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Updated: May 24, 2025
Macrophage Cholesterol Depletion and Its Effect on the Phagocytosis of Cryptococcus neoformans
Published on: December 19, 2014
Cryptococcosis
Hisako Kushima1,2, Hiroshi Ishii2
1Department of Infection Control and Prevention, Fukuoka University Chikushi Hospital.
Abstract:
Approximately one million new cases of cryptococcosis develop each year worldwide, resulting in approximately 600,000 deaths. Most cases occurred in HIV patients from African countries south of the Sahara Desert. In light of this situation, in 2022, the World Health Organization presented a list of priority fungal pathogens to guide research, development, and public health action, with Cryptococcus neoformans as the most important critical fungus. In contrast, a recent retrospective study in developed countries showed that 90% of cases with cryptococcosis were non-HIV patients, including immunocompetent individuals. Underlying diseases of non-HIV immunocompromised patients include cancer and solid organ transplantation. High serum titers cryptococcal antigens independently predicted the risk of central nervous system involvement. Even if the patient is asymptomatic, high antigen levels are considered a possibility of cryptococcal meningitis, and a spinal fluid examination may be recommended. The absence of a history of contact with pigeons should not be used as a basis for denying cryptococcosis because C. neoformans is often detected in old and dried feces of chickens other than pigeons. Donor-derived cryptococcosis is a unique feature of cryptococcosis in solid organ transplant recipients. Pre-transplant screening tests for cryptococcosis, pre-transplant treatment for the donor, and prophylactic antifungal therapy for the recipient may be useful. Defense against cryptococcal infection is regulated by various mechanisms, including Th1, Th2, and Th17 immune responses. Molecularly targeted medicines that target specific cytokines or surface antigen molecules have been widely used with excellent clinical efficacy for the treatment of various diseases. Since cryptococcosis has been recently reported to develop during the use of certain medicines, such as ibrutinib and eculizumab, clinicians need to be mindful that the number of similar cases may increase in the future.
Insights
Cryptococcosis, a serious fungal infection, causes 600,000 deaths annually, primarily in HIV patients in Africa. Emerging data show increased cases in non-HIV individuals, including immunocompetent ones, highlighting the need for broader awareness and diagnostic approaches.
Area of Science:
- Mycology
- Infectious Diseases
- Immunology
Background:
- Cryptococcosis is a significant global health threat, causing approximately 600,000 deaths annually, predominantly in HIV-positive individuals in sub-Saharan Africa.
- The World Health Organization identified Cryptococcus neoformans as a critical fungal pathogen in 2022 due to its high mortality and morbidity.
- Recent studies indicate a shift, with 90% of cryptococcosis cases in developed nations occurring in non-HIV patients, including immunocompetent individuals with underlying conditions like cancer or those who have undergone solid organ transplantation.
Purpose of the Study:
- To highlight the changing epidemiology of cryptococcosis, emphasizing its occurrence in non-HIV patients.
- To underscore the diagnostic significance of high serum cryptococcal antigen titers for predicting central nervous system involvement, including cryptococcal meningitis.
- To discuss unique aspects of cryptococcosis in solid organ transplant recipients and potential preventative strategies.
Main Methods:
- Review of global epidemiological data on cryptococcosis.
- Analysis of clinical presentation and risk factors in both HIV-positive and non-HIV patient populations.
- Examination of diagnostic markers, including serum cryptococcal antigen testing and spinal fluid analysis.
- Discussion of immune responses and emerging therapeutic considerations.
Main Results:
- High serum cryptococcal antigen titers are an independent predictor of central nervous system involvement and cryptococcal meningitis, even in asymptomatic patients.
- Cryptococcosis in solid organ transplant recipients can be donor-derived, necessitating pre-transplant screening and prophylactic measures.
- The immune defense against Cryptococcus involves Th1, Th2, and Th17 responses.
- Newer immunosuppressive therapies may be associated with an increased risk of cryptococcosis.
Conclusions:
- Cryptococcosis epidemiology is evolving, with a notable increase in non-HIV cases, requiring updated diagnostic and management strategies.
- Early detection through antigen testing and consideration of cryptococcal meningitis are crucial, irrespective of HIV status.
- Donor-derived infections and iatrogenic cryptococcosis associated with targeted therapies warrant increased clinical vigilance and preventative measures, particularly in transplant recipients.
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