In Lesotho, the Ministry of Health and key donors have made significant advancements to develop digital health solutions specific to HIV services including an eRegister which is interoperable with the health management information system, pharmacy services and the laboratory information system. New investments from the Millennium Challenge Corporation will expand digital health services to all reported communicable and non-communicable disease areas at health facilities throughout the country. This paper explores how digital health interventions designed to support comprehensive HIV care can be leveraged to provide universal digital health coverage. Specifically, three priority areas will be addressed: (i) governance, security, and system architecture (ii) power, connectivity, and equipment (iii) human resources and change management.

OBJECTIVE: Potentially preventable hospitalizations are inpatient admissions for a standard set of selected acute illnesses and chronic conditions that might have been avoided with preventive care or outpatient management. During 2010-2012, Alaska Native adults had higher rates of potentially preventable hospitalizations compared to other adults in Alaska. We evaluated potentially preventable hospitalizations among American Indian/Alaska Native (AI/AN) adults in the United States during 2016-2021. METHODS: We used hospital discharge data from the Indian Health Service National Patient Information Reporting System (NPIRS) to calculate and compare average annual age-adjusted rates of potentially preventable hospitalizations per 1000 AI/AN adults for two acute conditions (community-acquired pneumonia and urinary tract infection) and four chronic conditions (diabetes, heart failure, asthma/chronic obstructive pulmonary disease, and hypertension). RESULTS: Of 310,889 hospitalizations among AI/AN adults, 40,400 (13 %) were defined as potentially preventable for an annual rate of 7.6 per 1000 persons. Rates were stable during 2016-2019 (8.7 per 1000) but declined during 2020-2021 (5.9 per 1000), likely related to the COVID-19 pandemic. Older adults and rural residents had significantly higher rates of potentially preventable hospitalizations across all six conditions assessed, with community-acquired pneumonia having the highest hospitalization rate among adults aged ≥65 years (5.2 per 1000). CONCLUSIONS: Targeted preventive care and appropriate outpatient management for AI/AN elders living in rural areas might help improve health and reduce medical costs through decreased hospitalizations. Vaccination against respiratory infections could have the greatest impact in reducing preventable hospitalizations among AI/AN adults.

Salmonella enterica bacteria are a leading cause of foodborne illness in the United States; however, most Salmonella illnesses are not associated with known outbreaks, and predicting the source of sporadic illnesses remains a challenge. We used a supervised random forest model to determine the most likely sources responsible for human salmonellosis cases in the United States. We trained the model by using whole-genome multilocus sequence typing data from 18,661 Salmonella isolates from collected single food sources and used feature selection to determine the subset of loci most influential for prediction. The overall out-of-bag accuracy of the trained model was 91%; the highest prediction accuracy was for chicken (97%). We applied the trained model to 6,470 isolates from humans with unknown exposure to predict the source of infection. Our model predicted that >33% of the human-derived Salmonella isolates originated from chicken and 27% were from vegetables.

Estimating the number of illnesses caused by foodborne pathogens is critical for allocating resources and prioritizing interventions. We estimated the number of illnesses, hospitalizations, and deaths in the United States caused by 7 major foodborne pathogens by using surveillance data and other sources, adjusted for underreporting and underdiagnosis. Campylobacter spp., Clostridium perfringens, invasive Listeria monocytogenes, norovirus, nontyphoidal Salmonella serotypes, and Shiga toxin-producing Escherichia coli caused ≈9.9 million (90% credible interval [CrI] 5.9-15.4 million) domestically acquired foodborne illnesses in 2019. Together with Toxoplasma gondii, those pathogens caused 53,300 (90% CrI 35,700-74,500) hospitalizations and 931 (90% CrI 530‒1,460) deaths. Norovirus caused most illnesses (≈5.5 million illnesses, 22,400 hospitalizations), followed by Campylobacter spp. (1.9 million illnesses, 13,000 hospitalizations) and nontyphoidal Salmonella serotypes (1.3 million illnesses, 12,500 hospitalizations). Salmonella infection was the leading cause of death (n = 238). Foodborne illness estimates can inform policy and direct food safety interventions that reduce those illnesses.

