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}
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}
Felipe de Camargo Ribeiro, Karoline Kristina Kemmerich, Juliana Caparroz Gonçale, Juliana Campos Junqueira, Mohammad Mannan, Sunna Nabeela, Arnaldo Lopes Colombo, Priya Uppuluri
Candida albicans catheter-related candidemia is largely driven by microbial adhesion and biofilm formation on central venous catheters. Cells that disperse from these biofilms can enter the bloodstream, spread to distant organs, and sustain the cycle of infection. In this study, we investigated the virulence potential of C. albicans isolates obtained from the blood of catheterized patients experiencing persistent candidemia, comparing them to isolates that were cleared from the bloodstream early in the infection. Our results show that isolates persisting in the bloodstream for four days or longer, despite antifungal treatment, exhibited enhanced adherence, filamentation, and biofilm formation in vitro, along with increased expression of key virulence-related genes. Notably, cells dispersed from second-generation biofilms formed by these persistent isolates displayed even more pronounced pathogenic characteristics, including improved immune evasion. Furthermore, in vivo experiments using Galleria mellonella revealed that persistent isolates were significantly more virulent than their non-persistent counterparts.
{"title":"Candida albicans recovered from persistent candidemia exhibit enhanced virulence traits","authors":"Felipe de Camargo Ribeiro, Karoline Kristina Kemmerich, Juliana Caparroz Gonçale, Juliana Campos Junqueira, Mohammad Mannan, Sunna Nabeela, Arnaldo Lopes Colombo, Priya Uppuluri","doi":"10.1093/infdis/jiae631","DOIUrl":"https://doi.org/10.1093/infdis/jiae631","url":null,"abstract":"Candida albicans catheter-related candidemia is largely driven by microbial adhesion and biofilm formation on central venous catheters. Cells that disperse from these biofilms can enter the bloodstream, spread to distant organs, and sustain the cycle of infection. In this study, we investigated the virulence potential of C. albicans isolates obtained from the blood of catheterized patients experiencing persistent candidemia, comparing them to isolates that were cleared from the bloodstream early in the infection. Our results show that isolates persisting in the bloodstream for four days or longer, despite antifungal treatment, exhibited enhanced adherence, filamentation, and biofilm formation in vitro, along with increased expression of key virulence-related genes. Notably, cells dispersed from second-generation biofilms formed by these persistent isolates displayed even more pronounced pathogenic characteristics, including improved immune evasion. Furthermore, in vivo experiments using Galleria mellonella revealed that persistent isolates were significantly more virulent than their non-persistent counterparts.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848817","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}
Jason Y Tang, Trevor B Chen, Valentina L Kouznetsova, Igor F Tsigelny
Anelloviruses are among the most prevalent viruses within the human virome, detected in over 90% of healthy individuals. Despite their ubiquity, the role of anelloviruses in human health remains elusive. This review examines the potential associations of anelloviruses torque teno virus (TTV), torque teno midi virus (TTMDV), and torque teno mini virus (TTMV) with various cancers, highlighting the mixed conclusions from current epidemiological studies. Anelloviruses may modulate cancer development through abnormal gene fusion, immune response, and toll-like receptor 9 (TLR9) activation. On the other hand, anelloviruses might suppress tumor formation through TTV-derived apoptosis-inducing protein (TAIP) and NF-κB signaling inhibition. The high prevalence of anelloviruses in cancer patients could also be attributed to their immunocompromised status rather than a direct causative role of the viruses. This review underscores the need for more comprehensive studies, including in vitro and in vivo experiments, to clarify the role of anelloviruses in cancer development and progression.
