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- Ikuta, K. S., et al.
(author)
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Global mortality associated with 33 bacterial pathogens in 2019: a systematic analysis for the Global Burden of Disease Study 2019
- 2022
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In: Lancet. - : Elsevier BV. - 0140-6736. ; 400:10369, s. 2221-2248
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Journal article (peer-reviewed)abstract
- Background Reducing the burden of death due to infection is an urgent global public health priority. Previous studies have estimated the number of deaths associated with drug-resistant infections and sepsis and found that infections remain a leading cause of death globally. Understanding the global burden of common bacterial pathogens (both susceptible and resistant to antimicrobials) is essential to identify the greatest threats to public health. To our knowledge, this is the first study to present global comprehensive estimates of deaths associated with 33 bacterial pathogens across 11 major infectious syndromes. Methods We estimated deaths associated with 33 bacterial genera or species across 11 infectious syndromes in 2019 using methods from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, in addition to a subset of the input data described in the Global Burden of Antimicrobial Resistance 2019 study. This study included 343 million individual records or isolates covering 11 361 study-location-years. We used three modelling steps to estimate the number of deaths associated with each pathogen: deaths in which infection had a role, the fraction of deaths due to infection that are attributable to a given infectious syndrome, and the fraction of deaths due to an infectious syndrome that are attributable to a given pathogen. Estimates were produced for all ages and for males and females across 204 countries and territories in 2019. 95% uncertainty intervals (UIs) were calculated for final estimates of deaths and infections associated with the 33 bacterial pathogens following standard GBD methods by taking the 2.5th and 97.5th percentiles across 1000 posterior draws for each quantity of interest. Findings From an estimated 13.7 million (95% UI 10.9-17.1) infection-related deaths in 2019, there were 7.7 million deaths (5.7-10.2) associated with the 33 bacterial pathogens (both resistant and susceptible to antimicrobials) across the 11 infectious syndromes estimated in this study. We estimated deaths associated with the 33 bacterial pathogens to comprise 13.6% (10.2-18.1) of all global deaths and 56.2% (52.1-60.1) of all sepsis-related deaths in 2019. Five leading pathogens-Staphylococcus aureus, Escherichia coli, Streptococcus pneumoniae, Klebsiella pneumoniae, and Pseudomonas aeruginosa-were responsible for 54.9% (52.9-56.9) of deaths among the investigated bacteria. The deadliest infectious syndromes and pathogens varied by location and age. The age-standardised mortality rate associated with these bacterial pathogens was highest in the sub-Saharan Africa super-region, with 230 deaths (185-285) per 100 000 population, and lowest in the high-income super-region, with 52.2 deaths (37.4-71.5) per 100 000 population. S aureus was the leading bacterial cause of death in 135 countries and was also associated with the most deaths in individuals older than 15 years, globally. Among children younger than 5 years, S pneumoniae was the pathogen associated with the most deaths. In 2019, more than 6 million deaths occurred as a result of three bacterial infectious syndromes, with lower respiratory infections and bloodstream infections each causing more than 2 million deaths and peritoneal and intra-abdominal infections causing more than 1 million deaths. Interpretation The 33 bacterial pathogens that we investigated in this study are a substantial source of health loss globally, with considerable variation in their distribution across infectious syndromes and locations. Compared with GBD Level 3 underlying causes of death, deaths associated with these bacteria would rank as the second leading cause of death globally in 2019; hence, they should be considered an urgent priority for intervention within the global health community. Strategies to address the burden of bacterial infections include infection prevention, optimised use of antibiotics, improved capacity for microbiological analysis, vaccine development, and improved and more pervasive use of available vaccines. These estimates can be used to help set priorities for vaccine need, demand, and development. Copyright (c) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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- Okhuijsen-Pfeifer, C, et al.
