these results show that the brains of people with Alzheimer’s disease contain fungus macromolecules. To our knowledge, these findings are the first evidence that fungi can be discovered in the brain tissues of Alzheimer’s disease patients [64]. The specific impact of Aspergillus on people with Alzheimer’s disease is unknown, though. Alzheimer’s disease can make people more vulnerable to infections due to a weakened immune system, although there is no conclusive evidence linking it to an increased risk of Aspergillus infections [7]. However, patients with Alzheimer’s disease may be more prone to developing respiratory infections, including those caused by Aspergillus, due to their weakened immune systems and difficulties swallowing, which can result in aspirating food or liquids into the lungs. Respiratory infections, according to Tangaleela et al. [65], can aggravate Alzheimer’s disease symptoms and lead to consequences like pneumonia. Caretakers of individuals with Alzheimer’s disease must take steps to prevent respiratory infections, including ensuring a clean environment, watching out for infection warning signs, and seeking medical attention as soon as symptoms develop. If an Aspergillus infection is suspected, a healthcare practitioner can perform diagnostic testing and recommend appropriate treatment options, such as antifungal medication [66].

4.7 Depression

Although some evidence points to Aspergillus infections as a possible cause of depression in some individuals, the relationship between the two conditions is convoluted and poorly understood. Continual Aspergillus infections have been linked to depressive symptoms such as low mood, loss of interest in activities, and low energy, according to research. The physical side effects of the infection, such as fatigue, soreness, and breathing issues, are likely what are aggravating these emotions [8]. It is likely that depressive disorders raise the risk of Aspergillus infections because they can weaken the immune system and make patients more susceptible to infections [67]. This is so that stress and other factors associated with depression can have this effect [67].

4.8 Stroke

Multiple organs could be affected by aspergillosis that has spread throughout the body. According to Santa-Ramrez et al. [68], the most serious side effect is brain infection, which occurs in 10–15% of patients and has a fatality rate of more than 90% even while receiving guided antifungal medication. A CNS infection may be acquired through hematogenous spread (typically from a pulmonary center), contiguous dissemination from a paranasal sinus infection, or direct iatrogenic injection during cerebral invasive procedures [69]. Aspergillus spp. CNS infection has been linked to numerous different clinical features. Up to 65% of these patients may have focal deficits Nevertheless, just one case report and not any clinical series have been used to describe the prevalence of clinical manifestations of acute stroke [69].

One of the infections that Aspergillus, a type of fungus, can cause is invasive aspergillosis, a serious condition that can affect people with weakened immune systems. It is unknown how aspergillosis impacts stroke, despite research suggesting that some illnesses, such as pneumonia and urinary tract infections, can increase the risk of the condition. According to case reports and small studies, aspergillosis may cause strokes, especially in people with compromised immune systems. The risk of stroke is increased by invasive aspergillosis, which can cause brain blood vessel inflammation and damage. Additionally, aspergillosis-related blood clots have been connected to a higher risk of stroke [70]. More research is required to completely understand the relationship between aspergillosis and stroke.

4.9 Osteoporosis

A disorder called osteoporosis is characterized by a loss of bone mass and a higher risk of fractures. There is little data on how Aspergillus infections affect osteoporosis, but some studies have found a link between osteoporosis and persistent Aspergillus lung infections. This is due to the possibility of persistent inflammation brought on by Aspergillus infections, which can promote bone resorption and reduce bone growth [71]. Additionally, corticosteroids and other antifungal drugs used to treat Aspergillus infections can raise the risk of osteoporosis. By inhibiting bone production and increasing bone resorption, corticosteroids are known to reduce bone density [72]. The link between Aspergillus infection and osteoporosis is complicated and can change depending on the person and the severity of the infection, and it is crucial to remember.

4.10 Chronic kidney disease

Aspergillus infections can be extremely difficult to cure and can have serious negative effects on the health of patients with chronic kidney disease (CKD). Immunosuppressive medications, which are frequently administered to decrease inflammation and lower the risk of rejection following kidney transplantation, are frequently linked to Aspergillus infections in CKD patients. These drugs may lower immunological function, increasing the risk of fungal infections in patients [73]. Patients with CKD may experience severe effects from Aspergillus, especially if the infection is not identified and treated right once. Invasive pulmonary aspergillosis (IPA), a potentially fatal illness that can cause lung damage, sepsis, and death, is brought on by Aspergillus [74]. In addition to the infection’s direct effects, Aspergillus might aggravate the patient’s underlying CKD and further jeopardize their health. Mycotoxins, which the fungus generates, can harm the kidneys and cause acute renal injury or worsen underlying CKD [41]. As many antifungal drugs can be harmful to the kidneys, treating Aspergillus infections in CKD patients can be difficult and necessitate close monitoring of the patient’s renal function. To help the immune system more effectively combat the infection, immunosuppressive medicines may also need to be changed or stopped [75]. In conclusion, Aspergillus infections can have serious effects on the health of CKD patients, including deteriorating renal function and potentially fatal consequences. To lessen the effect of the infection on the patient’s health, early identification and fast treatment are crucial [75].

