HIV-related cryptococcal meningitis

Related Terms

Acquired immune deficiency syndrome, acquired immunodeficiency syndrome, AIDS, busse-buschke disease, central nervous system, cerebrospinal fluid, CNS, CNS infection, cryptococci, cryptococcic meningitis, cryptococcosis lung,cryptococcosis skin, Cryptococcus neoformans, CSF, encephalitis, European blastomycosis, HIV, human immunodeficiency virus, immune, immune defense system, immune system, immunocompetent, immunocompromised, immunodeficiency, infection, lumbar puncture, lymph node, meninges, meningitis, meningoencephalitis, pneumonitis, opportunistic infection, pulmonary infection, spinal tap, torular meningitis viral, torulosis, viral infection, virus, weakened immune system, yeast.

Background

Cryptococcus neoformans, a type of microscopic yeast that is found worldwide, can cause pulmonary infections that can potentially spread to other areas of the body. This infection is called cryptococcosis. Individuals who are immunocompromised, especially HIV/AIDS patients, are more susceptible to developing the infection.
Most infections develop after the yeast is inhaled into the lungs. Cryptococci have large polysaccharide (sugar) capsules that strongly resist phagocytosis. This means the body's immune system cells have to work hard to engulf the yeast organism.
The body's inflammatory reaction to the inhaled yeast causes a primary pulmonary-lymph node complex, which usually prevents the organism from spreading beyond the lungs. Most pulmonary infections are asymptomatic (cause no symptoms), but patients who are severely immunocompromised may develop diffuse interstitial pneumonitis (inflammation of the lungs).
C. neoformans can spread beyond the lungs, especially if the patient is immunocompromised. Dissemination (spread to other body parts) can occur during the initial stage of the infection or during reactivation of infection years later.
The most common site involved is the central nervous system (CNS, brain and spinal cord). Most patients with CNS infections suffer from altered mental states, behavioral changes, headache and fever. Focal (localized) neurologic signs are unusual.
The typical pathologic findings of CNS cryptococcosis include meningitis (infection and inflammation of the membranes that surround the brain and spinal cord), cryptococcomas (infectious inflammatory lesions, typically in the brain, but also found in the lung and elsewhere) and dilated spaces near blood vessels. Patients who have AIDS and cryptococcal meningitis account for more than 80% of the patients with cryptococcosis.
Significant differences are reported in the inflammatory response to cryptococcal meningoencephalitis (inflammation of the brain, spinal cord and meninges) among patients who have HIV/AIDS and those who do not have HIV/AIDS. Granulomatous inflammation (lumps formed from an accumulation of inflammatory cells) is not common in AIDS patients, while most patients without HIV/AIDS have granulomas.
If left untreated, cryptococcal meningitis results in death 100% of the time. Therefore, early diagnosis and treatment with amphotericin B is essential. Prior to the discovery of amphotericin B in 1955, 80% of patients with CNS involvement died within two years of diagnosis.

Author information

This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography

Bicanic T, Harrison TS. Cryptococcal meningitis. Br Med Bull. 2005 Apr 18;72:99-118. Print 2004.
Centers For Disease Control and Prevention (CDC). Division of Bacterial and Mycotic Diseases. Cryptococcosis. .
Natural Standard: The Authority on Integrative Medicine. .

Causes

Infection with either C. neoformans var neoformans or C. neoformans var gattii causes cryptococcal disease. The most common pathogen that infects patients who are immunocompromised is C. neoformans var neoformans. The most common pathogen that infects patients who are immunocompetent is C. neoformans var gattii.
The C. neoformans enters the body via the lungs, and causes a pulmonary infection. After the patient develops a pulmonary infection, the cryptococci yeast spreads throughout the body and may infect any organ. The organs most often involved include the central nervous system (CNS), bones, prostate, eyes and skin. The CNS is the main site of symptomatic infections in both immunocompetent and immunocompromised individuals.
Cryptococcal CNS infections usually involve both the brain and meninges (membranes that surround the brain and spinal cord). Immunocompetent hosts may present with either meningitis or focal cryptococcomas. Meningitis manifests with diffuse, nonfocal findings (such as altered mental status and vomiting), whereas cryptococcomas often manifest with focal neurologic (brain) defects.

