1. Cryptococcosis: Epidemiology of cryptococcal disease
Professor Malcolm D. Richardson
Mycology Reference Centre, Manchester
Manchester University NHS Foundation Trust

2. Intended learning outcomes
To be aware of the epidemiology of cryptococcal antigenaemia and meningitis
To be aware of the risk factors for acquiring cryptococcal disease

3. Cryptococcosis
Cryptococcosis refer to infections caused by any species of the genus Cryptococcus.
Cryptococcus spp. are capable of causing diseases in both immunocompetent and immunocompromised individuals.
Cryptococcal meningitis is the most common clinical manifestation of cryptococcosis.
Disseminated cryptococcal disease is largely associated with HIV/AIDS.

4. Cryptococcus & HIV
Cryptococcus is the 2nd or 3rd leading opportunistic infection in patients with HIV/AIDS.
Patients with CD4 <100 are the most at risk.
Cryptococcus is responsible for up to 15% (13-44%) of the HIV/AIDS deaths.
6% of the global HIV/AIDS population with under 100 CD4 cells are CrAg positive, with substantial geographical variability
Rajasingham et al. Lancet Infect Dis. 2017; 3099(17), pp. 1–9

5. Prevalence of CrAg Nigeria DR Congo Uganda Ethiopia Kenya Prevalence
Globally
Prevalence
South Africa
CD4 T-cell counts

6. Who are at risk? HIV (80-90%) Treatment with monoclonal antibodies
C. neoformans
HIV (80-90%)
Idiopathic CD4 lymphopenia
Lymphoproliferative malignancies and disorders
Long-term corticosteroid and /or immunosuppressive therapy
Solid organ & bone marrow transplant recipients
Sarcoidosis
Treatment with monoclonal antibodies
Rheumatological diseases
SLE
Rheumatoid arthritis
Hyper-IgM or Hyper-IgE syndromes
Decompensated chronic liver disease
Renal failure and /or peritoneal dialysis
Adult-onset immunodeficiency
Williamson PR, Jarvis JN, Panackal AA, et al. Cryptococcal meningitis: epidemiology, immunology, diagnosis and therapy.Nature reviews Neurology2017; 13:13-24.
Gastroenterology. 1988 Mar;94(3):
Cryptococcosis of the colon resembling Crohn's disease in a patient with the hyperimmunoglobulinemia E-recurrent infection (Job's) syndrome.
Hutto JO1, Bryan CS, Greene FL, White CJ, Gallin JI.
Author information
Abstract
A 29-yr-old woman presenting with granulomatous colitis and a chronic perirectal abscess was found to have localized cryptococcosis associated with the hyperimmunoglobulinemia E-recurrent infection (Job's) syndrome. Similarity to previous cases of esophageal cryptococcosis and ileocecal histoplasmosis suggests an association between the hyperimmunoglobulinemia E-recurrent infection syndrome and localized fungal infections of the alimentary tract. To our knowledge, this is the first well-documented case of cryptococcosis confined to the colon and perirectal tissues.
Williamson PR et al. Nature Rev Neurol. 2017; 13:13-24.

7. Who are at risk? C. gattii Predominantly immunocompetent individuals
Other risk factors1
HIV (10-20%)
Current Smoker
Age (>50 years)
History of invasive cancers
1MacDougall et al Emerg Infect Dis Feb;17(2):193-9.

8. Global burden of cryptococcal disease
Parks et al 2009
Parks et al:
Based on few provider-based cohort studies
Probably an over estimate of the actual burden
Rajasingham et al 2017
Rajasingham et al:
Decreased global burden
Mortality remains unchanged
65% (2009) vs. 80% (2017)
Sub-Saharan Africa still has majority of cases and deaths
Rajasingham et al. Lancet Infect Dis. 2017; 3099(17), pp. 1–9
Park et al. Aids. 2009; 23(4), pp. 525–30.

9. Cryptococcus is responsible for 15% of AIDS-related mortality globally
95% CI 10% to 19%).
CRAG prevalence of 6·0% among HIV/AIDS patients with CD4<100 cells/µL
Rajasingham et al. Lancet Infect Dis. 2017; 3099(17), pp. 1–9

10. Summary
HIV/AIDS is the most common risk factor for acquiring cryptococcal disease.
It accounts for up to 15% (13-44%) of AIDS-related deaths.
Global CrAg prevalence is up to 6%.

11. END