Evaluating the impact of public health investments in vaccination programs is crucial for ensuring their efficiency and effectiveness. Vaccine effectiveness (VE) studies, such as those using the test-negative design (TND), are commonly used to confirm the impact of vaccines and to guide future improvements. The TND, favored for its simplicity and cost efficiency, mitigates biases common in other epidemiological study designs. However, its validity can be compromised by inconsistent symptom definitions and retrospective data application. Here we summarize recent findings that highlight the need to address correlated vaccination behaviors when estimating VE, that suggest using negative control variables to reduce confounding, and that recommend accounting for prior infection history in VE studies to improve accuracy and reliability. These insights are important for refining VE estimation methods.
评估疫苗接种计划中公共卫生投资的影响对于确保其效率和效果至关重要。疫苗有效性（VE）研究，如采用阴性试验设计（TND）的研究，通常用于确认疫苗的影响并指导未来的改进。TND 因其简便性和成本效益而备受青睐，可减轻其他流行病学研究设计中常见的偏差。然而，由于症状定义不一致和回顾性数据的应用，其有效性可能会受到影响。在此，我们总结了最近的研究结果，这些结果强调了在估算 VE 时解决相关疫苗接种行为的必要性，建议使用负控制变量来减少混杂因素，并建议在 VE 研究中考虑既往感染史以提高准确性和可靠性。这些见解对于改进 VE 估算方法非常重要。
{"title":"Improved Methods for Vaccine Effectiveness Studies.","authors":"George N Okoli,Benjamin J Cowling","doi":"10.1093/infdis/jiae510","DOIUrl":"https://doi.org/10.1093/infdis/jiae510","url":null,"abstract":"Evaluating the impact of public health investments in vaccination programs is crucial for ensuring their efficiency and effectiveness. Vaccine effectiveness (VE) studies, such as those using the test-negative design (TND), are commonly used to confirm the impact of vaccines and to guide future improvements. The TND, favored for its simplicity and cost efficiency, mitigates biases common in other epidemiological study designs. However, its validity can be compromised by inconsistent symptom definitions and retrospective data application. Here we summarize recent findings that highlight the need to address correlated vaccination behaviors when estimating VE, that suggest using negative control variables to reduce confounding, and that recommend accounting for prior infection history in VE studies to improve accuracy and reliability. These insights are important for refining VE estimation methods.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439218","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}
Héctor Carmona-Salido, Sofía López-Solís, José Luis López-Hontangas, Carmen Amaro
Background In recent years, we have witnessed an unprecedented increase in the incidence of vibriosis due to global warming. Vibrio metoecus is a recently described V. cholerae-like species that has not been associated with septicemia death in humans. During follow-up of human vibriosis, we received a blood isolate from a patient with secondary septicemia who died a few hours after admission. Methods Phenotypic and genotypic methods failed to identify the isolate, which could only be identified by Average Nucleotide Identity after genome sequencing. The isolate was then subjected to a series of in vitro and ex vivo assays, complemented by comparative genomics focused on the identification of unique genetic traits. Strains and genomes from the same and related species (V. cholerae and V. mimicus) were used for analyses. Results The isolate was the only one able to resist and multiply in human serum. Its genome contained virulence genes shared with V. mimicus and/or V. cholerae, with those associated with sialic acid degradation within pathogenicity island 2 standing out. However, it also presented a unique gene cluster, flanked by a transposase gene, putatively related to surface polysaccharide pseudosialyzation. Conclusion In this study, we document the first case of death from septicemia due to V. metoecus and propose that the acquisition of surface pseudosialyzation genes would explain the ability of certain isolates of this species to survive in blood. Consequently, our discovery underscores the urgent need to monitor and study new emerging pathogenic species, as climate change may be facilitating their spread and increasing the risk of serious infections in humans.