Symptoms

General: Cryptococcosis usually starts with a pulmonary infection (in the lungs), which usually spreads to the central nervous system (CNS). If left untreated, the infection can continue to spread to other organs in the body, including the skin, prostate and medullary cavity (bone marrow) of the bones.
Pulmonary: Symptoms of cryptococcal pulmonary (lung) disease vary. Some patients are asymptomatic (experience no symptoms) while others, especially immunocompromised patients (like HIV/AIDS patients and organ transplant recipients), suffer from acute respiratory distress syndrome. Sometimes pulmonary disease manifests as a progressive mass that compresses important body tissues in the chest such as the vena cava (main veins to the heart).
Common symptoms include fever, general feeling of discomfort, dry cough, pleuritic pain (pain in the membrane surrounding the lungs), and rarely, blood in the sputum.
Less common symptoms include rales (crackling sound that occur when air moves through fluid-filled lungs), pleural effusions (fluid between the lining of the lung and the lining of the inside wall of the chest), cavitation (formation of cavities in a body tissue or an organ) and enlarged lymph nodes.
Central nervous system (CNS): Meningitis and meningoencephalitis are the most common manifestations of an infection that has spread to the CNS. This form of infection is fatal without treatment after two weeks to several years of the onset of symptoms.
Symptoms vary depending on the individual's overall health prior to infection. Some patients who are HIV-positive may have minimal or nonspecific symptoms when they are diagnosed with the condition. Common symptoms include headache, altered mental status (such as personality changes), confusion, lethargy, reduced consciousness, coma, nausea and vomiting. Other, less common, symptoms include fever, stiff neck, hearing defects and seizures. Dementia may indicate a condition called hydrocephalus (accumulation of cerebrospinal fluid in the brain) as a late complication.
Blurred vision, photophobia and double vision, may occur secondary to arachnoiditis (inflammation and scarring of the membranes covering the spinal cord), inflammation of the optic nerve and chorioretinitis (inflammation behind the retina).
Disseminated: If the infection continues to spread after lung and CNS infection, the skin, prostate and medullary cavity of the bones are the most likely organs to be affected next. Cutaneous (skin) manifestations occur in 10-15% of cases and usually take the form of papules, pustules, nodules, ulcers or draining sinuses. Cellulitis (inflamed connective tissue) with necrotizing vasculitis (inflamed blood vessels) is reported in patients who undergo organ transplantation.
Bone lesions develop in 5-10% of the patients. Bone lesions usually cause the breakdown of the bone, and they may be confused with tuberculosis or neoplasm (tumor growth).
Other less common forms of cryptococcosis include myocarditis (inflamed heart), chorioretinitis (inflamed choroid layer behind the retina in the eye), inflamed liver, peritonitis (inflamed lining of the abdominal cavity), kidney infection, enlarged prostate, myositis (inflamed muscle tissue) or adrenal involvement.

Diagnosis

General: The diagnosis is made on the basis of a series of tests, including a cerebrospinal fluid (CSF) culture and positive identification of the yeast.
It may be more difficult to diagnose AIDS patients who have cryptococcal meningitis because abnormalities in the CSF may have been caused by a different type of infection.
Lumbar puncture (spinal tap): A lumbar puncture, also called a spinal tap, may be performed to detect abnormalities in the cerebrospinal fluid (CSF). During the procedure, a needle is inserted in the lower back between two vertebrae to remove a sample of CSF. The CSF is then tested for the presence of the disease-causing yeast.
Blood culture: A sample of blood is taken from the patient. The sample is then taken to a laboratory and placed in conditions that allow the yeast to grow. A positive culture will identify the disease-causing organism.
Imaging studies: A computerized tomography (CT) scan and magnetic resonance imaging (MRI) are important diagnostic techniques in any patient who has HIV/AIDS with neurologic (brain) dysfunction. Several studies have shown that MRI is better than a CT scan in detecting abnormalities in CNS cryptococcosis. Normal MRI findings do not rule out a diagnosis of CNS cryptococcosis because the typical features of this infection occur in only 40% of patients. Intracranial mass lesions occur frequently in patients with AIDS.

