OBJECTIVES: . The United States Centers for Disease Control and Prevention (CDC) conducts active surveillance for typhoid fever cases caused by Salmonella enterica serovar Typhi (Typhi). Here we describe the characteristics of the first two cases of mph(A)-positive azithromycin-resistant Typhi identified through US surveillance. METHODS: . Isolates were submitted to public health laboratories, sequenced, and screened for antimicrobial resistance determinants and plasmids, as part of CDC PulseNet's routine genomic surveillance. Antimicrobial susceptibility testing and long-read sequencing were also performed. Basic case information (age, sex, travel, outcome) was collected through routine questionnaires; additional epidemiological data was requested through follow-up patient interviews. RESULTS: . The patients are related and both reported travel to India (overlapping travel dates) before illness onset. Both Typhi genomes belong to the GenoTyphi lineage 4.3.1.1 and carry the azithromycin-resistance gene mph(A) on a PTU-FE (IncFIA/FIB/FII) plasmid. These strains differ genetically from mph(A)-positive Typhi genomes recently reported from Pakistan, suggesting independent emergence of azithromycin resistance in India. CONCLUSIONS: . Cases of typhoid fever caused by Typhi strains resistant to all available oral treatment options are cause for concern and support the need for vaccination of travelers to Typhi endemic regions. US genomic surveillance serves as an important global sentinel for detection of strains with known and emerging antimicrobial resistance profiles, including strains from areas where routine surveillance is not conducted.

Bacterial relatedness measured using select chromosomal loci forms the basis of public health genomic surveillance. While approximating vertical evolution through this approach has proven exceptionally valuable for understanding pathogen dynamics, it excludes a fundamental dimension of bacterial evolution-horizontal gene transfer. Incorporating the accessory genome is the logical remediation and has recently shown promise in expanding epidemiological resolution for enteric pathogens. Employing k-mer-based Jaccard index analysis, and a novel genome length distance metric, we computed pangenome (i.e., core and accessory) relatedness for the globally important pathogen Salmonella enterica serotype Typhi (Typhi), and graphically express both vertical (homology-by-descent) and horizontal (homology-by-admixture) evolutionary relationships in a reticulate network of over 2,200 U.S. Typhi genomes. This analysis revealed non-random structure in the Typhi pangenome that is driven predominantly by the gain and loss of mobile genetic elements, confirming and expanding upon known epidemiological patterns, revealing novel plasmid dynamics, and identifying avenues for further genomic epidemiological exploration. With an eye to public health application, this work adds important biological context to the rapidly improving ways of analyzing bacterial genetic data and demonstrates the value of the accessory genome to infer pathogen epidemiology and evolution.IMPORTANCEGiven bacterial evolution occurs in both vertical and horizontal dimensions, inclusion of both core and accessory genetic material (i.e., the pangenome) is a logical step toward a more thorough understanding of pathogen dynamics. With an eye to public, and indeed, global health relevance, we couple contemporary tools for genomic analysis with decades of research on mobile genetic elements to demonstrate the value of the pangenome, known and unknown, annotated, and hypothetical, for stratification of Salmonella enterica serovar Typhi (Typhi) populations. We confirm and expand upon what is known about Typhi epidemiology, plasmids, and antimicrobial resistance dynamics, and offer new avenues of exploration to further deduce Typhi ecology and evolution, and ultimately to reduce the incidence of human disease.

BACKGROUND: In the US, yersinosis was understood to predominantly occur in winter and among Black or African American infants and Asian children. Increased use of culture-independent diagnostic tests (CIDTs) has led to marked increases in yersinosis diagnoses. METHODS: We describe differences in the epidemiology of yersiniosis diagnosed by CIDT versus culture in 10 US sites, and identify determinants of health associated with diagnostic method. RESULTS: Annual reported incidence increased from 0.3/100 000 in 2010 to 1.3/100 000 in 2021, particularly among adults ≥18 years, regardless of race and ethnicity, and during summer months. The proportion of CIDT-diagnosed infections increased from 3% in 2012 to 89% in 2021. An ill person's demographic characteristics and location of residence had a significant impact on their odds of being diagnosed by CIDT. CONCLUSIONS: Improved detection due to increased CIDT use has altered our understanding of yersinosis epidemiology, however differential access to CIDTs may still affect our understanding of yersinosis.

Background: International distribution of contaminated foods can be a source of Salmonella infections in people and can contribute to the spread of antimicrobial-resistant bacteria across countries. We report an investigation led by the United States Centers for Disease Control and Prevention, the Food and Drug Administration (FDA), and state governmental officials into a multistate outbreak of salmonellosis linked to pig ear pet treats. Methods: Pig ear treats and companion dogs were tested for Salmonella by state officials and the FDA. Products were traced back to the country of origin when possible. Cases were defined as outbreak illnesses in people associated with one of seven Salmonella serotypes genetically related to samples from pig ear pet treats, with isolation dates from June 2015 to September 2019. Whole genome sequencing (WGS) of isolates was used to predict antimicrobial resistance. Findings: The outbreak included 154 human cases in 34 states. Of these, 107 of 122 (88%) patients reported dog contact, and 65 of 97 (67%) reported contact with pig ear pet treats. Salmonella was isolated from 137 pig ear treats, including some imported from Argentina, Brazil, and Colombia, and from four dogs. WGS predicted 77% (105/137) of human and 43% (58/135) of pig ear treat isolates were resistant to ≥3 antimicrobial classes. Interpretation: This was the first documented United States multistate outbreak of Salmonella infections linked to pig ear pet treats. This multidrug-resistant outbreak highlights the interconnectedness of human health and companion animal ownership and the need for zoonotic pathogen surveillance to prevent human illness resulting from internationally transported pet food products. Funding: Animal Feed Regulatory Program Standards award. Animal and product testing conducted by FDA Vet-LIRN was funded by Vet-LIRN infrastructure grants ( PAR-22-063). © 2024

