Zinhle Cindi, A. Kawuma, G. Maartens, Y. Bradford, F. Venter, Simiso M Sokhela, N. Chandiwana, R. Wasmann, P. Denti, L. Wiesner, M. Ritchie, D. Haas, P. Sinxadi
Background Dolutegravir is a component of preferred antiretroviral therapy (ART) regimens. We characterised the pharmacogenetics of dolutegravir exposure following ART initiation in the ADVANCE trial in South Africa. Methods Genome-wide genotyping followed by imputation was performed. We developed a population pharmacokinetic model for dolutegravir using non-linear mixed-effects modelling. Linear regression models examined associations with unexplained variability in dolutegravir area under the concentration-time curve (AUCVAR). Results Genetic associations were evaluable in 284 individuals. Of nine polymorphisms previously associated with dolutegravir pharmacokinetics, the lowest P-value with AUCVAR was UGT1A1 rs887829 (P = 1.8 x 10-4), which was also associated with log10 bilirubin (P = 8.6 x 10-13). After adjusting for rs887829, AUCvar was independently associated with rs28899168 in the UGT1A locus (P = 0.02), as were bilirubin concentrations (P = 7.7 x 10-8). In the population pharmacokinetic model, rs887829 T/T and C/T were associated with 25.9% and 10.8% decreases in dolutegravir clearance, respectively, compared to C/C. The lowest P-value for AUCVAR genome-wide was CAMKMT rs343942 (P = 2.4 x 10-7). Conclusions In South Africa, rs887829 and rs28899168 in the UGT1A locus were independently associated with dolutegravir AUCVAR. The novel rs28899168 association warrants replication. This study enhances understanding of dolutegravir pharmacogenetics in Africa.
背景:多替韦是首选抗逆转录病毒治疗(ART)方案的一个组成部分。我们在南非的ADVANCE试验中描述了抗逆转录病毒治疗开始后多替格拉韦暴露的药理学特征。方法采用全基因组分型法进行基因代入。我们利用非线性混合效应模型建立了多维韦的群体药代动力学模型。线性回归模型检验了浓度-时间曲线(AUCVAR)下偏重区与未解释变异性的关系。结果284例个体可评价遗传关联。在先前与多替替韦药代动力学相关的9个多态性中，与AUCVAR相关的最低P值是UGT1A1 rs887829 (P = 1.8 x 10-4)，与log10胆红素相关(P = 8.6 x 10-13)。校正rs887829后，UGT1A位点的AUCvar与rs28899168独立相关(P = 0.02)，胆红素浓度也是如此(P = 7.7 x 10-8)。在群体药代动力学模型中，与C/C相比，rs887829 T/T和C/T分别与仑地韦清除率降低25.9%和10.8%相关。AUCVAR全基因组P值最低的是CAMKMT rs343942 (P = 2.4 × 10-7)。结论在南非，UGT1A位点的rs887829和rs28899168与偏重型AUCVAR独立相关。新的rs28899168关联值得复制。本研究增进了对非洲地替韦药物遗传学的了解。
{"title":"Pharmacogenetics of dolutegravir plasma exposure among Southern Africans living with HIV","authors":"Zinhle Cindi, A. Kawuma, G. Maartens, Y. Bradford, F. Venter, Simiso M Sokhela, N. Chandiwana, R. Wasmann, P. Denti, L. Wiesner, M. Ritchie, D. Haas, P. Sinxadi","doi":"10.1093/infdis/jiac174","DOIUrl":"https://doi.org/10.1093/infdis/jiac174","url":null,"abstract":"Background Dolutegravir is a component of preferred antiretroviral therapy (ART) regimens. We characterised the pharmacogenetics of dolutegravir exposure following ART initiation in the ADVANCE trial in South Africa. Methods Genome-wide genotyping followed by imputation was performed. We developed a population pharmacokinetic model for dolutegravir using non-linear mixed-effects modelling. Linear regression models examined associations with unexplained variability in dolutegravir area under the concentration-time curve (AUCVAR). Results Genetic associations were evaluable in 284 individuals. Of nine polymorphisms previously associated with dolutegravir pharmacokinetics, the lowest P-value with AUCVAR was UGT1A1 rs887829 (P = 1.8 x 10-4), which was also associated with log10 bilirubin (P = 8.6 x 10-13). After adjusting for rs887829, AUCvar was independently associated with rs28899168 in the UGT1A locus (P = 0.02), as were bilirubin concentrations (P = 7.7 x 10-8). In the population pharmacokinetic model, rs887829 T/T and C/T were associated with 25.9% and 10.8% decreases in dolutegravir clearance, respectively, compared to C/C. The lowest P-value for AUCVAR genome-wide was CAMKMT rs343942 (P = 2.4 x 10-7). Conclusions In South Africa, rs887829 and rs28899168 in the UGT1A locus were independently associated with dolutegravir AUCVAR. The novel rs28899168 association warrants replication. This study enhances understanding of dolutegravir pharmacogenetics in Africa.","PeriodicalId":22572,"journal":{"name":"The Indonesian Journal of Infectious Diseases","volume":"75 1","pages":"1616 - 1625"},"PeriodicalIF":0.0,"publicationDate":"2022-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88574670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anna Gibbs, K. Healy, Vilde Kaldhusdal, C. Sundling, Mathias Franzén-Boger, Gabriella Edfeldt, M. Buggert, J. Lajoie, K. Fowke, J. Kimani, D. Kwon, S. Andersson, J. Sandberg, K. Broliden, Haleh Davanian, M. Chen, Annelie Tjernlund
