AbstractObjectivespara-Aminosalicylic acid is an antifolate prodrug activated in the folate biosynthesis pathway of Mycobacterium tuberculosis (Mtb), ultimately inhibiting dihydrofolate reductase encoded by dfrA. Mutations in dfrA coding and upstream regions have not been thoroughly investigated. This study aimed to assess mutations in dfrA and its upstream regulatory region in clinical Mtb isolates.MethodsWe retrieved and analysed 6547 whole-genome sequences of Mtb clinical isolates. We identified 29 SNPs in the dfrA coding region and eight mutations in the thyA–dfrA upstream region. The most prevalent coding mutations and upstream mutations were selected for functional evaluation using thermal stability analysis, GFP reporter assays and para-aminosalicylic acid drug susceptibility test (DST).ResultsThe coding mutations Trp142→Gly, Gln28→Leu and Arg32→Pro were analysed for protein thermal stability and para-aminosalicylic acid susceptibility. Gln28→Leu showed increased thermal stability relative to the WT, whereas Trp142→Gly and Arg32→Pro exhibited reduced stability. Consistently, para-aminosalicylic acid DST demonstrated that Gln28→Leu conferred an 8-fold increase in para-aminosalicylic acid resistance, while Trp142→Gly and Arg32→Pro remained phenotypically susceptible. Moreover, GFP reporter assays revealed that G70T, G59T and C48A increased promoter activity by 13-fold, 4-fold and 3-fold, respectively, whereas the remaining mutations showed no significant effect. Findings were verified by para-aminosalicylic acid DST, where G70T, G59T and C48A showed para-aminosalicylic acid resistance compared with WT.ConclusionsBy integrating genomic analysis with functional assays of thermal stability, promoter activity and drug susceptibility, this study demonstrated that mutations in dfrA coding and upstream regulatory regions contribute to para-aminosalicylic acid resistance in Mtb clinical isolates.

Antimicrobial resistance (AMR) is a growing public health concern, influenced by public behaviours. This study aimed to systematically review and synthesize qualitative and quantitative studies on public knowledge, beliefs and behaviours related to antibiotics and AMR, and explore gender differences, in high-income countries.Materials and methodsEleven databases including Web of Science Core Collection, Medline and PsycINFO were searched for primary studies published between August 2014 and 12 June 2026. This article reports the high-income country subset of a larger global review; other results will be reported separately. We carried out a descriptive, non-meta-analytic synthesis at study- and country-level by calculating the mean, SD, median and range of the proportion of participants whose data demonstrated incorrect knowledge, misconceptions, and positive or negative behaviours. Gender differences were synthesized narratively. Qualitative data were synthesized under each outcome using deductive thematic analysis.ResultsOf 12 338 records identified, 121 were globally eligible. Thirty-three high-income country studies were included in this article (29 quantitative and 4 qualitative, with 33 252 participants). Cross-country variability was found in knowledge, beliefs and behaviours. Misunderstandings were prominent around the definition of AMR and its implications for health. Narrative gender differences were inconsistent and qualitative data were limited, but gave insight into potential drivers of behaviours.ConclusionsDespite international variations, knowledge gaps, misconceptions and counterproductive behaviours were widespread. Findings show that AMR is a system-wide issue that requires attention from all One Health stakeholders, and a unified, multi-faceted, multidisciplinary approach that can help tackle the continuing public health threat, and change behaviour to protect health.

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.MethodsWe 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%.Results323 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.ConclusionsThese 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.

Kluyvera spp. are increasingly recognised as significant pathogens in humans. Recent reports of carbapenemase-producing (CP) Kluyvera spp. raise a concern that they may be disseminating carbapenemases to other species undetected. Research on CP-Kluyvera spp. is scarce, and little is known about their characteristics.MethodsWe aimed to investigate the epidemiology of CP-Kluyvera spp. in Israel, characterise their antimicrobial resistance and examine mechanisms of transmission of carbapenemase genes. We performed a retrospective epidemiological analysis of all cases of CP-Kluyvera spp. reported to Israel's national surveillance system of carbapenem-resistant Enterobacterales from 2008 to 2023. Hospital-acquired cases were categorized as sporadic or part of an outbreak. Microbiological characterisation of 22 available isolates included antimicrobial susceptibility testing and whole genome sequencing.ResultsThere were 146 cases of CP-Kluyvera spp. in 2008-2023. 145 were detected in rectal screening samples, and one in a blood culture. The dominant reported species was K. ascorbata (60.3%), followed by K. cryocrescens (24%). The common carbapenemases were KPC (67.1%) and NDM (26.7%). 41.1% of hospital-acquired cases were classified as part of an outbreak.All characterised isolates were multidrug-resistant and produced at least one carbapenemase. Spread of carbapenemase genes in Kluyvera spp. was plasmid-driven by IncC and by Rep-A type plasmids.ConclusionsCases of CP-Kluyvera spp. increased annually. Spread of CP-Kluyvera was partially clonal, with both outbreaks and sporadic cases detected. We illustrated that Kluyvera spp. produce a variety of plasmid-borne ARGs, including carbapenemases, which could be horizontally transferred to additional bacterial species, revealing the increasing clinical significance of Kluyvera genus.

We conducted a systematic review and meta-analysis of group B Streptococcus (GBS) rectovaginal colonization prevalence, serotype distribution, and antimicrobial drug resistance (AMR) rates among pregnant women in the Asia-Pacific region. We included articles published in the MEDLINE, Embase, and PubMed databases during January 2014–October 2025. Overall, 1,623 studies were identified; 98 of those were included in the meta-analysis. Of 978,150 pregnant women, 172,973 were colonized with GBS; pooled estimated prevalence was 18.0% (95% CI 12%–23%). Studies from Southeast Asia were limited. GBS serotype distributions were reported in 24 studies; serotype III was the most common (range 5.0%–100.0%). Thirty studies included AMR rates; low (0%–2.0%) AMR rates were found for β-lactams. GBS colonization is common among pregnant women in the Asia-Pacific region. Continued surveillance of GBS prevalence will be needed, particularly in Pacific and Southeast Asian countries, to guide effective GBS prevention and treatment programs.

View abstract Background:Antimicrobial resistance is a global “silent pandemic” with dentistry contributing 10%–12% of outpatient antibiotic use. In low- and middle-income countries such as India, the absence of context-specific national dental antibiotic guidelines, widespread over-the-counter antibiotic access, and diagnostic limitations complicate rational prescribing and antimicrobial stewardship.Methods:A sequential explanatory mixed method study was conducted over 12 months in Varanasi. The quantitative component analyzed 2,844 dental prescriptions across primary, secondary, and tertiary care settings. Prescribing appropriateness was assessed using international evidence-based guidelines from the American Dental Association and Faculty of General dental Practice (UK). The qualitative component included 30 in-depth interviews with dental practitioners, analyzed using inductive thematic analysis to explore determinants of prescribing behavior.Results:Antibiotics were prescribed in 73.1% of cases, of which 69.6% were inappropriate. High prescribing rates observed in conditions where antibiotics are generally not indicated, including irreversible pulpitis (73.3%), apical periodontitis (92.3%), and implant procedures (100%). Broad-spectrum antibiotics predominated, particularly amoxicillin-clavulanic acid (43.0%) and cefpodoxime-clavulanic acid (21.7%). Qualitative findings identified that prescribing was driven by diagnostic uncertainty, defensive practice, patient expectations, and systemic constraints, including lack of national guidelines and unregulated antibiotic access.Conclusion:Inappropriate antibiotic prescribing in dentistry reflects a context-driven, multifactorial behavioral shaped by clinical, behavioral, and structural constraints rather than a simple knowledge deficit. Addressing this challenge requires context-specific national dental antibiotic guidelines, strengthened antimicrobial stewardship, improved diagnostic support, and regulatory enforcement. The proposed IDCARE+ framework offers a practical systems-based approach to promote rational antibiotic use in similar resource-constrained settings.

Variolation in China has a long history, yet the method remains underrepresented internationally, having limited recognition of medical rationale and indigenous development. We reviewed medical texts and records from late Imperial China and compared variolation chronology, techniques, and explanatory frameworks used in China versus India. Variolation in China was already in practice no later than the Chenghua–Longqing period of the Ming dynasty (1465–1572 CE), earlier than that reported in other countries. Sources from China described garment/blanket, lymph, and scab-derived inoculum methods for smallpox prevention. Scab-derived inocula, intranasal administration, and repeated passage techniques reflected empirical efforts to improve variolation reliability and reduce risk. Concepts of fetal toxin and seasonal pathogenic qi made variolation intelligible within contemporaneous medicine in China. Records from China predated sources from India and contained more detailed descriptions of variolation practices, supporting indigenous development and highlighting China’s central place in the early history of prophylactic inoculation.

Campylobacter spp. remain the leading bacterial cause of foodborne gastroenteritis in Western countries. We report sustained, previously unrecognized circulation of a multidrug-resistant Campylobacter coli sequence type 10042 lineage across Europe during 2018–2025. Whole-genome sequencing of 217 isolates from 9 countries spanning human, animal, food, and environmental sources identified cross-border clusters, including a large lineage linking primarily Portugal and Luxembourg, as well as Germany, Ireland, Spain, and the United Kingdom. Genomic data indicates ongoing clonal expansion with increasing diversification over time. Isolates exhibited a conserved multidrug-resistant phenotype, including resistance to fluoroquinolones, tetracyclines, and β-lactams; reduced susceptibility to carbapenems was observed. Resistance was associated with GyrA Thr86Ile, tet(O/32/O)/tet(O) genes, and blaOXA-61 promoter variants; variation in porA was linked to variable amoxicillin/clavulanic acid and ertapenem susceptibility. Those findings demonstrate that C. coli infections can involve sustained international transmission rather than sporadic cases and highlight the need for coordinated, cross-sector genomic surveillance to detect emerging antimicrobial-resistant lineages.

Highly pathogenic avian influenza H5Nx viruses remain a major zoonotic threat, yet global attention has focused largely on clade 2.3.4.4b, potentially overlooking major changes within long-endemic H5N1 lineages in Asia. Recent reports from South and Southeast Asia describe the emergence of reassortant clade 2.3.2.1 viruses alongside renewed human infections after apparent prolonged epidemiologic stability. Collectively, those events suggest a regional pattern rather than isolated anomalies. In this article, we argue that reassortment, rather than point mutation alone, might be an underrecognized driver of zoonotic risk in endemic H5N1 lineages and is reshaping those lineages. We examine why such events might be underrecognized in settings with entrenched poultry influenza, identify limitations of current surveillance systems, and call for integrated, real-time approaches linking genomic detection with phenotypic assessment across animal and human health sectors to enable timely risk assessment and coordinated public health action.