Drug-resistant shigellosis is increasing, particularly among men who have sex with men (MSM). During July-October 2022, an extended-spectrum beta-lactamase producing Shigella sonnei cluster of 9 patients was identified in Chicago, of whom 8 were MSM and 6 were festival attendees. The cluster also included 4 domestic travelers to Chicago. Sexual health care for MSM should include shigellosis diagnosis and prevention.

BACKGROUND: Because interventions are available to prevent further recurrence in patients with recurrent Clostridioides difficile infection (rCDI), we identified predictors of multiple rCDI (mrCDI) in adults at the time of presentation with initial CDI (iCDI). METHODS: iCDI was defined as a positive C difficile test in any clinical setting during January 2018-August 2019 in a person aged ≥18 years with no known prior positive test. rCDI was defined as a positive test ≥14 days from the previous positive test within 180 days after iCDI; mrCDI was defined as ≥2 rCDI. We performed multivariable logistic regression analysis. RESULTS: Of 18 829 patients with iCDI, 882 (4.7%) had mrCDI; 437 with mrCDI and 7484 without mrCDI had full chart reviews. A higher proportion of patients with mrCDI than without mrCDI were aged ≥65 years (57.2% vs 40.7%; P < .0001) and had healthcare (59.1% vs 46.9%; P < .0001) and antibiotic (77.3% vs 67.3%; P < .0001) exposures in the 12 weeks preceding iCDI. In multivariable analysis, age ≥65 years (adjusted odds ratio [aOR], 1.91; 95% confidence interval [CI], 1.55-2.35), chronic hemodialysis (aOR, 2.28; 95% CI, 1.48-3.51), hospitalization (aOR, 1.64; 95% CI, 1.33-2.01), and nitrofurantoin use (aOR, 1.95; 95% CI, 1.18-3.23) in the 12 weeks preceding iCDI were associated with mrCDI. CONCLUSIONS: Patients with iCDI who are older, on hemodialysis, or had recent hospitalization or nitrofurantoin use had increased risk of mrCDI and may benefit from early use of adjunctive therapy to prevent mrCDI. If confirmed, these findings could aid in clinical decision making and interventional study designs.

OBJECTIVE: Patients tested for Clostridioides difficile infection (CDI) using a 2-step algorithm with a nucleic acid amplification test (NAAT) followed by toxin assay are not reported to the National Healthcare Safety Network as a laboratory-identified CDI event if they are NAAT positive (+)/toxin negative (-). We compared NAAT+/toxin- and NAAT+/toxin+ patients and identified factors associated with CDI treatment among NAAT+/toxin- patients. DESIGN: Retrospective observational study. SETTING: The study was conducted across 36 laboratories at 5 Emerging Infections Program sites. PATIENTS: We defined a CDI case as a positive test detected by this 2-step algorithm during 2018-2020 in a patient aged ≥1 year with no positive test in the previous 8 weeks. METHODS: We used multivariable logistic regression to compare CDI-related complications and recurrence between NAAT+/toxin- and NAAT+/toxin+ cases. We used a mixed-effects logistic model to identify factors associated with treatment in NAAT+/toxin- cases. RESULTS: Of 1,801 cases, 1,252 were NAAT+/toxin-, and 549 were NAAT+/toxin+. CDI treatment was given to 866 (71.5%) of 1,212 NAAT+/toxin- cases versus 510 (95.9%) of 532 NAAT+/toxin+ cases (P < .0001). NAAT+/toxin- status was protective for recurrence (adjusted odds ratio [aOR], 0.65; 95% CI, 0.55-0.77) but not CDI-related complications (aOR, 1.05; 95% CI, 0.87-1.28). Among NAAT+/toxin- cases, white blood cell count ≥15,000/µL (aOR, 1.87; 95% CI, 1.28-2.74), ≥3 unformed stools for ≥1 day (aOR, 1.90; 95% CI, 1.40-2.59), and diagnosis by a laboratory that provided no or neutral interpretive comments (aOR, 3.23; 95% CI, 2.23-4.68) were predictors of CDI treatment. CONCLUSION: Use of this 2-step algorithm likely results in underreporting of some NAAT+/toxin- cases with clinically relevant CDI. Disease severity and laboratory interpretive comments influence treatment decisions for NAAT+/toxin- cases.

