BACKGROUND: Enteric infections are hypothesized to be associated with intussusception in children. A small increase in intussusception following rotavirus vaccination has been seen in some settings. We conducted post-marketing surveillance for intussusception following rotavirus vaccine, Rotavac introduction in India and evaluated association of intussusception with enteric pathogens. METHODS: In a case-control study nested within a large sentinel hospital-based surveillance program in India, stool samples from 272 children aged less than 2 years admitted for intussusception and 272 age-, gender- and location-matched controls were evaluated with Taqman array card based molecular assays to detect enteric viruses, bacterial enteropathogens and parasites. Matched case-control analysis with conditional logistic regression evaluated association of enteropathogens with intussusception. Population attributable fractions (PAF) were calculated for enteropathogens significantly associated with intussusception. RESULTS: The most prevalent enteropathogens in cases and controls were enteroaggregative Escherichia coli, adenovirus 40/41, adenovirus C serotypes and enteroviruses. Children with intussusception were more likely to harbor adenovirus C serotypes (adjusted odds-ratio (aOR) = 1.74; 95% confidence interval (CI) 1.06-2.87) and enteroviruses (aOR = 1.77; 95% CI 1.05-2.97) than controls. Rotavirus was not associated with increased intussusception risk. Adenovirus C (PAF = 16.9%; 95% CI 4.7% - 27.6%) and enteroviruses (PAF = 14.7%; 95% CI 4.2% - 24.1%) had the highest population attributable fraction for intussusception. CONCLUSION: Adenovirus C serotypes and enteroviruses were significantly associated with intussusception in Indian children. Rotavirus was not associated with risk of intussusception.

Respiratory syncytial virus (RSV) is the second most common pathogen causing infant mortality. Additionally, RSV is a major cause of morbidity and mortality in older adults (age ≥60 years) similar to influenza. A protein-based maternal vaccine and monoclonal antibody (mAb) are now market-approved to protect infants, while an mRNA and two protein-based vaccines are approved for older adults. First-year experience protecting infants with nirsevimab in high-income countries shows a major public health benefit. It is expected that the RSV vaccine landscape will continue to develop in the coming years to protect all people globally. The vaccine and mAb landscape remain active with 30 candidates in clinical development using four approaches: protein-based, live-attenuated and chimeric vector, mRNA, and mAbs. Candidates in late-phase trials aim to protect young infants using mAbs, older infants and toddlers with live-attenuated vaccines, and children and adults using protein-based and mRNA vaccines. This Review provides an overview of RSV vaccines highlighting different target populations, antigens, and trial results. As RSV vaccines have not yet reached low-income and middle-income countries, we outline urgent next steps to minimise the vaccine delay.

BACKGROUND: Of the 43 mpox cases reported by the WHO in South East Asia between January 2022 and March 2023, 24 (56%) were from India. OBJECTIVES: We describe the clinical and epidemiological profile of cases identified through India's hospital case-based surveillance. MATERIALS AND METHODS: We identified mpox cases as a positive result for mpox virus polymerase-chain-reaction assay, reported through surveillance from July 1, 2022 to January 7, 2023. Cases and clinicians were interviewed, and data were abstracted from the medical records. We conducted contact tracing among family, close social networks, and healthcare personnel staff for the first 17 cases. We collected the data on sociodemographics, clinical findings, and behavior, and described data using summary statistics. RESULTS: We identified 24 laboratory-confirmed cases (42% females, median age 30 years, range 22-38), including one death (case fatality rate 4.2%). We collected clinical and behavioural data from 21 of 24 cases. All had rashes with vesicles and genital lesions; 7 (33%) reported genital lesions as the first symptom; and 3 (13%) reported complications. Among the 21 cases, all were sexually active, none self-identified as men having sex with men (MSM), and 6 (29%) reported multiple sex partners. We identified 51 contacts of the first 17 reported cases, none reported symptoms suggestive of mpox. CONCLUSION: The clinical and behavioral characteristics of mpox cases in India are consistent with the global 2022 outbreak, with the exception that no cases in India reported MSM. Most were sexually active young adult economic migrants and developed genital lesions.

Drug overdose deaths remain a public health crisis in the United States; nearly 107,000 and nearly 108,000 deaths occurred in 2021 and 2022, respectively. Persons with mental health conditions are at increased risk for overdose. In addition, substance use disorders and non-substance-related mental health disorders (MHDs) frequently co-occur. Using data from CDC's State Unintentional Drug Overdose Reporting System, this report describes characteristics of persons in 43 states and the District of Columbia who died of unintentional or undetermined intent drug overdose and had any MHD. In 2022, 21.9% of persons who died of drug overdose had a reported MHD. Using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria, the most frequently reported MHDs were depressive (12.9%), anxiety (9.4%), and bipolar (5.9%) disorders. Overall, approximately 80% of overdose deaths involved opioids, primarily illegally manufactured fentanyls. Higher proportions of deaths among decedents with an MHD involved antidepressants (9.7%) and benzodiazepines (15.3%) compared with those without an MHD (3.3% and 8.5%, respectively). Nearly one quarter of decedents with an MHD had at least one recent potential opportunity for intervention (e.g., approximately one in 10 decedents were undergoing substance use disorder treatment, and one in 10 visited an emergency department or urgent care facility within 1 month of death). Expanding efforts to identify and address co-occurring mental health and substance use disorders (e.g., integrated screening and treatment) and strengthen treatment retention and harm reduction services could save lives.

