Environmental exposures are ubiquitous and play a significant, and sometimes understated, role in public health as they can lead to the development of various chronic and infectious diseases. In an ideal world, there would be sufficient experimental data to determine the health effects of exposure to priority environmental contaminants. However, this is not the case, as emerging chemicals are continuously added to this list, furthering the data gaps. Recently, simulation science has evolved and can provide appropriate solutions using a multitude of computational methods and tools. In its quest to protect communities across the country from environmental health threats, ATSDR employs a variety of simulation science tools such as Physiologically Based Pharmacokinetic (PBPK) modeling, Quantitative Structure-Activity Relationship (QSAR) modeling, and benchmark dose (BMD) modeling, among others. ATSDR's use of such tools has enabled the agency to evaluate exposures in a timely, efficient, and effective manner. ATSDR's work in simulation science has also had a notable impact beyond the agency, as evidenced by external researchers' widespread appraisal and adaptation of the agency's methodology. ATSDR continues to advance simulation science tools and their applications by collaborating with researchers within and outside the agency, including other federal/state agencies, NGOs, the private sector, and academia.

Rocky Mountain spotted fever (RMSF) is an ongoing public health crisis in Mexico, particularly in states bordering the United States. The national highest incidence and mortality of RMSF occur in this region, resulting in a case-fatality rate that ranges annually between 10% and 50%, primarily affecting vulnerable groups such as children, elderly adults, and persons living in poverty. Multiple biological, environmental, and social determinants can explain its growing presence throughout the country and how it challenges the health system and society. It is necessary to integrate resources and capacities from health authorities, research centers, and society to succeed in dealing with this problem. Through a scientific symposium, a group of academicians, U.S. health officials, and Mexican health authorities met on November 8-10, 2023, in Hermosillo, Mexico, to discuss the current situation of RMSF across the country and the challenges associated with its occurrence. An urgent call for action to improve national capacity against RMSF in the aspects of epidemiological and acarological surveillance, diagnosis, medical care, case and outbreak prevention, health promotion, and research was urged by the experts. The One Health approach is a proven multidisciplinary strategy to integrate policies and interventions to mitigate and prevent the burden of cases, deaths, and suffering caused by RMSF in Mexico.

Adult-onset asthma, notably prevalent among healthcare professionals, especially nurses, is often attributed to occupational factors such as exposure to cleaning agents. Studies consistently underscore the substantial role of such exposure in work-related asthma among hospital staff. We aimed to (a) identify and characterize current practices in cleaning and aerosolized medication administration; (b) assess changes in practices since a similar 2003 study of Texas healthcare workers; and (c) identify factors contributing to diverse exposures within healthcare job categories. We conducted focus groups with 38 participants in 6 healthcare settings, analyzing current practices, changes since 2003, and factors contributing to exposure diversity. We used a three-step approach for data analysis, including sociodemographic characterization, a scissor-and-sort technique for exposure description, and qualitative content analysis. Participants were primarily healthcare providers (76%) and housekeepers/cleaners (11%) who reported exposure to aerosolized medications, cleaning products, adhesives, and solvents. Participants reported transitioning from cleaning practices to new formulas with reduced odors and shifting from spray cleansers to wipes. Personal protective equipment (PPE) used during cleaning tasks varied, with training differing among job categories. Aerosolized medication administration varied among facilities, with reported medication types and protocol changes over time. The results emphasized the significance of maintaining uniform protection, disseminating knowledge, and consistently adhering to PPE protocols in the healthcare environment. Addressing the identified gaps in comprehension and potential sources of exposure variability requires additional focus on occupational health and safety initiatives.

Substances of unknown or variable composition, complex reaction products, and biological materials (UVCBs) are commonly found in the environment. However, assessing their human toxicological risk is challenging due to their variable composition and many constituents. Metal naphthenate salts are one such category of UVCBs that are the reaction products of naphthenic acids with metals to form complex mixtures. Metal naphthenates are often found or used in household and industrial materials with potential for human exposure, but very few of these materials have been evaluated for causing human health hazards. Herein, we evaluate metal naphthenates using predictions derived from read-across and quantitative structure-activity/property relationship (QSAR/QSPR) models. Accordingly, we first built a computational chemistry library by enumerating the structures of naphthenic acids and derived 11,850 QSAR-acceptable structures; then, we used open and commercial in silico tools on these structures to predict a set of physicochemical properties and toxicity endpoints. We then compared the QSAR/QSPR predictions with available experimental data on naphthenic acids to provide a more complete picture of the contributions of the components to the toxicity profiles of metal naphthenate mixtures. The available systematic acute oral toxicity values (LD(50)) and QSAR LD(50) predictions of all the naphthenic acid components indicated low concern for toxicity. The point of departure predictions for chronic repeated dose toxicity for the naphthenic acid components using QSAR models developed from studies on rats ranged from 25 to 50 mg/kg/day. These values are in good agreement with findings from studies on copper and zinc naphthenates, which had no observed adverse effect levels of 30 and 118 mg/kg/day, respectively. Hence, this study demonstrates how published in silico approaches can be used to identify the potential components of metal naphthenates for further testing, inform groupings of UVCBs such as naphthenates, as well as fill the data gaps using read-across and QSAR models to inform risk assessment.