Enteric bacterial infections are common among people who travel internationally. During 2017– | 23 2020, CDC investigated 41 multistate outbreaks of nontyphoidal Salmonella and Shiga toxin24 producing Escherichia coli (STEC) linked to international travel. Resistance to one or more | 25 antimicrobial agents was detected in at least 10% of isolates in 16 of 30 (53%) nontyphoidal | 26 Salmonella outbreaks and 8 of 11 (73%) STEC outbreaks evaluated by the National | 27 Antimicrobial Resistance Monitoring System. At least 10% of the isolates in 14 nontyphoidal | 28 Salmonella outbreaks conferred resistance to one or more of the clinically significant | 29 antimicrobials used in human medicine. This report describes the epidemiology and | 30 antimicrobial resistance patterns of these travel-associated multistate outbreaks. Investigating | 31 illnesses among returned travelers and collaboration with international partners could result in | 32 implementation of public health interventions to improve hygiene practices and food safety | 33 standards, and to prevent illness and spread of multidrug resistant organisms domestically and | 34 internationally

BACKGROUND: Phthalate exposures are ubiquitous during pregnancy and may contribute to racial and ethnic disparities in preterm birth. OBJECTIVES: We investigated race and ethnicity in the relationship between biomarkers of phthalate exposure and preterm birth by examining: a) how hypothetical reductions in racial and ethnic disparities in phthalate metabolites might reduce the probability of preterm birth; and b) exposure-response models stratified by race and ethnicity. METHODS: We pooled individual-level data on 6,045 pregnancies from 16 U.S. cohorts. We investigated covariate-adjusted differences in nine urinary phthalate metabolite concentrations by race and ethnicity [non-Hispanic White (White, 43%), non-Hispanic Black (Black, 13%), Hispanic/Latina (38%), and Asian/Pacific Islander (3%)]. Using g-computation, we estimated changes in the probability of preterm birth under hypothetical interventions to eliminate disparities in levels of urinary phthalate metabolites by proportionally lowering average concentrations in Black and Hispanic/Latina participants to be approximately equal to the averages in White participants. We also used race and ethnicity-stratified logistic regression to characterize associations between phthalate metabolites and preterm birth. RESULTS: In comparison with concentrations among White participants, adjusted mean phthalate metabolite concentrations were consistently higher among Black and Hispanic/Latina participants by 23%-148% and 4%-94%, respectively. Asian/Pacific Islander participants had metabolite levels that were similar to those of White participants. Hypothetical interventions to reduce disparities in metabolite mixtures were associated with lower probabilities of preterm birth for Black [13% relative reduction; 95% confidence interval (CI): - 34%, 8.6%] and Hispanic/Latina (9% relative reduction; 95% CI: - 19%, 0.8%) participants. Odds ratios for preterm birth in association with phthalate metabolites demonstrated heterogeneity by race and ethnicity for two individual metabolites (mono-n-butyl and monoisobutyl phthalate), with positive associations that were larger in magnitude observed among Black or Hispanic/Latina participants. CONCLUSIONS: Phthalate metabolite concentrations differed substantially by race and ethnicity. Our results show hypothetical interventions to reduce population-level racial and ethnic disparities in biomarkers of phthalate exposure could potentially reduce the probability of preterm birth. https://doi.org/10.1289/EHP12831.

Animal contact is an established risk factor for nontyphoidal Salmonella infections and outbreaks. During 2015-2018, the U.S. Centers for Disease Control and Prevention (CDC) and other U.S. public health laboratories began implementing whole-genome sequencing (WGS) of Salmonella isolates. WGS was used to supplement the traditional methods of pulsed-field gel electrophoresis for isolate subtyping, outbreak detection, and antimicrobial susceptibility testing (AST) for the detection of resistance. We characterized the epidemiology and antimicrobial resistance (AMR) of multistate salmonellosis outbreaks linked to animal contact during this time period. An isolate was considered resistant if AST yielded a resistant (or intermediate, for ciprofloxacin) interpretation to any antimicrobial tested by the CDC or if WGS showed a resistance determinant in its genome for one of these agents. We identified 31 outbreaks linked to contact with poultry (n = 23), reptiles (n = 6), dairy calves (n = 1), and guinea pigs (n = 1). Of the 26 outbreaks with resistance data available, we identified antimicrobial resistance in at least one isolate from 20 outbreaks (77%). Of 1,309 isolates with resistance information, 247 (19%) were resistant to ≥1 antimicrobial, and 134 (10%) were multidrug-resistant to antimicrobials from ≥3 antimicrobial classes. The use of resistance data predicted from WGS increased the number of isolates with resistance information available fivefold compared with AST, and 28 of 43 total resistance patterns were identified exclusively by WGS; concordance was high (>99%) for resistance determined by AST and WGS. The use of predicted resistance from WGS enhanced the characterization of the resistance profiles of outbreaks linked to animal contact by providing resistance information for more isolates.

BACKGROUND: Shigellosis is an acute diarrheal disease transmitted through contaminated food, water, objects, poor hand hygiene, or sexual activity. Healthcare providers (HCP) may not be aware of the multiple routes of Shigella transmission, populations at increased risk, or importance of antibiotic susceptibility testing (AST). This study assessed HCP knowledge and clinical practices regarding shigellosis and antibiotic resistance. METHODS: Porter Novelli Public Services administered a web-based survey (Fall DocStyles 2020) to HCP in the United States. Pediatricians, primary care physicians, nurse practitioners, and physician assistants completed questions about knowledge and clinical practice of acute diarrhea and shigellosis. RESULTS: Of 2196 HCP contacted, 1503 responded (68% response rate). Most identified contaminated food (85%) and water (79%) as routes of Shigella transmission; fewer recognized person-to-person contact (40%) and sexual activity (18%). Men who have sex with men (MSM) were identified as being at risk for shigellosis by 35% of respondents. Most reported counseling patients to wash hands (86%) and avoid food preparation (77%) when ill with shigellosis; 29% reported recommending avoiding sex. Many HCP reported treating shigellosis empirically with ciprofloxacin (62%) and azithromycin (32%), and 29% reported using AST to guide treatment. CONCLUSIONS: We identified several gaps in shigellosis knowledge among HCP including MSM as a risk group, person-to-person transmission, and appropriate antibiotic use. Improving HCP education could prevent the spread of shigellosis, including drug-resistant infections, among vulnerable populations.