BACKGROUND: Injection drug use (IDU) is a major contributor to the syndemic of viral hepatitis, human immunodeficiency virus, and drug overdose. However, information on IDU is frequently missing in national viral hepatitis surveillance data, which limits our understanding of the full extent of IDU-associated infections. Multiple imputation by chained equations (MICE) has become a popular approach to address missing data, but its application for IDU imputation is less studied. METHODS: Using the 2019-2021 National Notifiable Diseases Surveillance System acute hepatitis C case data and publicly available county-level measures, we evaluated listwise deletion (LD) and 3 models imputing missing IDU data through MICE: parametric logistic regression, semi-parametric predictive mean matching (PMM), and nonparametric random forest (RF) (both standard RF [sRF] and fast implementation of RF [fRF]). RESULTS: The estimated IDU prevalence among acute hepatitis C cases increased from 63.5% by LD to 65.1% by logistic regression, 66.9% by PMM, 76.0% by sRF, and 85.1% by fRF. Evaluation studies showed that RF-based MICE imputation, especially fRF, has the highest accuracy (as measured by smallest raw bias, percent bias, and root mean square error) and highest efficiency (as measured by smallest 95% confidence interval width) compared to LD and other models. Sensitivity analyses indicated that fRF remained robust when data were missing not at random. CONCLUSION: Our analysis suggested that RF-based MICE imputation, especially fRF, could be a valuable approach for addressing missing IDU data in the context of population-based surveillance systems like National Notifiable Diseases Surveillance System. The inclusion of imputed IDU data may enhance the effectiveness of future surveillance and prevention efforts for the IDU-driven syndemic.

IMPORTANCE: Hepatitis C can be cured with direct-acting antivirals (DAAs), but Medicaid programs have implemented fibrosis, sobriety, and prescriber restrictions to control costs. Although restrictions are easing, understanding their association with hepatitis C treatment rates is crucial to inform policies that increase access to lifesaving treatment. OBJECTIVE: To estimate the association of jurisdictional (50 states and Washington, DC) DAA restrictions and Medicaid expansion with the number of Medicaid recipients with filled prescriptions for DAAs. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used publicly available Medicaid documents and claims data from January 1, 2014, to December 31, 2021, to compare the number of unique Medicaid recipients treated with DAAs in each jurisdiction year with Medicaid expansion status and categories of fibrosis, sobriety, and prescriber restrictions. Medicaid recipients from all 50 states and Washington, DC, during the study period were included. Multilevel Poisson regression was used to estimate the association between Medicaid expansion and DAA restrictive policies on jurisdictional Medicaid DAA prescription fills. Data were analyzed initially from August 15 to November 15, 2023, and subsequently from April 15 to May 9, 2024. EXPOSURES: Jurisdictional Medicaid expansion status and fibrosis, sobriety, and prescriber DAA restrictions. MAIN OUTCOMES AND MEASURES: Number of people treated with DAAs per 100 000 Medicaid recipients per year. RESULTS: A total of 381 373 Medicaid recipients filled DAA prescriptions during the study period (57.3% aged 45-64 years; 58.7% men; 15.2% non-Hispanic Black and 52.2% non-Hispanic White). Medicaid nonexpansion jurisdictions had fewer filled DAA prescriptions per 100 000 Medicaid recipients per year than expansion jurisdictions (38.6 vs 86.6; adjusted relative risk [ARR], 0.56 [95% CI, 0.52-0.61]). Jurisdictions with F3 to F4 (34.0 per 100 000 Medicaid recipients per year; ARR, 0.39 [95% CI, 0.37-0.66]) or F1 to F2 fibrosis restrictions (61.9 per 100 000 Medicaid recipients per year; ARR, 0.62 [95% CI, 0.59-0.66]) had lower treatment rates than jurisdictions without fibrosis restrictions (94.8 per 100 000 Medicaid recipients per year). Compared with no sobriety restrictions (113.5 per 100 000 Medicaid recipients per year), 6 to 12 months of sobriety (38.3 per 100 000 Medicaid recipients per year; ARR, 0.65 [95% CI, 0.61-0.71]) and screening and counseling requirements (84.7 per 100 000 Medicaid recipients per year; ARR, 0.87 [95% CI, 0.83-0.92]) were associated with reduced treatment rates, while 1 to 5 months of sobriety was not statistically significantly different. Compared with no prescriber restrictions (97.8 per 100 000 Medicaid recipients per year), specialist consult restrictions was associated with increased treatment (66.2 per 100 000 Medicaid recipients per year; ARR, 1.05 [95% CI, 1.00-1.10]), while specialist required restrictions were not statistically significant. CONCLUSIONS AND RELEVANCE: In this cross-sectional study, Medicaid nonexpansion status, fibrosis, and sobriety restrictions were associated with a reduction in the number of people with Medicaid who were treated for hepatitis C. Removing DAA restrictions might facilitate treatment of more people diagnosed with hepatitis C.