{"title":"First Report of a Fatal Septicaemia Case Caused by Vibrio metoecus: A Comprehensive Functional and Genomic Study","authors":"Héctor Carmona-Salido, Sofía López-Solís, José Luis López-Hontangas, Carmen Amaro","doi":"10.1093/infdis/jiae481","DOIUrl":"https://doi.org/10.1093/infdis/jiae481","url":null,"abstract":"Background In recent years, we have witnessed an unprecedented increase in the incidence of vibriosis due to global warming. Vibrio metoecus is a recently described V. cholerae-like species that has not been associated with septicemia death in humans. During follow-up of human vibriosis, we received a blood isolate from a patient with secondary septicemia who died a few hours after admission. Methods Phenotypic and genotypic methods failed to identify the isolate, which could only be identified by Average Nucleotide Identity after genome sequencing. The isolate was then subjected to a series of in vitro and ex vivo assays, complemented by comparative genomics focused on the identification of unique genetic traits. Strains and genomes from the same and related species (V. cholerae and V. mimicus) were used for analyses. Results The isolate was the only one able to resist and multiply in human serum. Its genome contained virulence genes shared with V. mimicus and/or V. cholerae, with those associated with sialic acid degradation within pathogenicity island 2 standing out. However, it also presented a unique gene cluster, flanked by a transposase gene, putatively related to surface polysaccharide pseudosialyzation. Conclusion In this study, we document the first case of death from septicemia due to V. metoecus and propose that the acquisition of surface pseudosialyzation genes would explain the ability of certain isolates of this species to survive in blood. Consequently, our discovery underscores the urgent need to monitor and study new emerging pathogenic species, as climate change may be facilitating their spread and increasing the risk of serious infections in humans.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142440275","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}
{"title":"Vaccines for Use in Special Populations: Immunocompromised Hosts.","authors":"Michael G Ison","doi":"10.1093/infdis/jiae508","DOIUrl":"https://doi.org/10.1093/infdis/jiae508","url":null,"abstract":"","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439220","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}
Yun Lu,Kathryn Matuska,Rowan McEvoy,Hector S Izurieta,Jessica Rose Hervol,Mikhail Menis,Arnstein Lindaas,Whitney R Steele,Yoganand Chillarige,Michael Wernecke,Jeffrey A Kelman,Richard A Forshee
BACKGROUNDWe assessed the added benefit and waning effectiveness of a third COVID-19 vaccine dose (original formula) for preventing COVID-19-related outcomes.METHODSWe used Medicare claims data to conduct a retrospective cohort study in U.S. community-dwelling Medicare Fee-for-Service beneficiaries aged ≥65 years during the BA.1/BA.2 Omicron period (December 19, 2021 - March 26, 2022). We estimated relative vaccine effectiveness (RVE) of 3 versus 2 doses of mRNA COVID-19 vaccines using marginal structural Cox regression models.RESULTSAmong 8,135,020 eligible beneficiaries, 73.3% were 3-dose vaccinated by March 26, 2022. At 14-60 days since vaccination, a third dose provided significant added benefit against COVID-19-related hospitalization for Moderna (RVE: 77.2%; 95% confidence interval (CI): 76.0%, 78.4%) and Pfizer-BioNTech (RVE: 72.5%; 95% CI: 70.8%, 74.0%). Added benefit was lower >120 days. For those with prior medically attended COVID-19 diagnoses, Pfizer-BioNTech provided an added benefit for 120 days, while Moderna provided some added benefit >120 days. Added benefit for either vaccine was higher against death compared to less severe outcomes, which still decreased >120 days.CONCLUSIONSA third dose COVID-19 vaccine provided significant added benefit against COVID-19-related hospitalization and death, even for beneficiaries with prior medically attended COVID-19 diagnoses. This added benefit decreased after 4 months.
