Darren Suryawijaya Ong, Claire von Mollendorf, Kim Mulholland, Lien Anh Ha Do
Background Measles infections cause significant morbidity and mortality in low- and middle-income countries (LMICs), especially infants under nine months. Measles seroprevalence data in infants too young to be vaccinated can identify immunity gaps to inform immunisation strategies. Our systematic review and meta-analysis describes measles seroprevalence in infants <9 months in LMICs. Methods We systematically searched journal articles and conference abstracts from 1 January 2018 to 25 December 2024 across 10 databases and registers (PROSPERO: CRD42023429586). We included observational studies presenting measles antibody seroprevalence data from infants <9 months in LMICs. Studies underwent dual reviewer screening and risk of bias was assessed using an adapted Joanna Briggs Institute tool. Seropositivity estimates were pooled using a random-effects inverse variance model. We performed subgroup analyses by country income level, measles vaccine coverage and measles incidence. Results Among 1421 studies identified, 34 were included. Most studies were from middle-income countries (n=30/34) using hospital/health-centre data (n=22/34). Risk of bias was generally low or moderate (n=33/34). The meta-analysis included 20 studies (N=8230 infants) with high inter-study heterogeneity. Pooled seropositivity was highest at birth (81%, 95% CI: 75-88), decreasing to 30% (95% CI: 24-35) by four months, and lowest at seven months (18%, 95% CI: 0-41). Subgroup analyses showed minimal differences between categories. Conclusions Seventy percent of infants are seronegative by four months old and unprotected from measles before their first vaccine dose at 9-12 months. Early administration of measles-containing vaccines could provide sustained protection throughout infancy.
{"title":"Measles seroprevalence in infants under nine months of age in low- and middle-income countries: a systematic review and meta-analysis","authors":"Darren Suryawijaya Ong, Claire von Mollendorf, Kim Mulholland, Lien Anh Ha Do","doi":"10.1093/infdis/jiaf177","DOIUrl":"https://doi.org/10.1093/infdis/jiaf177","url":null,"abstract":"Background Measles infections cause significant morbidity and mortality in low- and middle-income countries (LMICs), especially infants under nine months. Measles seroprevalence data in infants too young to be vaccinated can identify immunity gaps to inform immunisation strategies. Our systematic review and meta-analysis describes measles seroprevalence in infants &lt;9 months in LMICs. Methods We systematically searched journal articles and conference abstracts from 1 January 2018 to 25 December 2024 across 10 databases and registers (PROSPERO: CRD42023429586). We included observational studies presenting measles antibody seroprevalence data from infants &lt;9 months in LMICs. Studies underwent dual reviewer screening and risk of bias was assessed using an adapted Joanna Briggs Institute tool. Seropositivity estimates were pooled using a random-effects inverse variance model. We performed subgroup analyses by country income level, measles vaccine coverage and measles incidence. Results Among 1421 studies identified, 34 were included. Most studies were from middle-income countries (n=30/34) using hospital/health-centre data (n=22/34). Risk of bias was generally low or moderate (n=33/34). The meta-analysis included 20 studies (N=8230 infants) with high inter-study heterogeneity. Pooled seropositivity was highest at birth (81%, 95% CI: 75-88), decreasing to 30% (95% CI: 24-35) by four months, and lowest at seven months (18%, 95% CI: 0-41). Subgroup analyses showed minimal differences between categories. Conclusions Seventy percent of infants are seronegative by four months old and unprotected from measles before their first vaccine dose at 9-12 months. Early administration of measles-containing vaccines could provide sustained protection throughout infancy.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143775288","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}
Isamu Tsuji, David Dominguez, Jonathan Hernandez, Eloi Kpamegan, José Victor Zambrana, Angel Balmaseda, Hansi Dean, Mayuri Sharma, Eva Harris
Antibody avidity is indicative of antibody affinity maturation following virus infection or vaccination. To determine correlation between preexisting anti-dengue virus (DENV) antibody avidity and secondary DENV exposure outcomes, we assessed anti-DENV antibody avidity, represented as avidity index (antibody response/dissociation rate) in sera of Nicaraguan Pediatric Dengue Cohort Study participants prior to symptomatic or inapparent secondary DENV infections. The avidity index was significantly higher in participants who subsequently developed inapparent versus symptomatic infections. Risk factor analysis suggested that odds of inapparent DENV infection increase as avidity index increases. Antibody avidity index is an important parameter for characterizing protective DENV immune responses.