Community engagement is vital to the development of people-centered, successful vaccination programs. The diverse Vaccination Acceptance Research Network (VARN) community brings together interdisciplinary professionals from across the immunization ecosystem who play a crucial role in vaccination acceptance, demand, and delivery. Over the course of the VARN2023 conference, researchers and practitioners alike shared ideas and experiences focused on strategies and approaches to building trust between communities and health systems to increase equity in vaccination. Health professionals and community members must have equal value in the design and delivery of community-centered immunization services, while key vaccination decision-makers must also consider community experiences, concerns, and expertise in program design and policymaking. Therefore, strategies for community engagement and cultivating trust with communities are crucial for the success of any immunization program. Furthermore, health workers need additional skills, support, and resources to effectively communicate complex information about immunization, including effective strategies for countering misinformation. This article summarizes three skills-building sessions offered at the VARN2023 conference, focused on human-centered design, motivational interviewing, and engaging with journalists to leverage the voices of communities. These sessions offered practical, evidence-based tools for use across geographic and social settings that can be used by practitioners, researchers, and other stakeholders to increase vaccination demand and uptake in their communities.

OBJECTIVE: Case investigation and contact tracing (CI/CT) are fundamental public health efforts widely used during the COVID-19 pandemic to mitigate transmission. This study investigated how state, local, and tribal public health departments used CI/CT during the COVID-19 pandemic, including CI/CT methodology, staffing models, training and support, and efforts to identify or prioritize populations disproportionately affected by COVID-19. METHODS: During March and April 2022, we conducted key informant interviews with up to 3 public health officials from 43 state, local, and tribal public health departments. From audio-recorded and transcribed interviews, we used the framework method to analyze key themes. RESULTS: Major adjustments to CI/CT protocols during the pandemic included (1) prioritizing populations for outreach; (2) implementing automated outreach for nonprioritized groups, particularly during COVID-19 surges; (3) discontinuing contact tracing and focusing exclusively on case investigation; and (4) adding innovations to provide additional support. Key informants also discussed the utility of having backup staffing to support overwhelmed public health departments and spoke to the difficulty in "right-sizing" the public health workforce, with COVID-19 surges leaving public health departments understaffed as case rates rose and overstaffed as case rates fell. CONCLUSIONS: When addressing future epidemics or outbreaks, public health officials should consider strategies that improve the effectiveness of CI/CT efforts over time, such as prioritizing populations based on disproportionate risk, implementing automated outreach, developing models that provide flexible additional staffing resources as cases rise and fall among local public health departments, incorporating demographic data in laboratory reporting, providing community connections and support, and having a system of self-notification of contacts.

BACKGROUND AIMS: The National Health and Nutrition Examination Survey (NHANES) underestimates the true prevalence of hepatitis C virus (HCV) infection. By accounting for populations inadequately represented in NHANES, we created two models to estimate the national hepatitis C prevalence among US adults during 2017-2020. APPROACH RESULTS: The first approach (NHANES+) replicated previous methodology by supplementing hepatitis C prevalence estimates among the US noninstitutionalized civilian population with a literature review and meta-analysis of hepatitis C prevalence among populations not included in the NHANES sampling frame. In the second approach (persons who inject drugs [PWID] adjustment), we developed a model to account for underrepresentation of PWID in NHANES by incorporating the estimated number of adult PWID in the United States and applying PWID-specific hepatitis C prevalence estimates. Using the NHANES+ model, we estimated HCV RNA prevalence of 1.0% (95% confidence interval [CI]: 0.5%-1.4%) among US adults in 2017-2020, corresponding to 2,463,700 (95% CI: 1,321,700-3,629,400) current HCV infections. Using the PWID adjustment model, we estimated HCV RNA prevalence of 1.6% (95% CI: 0.9%-2.2%), corresponding to 4,043,200 (95% CI: 2,401,800-5,607,100) current HCV infections. CONCLUSIONS: Despite years of an effective cure, estimated prevalence of hepatitis C in 2017-2020 remains unchanged from 2013-2016 when using comparable methodology. When accounting for increased injection drug use, estimated prevalence of hepatitis C is substantially higher than previously reported. National action is urgently needed to expand testing, increase access to treatment, and improve surveillance, especially among medically underserved populations, to support hepatitis C elimination goals.

BACKGROUND: Mechanisms underlying the pro gression of diabetic kidney disease to ESKD are not fully understood. METHODS: We performed global microRNA (miRNA) analysis on plasma from two cohorts consisting of 375 individuals with type 1 and type 2 diabetes with late diabetic kidney disease, and targeted proteomics analysis on plasma from four cohorts consisting of 746 individuals with late and early diabetic kidney disease. We examined structural lesions in kidney biopsy specimens from the 105 individuals with early diabetic kidney disease. Human umbilical vein endothelial cells were used to assess the effects of miRNA mimics or inhibitors on regulation of candidate proteins. RESULTS: In the late diabetic kidney disease cohorts, we identified 17 circulating miRNAs, represented by four exemplars (miR-1287-5p, miR-197-5p, miR-339-5p, and miR-328-3p), that were strongly associated with 10-year risk of ESKD. These miRNAs targeted proteins in the axon guidance pathway. Circulating levels of six of these proteins-most notably, EFNA4 and EPHA2-were strongly associated with 10-year risk of ESKD in all cohorts. Furthermore, circulating levels of these proteins correlated with severity of structural lesions in kidney biopsy specimens. In contrast, expression levels of genes encoding these proteins had no apparent effects on the lesions. In in vitro experiments, mimics of miR-1287-5p and miR-197-5p and inhibitors of miR-339-5p and miR-328-3p upregulated concentrations of EPHA2 in either cell lysate, supernatant, or both. CONCLUSIONS: This study reveals novel mechanisms involved in progression to ESKD and points to the importance of systemic factors in the development of diabetic kidney disease. Some circulating miRNAs and axon guidance pathway proteins represent potential targets for new therapies to prevent and treat this condition.