{"title":"Relative Effectiveness and Waning of a Third Dose of mRNA COVID-19 Vaccine in Medicare Beneficiaries Aged 65 Years and Older during the BA.1/BA.2 Omicron Period.","authors":"Yun Lu,Kathryn Matuska,Rowan McEvoy,Hector S Izurieta,Jessica Rose Hervol,Mikhail Menis,Arnstein Lindaas,Whitney R Steele,Yoganand Chillarige,Michael Wernecke,Jeffrey A Kelman,Richard A Forshee","doi":"10.1093/infdis/jiae503","DOIUrl":"https://doi.org/10.1093/infdis/jiae503","url":null,"abstract":"BACKGROUNDWe assessed the added benefit and waning effectiveness of a third COVID-19 vaccine dose (original formula) for preventing COVID-19-related outcomes.METHODSWe used Medicare claims data to conduct a retrospective cohort study in U.S. community-dwelling Medicare Fee-for-Service beneficiaries aged ≥65 years during the BA.1/BA.2 Omicron period (December 19, 2021 - March 26, 2022). We estimated relative vaccine effectiveness (RVE) of 3 versus 2 doses of mRNA COVID-19 vaccines using marginal structural Cox regression models.RESULTSAmong 8,135,020 eligible beneficiaries, 73.3% were 3-dose vaccinated by March 26, 2022. At 14-60 days since vaccination, a third dose provided significant added benefit against COVID-19-related hospitalization for Moderna (RVE: 77.2%; 95% confidence interval (CI): 76.0%, 78.4%) and Pfizer-BioNTech (RVE: 72.5%; 95% CI: 70.8%, 74.0%). Added benefit was lower >120 days. For those with prior medically attended COVID-19 diagnoses, Pfizer-BioNTech provided an added benefit for 120 days, while Moderna provided some added benefit >120 days. Added benefit for either vaccine was higher against death compared to less severe outcomes, which still decreased >120 days.CONCLUSIONSA third dose COVID-19 vaccine provided significant added benefit against COVID-19-related hospitalization and death, even for beneficiaries with prior medically attended COVID-19 diagnoses. This added benefit decreased after 4 months.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"39 1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439216","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}
Kara W Chew,Brooke McGinley,Carlee Moser,Jonathan Z Li,Teresa H Evering,Justin Ritz,Arzhang Cyrus Javan,David Margolis,David A Wohl,Michael D Hughes,Eric S Daar,Judith S Currier,Joseph J Eron,Davey M Smith,
We explored viral and symptom rebound after COVID-19 amubarvimab/romlusevimab monoclonal antibody therapy vs placebo in the randomized ACTIV-2/A5401 trial. Participants underwent nasal SARS-CoV-2 PCR at study days 3, 7, 14, and 28. Viral rebound was defined as RNA ≥3 and ≥0.5 log10 copies/mL increase from day 3 or 7, and symptom rebound as hospitalization or any moderate/severe symptom for ≥2 days after initial symptom improvement. There was no difference in viral rebound (∼5%/arm) (analysis population n=713) or symptom rebound among participants who initially improved (hazard ratio 0.95 (95% CI 0.52, 1.75, analysis population) n=574); <1% had both viral/symptom rebound.
{"title":"Viral and symptom rebound following anti-SARS-CoV-2 monoclonal antibody therapy in a randomized placebo-controlled trial.","authors":"Kara W Chew,Brooke McGinley,Carlee Moser,Jonathan Z Li,Teresa H Evering,Justin Ritz,Arzhang Cyrus Javan,David Margolis,David A Wohl,Michael D Hughes,Eric S Daar,Judith S Currier,Joseph J Eron,Davey M Smith,","doi":"10.1093/infdis/jiae501","DOIUrl":"https://doi.org/10.1093/infdis/jiae501","url":null,"abstract":"We explored viral and symptom rebound after COVID-19 amubarvimab/romlusevimab monoclonal antibody therapy vs placebo in the randomized ACTIV-2/A5401 trial. Participants underwent nasal SARS-CoV-2 PCR at study days 3, 7, 14, and 28. Viral rebound was defined as RNA ≥3 and ≥0.5 log10 copies/mL increase from day 3 or 7, and symptom rebound as hospitalization or any moderate/severe symptom for ≥2 days after initial symptom improvement. There was no difference in viral rebound (∼5%/arm) (analysis population n=713) or symptom rebound among participants who initially improved (hazard ratio 0.95 (95% CI 0.52, 1.75, analysis population) n=574); <1% had both viral/symptom rebound.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"229 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435980","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}
Derek J Williams, Shruti Gautam, C Buddy Creech, Natalia Jimenez, Evan J Anderson, Steven Bosinger, Tyler Grimes, Sandra R Arnold, Jonathan A McCullers, Johannes Goll, Kathryn M Edwards, Octavio Ramilo
Background Challenges remain in discerning microbiologic etiology and disease severity in childhood pneumonia. Defining host transcriptomic profiles during illness may facilitate improved diagnostic and prognostic approaches. Methods Using whole blood ribonucleic acid sequencing from 222 hospitalized children with radiographic pneumonia and 45 age-matched controls, we identified differentially expressed genes that best identified children according to detected microbial pathogens (viral-only vs. bacterial-only and typical vs. atypical bacterial [+/- viral co-detection]) and an ordinal measure of phenotypic severity (moderate, severe, very severe). Results Overall, 135 (61%) children had viral-only detections, 15 (7%) had typical bacterial (+/- viral co-detections), and 26 (12%) had atypical bacterial (+/- viral co-detections). Eleven DE genes distinguished between viral-only and bacterial-only detections. Sixteen DE genes distinguished between atypical and typical bacterial detections (+/- viral co-detections). Nineteen DE genes distinguished between levels of pneumonia severity, including four genes also identified in the viral-only vs. bacterial-only model (IGHGP, PI3, CD177, RAP1GAP1) and four genes from the typical vs atypical bacterial model (PRSS23, IFI27, OLFM4, and ABO). Conclusions We identified transcriptomic biomarkers associated with microbial detections and phenotypic severity in children hospitalized with pneumonia. These DE genes are promising candidates for validation and translation into diagnostic and prognostic tools.