{"title":"Anelloviruses and Cancer","authors":"Jason Y Tang, Trevor B Chen, Valentina L Kouznetsova, Igor F Tsigelny","doi":"10.1093/infdis/jiae626","DOIUrl":"https://doi.org/10.1093/infdis/jiae626","url":null,"abstract":"Anelloviruses are among the most prevalent viruses within the human virome, detected in over 90% of healthy individuals. Despite their ubiquity, the role of anelloviruses in human health remains elusive. This review examines the potential associations of anelloviruses torque teno virus (TTV), torque teno midi virus (TTMDV), and torque teno mini virus (TTMV) with various cancers, highlighting the mixed conclusions from current epidemiological studies. Anelloviruses may modulate cancer development through abnormal gene fusion, immune response, and toll-like receptor 9 (TLR9) activation. On the other hand, anelloviruses might suppress tumor formation through TTV-derived apoptosis-inducing protein (TAIP) and NF-κB signaling inhibition. The high prevalence of anelloviruses in cancer patients could also be attributed to their immunocompromised status rather than a direct causative role of the viruses. This review underscores the need for more comprehensive studies, including in vitro and in vivo experiments, to clarify the role of anelloviruses in cancer development and progression.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"51 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142832095","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}
Natalie Lorenz, Alex James, Tiaan Van Rooyen, Aimee Paterson, Ciara Ramiah, Lauren Carlton, Prachi Sharma, Michael G Baker, Richard Charlewood, Reuben McGregor, Nicole J Moreland
Surges in infections caused by respiratory pathogens have been documented in multiple settings after relaxation of pandemic restrictions. Antibodies to major antigens from respiratory syncytial virus and Group A Streptococcus waned significantly in a longitudinal adult cohort throughout the pandemic. This waning may have contributed to the pathogen-surges that followed.
大流行限制放宽后，呼吸道病原体引起的感染激增在多种情况下都有记录。在整个大流行期间，纵向成人队列中的呼吸道合胞病毒和 A 群链球菌主要抗原抗体明显减弱。这种减弱可能导致了随后的病原体激增。
{"title":"Decline of antibodies to major viral and bacterial respiratory pathogens during the COVID-19 pandemic","authors":"Natalie Lorenz, Alex James, Tiaan Van Rooyen, Aimee Paterson, Ciara Ramiah, Lauren Carlton, Prachi Sharma, Michael G Baker, Richard Charlewood, Reuben McGregor, Nicole J Moreland","doi":"10.1093/infdis/jiae611","DOIUrl":"https://doi.org/10.1093/infdis/jiae611","url":null,"abstract":"Surges in infections caused by respiratory pathogens have been documented in multiple settings after relaxation of pandemic restrictions. Antibodies to major antigens from respiratory syncytial virus and Group A Streptococcus waned significantly in a longitudinal adult cohort throughout the pandemic. This waning may have contributed to the pathogen-surges that followed.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"92 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823301","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}
Jianping Jiang, Lauren Komarow, Carol Hill, Angelique E Boutzoukas, Blake Hanson, Cesar A Arias, Robert A Bonomo, Scott Evans, Yohei Doi, Michael J Satlin, Gregory Weston, Eric Cober, Sandra Liliana Valderrama-Beltran, Soraya Salcedo Mendoza, Zhengyin Liu, Bettina C Fries, Paul Ananth Tambyah, Henry F Chambers, Vance G Fowler, David van Duin, Barry N Kreiswirth, Liang Chen
Background Despite the global public health threat posed by carbapenem-resistant Enterobacter spp., clinical and molecular epidemiological studies on international isolates remain scarce. Historically, the taxonomy of Enterobacter has been challenging, limiting our understanding of the clinical characteristics and outcomes of carbapenemase-producing Enterobacter spp. infections. Methods Hospitalized patients enrolled in the CRACKLE-2 study (ClinicalTrials.gov, NCT03646227) from 2016-2018 with cultures positive for carbapenemase-producing Enterobacter spp. were included. Clinical and microbiologic data were collected from health records. Whole genome sequencing was performed, and the population structures of selected predominant clones were analyzed. Results We enrolled 136 hospitalized patients with carbapenemase-producing Enterobacter spp. from 30 hospitals in 7 countries. Among the 136 isolates, eleven Enterobacter species were identified, with most isolates belonging to E. xiangfangensis (n=81, 60%) and E. hoffmannii (n=17, 13%), and carrying blaKPC (n=106, 78%) and blaNDM (n=12, 9%). Clinical characteristics and outcomes were similar among patients with E. xiangfangensis, E. hoffmannii or the other Enterobacter spp. 30-day mortality was 20% and older age at enrollment (adjusted odds ratio 1.42, 95% confidence interval 1.08-1.87) was associated with increased mortality. Sequence type (ST)171 E. xiangfangensis, ST78 E. hoffmannii, and ST93 E. xiangfangensis were the predominant clones, and the acquisition of fluoroquinolone resistance-associated mutations and carbapenemase-encoding plasmids contributed to their formation and global dissemination. Conclusions Our findings demonstrated that E. xiangfangensis and E. hoffmannii are common species among international carbapenemase-producing Enterobacter spp., potentially linked to the clonal spread of a few predominant clones that have acquired fluoroquinolone resistance and carbapenemase-encoding plasmids.
