Laboratory-based surveillance for enteric pathogens causing diarrhea is foundational for monitoring foodborne diseases in the United States. However, diarrheal illnesses are not always confirmed by laboratory testing, so estimates of the true number of illnesses must adjust for underdiagnosis, including underdiagnosis due to ill persons not seeking medical care or submitting a stool sample for laboratory testing. We assessed these factors among persons with an acute diarrheal illness who responded to the most recent Foodborne Diseases Active Surveillance Network (FoodNet) Population Survey (2018-2019). Multiple modes of administration (telephone, web-based) and multiple sampling frames were used to ask survey respondents in English or Spanish about diarrhea and other symptoms experienced in the 30 days before the interview and to ask if they had sought medical care or submitted a stool sample. Of 1018 respondents with an acute diarrheal illness, 22.0% had sought medical care and 4.7% submitted a stool sample. On multivariable analysis, older adults (aged 65 years and over), male respondents, and persons with a household income of ≥$40,000 per annum were significantly more likely to seek medical care, as were respondents reporting cough, fever, vomiting, recent international travel, or duration of diarrhea for ≥3 days. Older adults and persons with five or more loose stools in 24 h who sought medical care were significantly more likely to submit a stool sample. Ill respondents with a concurrent cough were less likely to submit a stool sample. Sociodemographic characteristics, symptoms, and international travel influence whether a patient with an acute diarrheal illness will seek care or submit a stool specimen. Accounting for these factors when analyzing surveillance data will likely produce more precise estimates of the true number of foodborne illnesses.

The FoodNet Population Survey is a periodic survey of randomly selected residents in 10 US sites on exposures and behaviors that may be associated with acute diarrheal infections and the health care sought for those infections. This survey is used to estimate the true disease burden of enteric illness in the United States and to estimate rates of exposure to potential sources of illness. Unlike previous FoodNet Population Surveys, this cycle used multiple sampling frames and administration modes, including cell phone and web-based questionnaires, that allowed for additional question topics and a larger sample size. It also oversampled children to increase representation of this population. Analytic modeling adjusted for mode effects when estimating the prevalence estimates of exposures and behaviors. This report describes the design, methodology, challenges, and descriptive results from the 2018-19 FoodNet Population Survey.

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.

Salmonella is estimated to be the leading bacterial cause of U.S. domestically-acquired foodborne illness. Large outbreaks of Salmonella attributed to ground beef have been reported in recent years. The demographic and sociodemographic characteristics of infected individuals linked to these outbreaks are poorly understood. We employed a retrospective case-control design; case-patients were people with laboratory-confirmed Salmonella infections linked to ground beef-associated outbreaks between 2012-2019, and controls were respondents to the 2018-2019 FoodNet Population Survey who reported eating ground beef and denied recent gastrointestinal illness. We used county-level CDC/ATSDR Social Vulnerability Index (SVI) to compare case-patient and controls. Case-patient status was regressed on county-level social vulnerability and individual-level demographic characteristics. We identified 376 case-patients and 1,321 controls in the FoodNet sites. Being a case-patient was associated with increased overall county-level social vulnerability (OR: 1.21 [95% CI: 1.07-1.36]) and socioeconomic vulnerability (OR: 1.24 [1.05-1.47]) when adjusted for individual-level demographics. Case-patient status was not strongly associated with the other SVI themes of household composition and disability, minority status and language, and housing type and transportation. Data on individual-level factors such as income, poverty, unemployment, and education could facilitate further analyses to understand this relationship.

BACKGROUND: Most U.S. acute gastroenteritis (AGE) episodes in children are attributed to norovirus, whereas very little information is available on adenovirus 40/41 (AdV40/41), astrovirus or sapovirus. The New Vaccine Surveillance Network (NVSN) conducted prospective, active, population-based AGE surveillance in young children. METHODS: We tested and typed stool specimens collected between December 2011 to June 2016 from one NVSN site in Kansas City for the three viruses, and calculated hospitalization and emergency department (ED) detection rate. RESULTS: Of 3,205 collected specimens, 2,453 (76.5%) were from AGE patients (339 inpatients and 2,114 ED patients) and 752 (23.5%) were from healthy controls (HC). In AGE patients, astrovirus was detected in 94 (3.8%), sapovirus in 252 (10.3%) and AdV40/41 in 101 (4.5%) of 2249 patients. In HC, astrovirus was detected in 13 (1.7%) and sapovirus in 15 (2.0%) specimens. Astrovirus type 1 (37.7%) and genogroup I sapoviruses (59.3%) were most prevalent.Hospitalization rates were 5 (AdV40/41), 4 (astrovirus) and 8 (sapovirus) per 100,000 children <11 years old, whereas ED rates were 2.4 (AdV40/41), 1.9 (astrovirus) and 5.3 (sapovirus) per 1000 children <5 years old. CONCLUSIONS: Overall, AdV40/41, astrovirus, and sapovirus were detected in 18.6% of AGE in a large pediatric hospital in Kansas City.

