Itay Bar-Or, Merav Weil, Hadar Assraf, Areej Kabat, Roberto Azar, Batya Mannasse, Virginia Levy, Leah Weiss, Rinat Vasserman, Elias Dawood, Irina Aguvaev, Roaa Matar, Alex Aydenzon, Amit Holdhaim, Zvi Cohen, Nofar Levi, Ilana S Fratty, Neta S Zuckerman, Lester M Shulman, Ella Mendelson, Danit Sofer, Oran Erster
{"title":"Clinical and environmental surveillance of poliovirus type 2 outbreak using a novel specific real-time quantitative PCR assay, Israel, 2022-2023","authors":"Itay Bar-Or, Merav Weil, Hadar Assraf, Areej Kabat, Roberto Azar, Batya Mannasse, Virginia Levy, Leah Weiss, Rinat Vasserman, Elias Dawood, Irina Aguvaev, Roaa Matar, Alex Aydenzon, Amit Holdhaim, Zvi Cohen, Nofar Levi, Ilana S Fratty, Neta S Zuckerman, Lester M Shulman, Ella Mendelson, Danit Sofer, Oran Erster","doi":"10.1093/infdis/jiaf387","DOIUrl":"https://doi.org/10.1093/infdis/jiaf387","url":null,"abstract":"Background An increase in the number of circulating vaccine derived poliovirus (VDPV) outbreaks is reported worldwide in recent years, necessitating improved surveillance and diagnostic tools. The current standard protocol for polio detection is lengthy, labor-intensive, and inefficient for direct wastewater testing. Methods Here we describe a multiplex poliovirus-2 (PV2) specific assay that directly detects PV2 RNA derived from Sabin-2 vaccine in wastewater and stool samples. The new PV2-specific assay was used for direct detection of PV2 in environmental and clinical samples. Results In-silico analysis suggested that the assay is specific for PV2 originated from Sabin-2 vaccine and identifies 98.3% of available sequences, including some with <95% similarity to the vaccine reference sequence. We show that the assay is specific for PV2 and does not identify 19 other enterovirus strains, including sabin-1 and Sabin-3 RNA. The new assay enabled fast detection of PV2 in suspected clinical samples, which was subsequently confirmed by isolation and sequencing. By analyzing 183 concentrated wastewater samples, we further show that the new assay specifically and directly identifies PV2 RNA, in the presence of PV1, PV3, and other enteroviruses RNA. Conclusions The assay provides quantitative results, allowing continuous monitoring of viral load dynamics. Comparison of the standard isolation protocol and the new assay showed excellent agreement in terms of specificity and sensitivity. This specific and rapid assay may therefore be a valuable tool for monitoring cVDPV2 outbreaks in real time, and promote the global efforts for eradication and containment poliovirus circulation","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144712348","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}
Brooke M Talbot,Natasia F Jacko,Katrina S Hofstetter,Tara Alahakoon,Kevin Bouiller,Timothy D Read,Michael Z David
{"title":"Methicillin-Resistant Staphylococcus aureus Bacteremia Relapses Show Diverse Genomic Profiles but Convergence in Bacteremia-Associated Genes.","authors":"Brooke M Talbot,Natasia F Jacko,Katrina S Hofstetter,Tara Alahakoon,Kevin Bouiller,Timothy D Read,Michael Z David","doi":"10.1093/infdis/jiaf352","DOIUrl":"https://doi.org/10.1093/infdis/jiaf352","url":null,"abstract":"BACKGROUNDRecurrence of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is a high risk complication for patients. Distinguishing persistent lineages from new infections is not standardized across clinical studies.METHODSWe investigated factors contributing to recurrence of MRSA bacteremia among subjects in Philadelphia, Pennsylvania. Subject demographics and clinical history were collected and paired with whole-genome sequences of infection isolates. Recurrent bacteremia episodes were recorded and defined as relapse infections (same lineage) or new infections by genomic criteria, where a relapse contained isolates ≤ 25 single nucleotide polymorphisms (SNP) different, and by clinical criteria. All isolates were assessed for pairwise SNP distances, common mutations, and signatures of within-host adaptation using the McDonald-Kreitman test. Clusters of transmission between relapse-associated isolates and other subject lineages were identified.RESULTSAmong 411 sequential subjects with MRSA bacteremia, 32 experienced recurrent bacteremia episodes, with 24 subjects having exclusively relapse infections, 6 with infections exclusively from a new strain, and 