BACKGROUND: Clusters of rapid HIV transmission indicate larger underlying networks that are not effectively reached by HIV prevention, testing, and care services. Starting in 2018, the Centers for Disease Control and Prevention (CDC) funded 59 U.S. health departments (HDs) to detect and respond to HIV clusters; HDs began reporting clusters to CDC in January 2020. METHODS: For clusters reported to CDC, we described cluster characteristics at detection, including detection method; size; HIV transmission category, defined as that of >50% of cluster members; and HD investigation and response activities. RESULTS: During 2020-2022, 45 HDs reported 322 HIV clusters, with most detected by molecular analysis of HIV sequences (75%). Most were detected in the South (46%) and three-quarters were predominant sexual transmission. Median cluster size at detection for molecular clusters was 10 persons (interquartile range 7-18). Among 205 clusters with follow-up data, investigation and response activities were conducted for 95%, including direct outreach to persons in clusters for partner services (64%), medical chart reviews (42%), and focused testing events (13%). Limited data on named partners tested showed that 11% received new HIV diagnoses. CONCLUSIONS: HD HIV cluster detection activities detected many clusters. Response activities were tailored for different clusters and intervened in networks with rapid transmission and high undiagnosed infection, as indicated by high positivity among partners. Cluster detection and response is an important tool to identify and address gaps in HIV prevention, testing, and care that facilitate rapid transmission.

Prescribed burning is an effective land management tool that provides a range of benefits, including ecosystem restoration and wildfire risk reduction. However, prescribed fires, just like wildfires, introduce smoke that degrades air quality. Furthermore, while prescribed fires help manage wildfire risk, they do not eliminate the possibility of wildfires. It is therefore important to also evaluate fire and smoke impacts from wildfires that may occur after a prescribed burn. In this study, we developed a framework for understanding the air quality and health related trade-offs between wildfires and prescribed fires by simulating a set of counterfactual scenarios including wildfires, prescribed fires, and postprescribed burn wildfires. We applied this framework to the case of the Gatlinburg wildfire and found that emissions from prescribed burns and subsequent wildfire were slightly lower than those from the wildfire itself. This reduction resulted in lower daily average concentrations and exposures of PM(2.5), O(3), and NO(2). Even considering the possibility of a postprescribed burn wildfire, prescribed fires reduced population-weighted daily average PM(2.5), daily maximum 8-h average O(3), and 1-h maximum NO(2) concentrations. In Sevier County, Tennessee where the wildfire occurred, these reductions reached 5.28 μg/m(3), 0.18 ppb, and 1.68 ppb, respectively. The prescribed fires also reduced the person-days smoke exposures from the wildfire. Our results suggest that although prescribed fires cannot eliminate the air quality impacts of wildfires, they can greatly reduce smoke exposure in downwind areas distant from the burn sites.

BACKGROUND: The One Health approach aims to balance and optimize the health of humans, animals, and ecosystems, recognizing that shared health outcomes are interdependent. A One Health approach to disease surveillance, control, and prevention requires infrastructure for coordinating, collecting, integrating, and analyzing data across sectors, incorporating human, animal, and environmental surveillance data, as well as pathogen genomic data. However, unlike data interoperability problems faced within a single organization or sector, data coordination and integration across One Health sectors requires engagement among partners to develop shared goals and capacity at the response level. Successful examples are rare; as such, we sought to develop a framework for local One Health practitioners to utilize in support of such efforts. METHODS: We conducted a systematic scientific and gray literature review to inform development of a One Health data integration framework. We discussed a draft framework with 17 One Health and informatics experts during semi-structured interviews. Approaches to genomic data integration were identified. RESULTS: In total, 57 records were included in the final study, representing 13 pre-defined frameworks for health systems, One Health, or data integration. These frameworks, included articles, and expert feedback were incorporated into a novel framework for One Health data integration. Two scenarios for genomic data integration were identified in the literature and outlined. CONCLUSIONS: Frameworks currently exist for One Health data integration and separately for general informatics processes; however, their integration and application to real-time disease surveillance raises unique considerations. The framework developed herein considers common challenges of limited resource settings, including lack of informatics support during planning, and the need to move beyond scoping and planning to system development, production, and joint analyses. Several important considerations separate this One Health framework from more generalized informatics frameworks; these include complex partner identification, requirements for engagement and co-development of system scope, complex data governance, and a requirement for joint data analysis, reporting, and interpretation across sectors for success. This framework will support operationalization of data integration at the response level, providing early warning for impending One Health events, promoting identification of novel hypotheses and insights, and allowing for integrated One Health solutions.