Abstract Background Mucosa-associated invariant T (MAIT) cells are innate-like T cells with specialized antimicrobial functions. Circulating MAIT cells are depleted in chronic human immunodeficiency virus (HIV) infection, but studies examining this effect in peripheral tissues, such as the female genital tract, are lacking. Methods Flow cytometry was used to investigate circulating MAIT cells in a cohort of HIV-seropositive (HIV+) and HIV-seronegative (HIV−) female sex workers (FSWs), and HIV− lower-risk women (LRW). In situ staining and quantitative polymerase chain reaction were performed to explore the phenotype of MAIT cells residing in paired cervicovaginal tissue. The cervicovaginal microbiome was assessed by means of 16S ribosomal RNA gene sequencing. Results MAIT cells in the HIV+ FSW group were low in frequency in the circulation but preserved in the ectocervix. MAIT cell T-cell receptor gene segment usage differed between the HIV+ and HIV− FSW groups. The TRAV1-2–TRAJ20 transcript was the most highly expressed MAIT TRAJ gene detected in the ectocervix in the HIV+ FSW group. MAIT TRAVJ usage was not associated with specific genera in the vaginal microbiome. Conclusions MAIT cells residing in the ectocervix are numerically preserved irrespective of HIV infection status and displayed dominant expression of TRAV1-2–TRAJ20. These findings have implications for understanding the role of cervical MAIT cells in health and disease.
{"title":"Preserved Mucosal-Associated Invariant T Cells in the Cervical Mucosa of HIV-Infected Women with Dominant Expression of the TRAV1-2–TRAJ20 T Cell Receptor α-Chain","authors":"Anna Gibbs, K. Healy, Vilde Kaldhusdal, C. Sundling, Mathias Franzén-Boger, Gabriella Edfeldt, M. Buggert, J. Lajoie, K. Fowke, J. Kimani, D. Kwon, S. Andersson, J. Sandberg, K. Broliden, Haleh Davanian, M. Chen, Annelie Tjernlund","doi":"10.1093/infdis/jiac171","DOIUrl":"https://doi.org/10.1093/infdis/jiac171","url":null,"abstract":"Abstract Background Mucosa-associated invariant T (MAIT) cells are innate-like T cells with specialized antimicrobial functions. Circulating MAIT cells are depleted in chronic human immunodeficiency virus (HIV) infection, but studies examining this effect in peripheral tissues, such as the female genital tract, are lacking. Methods Flow cytometry was used to investigate circulating MAIT cells in a cohort of HIV-seropositive (HIV+) and HIV-seronegative (HIV−) female sex workers (FSWs), and HIV− lower-risk women (LRW). In situ staining and quantitative polymerase chain reaction were performed to explore the phenotype of MAIT cells residing in paired cervicovaginal tissue. The cervicovaginal microbiome was assessed by means of 16S ribosomal RNA gene sequencing. Results MAIT cells in the HIV+ FSW group were low in frequency in the circulation but preserved in the ectocervix. MAIT cell T-cell receptor gene segment usage differed between the HIV+ and HIV− FSW groups. The TRAV1-2–TRAJ20 transcript was the most highly expressed MAIT TRAJ gene detected in the ectocervix in the HIV+ FSW group. MAIT TRAVJ usage was not associated with specific genera in the vaginal microbiome. Conclusions MAIT cells residing in the ectocervix are numerically preserved irrespective of HIV infection status and displayed dominant expression of TRAV1-2–TRAJ20. These findings have implications for understanding the role of cervical MAIT cells in health and disease.","PeriodicalId":22572,"journal":{"name":"The Indonesian Journal of Infectious Diseases","volume":"777 1","pages":"1428 - 1440"},"PeriodicalIF":0.0,"publicationDate":"2022-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76120096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nicole D Derksen-Lazet, Corline E J Parmentier, J. Wildenbeest, L. Bont