BACKGROUND: Pneumococcal conjugate vaccines (PCVs) introduced in childhood national immunization programs lowered vaccine-type invasive pneumococcal disease (IPD), but replacement with non-vaccine-types persisted throughout the PCV10/13 follow-up period. We assessed PCV10/13 impact on pneumococcal meningitis incidence globally. METHODS: The number of cases with serotyped pneumococci detected in cerebrospinal fluid and population denominators were obtained from surveillance sites globally. Site-specific meningitis incidence rate ratios (IRRs) comparing pre-PCV incidence to each year post-PCV10/13 were estimated by age (<5, 5-17 and ≥18 years) using Bayesian multi-level mixed effects Poisson regression, accounting for pre-PCV trends. All-site weighted average IRRs were estimated using linear mixed-effects regression stratified by age, product (PCV10 or PCV13) and prior PCV7 impact (none, moderate, or substantial). Changes in pneumococcal meningitis incidence were estimated overall and for product-specific vaccine-types and non-PCV13-types. RESULTS: Analyses included 10,168 cases <5 y from PCV13 sites and 2849 from PCV10 sites, 3711 and 1549 for 5-17 y and 29,187 and 5653 for ≥18 y from 42 surveillance sites (30 PCV13, 12 PCV10, 2 PCV10/13) in 30 countries, primarily high-income (84%). Six years after PCV10/PCV13 introduction, pneumococcal meningitis declined 48-74% across products and PCV7 impact strata for children <5 y, 35-62% for 5-17 y and 0-36% for ≥18 y. Impact against PCV10-types at PCV10 sites, and PCV13-types at PCV13 sites was high for all age groups (<5 y: 96-100%; 5-17 y: 77-85%; ≥18 y: 73-85%). After switching from PCV7 to PCV10/13, increases in non-PCV13-types were generally low to none for all age groups. CONCLUSION: Pneumococcal meningitis declined in all age groups following PCV10/PCV13 introduction. Plateaus in non-PCV13-type meningitis suggest less replacement than for all IPD. Data from meningitis belt and high-burden settings were limited.

BACKGROUND: Pneumococcal conjugate vaccines (PCVs) that are ten-valent (PCV10) and 13-valent (PCV13) became available in 2010. We evaluated their global impact on invasive pneumococcal disease (IPD) incidence in all ages. METHODS: Serotype-specific IPD cases and population denominators were obtained directly from surveillance sites using PCV10 or PCV13 in their national immunisation programmes and with a primary series uptake of at least 50%. Annual incidence rate ratios (IRRs) were estimated comparing the incidence before any PCV with each year post-PCV10 or post-PCV13 introduction using Bayesian multi-level, mixed-effects Poisson regressions, by site and age group. All site-weighted average IRRs were estimated using linear mixed-effects regression, stratified by product and previous seven-valent PCV (PCV7) effect (none, moderate, or substantial). FINDINGS: Analyses included 32 PCV13 sites (488 758 cases) and 15 PCV10 sites (46 386 cases) in 30 countries, primarily high income (39 sites), using booster dose schedules (41 sites). By 6 years after PCV10 or PCV13 introduction, IPD due to PCV10-type serotypes and PCV10-related serotype 6A declined substantially for both products (age <5 years: 83-99% decline; ≥65 years: 54-96% decline). PCV7-related serotype 19A increases before PCV10 or PCV13 introduction were reversed at PCV13 sites (age <5 years: 61-79% decline relative to before any PCV; age ≥65 years: 7-26% decline) but increased at PCV10 sites (age <5 years: 1·6-2·3-fold; age ≥65 years: 3·6-4·9-fold). Serotype 3 IRRs had no consistent trends for either product or age group. Non-PCV13-type IPD increased similarly for both products (age <5 years: 2·3-3·3-fold; age ≥65 years: 1·7-2·3-fold). Despite different serotype 19A trends, all-serotype IPD declined similarly between products among children younger than 5 years (58-74%); among adults aged 65 years or older, declines were greater at PCV13 (25-29%) than PCV10 (4-14%) sites, but other differences between sites precluded attribution to product. INTERPRETATION: Long-term use of PCV10 or PCV13 reduced IPD substantially in young children and more moderately in older ages. Non-vaccine-type serotypes increased approximately two-fold to three-fold by 6 years after introduction of PCV10 or PCV13. Continuing serotype 19A increases at PCV10 sites and declines at PCV13 sites suggest that PCV13 use would further reduce IPD at PCV10 sites. FUNDING: Bill & Melinda Gates Foundation as part of the WHO Pneumococcal Vaccines Technical Coordination Project.

