The Journal of Infectious Diseases最新文献

{"title":"PEPFAR Investments in National Public Health Institutes: HIV Control Through Strong Systems.","authors":"Andre R Verani,Eduardo Samo Gudo,Roma Chilengi,Shelly Bratton,Caroline R Carnevale,Lisa Nelson,Brittney Baack,Irene Benech,Andrew Auld,Elias Durry,Ruth Steinhouse,Haftom Taame Desta,Tajudeen Raji","doi":"10.1093/infdis/jiaf339","DOIUrl":"https://doi.org/10.1093/infdis/jiaf339","url":null,"abstract":"National public health institutes (NPHIs) are governmental institutions with a public health mandate, which often includes reference laboratories, surveillance, outbreak preparedness and response, research, public health workforce, scientific communication to translate data into policy, and more. NPHIs are applying public health expertise to help end HIV/AIDS as a public health threat by 2030, in coordination with other key stakeholders, including not just ministries of health but also national AIDS councils, bilateral and multilateral partners, the private sector, civil society, and others. The President's Emergency Plan for AIDS Relief (PEPFAR) has invested in NPHIs to strengthen their HIV-related public health systems (eg, workforce development, accreditation of reference laboratories, improvement of infrastructure) and directly support targeted HIV activities (eg, national surveys, reference laboratory services, workforce training). Here, we highlight 2 examples of African NPHIs that have partnered with PEPFAR over the years (Mozambique and Zambia). PEPFAR's investments in NPHIs can leverage other investments in global health security.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"53 1","pages":"S125-S129"},"PeriodicalIF":0.0,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103557","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":"Leveraging PEPFAR- and Global Fund-Supported Laboratory Network for Integrated Disease Testing: Lessons From Integrated HIV, Tuberculosis, and COVID-19 Testing in Nigeria.","authors":"McPaul Okoye,Catherine Okoi,Nicole Espy,Nwando Mba,Celestina Obiekea,Anthony Ahumibe,Kingsley Madubuike,Nnaemeka Ndodo,Innocent Okoli,Kingsley Njoku,Chibuzor Eneh,Afolabi Akinpelu,Olajumoke Babatunde,Philippe Chebu,Christopher Chime,Nnaemeka C Iriemenam,Clement Zeh,Patricia Hall-Edison,Obinna Nnadozie,Israel Audu,Victor Obianeri,Chika Onwuamah,Aminu Suleiman,Jibrin Kama,Catherine Godfrey,Chinyere Okolo,Emmanuel Agogo,Dhamari Naidoo,Chidozie Ezechukwu,Akudo Ikpeazu,Chukwuma Anyaike,Mahesh Swaminathan,Mary Boyd,Ifedayo Adetifa,Chikwe Ihekweazu","doi":"10.1093/infdis/jiaf334","DOIUrl":"https://doi.org/10.1093/infdis/jiaf334","url":null,"abstract":"The Nigeria Centre for Disease Control and Prevention, as part of the strategic approach to the COVID-19 outbreak response in Nigeria, coordinated the implementation of an integrated disease testing (IDT) strategy with support from multiple partners. This involved adaptation of existing US President's Emergency Plan for AIDS Relief (PEPFAR)- and Global Fund-supported molecular laboratory networks and integration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing into these. This enabled the country to provide large-scale testing and rapid return of results for SARS-CoV-2 from 2020 to 2022. IDT provided an opportunity for mainstreaming outbreak response into existing human immunodeficiency virus (HIV) and tuberculosis testing laboratories. Lessons learned from this have informed the adoption of IDT across the country laboratory network as an efficient approach to multiple disease testing and pandemic preparedness and response in Nigeria.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"56 1","pages":"S150-S154"},"PeriodicalIF":0.0,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103499","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":"Implementation of All-inclusive Global Purchasing Agreements for Viral Load and Infant Diagnosis in PEPFAR-Supported Countries.","authors":"George Alemnji,Clement Zeh,Ravikiran Bhairavabhotla,Matthew Wattleworth,Jason Williams","doi":"10.1093/infdis/jiaf336","DOIUrl":"https://doi.org/10.1093/infdis/jiaf336","url":null,"abstract":"The US President's Emergency Plan for AIDS Relief (PEPFAR) continues to support scaling up of human immunodeficiency virus (HIV) viral load (VL) and early infant diagnosis (EID) tests to meet UNAIDS 95-95-95 global targets. To improve price transparency and standardization of service-level agreements, and avoid outright purchase of laboratory instruments, PEPFAR in the 2018 Country Operational Plan recommended the transition of HIV VL and EID commodities to \"all-inclusive\" pricing agreements. This article highlights the process used in implementing this diagnostics procurement shift. Key benefits realized include significant cost savings of >$130 M; overall improvement of the health system by reducing the occurrence of reagent stock outs, unplanned instrument downtime, and test sample backlog and rejections; increased availability of VL and EID tests; and shortened turn-around time for delivery of test results. In this article, ee describe this process, along with the challenges faced, future opportunities, and recommendations.