The Journal of Infectious Diseases最新文献

{"title":"Impact of puberty on immune responses to Mycobacterium tuberculosis in South African adolescents","authors":"Léanie Kleynhans, Elizna Maasdorp, Candice I Snyders, James A Seddon","doi":"10.1093/infdis/jiaf293","DOIUrl":"https://doi.org/10.1093/infdis/jiaf293","url":null,"abstract":"Background As individuals progress through adolescence, their risk of tuberculosis (TB) increases and the type of disease that develops changes, with increasing cavitary formation and parenchymal tissue destruction. While it is widely assumed that the changes in risk and disease phenotype are due to puberty exerting an impact on host immune responses to Mycobacterium tuberculosis, this relationship has been poorly studied. Methods Teen TB was an observational study that recruited 50 adolescents with pulmonary TB and 50 TB-exposed controls in Cape Town, South Africa. Blood was collected at baseline, and again at month 2 from those with TB. Concentrations of 43 cytokines and 19 hormones were measured and compared between individuals with TB and controls and changes over time in those with TB. The relationship between Tanner stage and cytokine/endocrine concentrations were also assessed. Result IL-1ra, IP-10, SAP, cortisol, lipocalin-2 and resistin were higher, while ghrelin, T3 and DHEAS were lower, in adolescents with TB (vs healthy controls). DHEAS, progesterone, luteinizing hormone, testosterone, C-peptide, estradiol and cortisol were positively correlated, and T3 negatively correlated, with Tanner stage in healthy controls. In adolescents with TB, there was no association between Tanner stage and cytokine/endocrine markers. Conclusion While in healthy individuals there was a strong association between Tanner stage and endocrine markers, this relationship was absent in adolescents with TB. TB disease appears to disrupt the normal physiological process of puberty. This could have a substantial impact on growth and development for adolescents developing TB during this critical time.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144202156","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":"Genome-scale meta-analysis of host responses to Staphylococcus aureus identifies pathways for host-directed therapeutic targeting","authors":"Clark D Russell, Seraphima Goeldner-Thompson, Emilie Smith, Jonathan E Millar, Bo Wang, Nicholas Parkinson, Sara Clohisey Hendry, Maaike Swets, J Ross Fitzgerald, J Kenneth Baillie, David H Dockrell","doi":"10.1093/infdis/jiaf290","DOIUrl":"https://doi.org/10.1093/infdis/jiaf290","url":null,"abstract":"Background Staphylococcus aureus infections are frequently complicated by metastatic foci, recurrence, and death. Antimicrobial resistance and intracellular bacterial persistence limit the effectiveness of conventional antimicrobials. Host-directed therapies could improve outcomes, but the interpretive complexity of pathogen-host interactions impedes identification of critical responses suitable for therapeutic targeting. To address this, we performed a meta-analysis of genome-scale studies aiming to prioritise host responses to S. aureus. Methods Lists of genes associated with host responses to S. aureus were retrieved from systematically identified genome-scale studies, then integrated using the meta-analysis by information content (MAIC) algorithm. This generated a single aggregated gene list, ranked based on the cumulative evidence supporting each gene. Results MAIC prioritised 3867 host genes. Myeloid cell immune responses were enriched with specific hubs including TLR2, IL-17, IFNγ, and IL-1β. Non-canonical effector pathways were also enriched: autophagy (specific factors including mTOR and LAMP2), apoptosis (including BAD and BID), ferroptosis and iron metabolism (TFRC ranked 8/3876), and proteasomal antimicrobial responses (including PSME3 and the novel antimicrobial peptide PPP1CB). Prioritised genes were associated with GWAS traits related to platelet count. In a cohort of patients with S. aureus bacteraemia, platelet count was differentially associated with clinical outcomes. Targets with immediate therapeutic relevance included S. aureus/fibrin/platelet microthrombus formation (VWF, GP11b), S. aureus-induced platelet loss (ASGR2), autophagy (mTOR), BID-mediated apoptosis, and intracellular bacterial killing (IFNγ). Conclusions This in silico analysis identifies cytokine hubs associated with the response to S. aureus infection and prioritises additional host responses including apoptosis, autophagy, iron metabolism, and thrombosis as therapeutic targets.