{"title":"Molecular epidemiology and clinical characterization of carbapenemase-producing Enterobacter spp. from an international cohort","authors":"Jianping Jiang, Lauren Komarow, Carol Hill, Angelique E Boutzoukas, Blake Hanson, Cesar A Arias, Robert A Bonomo, Scott Evans, Yohei Doi, Michael J Satlin, Gregory Weston, Eric Cober, Sandra Liliana Valderrama-Beltran, Soraya Salcedo Mendoza, Zhengyin Liu, Bettina C Fries, Paul Ananth Tambyah, Henry F Chambers, Vance G Fowler, David van Duin, Barry N Kreiswirth, Liang Chen","doi":"10.1093/infdis/jiae616","DOIUrl":"https://doi.org/10.1093/infdis/jiae616","url":null,"abstract":"Background Despite the global public health threat posed by carbapenem-resistant Enterobacter spp., clinical and molecular epidemiological studies on international isolates remain scarce. Historically, the taxonomy of Enterobacter has been challenging, limiting our understanding of the clinical characteristics and outcomes of carbapenemase-producing Enterobacter spp. infections. Methods Hospitalized patients enrolled in the CRACKLE-2 study (ClinicalTrials.gov, NCT03646227) from 2016-2018 with cultures positive for carbapenemase-producing Enterobacter spp. were included. Clinical and microbiologic data were collected from health records. Whole genome sequencing was performed, and the population structures of selected predominant clones were analyzed. Results We enrolled 136 hospitalized patients with carbapenemase-producing Enterobacter spp. from 30 hospitals in 7 countries. Among the 136 isolates, eleven Enterobacter species were identified, with most isolates belonging to E. xiangfangensis (n=81, 60%) and E. hoffmannii (n=17, 13%), and carrying blaKPC (n=106, 78%) and blaNDM (n=12, 9%). Clinical characteristics and outcomes were similar among patients with E. xiangfangensis, E. hoffmannii or the other Enterobacter spp. 30-day mortality was 20% and older age at enrollment (adjusted odds ratio 1.42, 95% confidence interval 1.08-1.87) was associated with increased mortality. Sequence type (ST)171 E. xiangfangensis, ST78 E. hoffmannii, and ST93 E. xiangfangensis were the predominant clones, and the acquisition of fluoroquinolone resistance-associated mutations and carbapenemase-encoding plasmids contributed to their formation and global dissemination. Conclusions Our findings demonstrated that E. xiangfangensis and E. hoffmannii are common species among international carbapenemase-producing Enterobacter spp., potentially linked to the clonal spread of a few predominant clones that have acquired fluoroquinolone resistance and carbapenemase-encoding plasmids.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"44 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815798","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}
Shara Legg, David C Moylan, Neema Kamau, Misty P Latting, Dhruv Devdhara, Sunil K Pati, David K Crossman, Suresh B Boppana, Olaf Kutsch, Steffanie Sabbaj
While the role of breastmilk antibodies to protect infants from CMV has been investigated, the role of T-cells, have received little attention. We compared the frequency of memory T-cell populations in breastmilk between mothers of infants who acquired breastmilk HCMV (transmitters) and those with uninfected infants (non-transmitters). Non-transmitter moms had an increased frequency of CD8+ effector memory T-cells (Tem) in their breastmilk. In addition, we describe tissue resident memory T-cells (Trm) in breastmilk and demonstrate most were Tem. We present data that non-transmitter moms have increased frequency of CD8+ Trm T-cells in their breastmilk when compared to transmitters and that Trm frequency is inversely correlated with breastmilk HCMV VL. Lastly, using scRNA-seq analysis we identified a unique population of T-cells in non-transmitters and demonstrate that these cells comprise CD8+ Trm T-cells. These studies suggest that CD8+ Trm T-cells may play a role in preventing viral transmission via breastmilk to infants.