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"6 1","pages":"S155-S159"},"PeriodicalIF":0.0,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103514","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 major outer membrane protein P5 binds vitronectin to mediate serum resistance in non-typeable Haemophilus influenzae.","authors":"Sandra Jonsson,Martina Janoušková,Vaishnavi Venkatesh Rao,Junkal Garmendia,Yu-Ching Su,Kristian Riesbeck","doi":"10.1093/infdis/jiaf489","DOIUrl":"https://doi.org/10.1093/infdis/jiaf489","url":null,"abstract":"Acquisition of complement regulators is a virulence strategy used by non-typeable Haemophilus influenzae (NTHi) to evade complement-mediated killing by the host. The major outer membrane protein of NTHi, P5, binds C4b-binding protein and factor H to promote bacterial serum resistance. We show that P5 also binds vitronectin that inhibits the formation of the membrane attack complex at the terminal stage of the complement pathway. Heterologous surface expression of P5 variants from NTHi strains 3655, KR271, KR317 and P652 promoted vitronectin binding to the P5-expressing E. coli. In contrast, deletion of P5 from the NTHi strains reduced vitronectin binding. Vitronectin acquisition conferred serum resistance to P5-expressing E. coli, but not to NTHi ΔompP5 mutants. Using site-directed mutagenesis, extracellular loop 2 of the P5 variants was identified as the binding site for vitronectin. In conclusion, our findings highlight P5 as a receptor for vitronectin that promotes NTHi serum resistance.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"60 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103545","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":"Mycobacterium tuberculosis PE_PGRS62 protein inhibits type I IFN responses to promote HIV-2 replication by directly interacting with IRF3","authors":"Chaohu Pan, Hui Xu, Min Huang, Junyan He, Siqi Li, Xiaoyu Tao, Tingzhi Cao, Guoliang Zhang","doi":"10.1093/infdis/jiaf484","DOIUrl":"https://doi.org/10.1093/infdis/jiaf484","url":null,"abstract":"Co-infection with Mycobacterium tuberculosis (Mtb) and HIV-2 increased the viral load of HIV-2. Type I interferons (IFNs) are essential for limiting HIV-2 progression. However, it is unclear whether and how Mtb affects HIV-2 co-infection by regulating type I IFNs. Here, Mtb PE_PGRS62 protein was identified as an inhibitor of cGAS-STING-mediated type I IFN expression by performing functional screens. Ectopic expression of PE_PGRS62 impaired type I IFN expression stimulated by cytosolic DNA, while knockout of pe_pgrs62 potentiated Mtb-induced type I IFN and downstream IFN-stimulated gene. PE_PGRS62 interacts directly with IRF3 and inhibits the interaction of IRF3 with TBK1 as well as the binding of IRF3 to the IFNβ promoter. Furthermore, reduced HIV viral load was observed in pe_pgrs62 knockout Mtb-infected macrophages compared with wild type Mtb. These findings reveal an important mechanism by which Mtb infection promotes HIV-2 immune evasion.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"72 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089561","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":"Evaluation of Immunization Route in Induction of Vaccine-Mediated Anti-Gonococcal Immune Responses in a Murine Model of Ascending Infection","authors":"Kathryn A Matthias, Kristie L Connolly, Ann E Jerse, Ogan K Kumova, Andrew N Macintyre, Mary C Gray, Keena S Thomas, Alison K Criss, Ryszard A Zielke, Lixin Li, Aleksandra E Sikora, Fidel Ramirez-Bencomo, Angela Thistlethwaite, Jeremy P Derrick, Wei-En Lu, Margaret C Bash","doi":"10.1093/infdis/jiaf445","DOIUrl":"https://doi.org/10.1093/infdis/jiaf445","url":null,"abstract":"Background Identification of immune correlates in murine gonorrhea models has been hampered by study-dependent differences in vaccine antigens and administration routes. We previously showed that detergent-detoxified outer