Ototoxicity refers to the adverse effects of substances on auditory or vestibular functions. This study examines the evidence of ototoxicity's association with exposure to common environmental pollutants, as documented in toxicological profiles by the Agency for Toxic Substances and Disease Registry. Our aim was to evaluate whether the evidence supports modifying the charting of ototoxic effects in the summary tables of these toxicological profiles and providing a guide for scientists to access these data. Health outcomes of interest included hearing loss, vestibular effects, cochlear lesions, tonal alterations, cellular damage, and ototoxicity-related outcomes (neurological, nephrotoxic, hepatic, and developmental effects). We obtained ototoxicity information for 62 substances. Hearing-related effects were reported, along with neurological effects. Overall, 26 profiles reported strong evidence of ototoxicity, including 13 substances previously designated as ototoxic by other health and safety agencies. Commonly studied outcomes included hearing loss, damage to ear anatomy, and auditory dysfunction. Vestibular dysfunction and tinnitus are rarely studied. Our findings highlight the lack of conclusive evidence of ototoxic properties for many substances, especially for pesticides and herbicides. This review supports charting the evidence of ototoxicity separately in toxicological profiles' summary tables. Improving the communication of ototoxicity-related health effects might impact their recognition and prompt further research. A stronger evidence base could support improved prevention efforts in terms of serious health outcomes.

In the United States in 2021, an outbreak of 4 cases of Burkholderia pseudomallei, the etiologic agent of melioidosis and a Tier One Select Agent (potential for deliberate misuse and subsequent harm), resulted in 2 deaths. The causative strain, B. pseudomallei ATS2021, was unintentionally imported into the United States in an aromatherapy spray manufactured in India. We established that ATS2021 represents a virulent strain of B. pseudomallei capable of robust formation of biofilm at physiologic temperatures that may contribute to virulence. By using mouse melioidosis models, we determined median lethal dose estimates and analyzed the bacteriologic and histopathologic characteristics of the organism, particularly the potential neurologic pathogenesis that is probably associated with the bimA(Bm) allele identified in B. pseudomallei strain ATS2021. Our data, combined with previous case reports and the identification of endemic B. pseudomallei strains in Mississippi, support the concept that melioidosis is emerging in the United States.

BACKGROUND: Astrovirus is a leading cause of acute gastroenteritis in children worldwide. However, few prospective studies have analyzed astrovirus in community-dwelling pediatric populations in low- and middle-income countries. METHODS: We assessed the incidence, risk factors, clinical characteristics, genotypes, viral coinfections, and time distribution of astrovirus gastroenteritis in 443 healthy Nicaraguan children born in 2017 to 2018 who were followed for 36 months. Children were recruited from hospitals and birth records in an economically diverse neighborhood of León city. Astrovirus-positive episodes and genotypes were identified from stool with reverse transcription quantitative polymerase chain reaction and Sanger sequencing. RESULTS: Of 1708 total specimens tested, 80 children (18%) experienced at least 1 astrovirus episode, and 9 experienced repeat episodes, mostly during the rainy season (May-October). Initial astrovirus episodes were not associated with a lowered risk against future episodes. In exploratory analyses, home toilets were associated with a lower risk of future astrovirus episodes (hazard ratio, 0.19; 95% CI, .04-.91). Human astrovirus 5 episodes, representing 15% of all typed episodes, were associated with longer diarrhea and more symptomatic rotavirus coinfections. CONCLUSIONS: Astrovirus was a common cause of gastroenteritis in this cohort, and future studies should clarify the role of astrovirus genotype in clinical infection severity.

PURPOSE: We present findings from an assessment of award recipients' partners from the Centers for Disease Control and Prevention's Colorectal Cancer Control Program (CRCCP). We describe partners' processes of identifying and tracking patients undergoing stool-based screening. METHODS: We analyzed data from eight CRCCP award recipients purposively sampled and their partner health systems from 2019 to 2023. The data included number of stool-based tests distributed and returned; abnormal findings; referrals and completion of follow-up colonoscopies; and colonoscopy findings. We also report on strategies to improve tracking of stool-based tests and facilitation of follow-up colonoscopies. RESULTS: Five of eight CRCCP award recipients reported that all or some partner health systems were able to report stool test return rates. Six had health systems that were able to report abnormal stool test findings. Two reported that health systems could track time to follow-up colonoscopy completion from date of referral, while four could report colonoscopy completion but not the timeframe. Follow-up colonoscopy completion varied substantially from 24.2 to 75.5% (average of 47.9%). Strategies to improve identifying and tracking screening focused mainly on the use of electronic medical records; strategies to facilitate follow-up colonoscopy were multi-level. CONCLUSION: Health systems vary in their ability to track steps in the stool-based screening process and few health systems can track time to completion of follow-up colonoscopy. Longer time intervals can result in more advanced disease. CRCCP-associated health systems participating in this study could support the implementation of multicomponent strategies at the individual, provider, and health system levels to improve tracking and completion of follow-up colonoscopy.