Understanding disparities in salmonellosis burden is critical for developing effective, equitable prevention programs. Past efforts to characterize disparities were limited in scope and by the analytical methods available when the study was conducted. We aim to address this gap by identifying disparities in salmonellosis incidence between counties with different determinants of health (DOH) profiles. Using national U.S. Laboratory-based Enteric Disease Surveillance (LEDS) data for 1997-2019, age-adjusted county-level salmonellosis incidence/100,000 persons was calculated and linked to publicly available DOH data. We used hurdle counterfactual random forest (CFRF) to quantify, for each DOH, the risk that (i) ≥1 versus no cases were reported by a county, and (ii) when ≥1 case was reported, whether a high (≥16 cases/100,000 persons) or low incidence (≥1 & <4 cases/100,000 persons) was reported. Risk in both models was significantly associated with demographic DOH, suggesting a disparity between counties with different demographic profiles. Risk was also significantly associated with food, healthcare, physical, and socioeconomic environment. The risk was generally greater for counties with more negative food resources, and for under-resourced counties (e.g., fewer healthcare and social services, fewer grocery stores). Risk was also significantly higher if any extreme weather event occurred. The study also found that underreporting and underascertainment appeared to result in underestimation of salmonellosis incidence in economically marginalized and under-resourced communities. Overall, our analyses indicated that, regardless of other county characteristics, extreme weather was associated with increased salmonellosis incidence, and that certain communities were differentially disadvantaged toward a higher incidence. This information can facilitate the development of community-specific prevention efforts.

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.

Program evaluation is a critical tool for understanding and improving organizational activities and systems. This report updates the 1999 CDC Framework for Program Evaluation in Public Health (CDC. Framework for program evaluation in public health. MMWR Recomm Rep 1999;48[No. RR-11];1-40) by integrating major advancements in the fields of evaluation and public health, lessons learned from practical applications of the original framework, and current Federal agency policies and practices. A practical, nonprescriptive tool, the updated 2024 framework is designed to summarize and organize essential elements of program evaluation, and can be applied at any level from individual programs to broader systems by novices and experts for planning and implementing an evaluation. Although many of the key aspects from the 1999 framework remain, certain key differences exist. For example, this updated framework also includes six steps that describe the general process of evaluation planning and implementation, but some content and step names have changed (e.g., the first step has been renamed Assess context). The standards for high-quality evaluation remain central to the framework, although they have been updated to the five Federal evaluation standards. The most substantial change from the 1999 framework is the addition of three cross-cutting actions that are core tenets to incorporate within each evaluation step: engage collaboratively, advance equity, and learn from and use insights. The 2024 framework provides a guide for designing and conducting evaluation across many topics within and outside of public health that anyone involved in program evaluation efforts can use alone or in conjunction with other evaluation approaches, tools, or methods to build evidence, understand programs, and refine evidence-based decision-making to improve all program outcomes.

OBJECTIVES: Integrating pathogen genomic surveillance with bioinformatics can enhance public health responses by identifying risk and guiding interventions. This study focusses on the two predominant Campylobacter species, which are commonly found in the gut of birds and mammals and often infect humans via contaminated food. Rising incidence and antimicrobial resistance (AMR) are a global concern and there is an urgent need to quantify the main routes to human infection. METHODS: During routine US national surveillance (2009-2019), 8,856 Campylobacter genomes from human infections and 16,703 from possible sources were sequenced. Using machine learning and probabilistic models, we target genetic variation associated with host adaptation to attribute the source of human infections and estimate the importance of different disease reservoirs. RESULTS: Poultry was identified as the primary source of human infections, responsible for an estimated 68% of cases, followed by cattle (28%), and only a small contribution from wild birds (3%) and pork sources (1%). There was also evidence of an increase in multidrug resistance, particularly among isolates attributed to chickens. CONCLUSIONS: National surveillance and source attribution can guide policy, and our study suggests that interventions targeting poultry will yield the greatest reductions in campylobacteriosis and spread of AMR in the US. DATA AVAILABILITY: All sequence reads were uploaded and shared on NCBI's Sequence Read Archive (SRA) associated with BioProjects; PRJNA239251 (CDC / PulseNet surveillance), PRJNA287430 (FSIS surveillance), PRJNA292668 & PRJNA292664 (NARMS) and PRJNA258022 (FDA surveillance). Publicly available genomes, including reference genomes and isolates sampled worldwide from wild birds are associated with BioProject accessions: PRJNA176480, PRJNA177352, PRJNA342755, PRJNA345429, PRJNA312235, PRJNA415188, PRJNA524300, PRJNA528879, PRJNA529798, PRJNA575343, PRJNA524315 and PRJNA689604. Contiguous assemblies of all genome sequences compared are available at Mendeley data (assembled C. coli genomes doi: 10.17632/gxswjvxyh3.1; assembled C. jejuni genomes doi: 10.17632/6ngsz3dtbd.1) and individual project and accession numbers can be found in Supplementary tables S1 and S2, which also includes pubMLST identifiers for assembled genomes. Figshare (10.6084/m9.figshare.20279928). Interactive phylogenies are hosted on microreact separately for C. jejuni (https://microreact.org/project/pascoe-us-cjejuni) and C. coli (https://microreact.org/project/pascoe-us-ccoli).