2 patients with both relapse and new infections. No concordance between a genomic and a clinical definition of relapse was evident (Cohen κ = 0.18; confidence interval, -0.41). Recurrence-associated lineages exhibited signatures of positive selection (G test, < 0.01). Genes with SNPs occurring in multiple relapse lineages have roles in antibiotic resistance and virulence, including 5 lineages with mutations in mprF and 3 lineages with mutations in rpoB, which corresponded with evolved phenotypic changes in daptomycin and rifampin resistance.CONCLUSIONSRecurrent infections have a diverse strain background. Relapses can be readily distinguished from newly acquired infections using genomic sequencing but not clinical criteria.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144701239","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}
Maria Saeed,Elizabeth H Aitken,Myo T Naung,Caitlin Bourke,Kenneth W Wu,Rhea J Longley,Amy W Chung,Timon Damelang,Benson Kiniboro,Ivo Mueller,Stephen J Rogerson
{"title":"Association of a novel IgG3 allele with malaria in children from the Sepik region of Papua New Guinea.","authors":"Maria Saeed,Elizabeth H Aitken,Myo T Naung,Caitlin Bourke,Kenneth W Wu,Rhea J Longley,Amy W Chung,Timon Damelang,Benson Kiniboro,Ivo Mueller,Stephen J Rogerson","doi":"10.1093/infdis/jiaf390","DOIUrl":"https://doi.org/10.1093/infdis/jiaf390","url":null,"abstract":"BACKGROUNDSusceptibility to malaria can be influenced by host genetic factors, including immune response genes. Antibodies against Plasmodium antigens are known to play an important role in protection from clinical disease. Polymorphisms in these antibodies may result in different functional properties that could provide protection from malaria.METHODSImmunoglobulin G1 (IgG1) and IgG3 alleles and IgG3 hinge region were investigated by polymerase chain reaction (PCR) and Sanger sequencing in a longitudinal cohort of children aged 1-3 years (N=203) from East Sepik region of Papua New Guinea (PNG). Linear regression was used to investigate associations between immunoglobulin alleles and Plasmodium infections.RESULTSSeventy-eight percent of the children were either heterozygous (n=82, 40%) or homozygous (n=77, 38%) for IGHG3*30 (G3m29), a novel IgG3 allele. G3m29 has a long hinge region of 4 exons. Significantly fewer Plasmodium spp. infections were observed in children with the IGHG3*30 allele compared to children without the allele (β= -1.736, 95% CI [-3.39, -0.079], p=0.038). This effect was most noticeable for Plasmodium vivax asymptomatic infections as IGHG3*30 carriers had on average one fewer infection in the 18-month follow-up period as compared to non-IGHG3*30 allele carriers (β= -1.06; 95% CI [-2.01, -0.12], p=0.028). Additionally, IGHG3*30 allele carriers had significantly lower levels of IgG to P. vivax vaccine candidate proteins compared to non-IGHG3*30 allele carriers.CONCLUSIONSThe IGHG3*30 allele is highly prevalent in the East Sepik region and is associated with fewer Plasmodium spp. infections.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144720195","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}
Andy Liu,Lorenzo Giacani,Iskra Tuero,Jeffrey D Klausner
{"title":"Syphilis Pathogenesis: Host Immune Response versus Pathogen Immune Evasion.","authors":"Andy Liu,Lorenzo Giacani,Iskra Tuero,Jeffrey D Klausner","doi":"10.1093/infdis/jiaf388","DOIUrl":"https://doi.org/10.1093/infdis/jiaf388","url":null,"abstract":"Syphilis, caused by Treponema pallidum subspecies pallidum (T. pallidum), remains a significant global health problem despite being preventable and curable. The pathogen's ability to evade the immune system using virulence factor-based strategies and by invading immune-privileged sites enables persistent infection in the untreated host. This translational update describes the host innate and adaptive immune responses in syphilis and the sophisticated mechanisms employed by T. pallidum to avoid immune clearance. Recent advances in immune profiling have enhanced our understanding of the host immune response and identified potential biomarkers for disease staging and treatment monitoring. However, knowledge gaps remain regarding T. pallidum's immune evasion mechanisms, the dynamics of cellular and humoral immunity, and the characteristics of long-term protective immune responses against T. pallidum. Bridging these gaps by integrating microbiology, immunology, and multiomics approaches is crucial for advancing diagnostic tools, therapeutic strategies, and vaccine development to ultimately reduce the global burden of syphilis.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"96 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144701244","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 King, Kristin L Andrejko, Miwako Kobayashi, Wei Xing, Adam L Cohen, Wesley H Self, J Jackson Resser, Cynthia G Whitney, Adrienne Baughman, Mai Kio, Carlos G Grijalva, Jessica Traenkner, Nadine Rouphael, Joseph A Lewnard
