Tosin E Omole, Huong Mai Nguyen, Agata Marcinow, Myo Minn Oo, Naima Jahan, Aloysious Ssemaganda, Giulia Severini, Katherine K Thomas, Connie Celum, Nelly Mugo, Andrew Mujugira, James Kublin, Lawrence Corey, Aida Sivro, Jairam R Lingappa, Glenda Gray, Lyle R McKinnon
Background CD4+ T cells expressing α4β7 are optimal targets for HIV infections, with higher pre-HIV α4β7hi expression linked to increased HIV acquisition and progression in South African women. However, similar associations were not observed in men who have sex with men (MSM) or people who inject drugs (PWID) in the Americas, indicating need for further research. Methods This retrospective case-control study enrolled heterosexual men and women from South Africa (HIV Vaccine Trials Network; HVTN 503) and East Africa (Partners Pre-Exposure Prophylaxis/Couples’ Observational Study; PP/COS), quantifying α4β7 expression on CD4+ T cells as a predictor of subsequent HIV risk using flow cytometry analyses. Results Associations between α4β7hi expression and HIV acquisition varied across cohorts. In HVTN 503, women had a higher risk estimate compared to men, but this was not significant. In PP/COS, α4β7hi expression was generally protective, particularly in Ugandans. Additionally, α4β7hi expression inversely correlated with peak viral load in PP/COS but not in HVTN 503; in the latter cohort, α4β7hi expression was inversely correlated with the CD4/CD8 ratio and predicted rapid CD4+ T cell decline, similar to what was observed previously in South Africa. Conclusions These findings suggest that α4β7hi expression on CD4+ T cells may not predict HIV acquisition and progression in all contexts, which may be due to cohort effects, modes of transmission, viral clade, or other factors.
{"title":"Pre-HIV α4β7hi CD4+ T cells and HIV risk among heterosexual individuals in Africa","authors":"Tosin E Omole, Huong Mai Nguyen, Agata Marcinow, Myo Minn Oo, Naima Jahan, Aloysious Ssemaganda, Giulia Severini, Katherine K Thomas, Connie Celum, Nelly Mugo, Andrew Mujugira, James Kublin, Lawrence Corey, Aida Sivro, Jairam R Lingappa, Glenda Gray, Lyle R McKinnon","doi":"10.1093/infdis/jiae638","DOIUrl":"https://doi.org/10.1093/infdis/jiae638","url":null,"abstract":"Background CD4+ T cells expressing α4β7 are optimal targets for HIV infections, with higher pre-HIV α4β7hi expression linked to increased HIV acquisition and progression in South African women. However, similar associations were not observed in men who have sex with men (MSM) or people who inject drugs (PWID) in the Americas, indicating need for further research. Methods This retrospective case-control study enrolled heterosexual men and women from South Africa (HIV Vaccine Trials Network; HVTN 503) and East Africa (Partners Pre-Exposure Prophylaxis/Couples’ Observational Study; PP/COS), quantifying α4β7 expression on CD4+ T cells as a predictor of subsequent HIV risk using flow cytometry analyses. Results Associations between α4β7hi expression and HIV acquisition varied across cohorts. In HVTN 503, women had a higher risk estimate compared to men, but this was not significant. In PP/COS, α4β7hi expression was generally protective, particularly in Ugandans. Additionally, α4β7hi expression inversely correlated with peak viral load in PP/COS but not in HVTN 503; in the latter cohort, α4β7hi expression was inversely correlated with the CD4/CD8 ratio and predicted rapid CD4+ T cell decline, similar to what was observed previously in South Africa. Conclusions These findings suggest that α4β7hi expression on CD4+ T cells may not predict HIV acquisition and progression in all contexts, which may be due to cohort effects, modes of transmission, viral clade, or other factors.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884137","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}
Prabha Chandrasekaran, Irina Maljkovic Berry, Viviane Callier, Scott M Anthony, Krystle Hensley, Jens H Kuhn, Kathryn Shaw-Saliba, Stephen B Kennedy, Mark Kieh, Sarah M Browne, Ian Crozier, Richard T Davey, H Clifford Lane, Lisa E Hensley, Dean A Follmann
Background The robustness and persistence of vaccine antigen-induced antibodies are often used as proxy indicators of vaccine efficacy, but immune responses to vaccine vectors are typically less well-defined. Our study considered the kinetics of immunoglobulin (IgG) responses against the vector (vesicular stomatitis Indiana virus [VSIV]) nucleoprotein (N) and the inserted antigen (Ebola virus [EBOV]) glycoprotein (GP1,2) components of the rVSVΔG-ZEBOV-GP (rVSV-ZEBOV) vaccine and evaluated their use as biomarkers to confirm self-reported vaccination status. Methods From the Partnership for Research on Ebola Virus in Liberia (PREVAIL) I clinical trial (NCT02344407), we randomly selected 212 participants who received rVSV-ZEBOV (n=107) or placebo (n=105). Levels of IgG antibodies to EBOV GP1,2 or VSIV N were measured using the Filovirus Animal Non-Clinical Group (FANG) ELISA and a newly developed single-molecule array (Simoa) immunoassay, respectively. Results Anti-EBOV GP1,2 IgG and anti-VSIV N IgG were first detected 10–14 d post-vaccination, further increased at 28 d, and remained stable through 360 d. Antibody titers were significantly higher in women compared to men. Anti-EBOV GP1,2 and anti-VSIV N IgG titers were significantly correlated (p<0.001) at 28 d (r=0.47), 180 d (r=0.45), and 360 d (r=0.59). At 28 d, the area under the curve (AUC) of receiver operating characteristic (ROC) curves discriminated vaccinated from unvaccinated patients with high accuracy (AUC=0.965 for anti-VSIV N IgG; AUC=0.945 for anti-EBOV GP1,2 IgG [p<0.001]). Conclusions We report a reliable assay to measure vector-induced humoral responses after rVSV-ZEBOV vaccination and demonstrate the assay’s utility to confirm vaccination status.