Rapid and accurate diagnostics are needed to effectively detect and treat primary amoebic meningoencephalitis (PAM) caused by Naegleria fowleri (Nf). Delayed diagnosis and similarities to other causes of meningitis contribute to a case mortality rate of >97%. Thus, there is an unmet medical need for a non-invasive liquid biopsy diagnostic method. We sequenced Nf extracellular vesicles (EVs) and identified microRNAs, tRNAs and other small RNAs in Nf-EVs. From these data we selected two prevalent small RNAs as biomarker candidates. We developed an RT-qPCR assay and both small RNAs were detected in Nf-EVs and amoeba-conditioned media. In the mouse model of PAM both small RNA biomarkers were detected in 100% of mouse plasma samples at the end-stage of infection. Notably, smallRNA-1 was detected in the urine of infected mice at timepoints as early as 24h post infection (18/23 mice) and in the plasma as early as 60h post infection (8/8 mice). Additionally, smallRNA-1 was detected in 100% (n=6) of CSF samples from human PAM cases, and in whole blood samples, but not in human plasma from PAM cases. In this study, we discovered small RNAs as biomarkers of Nf infection, one which can be detected reliably in CSF, urine, and whole blood. The RT-qPCR assay is a highly sensitive diagnostic assay that can be conducted in ~3h after receipt of liquid biopsy. The data suggest detection of smallRNA-1 biomarker could provide earlier diagnosis of PAM and be used to monitor biomass of amoebae during treatment.

Creutzfeldt-Jakob disease (CJD) is a rare, fatal, rapidly progressive neurodegenerative disease resulting from an accumulation of misfolded prion proteins (PrP). CJD affects 1-2 new individuals per million each year, and the sporadic type accounts for 90% of those cases. Though the median age at onset and disease duration vary depending on the subtype of sporadic CJD (sCJD), the disease typically affects middle-aged to elderly individuals with a median survival of 4-6 months. sCJD in younger individuals is extremely rare. Here, we present a 21-year-old female who died with a sporadic prion disease. She presented with psychiatric symptoms followed by a rapidly progressive neurocognitive and motor decline. EEG was negative for periodic sharp wave complexes; however, brain MRI was suggestive of prion disease. The cerebrospinal fluid (CSF) real-time quaking-induced conversion (RT-QuIC) assay was indeterminate. Neuropathologic examination at autopsy revealed severe neuronal loss and gliosis with secondary white matter degeneration but minimal spongiform changes and PrP deposits in the cerebellum and neocortex by immunohistochemistry. Absence of pathogenic mutations and methionine/valine heterozygosity at codon 129 of the prion protein gene (PRNP), atypical type 1 protease-resistant PrP that lacks or shows underrepresentation of the diglycosylated PrP isoform by western blot analysis, and no acquired prion disease risk factors resulted in a final diagnosis of atypical sCJD. Very young onset sCJD often has atypical clinical presentations and disease progression, neuropathological examination results, and/or laboratory test results that may confound diagnosis. It is critical to perform thorough, comprehensive evaluations to make an accurate diagnosis, which includes autopsy confirmation with histology, prion protein typing and prion gene sequencing.

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

Peribunyavirids produce enveloped virions with three negative-sense RNA segments comprising 10.7-12.5 kb in total. The family includes globally distributed viruses in multiple genera. While most peribunyavirids are maintained in geographically restricted vertebrate-arthropod transmission cycles, others are arthropod-specific or do not have a known vector. Arthropods can be persistently infected. Human and other vertebrate animal infections occur through blood feeding by an infected vector arthropod, resulting in diverse human and veterinary clinical outcomes in a strain-specific manner. Reassortment can occur between members of the same genus. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Peribunyaviridae, which is available at ictv.global/report/peribunyaviridae.