{"title":"Anti-Dengue Virus Antibody Avidity Correlates with Protection Against Symptomatic Dengue Virus Infection","authors":"Isamu Tsuji, David Dominguez, Jonathan Hernandez, Eloi Kpamegan, José Victor Zambrana, Angel Balmaseda, Hansi Dean, Mayuri Sharma, Eva Harris","doi":"10.1093/infdis/jiaf171","DOIUrl":"https://doi.org/10.1093/infdis/jiaf171","url":null,"abstract":"Antibody avidity is indicative of antibody affinity maturation following virus infection or vaccination. To determine correlation between preexisting anti-dengue virus (DENV) antibody avidity and secondary DENV exposure outcomes, we assessed anti-DENV antibody avidity, represented as avidity index (antibody response/dissociation rate) in sera of Nicaraguan Pediatric Dengue Cohort Study participants prior to symptomatic or inapparent secondary DENV infections. The avidity index was significantly higher in participants who subsequently developed inapparent versus symptomatic infections. Risk factor analysis suggested that odds of inapparent DENV infection increase as avidity index increases. Antibody avidity index is an important parameter for characterizing protective DENV immune responses.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143775337","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 Linezolid shows therapeutic potential for pediatric gram-positive bacterial central nervous system infections (CNSIs). However, its efficacy, safety profile, and cerebrospinal fluid (CSF) pharmacokinetics require detailed evaluation. Methods This prospective two-center observational study enrolled children with confirmed or suspected gram-positive CNSIs. Clinical outcomes and adverse events were compared between linezolid-treated patients and a matched vancomycin cohort. Population pharmacokinetic (PopPK) modeling with nonlinear mixed-effects analysis quantified linezolid exposure in plasma and CSF. Results Among 45 matched pediatric CNSIs patients per group, linezolid demonstrated a 91.1% clinical response rate and 68.9% cure rate (vancomycin cure rate: 68.9%). However, non-inferiority to vancomycin was not established for the primary endpoint, possibly influenced by intergroup baseline variability and extended treatment duration. Adverse events occurred more frequently with linezolid, including gastrointestinal (48.9% vs. 24.4%, p = 0.02) and hematologic effects (73.3% vs. 53.3%, p = 0.05). Plasma trough concentrations > 7 µg/mL were correlated with elevated risk of leukopenia and neutropenia (odds ratio [OR] 9.38, 95% confidence interval [CI] 1.21–72.6; and OR 40.2, 95% CI 2.15–748.50). However, no treatment discontinuations occurred due to adverse events. The PopPK model analyzed 135 linezolid concentrations (90 plasma/45 CSF), identifying body weight as the primary covariate influencing distribution. Plasma and CSF trough concentrations showed a strong correlation (r = 0.87, 95% CI 0.75–0.98). Conclusions Linezolid demonstrated favorable clinical efficacy and tolerability in pediatric CNSIs, with CSF concentrations that correlated with plasma levels and exhibited predictable pharmacokinetics.