OBJECTIVE: Acute gastroenteritis (AGE) is the second leading cause of death in children worldwide. Objectively evaluating disease severity is critical for assessing future interventions. We used data from a large, prospective surveillance study to assess risk factors associated with severe presentation using modified Vesikari score (MVS) and Clark score (CS) of severity. METHODS: From December 1, 2012 to June 30, 2016, AGE surveillance was performed for children between 15 days and 17 years old in the emergency, inpatient, and outpatient settings at Vanderbilt's Monroe Carell Jr. Children's Hospital in Nashville, TN. Stool specimens were tested for norovirus, sapovirus, rotavirus, and astrovirus. We compared demographic and clinical characteristics, along with the MVS and CS, by viral detection status and by setting. RESULTS: Of the 6309 eligible children, 4216 (67%) were enrolled, with 3256 (77%) providing a stool specimen. The median age was 1.9 years, 52% were male, and 1387 (43%) of the stool samples were virus positive. Younger age, male sex, hospitalization, and rotavirus detection were significantly associated with higher mean MVS and CS. Non-Hispanic Black race and ethnicity was associated with a lower mean MVS and CS as compared with non-Hispanic white race and ethnicity. Prematurity and enrollment in the ED were associated with higher mean CS. The 2 scoring systems were highly correlated. CONCLUSIONS: Rotavirus continues to be associated with more severe pediatric illness compared with other viral causes of AGE. MVS and CS systems yielded comparable results and can be useful tools to assess AGE severity.

BACKGROUND: Asymptomatic SARS-CoV-2 infection in children is highly prevalent but its acute and chronic implications have been minimally described. METHODS: In this controlled case-ascertained household transmission study, we recruited asymptomatic children <18 years with SARS-CoV-2 nucleic acid testing performed at 12 tertiary care pediatric institutions in Canada and the United States. We attempted to recruit all test-positive children and 1 to 3 test-negative, site-matched controls. After 14 days' follow-up we assessed the clinical (ie, symptomatic) and combined (ie, test-positive, or symptomatic) secondary attack rates (SARs) among household contacts. Additionally, post-COVID-19 condition (PCC) was assessed in SARS-CoV-2-positive participating children after 90 days' follow-up. RESULTS: A total of 111 test-positive and 256 SARS-CoV-2 test-negative asymptomatic children were enrolled between January 2021 and April 2022. After 14 days, excluding households with co-primary cases, the clinical SAR among household contacts of SARS-CoV-2-positive and -negative index children was 10.6% (19/179; 95% CI: 6.5%-16.1%) and 2.0% (13/663; 95% CI: 1.0%-3.3%), respectively (relative risk = 5.4; 95% CI: 2.7-10.7). In households with a SARS-CoV-2-positive index child, age <5 years, being pre-symptomatic (ie, developed symptoms after test), and testing positive during Omicron and Delta circulation periods (vs earlier) were associated with increased clinical and combined SARs among household contacts. Among 77 asymptomatic SARS-CoV-2-infected children with 90-day follow-up, 6 (7.8%; 95% CI: 2.9%-16.2%) reported PCC. CONCLUSIONS: Asymptomatic SARS-CoV-2-infected children, especially those <5 years, are important contributors to household transmission, with 1 in 10 exposed household contacts developing symptomatic illness within 14 days. Asymptomatic SARS-CoV-2-infected children may develop PCC.

BACKGROUND: The endemic coronaviruses OC43, HKU1, NL63 and 229E cause cold-like symptoms and are related to SARS-CoV-2, but their natural histories are poorly understood. In a cohort of children followed from birth to 4 years, we documented all coronavirus infections, including SARS-CoV-2, to understand protection against subsequent infections with the same virus (homotypic immunity) or a different coronavirus (heterotypic immunity). METHODS: Mother-child pairs were enrolled in metropolitan Cincinnati during the third trimester of pregnancy in 2017-18. Mothers reported their child's socio-demographics, risk factors, and weekly symptoms. Mid-turbinate nasal swabs were collected weekly. Blood was collected at 6 weeks, 6, 12, 18, 24 months and annually thereafter. Infections were detected by testing nasal swabs by an RT-PCR multi-pathogen panel and by serum IgG responses. Health care visits were documented from pediatric records. Analysis was limited to 116 children with high sample adherence. Re-consent for monitoring SARS-CoV-2 infections from June 2020 through November 2021 was obtained for 74 (64%) children. RESULTS: We detected 345 endemic coronavirus infections (1.1 infections/child-year) and 21 SARS-CoV-2 infections (0.3 infections/child-year). Endemic coronavirus and SARS-CoV-2 infections were asymptomatic or mild. Significant protective homotypic immunity occurred after a single infection with OC43 (77%) and HKU1 (84%), and after two infections with NL63 (73%). No heterotypic protection against endemic coronaviruses or SARS-CoV-2 was identified. CONCLUSIONS: Natural coronavirus infections were common and resulted in strong homotypic immunity but not heterotypic immunity against other coronaviruses, including SARS-CoV-2. Endemic coronavirus and SARS-CoV-2 infections in this US cohort were typically asymptomatic or mild.