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144183866","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":"Differentiating SARS-CoV-2 antibody responses between infection and vaccination: challenges for epidemiological research","authors":"Sunav N Nayagam, William Coote, Matthew TC Carroll, Zheng Quan Toh, Paul V Licciardi, Michael J Abramson, Karen Walker-Bone, Tyler J Lane","doi":"10.1093/infdis/jiaf295","DOIUrl":"https://doi.org/10.1093/infdis/jiaf295","url":null,"abstract":"Some common COVID-19 vaccines elicit antibody responses that most serological tests are unable to differentiate from an infection response. This presents a challenge for COVID-19 surveillance and epidemiology. In this perspective, we examine the potential scale of this problem.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144202101","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":"Longitudinal Analysis of Nasopharyngeal Microbial Risk Markers for Fatal Acute Febrile Illness in a Zambian Birth Cohort","authors":"Aubrey R Odom, Jessica Anderson, Christopher J Gill, Rachel Pieciak, Arshad Ismail, William B MacLeod, W Evan Johnson, Rotem Lapidot","doi":"10.1093/infdis/jiaf292","DOIUrl":"https://doi.org/10.1093/infdis/jiaf292","url":null,"abstract":"Introduction Fatal acute febrile illness (fAFI) is a known predecessor of many infant mortality events in low-resource settings, yet early risk markers for this condition remain poorly understood. Nasopharyngeal (NP) microbiome patterns may influence the severity of these infections. Methods We analyzed longitudinal changes in the NP microbiota of Zambian infants with fAFI onset compared to healthy controls, aiming to identify microbial indicators associated with severe illness outcomes. We conducted a pooled analysis of a longitudinal nested case-control study comprised of 26 samples from 9 infants who developed fAFI compared with 69 samples from 10 healthy infants. Infants underwent nasopharyngeal sampling from 1 week through 14 weeks of age at 2–2.5-week intervals. We performed 16S rRNA gene amplicon sequencing on all infant nasopharyngeal (NP) samples and characterized NP microbiome maturation among infants with febrile acute febrile illness (fAFI(+)) and healthy controls (fAFI(−)). Results Beta diversity measures of fAFI(-) infants were markedly higher than those of fAFI(+) infants. The fAFI(+) infant NP microbiome was marked by lower abundances of Dolosigranulum, Haemophilus, Streptococcus, and Corynebacterium, with higher relative presence of Pseudomonas. Conclusions Our findings suggest that specific microbial community patterns and early NP microbiome dysbiosis may be associated with increased illness risk. These findings can motivate further studies to inform foundational markers for fAFI in infants, contributing to precision pediatric care.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144184121","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":"Anal Sex and Tenofovir Douche Sequence Impacts Colorectal Distribution of HIV Surrogate and Douche (DREAM-02)","authors":"Ruohui Zheng, Edward J Fuchs, Sridhar Nimmagadda, Lisa C Rohan, Lin Wang, Lynn N Bertagnolli, Sandra Massih, Brian S Caffo, Craig W Hendrix","doi":"10.1093/infdis/jiaf286","DOIUrl":"https://doi.org/10.1093/infdis/jiaf286","url":null,"abstract":"Background Men who have sex with men are at high risk of HIV acquisition through unprotected receptive anal intercourse (RAI). Behaviorally-congruent HIV PrEP has long been advocated by individuals who find adherence challenging or prefer minimizing systemic drug concentrations. We developed an event-driven, behaviorally-congruent rectal tenofovir (TFV) douche as a PrEP option for RAI and demonstrated product safety/acceptability in a previous clinical study. Here, our goal was to compare colorectal distribution of an HIV surrogate and TFV douche when the TFV douche preceded or followed simulated RAI (sRAI). Methods Five participants completed two paired study visits. At the first study visit, participants received an 111In-DTPA in TFV douche prior to sRAI using 99mTc-sulfur colloid in autologous semen as HIV surrogate. At the second study visit, the radiolabeled TFV douche was administered following radiolabeled sRAI. Colorectal distribution of both douche and HIV surrogate radioisotopes were assessed using SPECT/CT. Systemic permeability was assessed by plasma TFV concentrations. Results Colorectal distribution of the douche was not different between sequences. Conversely, the majority of HIV surrogate was within the rectosigmoid when the douche was administered prior to sRAI, but the distribution extended into descending colon when the douche was administered following sRAI. Regardless of sequence, an early plasma TFV peak, faster than other TFV-based products, at 20 minutes was observed. Conclusions Douching following RAI may increase HIV distribution in the colon with uncertain impact on HIV acquisition risk. The early plasma TFV suggests even more rapid time to protection than in prior studies.