Cryptococcus meningitis: Diagnosis and treatment

2021-07-22 05:56 PM

Cryptococcal meningitis should be considered, and in patients with persistent inflammation, appropriate laboratory tests are indicated to confirm the diagnosis.

Meningitis definition

What is a meningitis ? Is meningitis contagious ?

Meningitis (also called meningitis of the spine, spinal meningitis) is an inflammation of the membranes surrounding the brain and spinal cord, usually due to the spread of infection.

Which meningitis is contagious ?

Meningitis bacteria, the most serious meningitis, especially if it's meningitis meningococcal. It's spread by contact with an infected person. 

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Cryptococcal meningitis

Cryptococcal meningitis is a rare central nervous system infection, usually in immunocompromised individuals; The disease mainly has a long course, has a high mortality rate, and is difficult to diagnose without subclinical support. Cryptococcal meningitis requires intensive and prolonged treatment to prevent mortality and sequelae.

Cryptococcus meningitis diagnosis and treatment

Cryptococcal meningitis causes

Cryptococcus neotormans is a fungus present in soil contaminated with bird droppings, in some fruits, infecting people through the respiratory tract or skin wounds. Cryptococcus can cause lung disease, fungal infection, but the most common pathology is meningitis. The disease can be seen in normal people, but it is mostly seen in immunocompromised people such as HIV infection, prolonged use of corticosteroids, blood malignancies, sarcoid disease, etc. HIV-infected people are at risk of meningitis. due to Cryptococcus in the stage of severe immunodeficiency, CD4 < 100 cells/mm1 blood.

Cryptococcal meningitis should be considered in patients with persistent meningitis, especially those with HIV; Specify the appropriate tests to confirm the diagnosis.

Clinical cryptococcal meningitis symptoms

Cryptococcal meningitis progresses slowly

Main manifestations: headache, fever, nausea, confusion, possibly seizures. Vision loss is a common sign, progressing to blindness.

Examination: subtle meningeal signs; Paralysis of the cranial nerves is often asymmetrical.

Meningitis with rash (meningitis rash): Meningitis patients with bacteremia may have a necrotic skin rash. One of the late meningitis signs that bacterial meningitis causes.


Cryptococcal meningitis in HIV-infected people

Manifestations are less different from those not infected with HIV.

Patients may have symptoms of HIV infection at the same time, such as pharyngitis, skin rash, other diseases.

Cerebrospinal fluid (CSF) may be normal or minimally altered, and fungal concentrations in CSF are usually higher than in HIV-uninfected individuals.

Fungal manifestations in organs and organs other than the central nervous system are also seen with a higher frequency.

Recurrence with more severe symptoms is possible when the patient is on antiretroviral therapy (ART) as a manifestation of the immune reconstitution inflammatory syndrome.

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DNT: pressure increases; DNT protein increases, cells increase.

Computed tomography or cranial magnetic resonance imaging may show increased intracranial pressure; some patients have brain abscess caused by Cryptococcus.

Chest radiography can detect lung lesions in individuals with associated pneumonia, including local infiltrates, nodular or diffuse infiltrates, hilar lymphadenopathy, cavernous lesions, and pleural effusion.

Differential diagnosis

Tuberculous meningitis: gradual progression, meningeal signs are not obvious, there are focal neurological signs, CSF changes are mild, similar to cryptococcal meningitis. Diagnosis of tuberculous meningitis by PCR/CSF culture for TB, chest X-ray for TB lesions, computed tomography (CT) or MRI of the brain, etc. Colonoscopy and culture of fungal CSF will confirm Cryptococcus.

Toxoplasma encephalitis: is a disease that can be seen in HIV-infected people, develops slowly, presents with headache and impaired consciousness, similar to cryptococcal meningitis. Computed tomography or magnetic resonance imaging (MRI) of the brain will show the characteristic abscesses of Toxoplasma encephalitis.

Meningoencephalitis caused by A. cantonensis'. Eosinophilia in CSF and/or blood is suggestive of VMN caused by A. cantonensis and other helminthic larvae. A positive Cryptococcus test is the definitive diagnosis for cryptococcal meningitis and excludes the diagnosis of helminthic meningitis.

Diagnose the cause

Screening for melasma in cerebrospinal fluid: is a simple, fast and effective method to detect Cryptococcus fungus. DNT was freshly dyed with Chinese ink and examined for fungi. Some other staining methods are silver methenamine staining by the Gomori method, alcian blue staining. Cryptococcus fungi present in CSF, in addition to diagnostic value, is also a feature that indicates the severity of the disease.

Mushroom culture: c. neoformans can be isolated from CSF and/or blood; Grows in all bacterial and fungal cultures. The incubation period is 3 to 7 days.

Serological diagnosis: Cryptococcal polysaccharide antigen can be detected in the patient's CSF, blood, and urine. Latex agglutination tests and enzyme immunoassays have sensitivity and specificity >90%. False-negative results can be encountered when antigen levels in the CSF are too high.

Cryptococcal meningitis treatment

Patients with cryptococcal meningitis should be treated in higher-level settings with appropriate laboratory conditions and care.

Amphotericin B is the drug of choice for the treatment of cryptococcal meningitis; dose: 0.7-1 mg/kg/day, slow intravenous infusion; can be combined with flucytosine 100mg/kg/day. Amphotericin B can cause side effects such as fever, hypokalemia and hypomagnesemia, anemia, kidney failure; flucytosine can cause bone marrow suppression and decreased blood cell lines.

Fluconazole may be indicated from the outset for mild, uncomplicated cases of meningitis, or in the absence of amphotericin B. Fluconazole is also indicated as consolidating therapy after amphotericin B therapy. Fluconazole dose: 400- 900mg orally per day.

Treatment of raised intracranial pressure: drain CSF once daily or several times depending on the degree of increased intracranial pressure, drain 15-20ml each time or until the patient's headache subsides (mannitol and corticosteroids do not effective).

Cryptococcal meningitis patients who are not HIV-infected should be treated with amphotericin B for 6-10 weeks, or until symptoms of meningitis and fungal culture in CSF (a few milliliters of CSF are taken). 2 times negative. Patients should be continued on fluconazole therapy for 6-12 months.

HIV-infected patients should be treated with amphotericin B for at least 2 weeks; treatment-responsive patients can be switched to fluconazole for 8-10 weeks, followed by maintenance therapy (secondary prevention) with fluconazole 150-200 mg/day, for life; Discontinue use when patients on ART have CD4 count > 200 TB/mm3 > 6 months.

Cryptococcal meningitis has a high mortality rate; Some patients, after being treated and cured, may have permanent sequelae such as blindness, intellectual impairment.


People with HIV infection and immunocompromised persons due to underlying diseases or prolonged use of corticosteroids should avoid exposure to sources of fungal infection such as bird droppings.

People with HIV who are on antiretroviral therapy and whose immune systems are restored (CD4 > 200 cells/mm3 of blood) have a lower risk of cryptococcal meningitis.

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