疫苗抗原诱导抗体的稳健性和持久性通常被用作疫苗效力的代理指标，但对疫苗载体的免疫反应通常不太明确。我们的研究考虑了免疫球蛋白（IgG）对载体（水疱性口炎印第安纳病毒[VSIV]）核蛋白(N)和插入抗原（埃博拉病毒[EBOV]）糖蛋白（GP1,2）成分rVSVΔG-ZEBOV-GP （rVSV-ZEBOV）疫苗的反应动力学，并评估了它们作为生物标志物的用途，以确认自我报告的疫苗接种状态。方法从利比里亚埃博拉病毒研究伙伴关系（PREVAIL） I临床试验（NCT02344407）中随机选择212名接受rVSV-ZEBOV （n=107）或安慰剂（n=105）的参与者。分别采用丝状病毒动物非临床组（FANG） ELISA和新开发的单分子阵列（Simoa）免疫分析法检测EBOV GP1、2或VSIV N的IgG抗体水平。结果接种后10 ~ 14 d首次检测到ebov抗体GP1、2 IgG和vsiv抗体N IgG，接种后28 d进一步升高，接种后360 d保持稳定，女性抗体滴度明显高于男性。抗ebov GP1,2和抗vsiv N IgG滴度在28 d (r=0.47), 180 d （r=0.45）和360 d （r=0.59）时显著相关（p<0.001）。28 d时，受试者工作特征曲线（ROC）曲线下面积（AUC）区分接种者与未接种者准确率较高(抗vsv N IgG AUC=0.965；抗ebov GP1,2 IgG的AUC=0.945 [p<0.001])。我们报告了一种可靠的方法来测量rVSV-ZEBOV疫苗接种后载体诱导的体液反应，并证明了该方法在确认疫苗接种状态方面的实用性。
{"title":"Vector induced humoral responses after rVSVΔG-ZEBOV-GP immunization identify vaccinated individuals and correlate with Ebola virus glycoprotein antibodies","authors":"Prabha Chandrasekaran, Irina Maljkovic Berry, Viviane Callier, Scott M Anthony, Krystle Hensley, Jens H Kuhn, Kathryn Shaw-Saliba, Stephen B Kennedy, Mark Kieh, Sarah M Browne, Ian Crozier, Richard T Davey, H Clifford Lane, Lisa E Hensley, Dean A Follmann","doi":"10.1093/infdis/jiae632","DOIUrl":"https://doi.org/10.1093/infdis/jiae632","url":null,"abstract":"Background The robustness and persistence of vaccine antigen-induced antibodies are often used as proxy indicators of vaccine efficacy, but immune responses to vaccine vectors are typically less well-defined. Our study considered the kinetics of immunoglobulin (IgG) responses against the vector (vesicular stomatitis Indiana virus [VSIV]) nucleoprotein (N) and the inserted antigen (Ebola virus [EBOV]) glycoprotein (GP1,2) components of the rVSVΔG-ZEBOV-GP (rVSV-ZEBOV) vaccine and evaluated their use as biomarkers to confirm self-reported vaccination status. Methods From the Partnership for Research on Ebola Virus in Liberia (PREVAIL) I clinical trial (NCT02344407), we randomly selected 212 participants who received rVSV-ZEBOV (n=107) or placebo (n=105). Levels of IgG antibodies to EBOV GP1,2 or VSIV N were measured using the Filovirus Animal Non-Clinical Group (FANG) ELISA and a newly developed single-molecule array (Simoa) immunoassay, respectively. Results Anti-EBOV GP1,2 IgG and anti-VSIV N IgG were first detected 10–14 d post-vaccination, further increased at 28 d, and remained stable through 360 d. Antibody titers were significantly higher in women compared to men. Anti-EBOV GP1,2 and anti-VSIV N IgG titers were significantly correlated (p&lt;0.001) at 28 d (r=0.47), 180 d (r=0.45), and 360 d (r=0.59). At 28 d, the area under the curve (AUC) of receiver operating characteristic (ROC) curves discriminated vaccinated from unvaccinated patients with high accuracy (AUC=0.965 for anti-VSIV N IgG; AUC=0.945 for anti-EBOV GP1,2 IgG [p&lt;0.001]). Conclusions We report a reliable assay to measure vector-induced humoral responses after rVSV-ZEBOV vaccination and demonstrate the assay’s utility to confirm vaccination status.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"48 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884139","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}
Fernando Dias Gonçalves Lima, Kirsten Rozemeijer, Ramon P van der Zee, Stèfanie Dick, Timo J ter Braak, Debby E Geijsen, Philip Meijnen, Birgit I Lissenberg-Witte, Carel J M van Noesel, Henry J C de Vries, Jan M Prins, Renske D M Steenbergen
Introduction High-resolution anoscopy (HRA) to prevent anal cancer is complex and screening capacity is limited. Previously, we showed that DNA methylation analysis of anal high-grade squamous intraepithelial lesions (HSIL) biopsies can distinguish between HSIL with an increased cancer risk, and HSIL with a low cancer risk, in which treatment may be safely withheld. Here, we assessed the performance of methylation analysis in anal swabs to identify patients with underlying HSIL with an increased cancer risk. Methods A cross-sectional series of paired anal swabs and biopsies of 215 persons with HIV and swabs of 19 anal cancer patients were tested for 6 methylation markers. Data were analysed by logistic regression analysis. The primary endpoint was methylation-positive biopsy HSIL (M+HSIL), indicating increased cancer risk. Test performance on swabs of methylation markers, HPV and/or cytology, as well as cancer detection and HRA referral rates were calculated. Results Anal cancer swabs had the highest methylation levels. ZNF582, and marker panels ASCL1/ZNF582 and LHX8/ZNF582 yielded an area-under-the-curve of 0.68 to 0.70 to detect underlying M+HSIL. LHX8/ZNF582 methylation at 80% sensitivity corresponded to 43% fewer patients requiring HRA, without missing any anal cancers and detecting 79% of HPV16-positive HSIL-anal intraepithelial neoplasia grade 3. Methylation and HPV co-testing performed similarly to cytology and HPV co-testing. Conclusion DNA methylation levels in anal swabs reflect underlying anal disease. Methylation analysis could reduce HRA referrals substantially, while maintaining a high sensitivity for M+HSIL and detecting all cancers. These results encourage screening on anal swabs to preselect patients that require HRA.