背景 儿童肺炎的微生物病因学和疾病严重程度的辨别仍面临挑战。确定患病期间宿主的转录组特征有助于改进诊断和预后方法。方法 通过对 222 名住院的放射性肺炎患儿和 45 名年龄匹配的对照组患儿进行全血核糖核酸测序，我们根据检测到的微生物病原体（纯病毒与纯细菌、典型细菌与非典型细菌[+/-病毒共同检测]）和表型严重程度的顺序测量（中度、重度、极重度），确定了最能识别患儿的差异表达基因。结果 135（61%）名儿童只检测到病毒，15（7%）名儿童检测到典型细菌（+/-病毒共同检测），26（12%）名儿童检测到非典型细菌（+/-病毒共同检测）。11 个 DE 基因区分了纯病毒检测和纯细菌检测。16 个 DE 基因可区分非典型细菌检测和典型细菌检测（+/- 病毒共检测）。19 个 DE 基因可区分肺炎的严重程度，其中包括在纯病毒与纯细菌模型中也发现的 4 个基因（IGHGP、PI3、CD177、RAP1GAP1），以及典型与非典型细菌模型中的 4 个基因（PRSS23、IFI27、OLFM4 和 ABO）。结论 我们发现了与肺炎住院患儿微生物检测和表型严重程度相关的转录组生物标记物。这些 DE 基因有望得到验证并转化为诊断和预后工具。
{"title":"Transcriptomic Biomarkers Associated with Microbiological Etiology and Disease Severity in Childhood Pneumonia","authors":"Derek J Williams, Shruti Gautam, C Buddy Creech, Natalia Jimenez, Evan J Anderson, Steven Bosinger, Tyler Grimes, Sandra R Arnold, Jonathan A McCullers, Johannes Goll, Kathryn M Edwards, Octavio Ramilo","doi":"10.1093/infdis/jiae491","DOIUrl":"https://doi.org/10.1093/infdis/jiae491","url":null,"abstract":"Background Challenges remain in discerning microbiologic etiology and disease severity in childhood pneumonia. Defining host transcriptomic profiles during illness may facilitate improved diagnostic and prognostic approaches. Methods Using whole blood ribonucleic acid sequencing from 222 hospitalized children with radiographic pneumonia and 45 age-matched controls, we identified differentially expressed genes that best identified children according to detected microbial pathogens (viral-only vs. bacterial-only and typical vs. atypical bacterial [+/- viral co-detection]) and an ordinal measure of phenotypic severity (moderate, severe, very severe). Results Overall, 135 (61%) children had viral-only detections, 15 (7%) had typical bacterial (+/- viral co-detections), and 26 (12%) had atypical bacterial (+/- viral co-detections). Eleven DE genes distinguished between viral-only and bacterial-only detections. Sixteen DE genes distinguished between atypical and typical bacterial detections (+/- viral co-detections). Nineteen DE genes distinguished between levels of pneumonia severity, including four genes also identified in the viral-only vs. bacterial-only model (IGHGP, PI3, CD177, RAP1GAP1) and four genes from the typical vs atypical bacterial model (PRSS23, IFI27, OLFM4, and ABO). Conclusions We identified transcriptomic biomarkers associated with microbial detections and phenotypic severity in children hospitalized with pneumonia. These DE genes are promising candidates for validation and translation into diagnostic and prognostic tools.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"67 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142431446","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}
Kai Zhang, Qi Zhou, Hanyang Gu, Ming Yang, Xinghao Lin, Mengjie Wang, Huaqian Zhai, Feng Zhang, Yongneng Luo, LinJie Chen, Shuangshuang Wan, Yu Chen, Wei Chen, Dazhi Jin, Hui Hu
Clostridioides difficile infection (CDI) is a predominant cause of intestinal infections. The intrinsic enteric nervous system (ENS) occupies the intestinal tissue in large numbers and intricately regulates various aspects of intestinal function. Nonetheless, the specific effects of CDI on the intrinsic ENS remain underexplored. Herein, we employed the TcdB variant (TcdB2) derived from hypervirulent C. difficile to elucidate the impact of CDI on neurons located in colonic wall. We found that TcdB2 directly induced dose-dependent cytopathic effects on enteric neurons both in vitro and in adult mice colons. Notably, an increased expression of choline acetyltransferase (ChAT) and neural nitric oxide synthase (nNOS) in colonic neurons prior to the onset of cytopathic changes following treatment with TcdB2 were observed, both in vivo and in vitro. These findings suggest that during CDI, TcdB not only causes neuronal loss but also alters the composition of neurotransmitters in the ENS.