Bundibugyo virus disease (BVD), an Ebola virus species with no licensed vaccine or therapeutic, reemerged in May 2026 as a cross-border outbreak in Uganda and the Democratic Republic of the Congo. During a 2-day workshop, July 8–9, 2026, we conducted an early action review of the outbreak response using the 7-1-7 framework (7 days to detect, 1 day to notify, 7 days to complete early response actions) to assess timeliness and identify bottlenecks and enablers across 9 response pillars. Uganda declared its outbreak on May 15, 2026; by July 8, the country had recorded 20 confirmed cases (15 imported, 5 locally transmitted) and a case-fatality rate of 15%. Uganda met all 3 targets: detection in 6 days, notification in <1 day, and response completion in 2 days. Low clinical suspicion, cross-border data-sharing gaps, fragmented digital systems, and delayed community engagement were common bottlenecks; strong leadership and coordination structures were most cited enablers.

View abstract Objective:Evaluate outcomes of early versus late intravenous (IV)-to-oral antibiotic transition in patients with uncomplicated Enterobacterales bacteremia.Design:Multicenter, retrospective observational cohort study.Setting:Healthcare system with one tertiary care academic medical center and four community teaching hospitals.Patients:Adults with uncomplicated Enterobacterales bacteremia, clinical stability within 72 hours of antibiotic initiation, definitive source control, ability to take oral medication, and final susceptibility reports were included. The following were excluded: never received oral antibiotic; inadequate treatment duration; transitioned back to IV therapy; inappropriate antimicrobial therapy based on dosing or susceptibilities; transferred from outside institution; immunocompromised; pregnant.Methods:Early transition was considered IV-to-oral antibiotic transition by day 4 of therapy. The primary outcome was treatment failure within 30 days of antibiotic completion, a composite end point encompassing infection recurrence, escalation of antimicrobial therapy, infection-related re-admission, and death. Secondary outcomes included hospital length of stay and total antibiotic duration.Results:225 patients were included; 133 (59.1%) transitioned to oral antibiotics early and 92 (40.9%) transitioned late. There were no significant differences in the primary composite outcome of treatment failure for early transition versus late transition (6.0% vs 6.5%, P = .877). Early transition was associated with shorter median hospital length of stay (5 vs 7 d, P < .001) and total antibiotic duration (9 vs 12 d, P < .001).Conclusion:Early IV-to-oral antibiotic transition in patients with uncomplicated Enterobacterales bacteremia and clinical stability within 72 hours was effective with potential to reduce length of stay and total antibiotic duration.

Anaplasma capra is a recently discovered bacterial tickborne pathogen that was first identified in goats in 2012 and later in humans in China in 2015. We detected and genetically characterized A. capra in adult patients with suspected Crimean-Congo hemorrhagic fever (CCHF) in Turkey during the 2022 outbreak. We screened all patients for A. capra by using nested PCR targeting the gltA and groEL genes. We confirmed CCHF by molecular and serological tests. Of 263 patients, 6 (2.28%) were positive for A. capra. Sequence analysis revealed 84.16%–100% gltA gene similarity and 90.24%–100% groEL gene similarity with GenBank entries. Phylogenetic analysis confirmed all A. capra gene sequences belonged to genotype 1. Our results demonstrate clinical evidence of genotype 1 A. capra infection in humans. Our findings highlight the need for clinicians to consider A. capra in the differential diagnosis of CCHF-like symptoms, especially in endemic areas.

After its elimination from Mexico in 2003, myiasis caused by New World screwworm (NWS), Cochliomyia hominivorax, has recently reemerged as a public and animal health concern. We conducted a retrospective study of human New World screwworm myiasis cases reported through Mexico’s national surveillance system during April 13, 2025–March 14, 2026. Of 204 cases in official surveillance summaries, 202 had sufficient information for case-level clinical and epidemiologic analysis. Cases were concentrated in southern Mexico, particularly Chiapas, followed by Yucatán, Oaxaca, and Quintana Roo. Most (71.8%) cases occurred in men; mean patient age was 61.1 years. Lower limbs (55.0%) were the most frequently reported anatomic location, and 76.7% of patients had >1 concurrent condition. Six deaths were reported among patients with NWS myiasis; at the time of reporting, 1 death was attributed directly to NWS myiasis. Our findings support proactive clinical detection and integrated One Health surveillance along the expected northward spread of NWS.

The Orthomyxoviridae family includes influenza D virus (IDV), an emerging pathogen primarily affecting cattle and swine; there is evidence of cross-species transmission and potential zoonotic risk. Although active human infections have yet to be confirmed, high seroprevalence in cattle-exposed populations highlights the need for continued surveillance. We developed and validated a rapid, field-deployable reverse transcription loop-mediated isothermal amplification assay for IDV detection; specificity was 99.2% and sensitivity ranged from 95.6% (cycle quantification <30) to 81.8% (cycle quantification <40). This method offers a cost-effective, accessible alternative to quantitative reverse transcription PCR, enabling improved monitoring of IDV and reinforcing preparedness for emerging influenza threats.

Nontyphoidal Salmonella enterica serovar Hadar causes poultry-associated salmonellosis outbreaks in the United States. One persisting strain of Salmonella Hadar caused 5 multistate outbreaks resulting in ≈2,000 human cases during 2020–2023. The Centers for Disease Control and Prevention designated the strain as reoccurring, emerging, or persisting (REP), related within 26 core-genome allele differences. That REP strain has caused human illnesses by consumption of commercial poultry food products or contact with backyard poultry. To investigate the REP strain’s evolution and identify possible markers for source attribution, we performed phylogenetics and molecular clock analysis on 404 genomes subsampled from routine surveillance and outbreaks. The most recent common ancestor likely emerged in early 2018. We identified 2 clades: clade 1, associated with backyard poultry and other food sources, and clade 2, predominantly linked to commercial poultry products. We found 2 clade-specific single-nucleotide polymorphism markers; in silico screening of additional isolates supported their use for source attribution.

Highly pathogenic avian influenza (HPAI) A(H5N1) clade 2.3.4.4b virus continues to spread globally and sporadically transmits from avian reservoirs to mammalian hosts. In May 2024, H5N1 infections in young goats and alpacas in the United States were reported. Nevertheless, the overall susceptibility of camelids to clade 2.3.4.4b virus remains unclear. We conducted a controlled experimental infection study in 6 alpacas, assessing clinical signs, viral shedding, tissue distribution, and serologic responses after intranasal inoculation with HPAI H5N1 genotype B3.13 virus. Observed illness was generally mild; body temperature increased slightly and food intake reduced for up to 3 days postinfection. We detected viral RNA in nasal swab samples and confirmed infectious HPAI H5N1 virus. Immunohistochemistry and RNA in situ hybridization detected virus only in the nasopharyngeal tonsil and nasal conchae at 4 days postinfection. Our findings suggest alpacas are susceptible to productive H5N1 infection, highlighting implications for livestock surveillance and biosecurity in regions with ongoing circulation.

Bartonella quintana, the causative agent of trench fever, is a louseborne bacterial pathogen. During 2016−2017, we investigated B. quintana infection in macaques housed at 2 primate research institutes in Japan. We isolated B. quintana from 3 wild-caught Japanese macaques, which had been introduced into 1 institute in 2009. The macaques had received periodic ivermectin treatment every 1–2 years to control blood-feeding arthropods. Whole-genome comparisons revealed that the 3 isolates exhibit higher homology to a Japanese macaque–derived strain than to rhesus macaque–derived or human-derived strains. In addition, in all 3 isolates, the bepA locus was absent; we classified the trwL locus as structural variant C, consistent with known Japanese macaque–derived strains. Our findings suggest that B. quintana bacteremia in the macaques might have persisted for 7–8 years in captivity, and that the bacterium was not accidentally transmitted to them from humans by reverse zoonosis.

The province of Ontario, Canada, experienced a major resurgent outbreak of measles in 2025. We conducted wastewater surveillance concurrently with clinical-based surveillance to track measles incidence in southwestern Ontario, adjacent to the United States. Measles virus (MeV) signal in wastewater was positively associated with clinical cases but did not provide early alert of changes in measles incidence when resolved by epidemiologic week. Assessment of virus partitioning showed MeV RNA was broadly distributed in the liquid phase but is most concentrated in the solids. We adapted an assay for differentiation of vaccine and wild-type MeV and used it to detect vaccine genotype measles after a vaccination campaign targeting underserved groups. We estimated MeV shedding in wastewater through sampling of sewer laterals serving a hospital treating measles infections. This outbreak is a case study in which we highlighted the use of wastewater surveillance for measles while supporting method development in real time.

Crimean-Congo hemorrhagic fever (CCHF) during pregnancy is associated with severe maternal and fetal complications, but evidence remains limited to heterogeneous case reports. We synthesized patient-level data from published and unpublished cases identified through systematic database searches and direct collaboration with centers in CCHF-endemic areas. We harmonized patient-level clinical, laboratory, obstetric, treatment, and outcome data for 55 pregnancies. The maternal mortality rate was 28.8% (15/52), and fetal loss occurred in 57.4% (31/54) of cases. Maternal mortality rates increased with advancing gestation, reaching 31.3% in the third trimester, but fetal loss was highest (85.7%) in the first trimester. Ribavirin treatment during the third trimester was associated with lower observed maternal mortality rates (odds ratio 0.33, 95% CI 0.13–0.84; p = 0.031). Our findings highlight gestational age–specific risks of CCHF and support the need for standardized management protocols and strengthened CCHF surveillance during pregnancy in endemic regions.

Salmonella enterica subspecies enterica serovar Infantis carrying the blaCTX-M-65 gene has been increasingly detected globally, including in South Korea, since 2022. We analyzed 65 blaCTX-M-65–positive Salmonella Infantis isolates from humans, poultry, and wastewater collected during 2022–2024 by using whole-genome sequencing and phylogenomic analysis. All isolates were multidrug resistant, commonly to aminoglycosides, β-lactams, quinolones, tetracyclines, amphenicols, and folate pathway inhibitors. Phylogenetic analysis revealed high genetic similarity among isolates from humans, poultry, and wastewater, which were intermingled within monophyletic clades with high bootstrap support, indicating close genomic relatedness across sectors. Bayesian phylogeographic reconstruction suggested multiple potential introductions during 2018–2022, including 1 lineage related to isolates from the United States (clade I) and others related to isolates from the United Kingdom (clade II). Those findings highlight the emergence and genomic diversity of blaCTX-M-65–positive Salmonella Infantis in South Korea and support the value of continued genomic surveillance across sectors.

In this meta-analysis, we performed a literature search for articles relating to asymptomatic monkeypox virus (MPXV) detections published worldwide during May 12, 2022–September 13, 2024. The primary outcome was to determine the pooled prevalence of asymptomatic MPXV detections. We conducted a random-effects analysis that yielded a final pooled prevalence of 1.0% (95% prediction interval 0.1%–11.2%). Results did not substantially differ by geographic region or study design. Although those findings are reassuring, we did not evaluate infectivity or transmission potential among asymptomatic persons. MPXV continues to circulate globally; the viral dynamics that enable its persistence remain poorly understood and merit further study.