BACKGROUND: Widespread outbreaks of person-to-person transmitted hepatitis A virus (HAV), particularly among people who inject drugs (PWID), continue across the United States and globally. However, the herd immunity threshold and vaccination coverage required to prevent outbreaks are unknown. We used surveillance data and dynamic modeling to estimate herd immunity thresholds among PWID in 16 US states. METHODS: We used a previously published dynamic model of HAV transmission calibrated to surveillance data from outbreaks involving PWID in 16 states. Using state-level calibrated models, we estimated the basic reproduction number (R0) and herd immunity threshold for PWID in each state. We performed a meta-analysis of herd immunity thresholds to determine the critical vaccination coverage required to prevent most HAV outbreaks among PWID. RESULTS: Estimates of R0 for HAV infection ranged from 2.2 (95% confidence interval [CI], 1.9-2.5) for North Carolina to 5.0 (95% CI, 4.5-5.6) for West Virginia. Corresponding herd immunity thresholds ranged from 55% (95% CI, 47%-61%) for North Carolina to 80% (95% CI, 78%-82%) for West Virginia. Based on the meta-analysis, we estimated a pooled herd immunity threshold of 64% (95% CI, 61%-68%; 90% prediction interval, 52%-76%) among PWID. Using the prediction interval upper bound (76%) and assuming 95% vaccine efficacy, we estimated that vaccination coverage of 80% could prevent most HAV outbreaks. CONCLUSIONS: Hepatitis A vaccination programs in the United States may need to achieve vaccination coverage of at least 80% among PWID in order to prevent most HAV outbreaks among this population.

BACKGROUND: Organomodified nanoclays (ONC), two-dimensional montmorillonite with organic coatings, are increasingly used to improve nanocomposite properties. However, little is known about pulmonary health risks along the nanoclay life cycle even with increased evidence of airborne particulate exposures in occupational environments. Recently, oropharyngeal aspiration exposure to pre- and post-incinerated ONC in mice caused low grade, persistent lung inflammation with a pro-fibrotic signaling response with unknown mode(s) of action. We hypothesized that the organic coating presence and incineration status of nanoclays determine the inflammatory cytokine secretary profile and cytotoxic response of macrophages. To test this hypothesis differentiated human macrophages (THP-1) were acutely exposed (0-20 µg/cm(2)) to pristine, uncoated nanoclay (CloisNa), an ONC (Clois30B), their incinerated byproducts (I-CloisNa and I-Clois30B), and crystalline silica (CS) followed by cytotoxicity and inflammatory endpoints. Macrophages were co-exposed to lipopolysaccharide (LPS) or LPS-free medium to assess the role of priming the NF-κB pathway in macrophage response to nanoclay treatment. Data were compared to inflammatory responses in male C57Bl/6J mice following 30 and 300 µg/mouse aspiration exposure to the same particles. RESULTS: In LPS-free media, CloisNa exposure caused mitochondrial depolarization while Clois30B exposure caused reduced macrophage viability, greater cytotoxicity, and significant damage-associated molecular patterns (IL-1α and ATP) release compared to CloisNa and unexposed controls. LPS priming with low CloisNa doses caused elevated cathepsin B/Caspage-1/IL-1β release while higher doses resulted in apoptosis. Clois30B exposure caused dose-dependent THP-1 cell pyroptosis evidenced by Cathepsin B and IL-1β release and Gasdermin D cleavage. Incineration ablated the cytotoxic and inflammatory effects of Clois30B while I-CloisNa still retained some mild inflammatory potential. Comparative analyses suggested that in vitro macrophage cell viability, inflammasome endpoints, and pro-inflammatory cytokine profiles significantly correlated to mouse bronchioalveolar lavage inflammation metrics including inflammatory cell recruitment. CONCLUSIONS: Presence of organic coating and incineration status influenced inflammatory and cytotoxic responses following exposure to human macrophages. Clois30B, with a quaternary ammonium tallow coating, induced a robust cell membrane damage and pyroptosis effect which was eliminated after incineration. Conversely, incinerated nanoclay exposure primarily caused elevated inflammatory cytokine release from THP-1 cells. Collectively, pre-incinerated nanoclay displayed interaction with macrophage membrane components (molecular initiating event), increased pro-inflammatory mediators, and increased inflammatory cell recruitment (two key events) in the lung fibrosis adverse outcome pathway.

BACKGROUND: Bartonella quintana is a louse-borne bacterium that remains a neglected cause of endocarditis in low-resource settings. Our understanding of risk factors, clinical manifestations, and treatment of B. quintana endocarditis are biased by older studies from high-income countries. METHODS: We searched Pubmed Central, Medline, Scopus, Embase, EBSCO (CABI) Global Health, Web of Science and international trial registers for articles published before March 2023 with terms related to Bartonella quintana endocarditis. We included articles containing case-level information on B. quintana endocarditis and extracted data related to patient demographics, clinical features, diagnostic testing, treatment, and outcome. RESULTS: A total of 975 records were identified, of which 569 duplicates were removed prior to screening. In total, 84 articles were eligible for inclusion, describing a total of 167 cases. Infections were acquired in 40 different countries; 62 cases (37.1%) were acquired in low- and middle-income countries (LMICs). Disproportionately more female and pediatric patients were from LMICs. More patients presented with heart failure (n = 70/167 [41.9%]) than fever (n = 65/167 [38.9%]). Mean time from symptom onset to presentation was 5.1 months. Also, 25.7% of cases (n = 43/167) were associated with embolization, most commonly to the spleen and brain; 65.5% of antimicrobial regimens included doxycycline. The vast majority of cases underwent valve replacement surgery (n = 154/167, [98.0%]). Overall case fatality rate was 9.6% (n = 16/167). CONCLUSIONS: B. quintana endocarditis has a global distribution, and long delays between symptom onset and presentation frequently occur. Improved clinician education and diagnostic capacity are needed to screen at-risk populations and identify infection before endocarditis develops.