BACKGROUND: Sapovirus is an important cause of acute gastroenteritis in childhood. While vaccines against sapovirus may reduce gastroenteritis burden, a major challenge to their development is a lack of information about natural immunity. METHODS: We measured sapovirus-specific IgG in serum collected, between 2017 and 2020, of mothers soon after delivery and at 6 time points in Nicaraguan children until 3 years of age (n=112 dyads) using virus-like particles representing three sapovirus genotypes (GI.1, GI.2, GV.1). RESULTS: Sixteen (14.3%) of the 112 children experienced at least one sapovirus gastroenteritis episode, of which GI.1 was the most common genotype. Seroconversion to GI.1 and GI.2 was most common between 5 and 12 months of age, while seroconversion to GV.1 peaked at 18 to 24 months of age. All children who experienced sapovirus GI.1 gastroenteritis seroconverted and developed genotype-specific IgG. The impact of sapovirus exposure on population immunity was determined using antigenic cartography: newborns share their mothers' broadly binding IgG responses, which declined at 5 months of age and then increased as infants experienced natural sapovirus infections. CONCLUSION: By tracking humoral immunity to sapovirus over the first 3 years of life, this study provides important insights for the design and timing of future pediatric sapovirus vaccines.

Systemic racism and racialized poverty are socially produced structural determinants that shape health outcomes during infectious disease outbreaks. Public health emergencies compound vulnerabilities for survivors of intimate partner violence (IPV) and sexual violence (SV) and those who self-identify as people from racial and ethnic minority groups. We describe findings from an online survey designed to collect data on financial conditions faced by survivors of IPV and SV to understand these conditions during the COVID-19 pandemic. Our analyses were limited to a sample of women in the United States (91.4%, n = 523) who reported IPV or SV to whom we refer as survivors. We characterize the differences of economic stressors across White and aggregated categories of self-identified race, i.e., Black and Brown Latinx women and non-Black or non-Brown Latinx women of color, to highlight disparities between White and non-White populations in our sample. Logistic regressions were used to examine the relationships among racial categories, food insecurity, housing insecurity, and economic insecurity during the COVID-19 pandemic. Black and Brown Latinx women survivors were twice as likely as White women to report housing, financial, and economic insecurity during the COVID-19 pandemic. Approximately one-third of all survivors anticipated taking on more debt than they would want to cover their expenses due to COVID-19. The results of this study have implications for public health responses that involve coordinating economic relief measures among populations disparately affected by public health crises and disasters to ensure that the economic needs of the most impacted are addressed.

BACKGROUND: The Women's Health Needs Study (WHNS) collected information on the health characteristics, needs, and experiences, including female genital mutilation (FGM) experiences, attitudes, and beliefs, of women aged 18 to 49 years who were born, or whose mothers were born, in a country where FGM is prevalent living in the US. The purpose of this paper is to describe the WHNS design, methods, strengths and limitations, as well as select demographic and health-related characteristics of participants. METHODS: We conducted a cross-sectional survey from November 2020 -June 2021 in four US metropolitan areas, using a hybrid venue-based sampling (VBS) and respondent-driven sampling (RDS) approach to identify women for recruitment. RESULTS: Of 1,132 participants, 395 were recruited via VBS and 737 RDS. Most were born, or their mothers were born, in either a West African country (Burkina Faso, Guinea, Mali, Mauritania, Sierra Leone, The Gambia) (39.0%) or Ethiopia (30.7%). More than a third were aged 30-39 years (37.5%) with a majority who immigrated at ages ≥13 years (86.6%) and had lived in the United States for ≥5 years (68.9%). Medicaid was the top health insurer (52.5%), followed by private health insurance (30.5%); 17% of participants had no insurance. Nearly half of women reported 1-2 healthcare visits within the past 12 months (47.7%). One in seven did not get needed health care due to cost (14.8%). Over half have ever used contraception (52.1%) to delay or avoid pregnancy and 76.9% had their last pelvic and/or Papanicolaou (pap) exam within the past 3 years. More than half experienced FGM (55.0%). Nearly all women believed that FGM should be stopped (92.0%). CONCLUSION: The VBS/RDS approach enabled recruitment of a diverse study population. WHNS advances research related to the health characteristics, needs, and experiences of women living in the US from countries where FGM is prevalent.

The kidneys, heart and lungs are vital organ systems evaluated as part of acute or chronic toxicity assessments. New methodologies are being developed to predict these adverse effects based on in vitro and in silico approaches. This paper reviews the current state of the art in predicting these organ toxicities. It outlines the biological basis, processes and endpoints for kidney toxicity, pulmonary toxicity, respiratory irritation and sensitization as well as functional and structural cardiac toxicities. The review also covers current experimental approaches, including off-target panels from secondary pharmacology batteries. Current in silico approaches for prediction of these effects and mechanisms are described as well as obstacles to the use of in silico methods. Ultimately, a commonly accepted protocol for performing such assessment would be a valuable resource to expand the use of such approaches across different regulatory and industrial applications. However, a number of factors impede their widespread deployment including a lack of a comprehensive mechanistic understanding, limited in vitro testing approaches and limited in vivo databases suitable for modeling, a limited understanding of how to incorporate absorption, distribution, metabolism, and excretion (ADME) considerations into the overall process, a lack of in silico models designed to predict a safe dose and an accepted framework for organizing the key characteristics of these organ toxicants.