{"title":"DNA methylation analysis on anal swabs for anal cancer screening in people living with HIV","authors":"Fernando Dias Gonçalves Lima, Kirsten Rozemeijer, Ramon P van der Zee, Stèfanie Dick, Timo J ter Braak, Debby E Geijsen, Philip Meijnen, Birgit I Lissenberg-Witte, Carel J M van Noesel, Henry J C de Vries, Jan M Prins, Renske D M Steenbergen","doi":"10.1093/infdis/jiae627","DOIUrl":"https://doi.org/10.1093/infdis/jiae627","url":null,"abstract":"Introduction High-resolution anoscopy (HRA) to prevent anal cancer is complex and screening capacity is limited. Previously, we showed that DNA methylation analysis of anal high-grade squamous intraepithelial lesions (HSIL) biopsies can distinguish between HSIL with an increased cancer risk, and HSIL with a low cancer risk, in which treatment may be safely withheld. Here, we assessed the performance of methylation analysis in anal swabs to identify patients with underlying HSIL with an increased cancer risk. Methods A cross-sectional series of paired anal swabs and biopsies of 215 persons with HIV and swabs of 19 anal cancer patients were tested for 6 methylation markers. Data were analysed by logistic regression analysis. The primary endpoint was methylation-positive biopsy HSIL (M+HSIL), indicating increased cancer risk. Test performance on swabs of methylation markers, HPV and/or cytology, as well as cancer detection and HRA referral rates were calculated. Results Anal cancer swabs had the highest methylation levels. ZNF582, and marker panels ASCL1/ZNF582 and LHX8/ZNF582 yielded an area-under-the-curve of 0.68 to 0.70 to detect underlying M+HSIL. LHX8/ZNF582 methylation at 80% sensitivity corresponded to 43% fewer patients requiring HRA, without missing any anal cancers and detecting 79% of HPV16-positive HSIL-anal intraepithelial neoplasia grade 3. Methylation and HPV co-testing performed similarly to cytology and HPV co-testing. Conclusion DNA methylation levels in anal swabs reflect underlying anal disease. Methylation analysis could reduce HRA referrals substantially, while maintaining a high sensitivity for M+HSIL and detecting all cancers. These results encourage screening on anal swabs to preselect patients that require HRA.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884140","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 Amino acid (AA) substitutions in the fusion protein of respiratory syncytial virus (RSV) and their effects remain unclear. We aimed to analyze AA substitutions in main neutralizing epitopes of the fusion (F) protein. Methods We analyzed F protein genes of 236 RSV strains isolated from children hospitalized with RSV infection in Fukushima, Japan (June 2008–February 2023). AA substitutions were detected at antigenic sites II, V, and Ø, the main neutralizing epitopes. We conducted neutralization assays using site-specific mAbs to investigate the relationship between AA substitutions and mAb susceptibility. Finally, we examined viral replicative ability. Results Site Ⅱ: RSV strains isolated from children receiving palivizumab treatment exhibited the K272M substitution in RSV-A and K272E substitution in RSV-B, showing reduced susceptibility to site Ⅱ-specific antibody. Site Ⅴ: In RSV-A, >50% of strains isolated since 2022 harbored the V178I substitution; however, this did not change susceptibility to site Ⅴ-specific antibody. In RSV-B, L172Q/S173L mutant strains became predominant around 2016, leading to reduced susceptibility to site Ⅴ-specific antibodies. Site Ø: No AA substitutions were detected in RSV-A. In RSV-B, the I206M/Q209R mutant strain became predominant around 2018, leading to improved site Ø-specific antibody susceptibility and replicative ability. However, none of the substitutions reduced susceptibility to site Ø-specific antibodies. Conclusions The RSV F protein in Fukushima has naturally undergone AA substitutions with corresponding changes in antibody susceptibility. In addition to substitutions similar to those observed globally, unique substitutions have been observed. Therefore, AA substitutions and antibody susceptibility in various regions must be monitored.