Tobacco use is a major cause of preventable morbidity and mortality globally. Tobacco products, including smokeless tobacco (ST), generally contain tobacco-specific N-nitrosamines (TSNAs), such as N′-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-butanone (NNK), which are potent carcinogens that cause mutations in critical genes in human DNA. This review covers the series of biochemical and chemical transformations, related to TSNAs, leading from tobacco cultivation to cancer initiation. A key aim of this review is to provide a greater understanding of TSNAs: their precursors, the microbial and chemical mechanisms that contribute to their formation in ST, their mutagenicity leading to cancer due to ST use, and potential means of lowering TSNA levels in tobacco products. TSNAs are not present in harvested tobacco but can form due to nitrosating agents reacting with tobacco alkaloids present in tobacco during certain types of curing. TSNAs can also form during or following ST production when certain microorganisms perform nitrate metabolism, with dissimilatory nitrate reductases converting nitrate to nitrite that is then released into tobacco and reacts chemically with tobacco alkaloids. When ST usage occurs, TSNAs are absorbed and metabolized to reactive compounds that form DNA adducts leading to mutations in critical target genes, including the RAS oncogenes and the p53 tumor suppressor gene. DNA repair mechanisms remove most adducts induced by carcinogens, thus preventing many but not all mutations. Lastly, because TSNAs and other agents cause cancer, previously documented strategies for lowering their levels in ST products are discussed, including using tobacco with lower nornicotine levels, pasteurization and other means of eliminating microorganisms, omitting fermentation and fire-curing, refrigerating ST products, and including nitrite scavenging chemicals as ST ingredients. ©, This work was authored as part of the Contributor's official duties as an Employee of the United States Government and is therefore a work of the United States Government. In accordance with 17 U.S.C. 105, no copyright protection is available for such works under U.S. Law.

In 2016, CDC identified a multidrug-resistant (MDR) strain of Salmonella enterica serotype Newport that is now monitored as a persisting strain (REPJJP01). Isolates have been obtained from U.S. residents in all 50 states and the District of Columbia, linked to travel to Mexico, consumption of beef products obtained in the United States, or cheese obtained in Mexico. In 2021, the number of isolates of this strain approximately doubled compared with the 2018-2020 baseline and remained high in 2022. During January 1, 2021- December 31, 2022, a total of 1,308 isolates were obtained from patients, cattle, and sheep; 86% were MDR, most with decreased susceptibility to azithromycin. Approximately one half of patients were Hispanic or Latino; nearly one half reported travel to Mexico during the month preceding illness, and one third were hospitalized. Two multistate outbreak investigations implicated beef products obtained in the United States. This highly resistant strain might spread through travelers, animals, imported foods, domestic foods, or other sources. Isolates from domestic and imported cattle slaughtered in the United States suggests a possible source of contamination. Safe food and drink consumption practices while traveling and interventions across the food production chain to ensure beef safety are necessary in preventing illness.

Gas wells have often intersected mining resources, but unconventional shale well drilling has more recently challenged mines to balance the risk of interaction due to higher pressures and larger quantities of gas. Full extraction mining, such as the longwall method, induces ground movement that may influence the casings if wells are drilled within the mining area. The possibility of a casing shear would lead to the risk of unplanned gas migration into the mine. This has the potential to quickly overcome the ventilation system and reach the explosive range which, if ignited, can have catastrophic consequences on the health and safety of underground workers. The utilization of network software to model mine ventilation is a common practice in the mining industry as a predictive tool for planning and monitoring and can assist with a well breach scenario over a large mining area. This work focuses on a well breach in between two longwall panels after second panel mining with gas entering primarily through the gobs of the adjacent longwall panels. Applying the network software Ventsim, a gob zone and ventilation network were created to better understand the distribution of gas within the mine and the limitations and effectiveness of a ventilation system. The model shows both a transient flow simulation and steady state concentrations throughout the mine ventilation system. Using a standard Pittsburgh coal seam longwall ventilation scheme, we find that the system can dilute a significant inflow of up to 700 cfm of methane. © 2023, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