BACKGROUND: Fungal meningitis can be associated with epidural anesthesia procedures. Fusariosis is a rare infection typically affecting immunocompromised patients and rarely causes meningitis. During 2022-2023, public health officials responded to a large outbreak of Fusarium solani meningitis associated with epidural anesthesia in Durango, Mexico. METHODS: The public health response and epidemiological and clinical features of patients affected by this outbreak were described. Coordinated actions were addressed to identify the etiological agent, determine its drug susceptibility, develop diagnostic tests, and implement clinical and epidemiological protocols. Retrospective analyses of clinical variables and outcomes were performed to determine association with better patient survival. RESULTS: A total of 1801 persons exposed to epidural anesthesia were identified, of whom 80 developed meningitis. Fusarium solani was found in 3 brain biopsies and showed susceptibility to voriconazole and amphotericin B. After F solani polymerase chain reaction (PCR) implementation, 57 patients with meningitis were PCR-screened, and 31 (38.8%) had a positive result. Most patients were female (95%), and cesarean section was the most common surgical procedure (76.3%). The case fatality rate was 51.3% (41 patients) and the median hospitalization duration was 39.5 days (interquartile range, 18-86 days). Seventy-one patients (88.8%) received voriconazole/amphotericin B and 64 subjects (80%) additionally received steroids. Cox regression analysis showed an increased lethality risk in patients who received antifungal treatment after 5 days (hazard ratio, 2.1 [95% confidence interval, 1.01-4.48], P < .05). CONCLUSIONS: The F solani meningitis outbreak in Durango was an unprecedented medical challenge. Timely treatment and effective healthcare management were associated with better survival outcomes.

Objective. To compare Covid-19 risk factors, self-reported Covid-19 testing and infection, and Covid-19 vaccination among H-2A workers and agricultural workers without H-2A visas. Materials and methods. Farmworkers completed surveys at randomly selected sites in five U.S. states from March - August 2022. Descriptive statistics and bivariate analyses were conducted for key characteristics and outcomes. Results. A total of 532 H-2A workers and 748 non-H-2A workers participated in the surveys. H-2A workers had significantly higher Covid-19 primary vaccine series uptake than non-H-2A workers (94.7 vs. 65.9%). More than one in four H-2A workers (29.6%) continued working while ill or positive with Covid-19. Fewer H-2A than non-H-2A workers reported receiving a Covid-19 test (51.5 vs. 59.2%, respectively) and a positive test result for Covid-19 (24.5 vs. 44.9% among those tested). Conclusions. Although H-2A workers had a lower self-reported prevalence of Covid-19 and higher Covid-19 primary vaccine series uptake than non-H-2A workers, findings such as reporting to work while ill or positive for Covid-19 indicate areas for improvement by binational public health leaders.

BACKGROUND: Chronic lead exposure is associated with both subclinical and clinical cardiovascular disease. We evaluated whether declines in blood lead were associated with changes in systolic and diastolic blood pressure in adult American Indian participants from the SHFS (Strong Heart Family Study). METHODS AND RESULTS: Lead in whole blood was measured in 285 SHFS participants in 1997 to 1999 and 2006 to 2009. Blood pressure and measures of cardiac geometry and function were obtained in 2001 to 2003 and 2006 to 2009. We used generalized estimating equations to evaluate the association of declines in blood lead with changes in blood pressure; cardiac function and geometry measures were considered secondary. Mean blood lead was 2.04 μg/dL at baseline. After ≈10 years, mean decline in blood lead was 0.67 μg/dL. In fully adjusted models, the mean difference in systolic blood pressure comparing the highest to lowest tertile of decline (>0.91 versus <0.27 μg/dL) in blood lead was -7.08 mm Hg (95% CI, -13.16 to -1.00). A significant nonlinear association between declines in blood lead and declines in systolic blood pressure was detected, with significant linear associations where blood lead decline was 0.1 μg/dL or higher. Declines in blood lead were nonsignificantly associated with declines in diastolic blood pressure and significantly associated with declines in interventricular septum thickness. CONCLUSIONS: Declines in blood lead levels in American Indian adults, even when small (0.1-1.0 μg/dL), were associated with reductions in systolic blood pressure. These findings suggest the need to further study the cardiovascular impacts of reducing lead exposures and the importance of lead exposure prevention.

This manuscript describes the use of an analytical assay that combines transfection of mammalian cells and isotope dilution mass spectrometry (IDMS) for accurate quantification of antigen expression. Expired mRNA COVID-19 vaccine material was stored at 4 °C, room temperature (∼25 °C), and 56 °C over a period of 5 weeks. The same vaccine was also exposed to 5 freeze-thaw cycles. Every week, the spike protein antigenic expression in mammalian (BHK-21) cells was evaluated. Housekeeping proteins, β-actin and GAPDH, were simultaneously quantified to account for the variation in cell counts that occurs during maintenance and growth of cell cultures. Data show that vaccine stored at elevated temperatures results in reduced spike protein expression. Also, maintaining the vaccine in ultracold conditions or exposing the vaccine to freeze-thaw cycles had less effect on the vaccine's ability to produce the antigen in mammalian cells. We describe the use of IDMS as an antibody-free means to accurately quantify expressed protein from mammalian cells transfected with mRNA vaccine.