{"title":"TcdB from Hypervirulent Clostridioides difficile Induces Neuronal Loss and Neurotransmitter Alterations in the Intrinsic Enteric Nervous System","authors":"Kai Zhang, Qi Zhou, Hanyang Gu, Ming Yang, Xinghao Lin, Mengjie Wang, Huaqian Zhai, Feng Zhang, Yongneng Luo, LinJie Chen, Shuangshuang Wan, Yu Chen, Wei Chen, Dazhi Jin, Hui Hu","doi":"10.1093/infdis/jiae498","DOIUrl":"https://doi.org/10.1093/infdis/jiae498","url":null,"abstract":"Clostridioides difficile infection (CDI) is a predominant cause of intestinal infections. The intrinsic enteric nervous system (ENS) occupies the intestinal tissue in large numbers and intricately regulates various aspects of intestinal function. Nonetheless, the specific effects of CDI on the intrinsic ENS remain underexplored. Herein, we employed the TcdB variant (TcdB2) derived from hypervirulent C. difficile to elucidate the impact of CDI on neurons located in colonic wall. We found that TcdB2 directly induced dose-dependent cytopathic effects on enteric neurons both in vitro and in adult mice colons. Notably, an increased expression of choline acetyltransferase (ChAT) and neural nitric oxide synthase (nNOS) in colonic neurons prior to the onset of cytopathic changes following treatment with TcdB2 were observed, both in vivo and in vitro. These findings suggest that during CDI, TcdB not only causes neuronal loss but also alters the composition of neurotransmitters in the ENS.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"88 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142431444","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}
Background We observed a discrepancy between dengue NS1 antigen test and molecular diagnostics, with the emergence of (DENV) serotype 3 in Sri Lanka and sought to understand the cause for the rise in cases and high failure rates of molecular diagnostics. Methods Whole genomic sequencing was carried out in 22 DENV-3 samples. Phylogenetic and molecular clock analysis were done for genotype assignment and to understand the rate of evolution. Mutation analysis was done to understand the reasons for PCR non-detection. Results We identified two DENV-3 genotypes (I and III) co-circulating. DENV-3 genotype III strains shared a common ancestor with a sequence from India collected in 2022, while DENV-3 genotype I, was found to share a common ancestor with DENV-3 sequences from China. DENV-3 genotype III was detected by the modified CDC DENV-3 primers whereas, genotype I evaded detection due to key mutations at forward and reverse primer binding sites. We identified point mutations, C744T and A756G of the forward primer binding sites and in position G795A of the reverse primer binding sites which were not identified in DENV-3 genotype III. Furthermore, our Sri Lankan DENV-3 strains demonstrated a high root to tip ratio, compared to the previous DENV-3 sequences, indicating a high mutation rate during the points of sampling (year 2017 to 2023). Conclusion The co-circulation of multiple genotypes associated with an increase in cases highlights the importance of continuous surveillance of DENVs to identify mutations resulting in non-detection by diagnostics and differences in virulence.