{"title":"Effectiveness, safety, and pharmacokinetics of linezolid in pediatric bacterial central nervous system infections","authors":"Lvchang Zhu, Xinxin Zeng, Yi Shi, Yuhang Wu, Xiaoshan Zhang, Shanshan Xu, Xuben Yu, Lisu Huang","doi":"10.1093/infdis/jiaf169","DOIUrl":"https://doi.org/10.1093/infdis/jiaf169","url":null,"abstract":"Background Linezolid shows therapeutic potential for pediatric gram-positive bacterial central nervous system infections (CNSIs). However, its efficacy, safety profile, and cerebrospinal fluid (CSF) pharmacokinetics require detailed evaluation. Methods This prospective two-center observational study enrolled children with confirmed or suspected gram-positive CNSIs. Clinical outcomes and adverse events were compared between linezolid-treated patients and a matched vancomycin cohort. Population pharmacokinetic (PopPK) modeling with nonlinear mixed-effects analysis quantified linezolid exposure in plasma and CSF. Results Among 45 matched pediatric CNSIs patients per group, linezolid demonstrated a 91.1% clinical response rate and 68.9% cure rate (vancomycin cure rate: 68.9%). However, non-inferiority to vancomycin was not established for the primary endpoint, possibly influenced by intergroup baseline variability and extended treatment duration. Adverse events occurred more frequently with linezolid, including gastrointestinal (48.9% vs. 24.4%, p = 0.02) and hematologic effects (73.3% vs. 53.3%, p = 0.05). Plasma trough concentrations &gt; 7 µg/mL were correlated with elevated risk of leukopenia and neutropenia (odds ratio [OR] 9.38, 95% confidence interval [CI] 1.21–72.6; and OR 40.2, 95% CI 2.15–748.50). However, no treatment discontinuations occurred due to adverse events. The PopPK model analyzed 135 linezolid concentrations (90 plasma/45 CSF), identifying body weight as the primary covariate influencing distribution. Plasma and CSF trough concentrations showed a strong correlation (r = 0.87, 95% CI 0.75–0.98). Conclusions Linezolid demonstrated favorable clinical efficacy and tolerability in pediatric CNSIs, with CSF concentrations that correlated with plasma levels and exhibited predictable pharmacokinetics.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"60 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143775335","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}
Umesh Chopra, Maria Kondooparambil Sabu, Raju S Rajmani, Ayushi Devendrasingh Chaudhary, Shashi Kumar Gupta, Dipshikha Chakravortty
The upregulation of PD-L1 by various pathogens is a recognized strategy to evade the adaptive immune response. Salmonella infection also upregulates PD-L1 levels; however, the underlying mechanism remains unclear. Our study reveals that this upregulation is mediated by Salmonella pathogenicity island 2 (SPI-2) effectors, as PFA-fixed and STMΔssaV fail to alter PD-L1 levels. We have further investigated the role of the SPI-2 effector SseL (a deubiquitinase) in PD-L1 upregulation, and our study reveals SseL to be crucial for upregulating PD-L1 in vitro as well as in vivo murine models. STMΔsseL exhibits colonization defects in secondary infection sites such as the liver and spleen. Notably, STMΔsseL-infected mice show earlier mortality associated with heightened inflammation. Mechanistically, SseL stabilizes β-catenin, which translocates to the nucleus and leads to PD-L1 transcription, which is abrogated by the β-catenin/TCF inhibitor FH535. Collectively, our study elucidates the mechanism by which Salmonella mediates immune suppression through PD-L1 upregulation.