(author)
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Genome-wide association analyses of symptom severity among clozapine-treated patients with schizophrenia spectrum disorders
- 2022
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In: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 12:1, s. 145-
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Journal article (peer-reviewed)abstract
- Clozapine is the most effective antipsychotic for patients with treatment-resistant schizophrenia. However, response is highly variable and possible genetic underpinnings of this variability remain unknown. Here, we performed polygenic risk score (PRS) analyses to estimate the amount of variance in symptom severity among clozapine-treated patients explained by PRSs (R2) and examined the association between symptom severity and genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activity. Genome-wide association (GWA) analyses were performed to explore loci associated with symptom severity. A multicenter cohort of 804 patients (after quality control N = 684) with schizophrenia spectrum disorder treated with clozapine were cross-sectionally assessed using the Positive and Negative Syndrome Scale and/or the Clinical Global Impression-Severity (CGI-S) scale. GWA and PRS regression analyses were conducted. Genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activities were calculated. Schizophrenia-PRS was most significantly and positively associated with low symptom severity (p = 1.03 × 10−3; R2 = 1.85). Cross-disorder-PRS was also positively associated with lower CGI-S score (p = 0.01; R2 = 0.81). Compared to the lowest tertile, patients in the highest schizophrenia-PRS tertile had 1.94 times (p = 6.84×10−4) increased probability of low symptom severity. Higher genotype-predicted CYP2C19 enzyme activity was independently associated with lower symptom severity (p = 8.44×10−3). While no locus surpassed the genome-wide significance threshold, rs1923778 within NFIB showed a suggestive association (p = 3.78×10−7) with symptom severity. We show that high schizophrenia-PRS and genotype-predicted CYP2C19 enzyme activity are independently associated with lower symptom severity among individuals treated with clozapine. Our findings open avenues for future pharmacogenomic projects investigating the potential of PRS and genotype-predicted CYP-activity in schizophrenia.
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- Nayak, S., et al.
(author)
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Magnetic compensation, field-dependent magnetization reversal, and complex magnetic ordering in Co2TiO4
- 2015
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In: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 92:21
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Journal article (peer-reviewed)abstract
- The complex nature of magnetic ordering in the spinel Co2TiO4 is investigated by analyzing the temperature and magnetic field dependence of its magnetization (M), specific heat (C-p), and ac magnetic susceptibilities chi' and chi ''. X-ray diffraction of the sample synthesized by the solid-state reaction route confirmed the spinel structure whereas x-ray photoelectron spectroscopy shows its electronic structure to be Co2TiO4 = [Co2+][Co3+ Ti3+]O-4. From analysis of the temperature dependence of the dc paramagnetic susceptibility, the magnetic moments mu(A) = 3.87 mu(B) and mu(B) = 5.19 mu B on the A and B sites are determined with mu(B) in turn yielding mu(Ti3+) = 1.73 mu(B) and mu(Co3+) = 4.89 mu(B). Analysis of the dc and ac susceptibilities combined with the weak anomalies observed in the C-p vs T data shows the existence of a quasi-long-range ferrimagnetic state below T-N similar to 47.8K and a compensation temperature T-comp similar to 32 K, the latter characterized by sign reversal of magnetization with its magnitude depending on the applied magnetic field and the cooling protocol. Analysis of the temperature dependence of M (field cooled) and M (zero field cooled) data and the hysteresis loop parameters is interpreted in terms of large spin clusters. These results in Co2TiO4, significantly different from those reported recently in isostructural Co2SnO4 = [Co2+][Co2+ Sn4+]O-4, warrant further investigations of its magnetic structure using neutron diffraction.
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- Thota, S., et al.
(author)
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On the nature of magnetic state in the spinel Co2SnO4
- 2015
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In: Journal of Physics. - : IOP Publishing. - 0953-8984 .- 1361-648X. ; 27:16
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Journal article (peer-reviewed)abstract
- In the spinel Co2SnO4, coexistence of ferrimagnetic ordering below T-N similar or equal to 41K followed by a spin glass state below T-SG similar or equal to 39K was proposed recently based on the temperature dependence of magnetization M(T) data. Here new measurements of the temperature dependence of the specific heat C-P(T), ac-susceptibilities chi'(T) and chi ''(T) measured at frequencies between 0.51 and 1.2 kHz, and the hysteresis loop parameters (coercivity H-C(T) and remanence M-R(T)) in two differently prepared samples of Co2SnO4 are reported. The presence of the Co2+ and Sn4+ states is confirmed by x-ray photoelectron spectroscopy (XPS) yielding the structure: Co2SnO4 = [Co2+][Co2+Sn4+]O-4. The data of C-P versus T shows only an inflection near 39K characteristic of spin-glass ordering. The analysis of the frequency dependence of ac-magnetic susceptibility data near 39K using the Vogel-Fulcher law and the power-law of the critical slowing-down suggests the presence of spin clusters in the system which is close to a spin-glass state. With a decrease in temperature below 39K, the temperature dependence of the coercivity H-C and remanence M-R for the zero-field cooled samples show both H-C and M-R reaching their peak magnitudes near 25 K, then decreasing with decreasing T and becoming negligible below 15K. The plot of C-P/T versus T also yields a weak inflection near 15 K. This temperature dependence of HC and remanence MR is likely associated with the different magnitudes of the magnetic moments of Co2+ ions on the 'A' and 'B' sites and their different temperature dependence.
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