Cryptococcosis
Peer reviewed by Patient clinician teamLast updated by Dr Gurvinder Rull, MBBSLast updated 19 Feb 2010
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This describes infection by the encapsulated nonmycelial budding yeast cryptococcus which is found worldwide.
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Aetiology
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 .
Epidemiology
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
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Risk factors
Generally defective T-cell function predisposes to this infection, e.g:
HIV
Solid organ transplant recipients, eg liver transplant
Other risk factors include:
Diabetes mellitus
Hepatic cirrhosis
Haematological malignancies
Corticosteroid therapy
Sarcoidosis
Connective tissue disorders
Novel immunosuppressive monoclonal antibody therapies, eg infliximab
Presentation
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
Headache
Confusion
Altered mental status
Coma
Seizures
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.
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Investigations
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.
Management
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
Complications
Hydrocephalus
Long-term impairment of mental function
Prognosis
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
Prevention
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
Further reading and references
- Jarvis JN, Dromer F, Harrison TS, et al; Managing cryptococcosis in the immunocompromised host. Curr Opin Infect Dis. 2008 Dec;21(6):596-603.
- Shirley RM, Baddley JW; Cryptococcal lung disease. Curr Opin Pulm Med. 2009 May;15(3):254-60.
- Severo CB, Xavier MO, Gazzoni AF, et al; Cryptococcosis in children. Paediatr Respir Rev. 2009 Dec;10(4):166-71. Epub 2009 Jul 25.
- Nakamura S, Izumikawa K, Seki M, et al; Pulmonary cryptococcosis in late pregnancy and review of published literature. Mycopathologia. 2009 Mar;167(3):125-31. Epub 2008 Oct 18.
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Article history
The information on this page is written and peer reviewed by qualified clinicians.
19 Feb 2010 | Latest version

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