BACKGROUND: The second phase of the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) transitioned from scaling up HIV prevention and treatment to promoting sustainability and capacity building for programs monitoring performance and evaluating key program indicators. We assessed the success of a monitoring and evaluation (M&E) curriculum designed to build capacity in three PEPFAR-supported countries. METHODS: We customized M&E trainings based on country-specific epidemic control priorities in Ethiopia, Guatemala, and Cameroon. The M&E curriculum included five modules and three evaluation activities to assess impact: (i) in-person pre-post confidence assessment surveys (CAS), (ii) in-person pre-post knowledge tests (PPKT), and (iii) electronic 6-12 months post-training translating knowledge into practice (TKP) surveys. Pre- and post-training results were compared within and across countries and triangulation with the qualitative data evaluated overall success. RESULTS: Among 188 participants attending M&E trainings, 154 (82 %) responded to CAS and 165 (88 %) participants from Ethiopia and Cameroon completed PPKT. Overall CAS scores between pre- and post-test improved [Score mean difference:1.5-1.9]. PPKT indicated statistically significant knowledge gained. One out of five TKP respondents provided direct application examples from the M&E training. CONCLUSION: While feedback was predominantly positive overall, revisions were recommended for three of the five modules. Developing a customizable and adaptable M&E curriculum may sustain countries' ability to monitor their progress towards epidemic control.

Smoke from wildfires poses a substantial threat to health in communities near and far. To mitigate the extent and potential damage of wildfires, prescribed burning techniques are commonly employed as land management tools; however, they introduce their own smoke-related risks. This study investigates the impact of prescribed fires on daily average PM(2.5) and maximum daily 8-h averaged O(3) (MDA8-O(3)) concentrations and estimates premature deaths associated with short-term exposure to prescribed fire PM(2.5) and MDA8-O(3) in Georgia and surrounding areas of the Southeastern US from 2015 to 2020. Our findings indicate that over the study domain, prescribed fire contributes to average daily PM(2.5) by 0.94 ± 1.45 μg/m(3) (mean ± standard deviation), accounting for 14.0% of year-round ambient PM(2.5). Higher average daily contributions were predicted during the extensive burning season (January-April): 1.43 ± 1.97 μg/m(3) (20.0% of ambient PM(2.5)). Additionally, prescribed burning is also responsible for an annual average increase of 0.36 ± 0.61 ppb in MDA8-O(3) (approximately 0.8% of ambient MDA8-O(3)) and 1.3% (0.62 ± 0.88 ppb) during the extensive burning season. We estimate that short-term exposure to prescribed fire PM(2.5) and MDA8-O(3) could have caused 2665 (95% confidence interval (CI): 2249-3080) and 233 (95% CI: 148-317) excess deaths, respectively. These results suggest that smoke from prescribed burns increases the mortality. However, refraining from such burns may escalate the risk of wildfires; therefore, the trade-offs between the health impacts of wildfires and prescribed fires, including morbidity, need to be taken into consideration in future studies.

Candida auris is an emerging fungal pathogen that typically affects patients in healthcare settings. Data on C. auris cases in correctional facilities are limited but are needed to guide public health recommendations. We describe cases and challenges of providing care for 13 patients who were transferred to correctional facilities during January 2020-December 2022 after having a positive C. auris specimen. All patients had positive specimens identified while receiving inpatient care at healthcare facilities in geographic areas with high C. auris prevalence. Correctional facilities reported challenges managing patients and implementing prevention measures; those challenges varied by whether patients were housed in prison medical units or general population units. Although rarely reported, C. auris cases in persons who are incarcerated may occur, particularly in persons with known risk factors. Measures to manage cases and prevent C. auris spread in correctional facilities should address setting-specific challenges in healthcare and nonhealthcare correctional environments.

