ABSTRACT
BACKGROUND: European countries are still searching to eliminate or contain the Covid-19 pandemic. A variety of approaches have achieved different levels of success in limiting the spread of the disease early and preventing avoidable deaths. Governmental policy responses may explain these differences and this study aims to describe evidence about the effectiveness of containment measures throughout the course of the pandemic in five European countries (France, Germany, Italy, Spain and the UK). METHODS: The research approach adopted consisted of three steps: 1) Build a Containment Index (C.I.) that considers nine parameters to make an assessment on the strength of measures; 2) Develop dynamic epidemiological models for forecasting purposes; 3) Predict case numbers by assuming containment measures remain constant for a period of 30 days. RESULTS: Our analysis revealed that in the five European countries we compared, the use of different approaches definitively affected the effectiveness of containment measures for the Covid-19 pandemic. CONCLUSION: The evidence found in our research can be useful to inform policy makers' decisions when deciding to introduce or relax containment measures and their timing, both during the current pandemic or in addressing possible future health crises.
Subject(s)
COVID-19 , COVID-19/epidemiology , COVID-19/prevention & control , Europe/epidemiology , France/epidemiology , Germany , Humans , Pandemics/prevention & controlABSTRACT
Background: Recent reports on the use of hydroxychloroquine (HCQ) alone, or combined with azithromycin (AZM) in the management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have raised cardiac safety concerns. Currently, there is limited mechanistic data evaluating cardiac safety with HCQ and AZM therapy. Methods: Using comprehensive In Vitro ProArrhythmia Assay (CiPA) Schema IC50 paradigms, we examined the cardiac electrophysiological effects of HCQ and HCQ/AZM. Molecular modelling explored HCQ and AZM binding properties to hERG. Langendorff-perfused guinea-pig hearts were electrically and optically mapped by multi-electrode array and voltage (RH237) and Ca2+ (Rhod-2 AM) dyes. Human action potential and ion current reconstructions were performed in silico. Results: HCQ blocked IKr and IK1 with IC50 concentrations (10+-0.6 and 34+-5.0 microM) within the therapeutic range observed clinically. HCQ also blocked INa and ICaL but at higher IC50, whilst Ito and IKs were unaffected. Contrastingly, AZM produced minor inhibition of INa, ICaL, IKs, and IKr,, with no effect on IK1 and Ito. HCQ + AZM combined inhibited IKr and IK1 with IC50s of 7.7 +- 0.8 microM and 30.4 +- 3.0 microM, but spared INa, ICaL and Ito,. Molecular modelling confirmed potential HCQ binding to hERG. Cardiac mapping and ECG studies in isolated hearts demonstrated that HCQ slowed heart rate and ventricular conduction with associated prolongation of PR, QRS and QT intervals. Optical mapping demonstrated, and prolonged, more heterogeneous, action potential durations and intracellular Ca2+ transients. These effects were accentuated with combined HCQ+AZM treatment, which elicited electrical alternans, re-entrant circuits and wave breaks. Reconstruction in a human in-silico model demonstrated that this is attributable to the integrated action of HCQ and AZM reducing IKr, IKs and IK1. Conclusions: These data provide an electrophysiological basis for recent FDA guidelines cautioning against combined HCQ/AZM administration for the treatment of Covid-19 on the grounds of potential cardiac safety. We would strongly recommend monitoring of electrocardiographic QT interval with the use of this combination of medications.Competing Interest StatementThe authors have declared no competing interest.
ABSTRACT
Objective To understand the homology of sequence type 562 (ST562) strains of Burkholderia pseudomallei which circulated in two separate continents (Asia and Australia) at different times.Methods Spe Ⅰ restriction fragments and 4-locus multiple locus variable number tandem repeat analysis (MLVA-4) profiles were extracted from MSHR5858 (ST562 Australia strain) and 350105 (ST562 historical strain of Hainan) genomes respectively by in silico analysis and then compared with the PFGE and MLVA-4 results of five ST562 clinical isolates from Hainan to test their homology.Synteny and homology between MSHR5858 and 350105 genomes were evaluated with bioinformatics methods.Results Five ST562 clinical strains from Hainan shared same PFGE pattern (similarity ＞97％) and this pattern coincided to the map of Spe Ⅰ restriction fragments of Australian strain MSHR5858.The amounts of genomic restriction fragments (Spe Ⅰ) for MSHR5858 and 350105 were 31 and 34 respectively,with 31 of them matched by each other.Five ST562 clinical strains of Hainan were distinct by MLVA-4 profiles,among which HPPH43 (MLVA-4 profile:10,8,10,8) was close to Australia strain MSHR5858 (10,8,8,6),containing identical repeat numbers at VNTR loci 2341k and 1788k;while HK003 (11,8,15,7) and HK061 (11,8,17,7) similar to Hainan historical strain 350105 (11,8,11,8),with same repeat numbers at loci 2341k and 1788k also.High-degree synteny and consistency on genomic contents were observed between 350105 and MSHR5858,indicating a similar origin for the 2 strains.Conclusion All inter-continental and historical ST562 strains ofB.pseudomallei had similar genomic characteristics,supporting the assumption that they had a common origin.Also,it is possible that Hainan historical strain 350105 is the ancestor of all circulating ST562 strains.