{"title":"Pneumococcal serotype distribution and coverage of existing and pipeline pneumococcal vaccines","authors":"Laura M King, Kristin L Andrejko, Miwako Kobayashi, Wei Xing, Adam L Cohen, Wesley H Self, J Jackson Resser, Cynthia G Whitney, Adrienne Baughman, Mai Kio, Carlos G Grijalva, Jessica Traenkner, Nadine Rouphael, Joseph A Lewnard","doi":"10.1093/infdis/jiaf376","DOIUrl":"https://doi.org/10.1093/infdis/jiaf376","url":null,"abstract":"Background Next-generation pneumococcal conjugate vaccines (PCVs) target an expanding array of serotype antigens. We assessed the proportions of invasive pneumococcal disease (IPD) and pneumococcal acute respiratory infections (ARIs) caused by serotypes targeted by existing and pipeline PCVs, and annual U.S. pneumococcal disease burdens potentially preventable by these products. Methods We estimated serotype distribution and proportions of pneumococcal ARIs (acute otitis media [AOM; children only], sinusitis, non-bacteremic pneumonia) and IPD attributable to serotypes targeted by each PCV using Markov chain Monte Carlo approaches incorporating data from epidemiological studies and Active Bacterial Core Surveillance. We then estimated annual numbers of outpatient-managed ARIs, non-bacteremic pneumonia hospitalizations, and IPD cases potentially preventable by PCVs by multiplying disease incidence rates by PCV-targeted disease proportions and vaccine effectiveness estimates. Results In children, PCV15, PCV20, PCV24, PCV25, and PCV31 serotypes account for 16% (95% confidence interval: 15-17%), 31% (30-32%), 34% (32-35%), 43% (42-44%), and 68% (67-69%) of pneumococcal AOM, respectively. In adults, PCV15, PCV20, PCV21, PCV24, PCV25, and PCV31 serotypes account for 43% (38-47%), 52% (47-57%), 69% (64–73%), 65% (61-70%), 62% (57-67%), and 87% (83-90%) of pneumococcal non-bacteremic pneumonia. For IPD, 42-85% of pediatric and 42-94% of adult cases were due to PCV-targeted serotypes. PCV-preventable burdens encompassed 270,000-3,300,000 outpatient-managed ARIs, 2,000-17,000 pneumonia hospitalizations, and 3,000-14,000 IPD cases annually. Conclusions Across pneumococcal conditions, coverage and preventable burdens were lowest for PCV15 and highest for PCV31, with PCV21 also targeting sizeable burdens of adult disease. Comparative estimates of preventable disease burden may inform future policy.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144677664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Virological tools fail to properly identify \"unusual\" hepatitis C virus subtypes resistant to direct-acting antiviral drugs in The Gambia.","authors":"Erwan Vo-Quang,Christophe Rodriguez,Arnaud Ly,Gibril Ndow,Alexandre Soulier,Melissa Ndebi,Stéphane Chevaliez,Sainabou Drammeh,Isabelle Chemin,Vincent Leroy,Maud Lemoine,Jean-Michel Pawlotsky","doi":"10.1093/infdis/jiaf378","DOIUrl":"https://doi.org/10.1093/infdis/jiaf378","url":null,"abstract":"We evaluated the ability of the commercial Sentosa SQ Hepatitis C Virus Genotyping Assay to identify the HCV genotype subtype in patients from The Gambia. Subtype was determined from the Sentosa-generated NS5B sequences using 3 bioanalytical methods: the Sentosa SQ HCV Genotyping Assay bioanalytical tool, Geno2pheno, and the National Reference Center in-house method. The Sentosa assay result agreed with the reference method in only 2 of 13 cases. This study highlights the difficulty of correctly identifying HCV subtypes in a region of Africa with a high diversity of HCV genotype 1 and 2 subtypes that may be resistant to antivirals.