Birth is an inflammatory event for the newborn, characterized by elevations in interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α peripherally and/or centrally, as well as changes in brain microglia. However, the mechanism(s) underlying these responses is unknown. Toll-like receptors (TLRs) play crucial roles in innate immunity and initiate inflammatory cascades upon recognition of endogenous or exogenous antigens. Most TLR signaling depends on the adaptor molecule myeloid differentiation primary response 88 (MyD88). We independently varied MyD88 gene status in mouse dams and their offspring to determine whether the inflammatory response to birth depends on MyD88 signaling and, if so, whether that signaling occurs in the offspring, the mother, or both. We find that the perinatal surges in plasma IL-6 and brain expression of TNF-α depend solely on MyD88 gene status of the offspring, whereas postnatal increases in plasma IL-10 and TNF-α depend on MyD88 in both the pup and dam. Interestingly, MyD88 genotype of the dam primarily drives differences in offspring brain microglial density and has robust effects on developmental neuronal cell death. Milk cytokines were evaluated as a possible source of postnatal maternal influence; although we found high levels of CXCL1/GROα and several other cytokines in ingested post-partum milk, their presence did not require MyD88. Thus, the inflammatory response previously described in the late-term fetus and newborn depends on MyD88 (and, by extension, TLRs), with signaling in both the dam and offspring contributing. Unexpectedly, naturally-occuring neuronal cell death in the newborn is modulated primarily by maternal MyD88 gene status.

OBJECTIVE: Healthcare workers (HCWs) are at risk for work-related asthma, which may be affected by changes in cleaning practices. We examined associations of cleaning tasks and products with work-related asthma in HCWs in 2016, comparing them to prior results from 2003. METHODS: We estimated asthma prevalence by professional group, and explored associations of self-reported asthma with job-exposure matrix-based cleaning tasks/products in a representative Texas sample of 9914 physicians, nurses, respiratory/occupational therapists, and nurse aides. RESULTS: Response rate was 34.8%(n = 2,421). The weighted prevalences of physician-diagnosed(15.3%), work-exacerbated (4.1%), and new-onset asthma(NOA) (6.7%), and bronchial hyperresponsiveness symptoms(31.1%) were similar to 2003. NOA was associated with building surface cleaning(OR = 1.91; 95%CI:1.10-3.33), use of orthophthalaldehyde(OR = 1.77; 95%CI:1.15-2.72), bleach/quaternary compounds(OR = 1.91; 95%CI:1.10-3.33), and sprays(OR = 1.97; 95%CI:1.12-3.47). CONCLUSION: Prevalence of asthma/BHR appears unchanged, whereas associations of NOA with exposures to surface cleaning remained, and decreased for instrument cleaning.

INTRODUCTION: Postnatal care (PNC) is an underused service in the continuum of care for mothers and infants in sub-Saharan Africa. There is little evidence on health facility characteristics that influence PNC utilization. Understanding PNC use in the context of individual, community, and health facility characteristics may help in the development of programs for increased use. METHODS: We analyzed data from 4,353 women with recent births in Kigoma Region, Tanzania, and their use of PNC (defined as at least 1 checkup in a health facility in the region within 42 days of delivery). We used a mixed-effects multilevel logistic regression analysis to explain PNC use while accounting for household, individual, and community characteristics from a regionwide population-based reproductive health survey and for distance to and adequacy of proximal health facilities from a health facility assessment. RESULTS: PNC utilization rate was low (15.9%). Women had significantly greater odds of PNC if they had a high level of decision-making autonomy (adjusted odds ratio [aOR]: 1.56; 95% confidence interval [CI]=1.11, 2.17); had a companion at birth (aOR: 1.57; 95% CI=1.19, 2.07); had cesarean delivery (aOR: 2.27; 95% CI=1.47, 3.48); resided in Kasulu district (aOR: 3.28; 95% CI=1.94, 5.52); or resided in a community that had at least 1 adequate health facility within 5 km (aOR: 2.15; 95% CI=1.06, 3.88). CONCLUSION: Women's decision-making autonomy and presence of companionship at birth, as well as proximity to a health facility with adequate infrastructure, equipment, and workforce, were associated with increased PNC use. More efforts toward advocating for the health benefits of PNC using multiple channels and increasing quality of care in health facilities, including companionship at birth, can increase utilization rates.