BACKGROUND: Respiratory viral shedding is incompletely characterized by existing studies due to the lack of longitudinal nasal sampling and limited inclusion of healthy/asymptomatic children. We describe characteristics associated with prolonged virus detection by PCR in a community-based birth cohort. METHODS: Children were followed from birth to 2 years of age in the PREVAIL cohort. Weekly nasal swabs were collected and tested using the Luminex Respiratory Pathogen Panel. Weekly text surveys were administered to ascertain the presence of acute respiratory illnesses defined as fever and/or cough. Maternal reports and medical chart abstractions identified healthcare utilization. Prolonged virus detection was defined as a persistently positive test lasting >4 weeks. Factors associated with prolonged virus detection were assessed using mixed effects multivariable logistic regression. RESULTS: From a sub-cohort of 101 children with >70% weekly swabs collected, a total of 1489 viral infections were detected. Prolonged virus detection was found in 23.4% of viral infections overall, 39% of bocavirus infections, 33% of rhinovirus/enterovirus infections, 14% of RSV A infections, and 7% of RSV B infections. No prolonged detection was found for influenza A or B, coronavirus 229E or HKU1, and parainfluenza 2 or 4 virus infections. First lifetime infection with each virus, and co-detection of another respiratory virus were significantly associated with prolonged detection, while symptom status, child sex, and child age were not. CONCLUSIONS: Prolonged virus detection was observed in 1 in 4 viral infections in this cohort of healthy children and varied by pathogen, occurring most often for bocavirus and rhinovirus/enterovirus. Evaluating the immunological basis of how viral co-detections and recurrent viral infections impact duration of virus detection by PCR is needed to better understand the dynamics of prolonged viral shedding.

BACKGROUND: Rotavirus is a leading cause of severe pediatric gastroenteritis; two highly effective vaccines are used in the US. We aimed to identify correlates of immune response to rotavirus vaccination in a US cohort. METHODS: PREVAIL is a birth cohort of 245 mother-child pairs enrolled 2017-2018 and followed for 2 years. Infant stool samples and symptom information were collected weekly. Shedding was defined as RT-PCR detection of rotavirus vaccine virus in stools collected 4-28 days after dose one. Seroconversion was defined as a threefold rise in IgA between the six-week and six-month blood draws. Correlates were analyzed using generalized estimating equations and logistic regression. RESULTS: Pre-vaccination IgG (OR=0.84, 95% CI [0.75-0.94] per 100-unit increase) was negatively associated with shedding. Shedding was also less likely among infants with a single-nucleotide polymorphism inactivating FUT2 antigen secretion ("non-secretors") with non-secretor mothers, versus all other combinations (OR 0.37 [0.16-0.83]). Of 141 infants with data, 105 (74%) seroconverted; 78 (77%) had shed vaccine virus following dose one. Pre-vaccination IgG and secretor status were significantly associated with seroconversion. Neither shedding nor seroconversion significantly differed by vaccine product. DISCUSSION: In this US cohort, pre-vaccination IgG and maternal and infant secretor status were associated with rotavirus vaccine response.

BACKGROUND: The 2022 mpox outbreak has infected over 30 000 people in the USA, with cases declining since mid-August. Infections were commonly associated with sexual contact between men. Interventions to mitigate the outbreak included vaccination and a reduction in sexual partnerships. Understanding the contributions of these interventions to decreasing cases can inform future public health efforts. METHODS: We fit a dynamic network transmission model to mpox cases reported by Washington DC through 10 January 2023. This model incorporated both vaccine administration data and reported reductions in sexual partner acquisition by gay, bisexual or other men who have sex with men (MSM). The model output consisted of daily cases over time with or without vaccination and/or behavioural adaptation. RESULTS: We found that initial declines in cases were likely caused by behavioural adaptations. One year into the outbreak, vaccination and behavioural adaptation together prevented an estimated 84% (IQR 67% to 91%) of cases. Vaccination alone averted 79% (IQR 64% to 88%) of cases and behavioural adaptation alone averted 25% (IQR 10% to 42%) of cases. We further found that in the absence of vaccination, behavioural adaptation would have reduced the number of cases, but would have prolonged the outbreak. CONCLUSIONS: We found that initial declines in cases were likely caused by behavioural adaptation, but vaccination averted more cases overall and was key to hastening outbreak conclusion. Overall, this indicates that outreach to encourage individuals to protect themselves from infection was vital in the early stages of the mpox outbreak, but that combination with a robust vaccination programme hastened outbreak conclusion.

Despite the 2009 World Health Organization recommendation that all countries introduce rotavirus vaccines (RVV) into their national immunization programs, just 81 countries had introduced RVV by the end of 2015, leaving millions of children at risk for rotavirus morbidity and mortality. In response, the Rotavirus Accelerated Vaccine Introduction Network (RAVIN) was established in 2016 to provide support to eight Gavi-eligible countries that had yet to make an RVV introduction decision and/or had requested technical assistance with RVV preparations: Afghanistan, Bangladesh, Benin, Cambodia, Democratic Republic of Congo, Lao People's Democratic Republic, Myanmar, and Nepal. During 2016-2020, RAVIN worked with country governments and partners to support evidence-based immunization decision-making, RVV introduction preparation and implementation, and multilateral coordination. By the September 2020 program close-out, five of the eight RAVIN focus countries successfully introduced RVV into their routine childhood immunization programs. We report on the RAVIN approach, describe how the project responded collectively to an evolving RVV product landscape, synthesize common characteristics of the RAVIN country experiences, highlight key lessons learned, and outline the unfinished agenda to inform future new vaccine introduction efforts by countries and global partners.