ABSTRACT
Objective To analyze the spatial and temporal clustering characteristics of typhoid and paratyphoid fever and its change pattern in Yunnan, Guizhou and Guangxi provinces in southwestern China in recent years. Methods The incidence data of typhoid and paratyphoid fever cases at county level in 3 provinces during 2001-2012 were collected from China Information System for Diseases Control and Prevention and analyzed by the methods of descriptive epidemiology and geographic informatics. And the map showing the spatial and temporal clustering characters of typhoid and paratyphoid fever cases in three provinces was drawn. SaTScan statistics was used to identify the typhoid and paratyphoid fever clustering areas of three provinces in each year from 2001 to 2012. Results During the study period, the reported cases of typhoid and paratyphoid fever declined with year. The reported incidence decreased from 30.15 per 100000 in 2001 to 10.83 per 100000 in 2006 (annual incidence 21.12 per 100000);while during 2007-2012, the incidence became stable, ranging from 4.75 per 100000 to 6.83 per 100000 (annual incidence 5.73 per 100000). The seasonal variation of the incidence was consistent in three provinces, with majority of cases occurred in summer and autumn. The spatial and temporal clustering of typhoid and paratyphoid fever was demonstrated by the incidence map. Most high-incidence counties were located in a zonal area extending from Yuxi ofYunnan to Guiyang of Guizhou, but were concentrated in Guilin in Guangxi. Temporal and spatial scan statistics identified the positional shifting of class Ⅰ clustering area from Guizhou to Yunnan. Class Ⅰ clustering area was located around the central and western areas (Zunyi and Anshun) of Guizhou during 2001-2003, and moved to the central area of Yunnan during 2004-2012. Conclusion Spatial and temporal clustering of typhoid and paratyphoid fever existed in the endemic areas of southwestern China, and the clustering area covered a zone connecting the central areas of Guizhou and Yunnan. From 2004 to 2012, the most important clustering area shifted from Guizhou to Yunnan. Findings from this study provided evidence for the identifying key areas for typhoid and paratyphoid fever control and prevention and allocate health resources.
ABSTRACT
Objective To understand the homology of sequence type 562 (ST562) strains of Burkholderia pseudomallei which circulated in two separate continents (Asia and Australia) at different times.Methods Spe Ⅰ restriction fragments and 4-locus multiple locus variable number tandem repeat analysis (MLVA-4) profiles were extracted from MSHR5858 (ST562 Australia strain) and 350105 (ST562 historical strain of Hainan) genomes respectively by in silico analysis and then compared with the PFGE and MLVA-4 results of five ST562 clinical isolates from Hainan to test their homology.Synteny and homology between MSHR5858 and 350105 genomes were evaluated with bioinformatics methods.Results Five ST562 clinical strains from Hainan shared same PFGE pattern (similarity ＞97％) and this pattern coincided to the map of Spe Ⅰ restriction fragments of Australian strain MSHR5858.The amounts of genomic restriction fragments (Spe Ⅰ) for MSHR5858 and 350105 were 31 and 34 respectively,with 31 of them matched by each other.Five ST562 clinical strains of Hainan were distinct by MLVA-4 profiles,among which HPPH43 (MLVA-4 profile:10,8,10,8) was close to Australia strain MSHR5858 (10,8,8,6),containing identical repeat numbers at VNTR loci 2341k and 1788k;while HK003 (11,8,15,7) and HK061 (11,8,17,7) similar to Hainan historical strain 350105 (11,8,11,8),with same repeat numbers at loci 2341k and 1788k also.High-degree synteny and consistency on genomic contents were observed between 350105 and MSHR5858,indicating a similar origin for the 2 strains.Conclusion All inter-continental and historical ST562 strains ofB.pseudomallei had similar genomic characteristics,supporting the assumption that they had a common origin.Also,it is possible that Hainan historical strain 350105 is the ancestor of all circulating ST562 strains.
ABSTRACT
Objective To analyze the spatial and temporal clustering characteristics of typhoid and paratyphoid fever and its change pattern in Yunnan, Guizhou and Guangxi provinces in southwestern China in recent years. Methods The incidence data of typhoid and paratyphoid fever cases at county level in 3 provinces during 2001-2012 were collected from China Information System for Diseases Control and Prevention and analyzed by the methods of descriptive epidemiology and geographic informatics. And the map showing the spatial and temporal clustering characters of typhoid and paratyphoid fever cases in three provinces was drawn. SaTScan statistics was used to identify the typhoid and paratyphoid fever clustering areas of three provinces in each year from 2001 to 2012. Results During the study period, the reported cases of typhoid and paratyphoid fever declined with year. The reported incidence decreased from 30.15 per 100000 in 2001 to 10.83 per 100000 in 2006 (annual incidence 21.12 per 100000);while during 2007-2012, the incidence became stable, ranging from 4.75 per 100000 to 6.83 per 100000 (annual incidence 5.73 per 100000). The seasonal variation of the incidence was consistent in three provinces, with majority of cases occurred in summer and autumn. The spatial and temporal clustering of typhoid and paratyphoid fever was demonstrated by the incidence map. Most high-incidence counties were located in a zonal area extending from Yuxi ofYunnan to Guiyang of Guizhou, but were concentrated in Guilin in Guangxi. Temporal and spatial scan statistics identified the positional shifting of class Ⅰ clustering area from Guizhou to Yunnan. Class Ⅰ clustering area was located around the central and western areas (Zunyi and Anshun) of Guizhou during 2001-2003, and moved to the central area of Yunnan during 2004-2012. Conclusion Spatial and temporal clustering of typhoid and paratyphoid fever existed in the endemic areas of southwestern China, and the clustering area covered a zone connecting the central areas of Guizhou and Yunnan. From 2004 to 2012, the most important clustering area shifted from Guizhou to Yunnan. Findings from this study provided evidence for the identifying key areas for typhoid and paratyphoid fever control and prevention and allocate health resources.