Objective: This study explores how Field Epidemiology Training Programs (FETP) whose National Public Health Institutes (NPHI) are supported by U.S. Centers for Disease Control and Prevention (CDC) have contributed to strengthening essential public health functions. Methods: We conducted 96 semi-structured interviews with public health experts including NPHI staff, non-NPHI government staff, and staff from non-governmental and international organizations in Cambodia, Colombia, Liberia, Mozambique, Nigeria, Rwanda, and Zambia. We managed data using MAXQDA and employed direct content analysis to derive themes. Results: Three overarching themes emerged in relation to FETPs' role within the NPHIs' public health functions. These themes included contribution to improving country surveillance systems, role in providing leadership in outbreak responses, and strengthening countries' and the NPHIs' surveillance workforce capacity. Participants also shared challenges around FETPs' implementation and suggestions for improvement. Conclusion: The results demonstrate the value of FETPs in strengthening public health systems through building workforce capacity and improving surveillance systems. By identifying the successes of FETPs in contributing to essential public health functions, our findings might inform current and future FETP implementation and its integration into NPHIs.

Over 40 species of nonhuman primates host simian immunodeficiency viruses (SIVs). In natural hosts, infection is generally assumed to be nonpathogenic due to a long coevolutionary history between host and virus, although pathogenicity is difficult to study in wild nonhuman primates. We used whole-blood RNA-seq and SIV prevalence from 29 wild Ugandan red colobus (Piliocolobus tephrosceles) to assess the effects of SIV infection on host gene expression in wild, naturally SIV-infected primates. We found no evidence for chronic immune activation in infected individuals, suggesting that SIV is not immunocompromising in this species, in contrast to HIV in humans. Notably, an immunosuppressive gene, CD101, was upregulated in infected individuals. This gene has not been previously described in the context of nonpathogenic SIV infection. This expands the known variation associated with SIV infection in natural hosts, and may suggest a novel mechanism for tolerance of SIV infection in the Ugandan red colobus.

Variation in susceptibility is a known contributor to bias in studies estimating immune protection acquired from vaccination or natural infection. However, difficulty measuring this heterogeneity hinders assessment of its influence on estimates. Cohort studies, randomized trials, and post-licensure studies have reported reduced natural and vaccine-derived protection against rotavirus gastroenteritis in low- and middle-income countries (LMICs). We sought to understand differences in susceptibility among children enrolled in two birth-cohort studies of rotavirus in LMICs, and to explore the implications for estimation of immune protection. We re-analyzed data from studies conducted in Mexico City, Mexico and Vellore, India. Cumulatively, 573 unvaccinated children experienced 1418 rotavirus infections and 371 episodes of rotavirus gastroenteritis (RVGE) over 17,636 child-months. We developed a model characterizing susceptibility to rotavirus infection and RVGE among children, accounting for aspects of the natural history of rotavirus and differences in transmission rates between settings, and tested whether modelgenerated susceptibility measurements were associated with demographic and anthropometric factors. We identified greater variation in susceptibility to rotavirus infection and RVGE in Vellore than in Mexico City. In both cohorts, susceptibility to rotavirus infection and RVGE were associated with male sex, lower birth weight, lower maternal education, and having fewer siblings; within Vellore, susceptibility was also associated with lower socioeconomic status. Children who were more susceptible to rotavirus also experienced higher rates of diarrhea due to other causes. Simulations suggest that discrepant estimates of naturally-acquired immunity against RVGE can be attributed, in part, to between-setting differences in transmission intensity and susceptibility of children. We found that more children in Vellore than in Mexico City belong to a high-risk group for rotavirus infection and RVGE, and demonstrate that bias owing to differences in rotavirus transmission intensity and population susceptibility may hinder comparison of estimated immune protection against RVGE.Author summary Differences in susceptibility can help explain why some individuals, and not others, acquire infection and exhibit symptoms when exposed to infectious disease agents. However, it is difficult to distinguish between differences in susceptibility versus exposure in epidemiological studies. We developed a modeling approach to distinguish transmission intensity and susceptibility in data from cohort studies of rotavirus infection among children in Mexico City, Mexico, and Vellore, India, and evaluated how these factors may have contributed to differences in estimates of naturally-acquired immune protection between the studies. We found that more children were at “high risk” of acquiring rotavirus infection, and of experiencing gastroenteritis when infected, in Vellore versus Mexico City. The probability of belonging to this high-risk stratum was associated with recognized risk factors such as lower socioeconomic status, lower birth weight, and risk of diarrhea due to other causes. We also found the risk for rotavirus infections to cause symptoms declined with age, and was independent of acquired immunity. Together, these findings can account for estimates of lower protective efficacy of acquired immunity against rotavirus gastroenteritis in high-incidence settings, which mirrors estimates of reduced effectiveness of live oral rotavirus vaccines in low- and middle-income countries.

The advent of mRNA vaccine technology has been vital in rapidly creating and manufacturing COVID-19 vaccines at an industrial scale. To continue to accelerate this leading vaccine technology, an accurate method is needed to quantify antigens produced by the transfection of cells with a mRNA vaccine product. This will allow monitoring of protein expression during mRNA vaccine development and provide information on how changes to vaccine components affects the expression of the desired antigen. Developing novel approaches that allow for high-throughput screening of vaccines to detect changes in antigen production in cell culture prior to in vivo studies could aid vaccine development. We have developed and optimized an isotope dilution mass spectrometry method to detect and quantify the spike protein expressed after transfection of baby hamster kidney cells with expired COVID-19 mRNA vaccines. Five peptides of the spike protein are simultaneously quantified and provide assurance that protein digestion in the region of the target peptides is complete since results between the five peptides had a relative standard deviation of less than 15 %. In addition, two housekeeping proteins, actin and GAPDH, are quantified in the same analytical run to account for any variation in cell growth within the experiment. IDMS allows a precise and accurate means to quantify protein expression by mammalian cells transfected with an mRNA vaccine.