BACKGROUND: The nutritional status of children with cystic fibrosis (CF), as assessed by their body mass index percentile (BMIp), is a critical determinant of long-term health outcomes. While the intestinal microbiome plays an important role in nutrition, little is known regarding the relationship of the microbiome and BMIp in children with CF. METHODS: Pediatric patients (< 18 years old) with CF and healthy comparison patients (HCs) were enrolled in the study and stool samples obtained. BMIp was categorized as Green Zone (BMIp > 50th), Yellow Zone (BMIp 25th-49th) and Red Zone (BMIp < 25th). Intestinal microbiome assessment was performed via 16S rRNA gene sequencing; microbial richness, diversity, and differential species abundance were assessed. RESULTS: Stool samples were collected from 107 children with CF and 50 age-matched HCs. Compared to HCs, children with CF were found to have lower bacterial richness, alpha-diversity, and a different microbial composition. When evaluating them by their BMIp color zone, richness and alpha-diversity were lowest in those in the Red Zone. In addition, an unclassified amplicon sequence variant (ASV) of Blautia, a known butyrate-producing anaerobe, was of lowest abundance in children in the Red Zone. CONCLUSION: Children with CF have a dysbiotic intestinal microbiome with specific changes that accompany changes in BMIp. Longitudinal assessments of the microbiome and its metabolic activities over time are needed to better understand how improvements in the microbiome may improve nutrition and enhance long-term survival in children with CF.

During August 13–14, 2023, a new SARS-CoV-2 Omicron subvariant with a large number of mutations compared with previously circulating BA.2 variants (>30 amino acid differences in its spike protein) was identified by genomic sequencing in Denmark and Israel and subsequently designated BA.2.86 (1,2). Given near-simultaneous detections in multiple countries, including the United States, further information was needed regarding geographic spread of BA.2.86. Since January 2022, submissions to SARS-CoV-2 sequence repositories have declined by 95%,* substantially decreasing global capacity to monitor new variants. To fill gaps in global surveillance, CDC’s Traveler-based Genomic Surveillance (TGS) program was developed to provide early warning of new variants entering the United States by collecting samples from arriving international travelers (3).

BACKGROUND: To assist clinicians with identifying children at risk of severe outcomes, we assessed the association between laboratory findings and severe outcomes among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected children and determined if SARS-CoV-2 test result status modified the associations. METHODS: We conducted a cross-sectional analysis of participants tested for SARS-CoV-2 infection in 41 pediatric emergency departments in 10 countries. Participants were hospitalized, had laboratory testing performed, and completed 14-day follow-up. The primary objective was to assess the associations between laboratory findings and severe outcomes. The secondary objective was to determine if the SARS-CoV-2 test result modified the associations. RESULTS: We included 1817 participants; 522 (28.7%) SARS-CoV-2 test-positive and 1295 (71.3%) test-negative. Seventy-five (14.4%) test-positive and 174 (13.4%) test-negative children experienced severe outcomes. In regression analysis, we found that among SARS-CoV-2-positive children, procalcitonin ≥0.5 ng/mL (adjusted odds ratio [aOR], 9.14; 95% CI, 2.90-28.80), ferritin >500 ng/mL (aOR, 7.95; 95% CI, 1.89-33.44), D-dimer ≥1500 ng/mL (aOR, 4.57; 95% CI, 1.12-18.68), serum glucose ≥120 mg/dL (aOR, 2.01; 95% CI, 1.06-3.81), lymphocyte count <1.0 × 10(9)/L (aOR, 3.21; 95% CI, 1.34-7.69), and platelet count <150 × 10(9)/L (aOR, 2.82; 95% CI, 1.31-6.07) were associated with severe outcomes. Evaluation of the interaction term revealed that a positive SARS-CoV-2 result increased the associations with severe outcomes for elevated procalcitonin, C-reactive protein (CRP), D-dimer, and for reduced lymphocyte and platelet counts. CONCLUSIONS: Specific laboratory parameters are associated with severe outcomes in SARS-CoV-2-infected children, and elevated serum procalcitonin, CRP, and D-dimer and low absolute lymphocyte and platelet counts were more strongly associated with severe outcomes in children testing positive compared with those testing negative.

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.