BACKGROUND AND AIMS: A functional cure and therapeutic end point of chronic HBV infection is defined as the clearance of HBsAg from serum. Little is known about the long-term durability of HBsAg loss in the Alaskan Native population. APPROACH AND RESULTS: We performed a retrospective cohort study of Alaska Native patients with chronic HBV-monoinfection from January 1982 through December 2019. The original group in this cohort was identified during a 1982 to 1987 population-based screening for 3 HBV serologic markers in 53,000 Alaska Native persons. With close to 32,000 years of follow-up, we assessed the frequency and duration of HBsAg seroclearance (HBsAg-negative for > 6 mo). We examined factors associated with HBsAg clearance and followed persons for a median of 13.1 years afterward to assess the durability of HBsAg clearance. Among 1079 persons with an average length of follow-up of 33 years, 260 (24%) cleared HBsAg at a constant rate of 0.82% per person/per year. Of the 260 persons who cleared, 249 (96%) remained HBsAg-negative, while 11 persons had ≥ 2 transient HBsAg-positive results in subsequent follow-up. CONCLUSIONS: Of the patients with chronic HBV monoinfection, 0.82% of people per year achieved a functional cure. HBsAg seroclearance was durable for treated and nontreated patients and lasted, on average, over 13 years without seroreversion.

We evaluated factors associated with the presence of hepatitis A virus antibodies 23 years after initiating vaccination at ages 6-15 months. Among 67 participants, 86% (42/49) of those vaccinated at ages 12-15 months and 61% (11/18) of those vaccinated at 6 months remained seropositive at 23 years. Lack of maternal antibodies at enrollment and higher initial vaccine response were independently associated with higher antibody concentrations at 23 years. Further research is needed to assess the duration of hepatitis A vaccine protection and possible need for a booster dose.

Over 40% of all U.S. Salmonella illnesses are attributed to consumption of contaminated meat and poultry products each year. Determining which serotypes cause the most outbreak illnesses associated with specific meat and poultry types can inform prevention measures. We developed an approach to categorize serotypes using outbreak illness burden (high, moderate, low) and trajectory (increased, stable, decreased). We used data from 192 foodborne Salmonella outbreaks resulting in 7,077 illnesses, 1,330 hospitalizations, and 9 deaths associated with chicken, turkey, beef, or pork during 2012-2021. We linked each meat and poultry type to 1-3 serotypes that we categorized high outbreak illness burden and increased trajectory during 2021. Calculation and public display of outbreak illness burden and trajectory annually could facilitate prioritization of serotypes for prevention by federal and state health and regulatory agencies and by the meat and poultry industry.

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.

Few precise estimates of hospitalization and fatality rates from COVID-19 exist for naive populations, especially within demographic subgroups. We estimated rates among persons with SARS-CoV-2 infection in the United States during May 1-December 1, 2020, before vaccines became available. Both rates generally increased with age; fatality rates were highest for persons >85 years of age (24%) and lowest for children 1-14 years of age (0.01%). Age-adjusted case hospitalization rates were highest for African American or Black, not Hispanic persons (14%), and case-fatality rates were highest for Asian or Pacific Islander, not Hispanic persons (4.4%). Eighteen percent of hospitalized patients and 44.2% of those admitted to an intensive care unit died. Male patients had higher hospitalization (6.2% vs. 5.2%) and fatality rates (1.9% vs. 1.5%) than female patients. These findings highlight the importance of collecting surveillance data to devise appropriate control measures for persons in underserved racial/ethnic groups and older adults.

BACKGROUND: Haemophilus influenzae (Hi) can cause severe disease in children. This study aimed to identify risk factors related to invasive Hi disease in Alaska children and evaluate carriage in people around them. METHODS: From 2005 to 2011, we investigated episodes of invasive, typeable Hi disease in Alaska children <10 years old. Three age-matched control children were enrolled for each case-patient. We evaluated oropharyngeal Hi carriage in people in close contact with Hi case-patients (contacts) as well as control children and their household members. Individual and household risk factors for illness and carriage were evaluated using questionnaires and chart reviews. RESULTS: Thirty-eight of 44 (86%) children with invasive, typeable Hi disease were recruited: 20 Hi serotype a (53%), 13 serotype b (Hib) (34%) and 5 serotype f (13%). Children with the invasive Hi disease were more likely than controls to have underlying health problems (67% vs. 24%, P = 0.001), other carriers of any Hi in their household (61% vs. 15%, P < 0.001), and inadequate Hib vaccination (26% vs. 9%, P = 0.005). People who carried Hi were younger than noncarriers (mean 12.7 vs. 18.0 years, P = 0.008). The carriage was clustered within case-patient households, with carriage in 19% of household contacts, while only 6.3% of nonhousehold contacts and 5.5% of noncontacts carried the Hi serotype of interest ( P < 0.001). CONCLUSIONS: Factors associated with invasive Hi disease in children included underlying health problems, household carriage and inadequate Hib vaccination. The high level of carriage in case-patient households is important to consider when evaluating treatment and prophylaxis strategies.