Respiratory syncytial virus (RSV) causes a substantial disease burden among children, elderly and immunocompromised adults. Recognition of patient involvement in research is gradually increasing. Most research is being carried out without active patient involvement other than patients participating as study subjects, and most knowledge gained through research only partially reaches the general public. Since 2016, the RSV Patient Advisory Board has officially been involved as an advisory group in the Respiratory Syncytial Virus Consortium in Europe (RESCEU). What started as a small single-center initiative, is now growing towards an international organization providing patient perspectives as inputs to scientists, and improving awareness of RSV. This article summarizes the history, current role, and future aims of the RSV Patient Advisory Board as an advocate to improve patient involvement in research. RSV patients and their representatives are important stakeholders in setting the global research agenda, and educating patients, professionals, and the general public.
{"title":"Patient Involvement in RSV Research: Towards Patients Setting the Research Agenda.","authors":"Nicole D Derksen-Lazet, Corline E J Parmentier, J. Wildenbeest, L. Bont","doi":"10.1093/infdis/jiac110","DOIUrl":"https://doi.org/10.1093/infdis/jiac110","url":null,"abstract":"Respiratory syncytial virus (RSV) causes a substantial disease burden among children, elderly and immunocompromised adults. Recognition of patient involvement in research is gradually increasing. Most research is being carried out without active patient involvement other than patients participating as study subjects, and most knowledge gained through research only partially reaches the general public. Since 2016, the RSV Patient Advisory Board has officially been involved as an advisory group in the Respiratory Syncytial Virus Consortium in Europe (RESCEU). What started as a small single-center initiative, is now growing towards an international organization providing patient perspectives as inputs to scientists, and improving awareness of RSV. This article summarizes the history, current role, and future aims of the RSV Patient Advisory Board as an advocate to improve patient involvement in research. RSV patients and their representatives are important stakeholders in setting the global research agenda, and educating patients, professionals, and the general public.","PeriodicalId":22572,"journal":{"name":"The Indonesian Journal of Infectious Diseases","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72755798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K. Bajema, R. Gierke, M. Farley, W. Schaffner, A. Thomas, A. Reingold, L. Harrison, R. Lynfield, Kari E Burzlaff, S. Petit, M. Barnes, Salina M Torres, Paula M. Snippes Vagnone, B. Beall, T. Pilishvili
BACKGROUND Antibiotic-nonsusceptible invasive pneumococcal disease (NS-IPD) incidence declined dramatically in the United States following introduction of pneumococcal conjugate vaccines (PCVs) into the infant immunization schedule (7-valent PCV7 in 2000, replaced by the 13-valent PCV13 in 2010). We evaluated the long-term impact of PCVs on NS-IPD. METHODS We identified IPD cases through the Centers for Disease Control Active Bacterial Core surveillance during 1998-2018. Isolates intermediate or resistant to ≥1 antibiotic class were classified as nonsusceptible. We calculated annual rates of IPD (cases per 100,000 persons). RESULTS From 1998 through 2018, NS-IPD incidence decreased from 43.9 to 3.2 among children <5 years and from 19.8 to 9.4 among adults ≥65 years. Incidence of vaccine-type NS-IPD decreased in all age groups, while incidence of NVT NS-IPD increased in all age groups; the greatest absolute increase in NVT NS-IPD occurred among adults ≥65 years (2.3 to 7.2). During 2014-18, NVTs 35B, 33F, 22F, and 15A were the most common NS-IPD serotypes. CONCLUSIONS NS-IPD incidence decreased following PCV7 and PCV13 introduction in the United States. However, recent increases in NVT NS-IPD, most pronounced among older adults, have been observed. New higher valency PCVs containing the most common nonsusceptible serotypes, including 22F and 33F, could help further reduce NS-IPD.