OBJECTIVE: To describe demographics, pathogen distribution/seasonality, and risk factors in children seeking care for acute gastroenteritis (AGE) at a midwestern US emergency department during 5 postrotavirus vaccine years (2011-2016), and further, to compare the same data with matched healthy controls (HC). STUDY DESIGN: AGE and HC participants <11 years old enrolled in the New Vaccine Surveillance Network study between December 2011 to June 2016 were included. AGE was defined as ≥3 diarrhea episodes or ≥1 vomiting episode. Each HC's age was similar to an AGE participant's age. Pathogens were analyzed for seasonality effects. Participant risk factors for AGE illness and pathogen detections were compared between HC and a matched subset of AGE cases. RESULTS: One or more organisms was detected in 1159 of 2503 children (46.3%) with AGE compared with 99 of 537 HC (17.3%). Norovirus was detected most frequently among AGE (n = 568 [22.7%]) and second-most frequently in HC (n = 39 [6.8%]). Rotavirus was the second most frequently detected pathogen among AGE (n = 196 [7.8%]). Children with AGE were significantly more likely to have reported a sick contact compared with HC, both outside the home (15.6% vs 1.4%; P < .001) and inside the home (18.6% vs 2.1%; P < .001). Daycare attendance was higher among children with AGE (41.4%) compared with HC (29.5%; P < .001). The Clostridium difficile detection rate was slightly higher among HC (7.0%) than AGE (5.3%). CONCLUSIONS: Norovirus was the most prevalent pathogen among children with AGE. Norovirus was detected in some HC, suggesting potential asymptomatic shedding among HC. The proportion of AGE participants with a sick contact was approximately 10 times greater than that of HC.

Background: The 2022 mpox outbreak infected over 30,000 people in the United States. Infections were commonly associated with sexual contact between men. Interventions included vaccination and reductions in sexual partnerships. We estimated the averted infections attributable to each intervention using mathematical modeling. Method(s): We fit a dynamic network transmission model to mpox cases reported by the District of Columbia through January 2023. We incorporated vaccine administration data and reported reductions in sexual partnerships among gay, bisexual, or other men who have sex with men (MSM). Model output consisted of predicted cases over time with or without vaccination and/or behavior change. Result(s): We estimated initial case reductions were due to behavior change. Vaccination alone averted 64% [IQR:57%-72%] and behavior change alone averted 21% [IQR:11%-29%] of cases. Vaccination and behavior change together averted 80% [IQR:74%-85%] of cases. In the absence of vaccination, behavior change reduced cumulative cases but also prolonged the outbreak. Conclusion(s): Initial case declines were likely caused by behavior change, but vaccination averted more cases overall. Overall, this indicates that encouraging individuals to protect themselves was vital in the early outbreak, but that combination with a robust vaccination program was ultimately required for control. 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.

This brief methods paper is being published concomitantly with "Preliminary Incidence and Trends of Infections Caused by Pathogens Transmitted Commonly Through Food- Foodborne Diseases Active Surveillance Network, 10 U.S. Sites, 2016-2021" in Morbidity and Mortality Weekly Reports (MMWR). That article describes the application of the new model described here to analyze trends and evaluate progress towards the prevention of infection from enteric pathogens in the United States. 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.

Each year, infections from major foodborne pathogens are responsible for an estimated 9.4 million illnesses, 56,000 hospitalizations, and 1,350 deaths in the United States (1). To evaluate progress toward prevention of enteric infections in the United States, the Foodborne Diseases Active Surveillance Network (FoodNet) conducts surveillance for laboratory-diagnosed infections caused by eight pathogens transmitted commonly through food at 10 U.S. sites. During 2020-2021, FoodNet detected decreases in many infections that were due to behavioral modifications, public health interventions, and changes in health care-seeking and testing practices during the COVID-19 pandemic. This report presents preliminary estimates of pathogen-specific annual incidences during 2022, compared with average annual incidences during 2016-2018, the reference period for the U.S. Department of Health and Human Services' Healthy People 2030 targets (2). Many pandemic interventions ended by 2022, resulting in a resumption of outbreaks, international travel, and other factors leading to enteric infections. During 2022, annual incidences of illnesses caused by the pathogens Campylobacter, Salmonella, Shigella, and Listeria were similar to average annual incidences during 2016-2018; however, incidences of Shiga toxin-producing Escherichia coli (STEC), Yersinia, Vibrio, and Cyclospora illnesses were higher. Increasing culture-independent diagnostic test (CIDT) usage likely contributed to increased detection by identifying infections that would have remained undetected before widespread CIDT usage. Reducing pathogen contamination during poultry slaughter and processing of leafy greens requires collaboration among food growers and processors, retail stores, restaurants, and regulators.