Treatment

General: If left untreated, cryptococcal meningitis results in death 100% of the time. Therefore, early diagnosis and treatment with amphotericin B is essential. Prior to the discovery of amphotericin B in 1955, 80% of patients with CNS involvement died within two years of diagnosis.
The cerebrospinal fluid (CSF) pressure should be monitored during the initial therapy (first 12 weeks). Elevated pressures should be controlled by therapeutic CSF removal. A repeat lumbar puncture is recommended in all patients two weeks after the start of therapy to ensure that the treatment is working.
Amphotericin B: Initially, amphotericin B (Amphocin? or Fungizone?) is administered intravenously at 0.7-1mg/kg/d for two weeks, with or without 100 mg/kg/d of flucytosine. Other preparations of amphotericin B include liposomal amphotericin B (AmBisome?), amphotericin B lipid complex (Abelcet?), amphotericin B cholesteryl complex (Amphotec?), and amphotericin B colloidal dispersion (Amphocin?). None of these alternative forms of amphotericin B is better than standard, non-lipid amphotericin B (Amphocin? or Fungizone?). Treatment is followed by 400mg/d of fluconazole (Diflucan?) for a minimum of 10 weeks.
Fluconazole (Diflucan?): Once initial treatment is completed, a maintenance therapy of 200-400mg/d of fluconazole (Diflucan?) for life is recommended.
Surgery: In rare cases, a patient may develop complete obstruction of the ventricles and require a CSF shunt to relieve intracranial pressure.

Integrative therapies

Note: Currently, there is insufficient evidence available on the safety and effectiveness of integrative therapies for the prevention or treatment of cryptococcal meningitis. Most of the therapies listed below have been studied for related conditions, should be used only under the supervision of a qualified healthcare provider, and should not be used in replacement of other proven therapies or preventive measures. Cryptococcal meningitis is a potentially serious condition, for which other treatments are available.
Unclear or conflicting scientific evidence:
DMSO (dimethyl sulfoxide): DMSO may help treat intracranial pressure in the skull, but most research is vague and results are conflicting. The risks may be greater than potential benefits.
Avoid if allergic or hypersensitive to DMSO. Use caution with urinary tract cancer or liver and kidney dysfunction. Avoid if pregnant or breastfeeding.
Garlic: Preliminary study documented potential benefits of oral plus intravenous garlic in the management of cryptococcal meningitis. Further research is needed before recommending for or against the use of garlic in the treatment of this potentially serious condition, for which other treatments are available.
Caution is advised when taking garlic supplements, as adverse effects including an increase in bleeding and drug interactions are possible. Garlic supplements should not be used if pregnant or breastfeeding, unless otherwise directed by a doctor.
Ginseng: Preliminary study of Xuesaitong injection (XSTI, a preparation of Panax notoginseng) reports that it may help to decrease intracranial pressure. Further research is needed to confirm these results.
Avoid ginseng with known allergy to plants in the Araliaceae family. There has been a report of a serious life-threatening skin reaction, possibly caused by contaminants in ginseng formulations.
Selenium: Preliminary research shows a decrease of elevated intracranial pressure symptoms (headaches, nausea, vomiting, vertigo, unsteady walk, speech disorders and seizures) with use of selenium. More research is needed before a firm conclusion can be made.
Avoid if allergic or sensitive to products containing selenium. Avoid with history of non-melanoma skin cancer. Selenium is generally regarded as safe for pregnant or breastfeeding women. However, animal research reports that large doses of selenium may lead to birth defects.
Thymus extract: Preliminary evidence suggests that thymus extract has no clinical effect in patients with subacute sclerosing panencephalitis. Additional study is needed to better determine the potential role of thymus extract in encephalitis.
Avoid if allergic or hypersensitive to thymus extracts. Use bovine thymus extract supplements cautiously due to potential for exposure to the virus that causes "mad cow disease." Avoid use with an organ transplant or other forms of allografts or xenografts. Avoid if receiving immunosuppressive therapy or hormone therapy. Avoid with thymic tumors, myasthenia gravis (neuromuscular disorder) or untreated hypothyroidism. Avoid if pregnant or breastfeeding. Thymic extract increases human sperm motility and progression.

Prevention

Individuals who are immunocompromised have an increased risk of developing cryptococcosis. Therefore, it is recommended that HIV/AIDS patients receive highly active antiretroviral therapy (HAART) to restore the body's immune system and prevent opportunistic infections. This therapy usually combines drugs from at least two different classes of antiretroviral drugs, and it has been shown to suppress the virus. While these drugs cannot cure HIV infection or AIDS, they can suppress the virus.