{"title":"Impact of Pneumococcal Conjugate Vaccines on Antibiotic-Nonsusceptible Invasive Pneumococcal Disease in the United States.","authors":"K. Bajema, R. Gierke, M. Farley, W. Schaffner, A. Thomas, A. Reingold, L. Harrison, R. Lynfield, Kari E Burzlaff, S. Petit, M. Barnes, Salina M Torres, Paula M. Snippes Vagnone, B. Beall, T. Pilishvili","doi":"10.1093/infdis/jiac154","DOIUrl":"https://doi.org/10.1093/infdis/jiac154","url":null,"abstract":"BACKGROUND\u0000Antibiotic-nonsusceptible invasive pneumococcal disease (NS-IPD) incidence declined dramatically in the United States following introduction of pneumococcal conjugate vaccines (PCVs) into the infant immunization schedule (7-valent PCV7 in 2000, replaced by the 13-valent PCV13 in 2010). We evaluated the long-term impact of PCVs on NS-IPD.\u0000\u0000\u0000METHODS\u0000We identified IPD cases through the Centers for Disease Control Active Bacterial Core surveillance during 1998-2018. Isolates intermediate or resistant to ≥1 antibiotic class were classified as nonsusceptible. We calculated annual rates of IPD (cases per 100,000 persons).\u0000\u0000\u0000RESULTS\u0000From 1998 through 2018, NS-IPD incidence decreased from 43.9 to 3.2 among children <5 years and from 19.8 to 9.4 among adults ≥65 years. Incidence of vaccine-type NS-IPD decreased in all age groups, while incidence of NVT NS-IPD increased in all age groups; the greatest absolute increase in NVT NS-IPD occurred among adults ≥65 years (2.3 to 7.2). During 2014-18, NVTs 35B, 33F, 22F, and 15A were the most common NS-IPD serotypes.\u0000\u0000\u0000CONCLUSIONS\u0000NS-IPD incidence decreased following PCV7 and PCV13 introduction in the United States. However, recent increases in NVT NS-IPD, most pronounced among older adults, have been observed. New higher valency PCVs containing the most common nonsusceptible serotypes, including 22F and 33F, could help further reduce NS-IPD.","PeriodicalId":22572,"journal":{"name":"The Indonesian Journal of Infectious Diseases","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74948303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Assawakosri, S. Kanokudom, N. Suntronwong, Jiratchaya Puenpa, T. Duangchinda, W. Chantima, P. Pakchotanon, J. Mongkolsapaya, Nasamon Wanlapakorn, S. Honsawek, Y. Poovorawan
TO THE EDITOR—In reply to the correspondence from Tjan et al [1] regarding the heterologous booster in healthy adults previously immunized with 2 doses of CoronaVac [2], the additional knowledge on immunogenicity of the booster (third dose) with BNT162b2 in BNT162b2primed individuals against the BA.2 omicron variant will help promote the vaccine uptake and coverage in themidst of a surge in BA.2 omicron worldwide. As of February 2022, the omicron variant was further classified into 4 main sublineages, BA.1, BA.1.1, BA.2, and BA.3. Moreover, an epidemiological surveillance on coronavirus disease 2019 (COVID-19) showed that BA.2 sublineages have become the dominant variant globally [3]. In Thailand, the BA.2 sublineages have been detected since the end of January 2022. The proportion of BA.2 sublineages rapidly increased and accounted for more than 90% of positive cases reported in March 2022 [Puenpa J et al. unpublished]. Potent serum neutralizing antibody (nAbs) against BA.1 was observed after the heterologous booster in individuals previously immunized with 2 doses of CoronaVac [2]. Considering the waning immunity after primary series vaccination and the high transmissibility and potential immune escape of BA.2 sublineage, we further determined the immunogenicity of the mRNA-1273 booster against BA.1 and BA.2 in AZD1222-primed individuals using the 50% focus reduction neutralization test (FRNT50) as previously described [2].
