Overview  

Can you imagine a situation where a simple infection can turn into a devastating and life-threatening illness? This can be a reality when the already immunocompromised individuals living with HIV/AIDS acquire the insidious infection, fungal meningitis. As one of the leading causes of death in these patients, understanding fungal meningitis is crucial. In this article, we are going to explore fungal meningitis in HIV/AIDS individuals, its clinical features, diagnosis, management and its impact on patients' lives.

Definitions  

Meningitis   

Meningitis is defined as the inflammation of the protective coverings of the brain, the meninges. The meninges are a three-layered membranous structure that surround the brain within the skull and spinal cord to provide protection and structural support. Some people confuse meningitis with the distinct condition encephalitis, which refers to the inflammation of the brain tissue itself.¹ 

Meningitis can result from various causes ranging from infection, autoimmune reactions, cancer and drugs. All of the infectious microorganisms, like bacteria, viruses, fungi, and parasites, can cause meningitis. In the general population fungal meningitis is far less common than bacterial or viral meningitis, however, it poses a significant risk when it comes to patients with HIV/AIDS.¹ ​ 

HIV/AIDS 

AIDS is one of the most serious infectious diseases worldwide, which has resulted in around 40 million deaths since its discovery, however, numbers are declining due to the recent advancements in the identification process as well as in the treatment guidelines turning it into a more manageable chronic disease with better outcomes.  

It is caused by the human immunodeficiency virus, widely known as HIV. The virus's name reflects its impact on the body as it compromises the immune system. HIV is transmitted from person to person through blood and body fluids, and when it enters the body, it selectively targets and kills a specific type of white blood cells called “CD4+ T lymphocytes” which function to coordinate the immune response by activating and directing other immune cells to eliminate infection. HIV infection, if left untreated, will result in the condition known as acquired immunodeficiency syndrome (AIDS).  

When CD4+ cells count drops, the body’s immune defenses weaken, making it vulnerable to infections from microbes that are normally harmless for healthy individuals. This can lead to opportunistic infections, such as those caused by certain fungi.² ​

Fungi causing meningitis in HIV/AIDS 

According to the Centers for Disease Control and Prevention (CDC), there are few fungi that are known to cause fungal meningitis including:  

• Cryptococcus: cryptococci are the most common cause of fungal meningitis in HIV/AIDS, accounting for 13-44% of all deaths of HIV patients in sub-Saharan Africa.  They are found everywhere in the environment, like the soil, and are associated with bird droppings. The fungus enters the body through inhalation, where it can cause an infection in  the lungs³ ​
• Candida species: candida is widely known to be the cause of napkin rash and oral thrush in small babies. It also causes oral, vaginal and esophageal infection especially in HIV patients and in people with weak immunity. Although candidal meningitis is not common, it can be very challenging to discover or to manage⁴ ​ 
• Histoplasma capsulatum: results in chronic lung infection after inhaling fungal spores and is able to cause meningitis in individuals with HIV/AIDS
• Blastomyces: another fungus that is found in the soil and spreads through inhalation, resulting in chest infection with the possibility to disseminate to the rest of the body, including the meninges 
• Coccidioides

Risk factors  

Several factors increase the likelihood of fungal meningitis in AIDS patients such as: 

• Low CD4+ cells count (<100 cells per microliter of blood) and not on HIV treatment
• People on HIV treatment but still have high virus load in their blood and low CD4+ count
• Poor adherence to treatment and follow-up⁵ ​

Clinical manifestations 

Symptoms of fungal meningitis in HIV/AIDS are nonspecific, more chronic, and can overlap with symptoms of other diseases  as a result of the weakened immune response, however, the most frequently encountered features are: 

• Lethargy: the patient feels unwell and tired all the time 
• Fever: although fever can be a prominent symptom, it is usually of low grade and longer duration 
• Headache: headache is a common and early encountered feature  
• Altered mental status: the patient may feel confused, have memory disturbances and personality change. Coma and death can happen in the late stages 
• Nuchal rigidity: it refers to neck stiffness, which is a known sign of meningitis in general, that is less common in AIDS patients 
• Visual disturbances: due to the increased pressure of fluid within the skull or as a result of brain swelling as part of the inflammatory process^3,6​ 