BACKGROUND: Nontyphoidal Salmonella causes an estimated 1.35 million U.S. infections annually. Antimicrobial-resistant strains are a serious public health threat. We examined the association between resistance and the clinical outcomes of hospitalization, length-of-stay ≥3 days, and death. METHODS: We linked epidemiologic data from the Foodborne Diseases Active Surveillance Network with antimicrobial resistance data from the National Antimicrobial Resistance Monitoring System (NARMS) for nontyphoidal Salmonella infections from 2004-2018. We defined any resistance as resistance to ≥1 antimicrobial and clinical resistance as resistance to ampicillin, azithromycin, ceftriaxone, ciprofloxacin, or trimethoprim-sulfamethoxazole (for the subset of isolates tested for all five agents). We compared outcomes before and after adjusting for age, state, race/ethnicity, international travel, outbreak association, and isolate serotype and source. RESULTS: Twenty percent of isolates (1,105/5,549) had any resistance and 16% (469/2,969) had clinical resistance. Persons whose isolates had any resistance were more likely to be hospitalized (31% vs. 28%, P=0.01) or have length-of-stay ≥3 days (20% vs. 16%, P=0.01). Deaths were rare, but more common among those with any than no resistance (1.0% vs. 0.4%, P=0.01). Outcomes for patients whose isolates had clinical resistance did not differ significantly from those with no resistance. After adjustment, any resistance (adjusted odds ratio 1.23, 95% confidence interval 1.04-1.46) remained significantly associated with hospitalization. CONCLUSIONS: We observed a significant association between nontyphoidal Salmonella infections caused by resistant pathogens and likelihood of hospitalization. Clinical resistance was not associated with poorer outcomes, suggesting that factors other than treatment failure (e.g., strain virulence, strain source, host factors) may be important.

BACKGROUND: The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse Salmonella enterica serovar Typhi (Typhi) genomic data to inform public health action. This analysis, which marks 22 years since the publication of the first Typhi genome, represents the largest Typhi genome sequence collection to date (n=13,000). METHODS: This is a meta-analysis of global genotype and antimicrobial resistance (AMR) determinants extracted from previously sequenced genome data and analysed using consistent methods implemented in open analysis platforms GenoTyphi and Pathogenwatch. RESULTS: Compared with previous global snapshots, the data highlight that genotype 4.3.1 (H58) has not spread beyond Asia and Eastern/Southern Africa; in other regions, distinct genotypes dominate and have independently evolved AMR. Data gaps remain in many parts of the world, and we show the potential of travel-associated sequences to provide informal 'sentinel' surveillance for such locations. The data indicate that ciprofloxacin non-susceptibility (>1 resistance determinant) is widespread across geographies and genotypes, with high-level ciprofloxacin resistance (≥3 determinants) reaching 20% prevalence in South Asia. Extensively drug-resistant (XDR) typhoid has become dominant in Pakistan (70% in 2020) but has not yet become established elsewhere. Ceftriaxone resistance has emerged in eight non-XDR genotypes, including a ciprofloxacin-resistant lineage (4.3.1.2.1) in India. Azithromycin resistance mutations were detected at low prevalence in South Asia, including in two common ciprofloxacin-resistant genotypes. CONCLUSIONS: The consortium's aim is to encourage continued data sharing and collaboration to monitor the emergence and global spread of AMR Typhi, and to inform decision-making around the introduction of typhoid conjugate vaccines (TCVs) and other prevention and control strategies. FUNDING: No specific funding was awarded for this meta-analysis. Coordinators were supported by fellowships from the European Union (ZAD received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 845681), the Wellcome Trust (SB, Wellcome Trust Senior Fellowship), and the National Health and Medical Research Council (DJI is supported by an NHMRC Investigator Grant [GNT1195210]). | Salmonella Typhi (Typhi) is a type of bacteria that causes typhoid fever. More than 110,000 people die from this disease each year, predominantly in areas of sub-Saharan Africa and South Asia with limited access to safe water and sanitation. Clinicians use antibiotics to treat typhoid fever, but scientists worry that the spread of antimicrobial-resistant Typhi could render the drugs ineffective, leading to increased typhoid fever mortality. The World Health Organization has prequalified two vaccines that are highly effective in preventing typhoid fever and may also help limit the emergence and spread of resistant Typhi. In low resource settings, public health officials must make difficult trade-off decisions about which new vaccines to introduce into already crowded immunization schedules. Understanding the local burden of antimicrobial-resistant Typhi and how it is spreading could help inform their actions. The Global Typhoid Genomics Consortium analyzed 13,000 Typhi genomes from 110 countries to provide a global overview of genetic diversity and antimicrobial-resistant patterns. The analysis showed great genetic diversity of the different strains between countries and regions. For example, the H58 Typhi variant, which is often drug-resistant, has spread rapidly through Asia and Eastern and Southern Africa, but is less common in other regions. However, distinct strains of other drug-resistant Typhi have emerged in other parts of the world. Resistance to the antibiotic ciprofloxacin was widespread and accounted for over 85% of cases in South Africa. Around 70% of Typhi from Pakistan were extensively drug-resistant in 2020, but these hard-to-treat variants have not yet become established elsewhere. Variants that are resistant to both ciprofloxacin and ceftriaxone have been identified, and azithromycin resistance has also appeared in several different variants across South Asia. The Consortium’s analyses provide valuable insights into the global distribution and transmission patterns of drug-resistant Typhi. Limited genetic data were available fromseveral regions, but data from travel-associated cases helped fill some regional gaps. These findings may help serve as a starting point for collective sharing and analyses of genetic data to inform local public health action. Funders need to provide ongoing supportto help fill global surveillance data gaps. | eng