{"title":"Simultaneous co-circulation of two genotypes of dengue virus serotype 3 causing a large outbreak in Sri Lanka in year 2023","authors":"Dinuka Ariyaratne, Bhagya Senadheera, Heshan Kuruppu, Tibutius Thanesh Pramanayagam Jayadas, Laksiri Gomes, Diyanath Ranasinghe, Farha Bary, Ananda Wijewickrama, Sully Márquez je Je, Shannon Bennett, Chandima Jeewandara, Gathsaurie Neelika Malavige","doi":"10.1093/infdis/jiae474","DOIUrl":"https://doi.org/10.1093/infdis/jiae474","url":null,"abstract":"Background We observed a discrepancy between dengue NS1 antigen test and molecular diagnostics, with the emergence of (DENV) serotype 3 in Sri Lanka and sought to understand the cause for the rise in cases and high failure rates of molecular diagnostics. Methods Whole genomic sequencing was carried out in 22 DENV-3 samples. Phylogenetic and molecular clock analysis were done for genotype assignment and to understand the rate of evolution. Mutation analysis was done to understand the reasons for PCR non-detection. Results We identified two DENV-3 genotypes (I and III) co-circulating. DENV-3 genotype III strains shared a common ancestor with a sequence from India collected in 2022, while DENV-3 genotype I, was found to share a common ancestor with DENV-3 sequences from China. DENV-3 genotype III was detected by the modified CDC DENV-3 primers whereas, genotype I evaded detection due to key mutations at forward and reverse primer binding sites. We identified point mutations, C744T and A756G of the forward primer binding sites and in position G795A of the reverse primer binding sites which were not identified in DENV-3 genotype III. Furthermore, our Sri Lankan DENV-3 strains demonstrated a high root to tip ratio, compared to the previous DENV-3 sequences, indicating a high mutation rate during the points of sampling (year 2017 to 2023). Conclusion The co-circulation of multiple genotypes associated with an increase in cases highlights the importance of continuous surveillance of DENVs to identify mutations resulting in non-detection by diagnostics and differences in virulence.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142404965","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}
Adeel A Butt, Peng Yan, Abdul-Badi Abou-Samra, Obaid S Shaikh
Using the VA COVID-19 National Database, we created matched pairs of previously uninfected vaccinated (≥2 doses of an mRNA vaccine) and previously infected unvaccinated individuals. The incidence rate (per 1000 person-days) of breakthrough infection among vaccinated individuals (0.30, 95% CI 0.29-0.32) was similar to reinfection rate among unvaccinated individuals (0.31, 95% CI 0.30-0.32; p=0.5). The incidence rate of hospitalization/death was higher after reinfection (7.31, 95% CI 6.66-8.03) compared with rate after breakthrough infection (4.69, 95% CI 4.06-5.42; P<0.0001). Conclusion: The incidence of hospitalization/death is significantly higher after reinfection among unvaccinated individuals compared with breakthrough infection after vaccination.
利用退伍军人事务部 COVID-19 国家数据库，我们创建了先前未感染的接种过疫苗（≥2 剂 mRNA 疫苗）和先前感染过疫苗的未接种者的配对。接种疫苗者的突破性感染发生率（每千人日）（0.30，95% CI 0.29-0.32）与未接种疫苗者的再感染率（0.31，95% CI 0.30-0.32；P=0.5）相似。再感染后的住院/死亡发生率（7.31，95% CI 6.66-8.03）高于突破性感染后的发生率（4.69，95% CI 4.06-5.42；P<0.0001）。结论与接种疫苗后的突破性感染相比，未接种疫苗者再次感染后的住院/死亡发生率明显更高。
{"title":"COVID-19 Disease Incidence and Severity in Previously Infected Unvaccinated Compared with Previously Uninfected Vaccinated Persons","authors":"Adeel A Butt, Peng Yan, Abdul-Badi Abou-Samra, Obaid S Shaikh","doi":"10.1093/infdis/jiae484","DOIUrl":"https://doi.org/10.1093/infdis/jiae484","url":null,"abstract":"Using the VA COVID-19 National Database, we created matched pairs of previously uninfected vaccinated (≥2 doses of an mRNA vaccine) and previously infected unvaccinated individuals. The incidence rate (per 1000 person-days) of breakthrough infection among vaccinated individuals (0.30, 95% CI 0.29-0.32) was similar to reinfection rate among unvaccinated individuals (0.31, 95% CI 0.30-0.32; p=0.5). The incidence rate of hospitalization/death was higher after reinfection (7.31, 95% CI 6.66-8.03) compared with rate after breakthrough infection (4.69, 95% CI 4.06-5.42; P&lt;0.0001). Conclusion: The incidence of hospitalization/death is significantly higher after reinfection among unvaccinated individuals compared with breakthrough infection after vaccination.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142385160","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}