The Gram-negative Elizabethkingia express multiple antibiotic resistance and cause severe opportunistic infections. Vancomycin is commonly used to treat Gram-positive infections and has also been used to treat Elizabethkingia infections, even though Gram-negative organisms possess a vancomycin permeability barrier. Elizabethkingia anophelis appeared relatively vancomycin-susceptible and challenge with this drug led to morphological changes indicating cell lysis. In stark contrast, vancomycin growth challenge revealed that E. anophelis populations refractory to vancomycin emerged. In addition, E. anophelis vancomycin-selected mutants arose at high frequencies and demonstrated elevated vancomycin resistance and reduced susceptibility to other antimicrobials. All mutants possessed a SNP in a gene (vsr1 = vancomycin-susceptibility regulator 1) encoding a PadR family transcriptional regulator located in the putative operon vsr1-ORF551, which is conserved in other Elizabethkingia spp as well. This is the first report linking a padR homologue (vsr1) to antimicrobial resistance in a Gram-negative organism. We provide evidence to support that vsr1 acts as a negative regulator of vsr1-ORF551 and that vsr1-ORF551 upregulation is observed in vancomycin-selected mutants. Vancomycin-selected mutants also demonstrated reduced cell length indicating that cell wall synthesis is affected. ORF551 is a membrane-spanning protein with a small phage shock protein conserved domain. We hypothesize that since vancomycin-resistance is a function of membrane permeability in Gram-negative organisms, it is likely that the antimicrobial resistance mechanism in the vancomycin-selected mutants involves altered drug permeability.

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

OBJECTIVES: To assess postmortem vitamin A (VA) concentrations in children under 5 years of age and evaluate the association between vitamin A deficiency (VAD) and infectious causes of death (CoD). STUDY DESIGN: In this cross-sectional study from the Child Health and Mortality Prevention Surveillance (CHAMPS) Network, liver biopsies collected within 72 hours of death were analyzed from 405 stillbirths and children under 5 years in Kenya and South Africa. Total liver vitamin A (VA) concentrations were quantified using ultra-performance liquid chromatography, and cutoffs of ≤0.1 μmol/g, >0.1 to <0.7 μmol/g, ≥0.7 to <1.0 μmol/g, and ≥1.0 μmol/g were used to define VAD, adequate VA status, high VA, and hypervitaminosis A, respectively. Causes of death (CoD) were determined by expert panel review. RESULTS: Among 366 liver samples with viable extraction, pooled prevalences of VAD, adequacy, high VA, and hypervitaminosis were 34.2%, 51.1%, 6.0%, and 8.7%, respectively. VAD was more common among neonates compared with stillbirths, infants, or children, and among those with low birthweight, underweight, or stunting (p<0.05). When adjusting for site, age, and sex, there was no significant association of VAD with increased infectious CoD (OR 1.9, 95%CI 0.9, 3.8, p=0.073). In stratified analyses, VA deficient boys, but not girls, had an increased risk of infectious CoD (OR 3.4, 95%CI 1.3, 10.3, p=0.013). CONCLUSIONS: Definitive post-mortem assessment of VA status identified both VAD and VA excess among children under 5 years of age in Kenya and South Africa. VAD in boys was associated with increased risk of infectious mortality. Our findings may inform a transition from universal VA supplementation to targeted strategies in certain countries.

Hepatitis A is acquired through the fecal-oral route and is preventable by a safe and effective vaccine. Although hepatitis A is generally mild and self-limited, serious complications, including death, can occur. Since 2016, widespread hepatitis A outbreaks have been reported in 37 U.S. states, primarily among persons who use drugs and those experiencing homelessness. Nearly twice as many hepatitis A-related deaths were reported during 2016-2022 compared with 2009-2015. CDC analyzed data from 27 hepatitis A outbreak-affected states* that contributed data during August 1, 2016-October 31, 2022, to characterize demographic, risk factor, clinical, and cause-of-death data among 315 outbreak-related hepatitis A deaths from those states. Hepatitis A was documented as an underlying or contributing cause of death on 60% of available death certificates. Outbreak-related deaths peaked in 2019, and then decreased annually through 2022. The median age at death was 55 years; most deaths occurred among males (73%) and non-Hispanic White persons (84%). Nearly two thirds (63%) of decedents had at least one documented indication for hepatitis A vaccination, including drug use (41%), homelessness (16%), or coinfection with hepatitis B (12%) or hepatitis C (31%); only 12 (4%) had evidence of previous hepatitis A vaccination. Increasing vaccination coverage among adults at increased risk for infection with hepatitis A virus or for severe disease from infection is critical to preventing future hepatitis A-related deaths.

