Introduction

Candida is a type of fungus and one of the many kinds of yeasts. It exists on and in the human body without causing harm. The most common type of candida is the candida albicans, that can be seen in the mouth, gut and body of a healthy person, even the genitals and urinary organs.¹ This means it is among the normal flora of a human, but they are kept in check by the body's immune system. It can only cause harm to an individual if there is a destruction of the normal balance of healthy microorganisms in the body, including Candida. This causes it to grow into an infection which can be harmful to the body, at this point it is referred to as candidiasis.² 

There are two broad types of candidiasis; the localized candidiasis occurs at areas in the mouth, vaginal, penis and skin.^3,4 Meanwhile, when the infection moves beyond these areas and enters the blood or other inner organs such as the liver, kidney, heart or brain, it is called a systemic candidiasis. Systemic candidiasis are several and can be life-threatening for individuals whose immunity has been compromised or those who are hospitalised.⁵

Relevants of candida in high-risk men

We are most familiar with candidiasis when it is an infection in a woman's genitals and we explore these areas for discussions. While this is important, attention needs to be placed on some men who may be at risk of candidiasis due to several factors like:

• Coexisting conditions like diabetes, HIV/AIDS, obesity, and when immunity is impaired, men become very prone to both localized and systemic candidiasis⁶
• Structural features: infection appearing on the head of penis, typically known as balanitis and recurrent local infections are more common in males who are not circumcised and in those who have phimosis^4,7
• Exposure to prolonged use of corticosteroids or antibiotics may disrupt the balance of the natural flora. Systemic candidiasis can be caused by frequent hospital stay, hemodialysis, or the use of medical devices that penetrate through the body, such as catheters. Additionally, certain sexual behaviors and poor cleanliness raise the likelihood of overgrowth or transmission of the infection⁸

Candida infections in men can cause balanitis, and if the immune system is weakened, they can occasionally develop into invasive illness. For high-risk males, a systemic infection might result in serious problems that need immediate medical intervention.^4,5

Distribution of candida infection

Candida species often live on mucosal surfaces, skin, and in the gastrointestinal tract of healthy people without causing any issues. However, colonization rates are higher in patients with long hospital stay and those critically ill. Research shows that as many as 40 to 65% of patients in the Intensive Care Unit (ICU) of the hospital become colonized by Candida during their stay, but only a small number, usually less than 10%, go on to develop an infection.^9,10 In one large study involving nearly 10,000 patients, 40% had candida, but only 4.7% developed invasive candidiasis.¹¹ The risk of moving from colonization to infection rises with the number of colonized areas and when there are risk factors, such as mechanical ventilation and corticosteroid use.¹²

Mechanism of systemic candidiasis spread

Candida are usually harmless when the mucosal barriers are intact and the immune system is functioning well. However, Candida can change from being a harmless organism to a harmful one if the immune system weakens, medications disturb the microbiota, or physical protection is damaged.¹³

Candida usually needs to break through skin or mucosal barriers to spread throughout the body. This can happen through:^3,6,14

• Physical disturbances: Burns, wounds, surgery, intravenous catheter use, and damage to mucosal surfaces weaken the skin's barrier, allowing direct access to the blood circulation and deeper tissues
• Modified microbiota: Broad-spectrum antibiotics encourage invasion and overgrowth by reducing bacterial competition
• Weak Immune system: Conditions like diabetes, cancer, HIV/AIDS, or immunosuppressive drugs weaken the body's defenses at mucosal surfaces, making invasion easier
• Biofilm production: Biofilms act as a source for chronic infection and can introduce candida into the bloodstream, especially on medical devices like catheters

Once candida has crossed the mucosal barrier, it can spread to organs such as the kidneys, liver, spleen, heart, and brain by invading local tissues or potentially entering the bloodstream, leading to candidemia.

How does candida avoid immune cells and spread in the blood?

Candida must survive and escape the human immune response on various levels to spread systematically.