As of March 31, 2023, more than 30,000 monkeypox (mpox) cases had been reported in the United States in an outbreak that has disproportionately affected gay, bisexual, and other men who have sex with men (MSM) and transgender persons (1). JYNNEOS vaccine (Modified Vaccinia Ankara vaccine, Bavarian Nordic) was approved by the Food and Drug Administration (FDA) in 2019 for the prevention of smallpox and mpox via subcutaneous injection as a 2-dose series (0.5 mL per dose, administered 4 weeks apart) (2). To expand vaccine access, an Emergency Use Authorization was issued by FDA on August 9, 2022, for dose-sparing intradermal injection of JYNNEOS as a 2-dose series (0.1 mL per dose, administered 4 weeks apart) (3). Vaccination was available to persons with known or presumed exposure to a person with mpox (postexposure prophylaxis [PEP]), as well as persons at increased risk for mpox or who might benefit from vaccination (preexposure mpox prophylaxis [PrEP]) (4). Because information on JYNNEOS vaccine effectiveness (VE) is limited, a matched case-control study was conducted in 12 U.S. jurisdictions,(†) including nine Emerging Infections Program sites and three Epidemiology and Laboratory Capacity sites,(§) to evaluate VE against mpox among MSM and transgender adults aged 18-49 years. During August 19, 2022-March 31, 2023, a total of 309 case-patients were matched to 608 control patients. Adjusted VE was 75.2% (95% CI = 61.2% to 84.2%) for partial vaccination (1 dose) and 85.9% (95% CI = 73.8% to 92.4%) for full vaccination (2 doses). Adjusted VE for full vaccination by subcutaneous, intradermal, and heterologous routes of administration was 88.9% (95% CI = 56.0% to 97.2%), 80.3% (95% CI = 22.9% to 95.0%), and 86.9% (95% CI = 69.1% to 94.5%), respectively. Adjusted VE for full vaccination among immunocompromised participants was 70.2% (95% CI = -37.9% to 93.6%) and among immunocompetent participants was 87.8% (95% CI = 57.5% to 96.5%). JYNNEOS is effective at reducing the risk for mpox. Because duration of protection of 1 versus 2 doses remains unknown, persons at increased risk for mpox exposure should receive the 2-dose series as recommended by the Advisory Committee on Immunization Practices (ACIP),(¶) regardless of administration route or immunocompromise status.

BACKGROUND: In the United States, more than 30,000 cases of mpox (formerly known as monkeypox) had occurred as of March 1, 2023, in an outbreak disproportionately affecting transgender persons and gay, bisexual, and other men who have sex with men. In 2019, the JYNNEOS vaccine was approved for subcutaneous administration (0.5 ml per dose) to prevent mpox infection. On August 9, 2022, an emergency use authorization was issued for intradermal administration (0.1 ml per dose); however, real-world effectiveness data are limited for either route. METHODS: We conducted a case-control study based on data from Cosmos, a nationwide Epic electronic health record (EHR) database, to assess the effectiveness of JYNNEOS vaccination in preventing medically attended mpox disease among adults. Case patients had an mpox diagnosis code or positive orthopoxvirus or mpox virus laboratory result, and control patients had an incident diagnosis of human immunodeficiency virus (HIV) infection or a new or refill order for preexposure prophylaxis against HIV infection between August 15, 2022, and November 19, 2022. Odds ratios and 95% confidence intervals were estimated from conditional logistic-regression models, adjusted for confounders; vaccine effectiveness was calculated as (1 - odds ratio for vaccination in case patients vs. controls) × 100. RESULTS: Among 2193 case patients and 8319 control patients, 25 case patients and 335 control patients received two doses (full vaccination), among whom the estimated adjusted vaccine effectiveness was 66.0% (95% confidence interval [CI], 47.4 to 78.1), and 146 case patients and 1000 control patients received one dose (partial vaccination), among whom the estimated adjusted vaccine effectiveness was 35.8% (95% CI, 22.1 to 47.1). CONCLUSIONS: In this study using nationwide EHR data, patients with mpox were less likely to have received one or two doses of JYNNEOS vaccine than control patients. The findings suggest that JYNNEOS vaccine was effective in preventing mpox disease, and a two-dose series appeared to provide better protection. (Funded by the Centers for Disease Control and Prevention and Epic Research.).

BACKGROUND: Respiratory viral infections are a major cause of morbidity and hospitalization in young children. Nevertheless, the population burden of respiratory viral infections, especially asymptomatic cases, is not known due to the lack of prospective community-based cohort studies with intensive monitoring. METHODS: To address this gap, we enacted the PREVAIL cohort, a CDC-sponsored birth cohort in Cincinnati, Ohio where children were followed from birth to 2 years of age. Weekly text surveys were administered to mothers to record acute respiratory illnesses (ARIs), which were defined as the presence of cough or fever (≥38oC). Weekly mid-turbinate nasal swabs were collected and tested using the Luminex Respiratory Pathogen Panel, which detected 16 viral pathogens. Viral infection was defined as one or more positive tests from the same virus or viral subtype within 30 days of previous positive. Maternal report and medical chart abstractions identified health care utilization. RESULTS: From 4/2017 to 7/2020, 245 mother-infant pairs were recruited and followed. From the 13,781 nasal swabs tested, a total of 2,211 viral infections were detected, of which, 821 (37%) were symptomatic. Children experienced 9.4 respiratory viral infections/child-year; half were rhinovirus/enterovirus. Viral ARI incidence was 3.3 episodes/child-year. Emergency department visits or hospitalization occurred with only 15% of respiratory syncytial virus infections, 10% of influenza infections, and only 4% of all viral infections. Regardless of pathogen, most infections were asymptomatic or mild. CONCLUSIONS: Respiratory viral infections are common in children 0-2 years. Most viral infections are asymptomatic or non-medically attended, underscoring the importance of community-based cohort studies.