BACKGROUND: Campylobacter is the most common cause of bacterial diarrhea in the United States; resistance to macrolides and fluoroquinolones limits treatment options. We examined the epidemiology of US Campylobacter infections and changes in resistance over time. METHODS: The Foodborne Diseases Active Surveillance Network receives information on laboratory-confirmed Campylobacter cases from 10 US sites, and the National Antimicrobial Resistance Monitoring System receives a subset of isolates from these cases for antimicrobial susceptibility testing. We estimated trends in incidence of Campylobacter infection, adjusting for sex, age, and surveillance changes attributable to culture-independent diagnostic tests. We compared percentages of isolates resistant to erythromycin or ciprofloxacin during 2005-2016 with 2017-2018 and used multivariable logistic regression to examine the association of international travel with resistance. RESULTS: Adjusted Campylobacter incidence remained stable or decreased for all groups analyzed since 2012. Among 2449 linked records in 2017-2018, the median patient age was 40.2 years (interquartile range, 21.6-57.8 years), 54.8% of patients were male, 17.2% were hospitalized, and 0.2% died. The percentage of resistant infections increased from 24.5% in 2005-2016 to 29.7% in 2017-2018 for ciprofloxacin (P < .001) and from 2.6% to 3.3% for erythromycin (P = .04). Persons with recent international travel had higher odds than nontravelers of having isolates resistant to ciprofloxacin (adjusted odds ratio [aOR] varied from 1.7 to 10.6 by race/ethnicity) and erythromycin (aOR = 1.7; 95% confidence interval, 1.3-2.1). CONCLUSIONS: Campylobacter incidence has remained stable or decreased, whereas resistance to antimicrobials recommended for treatment has increased. Recent international travel increased the risk of resistance.

More than 7.15 million cases of domestically acquired infectious waterborne illnesses occurred in the United States in 2014, causing 120,000 hospitalizations and 6,600 deaths. We estimated disease incidence for 17 pathogens according to recreational, drinking, and nonrecreational nondrinking (NRND) water exposure routes by using previously published estimates. In 2014, a total of 5.61 million (95% credible interval [CrI] 2.97-9.00 million) illnesses were linked to recreational water, 1.13 million (95% CrI 255,000-3.54 million) to drinking water, and 407,000 (95% CrI 72,800-1.29 million) to NRND water. Recreational water exposure was responsible for 36%, drinking water for 40%, and NRND water for 24% of hospitalizations from waterborne illnesses. Most direct costs were associated with pathogens found in biofilms. Estimating disease burden by water exposure route helps direct prevention activities. For each exposure route, water management programs are needed to control biofilm-associated pathogen growth; public health programs are needed to prevent biofilm-associated diseases.

A qepA8+ Shigella flexneri was cultured from the stool of a traveler returning from India and East Asia. This chromosomally encoded qepA variant, has a six-base insertion, and may have been mobilized as part of a complex IS1-mediated composite transposon including catA1, aadA1, and blaOXA-1. In laboratory E. coli, qepA8 alone only conferred decreased ciprofloxacin susceptibility; however, it may work in combination with additional mechanisms to confer clinical resistance.

Background: We estimated SARS-CoV-2 Delta and Omicron-specific effectiveness of 2 and 3 mRNA COVID-19 vaccine doses in adults against symptomatic illness in US outpatient settings. Method(s): Between October 1, 2021, and February 12, 2022, research staff consented and enrolled eligible participants who had fever, cough, or loss of taste or smell and sought outpatient medical care or clinical SARS-CoV-2 testing within 10 days of illness onset. Using the test-negative design, we compared the odds of receiving 2 or 3 mRNA COVID-19 vaccine doses among SARS-CoV-2 cases versus controls using logistic regression. Regression models were adjusted for study site, age, onset week, and prior SARS-CoV-2 infection. Vaccine effectiveness (VE) was calculated as (1 - adjusted odds ratio) x 100%. Result(s): Among 3847 participants included for analysis, 574 (32%) of 1775 tested positive for SARS-CoV-2 during the Delta predominant period and 1006 (56%) of 1794 participants tested positive during the Omicron predominant period. When Delta predominated, VE against symptomatic illness in outpatient settings was 63% (95% CI: 51% to 72%) among mRNA 2-dose recipients and 96% (95% CI: 93% to 98%) for 3-dose recipients. When Omicron predominated, VE was 21% (95% CI: -6% to 41%) among 2-dose recipients and 62% (95% CI: 48% to 72%) among 3-dose recipients. Conclusion(s): In this adult population, 3 mRNA COVID-19 vaccine doses provided substantial protection against symptomatic illness in outpatient settings when the Omicron variant became the predominant cause of COVID-19 in the U.S. These findings support the recommendation for a 3rd mRNA COVID-19 vaccine dose. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

The emergence and spread of SARS-CoV-2 lineage B.1.1.7, first detected in the United Kingdom, has become a global public health concern because of its increased transmissibility. Over 2500 COVID-19 cases associated with this variant have been detected in the US since December 2020, but the extent of establishment is relatively unknown. Using travel, genomic, and diagnostic data, we highlight the primary ports of entry for B.1.1.7 in the US and locations of possible underreporting of B.1.1.7 cases. Furthermore, we found evidence for many independent B.1.1.7 establishments starting in early December 2020, followed by interstate spread by the end of the month. Finally, we project that B.1.1.7 will be the dominant lineage in many states by mid to late March. Thus, genomic surveillance for B.1.1.7 and other variants urgently needs to be enhanced to better inform the public health response.