{"title":"Amino acid substitutions in the fusion protein of respiratory syncytial virus in Fukushima, Japan during 2008–2023 and their effects","authors":"Hisao Okabe, Koichi Hashimoto, Sakurako Norito, Yuichiro Asano, Masatoki Sato, Yohei Kume, Mina Chishiki, Hajime Maeda, Fumi Mashiyama, Aya Takeyama, Hiromichi Murai, Kenji Nemoto, Masaki Ito, Shigeo Suzuki, Hiroko Sakuma, Kazuya Shirato, Hayato Go, Mitsuaki Hosoya","doi":"10.1093/infdis/jiae636","DOIUrl":"https://doi.org/10.1093/infdis/jiae636","url":null,"abstract":"Background Amino acid (AA) substitutions in the fusion protein of respiratory syncytial virus (RSV) and their effects remain unclear. We aimed to analyze AA substitutions in main neutralizing epitopes of the fusion (F) protein. Methods We analyzed F protein genes of 236 RSV strains isolated from children hospitalized with RSV infection in Fukushima, Japan (June 2008–February 2023). AA substitutions were detected at antigenic sites II, V, and Ø, the main neutralizing epitopes. We conducted neutralization assays using site-specific mAbs to investigate the relationship between AA substitutions and mAb susceptibility. Finally, we examined viral replicative ability. Results Site Ⅱ: RSV strains isolated from children receiving palivizumab treatment exhibited the K272M substitution in RSV-A and K272E substitution in RSV-B, showing reduced susceptibility to site Ⅱ-specific antibody. Site Ⅴ: In RSV-A, &gt;50% of strains isolated since 2022 harbored the V178I substitution; however, this did not change susceptibility to site Ⅴ-specific antibody. In RSV-B, L172Q/S173L mutant strains became predominant around 2016, leading to reduced susceptibility to site Ⅴ-specific antibodies. Site Ø: No AA substitutions were detected in RSV-A. In RSV-B, the I206M/Q209R mutant strain became predominant around 2018, leading to improved site Ø-specific antibody susceptibility and replicative ability. However, none of the substitutions reduced susceptibility to site Ø-specific antibodies. Conclusions The RSV F protein in Fukushima has naturally undergone AA substitutions with corresponding changes in antibody susceptibility. In addition to substitutions similar to those observed globally, unique substitutions have been observed. Therefore, AA substitutions and antibody susceptibility in various regions must be monitored.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884144","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 Current guidelines recommend combining a macrolide with a β-lactam antibiotic for the empirical treatment of moderate-to-high severity community-acquired pneumonia (CAP); however macrolide use is associated with potential adverse events and antimicrobial resistance. Methods We analysed electronic health data from 8,872 adults in Oxfordshire, UK, hospitalised with CAP between 01-January-2016 and 19-March-2024, who received either amoxicillin or co-amoxiclav as initial treatment. We examined the effects of adjunctive macrolides on 30-day all-cause mortality, time to hospital discharge, and changes in Sequential Organ Failure Assessment (SOFA) score, using inverse probability treatment weighting to address confounding by baseline severity. Subgroup analyses by severity and sensitivity analyses with missing covariates imputed were performed. Results There was no evidence of an association between the use of additional macrolides and 30-day mortality, with marginal odds ratios of 1.05 (95%CI 0.75-1.47) for amoxicillin with vs. without macrolide, and 1.12 (0.93-1.34) for co-amoxiclav with vs. without macrolide. No evidence of difference was found in time to discharge from additional macrolides to amoxicillin (restricted mean days lost +1.76 [-1.66,+5.19]), or co-amoxiclav (+0.44 [-1.63,+2.51]). There was also no evidence that macrolide use was associated with SOFA score decreases. Results were consistent across stratified analyses by pneumonia severity, and remained broadly similar in sensitivity analyses with missing data imputed. Conclusions At a population level, the addition of macrolides was not associated with improved clinical outcomes for CAP patients. The potential advantages of combining macrolides with a β-lactam antibiotic in CAP treatment should be balanced against the risks of adverse effects and antimicrobial resistance.
