The Journal of Infectious Diseases最新文献

{"title":"Evaluation of Three Recombinant Live-Attenuated Respiratory Syncytial Virus Vaccines RSV/ΔNS2/Δ1313/I1314L, RSV/6120/ΔNS2/1030s, and RSV/276 in RSV Seronegative Children","authors":"Coleen K Cunningham, Ruth A Karron, Elizabeth J McFarland, Mark J Giganti, Rachel Ketchum, Charlotte Perlowski, Jennifer Libous, Haley Brozik, Jennifer Oliva, Dwight E Yin, Patrick Jean-Philippe, Jack Moye, Elizabeth Schappell, Emily A Barr, Vivian Rexroad, Benjamin Johnston, Grace Malonga, Mariam Aziz, Tori Rutherford, Heidi Sallee, Jennifer Jao, Robert W Frenck, Jaime G Deville, Emmanuel B Walter, James Christopher Day, Stephen A Spector, Andrés Camacho-Gonzalez, Joanna Dobroszycki, Sharon Nachman, Mary E Paul, James Campbell, Xueqiao Liu, Lijuan Yang, Cindy Luongo, Peter L Collins, Ursula J Buchholz","doi":"10.1093/infdis/jiag489","DOIUrl":"https://doi.org/10.1093/infdis/jiag489","url":null,"abstract":"Background An effective RSV vaccine which elicits active immunity and lasting protection could have a significant impact on child health. This study evaluated safety and immunogenicity of three intranasal live-attenuated candidate RSV vaccines, RSV/ΔNS2/Δ1313/I1314L, RSV/6120/ΔNS2/1030s, and RSV/276 to placebo. Methods Healthy, RSV-seronegative children 6-24 months of age were randomized to receive one of three candidate vaccines or placebo in a blinded manner. Participants were monitored for vaccine reactogenicity and RSV serum antibodies and over the subsequent RSV season. Results Between years 2019 and 2023, 67 participants were randomized, including 20 each to RSV/ΔNS2/Δ1313/I1314L, RSV/6120/ΔNS2/1030s, and placebo arms and seven to the RSV/276 arm. The RSV/276 arm was closed early due to an excess of mild cough events in another study. The proportion (95% confidence interval) of children who experienced at least one solicited an adverse event during the 28 days after inoculation was 55% (32%, 77%) in the RSV/ΔNS2/Δ1313/I1314L arm, 40% (19%, 64%) in the RSV/6120/ΔNS2/1030s arm, 71% (29%, 96%) in the RSV/276 arm, and 55% (32%, 77%) in the placebo arm. Events were mostly Grade 1 and were often associated with other viruses. The proportion of children with a ≥4-fold increase in serum RSV-neutralizing antibody titer in each of the candidate vaccine arms (>70%) was significantly greater than in the placebo arm (15%). Conclusions RSV/ΔNS2/Δ1313/I1314L and RSV/6120/ΔNS2/1030s had excellent safety and immunogenicity; the assessment of RSV/276 was limited by the small sample size. RSV/ΔNS2/Δ1313/I1314L and RSV/6120/ΔNS2/1030s were deemed suitable for further evaluation.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149086551","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":"The host transcriptional response to real-world cryptococcosis in the setting of advanced HIV disease defines dysregulated immune responses that underlie increased vulnerability to infection","authors":"Beatrice Z Sim, Julie M Steinbrink, Cameron Miller, Alejandro Antonia, J Andrew Alspaugh, Deng B Madut, Manuela Carugati, John A Crump, Blandina T Mmbaga, James S Ngocho, Asia H Kipengele, Philoteus A Sakasaka, Nathaniel H Kalengo, Venance P Maro, Matthew P Rubach, Micah T McClain","doi":"10.1093/infdis/jiag497","DOIUrl":"https://doi.org/10.1093/infdis/jiag497","url":null,"abstract":"Background Cryptococcus causes life-threatening infections; however, immune programs driving pathogenesis of these infections in the human host remain incompletely described. We leveraged whole-blood transcriptomic analysis to define distinct, conserved elements of the host immune response in participants with cryptococcal infections. Methods RNA sequencing was performed on whole blood from adult febrile inpatients admitted to two hospitals in Moshi, Tanzania to compare gene expression between participants with cryptococcal, bacterial, or viral diseases, and adult community controls. Differential expression and gene set enrichment analyses were used to characterize expression differences between pathogen-class groups. Penalized logistic regression was