Cryptococcal Meningitis: a HIV/AIDS Associated Infection

Generally speaking, meningitis is an infection characterised by the inflammation of the meninges, the membranes that cover the brain and spinal cord. Meningitis is known to be caused by various kinds of microorganisms, including bacteria, fungi, and viruses [1]. Our focus here is meningitis caused by fungi.

What is Cryptococcal Meningitis?

Cryptococcal meningitis is a type of meningitis caused by the fungus Cryptococcus neoformans. It is one of the most important HIV-related opportunistic infections - infections that are much more common in people with weakened immune systems or altered microbiota, especially in developing countries [2].

The causal organism of cryptococcal infection is generally found in people with compromised immune systems. Globally, there are approximately 1,000,000 new cases yearly, and over 600,000 patients die from cryptococcal disease annually. Disseminated infections may occur, but meningitis remains the most severe manifestation of cryptococcal disease. It is estimated that about 181,000 deaths occur annually due to cryptococcal meningitis, with 75% occurring in sub-Saharan Africa. In the United States, there are an estimated 3400 cases annually, with up to 700 deaths occurring. Additionally, the disease accounts for 15% of AIDS-related deaths worldwide [3].

Causes

C. neoformans is the causative organism of cryptococcal meningitis. The fungus is found in soil in many parts of the world. In fact, bird droppings are a major source of C. neoformans. On occasions, another related fungus, Cryptococcus gatti may also cause the infection. Unlike C. neoformans, C. gatti is more likely to cause infection in a person with a healthy immune system. Although not found in bird droppings, C. gatti is associated with trees, usually eucalyptus trees [4].

Transmission

Cryptococcal meningitis is not spread from person to person. Instead, it is acquired by an individual when they inhale soil particles contaminated by bird droppings.

The fungus first infects the body, then the infection spreads to the central nervous system (consisting of the brain and spinal cord), thereby leading to cryptococcal meningitis [4].

Symptoms of Cryptococcal Meningitis

The symptoms usually develop gradually, often within a few days or weeks of exposure to the causative organism. Symptoms may include headaches, nausea, vomiting, lethargy, and sensitivity to light. In some cases, stiff neck and fever may be experienced [4].

If cryptococcal meningitis is left untreated, more serious symptoms such as brain damage, hearing loss, coma, and fluid in the brain may be experienced [1].

This form of meningitis may be fatal if left untreated quickly, especially in people with HIV/AIDS [1].

Diagnosis

To most accurately diagnose cryptococcal meningitis, a patient’s symptoms and medical history are used. If a person is suspected to have the fungus, a doctor will order a spinal tap to confirm the diagnosis. During a spinal tap, a doctor will extract spinal fluid by inserting a needle into the person’s spinal column, which is located just above their hips. The extracted fluid will be examined for signs of infection and to see if cryptococcus is the cause of the infection [4].

Negative staining with India Ink, an acidic dye used for visualizing the cerebral spinal fluid, is used to pinpoint the presence of the fungus. Specifically, the particles of the ink pigments cannot enter the cell capsule surrounding the yeast cells. This forms a zone of clearance around the cells known as a halo and allows for a quick identification of Cryptococcus neoformans [5].

Blood tests may also be ordered by a doctor in addition to doing a spinal tap [4].

Treatment

Antifungal drugs are used to treat cryptococcal meningitis. Most commonly, doctors use a regimen of amphotericin B and fluconazole. These drugs may be administered intravenously, usually for a long time. Both amphotericin B and fluconazole can have serious side effects, so a patient will be closely watched for signs of nephrotoxicity.  Once there is no longer any sign of cryptococcal meningitis in a patient’s spinal fluid, the doctor might adjust medications. This may include stopping the administration of amphotericin B to lower the risk of kidney problems. In some people with meningitis, draining the spinal fluid may be recommended to reduce pressure on the brain [1].

However, people with HIV/AIDS may need to take fluconazole indefinitely to prevent relapse [1].

There are various opportunistic infections associated with HIV/AIDS. Cryptococcal meningitis remains a prevalent one accompanied by high mortality and morbidity. People with underlying conditions are more at risk and should take more precautions. This includes seeing a doctor if they experience any of the symptoms of the infection. 

Glossary

Intravenously: by means of a vein.

Microbiota: microscopic organisms of a particular environment.

Morbidity: the condition of being diseased.

Mortality: the state or condition of being subject to death.

Nephrotoxicity: a kidney problem resulting from exposure to drug or toxin that causes kidney damage.

References

[1] G.Holm. (2018, Sept. 29). “Cryptococcal Meningitis,” Healthline, [Online]. Available: https://www.healthline.com/health/meningitis-cryptococcal. [Accessed 9 August 2020].

[2] B. J. Park, K. A. Wannemuehler, B. J. Marston, N. Govender, P. G. Pappas and T. M. Chiller, “Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS,” AIDS, vol. 23, no. 4, pp. 525-530, 2009.

[3] M. Poley, R. Koubek, L. Walsh and B. McGillen, “Cryptococcal Meningitis in an Apparent Immunocompetent Patient,” Journal of Investigative Medicine High Impact Case Reports, vol. 7, 2019.

[4] J. Fletcher (2018, Feb. 26). “Cryptococcal meningitis: Symptoms, risk factors, and complications,” Medical News Today, [Online]. Available: https://www.medicalnewstoday.com/articles/321031. [Accessed 10 August 2020].

[5] F. Makobi. (2020, Apr. 30). “Cryptococcus neoformans,” Microbenotes, [Online]. Available: https://microbenotes.com/cryptococcus-neoformans/. [Accessed 12 August 2020].