Swine influenza A viruses (IAV-S) caused the 2009 H1N1 pandemic and pose a future zoonotic and pandemic threat. Vietnam represents a critical hotspot for IAV-S emergence within East and Southeast Asia, with dense swine and human populations and intensive livestock trade. We conducted genomic surveillance of IAV-S in Vietnam during 2020–2024, extending previous surveillance from 2013–2019. We identified multiple co-circulating H1 and H3 clades, including pandemic H1N1, Eurasian avian-like, and European lineages, by conducting phylogenetic analysis of 56 IAV-S isolates (21 H1N1, 31 H1N2, and 4 H3N2). Three H1 clades persisted exclusively in Vietnam, circulating up to 12 years. Phylogeographic analysis revealed multiple independent introduction events from North America, Europe, China, Thailand, and Cambodia. We detected extensive reassortment that frequently involved pandemic H1N1 virus internal genes. We identified several lineage-specific mutations associated with mammalian adaptation. Our findings underscore the ongoing IAV-S evolution and need for sustained surveillance in Vietnam.

Many treatment recommendations for invasive mould infections, particularly those caused by rare moulds, rely on non-randomised comparative effectiveness research (CER), which is vulnerable to design and analytical limitations that can bias effect estimates. We systematically reviewed 117 non-randomised studies evaluating interventions for aspergillosis, mucormycosis, fusariosis, scedosporiosis, lomentosporiosis, or phaeohyphomycosis published from 2003 to 2024. We assessed structural susceptibility to bias from misalignment of eligibility, treatment assignment, and start of follow-up, and approaches to confounding adjustment.

Three months after a major cardiothoracic hospital in England relocated to a new building, two cases of Mycobacterium abscessus occurred among lung transplant recipients, triggering an outbreak investigation.MethodsRespiratory samples were collected from transplant recipients and patients with Cystic Fibrosis (CF) and non-CF bronchiectasis and tested for Mycobacterium abscessus (other patient groups on clinical request). Environmental sampling was undertaken in between 2019 and 2025. Whole genome sequencing (WGS) was performed on clinical and environmental specimens. An outbreak case was defined as a patient with a positive culture matching the strain from water samples on WGS. Epidemiological investigations included assessment of clinical outcomes; calculation of incidence rates; and a case-control study among transplant recipients.ResultsBetween May 2019 and June 2026, 40 outbreak cases occurred in lung transplant recipients (n=11), patients with CF (n=11) and non-CF bronchiectasis (n=14), and other patient groups (n=4), of which 19 were diagnosed with non-tuberculous mycobacterial pulmonary disease. The case-control study found no specific risk factors associated with lung transplant surgery or bronchoscopy. Environmental sampling showed that the outbreak strain had persisted and disseminated throughout the hospital water system. Following extensive control measures, including point-of-use filters and biocide treatment, incidence fell from 12.8 to 2.2 cases per year. No further case has been identified since June 2025, coinciding with a review of enhanced flushing.ConclusionsControl measures reduced the incidence of infection but did not eliminate the outbreak strain from the hospital water. Risk mitigation is needed for water systems where vulnerable patients are accommodated.

Empiric antibiotic selection for complicated urinary tract infections is increasingly complex due to the rising prevalence of multidrug-resistant organisms. We conducted a network meta-analysis to compare clinical efficacy and safety among existing empiric treatment options.MethodsWe performed a frequentist random-effects network meta-analysis of randomized controlled trials evaluating single-agent empiric regimens for adults with complicated urinary tract infections. The primary endpoints were clinical response, microbiological response, and serious adverse events. Ceftriaxone served as the common comparator.ResultsForty-seven trials were identified through a systematic search. In the primary analysis of 17 studies published after the year 2000, evaluating agents currently accessible in the United States, in which baseline ceftriaxone non-susceptibility among Enterobacterales averaged approximately 15%. Ceftriaxone demonstrated clinical response rates comparable to broader-spectrum alternatives. Although some agents achieved higher microbiological eradication, these differences did not translate into superior clinical cure rates. Safety profiles were stable across antibiotic classes, with no significant differences in serious adverse events compared to cephalosporins.ConclusionsCeftriaxone remains an effective empiric option for hemodynamically stable adults with complicated urinary tract infections, in settings with comparable resistance prevalence. These findings provide evidence to support antimicrobial stewardship efforts that prioritize narrower-spectrum agents, preserving broader-spectrum therapies for patients at highest risk for resistant pathogens.

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.MethodsThis 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.ResultsAmong 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).ConclusionIn 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.

Contemporary Australian guidelines for the management of melioidosis recommend a longer duration of intravenous antibiotics during the intensive phase of treatment; recurrent disease is now far less common. High rates of adverse drug reactions (ADRs) to the currently recommended minimum of three months of oral trimethoprim/sulfamethoxazole (TMP/SMX) eradication therapy questions the incremental value of this phase of treatment.MethodsIn this pilot, single-center, open-label, randomized control trial, adults with culture-confirmed melioidosis received either prolonged intravenous intensive phase therapy followed by oral eradication phase therapy with TMP/SMX (standard therapy) or prolonged intravenous intensive phase therapy alone (short course therapy). The primary outcome was culture-confirmed recurrence at two years. Secondary outcomes included clinical (culture-unconfirmed) recurrence and ADRs to TMP/SMX.ResultsAmong 33 participants, 5 had culture-confirmed recurrence: 0/16 in the standard therapy group and 5/17 (29%) in the short course therapy group. One participant (6%) in the standard therapy group had clinical recurrence. An ADR to TMP/SMX occurred in 13/16 (81%) in the standard therapy group, necessitating TMP/SMX cessation in 7/13 (44%), hospitalization in 5/13 (38%) and intensive care unit admission in 1/13 (8%).ConclusionsProlonged intravenous antibiotics alone will cure many patients with melioidosis, however some still require oral eradication therapy. The potential for recurrence of life-threatening melioidosis must be balanced against the high rate of significant ADRs to high-dose TMP/SMX. This necessitates a greater understanding of individuals at highest risk of recurrence and determination of the optimal dosing and duration of eradication therapy in those that need it.

Gonorrhoea, a bacterial sexually transmitted infection caused by Neisseria gonorrhoeae, is a major global public health concern due to rising incidence and increasing antimicrobial resistance. Absence of a licensed vaccine and limitations of animal models have impeded progress in the understanding of pathogenesis, immunity and development of novel therapeutics and vaccines. Controlled human infection studies (CHIS) offer a powerful approach to accelerate vaccine and antimicrobial development and improve understanding of host–pathogen interactions.MethodsAn international, multidisciplinary stakeholder workshop was convened in Oxford, UK (March 2025) to review current gonorrhoea CHIS activity, define research priorities and establish consensus standards for future studies through structured discussion.ResultsConsensus highlighted the continued value of CHIS with well-characterised strains such as FA1090, while supporting careful selection and characterisation of novel strains. Standardised, risk-based approaches to inoculum manufacture and quality assurance were recommended to enhance reproducibility and scalability. Expansion of CHIS to include additional anatomical sites and novel populations, including individuals with female reproductive anatomy, was identified as scientifically valuable but requiring careful ethical and safety evaluation. CHIS were recognised as uniquely positioned to advance vaccine and antimicrobial development by enabling early efficacy assessment, identification of correlates of protection and optimisation of treatment and prevention strategies.ConclusionsGonorrhoea CHIS are an underutilised but valuable research tool with potential to accelerate translational research against gonorrhoea. With robust ethical oversight, community engagement and international collaboration, expanded and harmonised CHIS could substantially advance prevention and treatment strategies.

AbstractRisk 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.

AbstractHuman 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.

To the  Editor—We read with interest the study by Yoshida et al evaluating the utility of repeat blood cultures for candidemia using 2 large electronic health record repositories [1]. The authors report that 23% of candidemia episodes in the Houston Methodist cohort and 45% in the MIMIC-IV cohort were first detected on cultures obtained after the index day, concluding that repeat cultures may provide diagnostic value when suspicion for candidemia persists.

AbstractCandida auris is an emerging, multidrug-resistant fungal pathogen of growing concern in solid organ transplantation, where colonization may have implications for pretransplant candidacy and post-transplant outcomes. Although C. auris screening is increasingly common in presurgical and critical care settings, no national or professional guidelines in the United States specify who, how, or when to screen, nor is there consensus on how screening results should impact patient care. Here, we examine the ethical significance of C. auris colonization in transplant candidacy decisions and outline the arguments for and against universal C. auris screening of solid organ recipients in the peritransplant period. We propose risk-based screening as a middle-ground approach for hospitals and physicians seeking to develop value-informed, evidence-based guidelines at a time when data are still emerging and evolving. Ultimately, the fundamental goal of pretransplant screening is harm reduction through preparedness and individualized risk assessment, not a proxy for institutional risk tolerance or an artifact of how a screening policy is applied.

People with human immunodeficiency virus (HIV) (PWH) experience substantially increased risk of anogenital cancer. Whether long-term antiretroviral therapy (ART) reduces anogenital cancer risk is unknown.MethodsA target trial emulation using a case-cohort design among Botswana adults aged 30–65, sampled via a probability-based household survey across 30 communities. Cases of cervical, vulvar, anal, and penile cancer were prospectively ascertained at the country's principal treatment centers. We estimated the marginal relative risk (RR) of incident anogenital cancer by ART duration, compared with adults without HIV, using g-computation from weighted models that accounted for shared determinants of human papillomavirus, and HIV infection, access to cancer care, and ART duration.Results14 312 participants were enrolled (42% PWH), including 1045 (79% PWH) with incident anogenital cancer—792 cervical, 106 vulvar, 80 anal, and 67 penile cancers. Compared with people without HIV, the marginal RR (95% CI) of anogenital cancer increased with longer durations of ART (P = .001) (no ART: 4.6; 4.3–5.0; <5 years: 4.0; 3.7–4.3; 5–9 years: 4.6; 4.2–5.0; ≥10 years: 7.4; 6.8–8.1). Individuals receiving ART for ≥10 years had the highest RR for each cancer evaluated: cervix, 4.4 (4.0 to 4.8); vulva, 36 (22–57); anus, 15 (11–20); and penis, 102 (42–250). Prior advanced HIV disease was associated with increased risk but this effect diminished on ART and contributed relatively little to overall risk.ConclusionsLong-term utilization of ART was not associated with a reduction in anogenital cancer risk. Improved prevention strategies are needed for PWH.

To the Editor—Khanam et al addressed recurrent typhoid using community and facility comparators [1]. In the facility-control analysis, febrile, blood-culture-negative controls were matched to index cases by age group (0–4, 5–14, or ≥15 years), trial arm, and fever-onset date within 14 days, and Cox analyses were stratified by matched set. The overall adjusted hazard ratio (HR) was 1.5 (95% CI, .8–2.8), which may be interpreted as an imprecise average association in the observed matched facility-control cohort.