BACKGROUND: Noncommunicable diseases (NCDs), especially hypertension and diabetes mellitus are on the increase in sub-Saharan Africa (SSA). Informal settlement dwellers exhibit a high prevalence of behavioural risk factors and are highly vulnerable to hypertension and diabetes. However, no study has assessed the prevalence of hypertension, diabetes, and NCDrisk factors among informal settlement dwellers in Sierra Leone. We conducted a study in June 2019 to determine the prevalence of hypertension, diabetes, and NCD risk factors among adults living in the largest Sierra Leonean informal settlement (KrooBay). METHODS AND MATERIALS: We conducted a community-based cross-sectional survey among adults aged ≥ 35 years in the KrooBay community. Trained healthcare workers collected data on socio-demographic characteristics and self-reported health behaviours using the World Health Organization STEPwise surveillance questionnaire for chronic disease risk factors. Anthropometric, blood glucose, and blood pressure measurements were performed following standard procedures. Logistics regression was used for analysis and adjusted odd ratios with 95% confidence intervals were calculated to identify risk factors associated with hypertension. RESULTS: Of the 418 participants, 242 (57%) were females and those below the age of 45 years accounted for over half (55.3%) of the participants. The prevalence of smoking was 18.2%, alcohol consumption was 18.8%, overweight was 28.2%, obesity was 17.9%, physical inactivity was 81.5%, and inadequate consumption of fruits and vegetables was 99%. The overall prevalence of hypertension was 45.7% (95% CI 41.0-50.5%), systolic hypertension was 34.2% (95% CI 29.6-38.8%), diastolic blood pressure was 39.9% (95% CI 35.2-44.6), and participants with diabetes were 2.2% (95% CI 0.7-3.6%). Being aged ≥ 55 years (AOR = 7.35, 95% CI 1.49-36.39) and > 60 years (AOR 8.05; 95% CI 2.22-29.12), separated (AOR = 1.34; 95% 1.02-7.00), cohabitating (AOR = 6.68; 95% CL1.03-14.35), vocational (AOR = 3.65; 95% CI 1.81-7.39 ) and having a university education (AOR = 4.62; 95% CI 3.09-6.91) were found to be independently associated with hypertension. CONCLUSION: The prevalence of hypertension,and NCD risk factors was high among the residents of the Kroobay informal settlement. We also noted a low prevalence of diabetes. There is an urgent need for the implementation of health education, promotion, and screening initiatives to reduce health risks so that these conditions will not overwhelm health services.

Together with plague, smallpox and typhus, epidemics of dysentery have been a major scourge of human populations for centuries(1). A previous genomic study concluded that Shigella dysenteriae type 1 (Sd1), the epidemic dysentery bacillus, emerged and spread worldwide after the First World War, with no clear pattern of transmission(2). This is not consistent with the massive cyclic dysentery epidemics reported in Europe during the eighteenth and nineteenth centuries(1,3,4) and the first isolation of Sd1 in Japan in 1897(5). Here, we report a whole-genome analysis of 331 Sd1 isolates from around the world, collected between 1915 and 2011, providing us with unprecedented insight into the historical spread of this pathogen. We show here that Sd1 has existed since at least the eighteenth century and that it swept the globe at the end of the nineteenth century, diversifying into distinct lineages associated with the First World War, Second World War and various conflicts or natural disasters across Africa, Asia and Central America. We also provide a unique historical perspective on the evolution of antibiotic resistance over a 100-year period, beginning decades before the antibiotic era, and identify a prevalent multiple antibiotic-resistant lineage in South Asia that was transmitted in several waves to Africa, where it caused severe outbreaks of disease.