{"title":"Tissue Resident CD8+T-cells as mediators of protective immunity in breastmilk transmission of HCMV","authors":"Shara Legg, David C Moylan, Neema Kamau, Misty P Latting, Dhruv Devdhara, Sunil K Pati, David K Crossman, Suresh B Boppana, Olaf Kutsch, Steffanie Sabbaj","doi":"10.1093/infdis/jiae618","DOIUrl":"https://doi.org/10.1093/infdis/jiae618","url":null,"abstract":"While the role of breastmilk antibodies to protect infants from CMV has been investigated, the role of T-cells, have received little attention. We compared the frequency of memory T-cell populations in breastmilk between mothers of infants who acquired breastmilk HCMV (transmitters) and those with uninfected infants (non-transmitters). Non-transmitter moms had an increased frequency of CD8+ effector memory T-cells (Tem) in their breastmilk. In addition, we describe tissue resident memory T-cells (Trm) in breastmilk and demonstrate most were Tem. We present data that non-transmitter moms have increased frequency of CD8+ Trm T-cells in their breastmilk when compared to transmitters and that Trm frequency is inversely correlated with breastmilk HCMV VL. Lastly, using scRNA-seq analysis we identified a unique population of T-cells in non-transmitters and demonstrate that these cells comprise CD8+ Trm T-cells. These studies suggest that CD8+ Trm T-cells may play a role in preventing viral transmission via breastmilk to infants.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"39 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809739","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}
Laura M Hagenah, Tomas Yeo, Kyra A Schindler, Jin H Jeon, Talia S Bloxham, Jennifer L Small-Saunders, Sachel Mok, David A Fidock
Background Piperaquine, used in combination with dihydroartemisinin, has been identified as a promising partner drug for uncomplicated treatment and chemoprevention of Plasmodium falciparum malaria in Africa. In light of the earlier spread of piperaquine resistance in Southeast Asia, mediated primarily by mutations in the drug efflux transporter PfCRT, we have explored whether PfCRT mutations would represent a probable path to piperaquine resistance becoming established in Africa. Methods We edited PfCRT mutations known to mediate piperaquine resistance in Southeast Asia into P. falciparum asexual blood stage parasites expressing three prevalent African mutant PfCRT haplotypes. Gene-edited clones were profiled in antimalarial concentration-response and competitive fitness assays. Results pfcrt-edited parasites expressing the contemporary Southeast Asian T93S or I218F mutations added to the GB4 and Cam783 haplotypes common in Africa did not mediate piperaquine resistance, with partial survival only at low drug concentrations. In contrast, parasites expressing these mutations on the rare PfCRT FCB haplotype, observed mostly in North-East Africa, acquired a moderate level of piperaquine resistance. Dd2GB4, Dd2Cam783, and Dd2FCB lines edited to express the T93S or I218F mutations showed increased susceptibility to chloroquine. Piperaquine-resistant African PfCRT isoforms conferred a substantial fitness cost, manifesting as reduced asexual blood stage parasite growth rates. Conclusions These findings suggest that piperaquine-resistant PfCRT mutations that emerged in Southeast Asia mediate resistance only in a limited subset of African PfCRT haplotypes, with fitness costs that we suspect would likely preclude dissemination in high-transmission malaria-endemic African regions.
{"title":"Plasmodium falciparum African PfCRT Mutant Isoforms Conducive to Piperaquine Resistance are Infrequent and Impart a Major Fitness Cost","authors":"Laura M Hagenah, Tomas Yeo, Kyra A Schindler, Jin H Jeon, Talia S Bloxham, Jennifer L Small-Saunders, Sachel Mok, David A Fidock","doi":"10.1093/infdis/jiae617","DOIUrl":"https://doi.org/10.1093/infdis/jiae617","url":null,"abstract":"Background Piperaquine, used in combination with dihydroartemisinin, has been identified as a promising partner drug for uncomplicated treatment and chemoprevention of Plasmodium falciparum malaria in Africa. In light of the earlier spread of piperaquine resistance in Southeast Asia, mediated primarily by mutations in the drug efflux transporter PfCRT, we have explored whether PfCRT mutations would represent a probable path to piperaquine resistance becoming established in Africa. Methods We edited PfCRT mutations known to mediate piperaquine resistance in Southeast Asia into P. falciparum asexual blood stage parasites expressing three prevalent African mutant PfCRT haplotypes. Gene-edited clones were profiled in antimalarial concentration-response and competitive fitness assays. Results pfcrt-edited parasites expressing the contemporary Southeast Asian T93S or I218F mutations