SLCO1B1 and NAT2 polymorphisms have been associated with the variability of Rifampicin and Isoniazid pharmacokinetic (PK). The objective of this study was to identify in African patients with tuberculosis (TB) or TB/H...SLCO1B1 and NAT2 polymorphisms have been associated with the variability of Rifampicin and Isoniazid pharmacokinetic (PK). The objective of this study was to identify in African patients with tuberculosis (TB) or TB/HIV co-infection, the SLCO1B1 and NAT2 polymorphisms, associated with the variability of Rifampicin and Isoniazid pharmacokinetic. TB or TB/HIV co-infected patients from Benin, Guinea, Senegal, and South Africa were included in this study. The blood samples collected were stored at -80˚C until DNA extractions. The DNA extracts were then frozen at -80˚C after quality control. Double stranded DNA of the samples were quantified using a fluorimetric method to select suitable samples for the preparation of 96-well microplates, containing 100 μl of DNA extract per well at the concentration of 20 ng/μl. Illumina HumanOmniExpress-24 v1.2 microarray genotyping was performed by an external vendor. The genotyping data were analyzed and the polymorphisms with a call rate < 95% or presenting a departure from the Hardy-Weinberg Equilibrium (HWE) were excluded. The correlation between significant genetic polymorphisms, the clearance, and the AUC were tested by a multiple linear regression model using the PLINK2 software. Out of 385 samples, five (05) were excluded after quality controls. After the frequency test, 384,586 SNPs failed the Hardy-Weinberg Equilibrium. Finally, 378 samples and 318,751 SNPs were included in the genetic analyses. The SLCO1B1 and NAT2 polymorphisms were associated with the variability of Rifampicin and Isoniazid PK parameters. There are SLCO1B1 and NAT2 polymorphisms carriers among TB and TB/HIV co-infected patients from Sub-Saharan Africa.展开更多
Background Cutaneous leishmaniasis(CL)is a wide-reaching infection of major public health concern.Iran is one of the six most endemic countries in the world.This study aims to provide a spatiotemporal visualization of...Background Cutaneous leishmaniasis(CL)is a wide-reaching infection of major public health concern.Iran is one of the six most endemic countries in the world.This study aims to provide a spatiotemporal visualization of CL cases in Iran at the county level from 2011 to 2020,detecting high-risk zones,while also noting the movement of high-risk clusters.Methods On the basis of clinical observations and parasitological tests,data of 154,378 diagnosed patients were obtained from the Iran Ministry of Health and Medical Education.Utilizing spatial scan statistics,we investigated the disease’s purely temporal,purely spatial,spatial variation in temporal trends and spatiotemporal patterns.At P=0.05 level,the null hypothesis was rejected in every instance.Results In general,the number of new CL cases decreased over the course of the 9-year research period.From 2011 to 2020,a regular seasonal pattern,with peaks in the fall and troughs in the spring,was found.The period of September–February of 2014–2015 was found to hold the highest risk in terms of CL incidence rate in the whole country[relative risk(RR)=2.24,P<0.001)].In terms of location,six signifcant high-risk CL clusters covering 40.6%of the total area of the country were observed,with the RR ranging from 1.87 to 9.69.In addition,spatial variation in the temporal trend analysis found 11 clusters as potential high-risk areas that highlighted certain regions with an increasing tendency.Finally,fve space-time clusters were found.The geographical displacement and spread of the disease followed a moving pattern over the 9-year study period afecting many regions of the country.Conclusions Our study has revealed signifcant regional,temporal,and spatiotemporal patterns of CL distribution in Iran.Over the years,there have been multiple shifts in spatiotemporal clusters,encompassing many diferent parts of the country from 2011 to 2020.The results reveal the formation of clusters across counties that cover certain parts of provinces,indicating the importance of conducting spatiotemporal analyses at the county level for studies that encompass entire countries.Such analyses,at a fner geographical scale,such as county level,might provide more precise results than analyses at the scale of the province.展开更多
文摘SLCO1B1 and NAT2 polymorphisms have been associated with the variability of Rifampicin and Isoniazid pharmacokinetic (PK). The objective of this study was to identify in African patients with tuberculosis (TB) or TB/HIV co-infection, the SLCO1B1 and NAT2 polymorphisms, associated with the variability of Rifampicin and Isoniazid pharmacokinetic. TB or TB/HIV co-infected patients from Benin, Guinea, Senegal, and South Africa were included in this study. The blood samples collected were stored at -80˚C until DNA extractions. The DNA extracts were then frozen at -80˚C after quality control. Double stranded DNA of the samples were quantified using a fluorimetric method to select suitable samples for the preparation of 96-well microplates, containing 100 μl of DNA extract per well at the concentration of 20 ng/μl. Illumina HumanOmniExpress-24 v1.2 microarray genotyping was performed by an external vendor. The genotyping data were analyzed and the polymorphisms with a call rate < 95% or presenting a departure from the Hardy-Weinberg Equilibrium (HWE) were excluded. The correlation between significant genetic polymorphisms, the clearance, and the AUC were tested by a multiple linear regression model using the PLINK2 software. Out of 385 samples, five (05) were excluded after quality controls. After the frequency test, 384,586 SNPs failed the Hardy-Weinberg Equilibrium. Finally, 378 samples and 318,751 SNPs were included in the genetic analyses. The SLCO1B1 and NAT2 polymorphisms were associated with the variability of Rifampicin and Isoniazid PK parameters. There are SLCO1B1 and NAT2 polymorphisms carriers among TB and TB/HIV co-infected patients from Sub-Saharan Africa.
文摘Background Cutaneous leishmaniasis(CL)is a wide-reaching infection of major public health concern.Iran is one of the six most endemic countries in the world.This study aims to provide a spatiotemporal visualization of CL cases in Iran at the county level from 2011 to 2020,detecting high-risk zones,while also noting the movement of high-risk clusters.Methods On the basis of clinical observations and parasitological tests,data of 154,378 diagnosed patients were obtained from the Iran Ministry of Health and Medical Education.Utilizing spatial scan statistics,we investigated the disease’s purely temporal,purely spatial,spatial variation in temporal trends and spatiotemporal patterns.At P=0.05 level,the null hypothesis was rejected in every instance.Results In general,the number of new CL cases decreased over the course of the 9-year research period.From 2011 to 2020,a regular seasonal pattern,with peaks in the fall and troughs in the spring,was found.The period of September–February of 2014–2015 was found to hold the highest risk in terms of CL incidence rate in the whole country[relative risk(RR)=2.24,P<0.001)].In terms of location,six signifcant high-risk CL clusters covering 40.6%of the total area of the country were observed,with the RR ranging from 1.87 to 9.69.In addition,spatial variation in the temporal trend analysis found 11 clusters as potential high-risk areas that highlighted certain regions with an increasing tendency.Finally,fve space-time clusters were found.The geographical displacement and spread of the disease followed a moving pattern over the 9-year study period afecting many regions of the country.Conclusions Our study has revealed signifcant regional,temporal,and spatiotemporal patterns of CL distribution in Iran.Over the years,there have been multiple shifts in spatiotemporal clusters,encompassing many diferent parts of the country from 2011 to 2020.The results reveal the formation of clusters across counties that cover certain parts of provinces,indicating the importance of conducting spatiotemporal analyses at the county level for studies that encompass entire countries.Such analyses,at a fner geographical scale,such as county level,might provide more precise results than analyses at the scale of the province.