Measles is a highly infectious, vaccine-preventable disease that can cause severe illness, hospitalization, and death. A measles outbreak associated with a migrant shelter in Chicago occurred during February-April 2024, in which a total of 57 confirmed cases were identified, including 52 among shelter residents, three among staff members, and two among community members with a known link to the shelter. CDC simulated a measles outbreak among shelter residents using a dynamic disease model, updated in real time as additional cases were identified, to produce outbreak forecasts and assess the impact of public health interventions. As of April 8, the model forecasted a median final outbreak size of 58 cases (IQR = 56-60 cases); model fit and prediction range improved as more case data became available. Counterfactual analysis of different intervention scenarios demonstrated the importance of early deployment of public health interventions in Chicago, with a 69% chance of an outbreak of 100 or more cases had there been no mass vaccination or active case-finding compared with only a 1% chance when those interventions were deployed. This analysis highlights the value of using real-time, dynamic models to aid public health response, set expectations about outbreak size and duration, and quantify the impact of interventions. The model shows that prompt mass vaccination and active case-finding likely substantially reduced the chance of a large (100 or more cases) outbreak in Chicago.

BACKGROUND: Microneedle patches (MNPs) have been ranked as the highest global priority innovation for overcoming immunisation barriers in low-income and middle-income countries. This trial aimed to provide the first data on the tolerability, safety, and immunogenicity of a measles and rubella vaccine (MRV)-MNP in children. METHODS: This single-centre, phase 1/2, double-blind, double-dummy, randomised, active-controlled, age de-escalation trial was conducted in The Gambia. To be eligible, all participants had to be healthy according to prespecified criteria, aged 18-40 years for the adult cohort, 15-18 months for toddlers, or 9-10 months for infants, and to be available for visits throughout the follow-up period. The three age cohorts were randomly assigned in a 2:1 ratio (adults) or 1:1 ratio (toddlers and infants) to receive either an MRV-MNP (Micron Biomedical, Atlanta, GA, USA) and a placebo (0·9% sodium chloride) subcutaneous injection, or a placebo-MNP and an MRV subcutaneous injection (MRV-SC; Serum Institute of India, Pune, India). Unmasked staff ransomly assigned the participants using an online application, and they prepared visually identical preparations of the MRV-MNP or placebo-MNP and MRV-SC or placebo-SC, but were not involved in collecting endpoint data. Staff administering the study interventions, participants, parents, and study staff assessing trial endpoints were masked to treatment allocation. The safety population consists of all vaccinated participants, and analysis was conducted according to route of MRV administration, irrespective of subsequent protocol deviations. The immunogenicity population consisted of all vaccinated participants who had a baseline and day 42 visit result available, and who had no protocol deviations considered to substantially affect the immunogenicity endpoints. Solicited local and systemic adverse events were collected for 14 days following vaccination. Unsolicited adverse events were collected to day 180. Age de-escalation between cohorts was based on the review of the safety data to day 14 by an independent data monitoring committee. Serum neutralising antibodies to measles and rubella were measured at baseline, day 42, and day 180. Analysis was descriptive and included safety events, seroprotection and seroconversion rates, and geometric mean antibody concentrations. The trial was registered with the Pan African Clinical Trials Registry PACTR202008836432905, and is complete. FINDINGS: Recruitment took place between May 18, 2021, and May 27, 2022. 45 adults, 120 toddlers, and 120 infants were randomly allocated and vaccinated. There were no safety concerns in the first 14 days following vaccination in either adults or toddlers, and age de-escalation proceeded accordingly. In infants, 93% (52/56; 95% CI 83·0-97·2) seroconverted to measles and 100% (58/58; 93·8-100) seroconverted to rubella following MRV-MNP administration, while 90% (52/58; 79·2-95·2) and 100% (59/59; 93·9-100) seroconverted to measles and rubella respectively, following MRV-SC. Induration at the MRV-MNP application site was the most frequent local reaction occurring in 46 (77%) of 60 toddlers and 39 (65%) of 60 infants. Related unsolicited adverse events, most commonly discolouration at the application site, were reported in 35 (58%) of 60 toddlers and 57 (95%) of 60 infants that had received the MRV-MNP. All local reactions were mild. There were no related severe or serious adverse events. INTERPRETATION: The safety and immunogenicity data support the accelerated development of the MRV-MNP. FUNDING: Bill & Melinda Gates Foundation.