{"title":"Addition of macrolide antibiotics for hospital treatment of community-acquired pneumonia","authors":"Jia Wei, A Sarah Walker, David W Eyre","doi":"10.1093/infdis/jiae639","DOIUrl":"https://doi.org/10.1093/infdis/jiae639","url":null,"abstract":"Background Current guidelines recommend combining a macrolide with a β-lactam antibiotic for the empirical treatment of moderate-to-high severity community-acquired pneumonia (CAP); however macrolide use is associated with potential adverse events and antimicrobial resistance. Methods We analysed electronic health data from 8,872 adults in Oxfordshire, UK, hospitalised with CAP between 01-January-2016 and 19-March-2024, who received either amoxicillin or co-amoxiclav as initial treatment. We examined the effects of adjunctive macrolides on 30-day all-cause mortality, time to hospital discharge, and changes in Sequential Organ Failure Assessment (SOFA) score, using inverse probability treatment weighting to address confounding by baseline severity. Subgroup analyses by severity and sensitivity analyses with missing covariates imputed were performed. Results There was no evidence of an association between the use of additional macrolides and 30-day mortality, with marginal odds ratios of 1.05 (95%CI 0.75-1.47) for amoxicillin with vs. without macrolide, and 1.12 (0.93-1.34) for co-amoxiclav with vs. without macrolide. No evidence of difference was found in time to discharge from additional macrolides to amoxicillin (restricted mean days lost +1.76 [-1.66,+5.19]), or co-amoxiclav (+0.44 [-1.63,+2.51]). There was also no evidence that macrolide use was associated with SOFA score decreases. Results were consistent across stratified analyses by pneumonia severity, and remained broadly similar in sensitivity analyses with missing data imputed. Conclusions At a population level, the addition of macrolides was not associated with improved clinical outcomes for CAP patients. The potential advantages of combining macrolides with a β-lactam antibiotic in CAP treatment should be balanced against the risks of adverse effects and antimicrobial resistance.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"59 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884141","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}
Jenna Alessandrini, Brendan T Smith, Tiffany Fitzpatrick, Sarah A Buchan
Background Socio-economic status (SES) is an important determinant of severe respiratory infections. Despite being a leading cause of hospitalization, limited attention has been given to social inequities in respiratory syncytial virus (RSV), particularly outside of childhood and beyond neighbourhood-level measures. This study aimed to quantify the burden of severe RSV disease across the age continuum by individual-level SES indicators. Methods We conducted a longitudinal descriptive study of Canadians (excluding Québec) ≥6 months of age using linked socio-demographic and hospitalization data from the 2016 Canadian Census Health and Environment Cohort (2016-2019). Crude and age-stratified International Classification of Diseases, 10th Revision, Canada (ICD-10-CA) coded RSV-related hospitalization rates, rate ratios (RRs), and rate differences (RDs) per 100,000 person-years were estimated across SES indicators using Poisson regression. Results Rates of RSV-related hospitalization were greatest among Canadians with lower compared to higher SES, as indicated through multiple measures including income (RD: 11.7 [95% confidence interval, 10.1-13.3]; RR: 2.8 [2.4-3.2]), education (RD: 18.7 [16.6-20.9]; RR: 3.3 [2.9-3.7]), and various indicators of poorer housing conditions including unaffordable housing and apartment-living. Inequities in RSV-related hospitalization varied by SES measure and age group; while rates were highest among 6-59-month- and ≥80-year-olds overall, some of the greatest relative SES inequities were among other age groups. Conclusions This work highlights novel individual-level social determinants influencing the burden of severe RSV disease. In addition to clinical characteristics, understanding SES factors role in age-specific RSV-related hospitalization risk is necessary to inform equitable prevention efforts, including delivery of emerging RSV immunizations.
{"title":"Socio-Economic Inequities in the Age-Specific Burden of Severe Respiratory Syncytial Virus (RSV) in Canada, 2016-2019","authors":"Jenna Alessandrini, Brendan T Smith, Tiffany Fitzpatrick, Sarah A Buchan","doi":"10.1093/infdis/jiae635","DOIUrl":"https://doi.org/10.1093/infdis/jiae635","url":null,"abstract":"Background Socio-economic status (SES) is an important determinant of severe respiratory infections. Despite being a leading cause of hospitalization, limited attention has been given to social inequities in respiratory syncytial virus (RSV), particularly outside of childhood and beyond neighbourhood-level measures. This study aimed to quantify the burden of severe RSV disease across the age continuum by individual-level SES indicators. Methods We conducted a longitudinal descriptive study of Canadians (excluding Québec) ≥6 months of age using linked socio-demographic and hospitalization data from the 2016 Canadian Census Health and Environment Cohort (2016-2019). Crude and age-stratified International Classification of Diseases, 10th Revision, Canada (ICD-10-CA) coded RSV-related hospitalization rates, rate ratios (RRs), and rate differences (RDs) per 100,000 person-years were estimated across SES indicators using Poisson regression. Results Rates of RSV-related hospitalization were greatest among Canadians with lower compared to higher SES, as indicated through multiple measures including income (RD: 11.7 [95% confidence interval, 10.1-13.3]; RR: 2.8 [2.4-3.2]), education (RD: 18.7 [16.6-20.9]; RR: 3.3 [2.9-3.7]), and various indicators of poorer housing conditions including unaffordable housing and apartment-living. Inequities in RSV-related hospitalization varied by SES measure and age group; while rates were highest among 6-59-month- and ≥80-year-olds overall, some of the greatest relative SES inequities were among other age groups. Conclusions This work highlights novel individual-level social determinants influencing the burden of severe RSV disease. In addition to clinical characteristics, understanding SES factors role in age-specific RSV-related hospitalization risk is necessary to inform equitable prevention efforts, including delivery of emerging RSV immunizations.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"86 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884143","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}
Rachel Mittelstaedt, Sanjat Kanjilal, David Helekal, Gregory K Robbins, Yonatan H Grad
Among doxycycline post-exposure prophylaxis (doxy-PEP) eligible men, Staphylococcus aureus tetracycline non-susceptibility is more prevalent than in the overall population and is associated with resistance to trimethoprim-sulfamethoxazole and clindamycin. Doxy-PEP may select for multi-drug-resistant S. aureus, underscoring the importance of surveillance.