BACKGROUND: Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), no antiviral agents have yet been shown to be efficacious. METHODS: We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. RESULTS: A total of 1062 patients underwent randomization (with 541 assigned to remdesivir and 521 to placebo). Those who received remdesivir had a median recovery time of 10 days (95% confidence interval [CI], 9 to 11), as compared with 15 days (95% CI, 13 to 18) among those who received placebo (rate ratio for recovery, 1.29; 95% CI, 1.12 to 1.49; P<0.001, by a log-rank test). In an analysis that used a proportional-odds model with an eight-category ordinal scale, the patients who received remdesivir were found to be more likely than those who received placebo to have clinical improvement at day 15 (odds ratio, 1.5; 95% CI, 1.2 to 1.9, after adjustment for actual disease severity). The Kaplan-Meier estimates of mortality were 6.7% with remdesivir and 11.9% with placebo by day 15 and 11.4% with remdesivir and 15.2% with placebo by day 29 (hazard ratio, 0.73; 95% CI, 0.52 to 1.03). Serious adverse events were reported in 131 of the 532 patients who received remdesivir (24.6%) and in 163 of the 516 patients who received placebo (31.6%). CONCLUSIONS: Our data show that remdesivir was superior to placebo in shortening the time to recovery in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.).

The present publication surveys several applications of in silico (i.e., computational) toxicology approaches across different industries and institutions. It highlights the need to develop standardized protocols when conducting toxicity-related predictions. This contribution articulates the information needed for protocols to support in silico predictions for major toxicological endpoints of concern (e.g., genetic toxicity, carcinogenicity, acute toxicity, reproductive toxicity, developmental toxicity) across several industries and regulatory bodies. Such novel in silico toxicology (IST) protocols, when fully developed and implemented, will ensure in silico toxicological assessments are performed and evaluated in a consistent, reproducible, and well-documented manner across industries and regulatory bodies to support wider uptake and acceptance of the approaches. The development of IST protocols is an initiative developed through a collaboration among an international consortium to reflect the state-of-the-art in in silico toxicology for hazard identification and characterization. A general outline for describing the development of such protocols is included and it is based on in silico predictions and/or available experimental data for a defined series of relevant toxicological effects or mechanisms. The publication presents a novel approach for determining the reliability of in silico predictions alongside experimental data. In addition, we discuss how to determine the level of confidence in the assessment based on the relevance and reliability of the information.

BACKGROUND: Field Epidemiology Training Program (FETP) has been adopted as an epidemiology and response capacity building strategy worldwide. FETP-Frontline was introduced in Ethiopia in 2017 as a three-month in-service training. In this study, we evaluated implementing partners' perspectives with the aim of understanding program effectiveness and identifying challenges and recommendations for improvement. METHODS: A qualitative cross-sectional design was utilized to evaluate Ethiopia's FETP-Frontline. Using a descriptive phenomenological approach, qualitative data were collected from FETP-Frontline implementing partners, including regional, zonal, and district health offices across Ethiopia. We collected data through in-person key informant interviews, using semi-structured questionnaires. Thematic analysis was conducted, assisted with MAXQDA, while ensuring interrater reliability by using the consistent application of theme categorization. The major themes that emerged were program effectiveness, knowledge and skills differences between trained and untrained officers, program challenges, and recommended actions for improvement. Ethical approval was obtained from the Ethiopian Public Health Institute. Informed written consent was obtained from all participants, and confidentiality of the data was maintained throughout. RESULTS: A total of 41 interviews were conducted with key informants from FETP-Frontline implementing partners. The regional and zonal level experts and mentors had a Master of Public Health (MPH), whereas district health managers were Bachelor of Science (BSc) holders. Majority of the respondents reflected a positive perception towards FETP-Frontline. Regional and zonal officers as well as mentors mentioned that there were observable performance differences between trained and untrained district surveillance officers. They also identified various challenges including lack of resources for transportation, budget constraints for field projects, inadequate mentorship, high staff turnover, limited number of staff at the district level, lack of continued support from stakeholders, and the need for refresher training for FETP-Frontline graduates. CONCLUSIONS: Implementing partners reflected a positive perception towards FETP-Frontline in Ethiopia. In addition to scaling-up the program to reach all districts to achieve the International Health Regulation 2005 goals, the program also needs to consider addressing immediate challenges, primarily lack of resources and poor mentorship. Continued monitoring of the program, refresher training, and career path development could improve retention of the trained workforce.