BACKGROUND: As a result of evidence suggesting phthalate toxicity, their use has decreased in recent years. However, new phthalates and non-phthalate replacements have emerged in their place, with unknown potential impacts on health. METHODS: We measured 15 phthalate, two di(2-ethylhexyl)terephthalate (DEHTP), and two di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH) urinary metabolites, collected up to three times during pregnancy from 994 women in Northern Puerto Rico (2011-2017). We used tests of linear trend to assess changes in concentrations over time and linear mixed models to identify predictors of exposure (sociodemographic characteristics, drinking water sources, diet, product use). RESULTS: Several phthalate metabolites decreased over the study period indicating decreased exposure, while the geometric mean of DEHTP metabolites (molecular sum) increased threefold between 2014 and 2017. Intraclass correlations revealed low to moderate reproducibility of these biomarkers across pregnancy. Several metabolites were associated with maternal age, income, education, pre-pregnancy BMI, drinking public water, use of cleaning and personal care products, and ice cream consumption. DINCH metabolite concentrations remained low throughout the study period. CONCLUSION: Although exposure to some phthalates may be decreasing, exposure to replacements, such as DEHTP, is increasing. Additional studies are needed to further characterize sources of phthalate replacement chemicals and potential exposure-related health effects among vulnerable populations.

Enteric pathogens, such as non-typhoidal Salmonella, Campylobacter and Escherichia coli, can reside in the intestinal tract of many animals, including livestock, companion animals, small mammals and reptiles. Often, these animals can appear healthy; nonetheless, humans can become infected after direct or indirect contact, resulting in a substantial illness burden. An estimated 14% of the 3.2 million illnesses that occur in the United States of America (USA) each year from such enteric pathogens are attributable to animal contact. Surveillance for enteric pathogens in the USA includes the compilation and interpretation of both laboratory and epidemiologic data. However, the authors feel that a collaborative, multisectoral and transdisciplinary - or One Health - approach is needed for data collection and analysis, at every level. In addition, they suggest that the future of enteric illness surveillance lies in the development of improved technologies for pathogen detection and characterisation, such as genomic sequencing and metagenomics. In particular, using whole-genome sequencing to compare genetic sequences of enteric pathogens from humans, food, animals and the environment, can help to predict antimicrobial resistance among these pathogens, determine their genetic relatedness and identify outbreaks linked to a common source. In this paper, the authors describe three recent, multi-state human enteric illness outbreaks linked to animal contact in the USA and discuss how integrated disease surveillance was essential to outbreak detection and response. Additional datasharing between public health and animal health laboratories and epidemiologists at the local, national, regional and international level may help to improve surveillance for emerging animal and human health threats and lead to new opportunities for prevention.

This case study is part of a series centered on the Centers for Disease Control and Prevention/National Healthcare Safety Network (NHSN) healthcare-associated infection (HAI) surveillance definitions. This specific case study focuses on the application of the Pneumonia (PNEU), Ventilator-associated event (VAE), and Bloodstream infections (BSI) surveillance definitions to a patient with COVID-19. The intent of the case study series is to foster standardized application of the NHSN HAI surveillance definitions among Infection Preventionists (IPs) and encourage accurate determination of HAI events.

Genetic differences between SARS-CoV-2 variants raise concerns about reinfection. Public health authorities monitored the incidence of suspected reinfection in Clark County, Nevada, USA, during March 2020-March 2022. Suspected reinfections, defined as a second positive PCR test collected >90 days after an initial positive test, were monitored through an electronic disease surveillance system. We calculated the proportion of all new cases per week that were suspected reinfections and rates per 1,000 previously infected persons by demographic groups. The rate of suspected reinfection remained <2.7% until December 2021, then increased to ≈11%, corresponding with local Omicron variant detection. Reinfection rates were higher among adults 18-50 years of age, women, and minority groups, especially persons identifying as American Indian/Alaska Native. Suspected reinfection became more common in Clark County after introduction of the Omicron variant, and some demographic groups are disproportionately affected. Public health surveillance could clarify the SARS-CoV-2 reinfection burden in communities.

The Centers for Disease Control and Prevention (CDC) has identified nontyphoidal Salmonella as one of the top five pathogens contributing to foodborne illnesses in the United States. Beef continues to be a common source of Salmonella outbreaks, despite the implementation of interventions at slaughter and processing facilities to reduce contamination of beef. We described Salmonella outbreaks linked to beef in the United States during 2012-2019, examined trends, and identified potential targets for intervention and prevention strategies. We queried CDC's Foodborne Disease Outbreak Surveillance System (FDOSS) for all foodborne nontyphoidal Salmonella outbreaks linked to beef as the single contaminated ingredient or implicated food, with the date of first illness onset from 2012 to 2019. Information on antimicrobial resistance (AR) for outbreak-related isolates was obtained from CDC's National Antimicrobial Resistance Monitoring System (NARMS). We calculated the number of outbreaks, outbreak-related illnesses, hospitalizations, and deaths overall, by beef processing category and Salmonella serotype. During 2012-2019, 27 Salmonella outbreaks were linked to beef consumption, resulting in 1103 illnesses, 254 hospitalizations, and two deaths. The most common category of beef implicated was nonintact raw, ground beef (12 outbreaks, 44%), followed by intact raw (six outbreaks, 22%). Ground beef was responsible for the most illnesses (800, 73%), both of the reported deaths, and was the source of the largest outbreak. AR data were available for 717 isolates from 25 (93%) outbreaks. Nine (36%) of these outbreaks had isolates resistant to one or more of the antibiotics tested by NARMS, of which eight (89%) contained multidrug-resistant isolates. Several outbreaks reported highlight challenges faced during investigations, areas where further research may be warranted, and opportunities to prevent future outbreaks along the farm-to-fork continuum.