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144184131","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":"Host determinants for the spread of PVL-positive Staphylococcus aureus in Sub-Saharan Africa","authors":"Tobias Grebe, Viktoria Rudolf, Christiane Sidonie Gouleu, Tomiwa Olumide Adesoji, Claujens Chastel Mfoutou Mapanguy, Mary Oladokun, Anke Siegmund, Le Thi Kieu Linh, Silke Niemann, Bettina Löffler, Ayola Akim Adegnika, Francine Ntoumi, Thirumalaisamy P Velavan, Adebayo Osagie Shittu, Frieder Schaumburg","doi":"10.1093/infdis/jiaf289","DOIUrl":"https://doi.org/10.1093/infdis/jiaf289","url":null,"abstract":"The Panton-Valentine leukocidin (PVL) of Staphylococcus aureus can be associated with severe and recurrent skin and soft tissue infections (SSTI). The prevalence of PVL is particularly high in Sub-Saharan Africa. We assessed in a multi-center cross-sectional study whether host-related factors could explain this high PVL prevalence. We find higher serum anti-PVL-IgG levels in participants from Africa (Gabon, Nigeria, Congo) compared to Europe (Germany). PVL-induced cytolysis of neutrophils is higher in Africans, linked to a polymorphism of the C5a receptor (rs11880097 T/G), the cellular target of the lukS subunit of PVL. The inflammasome response of monocytes to PVL is shifted towards IL-1β and IL-8 in Africans while Europeans have a stronger IL-18 response. Thus, African neutrophils are more susceptible to PVL, and monocytes exert a stronger Th1 immune response, eventually increasing the risk of tissue damage (e.g. due to a stronger recruitment of neutrophils via IL-1β and IL-8) in PVL-positive S. aureus SSTI in Africans.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"100 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210836","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":"Functional genomics of antibiotic susceptibility in Enterococcus faecalis from infective endocarditis","authors":"Yanhong Li, Madison E Stellfox, Kirsten M Evans, Emma G Mills, Kevin M Squires, Ava J Dorazio, Ryan K Shields, Daria Van Tyne","doi":"10.1093/infdis/jiaf272","DOIUrl":"https://doi.org/10.1093/infdis/jiaf272","url":null,"abstract":"Enterococcus faecalis is an opportunistic pathogen that causes infective endocarditis. Despite in vitro synergy of the recommended combination ampicillin and ceftriaxone (AC), E. faecalis infective endocarditis (EFIE) mortality remains high. We characterized 119 isolates from EFIE patients in our health system from 2018 to 2023 genomically and phenotypically. Three genetic lineages (ST6, ST40, and ST179) accounted for 41% of all infections. ST6 isolates were less susceptible to ceftriaxone and AC in dual-antibiotic checkerboard assays, but also exhibited decreased survival in dual-antibiotic killing assays using humanized AC exposures. ST6 isolates encoded a known genetic disruption affecting pbp4 as well as mutation of a putative hydrolase called phnP. Functional studies confirmed that both alterations contributed to altered AC susceptibility. Finally, we found that ampicillin plus daptomycin showed robust growth inhibition and killing against EFIE isolates with decreased AC susceptibility. These findings enhance our understanding of EFIE and may guide better therapeutic strategies.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"58 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176570","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":"Differences in Neutrophil Counts Between African and non-African Countries in two International Clinical Trials","authors":"Ruth N Moro, John L Johnson, Neil Martinson, Grace Muzanyi, Chi-Chiu Leung, Kwok-Chiu Chang, Ziyaad Waja, Stefan V Goldberg","doi":"10.1093/infdis/jiaf291","DOIUrl":"https://doi.org/10.1093/infdis/jiaf291","url":null,"abstract":"Background Differences in absolute neutrophil count (ANC) between African and non-African populations have been reported. Neutropenia has also been reported during rifamycin use. ANC values in current tables that assign severity grades to clinical or laboratory events (The National Cancer Institute Common Terminology Criteria for Adverse Events [CTCAE] and the National Institute of Allergy and Infectious Diseases Division of AIDS [DAIDS]) might not consistently be applicable among different populations. Methods During two international tuberculosis treatment trials, 337 participants received rifampin, and three groups of 361, 81, and 81 participants received 10, 15, and 20 mg/kg of rifapentine, respectively, for two months of daily treatment. ANC was measured at baseline, and after 2, 4, 6, 8, and 12 weeks of treatment. CTCAE versions 