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Human Metapneumovirus, Respiratory Syncytial Virus and Influenza Associated Pneumonia Hospitalizations in Colorado Adults Aged Over 50 Years: 2016-2023","authors":"Eric A F Simões, Robert J Suss, Dhananjay V Raje","doi":"10.1093/infdis/jiaf381","DOIUrl":"https://doi.org/10.1093/infdis/jiaf381","url":null,"abstract":"Background The objectives were to identify the frequency and risk factors for ICU admission and mortality associated with RSV, influenza, and HMPV pneumonia hospitalizations and to compare these rates with those admitted with other ARI caused by these viruses Methods This retrospective cohort study identified hospitalization encounters of adults’ aged 50 to 88 years with RSV, influenza and HMPV pneumonia between 2016 and 2023 in the Colorado Hospital Association database., . Multivariate logistic regression was used to estimate the adjusted odds of ICU admission and mortality. Results Of 2210 hospitalized patients with RSV pneumonia, 780 (35%) were admitted to the ICU and 205 (9.3%) died. For Influenza pneumonia these figures were 7174, 2332 (32.5%) and 545 (7.6%) and HMPV pneumonia 1482, 408 (27.5%) and 88 (5.9%) respectively. Dementia has the highest odds for ICU admission in patients with RSV pneumonia aOR 4.2 (1.34, 13.18), for influenza pneumonia it was chronic pulmonary disease aOR 2.99 (2.45, 3.66) and for HMPV pneumonia it was COPD without asthma aOR 5.04 (2.92, 8.7). Increasing age was associated with increasing rates of mortality for RSV and influenza. Chronic pulmonary disease, and COPD itself had &gt; 2 fold higher rates of mortality in patients with pneumonia for all three viruses while obesity, , diabetes and chronic renal disease didn’t. Increasing numbers of comorbidities significantly increase ICU admission and mortality rates in all 3 groups. Conclusions Pneumonia is a severe manifestation of ARI with RSV, influenza and HMPV with differing risk factors for ICU admission and mortality.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144677663","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}
Becky Gordon, Joyce U Nyiro, Harish Nair, Zakariya Sheikh, Esther Katama, Charles N Agoti, Ruonan Pei, Heather Zar, Ting Shi
{"title":"External validation of paediatric pneumonia and bronchiolitis risk scores to predict mortality in children hospitalised in Kenya: a retrospective cohort study","authors":"Becky Gordon, Joyce U Nyiro, Harish Nair, Zakariya Sheikh, Esther Katama, Charles N Agoti, Ruonan Pei, Heather Zar, Ting Shi","doi":"10.1093/infdis/jiaf377","DOIUrl":"https://doi.org/10.1093/infdis/jiaf377","url":null,"abstract":"Background Acute lower respiratory tract infections (ALRIs) are a leading cause of paediatric mortality in low- and middle-income countries. In recent years, substantial research has been done to enhance risk stratification of children presenting with ALRIs, in a bid to improve health outcomes in resource-limited settings. We sought to analyse the performance of several paediatric ALRI risk scores in the prediction of mortality among children hospitalised with ALRIs in Kenya. Methods We retrospectively analysed the data of 2182 children aged 2-24 months who were admitted to Kilifi County Referral Hospital, Kenya with severe ALRIs between January 2015 and December 2024. We evaluated the performance of 6 ALRI risk scores (RISC (HIV-Negative), mRISC, RISC-Malawi, PERCH, PREPARE, ReSVinet) in this population. Additionally, we created and evaluated a modified version of the ReSVinet score by including nutrition status. Discrimination was assessed using the area under the receiver operating characteristic curve (AUROC). Results The mid-upper arm circumference (MUAC) version of the RISC-Malawi score showed the highest discrimination for the outcome of in-hospital mortality (AUROC: 0.83, 95% CI: (0.79–0.86)), whilst all other scores showed acceptable discrimination (AUROC: 0.70–0.79). The modification of ReSVinet to include nutrition status significantly improved its AUROC from 0.72 to 0.79. Conclusion All risk scores showed at least fair performance in the prediction of in-hospital mortality within our dataset. The RISC-Malawi (MUAC) score appears to be the most promising candidate for future implementation, however further research is needed to evaluate the calibration, feasibility and clinical utility of these scores.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"98 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144677665","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}