{"title":"Staphylococcus aureus Tetracycline Resistance and Co-resistance in a Doxy-PEP-Eligible Population","authors":"Rachel Mittelstaedt, Sanjat Kanjilal, David Helekal, Gregory K Robbins, Yonatan H Grad","doi":"10.1093/infdis/jiae634","DOIUrl":"https://doi.org/10.1093/infdis/jiae634","url":null,"abstract":"Among doxycycline post-exposure prophylaxis (doxy-PEP) eligible men, Staphylococcus aureus tetracycline non-susceptibility is more prevalent than in the overall population and is associated with resistance to trimethoprim-sulfamethoxazole and clindamycin. Doxy-PEP may select for multi-drug-resistant S. aureus, underscoring the importance of surveillance.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"630 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884142","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}
Shadia Khandaker, Shilpee Sharma, Tom Hall, Suzanna Lim, Janne Lehtonen, Stephanie Leung, Zabed Bin Ahmed, Andrew Gorringe, Samir K Saha, Arnaud Marchant, Kirsty Le Doare, Aras Kadioglu, Neil French
Background Significant disparities in Group B Streptococcus (GBS) colonisation and neonatal disease rates have been documented across different geographical regions. For example, Bangladesh reports notably lower rates compared to the United Kingdom (UK) and Malawi. This study investigates whether this epidemiological variability correlates with the immune response to GBS in these regions. Methods Qualitative and quantitative analyses of naturally acquired immunoglobulin G (IgG) antibodies against GBS capsular polysaccharides (CPS) and the Alp protein family were conducted in serum samples from women of childbearing age in the UK, Bangladesh, and Malawi. The efficacy of these antibodies in clearing vaginal colonisation or protecting newborns from GBS infection was assessed using humanised mouse models. Results Bangladeshi women displayed the highest diversity in serotype distribution, with elevated immunoglobulin G (IgG) levels in the serum against GBS capsular polysaccharides (CPS)- Ia, Ib, II, III, IV, and V, as well as Alp family proteins. In contrast, Malawian sera demonstrated the weakest antibody response. Bangladeshi sera also showed heightened IgG-mediated complement deposition, opsonophagocytic killing and neonatal Fc receptor (FcRn)-binding while tested against CPS Ib. In a humanised FcRn mouse model, Bangladeshi sera led to faster clearance of GBS virulent serotype Ib vaginal colonisation. Additionally, offspring from dams passively immunised with Bangladeshi sera demonstrated notably increased survival rates. Conclusions This study demonstrates significant variability in the immune response to GBS across different geographical regions. These findings underscore the importance of understanding GBS-induced immune response in diverse populations, which may significantly impact vaccine efficacy in these regions.