BACKGROUND: Antimicrobial resistance in nontyphoidal Salmonella (NTS) can limit treatment options. We assessed the contribution of international travel to antimicrobial-resistant NTS infections. METHODS: We describe NTS infections reported to the Foodborne Diseases Active Surveillance Network during 2018-2019 that were screened for genetic resistance determinants, including those conferring decreased susceptibility to first line agents (ciprofloxacin, ceftriaxone, or azithromycin). We used multivariable logistic regression to assess the association between resistance and international travel during the seven days before illness began. We estimated the contribution of international travel to resistance using population attributable fractions and examined reported antimicrobial use. RESULTS: Among 9,301 NTS infections, 1,159 (12%) occurred after recent international travel. Predicted resistance to first-line antimicrobials was more likely following travel; the adjusted odds ratio [aOR] varied by travel region and was highest after travel to Asia (aOR 7.2, 95% CI 5.5-9.5). Overall, 19% (95% CI 17%-22%) of predicted resistance to first-line antimicrobials was attributable to international travel. More travelers than non-travelers receiving ciprofloxacin or other fluoroquinolones had isolates with predicted resistance to fluoroquinolones (29% vs 9%, p<0.01). CONCLUSIONS: International travel is a substantial risk factor for antimicrobial-resistant NTS infections. Understanding risks of resistant infection could help target prevention efforts.

In 2020-2021, a Colorado corrections facility experienced four COVID-19 outbreaks. Case counts, attack rates (ARs) in people who are detained or incarcerated (PDI), and mitigation measures used in each outbreak were compared to evaluate effects of combined strategies. Serial PCR testing, isolation/quarantine, and masking were implemented in outbreak 1. Daily staff antigen testing began in outbreak 2. Facility-wide COVID-19 vaccination started in outbreak 3 and coverage increased by the end of outbreak 4 (PDI: <1% to 59%, staff: 27% to 40%). Despite detection of variants of concern, outbreaks 3 and 4 had 97% lower PDI ARs (both 1%) than outbreak 2 (29%). Daily staff testing and increasing vaccination coverage, with other outbreak mitigation strategies, are important to reduce COVID-19 transmission in congregate settings.

Reports of Salmonella enterica I serotype 4,[5],12:i:- infections resistant to ampicillin, streptomycin, sulphamethoxazole, and tetracycline (ASSuT) have been increasing. We analyzed data from 5 national surveillance systems to describe the epidemiology, resistance traits, and genetics of infections with this Salmonella strain in the United States. We found ASSuT-resistant Salmonella 4,[5],12:i:- increased from 1.1% of Salmonella infections during 2009-2013 to 2.6% during 2014-2018; the proportion of Salmonella 4,[5],12:i:- isolates without this resistance pattern declined from 3.1% to 2.4% during the same timeframe. Among isolates sequenced during 2015-2018, a total of 69% were in the same phylogenetic clade. Within that clade, 77% of isolates had genetic determinants of ASSuT resistance, and 16% had genetic determinants of decreased susceptibility to ciprofloxacin, ceftriaxone, or azithromycin. Among outbreaks related to the multidrug-resistant clade, 63% were associated with pork consumption or contact with swine. Preventing Salmonella 4,[5],12:i:- carriage in swine would likely avert human infections with this strain.

A major polymorphism in the fucosyltransferase2 (FUT2) gene influences risk of multiple gut diseases, but its impact on the microbiome of breastfed infants was unknown. In individuals with an active FUT2 enzyme ("secretors"), the intestinal mucosa is abundantly fucosylated, providing mutualist bacteria with a rich endogenous source of fucose. Non-secretors comprise approximately one-fifth of the population, and they lack the ability to create this enzyme. Similarly, maternal secretor status influences the abundance of a breastfeeding mother's fucosylated milk oligosaccharides. We compared the impact of maternal secretor status, measured by FUT2 genotype, and infant secretor status, measured by FUT2 genotype and phenotype, on early infant fecal microbiome samples collected from 2-month-old exclusively breastfed infants (n = 59). Infant secretor status (19% non-secretor, 25% low-secretor, and 56% full-secretor) was more strongly associated with the infant microbiome than it was with the maternal FUT2 genotype. Alpha diversity was greater in the full-secretors than in the low- or non-secretor infants (p = 0.049). Three distinct microbial enterotypes corresponded to infant secretor phenotype (p = 0.022) and to the dominance of Bifidobacterium breve, B. longum, or neither (p &lt; 0.001). Infant secretor status was also associated with microbial metabolic capacity, specifically, bioenergetics pathways. We concluded that in exclusively breastfed infants, infant-but not maternal-secretor status is associated with infant microbial colonization and metabolic capacity.