Diagnosis  

Early diagnosis of fungal meningitis is essential for the proper management of the condition to achieve the best possible outcomes and follows the following steps: 

Clinical evaluation 

When dealing with HIV/AIDS patients, the doctor should be very alert and must have a high awareness of unusual infections and their atypical presentations to ensure that no serious condition is overlooked. A thorough medical history and physical examination are performed to search for features of fungal meningitis.     

Lab tests  

Blood tests  

Blood tests like culture and fungal markers like cryptococcal antigen (CrAg) can help direct the diagnosis process and guide the choice of therapy.  

Lumbar puncture  

Lumbar puncture is a procedure by which a needle is inserted into the lower back of the patient to draw the cerebrospinal fluid that is found surrounding the brain and the spinal cord. It is analysed microscopically and chemically to search for evidence of fungal growth.^3,6 ​ 

Imaging  

Neuroimaging like computerised tomography (CT) and magnetic resonance imaging (MRI) scans can help detect evidence of infection, but they are not always conclusive and their findings need to be correlated with the clinical symptoms and the lab results. Also, they can  detect the complications like hydrocephalus.⁷​ 

Treatment 

The effective management of fungal meningitis in HIV/AIDS involves supportive therapy, antifungal and antiretroviral treatments. Treatment duration depends on the response of the patient and typically takes weeks to months.  

Supportive therapy 

Supportive therapy aims to relieve the symptoms felt by the patient, which can be as simple as prescribing analgesics for a headache or as complicated as performing surgical procedures to reduce the pressure buildup within the skull.   

Antifungal medications  

Antifungal drugs are like antibiotics, which are specifically manufactured to destroy fungi and to reduce their growth. Such as: 

• Amphotericin B: the mainstay of treatment, especially for cryptococcal meningitis for both children and adults. However, it requires close monitoring to avoid drug toxicity
• Flucytosine: flucytosine is administered in combination with Amphotericin B in the initial phase of the treatment to achieve higher cure rates 
• Fluconazole: fluconazole was proved to be a safer drug with less toxicity, therefore, it is used in both early induction treatment and as maintenance therapy for long durations or even for life in patients with poor response to HIV treatment to protect against relapse   
• Itraconazole: can be used as an alternative or for other types of fungi^4,8,9 ​​ 

HIV treatment (Antiretroviral therapy - ART)  

Although the early initiation of ART is essential to guarantee immune restoration, choosing the appropriate timing is critical to avoid immune reconstitution inflammatory syndrome (IRIS) which refers to the worsening of the clinical situation as a result of the improved immune responses of the patient.³​  

Complications

• Hydrocephalus: is the accumulation of cerebrospinal fluid within the skull, leading to pressure buildup and brain compression 
• Neurological deficits: the patient can develop symptoms resembling a stroke, like paralysis, cognitive and visual impairment 
• Fungal spread:  the infection can extend to involve other body parts like the lungs³​

Prevention  

Some approaches can be taken to reduce the chances of developing fungal meningitis in individuals with HIV/AIDS   

• Early HIV recognition: Early diagnosis and initiation of ART is the cornerstone for the prevention of all opportunistic infections in HIV/AIDS  
• Adherence to ART therapy 
• Prophylactic antifungal therapy like fluconazole  
• Screening newly discovered patients for cryptococcal infection 
• Regular monitoring³​

Summary  

Fungal meningitis is a life-threatening condition that affects HIV/AIDS patients of all ages. It is caused by fungi like cryptococcus, candida, and histoplasma.  It requires prompt recognition and clinical evaluation, early initiation of treatment with antifungals and antiretroviral treatment, and regular follow-up to avoid the serious complications like hydrocephalus and visual loss.