致编辑:在Tjan等人[1]的信函中，我们回复了之前接种过2剂CoronaVac的健康成人[2]的异种增强剂，关于BNT162b2增强剂(第三剂)在BNT162b2引发的个体中对BA.2组克隆变体的免疫原性的额外知识，将有助于在全球BA.2组克隆激增期间促进疫苗的吸收和覆盖。截至2022年2月，该组粒变体进一步分为4个主要亚系，BA.1、BA.1.1、BA.2和BA.3。此外，对2019冠状病毒病(COVID-19)的流行病学监测显示，BA.2亚系已成为全球优势变异体[3]。在泰国，自2022年1月底以来一直检测到BA.2亚型。BA.2亚型的比例迅速增加，占2022年3月报告的阳性病例的90%以上[Puenpa J et al.未发表]。在先前接种过2剂CoronaVac的个体中，在异种增强剂后观察到针对BA.1的有效血清中和抗体(nab)[2]。考虑到一次系列疫苗接种后的免疫力下降，以及BA.2亚系的高传播性和潜在的免疫逃逸，我们采用先前描述的50%减焦中和试验(FRNT50)进一步确定了mRNA-1273增强剂对azd1222引物个体BA.1和BA.2的免疫原性[2]。
{"title":"Omicron BA.1, BA.2 and COVID-19 Booster Vaccination","authors":"S. Assawakosri, S. Kanokudom, N. Suntronwong, Jiratchaya Puenpa, T. Duangchinda, W. Chantima, P. Pakchotanon, J. Mongkolsapaya, Nasamon Wanlapakorn, S. Honsawek, Y. Poovorawan","doi":"10.1093/infdis/jiac158","DOIUrl":"https://doi.org/10.1093/infdis/jiac158","url":null,"abstract":"TO THE EDITOR—In reply to the correspondence from Tjan et al [1] regarding the heterologous booster in healthy adults previously immunized with 2 doses of CoronaVac [2], the additional knowledge on immunogenicity of the booster (third dose) with BNT162b2 in BNT162b2primed individuals against the BA.2 omicron variant will help promote the vaccine uptake and coverage in themidst of a surge in BA.2 omicron worldwide. As of February 2022, the omicron variant was further classified into 4 main sublineages, BA.1, BA.1.1, BA.2, and BA.3. Moreover, an epidemiological surveillance on coronavirus disease 2019 (COVID-19) showed that BA.2 sublineages have become the dominant variant globally [3]. In Thailand, the BA.2 sublineages have been detected since the end of January 2022. The proportion of BA.2 sublineages rapidly increased and accounted for more than 90% of positive cases reported in March 2022 [Puenpa J et al. unpublished]. Potent serum neutralizing antibody (nAbs) against BA.1 was observed after the heterologous booster in individuals previously immunized with 2 doses of CoronaVac [2]. Considering the waning immunity after primary series vaccination and the high transmissibility and potential immune escape of BA.2 sublineage, we further determined the immunogenicity of the mRNA-1273 booster against BA.1 and BA.2 in AZD1222-primed individuals using the 50% focus reduction neutralization test (FRNT50) as previously described [2].","PeriodicalId":22572,"journal":{"name":"The Indonesian Journal of Infectious Diseases","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87555355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xin Wang, You Li, T. Shi, Yiming Ma, Bhanu Wahi-Singh, R. Riley, H. Nair
Existing guidelines on respiratory syncytial virus (RSV) prophylaxis differ greatly by gestational age (GA) and other underlying risk factors, highlighting the data gaps in RSV disease burden among preterm infants. We will conduct a systematic review and individual participant data (IPD) meta-analysis of RSV global disease burden among preterm-born children. Three databases, Medline, Embase, and Global Health, will be searched for relevant studies on RSV disease burden for 2019 or before in preterm-born children published between 1 January 1995 and 31 December 2021. IPD will be sought by contacting the investigators identified from published literature and from existing collaboration networks. One-stage and 2-stage random-effects meta-analyses will be used to combine information from IPD and non-IPD studies to produce summary RSV burden estimates of incidence rate, hospital admission rate, and in-hospital case fatality ratio. The framework will be extended to examine subgroup(s) with the most substantial RSV disease burden.
