Cryptococcosis

This describes infection by the encapsulated nonmycelial budding yeast cryptococcus which is found worldwide.

Ätiologie

This largely severe opportunistic infection is caused by two serotypes in patients with defective T-cell mediated immunity, called: ¹

• Cryptococcus neoformans var grubii (serotype A - causes the large majority) and

• Cryptococcus neoformans var neoformans (serotype D).

C. neoformans is abundant in soil contaminated by pigeon droppings. It is still a major cause of mortality in HIV-infected individuals worldwide, despite the use of antiretroviral therapy.¹

There is a third cause of cryptococcosis, Cryptococcus gattii (previously C. neoformans var gattii serotypes B and C), which infects immunocompetent individuals and is associated with red gum trees. C. gattii is normally found in the tropics though it has now been isolated in Vancouver Island, Canada.

This article will focus on cryptococcosis caused by C. neoformans var grubii and C. neoformans var neoformans .

Epidemiologie

• Cryptococcosis is the most common cause of HIV-related meningitis in Central and Southern Africa, accounting for up to 40% of cases.¹

• Pulmonary cryptococcosis is also being increasingly recognised with one study reporting 7% prevalence in a group of South African miners (HIV prevalence of 24%).²

Risikofaktoren

Generally defective T-cell function predisposes to this infection, e.g:

• HIV

• Solid organ transplant recipients, eg liver transplant

Weitere Risikofaktoren sind:

• Diabetes mellitus

• Hepatic cirrhosis

• Haematological malignancies

• Corticosteroid therapy

• Sarkoidose

• Connective tissue disorders

• Novel immunosuppressive monoclonal antibody therapies, eg infliximab

Präsentation

Cryptococcus can affect several organs, but most patients will present with meningitis or meningoencephalitis. A thorough clinical assessment is therefore needed, looking especially for neurological signs and other sites of infection. Remember that HIV-infected patients may be asymptomatic or present with nonspecific symptoms, eg lethargy, weight loss.

Meningitis and meningoencephalitis

• Kopfschmerzen

• Verwirrung

• Altered mental status

• Koma

• Krampfanfälle

• Neurological signs include diplopia, ataxia and aphasia

Pulmonary cryptococcosis

• This is underdiagnosed

• Seen in between 25-55% of patients with AIDS who have cryptococcal meningitis²

• Patients are often asymptomatic

• Otherwise, can present with cough and pleuritic chest pain and/or dyspnoea

• Severe pneumonia with respiratory failure or acute respiratory distress syndrome may also be seen

Other manifestations include skin (eg papules, pustules, nodules, etc.), osteomyelitis, eye (chorioretinitis), hepatitis and myocarditis.

Nachforschungen

• Fungal burden can be determined by CSF, blood, and urine cultures.

• Cryptococcal antigen titres (can be measured in CSF and/or serum) - this is a better indicator of fungal burden and outcome.

• Blood tests - FBC, renal and liver function tests (this can help to detect other illnesses and to monitor drug toxicities, eg amphotericin B can lead to anaemia).

• Radiology - this partly depends on the site of infection, eg CXR in pulmonary disease and brain imaging in meningitis/meningoencephalitis (generally MRI scan is better than CT scan).¹²

• Other investigations - again, these may be specific to the site of infection, eg bronchoalveolar lavage in pulmonary cryptococcosis, liver biopsy.

Verwaltung

Antifungal therapy

This is divided into 3 phases: (based on Infectious Diseases Society of America guidelines)²

• Induction (initial therapy) - usually amphotericin B (may be liposomal formulation in renal impairment) and flucytosine

• Consolidation (clearance therapy) - fluconazole orally, usually for a minimum of 8 weeks

• Maintenance (suppression therapy) - lower dose oral fluconazole for 6-12 months

Discontinuation of therapy is usually based on an individual patient basis.

Isolated organ disease and treatment of immunocompetent patients may be different depending on the severity of the disease. For example, isolated mild-to-moderate pneumonia may be treated with high-dose fluconazole for 6-12 months, followed by a lower dose for maintenance.

Children and pregnant women

• The management of children is based on regimens used in adults and again consists of amphotericin B and fluconazole.³

• The management in pregnant women is more difficult but use of fluconazole (after delivery) has been used with successful outcomes.⁴

Komplikationen

• Hydrocephalus

• Long-term impairment of mental function

Prognose

Acute mortality from HIV-associated cryptococcal meningitis is unchanged, although long-term outcomes are improved provided the patient becomes established on antiretroviral therapy.¹

Higher mortality is associated with:¹

• Mycological failure at two weeks

• Initial disease dissemination

• High cryptococcal antigen titre (≥1:512)

• Lack of flucytosine during initial therapy

• Abnormal mental function

Prävention

Primary prophylaxis with fluconazole in HIV-infected patients whose CD4 count is <100 cells/mm³ has been used but it is not always effective.²