Lower respiratory tract infections (LRTIs) are a common cause of pediatric hospitalization, but distinguishing viral from bacterial etiologies based solely on clinical findings remains challenging. Multiplex real-time polymerase chain reaction (RT-qPCR) enables the simultaneous detection of multiple respiratory pathogen targets. However, molecular detection does not necessarily establish microbial causation, particularly for bacteria identified in upper respiratory tract specimens.ObjectivesTo describe respiratory pathogen detection and co-detection patterns in hospitalized children with LRTIs using multiplex RT-qPCR.DesignA single-center retrospective observational study.MethodsWe evaluated 242 hospitalized children with clinically diagnosed LRTIs who underwent multiplex respiratory RT-qPCR testing between October 2021 and April 2026 at a tertiary-care hospital in Istanbul, Türkiye. Nasopharyngeal swab specimens were analyzed for respiratory viral and bacterial targets. All listed targets, including SARS-CoV-2, were assessed in the total study population. Pathogen-specific detection frequencies and single- and multiple-pathogen detection patterns were evaluated. Molecular findings were additionally classified as viral-only, bacterial-only, viral–bacterial co-detection, or no pathogen detected.ResultsAt least one respiratory pathogen target was detected in 190 of 242 children (78.5%). Among pathogen-positive children, single-pathogen detection occurred in 103 (54.2%) and multiple-pathogen detection in 87 (45.8%). Dual detection was the most frequent multiple-detection pattern (53/87; 60.9%), followed by triple (21/87; 24.1%), quadruple (10/87; 11.5%), quintuple (2/87; 2.3%), and sextuple detection (1/87; 1.1%). The most frequently detected targets were Streptococcus pneumoniae (70/242; 28.9%), Haemophilus influenzae (56/242; 23.1%), and human rhinovirus (37/242; 15.3%). Viral-only detection occurred in 99 children (40.9%), bacterial-only detection in 28 (11.6%), viral–bacterial co-detection in 63 (26.0%), and no pathogen was detected in 52 (21.5%). Detection-pattern distributions differed according to calendar year (p=0.005) and season (p=0.016).ConclusionRespiratory pathogen detection and co-detection were common among hospitalized children. Viral-only detection was the most frequent pattern. Because nasopharyngeal bacterial detections may reflect upper-airway colonization, these findings should be interpreted as descriptive detection patterns rather than definitive evidence of LRTI causation.

Cephalexin is increasingly used as initial and oral transition therapy for severe infections, but optimal dosing in this setting remains uncertain.MethodsFour cephalexin pharmacokinetic (PK) datasets spanning preterm neonates through young adults were pooled to develop a unified population PK model. Simulations estimated probability of target attainment (PTA) and cumulative fractional response (CFR, target attainment weighted across the pathogen MIC distribution) across fT>MIC targets (free drug time above the minimum inhibitory concentration), MIC distributions for methicillin-susceptible Staphylococcus aureus (MSSA) and Enterobacterales, and multiple dosing regimens.ResultsSeventy-one subjects (age 9 days-29 years) contributed 360 plasma samples, best described by a one-compartment model with first-order absorption and lag time. Apparent volume and clearance scaled with fat-free mass, and clearance increased with post-menstrual age. Absorption was slower in neonates. Cephalexin 25 mg/kg/dose, maximum 1,000 mg, every 8 hours achieved 1-log kill targets for MSSA (PTA ≥98% for 35% fT>MIC at MIC = 4 mg/L); every 6-hour dosing was needed at MIC = 8 mg/L. For Enterobacterales, a 60% fT>MIC target was achieved only in infants <2 months. However, higher-dose regimens (37.5-50 mg/kg, maximum 1,500 mg, every 6 hours) achieved CFRs >90% for 40-50% fT>MIC targets when cefazolin MICs were ≤2 mg/L.ConclusionsCephalexin PK varies with age but is well-captured by a unified size- and maturation-scaled model. These data support dosing within the FDA-approved range for systemic MSSA infections. Higher-dose regimens are necessary for adequate target attainment against Enterobacterales. Appropriately dosed cephalexin represents a viable option for selected severe infections, including oral transition therapy.

The U.S. 2024–2025 influenza season was characterized by sustained elevated activity from November 2024–April 2025, with circulation of both influenza A(H1N1)pdm09 and A(H3N2), the latter of which included some antigenically drifted viruses.MethodsFrom October 1, 2024, to April 30, 2025, a multistate respiratory virus surveillance network enrolled adults hospitalized with acute respiratory illness in 26 U.S. medical centers. Influenza vaccine effectiveness (VE) against influenza-associated hospitalization and severe in-hospital outcomes was estimated using a test-negative study. The odds of influenza vaccination among influenza-positive case patients and influenza-negative control patients were compared using multivariable logistic regression; VE was calculated as (1 − adjusted odds ratio for vaccination) × 100, expressed as a percent.ResultsThe 2024–2025 seasonal influenza vaccine was effective against influenza-associated hospitalization (VE: 40% [95% confidence interval (CI): 32%–47%]), consistent across age group and influenza type/A subtype. Influenza vaccination also reduced the overall risk of all severe in-hospital outcomes evaluated, including standard oxygen therapy (VE: 41% [95% CI: 31%–50%]), non-invasive advanced respiratory support (VE: 38% [95% CI: 19%–52%]), invasive organ support (VE: 58% [95% CI: 44%–69%]), ICU admission (VE: 58% [95% CI: 47%–67%]), and death (VE: 52% [95% CI: 18%–71%]) with effectiveness varying by influenza A subtype and age.ConclusionsInfluenza vaccination reduced the risk of influenza-related hospitalization and severe in-hospital outcomes in adults during the severe 2024–2025 influenza season compared with those not vaccinated.

View abstract Antimicrobial stewardship (AMS) is important in outpatient sexual health care because bacterial sexually transmitted infection (STI) management frequently involves recurrent antimicrobial exposure within select populations. Antimicrobial resistance (AMR) has narrowed treatment options and prompted repeated revisions to treatment guidelines, specifically for gonorrhea. Doxycycline postexposure prophylaxis and recurrent antibiotic exposure have intensified stewardship concerns in sexual health care. As outpatient AMS programs grow nationally, merging expertise on sexual health could optimize care and address AMR. We propose a practical operational framework for integrating AMS into outpatient sexual health care through clinical decision support, appropriate diagnostic testing and stewardship-informed antimicrobial prescribing, coupling prescribing practices with AMR surveillance, coordinated oversight between STI and stewardship programs, and patient-centered counseling. Stewardship integration must preserve timely access to care and trust within sexual health services. AMS integration may help sustain antimicrobial effectiveness, strengthen clinical decision-making, and support equitable, evidence-informed sexual health care amid evolving STI epidemiology and emerging AMR threats.

View abstract Objective:To assess anti-infective use after over a decade of handshake stewardship by analyzing days of therapy per thousand patient days for all anti-infectives.Design:Retrospective evaluation pre- and post-implementation of handshake stewardship from October 2010 to September 2025.Setting:A pediatric hospital in Aurora, Colorado, with a licensed bed capacity of 472 beds. Handshake stewardship at our institution began in October 2013, after two years of planning (October 2011–September 2013); prior, there was no form of stewardship (October 2010–September 2011).Patients:All hospitalized patients administered anti-infectives during the study period.Methods:Days of therapy per thousand patient days were extracted from the electronic medical record and stratified by unit, medication, and route of administration. Antibacterial agents were grouped by National Healthcare Safety Network Antimicrobial Use and Resistance Module categories for pediatric resistant Gram-positive and hospital-onset infections. Yearly medians were utilized to define a refinement phase.Results:During 12 years of handshake stewardship (2013–2025), anti-infective use hospital-wide declined 33%. A maintenance phase, when refinement in anti-infective use was observed though overall use plateaued numerically, began in October 2021.Conclusions:The goal of stewardship is judicious use, not no use. We describe the maturation of a stewardship program over 12 years, demonstrating that handshake stewardship is both effective and sustainable, and that over time the focus shifts from decreased overall days of therapy per thousand patient days towards optimal use, reflected in fine-tuned use of specific agents.

Importance  Congenital TORCH (toxoplasmosis, syphilis, rubella, cytomegalovirus, or herpes simplex) infections are established causes of severe fetal injury, yet their population-level contribution to neurodevelopmental and psychiatric outcomes, independent of familial confounding, remains yet to be quantified.Objective  To investigate whether congenital TORCH infections are associated with neurodevelopmental and psychiatric outcomes, including autism and intellectual disability, as well as academic performance, using population-based and sibling-controlled analyses.Design, Setting, and Participants  This nationwide, population-based cohort study with sibling comparisons was conducted using linked data from Swedish national health, birth, insurance, education, and death registers. Individuals born in Sweden between 1987 and 2021, including individuals diagnosed with a congenital TORCH infection, were included. Full siblings were identified for within-family comparisons. Individuals were followed up from birth until death, emigration, or December 31, 2023. Data were analyzed from November ‎2025 to July 2026.Exposure  Clinically diagnosed congenital TORCH infections, identified from national registers, including cytomegalovirus, Toxoplasma gondii, rubella, and herpes simplex viruses.Main Outcomes and Measures  Autism (with and without co-occurring intellectual disability), intellectual disability (by severity), attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, Tourette and chronic tic disorders, nonaffective psychosis, and standardized school grades at age 16 years were assessed. Associations were estimated with hazard ratios (HRs) using Cox regression and sibling-comparison models.Results  Among 3 666 002 individuals born in Sweden, including 3 665 027 individuals without TORCH infections (1 883 911 male [51.4%]; mean [SD] follow-up, 20.50 [11.15] years) and 975 individuals with TORCH infections (532 male [54.6%]; mean [SD] follow-up, 18.70 [10.39] years), congenital TORCH infections were associated with increased risks of intellectual disability (HR, 7.22; 95% CI, 6.14-8.49) and autism (HR, 3.10; 95% CI, 2.55-3.76), with similar or greater HRs in sibling comparisons (intellectual disability: HR, 11.28; 95% CI, 5.97-21.33; autism: HR, 3.19; 95% CI, 1.97-5.15). Risks increased with greater severity of intellectual disability, with HRs ranging from 3.01; 95% CI, 2.21-4.11 for mild to 23.51; 95% CI, 18.06-30.60 for severe to profound intellectual disability) and were greater for autism with (HR, 6.23; 95% CI, 4.69-8.28) vs without (HR, 1.97; 95% CI, 1.51-2.57) co-occurring intellectual disability. No consistent associations were observed for obsessive-compulsive disorder, and associations with attention-deficit/hyperactivity disorder attenuated in sibling analyses. Individuals who were exposed had lower school grades in adolescence (TORCH-associated decrease = −1.50 points; 95% CI, −2.60 to −0.40 points).Conclusions and Relevance  In this study, congenital TORCH infections were rare but associated with intellectual disability and autism, with evidence of broader associated cognitive outcomes extending beyond diagnosed conditions, underscoring the importance of preventing specific vertically transmitted infections.

