Aspergillus fumigatus-a systematic review to inform the World Health Organization priority list of fungal pathogens.

Recognizing the growing global burden of fungal infections, the World Health Organization established a process to develop a priority list of fungal pathogens (FPPL). In this systematic review, we aimed to evaluate the epidemiology and impact of invasive infections caused by Aspergillus fumigatus to inform the first FPPL. The pre-specified criteria of mortality, inpatient care, complications and sequelae, antifungal susceptibility, risk factors, preventability, annual incidence, global distribution, and emergence were used to search for relevant articles between 1 January 2016 and 10 June 2021. Overall, 49 studies were eligible for inclusion. Azole antifungal susceptibility varied according to geographical regions. Voriconazole susceptibility rates of 22.2% were reported from the Netherlands, whereas in Brazil, Korea, India, China, and the UK, voriconazole susceptibility rates were 76%, 94.7%, 96.9%, 98.6%, and 99.7%, respectively. Cross-resistance was common with 85%, 92.8%, and 100% of voriconazole-resistant A. fumigatus isolates also resistant to itraconazole, posaconazole, and isavuconazole, respectively. The incidence of invasive aspergillosis (IA) in patients with acute leukemia was estimated at 5.84/100 patients. Six-week mortality rates in IA cases ranged from 31% to 36%. Azole resistance and hematological malignancy were poor prognostic factors. Twelve-week mortality rates were significantly higher in voriconazole-resistant than in voriconazole-susceptible IA cases (12/22 [54.5%] vs. 27/88 [30.7%]; P = .035), and hematology patients with IA had significantly higher mortality rates compared with solid-malignancy cases who had IA (65/217 [30%] vs. 14/78 [18%]; P = .04). Carefully designed surveillance studies linking laboratory and clinical data are required to better inform future FPPL.

Pichia kudriavzevii (Candida krusei): A systematic review to inform the World Health Organisation priority list of fungal pathogens.

In response to the growing global threat of fungal infections, in 2020 the World Health Organisation (WHO) established an Expert Group to identify priority fungi and develop the first WHO fungal priority pathogen list (FPPL). The aim of this systematic review was to evaluate the features and global impact of invasive infections caused by Pichia kudriavzevii (formerly known as Candida krusei). PubMed and Web of Science were used to identify studies published between 1 January 2011 and 18 February 2021 reporting on the criteria of mortality, morbidity (defined as hospitalisation and length of stay), drug resistance, preventability, yearly incidence, and distribution/emergence. Overall, 33 studies were evaluated. Mortality rates of up to 67% in adults were reported. Despite the intrinsic resistance of P. kudriavzevii to fluconazole with decreased susceptibility to amphotericin B, resistance (or non-wild-type rate) to other azoles and echinocandins was low, ranging between 0 and 5%. Risk factors for developing P. kudriavzevii infections included low birth weight, prior use of antibiotics/antifungals, and an underlying diagnosis of gastrointestinal disease or cancer. The incidence of infections caused by P. kudriavzevii is generally low (∼5% of all Candida-like blood isolates) and stable over the 10-year timeframe, although additional surveillance data are needed. Strategies targeting the identified risk factors for developing P. kudriavzevii infections should be developed and tested for effectiveness and feasibility of implementation. Studies presenting data on epidemiology and susceptibility of P. kudriavzevii were scarce, especially in low- and middle-income countries (LMICs). Thus, global surveillance systems are required to monitor the incidence, susceptibility, and morbidity of P. kudriavzevii invasive infections to inform diagnosis and treatment. Timely species-level identification and susceptibility testing should be conducted to reduce the high mortality and limit the spread of P. kudriavzevii in healthcare facilities.

Adjusting for comorbidity in incidence-based DALY calculations: an individual-based modeling approach.

BACKGROUND: The co-occurrence of two or more medical conditions in the same individual is not uncommon. If disability-adjusted life year (DALY) calculations are carried out for each condition separately, multimorbidity may lead to an overestimation of the morbidity component, the Years Lived with Disability (YLD). Adjusting for comorbidity may be straightforward if all symptoms have same onset and duration; however, when the comorbid health states occur at different time points, an analytical solution to the comorbidity problem becomes more complex. The aim of this study was to develop an individual-based modelling (IBM) approach to adjust incidence-based disease burden estimation for multimorbidity that allows simulating hypothetical individuals and tracking their disease history, including possible comorbidities, over time. METHODS: We demonstrated the IBM approach using an example of external comorbidity, i.e., colon cancer comorbid with healthcare-associated pneumonia (HAP) and by assuming an independent multiplicative model. First, each cumulative progression probabilities were converted to a daily transition probabilities. Second, disability weights for simultaneously experienced health states and duration in each health state were determined. Third, YLD, adjusted for comorbidity, was calculated at every time step. We simulated a cohort of 1000 colorectal cancer patients aged 65 years. Ninety-five percent uncertainty intervals around median YLD values were estimated by Monte Carlo methods. RESULTS: The median estimated YLD per 1000 cases (due to both cancer and HAP) adjusted for co-morbidity was 545 YLD/1000 (95% interval: 513-585). The impact of not adjusting disability weights for co-existent health states varied from minimal to small; YLD for colorectal cancer would be overestimated only slightly - by 1.6 YLD/1000 - by not adjusting for concurrent HAP. YLD for those HAP patients who have concurrent early-stage colorectal cancer would be overestimated by 2.3 YLD/1000. CONCLUSIONS: The computation of disease burden in the presence of multimorbidity using the incidence-based DALY approach can be handled through IBM. Our approach can be extended to other, more complicated multimorbidity scenarios which are responsible for a high current global disease burden, such as tuberculosis and HIV infection.