The International Circumpolar Surveillance (ICS) program is a population-based surveillance network for invasive bacterial diseases throughout Arctic countries and territories. The ICS quality control program for Streptococcus pneumoniae serotyping and antimicrobial susceptibility testing has been ongoing since 1999. Current participating laboratories include the Provincial Laboratory for Public Health in Edmonton, Alberta; Laboratoire de santé publique du Québec in Sainte-Anne-de-Bellevue, Québec; the Centers for Disease Control's Arctic Investigations Program in Anchorage, Alaska; the Neisseria and Streptococcus Reference Laboratory at Statens Serum Institut in Copenhagen, Denmark; the Department of Clinical Microbiology, Landspitali in Reykjavik, Iceland; and Public Health Agency of Canada's National Microbiology Laboratory in Winnipeg, Manitoba. From 2009 to 2020, 140 isolates of S. pneumoniae were distributed among the six laboratories as part of the quality control program. Overall serotype concordance was 96.9%, with 99.3% concordance to pool level. All participating laboratories had individual concordance rates >92% for serotype and >97% for pool. Overall concordance by modal minimum inhibitory concentration (MIC) for testing done by broth microdilution or Etest was 99.1%, and >98% for all antimicrobials tested. Categorical concordance was >98% by both CLSI and EUCAST criteria. For two laboratories performing disc diffusion, rates of concordance by modal MIC were >97% for most antimicrobials, except chloramphenicol (>93%) and trimethoprim/sulfamethoxazole (>88%). Data collected from 12 years of the ICS quality control program for S. pneumoniae demonstrate excellent (≥95%) overall concordance for serotype and antimicrobial susceptibility testing results across six laboratories. IMPORTANCE: Arctic populations experience several social and physical challenges that lead to the increased spread and incidence of invasive diseases. The International Circumpolar Surveillance (ICS) program was developed to monitor five invasive bacterial diseases in Arctic countries and territories. Each ICS organism has a corresponding interlaboratory quality control (QC) program for laboratory-based typing, to ensure the technical precision and accuracy of reference testing services for these regions, and identify and correct potential problems. Here, we describe the results of the ICS Streptococcus pneumoniae QC program, from 2009 to 2020. Excellent overall concordance was achieved for serotype and antimicrobial susceptibility testing results across six laboratories. Ongoing participation in these QC programs ensures the continuation of quality surveillance systems within Arctic populations that experience health disparities.

BACKGROUND: Persistent human papillomavirus (HPV) infection can cause anogenital and oropharyngeal cancers. Many HPV infections and HPV-associated cancers are vaccine-preventable. Studies suggest long-term persistence of vaccine-induced antibodies. However, data are limited among Alaska Native people. METHODS: During 2011-2014, we enrolled Alaska Native children aged 9-14 years who received a 3-dose series of quadrivalent HPV vaccine (4vHPV). We collected sera at 1 month and 1, 2, 3, and 5 years post-vaccination to evaluate trends in type-specific immunoglobulin G antibody concentrations for the 4vHPV types (HPV 6/11/16/18). RESULTS: All participants (N = 469) had detectable antibodies against all 4vHPV types at all timepoints post-vaccination. For all 4vHPV types, antibody levels peaked by 1 month post-vaccination and gradually declined in subsequent years. At 5 years post-vaccination, antibody levels were higher among children who received 4vHPV at a younger age. CONCLUSIONS: Alaska Native children maintained antibodies against all 4vHPV types at 5 years post-vaccination.