People involved in the criminal justice system have a 10-fold higher prevalence of hepatitis C than the general population, primarily because of higher rates of injection drug use.1 Universal hepatitis C screening and treatment for incarcerated populations is recommended by the US Centers for Disease Control and Prevention.1 However, to date, implementation of these recommendations at scale has been limited despite substantial gains in treatment effectiveness and efficiency during the past decade. Get Access

Importance  Understanding how neonatal unit colonization pressure, the proportion of infants carrying resistant bacteria on a unit, is associated with antibiotic-resistant bacterial acquisition risk can inform the design and implementation of effective infection prevention and control (IPC) interventions.Objectives  To describe resistant bacterial gene prevalence in European neonatal units and to assess the association between unit-level extended-spectrum β-lactamase (ESBL) colonization pressure and infant-level ESBL acquisition.Design, Setting, and Participants  Multicenter study in 24 tertiary neonatal units in 8 European countries (Estonia, Greece, Germany, Italy, Poland, Spain, Switzerland, and the United Kingdom) using repeated cross-sectional surveys collecting stool samples from infants over 4 surveys with 4-, 7-, and 14-day intervals, analyzed using real-time quantitative polymerase chain reaction (PCR) between January 2022 and June 2024 as part of the NeoIPC project. All infants present on the neonatal unit at 8:00 am on the day of the survey were eligible; infants could contribute to multiple surveys.Exposure  ESBL colonization pressure at previous survey.Main Outcome and Measure  Incident infant gut colonization with ESBL-harboring bacteria (ESBL-colonized). Bayesian hierarchical logistic regression modeling was used to assess the association between colonization pressure and infant-level acquisition risk on the neonatal unit.Results  Overall, 943 infants (547 of 943 male [58.0%]; median [IQR] gestational age, 34 [30-38] weeks, and median [IQR] birth weight, 2130 [1254-3084] g) contributed to 1847 infant-survey observations. Stool samples were collected and PCR results obtained in 1448 of 1847 infant surveys (78.4%). The most common genes detected were those encoding ESBLs (205 of 1448 samples [14.2%]), with high unit-level variation. In the colonization acquisition analysis, we included 829 samples from 533 infants hospitalized since birth who were either newly admitted since or not colonized at the previous survey time point; 90 of 533 infants (16.9%) became ESBL-colonized. Their median (IQR) gestational age was 34 (30-37) weeks, and median (IQR) length of stay at survey was 14 (5-32) days. Colonization pressure was associated with increased odds of becoming ESBL-colonized for all survey intervals (4-day interval: mean odds ratio [OR], 1.89; 95% credible interval [CrI], 1.22-2.94; 7-day interval: OR, 1.76; 95% CrI, 1.26-2.63; 14-day interval: OR, 1.73; 95% CrI, 1.15-2.52 per 10% increase of colonization pressure).Conclusions and Relevance  In this cross-sectional study, ESBL colonization pressure was associated with individual risk of acquiring ESBL on the neonatal unit. Unit-level interventions targeting colonization rather than infection may have important direct and indirect benefits in units with high colonization pressure.

Introduction Lyme disease (LD), the most frequently reported vector-borne disease in the US,1 is caused by infection with Borrelia burgdorferi sensu lato and transmitted through the bite of Ixodes ticks. However, Ixodes ticks also harbor other pathogens, including Anaplasma phagocytophilum and the malaria-like parasite Babesia microti.2,3 Co-infections with other pathogens can complicate diagnosis and treatment.4-6 However, the clinical burden of co-infections is evolving and frequently underappreciated. We sought to investigate patterns and frequencies of codetection of antibodies against B burgdorferi and other tick-borne pathogens in patients undergoing testing for tick-borne disease. Methods This cohort study was reviewed by the WCG Institutional Review Board, an independent ethical review board, and deemed to be exempt under federal regulation 45 CFR §46.104(d)(4). Reporting of this study follows the STROBE reporting guideline. We queried the Quest Diagnostics test database for individuals who had undergone tick-borne disease serological panel testing during the 5 years from January 2021 to December 2025 (eFigure and eMethods in Supplement 1). Data used were deidentified as required by the HIPAA Privacy Rule (45 CFR §164.514). Results without associated information on age, sex, or state of residence were excluded. We restricted the analysis to the first test from unique individuals identified in the period. We performed descriptive analysis of the data in Microsoft 365 (Microsoft Corp), and we used a log-binomial regression model to estimate seropositivity ratio and 95% CIs, with adjustment for age, sex, testing month, and region, using SAS version 9.4 (SAS Institute). Statistical testing was 2-sided, with P < .05 considered statistically significant. Results We included 193 260 individuals in the study cohort (108 878 female [56.3%] and 84 382 male [43.7%]; median [IQR] age, 51 [35-64] years). Most were adults (aged ≥18 years; 92.4%) and resided in the Northeast region (70.6%), and 40.7% were tested between June and August. Seropositivity was observed in 9609 individuals (5.0%) for B burgdorferi, 6003 individuals (3.1%) for A phagocytophilum, 6497 individuals (3.4%) for B microti, and 1980 individuals (1.0%) for Ehrlichia spp. Together, 13 014 individuals tested (6.7%) were seropositive for at least 1 non-LD tick-borne pathogen. Compared with individuals who were seronegative for B burgdorferi, individuals who were seropositive for B burgdorferi were more likely to be seropositive for A phagocytophilum, B microti, and Ehrlichia spp in all 4 US Census regions (Figure 1). While seropositivity for another tick-borne pathogen was observed in 5.5% of tested individuals who were seronegative for B burgdorferi, it was observed in 29.5% of individuals who were seropositive for B burgdorferi. The seropositivity ratio for other tick-borne pathogens in individuals with vs without laboratory evidence of LD was 4.46 (95% CI, 4.30-4.63; P < .001). Compared with individuals in other regions, individuals who were seropositive for B burgdorferi in the Northeast region tested seropositive more frequently for non-LD tick-borne pathogens (31.1% vs 13.6%-16.6%). Figure 1.  Bar Graph of Regional Seropositivity Rates of Tick-Borne Pathogens View LargeDownload (opens in new tab)Go to Figure in ArticleRates are shown in panels A through D stratified by laboratory evidence of Lyme disease (LD) status (LD positive [LD+] vs LD negative [LD−]). The number of individuals in the LD+ group was 8601 in Northeast, 571 in Midwest, 393 in South, and 44 in West regions, and the number of individuals in the LD− group was 127 895 in Northeast, 24 581 in Midwest, 27 901 in South, and 3274 in West regions. A phagocytophilum indicates Anaplasma phagocytophilum; B microti, Babesia microti. The IgM and IgG distribution heatmap shows an apparent antibody-type correlation among coseropositive individuals (Figure 2). Correlation with B burgdorferi IgM was observed across IgM of all other pathogens. B burgdorferi IgG was also correlated with B microti and A phagocytophilium IgG but not with Ehrlichia IgG. Figure 2.  Heatmap of Antibody-Detection Profiles Among Individuals Who Were Coseropositive View LargeDownload (opens in new tab)Go to Figure in ArticleThe 3 × 3 grids in panels A through C show the distribution of IgM and IgG antibodies detected among individuals who were coseropositive. Shading gradients represent the frequency of individuals appearing in each joint antibody category, with annotated values indicating absolute counts. A phagocytophilum indicates Anaplasma phagocytophilum; B burgdorferi, Borrelia burgdorferi; B microti, Babesia microti. Discussion In this large, national cohort study, individuals with laboratory evidence of LD had a higher likelihood of seropositivity for other tick-borne pathogens, most notably Anaplasma and Babesia. The strong association between seropositivity for B burgdorferi, A phagocytophilum, and B microti is consistent with underlying biology given that all 3 are transmitted by Ixodes scapularis ticks.2,3 The strong correlation between seropositivity for B burgdorferi and Ehrlichia, traditionally thought to be transmitted by Amblyomma americanum, is notable. This could be associated with cumulative exposure to multiple species of ticks driven by individual behaviors (eg, occupation, outdoor recreation), low-level cross-reactivity with Anaplasma, or exposure in some regions to Ehrlichia muris eauclairensis, which is transmitted by Ixodes scapularis ticks, unlike other Ehrlichia species. This study has limitations, including unknown clinical indications driving test ordering and unknown disease stage (eg, acute or chronic symptoms), a lack of molecular testing, and an unknown seropositivity level for non-LD tick-borne pathogens, as well as potential false-positive and false-negative serological results. False positivity may be more common with the less specific IgM component of serologic assays, which may partly explain the higher rates of coseropositivity observed across pathogens. Furthermore, coseropositivity does not prove active co-infection, and a standard 2-tier testing algorithm has lower sensitivity in early stage LD.7 While somewhat expected,8-10 the increased seropositivity for A phagocytophilum and B microti among individuals with laboratory evidence of LD reinforces the need for clinicians to maintain a high index of suspicion for non-LD tick-borne pathogens, particularly in the Northeast region. This clinical vigilance is especially critical given the highest rate of coseropositivity to Babesia, which is not susceptible to doxycycline, the first-line treatment for LD. Back to top Article Information Accepted for Publication: July 27, 2026.Published: September 18, 2026. doi:10.1001/jamanetworkopen.2026.34800Open Access: This is an open access article distributed under the terms of the CC-BY-NC-ND License, which does not permit alteration or commercial use, including those for text and data mining, AI training, and similar technologies. © 2026 Li Y et al. JAMA Network Open.Corresponding Author: Yonghong Li, PhD, Quest Diagnostics, 33608 Ortega Hwy, San Juan Capistrano, CA 92675 (yonghong.x.li2@questdiagnostics.com).Author Contributions: Dr Li had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.Concept and design: Li, Tong, Boyce.Acquisition, analysis, or interpretation of data: Li, Tong, Givens.Drafting of the manuscript: Li, Givens, Boyce.Critical review of the manuscript for important intellectual content: Tong, Givens, Boyce.Statistical analysis: Li, Tong.Administrative, technical, or material support: Givens.Supervision: Li, Boyce.Conflict of Interest Disclosures: Dr Boyce reported receiving personal fees from Galaxy Diagnostics outside the submitted work. No other disclosures were reported.Funding/Support: No specific funding was provided for this study other than regular employment compensation to the authors.Role of the Funder/Sponsor: Quest Diagnostics, the employer of Dr Li, Ms. Tong, and Dr Givens, had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, and decision to submit the manuscript for publication. Quest Diagnostics Scientific Publication Review committee reviewed and approved the manuscript.Data Sharing Statement: See Supplement 2.Additional Contributions: Elizabeth M. Marlowe, PhD, and Susan E. Realegeno, PhD (Quest Diagnostics), provided expert advice on serology testing and critical review of the draft manuscript. No compensation was received beyond usual salary. References 1.Kugeler  KJ, Schwartz  AM, Delorey  MJ, Mead  PS, Hinckley  AF.  Estimating the frequency of Lyme disease diagnoses, United States, 2010-2018.   Emerg Infect Dis. 2021;27(2):616-619. doi:10.3201/eid2702.202731PubMedGoogle ScholarCrossref2.Grimaudo  AT, Holcomb  KM, Burtis  JC,  et al.  Geographic variation in risk of blacklegged tick-borne coinfections in the eastern United States.   Ticks Tick Borne Dis. 2026;17(2):102610. doi:10.1016/j.ttbdis.2026.102610PubMedGoogle ScholarCrossref3.Swanson  SJ, Neitzel  D, Reed  KD, Belongia  EA.  Coinfections acquired from Ixodes ticks.   Clin Microbiol Rev. 2006;19(4):708-727. doi:10.1128/CMR.00011-06PubMedGoogle ScholarCrossref4.Horowitz  HW, Aguero-Rosenfeld  ME, Holmgren  D,  et al.  Lyme disease and human granulocytic anaplasmosis coinfection: impact of case definition on coinfection rates and illness severity.   Clin Infect Dis. 2013;56(1):93-99. doi:10.1093/cid/cis852PubMedGoogle ScholarCrossref5.Krause  PJ, Telford  SR  III, Spielman  A,  et al.  Concurrent Lyme disease and babesiosis: evidence for increased severity and duration of illness.   JAMA. 1996;275(21):1657-1660. doi:10.1001/jama.1996.03530450047031ArticlePubMedGoogle ScholarCrossref6.Sanchez-Vicente  S, Tokarz  R.  Tick-borne co-infections: challenges in molecular and serologic diagnoses.   Pathogens. 2023;12(11):1371. doi:10.3390/pathogens12111371PubMedGoogle ScholarCrossref7.Mead  P, Petersen  J, Hinckley  A.  Updated CDC recommendation for serologic diagnosis of Lyme disease.   MMWR Morb Mortal Wkly Rep. 2019;68(32):703. doi:10.15585/mmwr.mm6832a4PubMedGoogle ScholarCrossref8.Steere  AC, McHugh  G, Suarez  C, Hoitt  J, Damle  N, Sikand  VK.  Prospective study of coinfection in patients with erythema migrans.   Clin Infect Dis. 2003;36(8):1078-1081. doi:10.1086/368187PubMedGoogle ScholarCrossref9.Wormser  GP, McKenna  D, Scavarda  C,  et al.  Co-infections in persons with early Lyme disease, New York, USA.   Emerg Infect Dis. 2019;25(4):748-752. doi:10.3201/eid2504.181509PubMedGoogle ScholarCrossref10.Curcio  SR, Tria  LP, Gucwa  AL.  Seroprevalence of Babesia microti in individuals with Lyme disease.   Vector Borne Zoonotic Dis. 2016;16(12):737-743. doi:10.1089/vbz.2016.2020PubMedGoogle ScholarCrossref