used to identify gene expression signatures capable of identifying Cryptococcus disease. Results Out of 118 participants, 13 (11%) had cryptococcal disease and 41 (34.7%) were persons living with HIV (PLWH). Genes upregulated in response to cryptococcosis compared to non-acutely-infected community controls reflected complement activation, neutrophil activation, type I interferon signaling, and myeloid dendritic cell differentiation. When compared to combined bacterial or viral illnesses, cryptococcal disease demonstrated hyperactivation of both innate and humoral immune pathways. A series of classifiers were developed that distinguished between cryptococcal and combined bacterial or viral diseases with an AUC of 0.946. Conclusion Overall, the host response to cryptococcosis in individuals with advanced HIV as manifested in transcriptional profiles informs our understanding of the pathophysiology of and susceptibility to cryptococcal infection and may support development of novel diagnostic and therapeutic approaches.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149083823","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":"Population-level shift in ex vivo artemisinin susceptibility in Plasmodium falciparum : comparison of 2014–2015 and 2022–2024 surveys in northern Uganda","authors":"Mie Ikeda, Betty Balikagala, Naoko Yoshida, Megumi Kaneko-Ogawa, Jun Hirata, Makoto Hirai, Osbert T Katuro, Makoto Kubo, Naoyuki Fukuda, Miki Sakurai-Yatsushiro, Dennis A Anywar, Emmanuel I Odongo-Aginya, David M Ogwang, Nirianne M Q Palacpac, Toshihiro Horii, Toshihiro Mita","doi":"10.1093/infdis/jiag494","DOIUrl":"https://doi.org/10.1093/infdis/jiag494","url":null,"abstract":"Background Artemisinin (ART) partial resistance has been reported in Southeast Asia and East Africa, but its population-level phenotypic dynamics remain poorly understood. We aimed to evaluate population-level changes in ART susceptibility in Plasmodium falciparum in northern Uganda using an ex vivo quantitative ring-stage survival assay (qRSA), which assesses parasite survival across seven serial dihydroartemisinin (DHA) concentrations. Methods We conducted repeated cross-sectional surveys in 2014, 2015, 2022, and 2024 in Gulu, northern Uganda. Ex vivo qRSA was used to compare parasite survival across DHA concentrations before and after the known emergence of ART partial resistance. qRSA resistance level was operationally defined as the highest DHA concentration at which survival rate (SR) was ≥1%. Results 323 participants with uncomplicated symptomatic P. falciparum monoinfection were enrolled. qRSA data were obtained from 156 samples. After the known emergence of ART partial resistance, low-level parasite survival persisted toward progressively higher DHA concentrations, resulting in a shift toward higher qRSA resistance level. All pure kelch13 A675V mutants were classified at the highest qRSA resistance level (700 nM), whereas pure C469Y mutants were distributed across qRSA resistance levels from 87.5 to 700 nM. A similar, but less robust, shift was observed among kelch13 wild-type isolates, accompanied by increased SRs, particularly at 700 nM. Conclusions These findings suggest that the population-level shift in ART susceptibility was characterized by persistence of low-level survival toward higher DHA concentrations. Multi-concentration RSA may provide additional insights into early changes in ART susceptibility that are not captured by conventional binary resistance classifications.