BACKGROUND: The term "developmental disability" (DD) is inconsistently defined and applied depending on purpose and across sources, including in legislation. OBJECTIVE: This project aimed to identify existing definitions of disability and DD and to determine the extent to which each definition could be operationalized to produce prevalence estimates using data from U.S. national surveys. METHODS: Using data among children <18 years from the 2016-2018 National Health Interview Survey (NHIS) and National Survey of Children's Health (NSCH), we estimated the prevalence of two definitions of disability (Washington Group Short Set on Functioning, American Community Survey) and seven definitions of DD [Health and Human Services (ever/current), Developmental Disabilities Assistance and Bill of Rights Act of 2000 (1+, 2+, or 3+ components), and Diagnostic and Statistical Manual of Mental Disorders, 5th ed (ever/current)]. Complex sample design variables and weights were used to calculate nationally representative prevalence. RESULTS: Disability (NHIS: 5.2-6.3%; NSCH: 9.2-11.9%) and DD prevalence (NHIS: 0.6-18.0% and NSCH: 0.2-22.2%) varied depending on the definition and data source. For the same definition, NSCH prevalence estimates tended to be higher than NHIS estimates. CONCLUSIONS: The substantial variability in estimated prevalence of disability and DD among children in the United States may be in part due to the surveys not representing all components of each definition. Different or additional questions in national surveys may better capture existing definitions of disability and DD. Considering the data collection goals may help determine the optimal definition to provide useful information for public health action.

BACKGROUND: In 2015, the World Health Organization recommended that all people living with HIV begin antiretroviral treatment (ART) regardless of immune status, a policy known as 'Treat-All to end AIDS', commonly referred to as Treat-All. Almost all low- and middle-income countries adopted this policy by 2019. This study describes how linkage to treatment of newly diagnosed persons changed between 2015 and 2018 and how complementary policies may have similarly increased linkage for 13 African countries. These countries adopted and implemented Treat-All policies between 2015 and 2018 and were supported by the U.S. Government's President's Emergency Plan for AIDS Relief (PEPFAR). The focuses of this research were to understand 1) linkage rates to ART initiation before and after the adoption of Treat-All in each country; 2) how Treat-All implementation differed across these countries; and 3) whether complementary policies (including same-day treatment initiation, task-shifting, reduced ART visits, and reduced ART pickups) implemented around the same time may have increased ART linkage. METHODS: HIV testing and treatment data were collected by PEPFAR country programs in 13 African countries from 2015 to 2018. These countries were chosen based on the completeness of policy data and availability of program data during the study period. Program data were used to calculate proxy linkage rates. These rates were compared relative to the Treat All adoption period and the adoption of complementary policies. RESULTS: The 13 countries experienced an average increase in ART linkage of 29.3% over the entire study period. In examining individual countries, all but two showed increases in linkage to treatment immediately after Treat All adoption. Across all countries, those that had adopted four or more complementary policies showed an average increased linkage of 39.8% compared to 13.9% in countries with fewer than four complementary policies. CONCLUSIONS: Eleven of 13 country programs examined in this study demonstrated an increase in ART linkage after Treat-All policy adoption. Increases in linkage were associated with complementary policies. When exploring new public health policies, policymakers may consider which complementary policies might also help achieve the desired outcome of the public health policy.

Numerous studies have assessed the efficacy of environmentally based control methods to suppress populations of the blacklegged tick (Ixodes scapularis Say), but few of these estimated the cost of control. We estimated costs for a range of tick control methods (including habitat management, deer exclusion or population reduction, broadcast of acaricides, and use of host-targeted acaricides) implemented singly or in combination and applied to a model community comprising 320 residential properties and parklands. Using the high end for cost ranges, tick control based on a single method was estimated to have mean annual costs per household in the model community ranging from $132 for treating only forest ecotone with a broadcast synthetic acaricide to kill host-seeking ticks (or $404 for treating all residential forested habitat) to >$2,000 for deployment of bait boxes (SELECT TCS) across all residential tick habitat to treat rodents topically with acaricide to kill infesting ticks. Combining different sets of multiple methods in an integrated tick management program placed the annual cost between $508 and 3,192 annually per household in the model community, underscoring the disconnect between what people in Lyme disease endemic areas say they are willing to pay for tick control (not more than $100-150 annually) and the actual costs for tick control. Additional barriers to implementing community-based tick management programs within residential communities are discussed.

