29th July 2023

Cryptococcosis

The most clinically relevant form of this yeast is Cryptococcus neoformans, which can cause disease in both immunocompetent and immunosuppressed individuals. However, most fungal infections are more likely to cause serious and invasive diseases in the latter group. Patients with HIV/AIDs are particularly at risk, and mortality is as high as 12% in this demographic.

The yeast is surrounded by a gelatinous cell wall, which makes it resistant to conventional Gram staining techniques. Instead, the Indian ink stain is used to visualise the organisms. Cryptococcus is ubiquitous globally and particularly associated with soil and bird droppings.

Initial infection is generally asymptomatic and often remains so in healthy individuals. The disease manifests typically through haematogenous spread to other sites, or via reactivation of previously dormant infections, in immunosuppressed patients. When the infection causes a disease, it is known as cryptococcosis. The two most commonly affected body systems are the CNS and lungs, which are the focus of this topic.

Pulmonary cryptococcosis

Lung disease can be seen in both immunocompetent and immunosuppressed people but is more likely to cause serious disease in the latter.

The lungs are the initial site of any Cryptococcus infection, as the yeast enters the body through inhalation. Infection presents as a pneumonia-like illness, with cough, dyspnoea, chest pain, and fever the predominant symptoms. In patients with an intact immune system, this may be asymptomatic. Though the disease can become dormant, and for individuals carrying Cryptococcus, there is a risk of reactivation if they undergo an immunosuppressive insult.

Diagnosis can be made through chest x-ray or CT scan to demonstrate pneumonia, and then cultures confirming the presence of Cryptococcus, using the Indian ink stain. Serum assays include the ELISA technique. Blood cultures are used to assess for the presence of disseminated disease.

First line treatment is with fluconazole for an extended treatment course of 6-12 months. Severe or untreated pulmonary cryptococcosis can cause ARDS, which may be life-threatening.

Cryptococcal meningitis

This is the primary manifestation of cryptococcosis in patients with HIV/AIDS, and is an AIDS-defining illness associated with high mortality. It can occur in other immunocompromised people, too. The yeast reaches the meninges through haematogenous spread from the lungs, where it causes an insidious onset of subacute meningitis or meningoencephalitis.

The onset is generally over 1-2 weeks, with the predominant symptoms of headache, fever, and malaise. Neck stiffness, photophobia, and other focal neurological deficits are rare but may occur. Cryptococcal meningitis is fatal if untreated.

Diagnosis is made through CSF analysis following lumbar puncture. The characteristic profile is of lymphopaenia, high protein, and low glucose, but it may also be normal. CSF fluid can then be stained with Indian ink to demonstrate the organisms.

Treatment with antifungals consists of an induction, consolidation, and maintenance phase. Induction is with IV amphotericin B, of which the liposomal forms are now generally preferred, alongside oral flucytosine. Induction is successful when no Cryptococcus organisms are detected on repeat LP and the patient is clinically improving. Following this, fluconazole is given at a high dose for 8 weeks as consolidation. If the patient remains clinically stable, a lower dose is maintained for at least one year.

If a patient has comorbid HIV/AIDS, then appropriate antiretroviral treatment is also essential to prevent relapse.