BACKGROUND: Evidence suggests an increased risk of new-onset diabetes following COVID-19 infection. American Indian/Alaska Native (AI/AN) people were disparately impacted by the COVID-19 pandemic and historically have had higher diabetes incidence than other racial/ethnic groups in the US. We measured the association between COVID-19 infection and incident diabetes in AI/AN people. METHODS: We conducted a retrospective cohort study using de-identified patient data from the Indian Health Service's (IHS) National Patient Information Reporting System. We estimated age-adjusted diabetes incidence rates, incidence rate ratios, and adjusted hazard ratios among three cohorts spanning pre-pandemic (1/1/2018-2/28/2020) and pandemic (3/1/2020-12/31/2021) timeframes: 1) pre-pandemic cohort (1,503,085 individuals); 2) no-COVID-19 pandemic cohort (1,344,339 individuals); and 3) COVID-19 cohort (176,483 individuals). FINDINGS: The COVID-19 cohort had an increased hazard of diabetes compared to the no-COVID-19 group (adjusted hazard ratio (aHR) = 1.56; 95% CI: 1.50-1.62) and the pre-pandemic group (aHR = 1.27; 95% CI: 1.22-1.32). The association between COVID-19 infection and new-onset diabetes was stronger in those with severe COVID-19 illness. A sensitivity analysis comparing the COVID-19 cohort to members of other cohorts that had acute upper respiratory infections showed an attenuated but higher risk of new-onset diabetes in those with COVID-19. INTERPRETATION: AI/AN people diagnosed with COVID-19 had an elevated risk of a new diabetes diagnosis when compared to the no-COVID-19 group and the pre-pandemic group. The increased diabetes risk in the COVID-19 group remained in a sensitivity analysis that limited the comparator groups to individuals with an AURI diagnosis. FUNDING: US National Institute of Diabetes and Digestive and Kidney Diseases.

We fit a power law distribution to US foodborne disease outbreaks to assess underdetection and underreporting. We predicted that 788 fewer than expected small outbreaks were identified annually during 1998-2017 and 365 fewer during 2018-2019, after whole-genome sequencing was implemented. Power law can help assess effectiveness of public health interventions.

Information on the causative agent in an enteric disease outbreak can be used to generate hypotheses about the route of transmission and possible vehicles, to guide environmental assessments, and to target outbreak control measures. However, only about 40% of outbreaks reported in the United States include a confirmed etiology. The goal of this project was to identify clinical and demographic characteristics that can be used to predict the causative agent in an enteric disease outbreak and to use these data to develop an online tool for investigators to use during an outbreak when hypothesizing about the causative agent. Using data on enteric disease outbreaks from all transmission routes (animal contact, environmental contamination, foodborne, person-to-person, waterborne, unknown) reported to the U.S. Centers for Disease Control and Prevention, we developed random forest models to predict the etiology of an outbreak based on aggregated clinical and demographic characteristics at both the etiology category (i.e., bacteria, parasites, toxins, viruses) and individual etiology (Clostridium perfringens, Campylobacter, Cryptosporidium, norovirus, Salmonella, Shiga toxin-producing Escherichia coli, and Shigella) levels. The etiology category model had a kappa of 0.85 and an accuracy of 0.92, whereas the etiology-specific model had a kappa of 0.75 and an accuracy of 0.86. The highest sensitivities in the etiology category model were for bacteria and viruses; all categories had high specificities (>0.90). For the etiology-specific model, norovirus and Salmonella had the highest sensitivity and all etiologies had high specificities. When laboratory confirmation is unavailable, information on the clinical signs and symptoms reported by people associated with the outbreak, with other characteristics including case demographics and illness severity, can be used to predict the etiology or etiology category. An online publicly available tool was developed to assist investigators in their enteric disease outbreak investigations.

Cardiovascular diseases (CVDs) are a major source of morbidity and mortality worldwide. Despite a decline of ≈30% over the past decade, heart disease remains the leading killer of Americans.1 For rare and familial forms of CVD, we are increasingly recognizing single-gene mutations that impart relatively large effects on individual phenotype. Examples include inherited forms of cardiomyopathy, arrhythmias, and aortic diseases. However, the prevalence of monogenic disorders typically accounts for a small proportion of the total CVD observed in the population. CVDs in the general population are complex diseases, with several contributing genetic and environmental factors. Although recent progress in monogenic disorders has occurred, we have seen a period of intense investigation to identify the genetic architecture of more common forms of CVD and related traits. | | Genomics serves several roles in cardiovascular health and disease, including disease prediction, discovery of genetic loci influencing CVD, functional evaluation of these genetic loci to understand mechanisms, and identification of therapeutic targets. For single-gene CVDs, progress has led to several clinically useful diagnostic tests, extending our ability to inform the management of afflicted patients and their family members. However, there has been little progress in developing genetic testing for complex CVD because individual common variants have only a modest impact on risk. The study of the genomics of complex CVDs is further challenged by the influence of environmental variables, phenotypic heterogeneity, and pathogenic complexity. Characterization of the clinical phenotype requires consideration of the clinical details of the diseases and traits under study.