membrane vesicles (dOMVs) isolated from a PorA-, PorB-, and RmpM-deficient meningococcal strain (ΔABR) elicit antibodies that cross-react with Neisseria gonorrhoeae and enhance gonococcal clearance in a mouse model of lower reproductive tract infection. In this study, we investigated whether (1) ΔABR dOMVs can protect mice from ascending gonococcal infection and (2) vaccination route influences immune responses. Methods Mice were vaccinated subcutaneously (SC) or intraperitoneally (IP) and then vaginally inoculated with gonococci. Bioburden of mice was measured and assessed relative to ΔABR dOMV-induced cellular and humoral immune responses. Results Subcutaneous and intraperitoneal vaccination accelerated gonococcal clearance from the lower and upper reproductive tract at similar rates. Probing of gonococcal protein microarrays with immune sera from the 2 groups identified multiple vaccine targets that were commonly immunogenic. Despite comparable clearance patterns in vaccinated mice, differences in immune induction were observed that were dependent on administration route. SC immunized mice demonstrated a neutrophil influx that correlated with decreased vaginal bioburden; higher serum bactericidal activity against nonsialylated gonococci was also noted. In contrast, IP immunization induced higher serum and vaginal IgA levels, serum bactericidal activity against sialylated gonococci, and antigonococcal opsonophagocytic killing activity of neutrophils. Conclusions This work demonstrates that ΔABR dOMVs protect against ascending gonococcal infection and that cellular and functional antibody responses to the same candidate vaccine may vary depending on immunization route.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089598","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":"Immune Correlates and Vaccine Immunobridging: Statistical Innovations, Challenges, and Opportunities","authors":"Marco Carone, Charles J Wolock, Antonio Olivas-Martinez, Andrea Rotnitzky, Peter B Gilbert","doi":"10.1093/infdis/jiaf451","DOIUrl":"https://doi.org/10.1093/infdis/jiaf451","url":null,"abstract":"In immunobridging, an investigational vaccine is approved based on a randomized trial of this vaccine versus an approved vaccine with an immunogenicity primary endpoint. Justification for immunobridging requires demonstration that meeting trial success criteria implies the investigational vaccine provides worthwhile protection against a relevant endpoint for a context of use. We consider recent statistical approaches whose integration supports immunobridging: (1) variable importance prediction analysis characterizing immune markers as correlates of risk; (2) controlled risk causal analysis evaluating markers as correlates of protection; and (3) transportability analysis combining data from efficacy and immunobridging trials for estimating investigational versus approved relative-vaccine efficacy.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089605","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":"Spontaneous Clearance of PCR-positive Plasmodium vivax Parasitemia in Northwestern Thailand: An Epidemiological Perspective","authors":"Pyae Linn Aung, Piyarat Sripoorote, Pattamaporn Petchvijit, Kritsana Suk-aum, Khaing Zin Zin Htwe, Saranath Lawpoolsri, Wang Nguitragool, Liwang Cui, Jaranit Kaewkungwal, Jetsumon Sattabongkot","doi":"10.1093/infdis/jiaf473","DOIUrl":"https://doi.org/10.1093/infdis/jiaf473","url":null,"abstract":"Background Asymptomatic, low-density Plasmodium vivax infections pose a significant challenge to malaria elimination because of their subclinical presentation and potential for ongoing transmission. However, the natural history of such untreated infections, including the extent to which they resolve spontaneously, remains poorly understood and has not been systematically studied for P. vivax. Methods We conducted a longitudinal cohort study from 2018 to 2023 in northwestern Thailand, incorporating 14 rounds of mass blood surveys (MBS) covering approximately 5,000 individuals. Blood samples were screened for P. vivax using both microscopy and PCR. Participants with PCR-positive, submicroscopic parasitemia were followed in subsequent surveys to assess infection dynamics. Turnbull survival analysis estimated time to spontaneous clearance, and Cox proportional hazards models identified demographic factors associated with clearance. Results Among 210 P. vivax infections detected by microscopy and/or PCR, 154 were detected only by PCR. After excluding individuals lost to follow-up or with coinfections, 