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

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

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.

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

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

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):808-12. 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.

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. 2011 Feb;17(2):193-9. DOI: 10.3201/eid1702.101020.

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.

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

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%.

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