added to the GB4 and Cam783 haplotypes common in Africa did not mediate piperaquine resistance, with partial survival only at low drug concentrations. In contrast, parasites expressing these mutations on the rare PfCRT FCB haplotype, observed mostly in North-East Africa, acquired a moderate level of piperaquine resistance. Dd2GB4, Dd2Cam783, and Dd2FCB lines edited to express the T93S or I218F mutations showed increased susceptibility to chloroquine. Piperaquine-resistant African PfCRT isoforms conferred a substantial fitness cost, manifesting as reduced asexual blood stage parasite growth rates. Conclusions These findings suggest that piperaquine-resistant PfCRT mutations that emerged in Southeast Asia mediate resistance only in a limited subset of African PfCRT haplotypes, with fitness costs that we suspect would likely preclude dissemination in high-transmission malaria-endemic African regions.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809741","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}
Cesc Bertran-Cobo, Elin Dumont, Naqib Rafieqin Noordin, Meng-Yee Lai, William Stone, Kevin K A Tetteh, Chris Drakeley, Sanjeev Krishna, Yee-Ling Lau, Samuel C Wassmer
Background Malaria remains a major public health concern with substantial morbidity and mortality worldwide. In Malaysia, the emergence of Plasmodium knowlesi has led to a surge in zoonotic malaria cases and deaths in recent years. Signs of cerebral involvement have been observed in a noncomatose, fatal case of knowlesi infection, but the potential impact of this malaria species on the brain remains unexplored. To address this gap, we investigated circulating levels of brain injury, inflammation, and vascular biomarkers in a cohort of knowlesi-infected patients and controls. Methods Archived plasma samples from 19 Malaysian patients with symptomatic knowlesi infection and 19 healthy, age-matched controls were analyzed. Fifty-two biomarkers of brain injury, inflammation, and vascular activation were measured. Wilcoxon tests were used to examine group differences, and biomarker profiles were explored through hierarchical clustering heatmap analysis. Results Bonferroni-corrected analyses revealed significantly elevated brain injury biomarker levels in knowlesi-infected patients, including S100B (P < .0001), Tau (P = .0007), UCH-L1 (P < .0001), αSyn (P < .0001), Park7 (P = .0006), NRGN (P = .0022), and TDP-43 (P = .005). Compared to controls, levels were lower in the infected group for BDNF (P < .0001), CaBD (P < .0001), CNTN1 (P < .0001), NCAM-1 (P < .0001), GFAP (P = .0013), and KLK6 (P = .0126). Hierarchical clustering revealed distinct group profiles for brain injury and vascular activation biomarkers. Conclusions Our findings highlight for the first time a potential impact of P knowlesi infection on the brain, with specific changes in cerebral injury and endothelial activation biomarker profiles. Further studies are warranted to investigate the pathophysiology and clinical significance of these altered markers, through neuroimaging and long-term neurocognitive assessments.
{"title":"Plasmodium knowlesi Infection Is Associated With Elevated Circulating Biomarkers of Brain Injury and Endothelial Activation","authors":"Cesc Bertran-Cobo, Elin Dumont, Naqib Rafieqin Noordin, Meng-Yee Lai, William Stone, Kevin K A Tetteh, Chris Drakeley, Sanjeev Krishna, Yee-Ling Lau, Samuel C Wassmer","doi":"10.1093/infdis/jiae553","DOIUrl":"https://doi.org/10.1093/infdis/jiae553","url":null,"abstract":"Background Malaria remains a major public health concern with substantial morbidity and mortality worldwide. In Malaysia, the emergence of Plasmodium knowlesi has led to a surge in zoonotic malaria cases and deaths in recent years. Signs of cerebral involvement have been observed in a noncomatose, fatal case of knowlesi infection, but the potential impact of this malaria species on the brain remains unexplored. To address this gap, we investigated circulating levels of brain injury, inflammation, and vascular biomarkers in a cohort of knowlesi-infected patients and controls. Methods Archived plasma samples from 19 Malaysian patients with symptomatic knowlesi infection and 19 healthy, age-matched controls were analyzed. Fifty-two biomarkers of brain injury, inflammation, and vascular activation were measured. Wilcoxon tests were used to examine group differences, and biomarker profiles were explored through hierarchical clustering heatmap analysis. Results Bonferroni-corrected analyses revealed significantly elevated brain injury biomarker levels in knowlesi-infected patients, including S100B (P &lt; .0001), Tau (P = .0007), UCH-L1 (P &lt; .0001), αSyn (P &lt; .0001), Park7 (P = .0006), NRGN (P = .0022), and TDP-43 (P = .005). Compared to controls, levels were lower in the infected group for BDNF (P &lt; .0001), CaBD (P &lt; .0001), CNTN1 (P &lt; .0001), NCAM-1 (P &lt; .0001), GFAP (P = .0013), and KLK6 (P = .0126). Hierarchical clustering revealed distinct group profiles for brain injury and vascular activation biomarkers. Conclusions Our findings highlight for the first time a potential impact of P knowlesi infection on the brain, with specific changes in cerebral injury and endothelial activation biomarker profiles. Further studies are warranted to investigate the pathophysiology and clinical significance of these altered markers, through neuroimaging and long-term neurocognitive assessments.