Ferrets represent the preferred animal model for assessing the transmission potential of newly emerged zoonotic influenza viruses. However, heterogeneity among established experimental protocols and facilities across different laboratories may lead to variable results, complicating interpretation of transmission experimental data. Between 2018-2020, a global exercise was conducted by 11 participating laboratories to assess the range of variation in ferret transmission experiments using two common stock H1N1 influenza viruses that possess different transmission characteristics in ferrets. Inoculation route, dose, and volume were standardized, and all participating laboratories followed the same experimental conditions for respiratory droplet transmission, including a strict 1:1 donor:contact ratio. Additional host and environmental parameters likely to affect influenza transmission kinetics were monitored throughout. Overall transmission outcomes for both viruses across 11 laboratories were concordant, suggesting the robustness of the ferret model for zoonotic influenza risk assessment. To attain high confidence in identifying zoonotic influenza viruses with moderate-to-high or low transmissibility, our analyses support that as few as three but as many as five laboratories, respectively, would need to independently perform viral transmission experiments with concordant results. This exercise facilitates the development of a more homogenous protocol for ferret transmission experiments that are employed for the purposes of risk assessment.Competing Interest StatementThe authors have declared no competing interest.

Background Coronavirus disease 2019 (COVID-19), the respiratory disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in Wuhan, China and has since become pandemic. As part of initial response activities in the United States, enhanced contact investigations were conducted to enable early identification and isolation of additional cases and to learn more about risk factors for transmission.Methods Close contacts of nine early travel-related cases in the United States were identified. Close contacts meeting criteria for active monitoring were followed, and selected individuals were targeted for collection of additional exposure details and respiratory samples. Respiratory samples were tested for SARS-CoV-2 by real-time reverse transcription polymerase chain reaction (RT-PCR) at the Centers for Disease Control and Prevention.Results There were 404 close contacts who underwent active monitoring in the response jurisdictions; 338 had at least basic exposure data, of whom 159 had ≥1 set of respiratory samples collected and tested. Across all known close contacts under monitoring, two additional cases were identified; both secondary cases were in spouses of travel-associated case patients. The secondary attack rate among household members, all of whom had ≥1 respiratory sample tested, was 13% (95% CI: 4 – 38%).Conclusions The enhanced contact tracing investigations undertaken around nine early travel-related cases of COVID-19 in the United States identified two cases of secondary transmission, both spouses. Rapid detection and isolation of the travel-associated case patients, enabled by public awareness of COVID-19 among travelers from China, may have mitigated transmission risk among close contacts of these cases.Competing Interest StatementThe authors have declared no competing interest.Funding StatementNo external funding was sought or received.Author DeclarationsAll relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript.YesAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesData may be available upon reasonable request.

BACKGROUND: Transmission of respiratory pathogens such as SARS-CoV-2 depends on patterns of contact and mixing across populations. Understanding this is crucial to predict pathogen spread and the effectiveness of control efforts. Most analyses of contact patterns to date have focussed on high-income settings. METHODS: Here, we conduct a systematic review and individual-participant meta-analysis of surveys carried out in low- and middle-income countries and compare patterns of contact in these settings to surveys previously carried out in high-income countries. Using individual-level data from 28,503 participants and 413,069 contacts across 27 surveys we explored how contact characteristics (number, location, duration and whether physical) vary across income settings. RESULTS: Contact rates declined with age in high- and upper-middle-income settings, but not in low-income settings, where adults aged 65+ made similar numbers of contacts as younger individuals and mixed with all age-groups. Across all settings, increasing household size was a key determinant of contact frequency and characteristics, but low-income settings were characterised by the largest, most intergenerational households. A higher proportion of contacts were made at home in low-income settings, and work/school contacts were more frequent in high-income strata. We also observed contrasting effects of gender across income-strata on the frequency, duration and type of contacts individuals made. CONCLUSIONS: These differences in contact patterns between settings have material consequences for both spread of respiratory pathogens, as well as the effectiveness of different non-pharmaceutical interventions. FUNDING: This work is primarily being funded by joint Centre funding from the UK Medical Research Council and DFID (MR/R015600/1).