{"title":"Salmonella effector SseL induces PD-L1 up-regulation and T cell inactivation via β-catenin signalling axis","authors":"Umesh Chopra, Maria Kondooparambil Sabu, Raju S Rajmani, Ayushi Devendrasingh Chaudhary, Shashi Kumar Gupta, Dipshikha Chakravortty","doi":"10.1093/infdis/jiaf131","DOIUrl":"https://doi.org/10.1093/infdis/jiaf131","url":null,"abstract":"The upregulation of PD-L1 by various pathogens is a recognized strategy to evade the adaptive immune response. Salmonella infection also upregulates PD-L1 levels; however, the underlying mechanism remains unclear. Our study reveals that this upregulation is mediated by Salmonella pathogenicity island 2 (SPI-2) effectors, as PFA-fixed and STMΔssaV fail to alter PD-L1 levels. We have further investigated the role of the SPI-2 effector SseL (a deubiquitinase) in PD-L1 upregulation, and our study reveals SseL to be crucial for upregulating PD-L1 in vitro as well as in vivo murine models. STMΔsseL exhibits colonization defects in secondary infection sites such as the liver and spleen. Notably, STMΔsseL-infected mice show earlier mortality associated with heightened inflammation. Mechanistically, SseL stabilizes β-catenin, which translocates to the nucleus and leads to PD-L1 transcription, which is abrogated by the β-catenin/TCF inhibitor FH535. Collectively, our study elucidates the mechanism by which Salmonella mediates immune suppression through PD-L1 upregulation.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"49 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653431","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}
Jessica Y Wong, Justin K Cheung, Anne M Presanis, Daniela De Angelis, A Danielle Iuliano, Peng Wu, Benjamin J Cowling
Background Assessing the impact of influenza epidemics provides useful information to assess both population and healthcare system burden and can inform prevention and control measures for seasonal epidemics, such as vaccination and antivirals. Furthermore, it is an important component of pandemic preparedness. Methods We assessed and compared three influenza impact parameters: influenza-associated excess respiratory mortality, hospitalizations and ICU admissions, under the World Health Organization Pandemic Influenza Severity Assessment framework. We used a generalized additive model to estimate these parameters from 1998 through 2019 in Hong Kong based on historical mortality, hospitalization, ICU admission and influenza surveillance data. Intensity thresholds by influenza type were estimated using quantiles from the distribution of peak values of the parameters from 1998 through 2017 and were compared to the real-time estimates of excess parameters in 2018-2019. Influenza death and hospitalization data were used for validation. Findings There was good agreement between the different impact parameters after comparing the 2018-2019 data to the thresholds. The 2019 influenza A epidemic was characterized as having moderate impact overall and in all age groups, except 0-64 years for whom the excess ICU impact was high; whereas the 2018 influenza B epidemic was characterized as having very high impact overall and in all age groups. Interpretation The impact of influenza epidemics can vary from year to year. The PISA framework facilitates the impact assessment of seasonal influenza epidemics using different data sources and can be implemented in both real-time or at the end of seasons as policy makers and public health officials prepare for the next seasonal epidemic.
{"title":"Assessing the impact of influenza epidemics in Hong Kong","authors":"Jessica Y Wong, Justin K Cheung, Anne M Presanis, Daniela De Angelis, A Danielle Iuliano, Peng Wu, Benjamin J Cowling","doi":"10.1093/infdis/jiaf140","DOIUrl":"https://doi.org/10.1093/infdis/jiaf140","url":null,"abstract":"Background Assessing the impact of influenza epidemics provides useful information to assess both population and healthcare system burden and can inform prevention and control measures for seasonal epidemics, such as vaccination and antivirals. Furthermore, it is an important component of pandemic preparedness. Methods We assessed and compared three influenza impact parameters: influenza-associated excess respiratory mortality, hospitalizations and ICU admissions, under the World Health Organization Pandemic Influenza Severity Assessment framework. We used a generalized additive model to estimate these parameters from 1998 through 2019 in Hong Kong based on historical mortality, hospitalization, ICU admission and influenza surveillance data. Intensity thresholds by influenza type were estimated using quantiles from the distribution of peak values of the parameters from 1998 through 2017 and were compared to the real-time estimates of excess parameters in 2018-2019. Influenza death and hospitalization data were used for validation. Findings There was good agreement between the different impact parameters after comparing the 2018-2019 data to the thresholds. The 2019 influenza A epidemic was characterized as having moderate impact overall and in all age groups, except 0-64 years for whom the excess ICU impact was high; whereas the 2018 influenza B epidemic was characterized as having very high impact overall and in all age groups. Interpretation The impact of influenza epidemics can vary from year to year. The PISA framework facilitates the impact assessment of seasonal influenza epidemics using different data sources and can be implemented in both real-time or at the end of seasons as policy makers and public health officials prepare for the next seasonal epidemic.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"56 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661192","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}
Longitudinal measurements of respiratory syncytial virus (RSV) immunity over 4 winter seasons reveal that viral neutralization titers, RSV prefusion F protein (pre-F)–specific immunoglobulin M and immunoglobulin G (IgG) levels, and RSV antibody–dependent cellular phagocytosis function gradually returned to prepandemic levels in female healthcare and school workers of childbearing age after 2 winter seasons, following the resurgence of RSV cases in the Vancouver metropolitan region (British Columbia, Canada). In contrast, pre-F IgG avidity profiles remained unchanged. These findings support the notion that repeated viral infections are necessary to maintain high RSV antibody levels in the population.