BACKGROUND: The Child Health and Mortality Prevention Surveillance Network (CHAMPS) identifies causes of under-5 mortality in high mortality countries. OBJECTIVE: To address challenges in postmortem nutritional assessment, we evaluated the impact of anthropometry training and the feasibility of 3D imaging on data quality within the CHAMPS Kenya site. DESIGN: Staff were trained using World Health Organization (WHO)-recommended manual anthropometry equipment and novel 3D imaging methods to collect postmortem measurements. Following training, 76 deceased children were measured in duplicate and were compared to measurements of 75 pre-training deceased children. Outcomes included measures of data quality (standard deviations of anthropometric indices and digit preference scores (DPS)), precision (absolute and relative technical errors of measurement, TEMs or rTEMs), and accuracy (Bland-Altman plots). WHO growth standards were used to produce anthropometric indices. Post-training surveys and in-depth interviews collected qualitative feedback on measurer experience with performing manual anthropometry and ease of using 3D imaging software. RESULTS: Manual anthropometry data quality improved after training, as indicated by DPS. Standard deviations of anthropometric indices exceeded limits for high data quality when using the WHO growth standards. Reliability of measurements post-training was high as indicated by rTEMs below 1.5%. 3D imaging was highly correlated with manual measurements; however, on average 3D scans overestimated length and head circumference by 1.61 cm and 2.27 cm, respectively. Site staff preferred manual anthropometry to 3D imaging, as the imaging technology required adequate lighting and additional considerations when performing the measurements. CONCLUSIONS: Manual anthropometry was feasible and reliable postmortem in the presence of rigor mortis. 3D imaging may be an accurate alternative to manual anthropometry, but technology adjustments are needed to ensure accuracy and usability.

Author summary  • Human immunodeficiency virus (HIV) drug resistance has implications for antiretroviral treatment strategies and for containing the HIV pandemic because the development of HIV drug resistance leads to the requirement for antiretroviral drugs that may be less effective, less well-tolerated, and more expensive than those used in first-line regimens.  • HIV drug resistance studies are designed to determine which HIV mutations are selected by antiretroviral drugs and, in turn, how these mutations affect antiretroviral drug susceptibility and response to future antiretroviral treatment regimens.  • Such studies collectively form a vital knowledge base essential for monitoring global HIV drug resistance trends, interpreting HIV genotypic tests, and updating HIV treatment guidelines.  • Although HIV drug resistance data are collected in many studies, such data are often not publicly shared, prompting the need to recommend best practices to encourage and standardize HIV drug resistance data sharing.  • In contrast to other viruses, sharing HIV sequences from phylogenetic studies of transmission dynamics requires additional precautions as HIV transmission is criminalized in many countries and regions.  • Our recommendations are designed to ensure that the data that contribute to HIV drug resistance knowledge will be available without undue hardship to those publishing HIV drug resistance studies and without risk to people living with HIV.

BACKGROUND: Neonates admitted to the neonatal intensive care unit (NICU) are at risk for healthcare-associated infections, including central line-associated bloodstream infections. We aimed to characterize the epidemiology of bloodstream infections among neonates with central venous catheters admitted to three Indian NICUs. METHODS: We conducted a prospective cohort study in three tertiary NICUs, from May 1, 2017 until July 31, 2019. All neonates admitted to the NICU were enrolled and followed until discharge, transfer, or death. Cases were defined as positive blood cultures in neonates with a central venous catheter in place for greater than 2 days or within 2 days of catheter removal. RESULTS: During the study period, 140 bloodstream infections were identified in 131 neonates with a central venous catheter. The bloodstream infection rate was 11.9 per 1000 central line-days. Gram-negative organisms predominated, with 38.6% of cases caused by Klebsiella spp. and 14.9% by Acinetobacter spp. Antimicrobial resistance was prevalent among Gram-negative isolates, with 86.9% resistant to third- or fourth-generation cephalosporins, 63.1% to aminoglycosides, 61.9% to fluoroquinolones, and 42.0% to carbapenems. Mortality and length of stay were greater in neonates with bloodstream infection than in neonates without bloodstream infection (unadjusted analysis, p <  0.001). CONCLUSIONS: We report a high bloodstream infection rate among neonates with central venous catheters admitted to three tertiary care NICUs in India. Action to improve infection prevention and control practices in the NICU is needed to reduce the morbidity and mortality associated with BSI in this high-risk population.

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

The United States has a goal to eliminate hepatitis C as a public health threat by 2030. To accomplish this goal, hepatitis C virus (HCV) care cascades (hereinafter, HCV cascades) can be used to measure progress toward HCV elimination and identify disparities in HCV testing and care. In this topical review of HCV cascades, we describe common definitions of cascade steps, review the application of HCV cascades in health care and public health settings, and discuss the strengths and limitations of data sources used. We use examples from the Massachusetts Department of Public Health as a case study to illustrate how multiple data sources can be leveraged to produce HCV cascades for public health purposes. HCV cascades in health care settings provide actionable data to improve health care quality and delivery of services in a single health system. In public health settings at jurisdictional and national levels, HCV cascades describe HCV diagnosis and treatment for populations, which can be challenging in the absence of a single data source containing complete, comprehensive, and timely data representing all steps of a cascade. Use of multiple data sources and strategies to improve interoperability of health care and public health data systems can advance the use of HCV cascades and speed progress toward HCV elimination.