As of November 14, 2022, monkeypox (mpox) cases had been reported from more than 110 countries, including 29,133 cases in the United States.* Among U.S. cases to date, 95% have occurred among males (1). After the first confirmed U.S. mpox case on May 17, 2022, limited supplies of JYNNEOS vaccine (Modified Vaccinia Ankara vaccine, Bavarian Nordic) were made available to jurisdictions for persons exposed to mpox. JYNNEOS vaccine was approved by the Food and Drug Administration (FDA) in 2019 as a 2-dose series (0.5 mL per dose, administered subcutaneously) to prevent smallpox and mpox disease.() On August 9, 2022, FDA issued an emergency use authorization to allow administration of JYNNEOS vaccine by intradermal injection (0.1 mL per dose) (2). A previous report on U.S. mpox cases during July 31-September 3, 2022, suggested that 1 dose of vaccine offers some protection against mpox (3). This report describes demographic and clinical characteristics of cases occurring 14 days after receipt of 1 dose of JYNNEOS vaccine and compares them with characteristics of cases among unvaccinated persons with mpox and with the vaccine-eligible vaccinated population in participating jurisdictions. During May 22-September 3, 2022, among 14,504 mpox cases reported from 29 participating U.S. jurisdictions,() 6,605 (45.5%) had available vaccination information and were included in the analysis. Among included cases, 276 (4.2%) were among persons who had received 1 dose of vaccine 14 days before illness onset. Mpox cases that occurred in these vaccinated persons were associated with lower percentage of hospitalization (2.1% versus 7.5%), fever, headache, malaise, myalgia, and chills, compared with cases in unvaccinated persons. Although 1 dose of JYNNEOS vaccine offers some protection from disease, mpox infection can occur after receipt of 1 dose, and the duration of protection conferred by 1 dose is unknown. Providers and public health officials should therefore encourage persons at risk for acquiring mpox to complete the 2-dose vaccination series and provide guidance and education regarding nonvaccine-related prevention strategies (4).

As of October 28, 2022, a total of 28,244* monkeypox (mpox) cases have been reported in the United States during an outbreak that has disproportionately affected gay, bisexual, and other men who have sex with men (MSM) (1). JYNNEOS vaccine (Modified Vaccinia Ankara vaccine, Bavarian Nordic), administered subcutaneously as a 2-dose (0.5 mL per dose) series (with doses administered 4 weeks apart), was approved by the Food and Drug Administration (FDA) in 2019 to prevent smallpox and mpox disease (2); an FDA Emergency Use Authorization issued on August 9, 2022, authorized intradermal administration of 0.1 mL per dose, increasing the number of persons who could be vaccinated with the available vaccine supply(†) (3). A previous comparison of mpox incidence during July 31-September 3, 2022, among unvaccinated, but vaccine-eligible men aged 18-49 years and those who had received ≥1 JYNNEOS vaccine dose in 32 U.S. jurisdictions, found that incidence among unvaccinated persons was 14 times that among vaccinated persons (95% CI = 5.0-41.0) (4). During September 4-October 1, 2022, a total of 205,504 persons received JYNNEOS vaccine dose 2 in the United States.(§) To further examine mpox incidence among persons who were unvaccinated and those who had received either 1 or 2 JYNNEOS doses, investigators analyzed data on 9,544 reported mpox cases among men(¶) aged 18-49 years during July 31-October 1, 2022, from 43 U.S. jurisdictions,** by vaccination status. During this study period, mpox incidence (cases per 100,000 population at risk) among unvaccinated persons was 7.4 (95% CI = 6.0-9.1) times that among persons who received only 1 dose of JYNNEOS vaccine ≥14 days earlier and 9.6 (95% CI = 6.9-13.2) times that among persons who received dose 2 ≥14 days earlier. The observed distribution of subcutaneous and intradermal routes of administration of dose 1 among vaccinated persons with mpox was not different from the expected distribution. This report provides additional data suggesting JYNNEOS vaccine provides protection against mpox, irrespective of whether the vaccine is administered intradermally or subcutaneously. The degree and durability of such protection remains unclear. Persons eligible for mpox vaccination should receive the complete 2-dose series to optimize strength of protection(††) (5).

To evaluate progress toward prevention of enteric infections in the United States, the Foodborne Diseases Active Surveillance Network (FoodNet) conducts active population-based surveillance for laboratory-diagnosed infections caused by Campylobacter, Cyclospora, Listeria, Salmonella, Shiga toxin-producing Escherichia coli (STEC), Shigella, Vibrio, and Yersinia at 10 U.S. sites. This report summarizes preliminary 2021 data and describes changes in annual incidence compared with the average annual incidence for 2016-2018, the reference period for the U.S. Department of Health and Human Services' (HHS) Healthy People 2030 goals for some pathogens (1). During 2021, the incidence of infections caused by Salmonella decreased, incidence of infections caused by Cyclospora, Yersinia, and Vibrio increased, and incidence of infections caused by other pathogens did not change. As in 2020, behavioral modifications and public health interventions implemented to control the COVID-19 pandemic might have decreased transmission of enteric infections (2). Other factors (e.g., increased use of telemedicine and continued increase in use of culture-independent diagnostic tests [CIDTs]) might have altered their detection or reporting (2). Much work remains to achieve HHS Healthy People 2030 goals, particularly for Salmonella infections, which are frequently attributed to poultry products and produce, and Campylobacter infections, which are frequently attributed to chicken products (3).