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Blood and surveillance cultures from an injured service member from Ukraine grew Acinetobacter baumannii, Klebsiella pneumoniae, Enterococcus faecium, and 3 distinct Pseudomonas aeruginosa strains. Isolates were nonsusceptible to most antibiotics and carried an array of antibiotic resistant genes, including carbapenemases (bla , bla , bla , bla , bla ) and 16S methyltransferases (armA and rmtB4).

A vaccine to prevent infection and disease caused by Plasmodium vivax is needed both to reduce the morbidity caused by this parasite and as a key component in efforts to eradicate malaria worldwide. Vivax malaria protein 1 (VMP001), a novel chimeric protein that incorporates the amino- and carboxy- terminal regions of the circumsporozoite protein (CSP) and a truncated repeat region that contains repeat sequences from both the VK210 (type 1) and the VK247 (type 2) parasites, was developed as a vaccine candidate for global use. We conducted a first-in-human Phase 1 dose escalation vaccine study with controlled human malaria infection (CHMI) of VMP001 formulated in the GSK Adjuvant System AS01B. A total of 30 volunteers divided into 3 groups (10 per group) were given 3 intramuscular injections of 15 μg, 30 μg, or 60 μg respectively of VMP001, all formulated in 500 μL of AS01B at each immunization. All vaccinated volunteers participated in a P. vivax CHMI 14 days following the third immunization. Six non-vaccinated subjects served as infectivity controls. The vaccine was shown to be well tolerated and immunogenic. All volunteers generated robust humoral and cellular immune responses to the vaccine antigen. Vaccination did not induce sterile protection; however, a small but significant delay in time to parasitemia was seen in 59% of vaccinated subjects compared to the control group. An association was identified between levels of anti-type 1 repeat antibodies and prepatent period. This trial was the first to assess the efficacy of a P. vivax CSP vaccine candidate by CHMI. The association of type 1 repeat-specific antibody responses with delay in the prepatency period suggests that augmenting the immune responses to this domain may improve strain-specific vaccine efficacy. The availability of a P. vivax CHMI model will accelerate the process of P. vivax vaccine development, allowing better selection of candidate vaccines for advancement to field trials.

Background Extra-intestinal pathogenic Escherichia coli (ExPEC) are a leading cause of bloodstream and urinary tract infections worldwide. Over the last two decades, increased rates of antibiotic resistance in E. coli have been reported, further complicating treatment. Worryingly, specific lineages expressing extended-spectrum β -lactamases (ESBLs) and fluoroquinolone resistance have proliferated and are now considered a serious threat. Obtaining contemporary information on the epidemiology and prevalence of these circulating lineages is critical for containing their spread globally and within the clinic. Methods Whole-genome sequencing (WGS), phylogenetic analysis, and antibiotic susceptibility testing were performed for a complete set of 2075 E. coli clinical isolates collected from 1776 patients at a large tertiary healthcare network in the USA between October 2019 and September 2020. Results The isolates represented two main phylogenetic groups, B2 and D, with six lineages accounting for 53% of strains: ST-69, ST-73, ST-95, ST-131, ST-127, and ST-1193. Twenty-seven percent of the primary isolates were multidrug resistant (MDR) and 5% carried an ESBL gene. Importantly, 74% of the ESBL -E.coli were co-resistant to fluoroquinolones and mostly belonged to pandemic ST-131 and emerging ST-1193. SNP-based detection of possible outbreaks identified 95 potential transmission clusters totaling 258 isolates (12% of the whole population) from ≥ 2 patients. While the proportion of MDR isolates was enriched in the set of putative transmission isolates compared to sporadic infections (35 vs 27%, p = 0.007), a large fraction (61%) of the predicted outbreaks (including the largest cluster grouping isolates from 12 patients) were caused by the transmission of non-MDR clones. Conclusion By coupling in-depth genomic characterization with a complete sampling of clinical isolates for a full year, this study provides a rare and contemporary survey on the epidemiology and spread of E. coli in a large US healthcare network. While surveillance and infection control efforts often focus on ESBL and MDR lineages, our findings reveal that non-MDR isolates represent a large burden of infections, including those of predicted nosocomial origins. This increased awareness is key for implementing effective WGS-based surveillance as a routine technology for infection control.

Carbapenemase-producing Pseudomonas aeruginosa is a major cause of healthcare-associated infections worldwide and is associated with high mortality due to limited treatment options. In this study, we characterize the emergence and international spread of a previously underrecognized lineage of P. aeruginosa that has independently acquired and stabilized multiple resistance genes, including those encoding VIM, IMP, NDM, and Dutch imipenemase carbapenemases. Using genomic sequencing and evolutionary analyses, we show how this lineage emerged in the late 19th century and has since adapted by integrating resistance genes directly into its chromosome, promoting long-term stability and outbreak potential. Strikingly, we link its global expansion to population movements, soldier evacuations, and healthcare disruptions during armed conflicts in Afghanistan and Ukraine. This work reveals how political instability can drive the spread of multidrug-resistant bacteria and underscores the value of high-resolution surveillance to detect and contain emerging threats before they become dominant in clinical settings.