Colistin is a last-resort antibiotic used to treat infections caused by multidrug-resistant Gram-negative bacteria. People with a history of travel to the Dominican Republic have become sick with pathogenic bacteria carrying the mobile colistin resistance gene, mcr-1, during and after traveling. This investigation aimed to identify mcr genes in Enterobacteriaceae isolated from food animal sources in the Dominican Republic. Three hundred and eleven samples were tested, from which 1354 bacterial isolates were obtained. Real-time PCR tests showed that 70.7% (220 out of 311) of the samples and 3.2% (44 out of 1354) of the isolates tested positive for the mcr gene. All RT-PCR presumptive mcr-positive isolates (n = 44) and a subset (n = 133) of RT-PCR presumptive mcr-negative isolates were subjected to whole-genome sequencing. WGS analysis showed that 39 isolates carried the mcr gene, with 37 confirmed as positive through RT-PCR and two as negative. Further, all of the mcr-positive genomes were identified as Escherichia coli and all contained a IncX4 plasmid replicon. Resistant determinants for other antibiotics important for human health were found in almost all isolates carrying mcr genes.

Among persons with an initial Clostridioides difficile infection (CDI) across 10 US sites in 2018 compared with 2013, 18.3% versus 21.1% had 1 recurrent CDI (rCDI) within 180 days. We observed a 16% lower adjusted risk of rCDI in 2018 versus 2013 (P<.0001).

Generally, hypertension control programs are cost-effective, including in low- and middle-income countries, but country governments and civil society are not likely to support hypertension control programs unless value is demonstrated in terms of public health benefits, budget impact, and value-for-investment for the individual country context. The World Health Organization (WHO) and the Pan American Health Organization (PAHO) established a standard, simplified Global HEARTS approach to hypertension control, including preferred antihypertensive medicines and blood pressure measurement devices. The objective of this study is to report on health economic studies of HEARTS hypertension control package cost (especially medication costs), cost-effectiveness, and budget impact and describe mathematical models designed to translate hypertension control program data into the optimal approach to hypertension care service delivery and financing, especially in low- and middle-income countries. Early results suggest that HEARTS hypertension control interventions are either cost-saving or cost-effective, that the HEARTS package is affordable at between US$ 18-44 per person treated per year, and that antihypertensive medicines could be priced low enough to reach a global standard of an average <US$ 5 per patient per year in the public sector. This health economic evidence will make a compelling case for government ownership and financial support for national scale hypertension control programs.

IMPORTANCE: Phthalate exposure is widespread among pregnant women and may be a risk factor for preterm birth. OBJECTIVE: To investigate the prospective association between urinary biomarkers of phthalates in pregnancy and preterm birth among individuals living in the US. DESIGN, SETTING, AND PARTICIPANTS: Individual-level data were pooled from 16 preconception and pregnancy studies conducted in the US. Pregnant individuals who delivered between 1983 and 2018 and provided 1 or more urine samples during pregnancy were included. EXPOSURES: Urinary phthalate metabolites were quantified as biomarkers of phthalate exposure. Concentrations of 11 phthalate metabolites were standardized for urine dilution and mean repeated measurements across pregnancy were calculated. MAIN OUTCOMES AND MEASURES: Logistic regression models were used to examine the association between each phthalate metabolite with the odds of preterm birth, defined as less than 37 weeks of gestation at delivery (n=539). Models pooled data using fixed effects and adjusted for maternal age, race and ethnicity, education, and prepregnancy body mass index. The association between the overall mixture of phthalate metabolites and preterm birth was also examined with logistic regression. G-computation, which requires certain assumptions to be considered causal, was used to estimate the association with hypothetical interventions to reduce the mixture concentrations on preterm birth. RESULTS: The final analytic sample included 6045 participants (mean [SD] age, 29.1 [6.1] years). Overall, 802 individuals (13.3%) were Black, 2323 (38.4%) were Hispanic/Latina, 2576 (42.6%) were White, and 328 (5.4%) had other race and ethnicity (including American Indian/Alaskan Native, Native Hawaiian, >1 racial identity, or reported as other). Most phthalate metabolites were detected in more than 96% of participants. Higher odds of preterm birth, ranging from 12% to 16%, were observed in association with an interquartile range increase in urinary concentrations of mono-n-butyl phthalate (odds ratio [OR], 1.12 [95% CI, 0.98-1.27]), mono-isobutyl phthalate (OR, 1.16 [95% CI, 1.00-1.34]), mono(2-ethyl-5-carboxypentyl) phthalate (OR, 1.16 [95% CI, 1.00-1.34]), and mono(3-carboxypropyl) phthalate (OR, 1.14 [95% CI, 1.01-1.29]). Among approximately 90 preterm births per 1000 live births in this study population, hypothetical interventions to reduce the mixture of phthalate metabolite levels by 10%, 30%, and 50% were estimated to prevent 1.8 (95% CI, 0.5-3.1), 5.9 (95% CI, 1.7-9.9), and 11.1 (95% CI, 3.6-18.3) preterm births, respectively. CONCLUSIONS AND RELEVANCE: Results from this large US study population suggest that phthalate exposure during pregnancy may be a preventable risk factor for preterm delivery.