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"63 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149077623","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":"Low birthweight and prematurity, but not malaria chemoprevention, are associated with reduced pneumococcal vaccine immunogenicity in Ugandan infants","authors":"Kenneth Musinguzi, Alyssa N Sbarra, Florian Bach, Felistas Nankya, Karen Bino Achom, Caroline Mwubaha, Patience Nayebare, Evelyn Nansubuga, Abel Kakuru, Jimmy Kizza, Zedekiah Maato, Emmanuel Arinaitwe, Kathleen Dantzler Press, Bernard Ssentalo Bagaya, Stephen Tukwasibwe, Isaac Ssewanyana, Joaniter Immaculate Nankabirwa, Moses Robert Kamya, Grant Dorsey, Saki Takahashi, Prasanna Jagannathan","doi":"10.1093/infdis/jiag488","DOIUrl":"https://doi.org/10.1093/infdis/jiag488","url":null,"abstract":"Background Malaria exposure has been hypothesized to alter immune responses to childhood vaccines, but evidence is inconsistent. We evaluated whether early-life malaria exposure and perennial malaria chemoprevention (PMC) modify antibody responses to the 10-valent pneumococcal conjugate vaccine (PCV-10) among infants in a high malaria transmission setting in eastern Uganda. Methods This study was nested within the MIC-DroP trial (NCT04978272) whereby 202 infants were selected for inclusion. Serotype-specific IgG concentrations were measured using an in-house multiplex seroassay from samples obtained at 8 and 24 weeks of age. Immunogenicity was quantified as the log10 fold-change in IgG concentration between the 8 and 24-week timepoints, and seroconversion as ≥0.35 μg/mL at week 24 (i.e., seropositive). Generalized estimating equation models were used to assess associations of PCV-10 immunogenicity and seroconversion with malaria exposure, malaria chemoprevention and birth outcomes. Results Among the 195 of 202 infants who completed the three-dose PCV-10 series, neither infant PMC nor malaria exposure from study enrollment to 14 weeks were associated with PCV-10 immunogenicity or seroconversion. In contrast, low birthweight (<2500g) was associated with lower immunogenicity (82% lower [95% confidence interval (CI): 43-94%] antibody fold-change, p=0.003) and reduced odds of seroconversion (OR=0.19 [95% CI: 0.06-0.57], p=0.003); preterm birth (<37 weeks) showed similar associations (79% lower [95% CI: 24-94%] antibody fold-change, p=0.018; OR=0.181 [95% CI: 0.05-0.65], p=0.009). Conclusion In this malaria-endemic setting, early-life malaria exposure and chemoprevention did not measurably alter PCV-10 antibody responses. However, low birthweight and prematurity were associated with reduced vaccine immunogenicity.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149067339","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":"Changes in Doravirine Pharmacokinetics During Pregnancy: A Longitudinal Single Dose Study","authors":"Amanda Poliseno, Lisa Rahangdale, Amanda Schauer, Craig Sykes, Cynthia Gay, Emma Trawick, Angela D M Kashuba","doi":"10.1093/infdis/jiag484","DOIUrl":"https://doi.org/10.1093/infdis/jiag484","url":null,"abstract":"Physiological changes during pregnancy may alter the pharmacokinetics of antiretrovirals, but pregnancy pharmacokinetic/dynamic data may lag years after drug approval. This single-dose approach allows for earlier data generation, estimating total and protein-unbound doravirine pharmacokinetics in women living with HIV during their second trimester, third trimester, and postpartum.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149048648","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":"Risk maps and spatial models for clinical infectious disease decision-making","authors":"Seth D Judson","doi":"10.1093/infdis/jiag480","DOIUrl":"https://doi.org/10.1093/infdis/jiag480","url":null,"abstract":"Risk maps and spatial models provide key information about the endemicity and spread of infectious diseases. Novel data streams and statistical techniques, with the aid of artificial intelligence, create the opportunity for modern risk maps. To ensure that these tools are useful for clinical decision-making, we need to understand how risk maps are used, how they are developed, and how they can be improved. This will be especially important for zoonotic, vector-borne, and environmental infectious diseases in the era of environmental change and globalization.