背景 据记录，不同地理区域的 B 群链球菌 (GBS) 定植率和新生儿患病率存在显著差异。例如，孟加拉国的发病率明显低于英国和马拉维。本研究探讨了这一流行病学变异是否与这些地区对 GBS 的免疫反应有关。方法 对英国、孟加拉国和马拉维育龄妇女血清样本中针对 GBS 胶囊多糖 (CPS) 和 Alp 蛋白家族的天然免疫球蛋白 G (IgG) 抗体进行定性和定量分析。使用人源化小鼠模型评估了这些抗体在清除阴道定植或保护新生儿免受 GBS 感染方面的功效。结果 孟加拉国妇女的血清型分布多样性最高，血清中针对 GBS 胶囊多糖 (CPS)--Ia、Ib、II、III、IV 和 V 以及 Alp 家族蛋白的免疫球蛋白 G (IgG) 含量升高。相比之下，马拉维血清的抗体反应最弱。在针对 CPS Ib 的测试中，孟加拉国血清还显示出更强的 IgG 介导的补体沉积、嗜蛋白细胞杀伤和新生儿 Fc 受体（FcRn）结合能力。在人源化 FcRn 小鼠模型中，孟加拉国血清能更快地清除 GBS 毒性血清 Ib 型阴道定植。此外，用孟加拉国血清被动免疫母鼠的后代存活率明显提高。结论 本研究表明，不同地理区域对 GBS 的免疫反应存在显著差异。这些发现强调了了解 GBS 在不同人群中引起的免疫反应的重要性，这可能会极大地影响疫苗在这些地区的疗效。
{"title":"Diversity in Naturally Acquired Immunity to Group B Streptococcus: A Comparative Study of Women from Bangladesh, Malawi, and the United Kingdom","authors":"Shadia Khandaker, Shilpee Sharma, Tom Hall, Suzanna Lim, Janne Lehtonen, Stephanie Leung, Zabed Bin Ahmed, Andrew Gorringe, Samir K Saha, Arnaud Marchant, Kirsty Le Doare, Aras Kadioglu, Neil French","doi":"10.1093/infdis/jiae607","DOIUrl":"https://doi.org/10.1093/infdis/jiae607","url":null,"abstract":"Background Significant disparities in Group B Streptococcus (GBS) colonisation and neonatal disease rates have been documented across different geographical regions. For example, Bangladesh reports notably lower rates compared to the United Kingdom (UK) and Malawi. This study investigates whether this epidemiological variability correlates with the immune response to GBS in these regions. Methods Qualitative and quantitative analyses of naturally acquired immunoglobulin G (IgG) antibodies against GBS capsular polysaccharides (CPS) and the Alp protein family were conducted in serum samples from women of childbearing age in the UK, Bangladesh, and Malawi. The efficacy of these antibodies in clearing vaginal colonisation or protecting newborns from GBS infection was assessed using humanised mouse models. Results Bangladeshi women displayed the highest diversity in serotype distribution, with elevated immunoglobulin G (IgG) levels in the serum against GBS capsular polysaccharides (CPS)- Ia, Ib, II, III, IV, and V, as well as Alp family proteins. In contrast, Malawian sera demonstrated the weakest antibody response. Bangladeshi sera also showed heightened IgG-mediated complement deposition, opsonophagocytic killing and neonatal Fc receptor (FcRn)-binding while tested against CPS Ib. In a humanised FcRn mouse model, Bangladeshi sera led to faster clearance of GBS virulent serotype Ib vaginal colonisation. Additionally, offspring from dams passively immunised with Bangladeshi sera demonstrated notably increased survival rates. Conclusions This study demonstrates significant variability in the immune response to GBS across different geographical regions. These findings underscore the importance of understanding GBS-induced immune response in diverse populations, which may significantly impact vaccine efficacy in these regions.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"91 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841173","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}
Cheryl L Day, Irene N Njuguna, Lisa Marie Cranmer, Wendy E Whatney, Rachel A Pearson, Cecilia S Lindestam Arlehamn, Alessandro Sette, Sylvia M LaCourse, Jaclyn N Escudero, Loren E Sasser, Cyrus Mugo, Hellen Moraa Okinyi, Elizabeth Maleche-Obimbo, Dalton C Wamalwa, Grace C John-Stewart
Background Despite immune restoration after initiation of antiretroviral treatment (ART), the risk of tuberculosis (TB) persists in children living with HIV (CLHIV). We determined patterns of immune restoration of mycobacteria-specific T cells following ART in CLHIV. Methods CD4 and CD8 T cell activation and memory phenotype and functional profiles before and 6 months after ART were evaluated in peripheral blood mononuclear cells (PBMCs) from CLHIV enrolled in the PUSH study (NCT02063880) in Nairobi, Kenya. T cell expression of cytokines and activation induced markers (AIM) were measured following stimulation of PBMCs with a pool of 300 peptides from TB (MTB300) or staphylococcal enterotoxin B (SEB). Results Among 47 CLHIV of median age 1.5 years, SEB-induced Th1 cytokine+ and AIM+ CD4 cell frequencies increased significantly after 6 months ART. Although MTB300-specific CD4 and CD8 cell frequency did not increase after ART, polyfunctional capacity of MTB300-specific CD4 cells expressing combinations of Th1 cytokines with CD40L increased significantly after ART. Baseline age, immune activation, and effector memory CD4 levels were associated with less restoration of MTB300-specific polyfunctional CD4 cells, whereas CD4% and levels of naïve CD4 cells following ART were associated with improved MTB300-specific polyfunctional capacity. Conclusions Despite increases in Th1 cytokine production, deficits in mycobacteria-specific CD4 cells persisted 6 months after ART, with higher deficits in older CLHIV with more immunosuppression, higher immune activation, and lower proportion of naïve CD4 cells. These findings may explain persistent TB risk during early ART among CLHIV and identify those at highest risk.