BACKGROUND: Folate and vitamin B12 deficiencies in pregnant women are associated with increased risk for adverse maternal and infant health outcomes, including neural tube defects (NTDs). METHODS: A population-based cross-sectional survey was conducted in two rural areas in Ambala District, Haryana, India in 2017 to assess baseline folate and vitamin B12 status among women of reproductive age (WRA) and predict the prevalence of NTDs. We calculated the prevalence of folate and vitamin B12 deficiency and insufficiency by demographic characteristics among 775 non-pregnant, non-lactating WRA (18-49 years). Using red blood cell (RBC) folate distributions and an established Bayesian model, we predicted NTD prevalence. All analyses were conducted using SAS-callable SUDAAN Version 11.0.4 to account for complex survey design. RESULTS: Among WRA, 10.1% (95% CI: 7.9, 12.7) and 9.3% (95% CI: 7.4, 11.6) had serum (<7 nmol/L) and RBC folate (<305 nmol/L) deficiency, respectively. The prevalence of RBC folate insufficiency (<748 nmol/L) was 78.3% (95% CI: 75.0, 81.3) and the predicted NTD prevalence was 21.0 (95% uncertainly interval: 16.9, 25.9) per 10,000 live births. Prevalences of vitamin B12 deficiency (<200 pg/mL) and marginal deficiency (≥200 pg/mL and ≤300 pg/mL) were 57.7% (95% CI: 53.9, 61.4) and 23.5% (95% CI: 20.4, 26.9), respectively. CONCLUSIONS: The magnitude of folate insufficiency and vitamin B12 deficiency in this Northern Indian population is a substantial public health concern. The findings from the survey help establish the baseline against which results from future post-fortification surveys can be compared.

INTRODUCTION: Data on the long-term and comprehensive cost of violence are essential for informed decision making on the future benefits of resources directed toward violence prevention. This review aimed to summarize original per person estimates of the attributable cost of interpersonal violence to support public health economic research and decision making. METHODS: In 2023, English-language peer-reviewed journal articles published 2000-2022 with high-income country focus reporting original per person average cost of violence estimates were identified using index terms in multiple databases. Study content including violence type (e.g., adverse childhood experiences, ACEs), timeline and payer cost perspective (e.g., hospitalization event-only health care payer cost), and associated per person cost estimates were summarized. Costs are 2022 USD. RESULTS: Per person cost estimates related to ACEs, community violence, sexual violence, intimate partner violence, homicide, firearm violence, youth violence, workplace violence, and bullying from 73 studies (majority U.S. focus) were summarized. For example, among 23 studies with ACEs focus, monetary estimates ranged from $390 for ACE-related annual health care out-of-pocket costs per U.S. adult with 3+ ACEs to $20.2m for the lifetime societal economic burden of a U.S. child maltreatment fatality. CONCLUSIONS: This review provides a descriptive summary of available per person cost of violence estimates. Results can help public health professionals describe the economic burden of violence, identify the best available estimate for a particular public health question, and address data gaps. Ultimately, understanding the long-term and comprehensive cost of violence is necessary to anticipate the economic benefits of prevention.

OBJECTIVES: To evaluate the incidence of a candidate definition of healthcare facility-onset, treated Clostridioides difficile (CD) infection (cHT-CDI) and to identify variables and best model fit of a risk-adjusted cHT-CDI metric using extractable electronic heath data. METHODS: We analyzed 9,134,276 admissions from 265 hospitals during 2015-2020. The cHT-CDI events were defined based on the first positive laboratory final identification of CD after day 3 of hospitalization, accompanied by use of a CD drug. The generalized linear model method via negative binomial regression was used to identify predictors. Standardized infection ratios (SIRs) were calculated based on 2 risk-adjusted models: a simple model using descriptive variables and a complex model using descriptive variables and CD testing practices. The performance of each model was compared against cHT-CDI unadjusted rates. RESULTS: The median rate of cHT-CDI events per 100 admissions was 0.134 (interquartile range, 0.023-0.243). Hospital variables associated with cHT-CDI included the following: higher community-onset CDI (CO-CDI) prevalence; highest-quartile length of stay; bed size; percentage of male patients; teaching hospitals; increased CD testing intensity; and CD testing prevalence. The complex model demonstrated better model performance and identified the most influential predictors: hospital-onset testing intensity and prevalence, CO-CDI rate, and community-onset testing intensity (negative correlation). Moreover, 78% of the hospitals ranked in the highest quartile based on raw rate shifted to lower percentiles when we applied the SIR from the complex model. CONCLUSIONS: Hospital descriptors, aggregate patient characteristics, CO-CDI burden, and clinical testing practices significantly influence incidence of cHT-CDI. Benchmarking a cHT-CDI metric is feasible and should include facility and clinical variables.