Background The Russian invasion of Ukraine in 2022 has placed extraordinary pressure on hospitals there. One consequence of this has been the alarming increase in infections caused by multi-drug resistant organisms (MDROs), both within Ukraine and among the Ukrainian diaspora. The original source of these MDROs remains obscure although nosocomial origin is suspected. Here, we analyzed a collection of Acinetobacter baumannii and Pseudomonas aeruginosa collected from Ukraine before and after the invasion to glean a greater understanding of their relationship and origins. Methods Genomic analysis was conducted on 167 A. baumannii and 93 P. aeruginosa cultured from 223 Ukrainian patients hospitalized in Ukraine or other European countries. Fifty-three isolates were cultured between 2014 and 2021, prior to the invasion, and the remaining 207 after. Results Highly genetically related extensively-drug resistant (XDR) clones were identified that spanned the pre- and post-invasion periods. For A. baumannii , isolates encompassed three sequence types (STs), including carbapenemase-producing strains from ST-2 ( bla OXA-23 ) and ST-78 ( bla OXA-72 ), as well as ST-400 carrying the ESBL bla GES-11 . For P. aeruginosa , isolates encompassed three STs: ST-773 carrying bla NDM-1 , ST-1047 carrying bla IMP-1 , and ST-244. For all, the mobile genetic elements associated with carbapenemase carriage were fully characterized. Notably, post-invasion ST-773 and ST-1047 P. aeruginosa had a signature of host adaptation with multiple loss-of-function mutations in the quorum-sensing regulator LasR, known to modulate immune responses and provide survival advantages in animal models of infection. Conclusions XDR epidemic clones circulating in Ukraine and across Europe since 2022 share a close genetic relationship to historical strains from Ukraine. In some cases, direct links to medical facilities within Ukraine can be inferred. These data suggest that surveillance efforts should focus on tracking nosocomial transmission within Ukrainian hospitals while infection control efforts are being disrupted by the ongoing Russian invasion.

Whole-genome sequencing is revolutionizing bacterial outbreak investigation, but its application to the clinic remains limited. In 2020, prospective and retrospective surveillance detected a Pseudomonas aeruginosa outbreak with 253 isolates collected from 82 patients in 26 wards of a hospital. Its origin was dated to the late 1990s, just after the facility opened, and patient-to-patient and environment-to-patient cases of transmission were inferred. Over time, two epidemic subclones evolved in separate hosts and hospital areas, including newly opened wards, and hospital-wide sampling confirmed reservoirs persisted in the plumbing. Pathoadaptive mutations in genes associated with virulence, cell wall biogenesis, and antibiotic resistance were identified. While the latter correlated with the acquisition of phenotypic resistances to first (cephalosporin), second (carbapenems), and third (colistin) lines of treatment, maximum parsimony suggested that a truncation in a lipopolysaccharide component coincided with the emergence of a subclone prevalent in long-term infections. Since initial identification, extensive infection control efforts guided by routine, near real-time surveillance have proved successful at slowing transmission. Many bacteria thrive in moist hospital environments, such as sinks, drains and medical equipment, and pose a significant infection risk. For example, the bacterium Pseudomonas aeruginosa can cause severe infections in patients with burns, wounds or weakened immune systems. This species can further develop resistance to many antibiotics, making infections more difficult to treat and control. Hospitals use infection prevention programs to detect and limit bacterial spread. But identifying how and where the bacteria persist remains a challenge. To reveal hidden outbreaks and identify environmental sources, scientists have started using genome sequencing – the process of reading a bacterium’s complete genetic code – to monitor how hospital infections begin and propagate. To underscore the value of this method, Stribling et al. investigated a decades-long Pseudomonas aeruginosa outbreak in a hospital in the United States, despite ongoing infection control efforts. By sequencing the genomes of more than 250 bacterial samples collected over ten years, the team traced the outbreak’s origin to the late 1990s, soon after the hospital opened. The same strain spread across multiple wards and evolved into two related subgroups. Genetic and environmental analyses revealed that contaminated sink drains acted as long-term reservoirs, repeatedly infecting patients even years apart. The bacteria gradually became resistant to several major antibiotics. Guided by these genomic insights, targeted infection control actions – such as sink decontamination and routine genomic monitoring –finally reduced new infections and helped contain the outbreak. The findings of Stribling et al. demonstrate how routine genome sequencing can uncover hidden infection routes and guide more effective hospital control measures. Public health systems could use similar approaches to detect outbreaks earlier and prevent prolonged hospital contamination. Before this can become routine, hospitals will need access to affordable sequencing technologies, trained personnel and real-time data sharing. In the long run, such integrated genomic surveillance could protect patients and reduce the global burden of antibiotic-resistant infections.

