The main infectious agent responsible for cryptococcosis is the fungus Cryptococcus neoformans, an encapsulated yeast mainly spread by airborne transmission that is present in soil and organic debris. The geographical distribution of Cryptococcus neoformans is widespread; the pathogen is found all over the world. Cryptococcus gattii is less widespread and is mainly found in certain tree species in tropical areas.
The most common clinical form of cryptococcosis is disseminated meningoencephalitis (in more than 60% of cases, and in more than 80% of cases in patients with HIV). The symptoms are variable: headache and moderate fever are experienced by more than 70% of patients, while dizziness, irritability, confusion, convulsions, drowsiness or even coma, cranial nerve palsy and motor deficiency may occur in 20 to 50% of cases. Rapid development of symptoms and signs of intracranial hypertension can indicate a poor prognosis. In the absence of treatment, worsening of symptoms and death are inevitable. With treatment, premature mortality still occurs in around 27% of non-HIV patients and 14% of patients with HIV.
Infection can also be localized to the lungs, leading to a pneumonia-like illness with non-specific symptoms (cough and moderate fever), or to any other organ. Skin lesions caused when the yeast spreads in the bloodstream can appear as painless papules that can become ulcerous. Some patients are asymptomatic. Infection is diagnosed by direct examination or histology to determine the presence of yeast surrounded by a clear halo in tissue or fluid samples; by the identification of Cryptococcus neoformans in these samples; and/or by the detection of the specific antigen in a blood serum or cerebrospinal fluid sample. Rapid tests have been developed for bedside diagnosis.
Cryptococcosis is responsible for 15% of deaths related to human immunodeficiency virus (HIV), the majority in Sub-Saharan Africa. It is a typically opportunistic infection in immunocompromised HIV patients with a CD4 count of less than 200/mm3 or patients with another form of immunosuppression, for example caused by an organ transplant, systemic disease or hemopathy. In France, around 40% of cryptococcosis cases are HIV-related.
The fungus Cryptococcus neoformans is present in the environment, and contamination generally occurs by inhalation. Direct inoculation via skin wounds can cause skin lesions such as paronychia or cellulitis, and the infection can sometimes spread to other parts of the body in immunocompromised patients. But there is no human-to-human transmission, apart from some rare observations reported after organ transplants. Rare cases have been reported in people who have cleaned surfaces that were highly contaminated with pigeon droppings, and close contact with pigeons is therefore not recommended for immunocompromised individuals. Cryptococcus gattii is found in trees such as eucalyptus and is also spread by inhalation.
Several weeks of antifungal treatment is required. In severe cases (meningoencephalitis and severe pulmonary disease), treatment involves a combination of liposomal amphotericin B and 5-fluorocytosine, followed by high-dose fluconazole. In the event of intracranial hypertension, lumbar punctures are also performed. Clinical improvement is generally slow, taking one to two weeks, and remission is only achieved after at least six weeks of initial treatment. Sequelae may remain after recovery. Prophylactic treatment for relapses is systematically administered in HIV patients until full, stable immune reconstitution has been achieved with antiretroviral therapy.
At the Institut Pasteur
The Molecular Mycology Unit, led by Françoise Dromer, which also hosts the National Reference Center for Invasive Mycoses & Antifungals (NRCMA) is involved in a large-scale therapeutic research program in Africa in collaboration with the ANRS and St. George's, University of London. NRCMA characterizes strains isolated in France and is responsible for epidemiological surveillance of cryptococcosis in the country.
The Molecular Mycology Unit also investigates factors involved in the virulence and dormancy of Cryptococcus neoformans and conducts research on the pathophysiology of infection and the development of new tests.
The RNA Biology of Fungal Pathogens Unit, led by Guilhem Janbon, focuses on the extracellular vesicles produced by the fungus, especially their role in regulating resistance to antifungal drugs and their potential use as vaccine candidates.
The Institut Pasteur teams working on cryptococcosis
led by Françoise Dromer
RNA Biology of Fungal Pathogens Unit
led by Guilhem Janbon
Surveillance and public health