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Background Cryptococcus species can cause severe disseminated infections in immunocompromised hosts. This study investigated the epidemiological features and trends in disseminated cryptococcosis in Japan. Methods We used publicly available Infectious Diseases Weekly Reports to obtain data on the incidence of disseminated cryptococcosis in Japan from 2015 to 2021. Patient information, including age, sex, and regional and seasonal data, were extracted. The Joinpoint regression program was used to determine the age-adjusted incidence rate (AAR) per 100,000 population, annual percentage change (APC), and average APC (AAPC). Results A total of 1047 cases of disseminated cryptococcosis were reported, of which those aged ≥ 70 years accounted for 68.8%. The AAR in men was significantly higher than that in women (median: 0.13 vs. 0.09: p  = 0.0024). APC for the overall cases increased by 9.9% (95% confidence interval [95% CI] − 5.4–27.7) from 2015 to 2018 and then decreased by 3.3% (95% CI − 15.5–10.7) from 2018 to 2021. AAPC for the entire study period was 3.1% (95% CI − 1.5–8.0), indicating a possible increase in its number, although not statistically significant. In terms of regional distribution, the average AAR was highest in Shikoku District (0.17) and lowest in Hokkaido District (0.04). Northern Japan exhibited a significantly lower median AAR (median [interquartile range]: 0.06 [0.05, 0.08]) than the Eastern (0.12 [0.12, 0.13]), Western (0.11 [0.10, 0.13]), and Southern (0.14 [0.12, 0.15]) regions. No seasonal variation in incidence was observed. Conclusion The prevalence of disseminated cryptococcosis has not increased in Japan. Geographically, the incidence is lower in Northern Japan. Further investigations that incorporate detailed clinical data are required.

Fingolimod is a multiple sclerosis disease-modifying therapy which sequestrates lymphocytes in the lymph nodes, thereby reducing peripheral blood lymphocytes. Cryptococcal infection is an important adverse effect which should be recognised. We report a case of cutaneous and central nervous system infection who presented with isolated cutaneous symptoms in the absence of neurological or systemic manifestations.

Background Coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first reported in Wuhan, China. Due to the rapid spread globally, it was declared a pandemic in March 2020. Social distancing and lockdown measures were introduced to limit transmission. These strategies could potentially impact the diagnosis and treatment of patients with advanced HIV who are susceptible to secondary infections like cryptococcal disease. In South Africa, reflexed cryptococcal antigenaemia (CrAg) testing and pre-emptive antifungal treatment are recommended preceding antiretroviral therapy initiation for patients with a CD4<100 cells/[mu]l. This study aimed to assess the impact of COVID-19 on CrAg testing in South Africa. Methods Specimen-level data was extracted for individuals [greater than or equal to]15 years from the National Health Laboratory Services repository for calendar years 2018 to 2021. Test volumes and CrAg positivity were assessed at national and provincial levels, by age category and gender. The percentage change in annual and monthly CrAg test volumes for 2020 and 2021 (during lockdown levels) are compared to data reported for 2018. The monthly median CD4 and the percentage of samples with a count 75-<100 cells/[mu]l were assessed. Results Specimen data of 11 944 929 CD4 results included 1 306 456 CrAg tests. Annual CD4 and CrAg test volumes declined by 22.4% and 27.8% for 2020 and 2021 respectively (relative to 2018). There were 23 670 CrAg positive outcomes in 2018 compared to 21 399 (-9.6%) and 17 847 (-24.6%) in 2020 and 2021 respectively. A monthly test volume reduction of up to 36.6%, 35.5%, 36.1% and 13.3% was reported for infection waves one to four. CrAg detection increased from 6.3% in 2018 to 7.5% in 2020. More testing was offered to males (>56%) with a higher detection rate of 8.1% in 2020. Between 81.0% and 81.8% of testing was for patients aged 20 to 49 years. The monthly percentage of specimens <25 cells/[mu]l ranged from 30.2% (June 2019) to 35.3% (August 2020). Overall, the monthly median CD4 ranged from 39 (IQR: 15-70)(August 2020) to 45 (IQR: 19-72)(March 2019) cells/[mu]l. In 2020, the provincial percentage change in CrAg test volumes ranged from 2.9% to -33.7%. Conclusion Our findings confirmed the impact of lockdown measures on both the absolute number of CrAg tests performed and detection (increase in 2020). A smaller impact on the median CD4 was noted. The long-term impact on patient management in immune- compromised individuals needs further investigation.

Background Cryptococcosis is one of the most frequent fungal eye infections in patients with immunosuppression. Currently, treatment approaches for non-meningeal, non-pulmonary cryptococcosis are based on those used for cryptococcal meningitis or pneumonia. Case presentation We present a rare case of non-meningeal, non-pulmonary cryptococcosis with clinical manifestations limited to one eye of a cadaveric kidney transplant recipient with chronic-active antibody-mediated rejection. Typical manifestations, diagnosis, and treatments, including antifungal therapies, adjunctive therapies, and immunosuppression reduction, are discussed. After timely diagnosis and treatment, her visual acuity recovered to baseline without recurrence or sequelae of cryptococcosis. Conclusions Clinicians should be aware of rare presentations of fungal infections, especially when a kidney transplant recipient with rejection has been treated with intensive immunosuppressants. Early diagnosis with individualized therapies may have a favorable prognosis.