Importance  Interleukin (IL)-17 inhibitors have emerged as effective therapies for moderate to severe hidradenitis suppurativa (HS), but concerns remain regarding their potential association with inflammatory bowel disease (IBD). It is known that there is an increased risk of IBD in HS populations, but it remains unclear whether IL-17 inhibition increases the IBD risk or unmasks underlying disease.Objective  To evaluate the incidence of IBD in patients with HS treated with IL-17 inhibitors and to compare IBD event rates between treatment and placebo groups.Data Sources  PubMed, Embase, and the Cochrane CENTRAL were searched from inception through November 2025.Study Selection  Randomized clinical trials (RCTs), nonrandomized studies, and case reports reporting IBD outcomes in patients with HS treated with IL-17 inhibitors were included. Of 1467 records identified, 24 studies met inclusion criteria (10 RCTs, 11 nonrandomized studies, and 3 case reports).Data Extraction and Synthesis  Extracted variables included study design, IL-17 inhibitor, study duration, dosing regimen, sample size, patient age, sex, baseline personal or family history of IBD, new-onset IBD, relapse of preexisting IBD, IBD subtype and clinical features, and time to IBD onset.Main Outcomes and Measures  Incidence of IBD event, defined as new-onset or worsening Crohn disease or ulcerative colitis during IL-17 inhibitor treatment in a patient with HS. For RCTs, pooled risk differences were calculated using a common effects Mantel-Haenszel model. For nonrandomized studies, a single group meta-analysis of proportions was performed to estimate pooled IBD incidence. Case reports were synthesized qualitatively.Results  Across 10 RCTs, new-onset IBD occurred in 6 of 2572 patients treated with IL-17 inhibitors (0.23%) and in 0 of 1066 patients treated with placebo through week 16. There was no significant difference between groups (risk difference, 0.002; 95% CI, −0.003 to 0.007). In nonrandomized studies, 7 new-onset IBD events occurred among 469 patients (crude incidence, 1.49%), with a pooled incidence of 3.90% (95% CI, 2.30%-6.50%). Across randomized trials, long-term extension studies, and nonrandomized studies, 17 new-onset cases and 4 IBD flares were reported.Conclusions  In this systematic review and meta-analysis, IBD events were rare. No significant increase in IBD risk was observed with IL-17 inhibitors, although low event rates and inconsistent reporting limited interpretation.

Expanding testing and treatment of hepatitis C virus (HCV) infections is an essential component of national hepatitis C elimination plans.1,2 Compared with the general population in the US, state prison systems have substantially higher prevalence of current HCV infection (8.7% vs 1.6%), making them vital venues for testing and treatment.3,4 In July 2016, California Correctional Health Care Services (CCHCS) began implementing multiple strategies toward achieving elimination of hepatitis C within the state prison system, including universal opt-out testing on entry, gradual treatment eligibility expansions, and linkage to substance use disorder (SUD) treatment.5 With a universal opt-out approach, all entrants receive HCV testing regardless of their reported risk behaviors, unless they explicitly decline. This study characterizes HCV testing and treatment outcomes among individuals entering incarceration into California state prisons overall, by year, and by key individual-level characteristics. Methods This cross-sectional study was determined by the Stanford University institutional review board to be non–human participants research because deidentified secondary information was used; therefore, written informed consent was not required. We followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines. We analyzed individual-level electronic health record data from all adults entering California prisons, termed entrants, between July 1, 2016, and June 30, 2023. We quantified the percentages of entrants receiving an HCV antibody test within 4 weeks of entry, antibody positive (ever infected) among entrants tested, RNA positive (currently infected) among those with antibody positive results, and initiating direct-acting antiviral (DAA) treatment within 1 year among those with RNA positive results. To accommodate CCHCS care guidelines during the study period, which required a minimum sentence length of 5 to 8 months for DAA treatment, we restricted our analysis to entrants with at least 6 months of follow-up. We reported on outcomes overall and by fiscal year (July 1 to June 30), and we stratified by sex, age group, documented race and ethnicity, prior incarceration in a California prison, anticipated length of incarceration, and SUD history. We identified predictors associated with testing, test positivity, and treatment using multivariable logistic regression. Additional methodologic details are provided in the eMethods in Supplement 1. Results From July 2016 to June 2023, 176 967 individuals meeting eligibility criteria entered California prisons. Of entrants, 133 639 (76%) were tested for HCV antibody, 25 455 (19% of those tested; 14% of entrants) were ever infected with HCV, and 16 738 (66% of those ever infected; 9% of entrants) were currently infected (Table). A total of 7479 entrants (45% of those currently infected; 4% of entrants) initiated DAA treatment within 1 year. Among individuals initiating treatment within 1 year, 3837 (51%) started within 6 months of their positive test at entry. Among individuals who did not initiate DAA treatment, 4289 (46%) were released between 6 months and 1 year of entry. In a sensitivity analysis removing the 6-month follow-up restriction, the percentage initiating DAA treatment decreased from 7479 (45%) to 7613 (36%). From fiscal year 2017-2018 to 2022-2023, testing and treatment percentages increased (26 024 [80%] to 21 368 [92%] for testing and 675 [20%] to 1770 [76%] for treatment), antibody positivity remained largely stable (4628 [18%] to 4210 [20%]), and RNA positivity decreased (3327 [72%] to 2326 [55%]) (Figure). Table.  Hepatitis C Virus Testing and Treatment on Entry to California State Prisons by Demographic and Carceral Characteristics, Fiscal Years 2016-2017 to 2022-2023View LargeDownload (opens in new tab)Go to Figure in ArticleCharacteristicEntrant, No.No. (%)Antibody testPositive antibody testPositive RNA testDAA initiationOverall176 967133 639 (75.5)25 455 (19.0)16 738 (65.8)7479 (44.7)Sex Female10 63110 041 (94.5)1413 (14.1)786 (55.6)267 (34.0) Male166 336123 598 (74.3)24 042 (19.5)15 952 (66.4)7212 (45.2)Age group, ya 18-2964 04748 049 (75.0)6096 (12.7)4487 (73.6)1951 (43.5) 30-4991 85269 858 (76.1)14 270 (20.4)9504 (66.6)4359 (45.9) ≥5021 06815 732 (74.7)5089 (32.3)2747 (54.0)1169 (42.6)Race and ethnicityb American Indian or Alaska Native19061531 (80.3)472 (30.8)263 (55.7)110 (41.8) Asian or Pacific Islander26202027 (77.4)97 (4.8)52 (53.6)23 (44.2) Black40 99630 503 (74.4)1760 (5.8)1038 (59.0)447 (43.1) Hispanic82 35961 615 (74.8)12 145 (19.7)8487 (69.9)3915 (46.1) White42 51133 137 (77.9)10 291 (31.1)6422 (62.4)2764 (43.0) Otherc65754826 (73.4)690 (14.3)476 (69.0)220 (46.2)Previously incarcerated in a California state prison Yes102 92973 287 (71.2)20 790 (28.4)13 611 (65.5)6207 (45.6) No74 03860 352 (81.5)4665 (7.7)3127 (67.0)1272 (40.7)Time expected to serve, yd <160 80948 288 (79.4)9085 (18.8)5876 (64.7)1677 (28.5) 1-271 21852 971 (74.4)11 002 (20.8)7222 (65.6)3895 (53.9) 3-931 74522 314 (70.3)3894 (17.5)2647 (68.0)1421 (53.7) ≥1013 19510 066 (76.3)1474 (14.6)993 (67.4)486 (48.9)SUD statuse Assessed, SUD identified45 79740 072 (87.5)12 830 (32.0)8365 (65.2)4843 (57.9) Screened negative or assessed, no SUD identified60 73950 259 (82.7)5016 (10.0)3108 (62.0)1367 (44.0) Not screened or assessed, no SUD program70 43143 308 (61.5)7609 (17.6)5265 (69.2)1269 (24.1)Fiscal yearf 2016-201731 3284995 (15.9)829 (16.6)476 (57.4)26 (5.5) 2017-201832 53126 024 (80.0)4628 (17.8)3327 (71.9)675 (20.3) 2018-201932 67428 541 (87.4)5483 (19.2)3963 (72.3)1716 (43.3) 2019-202020 84518 568 (89.1)3463 (18.7)2426 (70.1)752 (31.0) 2020-202113 46712 165 (90.3)2348 (19.3)1460 (62.2)845 (57.9) 2021-202222 78821 978 (96.4)4494 (20.4)2760 (61.4)1695 (61.4) 2022-202323 33421 368 (91.6)4210 (19.7)2326 (55.2)1770 (76.1) Figure.  Bar and Line Graphs Showing Changes in Hepatitis C Virus Testing and Treatment on Entry to California State Prisons, Fiscal Years 2016-2017 to 2022-2023 View LargeDownload (opens in new tab)Go to Figure in ArticleConditional percentages were calculated as follows: antibody testing is calculated among all entrants; antibody positivity is calculated among entrants with an antibody test; RNA positivity is calculated among all entrants with a positive antibody test; and DAA treatment is calculated among all entrants with a positive RNA test. The decline in antibody testing and DAA treatment observed in 2020 and 2021 coincide with the COVID-19 pandemic, which considerably impacted the prison health system. Lines connect values calculated over 6-month periods, and bars reflect counts over 6-month periods beginning with the period from July 1 to December 31, 2016. DAA indicates direct-acting antiviral. Although antibody and RNA positivity percentages differed across age and racial and ethnic groups, treatment initiation was similar (Table). Current HCV infection prevalence among tested entrants was highest among male, older, and Hispanic entrants, as well as entrants who had previously been incarcerated in a California prison. Individuals with identified SUD had substantially higher antibody positivity (odds ratio [OR], 4.0; 95% CI, 3.9-4.2) and DAA initiation (OR, 1.4; 95% CI, 1.3-1.6), compared with individuals without an identified SUD. Discussion CCHCS implemented universal opt-out HCV testing and treatment on entry as part of a wide-scale effort to eliminate hepatitis C; this implementation was associated with effective and equitable increases in access to hepatitis C treatment, particularly for those with SUD. Although we document subgroup heterogeneity in RNA positivity, the high overall current infection rate among entrants supports opt-out universal screening strategies.3,6 Furthermore, higher DAA initiation among individuals with current HCV infection and SUD underscores the value of integrated SUD and hepatitis C treatment programs. Our primary limitation is that results from California may not generalize to other states due to differences in prison systems, demographics, and epidemiology. Efforts to expand testing and treatment were supported by changes to CCHCS’s HCV care-delivery model, including providing training and decision-support tools that enabled task shifting of clinical workups, treatment monitoring, and risk-reduction counseling to primary care teams and nurses.5 Additionally, treatment expansion required a commitment of up-front funding from the state of $105.8 million per year for 3 years.7 Although other studies have found that investments in treatment can yield downstream health care savings by preventing liver-related complications, future work should evaluate the long-term health and economic effects of CCHCS’s HCV testing and treatment strategies.8-10 Back to top Article Information Accepted for Publication: June 30, 2026.Published Online: September 14, 2026. doi:10.1001/jamainternmed.2026.4041Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2026 Ye Z et al. JAMA Internal Medicine.Corresponding Author: Marissa B. Reitsma, PhD, Department of Health Policy, School of Medicine, Stanford University, 615 Crothers Way, Encina Commons, Stanford, CA 94305 (mreitsma@stanford.edu).Author Contributions: Dr Reitsma had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.Concept and design: Ye, Lucas, Furukawa, Honeycutt, Krawiec, Salomon, Reitsma.Acquisition, analysis, or interpretation of data: Ye, Lucas, Furukawa, Kalauokalani, Puente, Salomon, Reitsma.Drafting of the manuscript: Ye, Krawiec, Salomon, Reitsma.Critical review of the manuscript for important intellectual content: All authors.Statistical analysis: Ye, Salomon, Reitsma.Obtained funding: Furukawa, Puente, Salomon.Administrative, technical, or material support: Ye, Lucas, Furukawa, Honeycutt, Kalauokalani, Krawiec, Puente, Salomon.Supervision: Furukawa, Kalauokalani, Krawiec, Salomon, Reitsma.Conflict of Interest Disclosures: None reported.Funding/Support: This work was supported by award NU38PS004651 from the US Centers for Disease Control and Prevention National Center for HIV, Viral Hepatitis, STD, and TB Prevention Epidemiologic and Economic Modeling Agreement.Role of the Funder/Sponsor: Employees of the funder participated as coauthors on the study and contributed to the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication as described in the Author Contributions section. The funder had no other role in these processes.Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the US Centers for Disease Control and Prevention or the other authors’ affiliated institutions.Data Sharing Statement: See Supplement 2. References 1.US Department of Health and Human Services. Viral hepatitis national strategic plan: a roadmap to elimination for the US (2021-2025). Accessed July 28, 2026. https://www.hhs.gov/sites/default/files/Viral-Hepatitis-National-Strategic-Plan-2021-2025.pdf2.Akiyama  MJ, Bialek  T, Simonson  R.  The carceral-community cascade and HCV elimination.   JAMA. 2025;333(5):369-370. doi:10.1001/jama.2024.20602ArticlePubMedGoogle ScholarCrossref3.Hall  EW, Bradley  H, Barker  LK,  et al.  Estimating hepatitis C prevalence in the US, 2017-2020.   Hepatology. 2025;81(2):625-636. doi:10.1097/HEP.0000000000000927PubMedGoogle ScholarCrossref4.Spaulding  AC, Kennedy  SS, Osei  J,  et al.  Estimates of hepatitis C seroprevalence and viremia in state prison populations in the US.   J Infect Dis. 2023;228(suppl 3):s160-s167. doi:10.1093/infdis/jiad227PubMedGoogle ScholarCrossref5.Lucas  KD, Krawiec  A, Wada  J, Kanan  RJ.  The hepatitis C care cascade in California state prisons: screening and treatment scale-up and progress toward elimination, 2016-2023.   Clin Liver Dis (Hoboken). 2024;23(1):e0117. doi:10.1097/CLD.0000000000000117PubMedGoogle ScholarCrossref6.McNamara  M, Furukawa  N, Cartwright  EJ.  Advancing hepatitis C elimination through opt-out universal screening and treatment in carceral settings, US.   Emerg Infect Dis. 2024;30(13)(suppl 1):S80-S87. doi:10.3201/eid3013.230859PubMedGoogle ScholarCrossref7.State of California. 2018-2019 State budget 5225 Department of Corrections and Rehabilitation. Accessed July 28, 2026. https://ebudget.ca.gov/publication/e/2018-19/Department/52258.Chhatwal  J, Aaron  A, Zhong  H,  et al. Projected health benefits and health care savings from the US national hepatitis C elimination initiative. National Bureau of Economic Research. Published April 2023. Accessed July 28, 2026. https://www.nber.org/papers/w311399.Congressional Budget Office. Budgetary effects of policies that would increase hepatitis C treatment. Accessed July 28, 2026. https://www.cbo.gov/publication/6040710.Abimbola  TO, Symum  H, Van Handel  M, Teshale  E, Thompson  W.  Lifetime medical costs of chronic hepatitis C in the US.   BMC Health Serv Res. 2026;26(1):609. doi:10.1186/s12913-026-14360-1PubMedGoogle ScholarCrossref