OBJECTIVES: The incidence of hepatitis A declined in the United States following the introduction of hepatitis A vaccines, before increasing in the setting of recent widespread outbreaks associated with person-to-person transmission. We describe the hepatitis A epidemiology in the United States, identify susceptible populations over time, and demonstrate the need for improved hepatitis A vaccination coverage, especially among adults at increased risk for hepatitis A. METHODS: We calculated the hepatitis A incidence rates for sociodemographic characteristics and percentages for risk factors and clinical outcomes for hepatitis A cases reported to the National Notifiable Diseases Surveillance System during 1990-2020. We generated nationally representative estimates and 95% CIs of hepatitis A seroprevalence during 1976-March 2020 and self-reported hepatitis A vaccination coverage during 1999-March 2020 for the noninstitutionalized civilian US population using data from the National Health and Nutrition Examination Survey. RESULTS: Overall, the rate per 100 000 population of reported cases of hepatitis A virus infection in the United States declined 17.3-fold, from 10.4 during 1990-1998 to 0.6 during 2007-2015, and then increased to 2.8 during 2016-2020. The overall hepatitis A seroprevalence in the United States increased from 38.2% (95% CI, 36.2%-40.1%) during 1976-1980 to 47.3% (95% CI, 45.4%-49.2%) during 2015-March 2020. The prevalence of self-reported hepatitis A vaccination coverage in the United States increased more than 2.5-fold, from 16.3% (95% CI, 15.0%-17.7%) during 1999-2006 to 41.9% (95% CI, 40.2%-43.7%) during 2015-March 2020. CONCLUSIONS: Hepatitis A epidemiology in the United States changed substantially during 1976-2020. Improved vaccination coverage, especially among adults recommended for vaccination by the Advisory Committee on Immunization Practices, is vital to stop current hepatitis A outbreaks associated with person-to-person transmission in the United States and prevent similar future recurrences.

The overlapping epidemics of hepatitis C virus (HCV) and HIV infection stem from underlying behaviors and health disparities among disproportionately affected populations, especially people who inject drugs (PWID). Characterizing the prevalence of HCV-HIV coinfection offers improved data to address these underlying determinants of health. We performed a literature search for articles that describe US populations, were published during 2005-2021, and summarized evidence of the prevalence of HCV infection in recent HIV clusters and outbreaks among PWID. In population- and community-based studies, HCV antibody prevalence among PWID with HIV ranged from 10.7% to 71.4%, depending on the setting and study design. HCV-HIV coinfection ranged from 70% to 94% among 5 larger HIV clusters or outbreaks among PWID during 2014-2021; where characterized, HCV diagnosis preceded HIV detection by a median of 4 to 5 years. Robust modernized surveillance is needed to support and measure the progress of city, state, and national activities for ending the HIV epidemic and eliminating hepatitis C. Developing and leveraging surveillance systems can identify missed opportunities for prevention, evaluate care, and build capacity for outbreak investigation. In addition, improved data on injection drug use are crucial to inform efforts for improved HCV and HIV testing, prevention, and treatment in settings that serve PWID. By providing data in a wholistic, integrated manner, public health surveillance programs can support efforts to overcome inefficiencies of disease-specific silos, accelerate delivery of preventive and clinical services, and address the excess disease burden and health disparities associated with HCV-HIV coinfection.

During 2017-March 2020, approximately 2.2 million noninstitutionalized civilian U.S. adults had hepatitis C; one-third were unaware of their infection. Prevalence was substantially higher among persons who were uninsured or experiencing poverty. Unrestricted access to testing and curative treatment is urgently needed to reduce disparities and achieve 2030 elimination goals.

BACKGROUND: Drug-resistant gram-negative (GN) pathogens are a common cause of neonatal sepsis in low- and middle-income countries. Identifying GN transmission patterns is vital to inform preventive efforts. METHODS: We conducted a prospective cohort study, 12 October 2018 to 31 October 2019 to describe the association of maternal and environmental GN colonization with bloodstream infection (BSI) among neonates admitted to a neonatal intensive care unit (NICU) in Western India. We assessed rectal and vaginal colonization in pregnant women presenting for delivery and colonization in neonates and the environment using culture-based methods. We also collected data on BSI for all NICU patients, including neonates born to unenrolled mothers. Organism identification, antibiotic susceptibility testing, and next-generation sequencing (NGS) were performed to compare BSI and related colonization isolates. RESULTS: Among 952 enrolled women who delivered, 257 neonates required NICU admission, and 24 (9.3%) developed BSI. Among mothers of neonates with GN BSI (n = 21), 10 (47.7%) had rectal, 5 (23.8%) had vaginal, and 10 (47.7%) had no colonization with resistant GN organisms. No maternal isolates matched the species and resistance pattern of associated neonatal BSI isolates. Thirty GN BSI were observed among neonates born to unenrolled mothers. Among 37 of 51 BSI with available NGS data, 21 (57%) showed a single nucleotide polymorphism distance of ≤5 to another BSI isolate. CONCLUSIONS: Prospective assessment of maternal GN colonization did not demonstrate linkage to neonatal BSI. Organism-relatedness among neonates with BSI suggests nosocomial spread, highlighting the importance of NICU infection prevention and control practices to reduce GN BSI.

During 2013-2016, an estimated 2.4 million people in the United States were living with hepatitis C virus (HCV) infection.1 With the availability of curative treatment since 2013, the United States has established a goal of eliminating hepatitis C as a public health threat by 2030.2 HCV clearance cascades (hereinafter, HCV cascades) are an important tool to track progress toward elimination, across jurisdictions and at a national level, and to identify disparities in access to testing and treatment. HCV cascades are a sequence of steps that follow progression from testing and treatment to clearance and subsequent infection and can be used to inform public health interventions to facilitate progression along the cascade. | Many HCV cascades are developed in a single or regional health system in which both treatment and laboratory data are available. However, an important goal for health departments is to develop population-level cascades that capture data on HCV infection status for all people living in a jurisdiction who might seek care across various health settings. In the absence of treatment information, which is not always readily available in health department surveillance systems, HCV laboratory results can be used to develop HCV cascades. Here, we describe a standardized, laboratory result–based HCV cascade developed by the Centers for Disease Control and Prevention (CDC) as a guide for health departments (Figure 1, Supplemental Material).