Background Cryptococcus is one of the major fungal pathogens infecting the lungs. Pulmonary cryptococcal infection is generally considered a community-acquired condition caused by inhalation of dust contaminated with fungal cells from the environment. Here, we report a case developing pulmonary cryptococcosis 3 months after hospital admission, which has rarely been reported before. Case presentation A 73-year-old female patient who was previously immunocompetent experienced persistent dry cough for 2 weeks, 3 months after admission. Chest computed tomography (CT) showed a new solitary pulmonary nodule developed in the upper lobe of the left lung. Staining and culture of expectorated sputum smears were negative for bacteria, acid-fast bacilli, or fungus. The patient then underwent biopsy of the lesion. Histopathology findings and a positive serum cryptococcal antigen titer (1:8) indicated pulmonary cryptococcosis. Daily intravenous 400 mg fluconazole was administered initially followed by oral fluconazole therapy. Follow-up chest CT after 3 months of antifungal therapy showed complete disappearance of the pulmonary nodule. Respiratory symptoms of the patient also resolved. A complete investigation excluded the possibility of a patient-to-patient transmission or primarily acquiring the infection from the hospital environment. Based on the patient’s history of exposure to pigeons before admission and recent steroid and azathioprine use after admission for the treatment of myasthenic crisis, reactivation of a latent pulmonary cryptococcal infection acquired before admission, in this case, is impressed. Conclusions Although rarely reported, pulmonary cryptococcal infection should be included in the differential diagnosis of hospitalized patients with respiratory symptoms, especially in those with predisposing risk factors. Chest image studies and further surgical biopsy are needed for confirmation.

Cryptococcosis is the leading cause of death among people with HIV in Sub-Saharan Africa. The lack of optimum diagnoses and medications significantly impair the management of the disease. We investigated the burden of cryptococcosis and related mortality among people with HIV and suspected sepsis in Ethiopia. We conducted a prospective study at (1) Adama Hospital Medical College and (2) Asella Referral and Teaching Hospital from September 2019 to November 2020. We enrolled adult, HIV-infected patients presenting with suspected sepsis and assessed their 28-day survival rates. We performed blood cultures and cryptococcal antigen (CrAg) testing. In total, 82 participants were enrolled with a median age of 35 years, and 61% were female. Overall, eleven (13%) had positive CrAg tests, of which five grew Cryptococcus in blood cultures. Despite high-dose fluconazole (1200 mg/d) monotherapy being given to those with positive CrAg tests, the 28-day mortality was 64% (7/11), with mortality being significantly higher than among the CrAg-negative patients (9% (6/71); p < 0.001). Cryptococcosis was the leading cause of mortality among HIV-infected sepsis patients in this Ethiopian cohort. The CrAg screening of HIV-infected patients attending an emergency department can minimize the number of missed cryptococcosis cases irrespective of the CD4 T cell count and viral load. These findings warrant the need for a bundle approach for the diagnosis of HIV-infected persons presenting with sepsis in low- and middle-income countries.

We polled infectious disease specialists about cryptococcal antigen screening for patients initiating HIV antiretroviral therapy. Of 215 respondents, 33% reported typically obtaining screening for patients with CD4 counts <200 cells/mm and 63% for counts <100 CD4 cells/mm . Uncertainty about cryptococcal antigen screening benefits and recommendations suggests opportunities for education and increased screening.

Cryptococcus spp., in particular Cryptococcus neoformans and Cryptococcus gattii, have an enormous impact on human health worldwide. The global burden of cryptococcal meningitis is almost a quarter of a million cases and 181,000 deaths annually, with mortality rates of 100% if infections remain untreated. Despite these alarming statistics, treatment options for cryptococcosis remain limited, with only three major classes of drugs approved for clinical use. Exacerbating the public health burden is the fact that the only new class of antifungal drugs developed in decades, the echinocandins, displays negligible antifungal activity against Cryptococcus spp., and the efficacy of the remaining therapeutics is hampered by host toxicity and pathogen resistance. Here, we describe the current arsenal of antifungal agents and the treatment strategies employed to manage cryptococcal disease. We further elaborate on the recent advances in our understanding of the intrinsic and adaptive resistance mechanisms that are utilized by Cryptococcus spp. to evade therapeutic treatments. Finally, we review potential therapeutic strategies, including combination therapy, the targeting of virulence traits, impairing stress response pathways and modulating host immunity, to effectively treat infections caused by Cryptococcus spp. Overall, understanding of the mechanisms that regulate anti-cryptococcal drug resistance, coupled with advances in genomics technologies and high-throughput screening methodologies, will catalyse innovation and accelerate antifungal drug discovery.Cryptococcosis is a serious fungal infection for which treatment options are limited. In this Review, Cowen and colleagues discuss the current antifungal treatments available for cryptococcal infections, the challenges in developing new treatments, and ongoing efforts to identify novel therapies.