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

Prescribed burning is a major source of a fine particular matter, especially in the southeastern United States, and quantifying emissions from burning operations accurately is an integral part of ascertaining air quality impacts. For instance, a critical factor in calculating fire emissions is identifying fire activity information (e.g., location, date/time, fire type, and area burned) and prior estimations of prescribed fire activity used for calculating emissions have either used burn permit records or satellite-based remote sensing products. While burn permit records kept by state agencies are a reliable source, they are not always available or readily accessible. Satellite-based remote sensing products are currently used to fill the data gaps, especially in regional studies; however, they cannot differentiate prescribed burns from the other types of fires. In this study, we developed novel algorithms to distinguish prescribed burns from wildfires and agricultural burns in a satellite-derived product, Fire INventory from NCAR (FINN). We matched and compared the burned areas from permit records and FINN at various spatial scales: individual fire level, 4 km grid level, and state level. The methods developed in this study are readily usable for differentiating burn type, matching and comparing the burned area between two datasets at various resolutions, and estimating prescribed burn emissions. The results showed that burned areas from permits and FINN have a weak correlation at the individual fire level, while the correlation is much higher for the 4 km grid and state levels. Since matching at the 4 km grid level showed a relatively higher correlation and chemical transport models typically use grid-based emissions, we used the linear regression relationship between FINN and permit burned areas at the grid level to adjust FINN burned areas. This adjustment resulted in a reduction in FINN-burned areas by 34%. The adjusted burned area was then used as input to the BlueSky Smoke Modeling Framework to provide long-term, three-dimensional prescribed burning emissions for the southeastern United States. In this study, we also compared emissions from different methods (FINN or BlueSky) and different data sources (adjusted FINN or permits) to evaluate uncertainties of our emission estimation. The comparison results showed the impacts of the burned area, method, and data source on prescribed burning emission estimations. © 2023 by the authors.

The large amounts of opioids and the emergence of increasingly potent illicitly manufactured synthetic opioids circulating in the unregulated drug supply in North America and Europe are fueling not only the ongoing public health crisis of overdose deaths but also raise the risk of another type of disaster: deliberate opioid release with the intention to cause mass harm. Synthetic opioids are highly potent, rapidly acting, can cause fatal ventilatory depression, are widely available, and have the potential to be disseminated for mass exposure, for example, if effectively formulated, via inhalation or ingestion. As in many other chemical incidents, the health consequences of a deliberate release of synthetic opioid would manifest quickly, within minutes. Such an incident is unlikely, but the consequences could be grave. Awareness of the risk of this type of incident and preparedness to respond are required to save lives and reduce illness. Coordinated planning across the entire local community emergency response system is also critical. The ability to rapidly recognize the opioid toxidrome, education on personal protective actions, and training in medical management of individuals experiencing an opioid overdose are key components of preparedness for an opioid mass casualty incident.

Diaz et al. highlight the potential for severe airway reactivity and perioperative challenges when performing bronchoscopy and BAL in patients with EVALI, and Russell and Cevik stress the importance of ruling out infectious causes in these patients. These two points reflect the complexities of evaluating patients with EVALI and managing their care. Recent Centers for Disease Control and Prevention clinical guidance emphasizes that the decision to perform a bronchoscopy and BAL should be made on a case-by-case basis and in consultation with pulmonary specialists.1 Many patients with EVALI have required intubation and mechanical ventilation, and consultation with critical care specialists is also recommended.

BACKGROUND: Industrial chemicals are increasingly recognized as potential developmental neurotoxicants. Di(2-ethylhexyl) phthalate (DEHP), used to impart flexibility and temperature tolerance to polyvinylchloride, and bisphenol A (BPA), used to manufacture polycarbonate, are commonly present in medical devices. The magnitude of exposure in neonates during hospitalization for cardiac operations is unknown. METHODS: We quantified urinary concentrations of DEHP metabolites and BPA preoperatively and postoperatively in neonates undergoing cardiac operations and their mothers. Urinary concentrations of these biomarkers reflect recent exposures (half-lives are approximately 6 to 24 hours). Biomarker concentrations in mothers' and infants' preoperative and postoperative samples were compared. RESULTS: Operations were performed in 18 infants (mean age, 5 ± 4 [SD] days). The maternal sample was obtained on postpartum day 4 ± 4. The preoperative urine sample was obtained on day-of-life 4 ± 2 and the postoperative sample on day-of-life 6 ± 4. Mean maternal concentrations for DEHP metabolites and BPA were at the 50th percentile for females in the United States general population. Infant preoperative concentrations of 1 DEHP metabolite and BPA were significantly higher than maternal concentrations. Postoperative concentrations for all DEHP metabolites were significantly greater than preoperative concentrations. CONCLUSIONS: There is considerable perioperative exposure to DEHP and BPA for neonates undergoing cardiac operations. Infant concentrations for both BPA and DEHP metabolites were significantly higher than maternal concentrations, consistent with the infant's exposure to medical devices. Further study is needed to determine the potential role of these suspect neurotoxicants in the etiology of neurodevelopmental disability after cardiac operations.