{"title":"Patterns and cofactors of polyfunctional mycobacteria-specific T cell response restoration following 6-month antiretroviral treatment in children living with HIV","authors":"Cheryl L Day, Irene N Njuguna, Lisa Marie Cranmer, Wendy E Whatney, Rachel A Pearson, Cecilia S Lindestam Arlehamn, Alessandro Sette, Sylvia M LaCourse, Jaclyn N Escudero, Loren E Sasser, Cyrus Mugo, Hellen Moraa Okinyi, Elizabeth Maleche-Obimbo, Dalton C Wamalwa, Grace C John-Stewart","doi":"10.1093/infdis/jiae630","DOIUrl":"https://doi.org/10.1093/infdis/jiae630","url":null,"abstract":"Background Despite immune restoration after initiation of antiretroviral treatment (ART), the risk of tuberculosis (TB) persists in children living with HIV (CLHIV). We determined patterns of immune restoration of mycobacteria-specific T cells following ART in CLHIV. Methods CD4 and CD8 T cell activation and memory phenotype and functional profiles before and 6 months after ART were evaluated in peripheral blood mononuclear cells (PBMCs) from CLHIV enrolled in the PUSH study (NCT02063880) in Nairobi, Kenya. T cell expression of cytokines and activation induced markers (AIM) were measured following stimulation of PBMCs with a pool of 300 peptides from TB (MTB300) or staphylococcal enterotoxin B (SEB). Results Among 47 CLHIV of median age 1.5 years, SEB-induced Th1 cytokine+ and AIM+ CD4 cell frequencies increased significantly after 6 months ART. Although MTB300-specific CD4 and CD8 cell frequency did not increase after ART, polyfunctional capacity of MTB300-specific CD4 cells expressing combinations of Th1 cytokines with CD40L increased significantly after ART. Baseline age, immune activation, and effector memory CD4 levels were associated with less restoration of MTB300-specific polyfunctional CD4 cells, whereas CD4% and levels of naïve CD4 cells following ART were associated with improved MTB300-specific polyfunctional capacity. Conclusions Despite increases in Th1 cytokine production, deficits in mycobacteria-specific CD4 cells persisted 6 months after ART, with higher deficits in older CLHIV with more immunosuppression, higher immune activation, and lower proportion of naïve CD4 cells. These findings may explain persistent TB risk during early ART among CLHIV and identify those at highest risk.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"60 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848926","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}
Kelsie Cassell, Joshua L Warren, Christopher Heneghen, Daniel M Weinberger
Background Multiple studies have shown a positive relationship between weather events and, 1 to 2 weeks later, Legionnaires’ disease (LD) cases. Narrowing this time window of association can help determine whether the mechanism linking rainfall and relative humidity to sporadic LD is direct or indirect. Due to the large number of daily water interactions and low incidence of LD, we propose a new Bayesian modeling approach to disentangle the potential for a direct vs. indirect exposure to precipitation. Methods Incubation period distributions were used to redistribute LD cases to their estimated day of exposure. Then Bayesian distributed lag models were fit to estimate cases per day of exposure with predictor variables for rainfall and absolute humidity. Sensitivity analyses explored the impact of relatively humidity, rainfall post-estimated date of exposure and randomized rainfall to validate our results. Results One standard deviation increase in rainfall 2 and 3 days prior to the date of estimated exposure was associated with an approximately 15% increase in LD risk (per day). When heavy rainfall occurred 0 to 3 days prior to estimated exposure, risk increased by more than 40%, peaking at a 51% increased risk of LD 2 days after heavy rainfall. Discussion Our findings of a 2- and 3-day lag between rainfall and the date of estimated exposure is consistent with an indirect link with rainfall, rather than a same-day exposure. Potential pathways that can indirectly link rainfall to LD cases include rainfall-mediated declines in public water supplies but greater environmental sampling research is needed.
{"title":"Incorporating incubation period distributions to precisely estimate the association between rainfall and Legionella infection","authors":"Kelsie Cassell, Joshua L Warren, Christopher Heneghen, Daniel M Weinberger","doi":"10.1093/infdis/jiae625","DOIUrl":"https://doi.org/10.1093/infdis/jiae625","url":null,"abstract":"Background Multiple studies have shown a positive relationship between weather events and, 1 to 2 weeks later, Legionnaires’ disease (LD) cases. Narrowing this time window of association can help determine whether the mechanism linking rainfall and relative humidity to sporadic LD is direct or indirect. Due to the large number of daily water interactions and low incidence of LD, we propose a new Bayesian modeling approach to disentangle the potential for a direct vs. indirect exposure to precipitation. Methods Incubation period distributions were used to redistribute LD cases to their estimated day of exposure. Then Bayesian distributed lag models were fit to estimate cases per day of exposure with predictor variables for rainfall and absolute humidity. Sensitivity analyses explored the impact of relatively humidity, rainfall post-estimated date of exposure and randomized rainfall to validate our results. Results One standard deviation increase in rainfall 2 and 3 days prior to the date of estimated exposure was associated with an approximately 15% increase in LD risk (per day). When heavy rainfall occurred 0 to 3 days prior to estimated exposure, risk increased by more than 40%, peaking at a 51% increased risk of LD 2 days after heavy rainfall. Discussion Our findings of a 2- and 3-day lag between rainfall and the date of estimated exposure is consistent with an indirect link with rainfall, rather than a same-day exposure. Potential pathways that can indirectly link rainfall to LD cases include rainfall-mediated declines in public water supplies but greater environmental sampling research is needed.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841174","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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