Background Hemodialysis (HD) patients represent a high-risk group for hepatitis B infection. It is crucial to administer hepatitis B vaccination and stimulate higher and more sustained levels of anti-HBs. Our aim is to enhance the immunogenicity and persistence by implementing high-dose and prolonged hepatitis B vaccine schedule regimen in HD patients. Methods We conducted this multicenter, randomized, parallel-controlled trial between July 2020 and February 2023 at 11 hospitals in Shanxi province, China. A total of 504 HD patients were enrolled. All participants randomly allocated in a ratio of 1:1:1 to receive recombinant HBV vaccine of 3 standard doses (20 μg) at 0-1-6 months (IM20×3 group), 4 standard doses at 0-1-2-6 months (IM20×4 group), or 4 triple doses (60 μg) at 0-1-2-6 months (IM60×4 group). Results The vaccine-elicited antibody response peaked at month 7. The follow-up outcomes ranging from month 7 to 30 revealed that the response rates of anti-HBs decreased from 85.9% (134/156) to 33.0% (33/100) in IM20×3 group, from 92.5% (135/146) to 53.9% (56/104) in IM20×4 group and from 95.4% (145/152) to 57.3% (55/96) in IM60×4 group. The duration of vaccine-induced response with 75% of patients maintained protective antibody were 21.0 months in IM20×3 group, 25.7 months in IM20×4 group (vs. IM20×3 group, P=0.056) and 29.2 months in IM60×4 group (vs. IM20×3 group, P=0.034). All the adverse reactions were mild. Conclusions The four-triple-dose hepatitis B vaccination regimens could enhance the immunogenicity and 2-year duration in HD patients. The trial was registered with Clinical Trials.gov, number NCT03962881. https://classic.clinicaltrials.gov/ct2/show/NCT03962881?term=NCT03962881&draw=2&rank=1.
{"title":"Immunogenicity, safety, and persistence induced by triple- and standard-strength four-dose hepatitis B vaccination regimens in hemodialysis patients: A multicenter, randomized, parallel-controlled trial in Six cities in Shanxi Province","authors":"Tian Yao, Yandi Li, Yidan Zhang, Yangle Sun, Yana Guo, Jianmin Wang, Xiaohui Song, Wei Zhang, Baozhu Wei, Jingen Bai, Hui Wang, Weimin Yu, Huiyuan Wang, Lu Jiao, Yinqiang Diao, Liming Liu, Shuaishuai Shi, Jie Yang, Xiaojun Ren, Wenyuan Liu, Jingai Fang, Suping Wang, Xiaofeng Liang, Yongliang Feng","doi":"10.1093/infdis/jiae494","DOIUrl":"https://doi.org/10.1093/infdis/jiae494","url":null,"abstract":"Background Hemodialysis (HD) patients represent a high-risk group for hepatitis B infection. It is crucial to administer hepatitis B vaccination and stimulate higher and more sustained levels of anti-HBs. Our aim is to enhance the immunogenicity and persistence by implementing high-dose and prolonged hepatitis B vaccine schedule regimen in HD patients. Methods We conducted this multicenter, randomized, parallel-controlled trial between July 2020 and February 2023 at 11 hospitals in Shanxi province, China. A total of 504 HD patients were enrolled. All participants randomly allocated in a ratio of 1:1:1 to receive recombinant HBV vaccine of 3 standard doses (20 μg) at 0-1-6 months (IM20×3 group), 4 standard doses at 0-1-2-6 months (IM20×4 group), or 4 triple doses (60 μg) at 0-1-2-6 months (IM60×4 group). Results The vaccine-elicited antibody response peaked at month 7. The follow-up outcomes ranging from month 7 to 30 revealed that the response rates of anti-HBs decreased from 85.9% (134/156) to 33.0% (33/100) in IM20×3 group, from 92.5% (135/146) to 53.9% (56/104) in IM20×4 group and from 95.4% (145/152) to 57.3% (55/96) in IM60×4 group. The duration of vaccine-induced response with 75% of patients maintained protective antibody were 21.0 months in IM20×3 group, 25.7 months in IM20×4 group (vs. IM20×3 group, P=0.056) and 29.2 months in IM60×4 group (vs. IM20×3 group, P=0.034). All the adverse reactions were mild. Conclusions The four-triple-dose hepatitis B vaccination regimens could enhance the immunogenicity and 2-year duration in HD patients. The trial was registered with Clinical Trials.gov, number NCT03962881. https://classic.clinicaltrials.gov/ct2/show/NCT03962881?term=NCT03962881&draw=2&rank=1.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"63 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142385640","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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