4.11 Oral disease

A particular kind of fungus called Aspergillus can infect the human body, including the oral cavity. Various effects on oral health may result from these infections. Oral aspergillosis is one of the most prevalent Aspergillus infections of the oral cavity. This can happen to persons who have compromised immune systems, such as those who have cancer, HIV/AIDS, or other immune-compromising diseases. Additionally, it might happen to patients who have undergone particular dental treatments, like tooth extractions [76]. Several symptoms, such as discomfort, swelling, and redness in the afflicted area, can be brought on by oral aspergillosis. Along with making it difficult to speak or swallow, it can also lead to the emergence of sores or ulcers [77]. Aspergillus infections can contribute to the development or aggravation of other oral disorders in addition to causing direct harm to the oral cavity. For instance, Aspergillus infections can raise your risk of getting gum disease, periodontitis, and other oral infections [76].

4.12 Heart disease

Infections with Aspergillus primarily affect the respiratory system, but they can also spread to other bodily organs, such as the heart. For people with heart problems, Aspergillus infections can have severe negative effects. The fungus can inflame the heart muscle, which can result in cardiac failure, arrhythmias, and pain in the chest. Additionally, Aspergillus can infect the heart valves, which increases the risk of endocarditis and damages the heart valves [78]. Aspergillus infections are more likely to occur in those with compromised immune systems, such as those with HIV/AIDS or those receiving chemotherapy. But if they breathe in a lot of Aspergillus spores, even those with strong immune systems can have Aspergillus infections [8]. Antifungal medications are frequently used to treat Aspergillus infections in people with heart disease because they can assist to destroy the fungus and reduce inflammation. To correct heart valve damage brought on by the infection in some circumstances, surgery may be required [79]. By avoiding places where the fungus is prone to grow, such as damp or moldy locations, and by wearing protective masks when dealing with soil, compost, or other organic materials, people with heart disease should take precautions to prevent Aspergillus infections.

5. Conclusion

Aspergillus is a genus of fungi that can infect people with weakened immune systems, especially those who already have ongoing diseases. People with persistent infections may experience everything from minor symptoms to potentially fatal complications as a result of Aspergillus infections. Invasive pulmonary aspergillosis (IPA), which happens when the fungus penetrates the lungs and produces inflammation, is one of the most prevalent kinds of Aspergillus infections. This may result in symptoms including fever, coughing, pain in the chest, and shortness of breath. IPA can be particularly harmful in patients with chronic infections, since their compromised immune systems may not be able to successfully fight off the infection. Infections with Aspergillus can also affect the skin, nails, and sinuses in addition to other regions of the body. These infections may be more difficult to treat in patients with persistent infections and may call for more drastic measures, such as surgery or antifungal drugs. People with chronic infections may further endure psychological and emotional repercussions in addition to the physical signs and symptoms of Aspergillus infections. The ongoing risk of infection can be stressful and traumatic, and the necessity for repeated medical treatments can interfere with normal life. People with persistent infections may experience significant and wide-ranging impacts from Aspergillus infections. People with chronic infections need to take precautions to reduce their chance of contracting Aspergillus infections, such as maintaining excellent hygiene and avoiding mold and other environmental triggers. Additionally, it is crucial for medical professionals to keep an eye out for any indications of Aspergillus infections in this population and to offer fast and effective treatment when necessary. In conclusion, Aspergillus infections can affect patients with chronic illnesses in a variety of ways, ranging from medical symptoms to psychological distress. Healthcare professionals and patients alike should be aware of these hazards and take precautions to reduce them. Despite the difficulties presented by Aspergillus infections, persons with chronic infections can lead healthy, fulfilling lives with the right treatment and management, and also more research is need in the area of Aspergillus and aspergillosis in people living with chronic diseases to establish more mechanisms and associations between these fungi and other infections.