{"title":"Global Disease Burden of Respiratory Syncytial Virus in Preterm Children in 2019: A Systematic Review and Individual Participant Data Meta-Analysis Protocol.","authors":"Xin Wang, You Li, T. Shi, Yiming Ma, Bhanu Wahi-Singh, R. Riley, H. Nair","doi":"10.1093/infdis/jiac078","DOIUrl":"https://doi.org/10.1093/infdis/jiac078","url":null,"abstract":"Existing guidelines on respiratory syncytial virus (RSV) prophylaxis differ greatly by gestational age (GA) and other underlying risk factors, highlighting the data gaps in RSV disease burden among preterm infants. We will conduct a systematic review and individual participant data (IPD) meta-analysis of RSV global disease burden among preterm-born children. Three databases, Medline, Embase, and Global Health, will be searched for relevant studies on RSV disease burden for 2019 or before in preterm-born children published between 1 January 1995 and 31 December 2021. IPD will be sought by contacting the investigators identified from published literature and from existing collaboration networks. One-stage and 2-stage random-effects meta-analyses will be used to combine information from IPD and non-IPD studies to produce summary RSV burden estimates of incidence rate, hospital admission rate, and in-hospital case fatality ratio. The framework will be extended to examine subgroup(s) with the most substantial RSV disease burden.","PeriodicalId":22572,"journal":{"name":"The Indonesian Journal of Infectious Diseases","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72788629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yufei Zhang, Jindong Gao, Kun Huang, Ya Zhao, Xianfeng Hui, Ting Wang, Changmin Hu, Xiaomei Sun, Ying Yang, Chao Wu, Xi Chen, Zhong Zou, Lianzhong Zhao, M. Jin
Abstract Isolated reports of new-onset diabetes in patients with COVID-19 have led researchers to hypothesise that SARS-CoV-2 infects the human exocrine and endocrine pancreatic cells ex vivo and in vivo. However, existing research lacks experimental evidence indicating that SARS-CoV-2 can infect pancreatic tissue. Here, we found that cats infected with a high dose of SARS-CoV-2 exhibited hyperglycaemia. We also detected SARS-CoV-2 RNA in the pancreatic tissues of these cats, and immunohistochemical staining revealed the presence of SARS-CoV-2 nucleocapsid protein (NP) in the islet cells. SARS-CoV-2 NP and Spike proteins were primarily detected in Glu+ cells, and most Glu+ cells expressed ACE2. Additionally, immune protection experiments conducted on cats showed that the blood glucose levels of immunised cats did not increase post-challenge. Our data indicate the cat pancreas as a SARS-CoV-2 target and suggest that the infection of Glu+ cells could contribute to the metabolic dysregulation observed in SARS-CoV-2-infected cats.
{"title":"SARS-CoV-2 infection causes hyperglycaemia in cats","authors":"Yufei Zhang, Jindong Gao, Kun Huang, Ya Zhao, Xianfeng Hui, Ting Wang, Changmin Hu, Xiaomei Sun, Ying Yang, Chao Wu, Xi Chen, Zhong Zou, Lianzhong Zhao, M. Jin","doi":"10.1093/infdis/jiac143","DOIUrl":"https://doi.org/10.1093/infdis/jiac143","url":null,"abstract":"Abstract Isolated reports of new-onset diabetes in patients with COVID-19 have led researchers to hypothesise that SARS-CoV-2 infects the human exocrine and endocrine pancreatic cells ex vivo and in vivo. However, existing research lacks experimental evidence indicating that SARS-CoV-2 can infect pancreatic tissue. Here, we found that cats infected with a high dose of SARS-CoV-2 exhibited hyperglycaemia. We also detected SARS-CoV-2 RNA in the pancreatic tissues of these cats, and immunohistochemical staining revealed the presence of SARS-CoV-2 nucleocapsid protein (NP) in the islet cells. SARS-CoV-2 NP and Spike proteins were primarily detected in Glu+ cells, and most Glu+ cells expressed ACE2. Additionally, immune protection experiments conducted on cats showed that the blood glucose levels of immunised cats did not increase post-challenge. Our data indicate the cat pancreas as a SARS-CoV-2 target and suggest that the infection of Glu+ cells could contribute to the metabolic dysregulation observed in SARS-CoV-2-infected cats.","PeriodicalId":22572,"journal":{"name":"The Indonesian Journal of Infectious Diseases","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76318595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nadine Peart Akindele, L. Pieterse, San Suwanmanee, D. Griffin
Abstract Multisystem inflammatory syndrome in children (MIS-C) can complicate infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but differences in the immune responses during MIS-C compared to coronavirus disease 2019 (COVID-19) are poorly understood. We longitudinally compared the amounts and avidity of plasma anti-nucleocapsid (N) and spike (S) antibodies, phenotypes of B cells, and numbers of virus-specific antibody-secreting cells in circulation of children hospitalized with COVID-19 (n = 10) and with MIS-C (n = 12). N-specific immunoglobulin G (IgG) was higher early after presentation for MIS-C than COVID-19 patients and avidity of N- and S-specific IgG at presentation did not mature further during follow-up as it did for COVID-19. Both groups had waning proportions of B cells in circulation and decreasing but sustained production of virus-specific antibody-secreting cells for months. Overall, B-cell responses were similar, but those with MIS-C demonstrated a more mature antibody response at presentation compared to COVID-19, suggesting a postinfectious entity.