Avoid being recognised by immune systems 

• Structural changes: The ability to change between the hyphal form and the yeast form helps it avoid the immune system. The hyphal forms are better at breaking through barriers and escaping phagocytosis- a process of being engulfed by the immune cell¹³
• Matrix of biofilms: The biofilm matrix blocks immune cells and antifungal treatments¹⁴
• Both suppression and avoidance: The fungus reduces immune recognition by producing fewer immunogenic proteins, covering some fungal cell wall components (like β-glucans), and altering the host’s pattern recognition receptor (PRR) signaling^{16, 17}

Active host immunity resistance 

• Inhibition of phagocytosis: Candida hyphae can physically disrupt or escape phagocytes, that is, immune cells like neutrophils and macrophages. Phagocytes can physically disrupt and escape when they encounter hyphae¹³ 
• Antioxidant production: Enzymes prevent fungal death by removing reactive oxygen species created by immune cells¹⁶ 
• The defenses of the host decline: Candida can break down host proteins, disrupt cellular barriers, and evade immune system molecules through the production of aspartic proteases, phospholipases, and lipases¹³ 
• Disruption of cytokine and complement networks: Candida can affect cytokine responses and block complement activation, which impairs the efficient destruction and recruitment of the immune system¹⁷

Survival and Dispersal to organs 

While candida are inside the bloodstream, the following happens:

• Innate immunity quickly clears many pathogens, the immune-evasive Candida cells can survive, especially in people with weakened immune systems^18,19 
• The liver and spleen macrophages act as filters. When they gather Candida cells, they spread to other organs. 
• Catheters and intravascular devices are hotspots for ongoing fungal invasion and biofilm shedding¹⁴ 

When the organs face invasive candidiasis, it leads to serious symptoms. In some cases, this can result in death, heart disease, meningitis, and pus formation.

Factors increasing the susceptibility of candida infection in high-risk male patients 

There are several factors that increase the chances of high-risk male patients in getting candida infection, they include medical factors, hospital-related factors and behavioural factors.

Medical factors

• Diabetes mellitus: One established risk factor for candidiasis is diabetes. High blood sugar reduces the body’s ability to fight infection and encourages the growth of Candida, especially in the genitourinary tract and the mouth. People with diabetes are one to three times more likely to develop candidiasis than those without diabetes because they struggle with glucose control, which makes them more vulnerable to infections^20,21
• HIV/AIDS: The immune system weakness that comes with HIV/AIDS hampers mucosal immunity and cell-mediated responses. As a result, these patients are very susceptible to systemic and localized Candida infections. Oral and esophageal candidiasis are common infections with severe HIV disease²²
• Cancer chemotherapy: Cancer treatments that use cytotoxic drugs can lead to neutropenia- reduction in neutrophils and damage to mucosal barriers, making it easier for Candida species to colonize and invade. Patients undergoing chemotherapy are at higher risk for severe, invasive candidiasis, especially if they have blood-related cancers^22,23
• Organ transplant: Immunosuppression, the use of central lines, and frequent exposure to broad-spectrum antibiotics put solid organ and hematopoietic stem cell transplant recipients at greater risk. Infections typically appear several weeks after transplantation, and non-albicans Candida infections are becoming more common in these patients^22,23
• Prolong antibiotics use: Frequent or prolonged use of broad-spectrum antibiotics disrupts normal bacterial flora, leading to uncontrolled Candida growth and a higher risk of systemic fungal infections. Even a seven-day course of these medications significantly raises the risk for invasive candidiasis and related mortality^24,25

Hospital-related factors

• Central Venous Catheters (CVCs): Candida bloodstream infections are a serious risk associated with CVCs. This risk is mainly due to biofilm forming on the surfaces of CVCs. Candidemia from CVCs leads to high rates of illness and deat²⁶
• Total Parental Nutrition (TPN): In the circulatory system, parenteral feeding creates a nutrient-rich environment that promotes the growth of Candida and biofilm production. Many studies have identified total parenteral nutrition (TPN) as an independent risk factor for candidemia, especially in critically ill and neutropenic patients²⁷
• Prolong hospital stay and ICU admission: The intensive care unit (ICU) and long-term hospital patients are particularly vulnerable. This is due to the invasive procedures they undergo, mechanical ventilation, use of broad-spectrum antibiotics, and weakened immune systems. Longer stays in the intensive care unit increase the rates of invasive candidiasis, resulting in higher mortality rates²⁸

Behaviour factors 

• Poor genital Hygiene: A good environment for the growth and infection of Candida is caused by inadequate genital hygiene, especially in uncircumcised men. The risk increases with insufficient washing, especially behind the foreskin, and not drying the area properly⁷
• Smoking, alcohol and drug use: One specific risk factor for oral candidiasis is smoking cigarettes. Smoking weakens the protective layer and lowers mucosal immunity, which allows Candida to grow and spread. Drinking alcohol and taking psychotropic medications, including opioids, raises the overall risk of infection and increases the number of Candida species in the mouth^29,30

Summary

Systemic candidiasis is a serious and often life-threatening fungal infection. It happens when Candida species, mainly Candida albicans, spread through the bloodstream. The clinical signs can vary greatly, but some key features and complications are well described in the literature.