101 participants were analyzed. Most infections (72, 69.9%) cleared spontaneously within three subsequent MBS. Turnbull survival analysis revealed that the probability of persistent infections declined to 25.0% (95%CI: 4.0–100.0) by day 47 and 7.0% (95%CI: 1.0–38.0) by day 232. Clearance was not significantly associated with age, sex, nationality, occupation, or education. Conclusions A considerable proportion of submicroscopic P. vivax infections resolved spontaneously without treatment, providing the first field-based evidence of this phenomenon. These findings suggest a role for naturally acquired immunity and highlight implications for surveillance and targeted intervention strategies in malaria elimination contexts.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089609","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":"Phylogenetic context of antibiotic resistance provides insights into the dynamics of resistance emergence and spread","authors":"Kyle J Gontjes, Aryan Singh, Sarah E Sansom, James D Boyko, Stephen A Smith, Ebbing Lautenbach, Evan Snitkin","doi":"10.1093/infdis/jiaf478","DOIUrl":"https://doi.org/10.1093/infdis/jiaf478","url":null,"abstract":"Background To ameliorate the antibiotic resistance crisis, the drivers of resistance emergence and resistance spread must be better understood. Methods Whole-genome sequencing and susceptibility testing were performed on clinical carbapenem-resistant Klebsiella pneumoniae isolates collected from August 2014 to July 2015 across 12 long-term acute care hospitals. Ancestral state reconstruction partitioned patients with resistant strains into those that likely acquired resistance via de novo evolution or cross-transmission. Logistic regression was used to evaluate the associations between patient characteristics/exposures and these two pathways: resistance due to predicted within-host emergence of resistance, and resistance due to predicted cross-transmission. This framework is available in the user-friendly R package, phyloAMR (https://github.com/kylegontjes/phyloAMR). Results Phylogenetic analysis of 386 epidemic lineage carbapenem-resistant Klebsiella pneumoniae sequence type 258 isolates revealed differences in the relative contribution of de novo evolution and cross-transmission to the burden of resistance to five antibiotics. Clade-specific variations in rates of resistance emergence and their frequency and magnitude of spread were detected for each antibiotic. Phylogenetically-informed regression modeling identified distinct clinical risk factors associated with each pathway. Exposure to the cognate antibiotic was an independent risk factor for resistance emergence (trimethoprim-sulfamethoxazole, colistin, and novel beta-lactam/beta-lactamase inhibitors) and resistance spread (trimethoprim-sulfamethoxazole, amikacin, and colistin). In addition to antibiotic exposures, comorbidities (e.g., stage IV+ decubitus ulcers) and indwelling medical devices (e.g., gastrostomy tubes) were detected as unique risk factors for resistance spread. Conclusions Phylogenetic contextualization generated insights and hypotheses into how bacterial genetic background, patient characteristics, and clinical practices influence the emergence and spread of antibiotic resistance.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089600","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":"Disparate kinetics of viable virus shedding in immunocompromised patients: SARS-CoV-2 versus influenza virus – a prospective real-world cohort study","authors":"So Yun Lim, Jungmin Lee, Ji-Soo Kwon, Euijin Chang, Joo-Yeon Lee, Man-Seong Park, Sung-Han Kim","doi":"10.1093/infdis/jiaf479","DOIUrl":"https://doi.org/10.1093/infdis/jiaf479","url":null,"abstract":"There are limited data comparing viral shedding between influenza and SARS-CoV-2 in immunocompromised patients. We prospectively enrolled 70 SARS-CoV-2 and 16 influenza patients, with 48 SARS-CoV-2 patients matched to 16 influenza patients by propensity score. Weekly-collected respiratory samples were subjected to viral culture and antigen testing. In matched cohorts, the time to culture-confirmed viral clearance was shorter for influenza than SARS-CoV-2 (median, 4.5 vs. 29 days; adjusted Hazard Ratio [aHR] 27.5; P <0.001), and antigen negativity occurred faster (3 vs. 23 days; aHR 19.2; P <0.001). These findings show different clearance kinetics for influenza and SARS-CoV-2 in immunocompromised patients.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089604","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}