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805304","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}
Ana K Pitol, Siobhan Richards, Patrick Mirindi, Hibak O Mahamed, April Baller, Grant L Hughes, Sara E Beck
Background The declaration of mpox as a Public Health Emergency of International Concern highlights the need for interventions to interrupt virus transmission, including transmission via fabrics. Current World Health Organization guidance on clothes washing is based on a general consensus of virus inactivation; however, there is uncertainty about the efficacy of laundry detergents and disinfectants or the reduction of risk achieved by washing clothes for monkeypox virus (MPXV) specifically. Methods This study investigates the efficacy of manual washing for inactivating MPXV from clothes. Using a simulated washing method, we evaluated the efficacy of commonly-used laundry products and high temperature water for inactivating MPXV on fabrics. Cotton and polyester fabrics were inoculated with MPXV for 1 min, placed in a microcentrifuge tube containing water or water with test product for 20 minutes, with agitation every 5 min to simulate manual washing. Results Sodium hypochlorite, liquid sanitizer, and two powdered laundry detergents dissolved in room temperature water, as well as 70-degree water alone, completely inactivated MPXV (>3 log10reduction or >99.9% inactivation) on both cotton and polyester fabrics. Conclusion Given the expected concentrations of MPXV on fabrics, the low transfer rate of viruses from porous surfaces to skin, the effective inactivation of laundry processes, and the expected doses required for infection, we expect the risk of transmission after laundering contaminated fabrics to be low. This study provides evidence to support WHO guidance for MPXV inactivation, reducing the viral load on fabrics to prevent the spread of mpox in both healthcare and household settings.
{"title":"Efficacy of laundry practices in eliminating monkeypox virus (MPXV) from fabrics","authors":"Ana K Pitol, Siobhan Richards, Patrick Mirindi, Hibak O Mahamed, April Baller, Grant L Hughes, Sara E Beck","doi":"10.1093/infdis/jiae606","DOIUrl":"https://doi.org/10.1093/infdis/jiae606","url":null,"abstract":"Background The declaration of mpox as a Public Health Emergency of International Concern highlights the need for interventions to interrupt virus transmission, including transmission via fabrics. Current World Health Organization guidance on clothes washing is based on a general consensus of virus inactivation; however, there is uncertainty about the efficacy of laundry detergents and disinfectants or the reduction of risk achieved by washing clothes for monkeypox virus (MPXV) specifically. Methods This study investigates the efficacy of manual washing for inactivating MPXV from clothes. Using a simulated washing method, we evaluated the efficacy of commonly-used laundry products and high temperature water for inactivating MPXV on fabrics. Cotton and polyester fabrics were inoculated with MPXV for 1 min, placed in a microcentrifuge tube containing water or water with test product for 20 minutes, with agitation every 5 min to simulate manual washing. Results Sodium hypochlorite, liquid sanitizer, and two powdered laundry detergents dissolved in room temperature water, as well as 70-degree water alone, completely inactivated MPXV (&gt;3 log10reduction or &gt;99.9% inactivation) on both cotton and polyester fabrics. Conclusion Given the expected concentrations of MPXV on fabrics, the low transfer rate of viruses from porous surfaces to skin, the effective inactivation of laundry processes, and the expected doses required for infection, we expect the risk of transmission after laundering contaminated fabrics to be low. This study provides evidence to support WHO guidance for MPXV inactivation, reducing the viral load on fabrics to prevent the spread of mpox in both healthcare and household settings.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805349","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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