{"title":"B-Cell Responses in Hospitalized Severe Acute Respiratory Syndrome Coronavirus 2–Infected Children With and Without Multisystem Inflammatory Syndrome","authors":"Nadine Peart Akindele, L. Pieterse, San Suwanmanee, D. Griffin","doi":"10.1093/infdis/jiac119","DOIUrl":"https://doi.org/10.1093/infdis/jiac119","url":null,"abstract":"Abstract Multisystem inflammatory syndrome in children (MIS-C) can complicate infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but differences in the immune responses during MIS-C compared to coronavirus disease 2019 (COVID-19) are poorly understood. We longitudinally compared the amounts and avidity of plasma anti-nucleocapsid (N) and spike (S) antibodies, phenotypes of B cells, and numbers of virus-specific antibody-secreting cells in circulation of children hospitalized with COVID-19 (n = 10) and with MIS-C (n = 12). N-specific immunoglobulin G (IgG) was higher early after presentation for MIS-C than COVID-19 patients and avidity of N- and S-specific IgG at presentation did not mature further during follow-up as it did for COVID-19. Both groups had waning proportions of B cells in circulation and decreasing but sustained production of virus-specific antibody-secreting cells for months. Overall, B-cell responses were similar, but those with MIS-C demonstrated a more mature antibody response at presentation compared to COVID-19, suggesting a postinfectious entity.","PeriodicalId":22572,"journal":{"name":"The Indonesian Journal of Infectious Diseases","volume":"23 1","pages":"822 - 832"},"PeriodicalIF":0.0,"publicationDate":"2022-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80559119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-16DOI: 10.1101/2022.04.15.22273412
E. Grebe, Elaine A. Yu, M. Bravo, A. Welte, R. Bruhn, M. Stone, Valerie Green, P. Williamson, Leora R. Feldstein, Jefferson M. Jones, M. Busch, B. Custer
To inform public health policy, it is critical to monitor COVID-19 vaccine effectiveness (VE), including against acquiring infection. We estimated VE using a retrospective cohort study among repeat blood donors who donated during the first half of 2021, demonstrating a viable approach for monitoring of VE via serological surveillance. Using Poisson regression, we estimated overall VE was 88.8% (95% CI: 86.2-91.1), adjusted for demographic covariates and variable baseline risk. Time since first reporting vaccination, age, race-ethnicity, region, and calendar time were statistically significant predictors of incident infection. Studies of VE during periods of Delta and Omicron spread are underway.