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: Culture-independent diagnostic testing (CIDT) provides rapid results to clinicians and is quickly displacing traditional detection methods. Increased CIDT use and sensitivity likely result in higher case detection but might also obscure infection trends. Severe illness outcomes, such as hospitalization and death, are likely less affected by changes in testing practices and can be used as indicators of the expected case incidence trend had testing methods not changed. METHODS: Using US Foodborne Diseases Active Surveillance Network data during 1996-2019 and mixed effects quasi-Poisson regression, we estimated the expected yearly incidence for nine enteric pathogens. RESULTS: Removing the effect of CIDT use, CIDT panel testing and culture-confirmation of CIDT testing, the modelled incidence in all but three pathogens (Salmonella, Shigella, STEC O157) was significantly lower than the observed and the upward trend in Campylobacter was reversed from an observed 2.8% yearly increase to a modelled -2.8% yearly decrease (95% credible interval: -4.0, -1.4). CONCLUSIONS: Severe outcomes may be useful indicators in evaluating trends in surveillance systems that have undergone a marked change.

BACKGROUND: Adults aged ≥65 years, adults with certain underlying medical conditions, and persons experiencing homelessness are at increased risk for invasive pneumococcal disease (IPD). Two new pneumococcal conjugate vaccines, 15-valent pneumococcal conjugate vaccine (PCV15) and 20-valent pneumococcal conjugate vaccine (PCV20), were recently approved for use in U.S. adults. We described the epidemiology of IPD among Alaska adults and estimated the proportion of IPD cases potentially preventable by new vaccines. METHODS: We used statewide, laboratory-based surveillance data to calculate and compare IPD incidence rates and 95% confidence intervals (CI) among Alaska adults aged ≥18 years during 2011-2020 and estimate the proportion of IPD cases that were caused by serotypes in PCV15 and PCV20. RESULTS: During 2011-2020, 1,164 IPD cases were reported among Alaska adults for an average annual incidence of 21.3 cases per 100,000 adults per year (95% CI: 20.1-22.5). Incidence increased significantly during the study period (p<0.01). IPD incidence among Alaska Native adults was 4.7 times higher than among non-Alaska Native adults (95% CI: 4.2-5.2). Among adults experiencing homelessness in Anchorage, IPD incidence was 72 times higher than the general adult population (95% CI: 59-89). Overall, 1,032 (89%) Alaska adults with IPD had an indication for pneumococcal vaccine according to updated vaccination guidelines; 456 (39%) and 700 (60%) cases were caused by serotypes in PCV15 and PCV20, respectively. CONCLUSIONS: Use of PCV15 and PCV20 could substantially reduce IPD among adults in Alaska, including Alaska Native adults and adults experiencing homelessness.

Listeria monocytogenes can cause severe foodborne illness, including miscarriage during pregnancy or death in newborn infants. When outbreaks of L. monocytogenes illness occur, it may be possible to determine the food source of the outbreak. However, most reported L. monocytogenes illnesses do not occur as part of a recognized outbreak and most of the time the food source of sporadic L. monocytogenes illness in people cannot be determined. In the United States, L. monocytogenes isolates from patients, foods, and environments are routinely sequenced and analyzed by whole genome multilocus sequence typing (wgMLST) for outbreak detection by PulseNet, the national molecular surveillance system for foodborne illnesses. We investigated whether machine learning approaches applied to wgMLST allele call data could assist in attribution analysis of food source of L. monocytogenes isolates. We compiled isolates with a known source from five food categories (dairy, fruit, meat, seafood, and vegetable) using the metadata of L. monocytogenes isolates in PulseNet, deduplicated closely genetically related isolates, and developed random forest models to predict the food sources of isolates. Prediction accuracy of the final model varied across the food categories; it was highest for meat (65%), followed by fruit (45%), vegetable (45%), dairy (44%), and seafood (37%); overall accuracy was 49%, compared with the naive prediction accuracy of 28%. Our results show that random forest can be used to capture genetically complex features of high-resolution wgMLST for attribution of isolates to their sources.

Abstract CDC and health departments investigate foodborne disease outbreaks to identify a source. To generate and test hypotheses about vehicles, investigators typically compare exposure prevalence among case-patients with the general population using a one-sample binomial test. We propose a Bayesian alternative that also accounts for uncertainty in the estimate of exposure prevalence in the reference population. We compared exposure prevalence in a 2020 outbreak of Escherichia coli O157:H7 illnesses linked to leafy greens with 2018-2019 FoodNet Population Survey estimates. We ran prospective simulations using our Bayesian approach at three time points during the investigation. The posterior probability that leafy green consumption prevalence was higher than the general population prevalence increased as additional case-patients were interviewed. Probabilities were >0.70 for multiple leafy green items 2 weeks before the exact binomial p-value was statistically significant. A Bayesian approach to assessing exposure prevalence among cases could be superior to the one-sample binomial test typically used during foodborne outbreak investigations.

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.