The human microbiome is comprised of a complex and diverse community of organisms that is subject to dynamic changes over time. As such, cross-sectional studies of the microbiome provide a multitude of information for a specific body site at a particular time, but they fail to account for temporal changes in microbial constituents resulting from various factors. To address this shortcoming, longitudinal research studies of the human microbiome investigate the influence of various factors on the microbiome of individuals within a group or community setting. These studies are vital to address the effects of host and/or environmental factors on microbiome composition as well as the potential contribution of microbiome members during the course of an infection. The relationship between microbial constituents and disease development has been previously explored for skin and soft tissue infections (SSTIs) within congregate military trainees. Accordingly, approximately 25% of the population carries Staphylococcus aureus within their nasal cavity, and these colonized individuals are known to be at increased risk for SSTIs. To examine the evolution of the nasal microbiota of U.S. Army Infantry trainees, individuals were sampled longitudinally from their arrival at Fort Benning, Georgia, until completion of their training 90 days later. These samples were then processed to determine S. aureus colonization status and to profile the nasal microbiota using 16S rRNA gene-based methods. Microbiota stability differed dramatically among the individual trainees; some subjects exhibited great stability, some subjects showed gradual temporal changes and some subjects displayed a dramatic shift in nasal microbiota composition. Further analysis utilizing the available trainee metadata suggests that the major drivers of nasal microbiota stability may be S. aureus colonization status and geographic origin of the trainees. Nasal microbiota evolution within the congregate setting imposed by military training is a complex process that appears to be affected by numerous factors. This finding may indicate that future campaigns to prevent S. aureu s colonization and future SSTIs among high-risk military trainees may require a ‘personalized’ approach.

People living in close quarters, such as military trainees, are at increased risk for skin and soft tissue infections (SSTI), especially those caused by methicillin-resistant (MRSA). The serum immune factors associated with the onset of SSTI are not well understood. We conducted a longitudinal study of SSTIs, enrolling US Army trainees before starting military training and following up for 14 weeks. Samples were collected on Day 0, 56, and 90. Serum chemokines and cytokines among 16 SSTI cases and 51 healthy controls were evaluated using an electro-chemiluminescence based multiplex assay platform. Of 54 tested cytokines, 12 were significantly higher among SSTI cases as compared to controls. Among the cases, there were correlations between factors associated with vascular injury (i.e., VCAM-1, ICAM-1, and Flt1), the angiogenetic factor VEGF, and IL-10. Unsupervised machine learning (Principal Component Analysis) revealed that IL10, IL17A, C-reactive protein, ICAM1, VCAM1, SAA, Flt1, and VGEF were indicative of SSTI. The study demonstrates the power of immunoprofiling for identifying factors predictive of pre-illness state of SSTI thereby identifying early stages of an infection and individuals susceptible to SSTI.

Using regionally linked facility and household surveys, we measured the quality of integrated antenatal care and malaria in pregnancy services in Kenya, Namibia, Senegal, and Tanzania. We examined country heterogeneities for the association of integrated antenatal and malaria service quality scores with insecticide-treated bed net (ITN) use in pregnant women and children under-five and intermittent preventive treatment in pregnancy (IPTp-2) uptake. Malaria in pregnancy service quality was low overall. Our findings suggest modest, positive associations between malaria in pregnancy quality and ITN use and IPTp-2 uptake across pooled models and for most studied countries, with evidence of heterogeneity in the strength of associations and relevant confounding factors. Antenatal care quality generally was not associated with the study outcomes, although a positive interaction with malaria in pregnancy quality was present for pooled ITN use models. The improved quality of malaria services delivered during formal antenatal care can help address low coverage and usage rates of preventive malaria interventions in pregnancy and childhood. Study findings may be used to target quality improvement efforts at the sub-national level. Study methods may be adapted to identify low-performing facilities for intervention and adaption to other areas of care, such as HIV/AIDS, child immunizations, and postnatal care.

Primaquine is used to eradicate the hepatic or hypnozoite form of Plasmodium vivax that may lead to relapse of infection. Host genetic factors may play a role in the activity of primaquine therapy. To the Editor: Primaquine is the only medication approved by the Food and Drug Administration to eradicate the hypnozoites of Plasmodium vivax, but relapses of P. vivax malaria due to drug failure occur. 1 Human cytochrome P-450 isoenzyme 2D6 (CYP2D6) may be a key enzyme involved in metabolizing primaquine into redox-active metabolites against hypnozoites in the liver. 2 , 3 As part of a phase 1 clinical trial of a vaccine against P. vivax (Study of VMP001 and AS01B in Healthy Malaria-Naive Adults; ClinicalTrials.gov number, NCT01157897), 33 participants were exposed to P. vivax sporozoites from the bites of infected mosquitoes. Parasitemia developed in . . .