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149048647","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":"The Effect of Pertussis Vaccination During Pregnancy on Pertussis and Diphtheria Immunity in Children at 3 and 4 Years of Age","authors":"Milja Miettinen, Mikko Lehtosalo, Alex-Mikael Barkoff, Denise Anabe, Johanna Teräsjärvi, Aapo Knuutila, Jussi Mertsola, Qiushui He, Lauri Ivaska","doi":"10.1093/infdis/jiag472","DOIUrl":"https://doi.org/10.1093/infdis/jiag472","url":null,"abstract":"Pertussis vaccination during pregnancy protects young infants but blunts their antibody responses to primary immunization; the duration of this effect beyond infancy is unknown. In a clinical trial, we followed children born to tetanus-diphtheria-acellular pertussis-vaccinated (n=47) and unvaccinated (n=22) mothers to 4 years of age. At both 3 and 4 years, children born to Tdap-vaccinated mothers had lower anti-pertussis toxin and anti-diphtheria toxin IgG concentrations than control children, and pertussis toxin seropositivity and diphtheria seroprotection rates were low in both groups. After a preschool acellular pertussis booster at 4 years, antibody concentrations increased to comparable levels in both groups.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149020680","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":"Brief exposure to hyperoxia is associated with reduced Plasmodium falciparum in vitro tolerance to Dihydroartemisinin","authors":"Standwell C Nkhoma, Amel O A Ahmed, Sujatha Rashid, Robert E Molestina","doi":"10.1093/infdis/jiag490","DOIUrl":"https://doi.org/10.1093/infdis/jiag490","url":null,"abstract":"The ring-stage survival assay (RSA) is a valuable tool for assessing in vitro Plasmodium falciparum tolerance to Dihydroartemisinin. However, laboratories with unreliable or no access to premixed commercial gas may not perform the RSA under the recommended physiological normoxia. We measured survival rates of ART-sensitive and ART-resistant strains in the normoxic commercial gas and hyperoxic candle jar gas. RSA read-outs for ART-resistant strains were significantly lower (p<0.05) under hyperoxia compared to physiological normoxia, whereas those of ART-sensitive strains were unaltered. These findings have important implications for interlaboratory comparison of RSA data and understanding the mechanisms of resistance to endoperoxide drugs.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149033078","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":"HPV33 and HPV45 sublineage antigenicity defined by neutralizing antibodies elicited during natural infection","authors":"Kazutomo Yokoya, Kavita Panwar, Vanessa Tenet, Rana Hussain, Filomeno Coelho da Silva, Lisa Mirabello, John T Schiller, Gary M Clifford, Simon Beddows","doi":"10.1093/infdis/jiag487","DOIUrl":"https://doi.org/10.1093/infdis/jiag487","url":null,"abstract":"Human Papillomavirus variants are classified into lineages and sublineages based upon their genome sequence, but the impact of variation on the function of encoded proteins is unclear. We used a global panel of natural infection sera and relational antigenic maps to assess HPV33 and HPV45 neutralizing antibody specificity. HPV33 A2, A3, B and C variants were spatially resolved ∼5-fold distant from the A1 reference while HPV45 variants were resolved within ∼2-fold with differences mapped to residues on the capsid surface. These data inform the degree of lineage and sublineage specificity within the natural infection humoral immune response to oncogenic HPV.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149048650","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":"Rationale for a live-attenuated vaccine for cryptosporidiosis","authors":"A Clinton White, Sara M Dann, Alejandro Castellanos-Gonzalez","doi":"10.1093/infdis/jiag471","DOIUrl":"https://doi.org/10.1093/infdis/jiag471","url":null,"abstract":"Natural Cryptosporidium infection causes development of protective immunity. Live-attenuated vaccines stimulate both adaptive and “trained” innate immune responses. With advances in parasite genetics, target identification, and in vitro cultivation, we now propose development of a live-attenuated vaccine for cryptosporidiosis.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"226 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149022393","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}