Human papillomaviruses (HPVs) are responsible for causing most cervical cancers and also other cancers. Thankfully, safe and highly effective anticancer HPV vaccines have been available for nearly 2 decades, and some countries, notably Australia, are aiming to eliminate cervical cancer by 2035—less than 10 years from now—using HPV vaccines.1 This study asks an important public health question that pediatricians and parents might also ask: do females who originally received 2 doses of HPV vaccine in elementary school need a third dose in high school? That is, are 2 doses noninferior to 2 + 1 doses? HPV vaccines were initially approved on a 3-doses over 6-month schedule. In 2008, the province of Quebec, Canada, started a school-based vaccination program with quadrivalent (4-strain) HPV vaccine recommending 2 doses during the fourth grade and a third dose in the ninth grade, 5 years later. However, in 2013 when the ninth graders were due to receive a third dose, Quebec authorities cancelled the third vaccination based on mathematical modeling studies and other evidence, including emerging herd immunity, but only under the condition that a trial comparing 2 doses to 2 + 1 doses be completed.2 To answer the call of the Quebec public health authorities, investigators completed this large and innovative randomized trial.3 They randomized 3356 females with a mean age of approximately 15 years who had already received 2 doses 5 years earlier, with half receiving an HPV vaccine booster dose during their initial visit and the other half undergoing observation without a placebo. The participants self-collected vaginal swabs every 6 months for at least 5 years. The primary outcome was persistent HPV-16 or HPV-18 DNA detected in consecutive swabs (these 2 genotypes cause 70% of cervical cancers worldwide). One of the innovations implemented midway through the trial was that investigators only tested every other swab for HPV DNA and then tested the swabs immediately before and after only if the initial tested swab was positive. You have to appreciate the cost-effectiveness and efficiency of this approach! After a median follow-up of 10.9 years after the first dose and after collecting more than 36 000 samples, investigators found that almost the exact same proportion of participants in each group had no positive HPV DNA detected, 60.4% in the 2 + 1 booster intervention group and 60.2% in the standard 2-dose control group. When they looked specifically at the persistence of the HPV-16 and HPV-18 genotypes, their primary outcome, only 1 participant (0.1%) in the 2 + 1–dose group had a confirmed time-limited persistent HPV-16 infection, and there were none in the 2-dose control group. Even looking at single positive tests, there were only 8 (0.1%) HPV-16 or HPV-18 types detected in the 2-dose group and 15 (0.2%) in the 2 + 1–dose group. Video Preventing Genital HPV—2 vs 3 Vaccine Doses? Data From a Clinical Trial HPV vaccinations—are all 3 doses needed to protect against cervical HPV infection? JAMA Network Open Editor in Chief Eli Perencevich, MD, MS, discusses his 2025 pick for Editor’s Choice: Clinical Trials of the Year and explains why it highlights how public health decisions should be made. There were not enough persistent infections to test for noninferiority. This was unfortunate for the investigators but great news for the people of Quebec because it shows that the vaccine program was highly successful. It also validates what the mathematical modeling and herd immunity estimates suggested way back in 2013. I hope this cohort is followed up for years since the exact duration of protection is not known, and perhaps the benefits of the booster dose will be seen in future years. But for now, 2 doses (or even a 1-dose schedule, as many countries are implementing) seem to be enough. To me, this trial, this story, highlights how evidence-based public health decisions should be made: with epidemiological studies, mathematical models, and randomized trials like this trial in JAMA Network Open each playing their role. Back to top Article Information Published: September 16, 2026. doi:10.1001/jamanetworkopen.2026.36217Open Access: This is an open access article distributed under the terms of the CC-BY-NC-ND License, which does not permit alteration or commercial use, including those for text and data mining, AI training, and similar technologies. © 2026 Perencevich EN. JAMA Network Open.Corresponding Author: Eli N. Perencevich, MD, MS, The University of Iowa, Department of Internal Medicine, Carver College of Medicine, CADRE (152), Iowa City VA Medical Center, 601 Hwy 6W, Iowa City, IA 52246 (Eli.Perencevich@jamanetwork.org).Conflict of Interest Disclosures: None reported. References 1.Australia on track to eliminate cervical cancer by 2035. News release. The Hon Rebecca White MP, Assistant Minister for Health and Aged Care, Assistant Minister for Indigenous Health, Assistant Minister for Women. November 19, 2025. Accessed August 7, 2026. https://www.health.gov.au/ministers/the-hon-rebecca-white-mp/media/australia-on-track-to-eliminate-cervical-cancer-by-2035?language=en2.Comité sur l'immunisation du Québec. HPV immunization of Quebec pre-adolescents: two or three doses? Institut national de santé publique du Québec. June 20, 2014. Accessed August 7, 2026. https://www.inspq.qc.ca/en/publications/18373.Sauvageau  C, Mayrand  MH, Ouakki  M,  et al.  Protection against persistent HPV-16/18 infection after different number of doses of quadrivalent vaccine in girls and young women: a randomized clinical trial.   JAMA Netw Open. 2025;8(7):e2519095. doi:10.1001/jamanetworkopen.2025.19095ArticlePubMedGoogle ScholarCrossref

View abstract The Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria (PACCARB) was established to advise the government on strategies to mitigate antimicrobial resistance (AMR) and its increasing threat to public health and national security. Its members included experts from diverse disciplines such as healthcare, veterinary medicine, industry, public health, and agriculture who were positioned to interface with key stakeholders and the public in an aspirational multidisciplinary approach to combating AMR. The council was successful in elevating AMR as a national priority and played a crucial role in watershed events for antimicrobial stewardship (AS) such as the development of the second National Action Plan for Combating Antibiotic-Resistant Bacteria and the requirement for hospitals to establish antimicrobial stewardship programs (ASPs). Additionally, PACCARB was responsible for reframing the discourse on AMR through the context of One Health and evolved domestic efforts into global collaboration. While PACCARB’s future remains uncertain, stakeholder organizations must continue to advocate for policy in favor of AMR surveillance and prevention to avoid losing the momentum which PACCARB generated over the course of the last decade.