Candida haemulonii complex species can be multidrug-resistant (MDR) and cause infections such as candidemia. This study determined the genetic relationship between isolates from Brazil and the United States through whole-genome sequencing and performed antifungal susceptibility testing to investigate drug resistance. Contrary to what is widely described, most isolates were susceptible to azoles. However, an atypical susceptibility profile was found in 50% of C. pseudohaemulonii strains including resistance to the three echinocandins. Isolates from both countries formed distinct clusters with wide genetic diversity. Isolates from three hospitals in Brazil were clonal and involved in candidemia cases, pointing to the importance of improving hospital infection control measures and molecular identification. | Candida haemulonii complex species is worldwide distributed and this study aimed to evaluate the resistance to antifungal drugs in cases from Brazil and the United States, and also compare their genetic relationship. Fifty strains were studied, most of them from Brazil were from cases of bloodstream infections while the strains from the United States came from cases of wounds and may be associated with diabetic patients. The vast majority of strains were resistant to amphotericin B, one of the most effective drugs, and susceptible to fluconazole. In addition, 50% of C. pseudohaemulonii strains were resistant to echinocandins. The strains from Brazil and the United States had no genetic relationship and formed two distinct groups. In 3 Brazilian hospitals, strains were clonal indicating an intrahospital transmission. Our findings contribute to guiding therapy in bloodstream fungal infections caused by Candida haemulonii species and alert for nosocomial transmission of this yeast complex species. | eng

We documented the contributions of Field Epidemiology Training Program (FETP) trainees and graduates to global COVID-19 preparedness and response efforts. During February-July 2021, we conducted surveys designed in accordance with the World Health Organization's COVID-19 Strategic Preparedness and Response Plan. We quantified trainee and graduate engagement in responses and identified themes through qualitative analysis of activity descriptions. Thirty-two programs with 2,300 trainees and 7,372 graduates reported near-universal engagement across response activities, particularly those aligned with the FETP curriculum. Graduates were more frequently engaged than were trainees in pandemic response activities. Common themes in the activity descriptions were epidemiology and surveillance, leading risk communication, monitoring and assessment, managing logistics and operations, training and capacity building, and developing guidelines and protocols. We describe continued FETP contributions to the response. Findings indicate the wide-ranging utility of FETPs to strengthen countries' emergency response capacity, furthering global health security.

Monkeypox virus (MPXV), an Orthopoxvirus that can cause monkeypox (mpox) disease in humans, was rarely seen outside Africa before 2022. Since May 2022, mpox has been reported in multiple countries and regions without endemic transmission, including the United States (1). New York City (NYC) quickly became one of the major foci of the 2022 outbreak after the first case in a NYC resident was diagnosed on May 19.* Epidemiologic profiles and clinical characteristics of mpox cases in the United States during this outbreak have been described (2,3), but previous summaries were limited by incomplete data or inclusion of only a subset of cases (2,3). Most case investigation data from mpox cases reported to the NYC Department of Health and Mental Hygiene (DOHMH) surveillance system have a high degree of completeness for gender, race or ethnicity, sexual orientation, and clinical signs and symptoms. To describe the characteristics of mpox in NYC, case investigation data for NYC residents with mpox diagnosed during May 19–July 15, 2022, were analyzed. Using a standardized form, DOHMH staff members attempted to interview all NYC residents with probable (a positive non-variola Orthopoxvirus polymerase chain reaction [PCR] test result)† or confirmed (a positive MPXV–specific PCR test result) mpox reported to DOHMH through mandated laboratory reporting. For patients who declined an interview or were unreachable, information obtained from medical care providers during DOHMH consultation calls was used. This activity was reviewed by CDC and conducted consistent with applicable federal law and CDC policy.§

BACKGROUND: Human immunodeficiency virus drug resistance (HIVDR) can negatively impact the effectiveness of antiretroviral therapy (ART). We aimed to estimate the prevalence of pretreatment HIVDR (PDR) among ART initiators and the prevalence of viral load (VL) suppression and acquired HIVDR among individuals receiving ART for 12 ± 3 months (ADR12) and ≥48 months (ADR48) in El Salvador. METHODS: Nationally representative cross-sectional PDR, ADR12 and ADR48 surveys were conducted among adults with HIV from October 2018 to August 2019, following World Health Organization-recommended methods. Demographic and clinic data and blood specimens were collected. RESULTS: Two hundred sixty participants were enrolled in the PDR survey, 230 in ADR12 and 425 in ADR48. Twenty-seven percent (95% confidence interval [CI], 17.1%-39.9%) of ART initiators had PDR to efavirenz or nevirapine. The prevalence of VL suppression was 88.8% (95% CI, 83.1%-92.8%) in ADR12 and 80.5% (95% CI, 76.6%-84.0%) in ADR48 surveys. Among people with HIV receiving a first-line nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART regimens and with unsuppressed VL, the prevalence of ADR to efavirenz or nevirapine was 72.0% (95% CI, 32.3%-93.3%) and 95.0% (68.5%-99.4%) in the ADR12 and ADR28 surveys, respectively. ADR12 to boosted protease inhibitors (PI/r) or integrase strand transfer inhibitors (INSTIs) was not observed. ADR48 was 1.3% (95% CI, 0.2%-9.6%) and 2.1% (0.3%-13.7%), respectively. CONCLUSIONS: Programmatic improvements in ART delivery are urgently needed in El Salvador to address the high levels of resistance to efavirenz or nevirapine among ART initiators and the low VL suppression prevalence among individuals on treatment.