{"title":"Recovery of Antibody Immunity After a Resurgence of Respiratory Syncytial Virus Infections","authors":"Frederic Reicherz, Marina Viñeta Paramo, Jeffrey N Bone, Alexanne Lavoie, Sirui Li, Liam Golding, Agatha Jassem, Allison Watts, Bahaa Abu-Raya, Pascal M Lavoie","doi":"10.1093/infdis/jiaf101","DOIUrl":"https://doi.org/10.1093/infdis/jiaf101","url":null,"abstract":"Longitudinal measurements of respiratory syncytial virus (RSV) immunity over 4 winter seasons reveal that viral neutralization titers, RSV prefusion F protein (pre-F)–specific immunoglobulin M and immunoglobulin G (IgG) levels, and RSV antibody–dependent cellular phagocytosis function gradually returned to prepandemic levels in female healthcare and school workers of childbearing age after 2 winter seasons, following the resurgence of RSV cases in the Vancouver metropolitan region (British Columbia, Canada). In contrast, pre-F IgG avidity profiles remained unchanged. These findings support the notion that repeated viral infections are necessary to maintain high RSV antibody levels in the population.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653433","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}
Tarek El Hindi, Maria Theresa Alera, Lulu Bravo, Edson Duarte Moreira, Reynaldo Dietze, Ana Lucia Oliveira, Veerachai Watanaveeradej, Yuan Zhao, Ivo Sonderegger, Vianney Tricou, Nicolas Folschweiller, Shibadas Biswal
Background TAK-003 has been shown to be well tolerated and effective against symptomatic dengue disease and hospitalization, irrespective of baseline serostatus. Most infections are asymptomatic/subclinical. This study assessed whether TAK-003 could protect against asymptomatic/subclinical infections by evaluating increased neutrlizing antibody titers (NAb) after natural infection. Methods DEN-301(NCT02747927) is a phase 3 trial among 4- to 16-year-old participants who received 2 doses of TAK-003/placebo 3 months apart. These exploratory analyses used NAb measured during the trial. As no well-accepted definition for asymptomatic infection exists, 3 algorithms were evaluated: (1) 4-fold increase in NAb, (2) 4-fold increase in NAb and a minimum titer of 40, and (3) 4-fold increase in NAb and a minimum titer of 4-fold lower-limit-of-quantification. Months 4-9, 9-15, and 15-27 after first vaccination were analyzed. Results NAb from 3765 participants were analyzed. From months 4-9, vaccine efficacy (VE) against asymptomatic infection was 51.1%(30.4 to 65.6), 36.1%(6.7–56.3), and 27.3%(−8.2 to 51.2) for algorithms 1, 2, and 3, respectively. VE in baseline seropositive participants per algorithms 1, 2, and 3 was 54.8%(28.8 to 71.3), 47.9%(16.8 to 67.4), and 44.3%(9.9 to 65.6), respectively, and in baseline seronegative participants was 44.4%(2.1 to 68.4), 4.6%(–85.1 to 50.8), and −29.3%(−172.1 to 38.6), respectively. VE against asymptomatic infection gradually decreased from months 4-9 to 9-15 and months 9-15 to 15-27. Conclusions The variability in VE algorithms indicates challenges in accurately assessing VE against asymptomatic infections. TAK-003 had a modest impact on asymptomatic dengue infections in the first months post-vaccination, mainly in baseline seropositive participants.
