Cryptococcus neoformans, a global threat to human health.

BACKGROUND: Emerging fungal pathogens pose important threats to global public health. The World Health Organization has responded to the rising threat of traditionally neglected fungal infections by developing a Fungal Priority Pathogens List (FPPL). Taking the highest-ranked fungal pathogen in the FPPL, Cryptococcus neoformans, as a paradigm, we review progress made over the past two decades on its global burden, its clinical manifestation and management of cryptococcal infection, and its antifungal resistance. The purpose of this review is to drive research efforts to improve future diagnoses, therapies, and interventions associated with fungal infections. METHODS: We first reviewed trends in the global burden of HIV-associated cryptococcal infection, mainly based on a series of systematic studies. We next conducted scoping reviews in accordance with the guidelines described in the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews using PubMed and ScienceDirect with the keyword Cryptococcus neoformans to identify case reports of cryptococcal infections published since 2000. We then reviewed recent updates on the diagnosis and antifungal treatment of cryptococcal infections. Finally, we summarized knowledge regarding the resistance and tolerance of C. neoformans to approved antifungal drugs. RESULTS: There has been a general reduction in the estimated global burden of HIV-associated cryptococcal meningitis since 2009, probably due to improvements in highly active antiretroviral therapies. However, cryptococcal meningitis still accounts for 19% of AIDS-related deaths annually. The incidences of CM in Europe and North America and the Latin America region have increased by approximately two-fold since 2009, while other regions showed either reduced or stable numbers of cases. Unfortunately, diagnostic and treatment options for cryptococcal infections are limited, and emerging antifungal resistance exacerbates the public health burden. CONCLUSION: The rising threat of C. neoformans is compounded by accumulating evidence for its ability to infect immunocompetent individuals and the emergence of antifungal-resistant variants. Emphasis should be placed on further understanding the mechanisms of pathogenicity and of antifungal resistance and tolerance. The development of novel management strategies through the identification of new drug targets and the discovery and optimization of new and existing diagnostics and therapeutics are key to reducing the health burden.

Routine HIV testing in acute care hospitals: Changing practice to curb a local HIV epidemic in Vancouver, BC.

Early treatment of HIV infection increases life expectancy and reduces infectivity; however, delayed HIV diagnosis remains common. Implementation and sustainability of hospital-based routine HIV testing in Vancouver, British Columbia, was evaluated to address a local HIV epidemic by facilitating earlier diagnosis and treatment. Public health issued a recommendation in 2011 to offer HIV testing to all patients presenting to three Vancouver hospitals as part of routine care, including all patients admitted to medical/surgical units with expansion to emergency departments (ED). We evaluated acceptability, feasibility, and effectiveness from 2011 to 2014 and continued monitoring through 2016 for sustainability. Between October 2011-December 2016, 114,803 HIV tests were administered at the three hospitals; an 11-fold increase following implementation of routine testing. The rate of testing was sustained and remained high through 2018. Of those tested, 151 patients were diagnosed with HIV for a testing yield of 0.13%. Review of 12,996 charts demonstrated 4935/5876 (96·9%) of admitted patients agreed to have an HIV test when offered. People diagnosed in hospital were significantly more likely to be diagnosed with acute stage (aOR 1·96, 95% CI 1·19, 3·23) infection, particularly those diagnosed in the ED. This study provides practice-based evidence of the feasibility, acceptability, and effectiveness of implementing a recommendation for routine HIV testing among inpatient and emergency department admissions, as well as the ability to normalize and sustain this change. Routine hospital-based HIV testing can increase diagnoses of acute HIV infection and facilitate earlier initiation of antiretroviral treatment.

Changing risk and presentation of overdose associated with consumption of street drugs at a supervised injection site in Vancouver, Canada.

BACKGROUND: British Columbia is experiencing a public health emergency due to overdoses resulting from consumption of street drugs contaminated with fentanyl. While the risk of overdoses appears to be increasing, the overdose rate and severity of overdose presentations have yet to be quantified. METHODS: Insite is a supervised injection site in Vancouver. Data from Insite's client database from January 2010 to June 2017 were used to calculate overdose rates as well as the proportion of overdoses involving rigidity and naloxone administration over time in order to estimate changes in the risk and severity of overdose resulting from changes in the local drug supply. RESULTS: The overdose rate increased significantly for all drug categories. Heroin used alone or with other drugs continues to be associated with the highest overdose rate. The overdose rate associated with heroin increased from 2.7/1000 visits to 13/1000 visits over the study period, meaning that clients were 4.8 times more likely to overdose in the most recent period as in the baseline period. The proportion of overdose events involving rigidity, a known complication of intravenous fentanyl use, increased significantly from 10.4% to 18.9%. The proportion of overdoses requiring naloxone administration increased significantly from 48.4% to 57.1% and is now similar across all drug categories. CONCLUSIONS: The risk and severity of overdoses at Insite have increased since the emergence of illicit fentanyl. This information derived from supervised injection site data can be used to inform local harm reduction efforts and the response to the overdose emergency.

[Study on the changes of demography and behavioral characteristics of drug users in Beijing].

OBJECTIVE: To understand the demography changes and behaviors in drug users. METHOD: Self-reported questionnaires was used and longitudinal investigation was conducted in one of the detoxication centers in Beijing in 1998 and 2000. Drug users were randomly chosen. RESULTS: Results showed that age of drug users tend to become younger with the numbers of drug users aged below 25, increased from 18.7% in 1998 to 28.2% in 2000. Majority of drug users remained males, but the proportion of females seemed to increase. Distribution of occupation showed that the largest increase fell among individual enterprisers, from 15.2% in 1998 to 25.9% in 2000. With educational back-ground, the proportion of lower than elementary education level, including illiterate, increased. Fifty percent of drug users were unmarried which increased from 40.8% in 1998 to 53.2% in 2000. Needle sharing was quite common, 16.5% in 1998 and 11.9% in 2000, but the decrease was not statistically significant (P > 0.05). Fifty-seven point three percent of the injecting drug users did not have constant partners to share equipments. Proportion of extra-marriage sexual practice increased from 12.5% in 1998 to 27.5% in 2000, and significant difference (Chi-square = 12.50, P < 0.001). Multiple partners in extra-married drug users was also found (mean = 2). Compared to 1998, condom use during every sexual practice increased in 2000, but 47.7% drug users still never used condom. CONCLUSION: In summary, as the quick increase of drug users, sharing of injecting equipment and high-risk sexual behavior, including multiple partners and unprotected sex, were quite common, with the possibility of HIV epidemic in drug users.