2.0–4.0 and DAIDS version 2.0 define neutropenia grade 3 as ANC 500–999/mm3 and ANC 400–599/mm3, respectively. We analyzed factors associated with neutropenia. Results Baseline median ANC was lower in Black African participants than in Black non-African participants (p=0.004). CTCAE-defined ≥Grade 3 neutropenia occurred in 32 (28 in Africa) participants. Proportions did not differ between rifapentine doses. Only 4 events would have been reported by DAIDS criteria. All neutropenia events resolved spontaneously without interrupting treatment. Enrollment in an African country was an independent factor associated with the development of neutropenia. Discussion Differences in baseline median ANC can result in misclassification of adverse events or inappropriate clinical management. Development and use of population-specific normal values of ANC could improve guidance for research and clinical management.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"81 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144183871","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":"Impact of Population Immunity and Public Health Measures on the Transmission of Omicron Subvariants BA.2 and BA.5 in Hong Kong","authors":"Can Wang, Hsiang-Yu Yuan, Eric H Y Lau, Benjamin J Cowling, Dennis K M Ip, Tim K Tsang","doi":"10.1093/infdis/jiaf287","DOIUrl":"https://doi.org/10.1093/infdis/jiaf287","url":null,"abstract":"Background The rapid evolution of SARS-CoV-2 and population-level vaccine administration significantly shift the population immunity. In Hong Kong, these shifts, coupled with the emergence of Omicron BA.5 with a strong ability of immune evasion, necessitate a deeper understanding of how population immunity and public health and social measures have shaped the epidemic dynamics across age groups within the population. Methods We developed an age-structured, multi-strain model and estimated key parameters including transmissibility for the emerging BA.5, the effects of PHSMs on transmission, and contributions of natural infection and vaccination to age-specific immunity against infection of each subvariant over time. Results We found that reactive PHSMs implemented in February 2022 decreased the time-varying effective reproductive number without the effect of immunity RtWI by 67% (95% CrI: 52–78%). However, subsequent relaxation of control measures since April 2022, alongside the enhanced transmissibility of BA.5, drove RtWI back to 3.4 (95% CrI: 2.8–4.1) by late May. Prior to the fifth wave, only 15% of the Hong Kong population had immunity and protected against BA.2 infection. Population immunity against BA.2 infection then increased significantly to 55% within 2 months given 47% cumulative infections and > 30% vaccination uptake. Subsequently, with the emergence of BA.5, population immunity against BA.5 infection was 15% lower than that against BA.2 during the end of May. Conclusions Our findings underscore the dynamic interplay between population immunity, PHSMs, and variant transmissibility and highlight the potential risks posed by immune-evasive variants in the context of waning immunity and control relaxation.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144165262","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":"HIV-Superinfection in Kidney Transplant Recipients with HIV who Received Organs from Donors with HIV","authors":"Gracie M Rozek, Ping Yang, Yolanda Eby, Sarah E Benner, Craig Martens, Feben Habtehyimer, Maggie Chahoud, Diane Brown, Niraj M Desai, Sander Florman, Meenakshi M Rana, Marcus R Pereira, Jonathan Hand, Sapna A Mehta, Joanna Schaenman, Carlos A Q Santos, Saima Aslam, Nahel Elias, Jonah Odim, Megan Morsheimer, Dorry L Segev, Christine M Durand, Aaron A R Tobian, Andrew D Redd","doi":"10.1093/infdis/jiaf284","DOIUrl":"https://doi.org/10.1093/infdis/jiaf284","url":null,"abstract":"Transplantation of kidneys from donors with HIV to recipients with HIV (HIV D+/R+) has been shown to be safe and effective, but there is a unique risk of donor-derived HIV-superinfection (HIV-SI) in these recipients. Recipients from a multicenter observational HIV D+/R+ study were examined for HIV-SI using site-directed next-generation sequencing (Illumina). Eighteen HIV D+/R+ kidney transplant recipients had both baseline and follow-up samples that successfully amplified. One recipient was confirmed to have experienced donor-derived HIV-SI at week 26, but did not experience any clinically significant changes. HIV-SI in HIV D+/R+ transplant recipients is rare, and the clinical ramifications appear negligible.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"58 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144165509","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}