{"title":"Estimated Efficacy of TAK-003 Against Asymptomatic Dengue Infection in Children/Adolescents Participating in the DEN-301 Trial in Asia Pacific and Latin America","authors":"Tarek El Hindi, Maria Theresa Alera, Lulu Bravo, Edson Duarte Moreira, Reynaldo Dietze, Ana Lucia Oliveira, Veerachai Watanaveeradej, Yuan Zhao, Ivo Sonderegger, Vianney Tricou, Nicolas Folschweiller, Shibadas Biswal","doi":"10.1093/infdis/jiaf145","DOIUrl":"https://doi.org/10.1093/infdis/jiaf145","url":null,"abstract":"Background TAK-003 has been shown to be well tolerated and effective against symptomatic dengue disease and hospitalization, irrespective of baseline serostatus. Most infections are asymptomatic/subclinical. This study assessed whether TAK-003 could protect against asymptomatic/subclinical infections by evaluating increased neutrlizing antibody titers (NAb) after natural infection. Methods DEN-301(NCT02747927) is a phase 3 trial among 4- to 16-year-old participants who received 2 doses of TAK-003/placebo 3 months apart. These exploratory analyses used NAb measured during the trial. As no well-accepted definition for asymptomatic infection exists, 3 algorithms were evaluated: (1) 4-fold increase in NAb, (2) 4-fold increase in NAb and a minimum titer of 40, and (3) 4-fold increase in NAb and a minimum titer of 4-fold lower-limit-of-quantification. Months 4-9, 9-15, and 15-27 after first vaccination were analyzed. Results NAb from 3765 participants were analyzed. From months 4-9, vaccine efficacy (VE) against asymptomatic infection was 51.1%(30.4 to 65.6), 36.1%(6.7–56.3), and 27.3%(−8.2 to 51.2) for algorithms 1, 2, and 3, respectively. VE in baseline seropositive participants per algorithms 1, 2, and 3 was 54.8%(28.8 to 71.3), 47.9%(16.8 to 67.4), and 44.3%(9.9 to 65.6), respectively, and in baseline seronegative participants was 44.4%(2.1 to 68.4), 4.6%(–85.1 to 50.8), and −29.3%(−172.1 to 38.6), respectively. VE against asymptomatic infection gradually decreased from months 4-9 to 9-15 and months 9-15 to 15-27. Conclusions The variability in VE algorithms indicates challenges in accurately assessing VE against asymptomatic infections. TAK-003 had a modest impact on asymptomatic dengue infections in the first months post-vaccination, mainly in baseline seropositive participants.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653434","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}
Marisa Salazar, Paul Schaughency, Thomas B Nutman, Sasisekhar Bennuru
Human lymphatic filariasis (LF) is primarily caused by helminth parasites Wuchereria bancrofti (Wb) and Brugia malayi (Bm). Detecting parasitic circulating cell free nucleic acids (ccfDNA/ccfRNA) in plasma is a promising approach for detection of active infections. Plasma-RNAseq analyses from individuals with active Wb infection and uninfected controls identified 6 RNA targets that were specific to Wb and/or Bm. Assays developed to detect either ccfDNA and ccfRNA were successfully used in Wb-infected individuals, but DNA-based assays targeting WbTR1 was found to be the most sensitive biomarker of Wb circulating cell free nucleic acids. Plasma-derived ccfDNA was identified in 71 % (of all mf-positive individuals) Wb infection from India, Cook Islands, Mali, Haiti and Guyana. Following definitive treatment, time course analyses indicated that WbTR1 ccfDNA levels were undetectable within a year. Overall, ccfDNA/RNA detection in LF holds promise for assessment of infection and treatment response in Wb and Bm infections.