(opens in new tab) RCT: AI Chatbot Use for for Human Papillomavirus Vaccine Literacy in JapanVisual Abstract. View LargeDownload Go to Figure in ArticleImportance  Persistent misinformation and low confidence impede human papillomavirus (HPV) vaccine uptake in Japan. Artificial intelligence (AI)–driven conversational agents may provide scalable vaccine education, but randomized evidence for HPV vaccine communication remains limited.Objective  To determine whether an AI-driven HPV vaccine chatbot improves caregiver HPV vaccine literacy compared with a government leaflet.Design, Setting, and Participants  Parallel-group randomized clinical trial (RCT) conducted through a national research panel of female caregivers in Japan with unvaccinated daughters aged 12 to 18 years from November 30 to December 27, 2024, with 2-week follow-up.Interventions  Participants were randomized 1:1 to an AI-driven HPV vaccine chatbot or standard government HPV vaccine leaflet.Main outcomes and measures  The primary outcome was an HPV vaccine literacy, evaluated immediately after intervention to estimate immediate intervention efficacy and evaluated at 2-week follow-up to estimate durability. HPV vaccine literacy was measured using 7 factual questions about HPV and HPV vaccination; scores are shown on a 0 to 7 scale, with higher scores indicating more correct responses.The secondary outcome was decision to vaccinate at 2-week follow-up.Results  Among 848 randomized participants, 704 of 841 (83.7%) were included in the immediate modified intention-to-treat (mITT) analysis (353 chatbot, 351 leaflet) and 477 of 841 (56.7%) in the mITT analysis at 2 weeks (237 chatbot, 240 leaflet). A total of 447 of 703 participants (63.6%) were aged 40 to 49 years and had college or university education (472 of 703 participants [67.1%]). Immediately after the intervention, analysis of covariance-adjusted literacy was higher with the chatbot (adjusted mean difference, 0.30 points on the 0 to 7 scale; 95% CI, 0.18-0.43 points; P < .001). At the 2-week durability assessment, mean (SD) literacy increased by 0.40 (1.21) with the chatbot vs 0.28 (1.13) points with the leaflet; adjusted literacy again favored the chatbot (adjusted mean difference, 0.30 points; 95% CI, 0.13-0.47; P < .001). At 2 weeks, caregivers’ vaccination decisions did not differ between groups (102 of 253 participants [40.3%] vs 103 of 260 participants [39.6%]; adjusted odds ratio, 0.74; 95% CI, 0.41 to 1.33; P = .31).Conclusions and Relevance  In this RCT of female caregivers in Japan, an AI-driven HPV vaccine chatbot produced higher adjusted HPV vaccine literacy than a government leaflet immediately after intervention and at 2-week follow-up, without a measurable short-term effect on vaccination decision. Conversational AI may complement official materials and health care professional recommendations.Trial Registration  ClinicalTrials.gov Identifier: NCT06702423

Sohani et al1 report a systematic review and bayesian meta-analysis of 110 randomized clinical trials of cefepime vs other β-lactam antibiotics in 22 598 patients. Across all trials, they found a 94.4% posterior probability that cefepime was associated with higher all-cause mortality. Restricted to the 73 peer-reviewed published trials, that probability rose to 98.6%, corresponding to a number needed to harm of 111 to 227. The signal was evident in adults but not children, was most pronounced in febrile neutropenia, and persisted across comparator agents and dosing strategies. The authors stop appropriately short of recommending against cefepime, calling instead for a more nuanced reading of its safety in future guidance. This study is the latest turn in a debate now 2 decades old. In 2007, Yahav et al2 reported a 26% relative increase in mortality with cefepime, prompting an investigation by the US Food and Drug Administration (FDA). That investigation assembled trial-level data from 88 studies and patient-level data from 35 and found a 30-day all-cause mortality of 5.63% with cefepime and 5.68% with comparators.3 The FDA concluded that the data did not demonstrate excess mortality, and cefepime has remained first-line treatment for febrile neutropenia in society guidance ever since. Sohani et al1 now reach a different conclusion from a larger evidence base, and clinicians may reasonably ask which analysis to believe. The bayesian framing here is a genuine contribution. It replaces the sterile binary of statistical significance with a probability of harm, which is closer to how clinicians reason. But a probability of harm is easily mistaken for a magnitude of harm. The pooled estimate is an odds ratio of 1.10 with a credible interval that includes no effect and an absolute risk difference of 0.4 percentage points. A high probability of a small effect is not evidence of a large one. The authors are careful on this point; readers may not be. The analysis also contains a tension it cannot resolve. The 37 unpublished trials, most of them submitted to the FDA, point in the opposite direction from the published literature, with greater than 98% posterior probability that they arise from a different distribution. The authors read this as possible publication bias. It may equally reflect systematic differences in enrolled populations, illness severity, dosing, comparators, or outcome ascertainment, none of which can be examined because these trials have never been described in detail. Both readings point to the same remedy. Twenty years of reanalyzing summary estimates is a poor substitute for access to the underlying patient-level data, and the case for releasing it is now overwhelming. All-cause mortality is likewise a blunt instrument for drug safety in the population that dominates this analysis. In febrile neutropenia, which contributed the largest share of trials, death commonly reflects progression of an underlying malignant neoplasm rather than antibiotic failure. Randomization should balance such deaths on average, and the authors defend the outcome on that basis. Yet when the absolute difference is well under 1 percentage point and is drawn from small, largely open-label trials conducted before 2010, modest prognostic imbalance can move the estimate. This is a signal, not a verdict. Most consequentially, the trials that generate this signal bear limited resemblance to contemporary practice. Randomized clinical trials fix the regimen, indication, and population and exclude the confounding conditions that fill our hospitals. Cefepime in the clinical setting is given empirically, often in combination, and deescalated once an organism is identified. Where cefepime has been studied under conditions nearer to practice, the results have not aligned. In the ACORN trial, 2511 adults randomized to cefepime (2 g every 8 hours) or piperacillin-tazobactam showed no difference in the primary outcome of acute kidney injury or death at 14 days (odds ratio, 0.95; 95% CI, 0.80-1.13).4 In a cohort study using a 15-month piperacillin-tazobactam shortage as an instrumental variable, Chanderraj et al5 found 90-day mortality to be 5.0% higher with piperacillin-tazobactam than with cefepime. That study has drawn methodological criticism with some force, but 3 designs pointing in 3 directions are themselves informative; this is not a drug with a large, consistent, reproducible effect on mortality. What might explain the signal? Two mechanisms are plausible, and both concern drug exposure rather than the molecule itself. The first is underexposure. Andreatos et al6 found that the mortality signal in febrile neutropenia concentrated in trials using low-dose cefepime. Many trials in the current analysis are decades old and used regimens that would now be considered inadequate. They also predate the 2014 revision of Clinical and Laboratory Standards Institute breakpoints, which created the susceptible dose–dependent category for Enterobacterales precisely because conventional dosing does not reliably maintain concentrations above the minimum inhibitory concentration for organisms at the upper end of the susceptible range. Some of these excess deaths may therefore represent undertreatment rather than toxic effects. The second mechanism is overexposure. Cefepime accumulates when kidney function is impaired or dosing is not adjusted, producing encephalopathy, myoclonus, and nonconvulsive status epilepticus, and these neurotoxic effects have been linked to prolonged hospitalization and death.7 The ACORN study, which found no mortality difference, nonetheless confirmed the neurologic hazard prospectively: Patients receiving cefepime experienced more neurologic dysfunction.4 These mechanisms converge. Cefepime’s therapeutic window is narrower than its 30-year track record suggests, bounded on one side by the pathogen’s minimum inhibitory concentration and on the other by the patient’s kidneys. That is a dosing problem, and dosing problems are tractable. The proper response is therefore not to strike cefepime from febrile neutropenia guidelines, or to avoid it for susceptible Pseudomonas aeruginosa, but to dose it adequately, at 2 g every 8 hours and by prolonged infusion where appropriate, with rigorous kidney adjustment and a low threshold for suspecting neurotoxic effects. Dosing adequately, however, presumes that we can estimate kidney function accurately, and often we cannot. Even the race-free estimated glomerular filtration rate (eGFR) equations now recommended by the National Kidney Foundation and American Society of Nephrology remain imperfect guides to cefepime dosing. Although the combined creatinine–cystatin C eGFR equation most closely approximates measured GFR, even this more accurate approach retains meaningful imprecision, with estimates often varying by as much as 30%.8 Critical illness amplifies it further. The contemporary β-lactam target is a free drug concentration of 4 to 8 times the organism’s minimum inhibitory concentration across the dosing interval, yet at least half of critically ill patients fail to reach it even with prolonged infusions. That margin is narrower for cefepime than for other β-lactams. Piperacillin remains safe at 10 times its breakpoint (16 mg/L), whereas cefepime concentrations only 3 to 4 times its breakpoint (8 mg/L) have been linked to neurotoxic effects.8 Although the evidence is heterogeneous, β-lactam therapeutic drug monitoring improves target attainment and, in some studies, clinical and microbiologic cure.8 It warrants prospective evaluation, but the case for broader adoption is strong, particularly for cefepime, where either underexposure or overexposure can plausibly contribute to harm. Sohani et al1 have meticulously quantified an uncertainty that has too often been waved away. The work that remains is not another reanalysis of the same aging trials. It is a release of the FDA data and rigorous prospective study of optimized dosing. Cefepime is not a dangerous drug in search of a replacement; it is a useful drug in search of a dose. Back to top Article Information Published: September 10, 2026. doi:10.1001/jamanetworkopen.2026.32904Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2026 Uslan DZ et al. JAMA Network Open.Corresponding Author: Daniel Z. Uslan, MD, MBA, Division of Infectious Diseases, David Geffen School of Medicine at UCLA, 924 Westwood Blvd, #200, Los Angeles, CA 90024 (duslan@mednet.ucla.edu).Conflict of Interest Disclosures: None reported. 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