{"title":"COVID-19 vaccine effectiveness against SARS-CoV-2 infection in the United States prior to the Delta and Omicron-associated surges: a retrospective cohort study of repeat blood donors","authors":"E. Grebe, Elaine A. Yu, M. Bravo, A. Welte, R. Bruhn, M. Stone, Valerie Green, P. Williamson, Leora R. Feldstein, Jefferson M. Jones, M. Busch, B. Custer","doi":"10.1101/2022.04.15.22273412","DOIUrl":"https://doi.org/10.1101/2022.04.15.22273412","url":null,"abstract":"To inform public health policy, it is critical to monitor COVID-19 vaccine effectiveness (VE), including against acquiring infection. We estimated VE using a retrospective cohort study among repeat blood donors who donated during the first half of 2021, demonstrating a viable approach for monitoring of VE via serological surveillance. Using Poisson regression, we estimated overall VE was 88.8% (95% CI: 86.2-91.1), adjusted for demographic covariates and variable baseline risk. Time since first reporting vaccination, age, race-ethnicity, region, and calendar time were statistically significant predictors of incident infection. Studies of VE during periods of Delta and Omicron spread are underway.","PeriodicalId":22572,"journal":{"name":"The Indonesian Journal of Infectious Diseases","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78518710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K. Wamae, K. Kimenyi, Victor Osoti, Z. D. de Laurent, L. Ndwiga, Oksana Kharabora, N. Hathaway, J. Bailey, J. Juliano, P. Bejon, L. Ochola-Oyier
Abstract Background Genotyping Plasmodium falciparum subpopulations in malaria infections is an important aspect of malaria molecular epidemiology to understand within-host diversity and the frequency of drug resistance markers. Methods We characterized P. falciparum genetic diversity in asymptomatic infections and subsequent first febrile infections using amplicon sequencing (AmpSeq) of ama1 in Coastal Kenya. We also examined temporal changes in haplotype frequencies of mdr1, a drug-resistant marker. Results We found >60% of the infections were polyclonal (complexity of infection [COI] >1) and there was a reduction in COI over time. Asymptomatic infections had a significantly higher mean COI than febrile infections based on ama1 sequences (2.7 [95% confidence interval {CI}, 2.65–2.77] vs 2.22 [95% CI, 2.17–2.29], respectively). Moreover, an analysis of 30 paired asymptomatic and first febrile infections revealed that many first febrile infections (91%) were due to the presence of new ama1 haplotypes. The mdr1-YY haplotype, associated with chloroquine and amodiaquine resistance, decreased over time, while the NY (wild type) and the NF (modulates response to lumefantrine) haplotypes increased. Conclusions This study emphasizes the utility of AmpSeq in characterizing parasite diversity as it can determine relative proportions of clones and detect minority clones. The usefulness of AmpSeq in antimalarial drug resistance surveillance is also highlighted.
{"title":"Amplicon Sequencing as a Potential Surveillance Tool for Complexity of Infection and Drug Resistance Markers in Plasmodium falciparum Asymptomatic Infections","authors":"K. Wamae, K. Kimenyi, Victor Osoti, Z. D. de Laurent, L. Ndwiga, Oksana Kharabora, N. Hathaway, J. Bailey, J. Juliano, P. Bejon, L. Ochola-Oyier","doi":"10.1093/infdis/jiac144","DOIUrl":"https://doi.org/10.1093/infdis/jiac144","url":null,"abstract":"Abstract Background Genotyping Plasmodium falciparum subpopulations in malaria infections is an important aspect of malaria molecular epidemiology to understand within-host diversity and the frequency of drug resistance markers. Methods We characterized P. falciparum genetic diversity in asymptomatic infections and subsequent first febrile infections using amplicon sequencing (AmpSeq) of ama1 in Coastal Kenya. We also examined temporal changes in haplotype frequencies of mdr1, a drug-resistant marker. Results We found >60% of the infections were polyclonal (complexity of infection [COI] >1) and there was a reduction in COI over time. Asymptomatic infections had a significantly higher mean COI than febrile infections based on ama1 sequences (2.7 [95% confidence interval {CI}, 2.65–2.77] vs 2.22 [95% CI, 2.17–2.29], respectively). Moreover, an analysis of 30 paired asymptomatic and first febrile infections revealed that many first febrile infections (91%) were due to the presence of new ama1 haplotypes. The mdr1-YY haplotype, associated with chloroquine and amodiaquine resistance, decreased over time, while the NY (wild type) and the NF (modulates response to lumefantrine) haplotypes increased. Conclusions This study emphasizes the utility of AmpSeq in characterizing parasite diversity as it can determine relative proportions of clones and detect minority clones. The usefulness of AmpSeq in antimalarial drug resistance surveillance is also highlighted.","PeriodicalId":22572,"journal":{"name":"The Indonesian Journal of Infectious Diseases","volume":"38 1","pages":"920 - 927"},"PeriodicalIF":0.0,"publicationDate":"2022-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86505482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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