{"title":"Circulating cell-free Nucleic Acid Detection for W. bancrofti infections","authors":"Marisa Salazar, Paul Schaughency, Thomas B Nutman, Sasisekhar Bennuru","doi":"10.1093/infdis/jiaf147","DOIUrl":"https://doi.org/10.1093/infdis/jiaf147","url":null,"abstract":"Human lymphatic filariasis (LF) is primarily caused by helminth parasites Wuchereria bancrofti (Wb) and Brugia malayi (Bm). Detecting parasitic circulating cell free nucleic acids (ccfDNA/ccfRNA) in plasma is a promising approach for detection of active infections. Plasma-RNAseq analyses from individuals with active Wb infection and uninfected controls identified 6 RNA targets that were specific to Wb and/or Bm. Assays developed to detect either ccfDNA and ccfRNA were successfully used in Wb-infected individuals, but DNA-based assays targeting WbTR1 was found to be the most sensitive biomarker of Wb circulating cell free nucleic acids. Plasma-derived ccfDNA was identified in 71 % (of all mf-positive individuals) Wb infection from India, Cook Islands, Mali, Haiti and Guyana. Following definitive treatment, time course analyses indicated that WbTR1 ccfDNA levels were undetectable within a year. Overall, ccfDNA/RNA detection in LF holds promise for assessment of infection and treatment response in Wb and Bm infections.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143641079","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}
Mrinalini Kala, Mame Diarra Bousso Ndiaye, Erin Kelley, Maxx Harvey, Farhan Babur, Garrett Grischo, Jessica S Marshall, Jinhee Yi, Anna L Engelbrektson, John A Altin, Bridget M Barker, Paul Keim, Kenneth S Knox, Erik W Settles
Background Valley fever (VF) is a common cause of community acquired pneumonia in the American Southwest. Diagnosis is challenging due to VF’s similarities to other pulmonary diseases. The VF T-cell response is important to control the disease and measuring this response holds promise as an improved diagnostic. Objective Identification of VF T-cell epitopes and development of disease diagnostics and efficacy monitoring for vaccine trials. Methods We identified VF specific T-cell epitopes by using their ability to bind the Major Histocompatibility Complex Class II (MHC II) molecules and T-cell stimulation. We performed MHC binding prediction on known and unknown Coccidioides antigens and then empirically tested the predictions on unknown antigens with an in vitro multiplex MHC binding analysis. Peripheral blood mononuclear cells from clinical Coccidioides infections, and endemic or nonendemic healthy controls were stimulated with the identified peptides and evaluated for immunologic memory responses. Results A total of 108 Coccidioides peptides were identified by MHC class II binding. The 108 peptides (NAU108) were synthesized, pooled, and jointly evaluated for immunogenicity in VF positive individuals. The peptides re-activated memory CD4+ T-cells in VF confirmed and endemic VF specimens when compared to non-endemic control samples as determined by activation marker and cytokine secretion. Conclusion This study identified peptides that when pooled had immunogenic properties in humans infected with Coccidioides that can be used to distinguish infected individuals from endemic area healthy controls or non-exposed individuals outside the endemic area. This approach holds relevance for the development of diagnostic assays for VF.
背景 谷热（VF）是美国西南部社区获得性肺炎的常见病因。由于谷热与其他肺部疾病相似，因此诊断具有挑战性。谷热 T 细胞反应对控制疾病非常重要，而测量这种反应有望改进诊断方法。目标 识别 VF T 细胞表位，为疫苗试验开发疾病诊断和疗效监测工具。方法 我们通过与主要组织相容性复合物 II 类（MHC II）分子结合的能力和 T 细胞刺激来鉴定 VF 特异性 T 细胞表位。我们对已知和未知的球孢子菌抗原进行了MHC结合预测，然后通过体外多重MHC结合分析对未知抗原的预测进行了经验性测试。用鉴定出的多肽刺激临床球孢子虫感染者、地方病或非地方病健康对照者的外周血单核细胞，并评估其免疫记忆反应。结果 通过 MHC II 类结合共鉴定出 108 种球虫肽。对这 108 种多肽（NAU108）进行了合成、汇集，并对 VF 阳性个体的免疫原性进行了联合评估。与非流行性对照样本相比，通过活化标记和细胞因子分泌的测定，这些肽能重新激活VF确诊样本和VF流行样本中的记忆CD4+T细胞。结论 本研究发现了在感染球孢子虫的人体中具有免疫原性的多肽，这些多肽汇集在一起后可用于区分感染者与流行区健康对照组或流行区外未受感染者。这种方法对开发 VF 诊断测定具有现实意义。
{"title":"Identification of Coccidioidomycosis immunoreactive peptides that recall T-cell responses indicating past exposure","authors":"Mrinalini Kala, Mame Diarra Bousso Ndiaye, Erin Kelley, Maxx Harvey, Farhan Babur, Garrett Grischo, Jessica S Marshall, Jinhee Yi, Anna L Engelbrektson, John A Altin, Bridget M Barker, Paul Keim, Kenneth S Knox, Erik W Settles","doi":"10.1093/infdis/jiaf118","DOIUrl":"https://doi.org/10.1093/infdis/jiaf118","url":null,"abstract":"Background Valley fever (VF) is a common cause of community acquired pneumonia in the American Southwest. Diagnosis is challenging due to VF’s similarities to other pulmonary diseases. The VF T-cell response is important to control the disease and measuring this response holds promise as an improved diagnostic. Objective Identification of VF T-cell epitopes and development of disease diagnostics and efficacy monitoring for vaccine trials. Methods We identified VF specific T-cell epitopes by using their ability to bind the Major Histocompatibility Complex Class II (MHC II) molecules and T-cell stimulation. We performed MHC binding prediction on known and unknown Coccidioides antigens and then empirically tested the predictions on unknown antigens with an in vitro multiplex MHC binding analysis. Peripheral blood mononuclear cells from clinical Coccidioides infections, and endemic or nonendemic healthy controls were stimulated with the identified peptides and evaluated for immunologic memory responses. Results A total of 108 Coccidioides peptides were identified by MHC class II binding. The 108 peptides (NAU108) were synthesized, pooled, and jointly evaluated for immunogenicity in VF positive individuals. The peptides re-activated memory CD4+ T-cells in VF confirmed and endemic VF specimens when compared to non-endemic control samples as determined by activation marker and cytokine secretion. Conclusion This study identified peptides that when pooled had immunogenic properties in humans infected with Coccidioides that can be used to distinguish infected individuals from endemic area healthy controls or non-exposed individuals outside the endemic area. This approach holds relevance for the development of diagnostic assays for VF.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143635549","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}
Michał Kanoza, Justyna Folkert, Izabela Ciastoń, Amir Aliramezani, Jan Potempa, Joanna Koziel, Jakub M Kwiecinski
Neutrophil elastase (NE), the main protease of neutrophils, is involved in many of their functions, including prevention of infections. Despite its general importance, NE was previously thought to play no role in infections caused by Staphylococcus aureus, one of the leading bacterial pathogens. Here, using transgenic mice deficient in NE and a mouse model of localized skin infection, we demonstrate that NE is in fact needed for the containment of S. aureus and prevention of the systemic spread of this bacterium. This is apparently due to the role of NE in the formation of neutrophil extracellular traps.
{"title":"Neutrophil elastase limits spread of Staphylococcus aureus during skin infection","authors":"Michał Kanoza, Justyna Folkert, Izabela Ciastoń, Amir Aliramezani, Jan Potempa, Joanna Koziel, Jakub M Kwiecinski","doi":"10.1093/infdis/jiaf128","DOIUrl":"https://doi.org/10.1093/infdis/jiaf128","url":null,"abstract":"Neutrophil elastase (NE), the main protease of neutrophils, is involved in many of their functions, including prevention of infections. Despite its general importance, NE was previously thought to play no role in infections caused by Staphylococcus aureus, one of the leading bacterial pathogens. Here, using transgenic mice deficient in NE and a mouse model of localized skin infection, we demonstrate that NE is in fact needed for the containment of S. aureus and prevention of the systemic spread of this bacterium. This is apparently due to the role of NE in the formation of neutrophil extracellular traps.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143641094","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：