This article summarizes what is currently known about the 2019 novel coronavirus and offers interim guidance.

A record number of 2,912 drug overdose deaths occurred in Maryland during the 12-month period July 1, 2020-June 30, 2021. Illicitly manufactured fentanyl, fentanyl analogs, or both* were involved in 84% of these deaths.(†) Timely identification of illicit drug market changes (e.g., fentanyl rapidly replacing heroin) could improve the public health response, specifically communications about risks for novel psychoactive substances. During November 19, 2021-August 31, 2022, the National Institute of Standards and Technology (NIST)(§) tested 496 deidentified drug paraphernalia samples that staff members collected at eight Maryland syringe services programs (SSPs), also known as needle exchange programs,(¶) in partnership with the Maryland Department of Health Center for Harm Reduction Services (CHRS).** All test results were available within 48 hours. Among the 496 paraphernalia samples collected, 367 (74.0%) tested positive for an opioid, and 364 (99.2%) of these samples contained fentanyl or fentanyl analogs. Approximately four fifths of fentanyl-positive samples also tested positive for the veterinary medicine xylazine, a sedative that when combined with opioids might increase the potential for fatal respiratory depression and soft tissue infections when injected (1). For 248 of the 496 samples, SSP participants also completed a questionnaire about the drugs they had intended to purchase. Among the 212 participants who had intended to buy an opioid, 87.7% were exposed to fentanyl, fentanyl analogs, or both, and 85.8% were unknowingly exposed to xylazine. Results improved awareness of fentanyl and xylazine among SSP staff members and galvanized efforts to enhance SSPs' wound care services for participants experiencing soft tissue injuries possibly associated with injecting xylazine. Rapid analysis of drug paraphernalia can provide timely data on changing illicit drug markets that can be used to mitigate the harms of drug use more effectively.

BACKGROUND: No rabies post-exposure prophylaxis (PEP) failure has been documented in humans in the United States using modern cell-culture vaccines. In January 2021, an 84-year-old male died from rabies six months after being bitten by a rabid bat despite receiving timely rabies post-exposure prophylaxis (PEP). We investigated the cause of breakthrough infection. METHODS: We reviewed medical records, laboratory results, and autopsy findings, and performed whole genome sequencing (WGS) to compare patient and bat virus sequences. Storage, administration, and integrity of PEP biologics administered to the patient were assessed; samples from leftover rabies immunoglobulin were evaluated for potency. We conducted risk assessments for persons potentially exposed to the bat and for close contacts of the patient. RESULTS: Rabies virus antibodies present in serum and cerebrospinal fluid were non-neutralizing. Antemortem blood testing revealed the patient had unrecognized monoclonal gammopathy of unknown significance. Autopsy findings showed rabies meningoencephalitis and metastatic prostatic adenocarcinoma. Rabies virus sequences from the patient and the offending bat were identical by WGS. No deviations were identified in potency, quality control, administration, or storage of administered PEP. Of 332 persons assessed for potential rabies exposure to the case patient, three (0.9%) warranted PEP. CONCLUSION: This is the first reported failure of rabies PEP in the Western Hemisphere using a cell culture vaccine. Host-mediated primary vaccine failure attributed to previously unrecognized impaired immunity is the most likely explanation for this breakthrough infection. Clinicians should consider measuring rabies neutralizing antibody titers after completion of PEP if there is any suspicion for immunocompromise.

Abstract Estuaries provide a suite of ecosystem services to people but are also under heavy stress from human development including excess nutrient loading and alterations in benthic habitat that affect nutrient cycling. Here we examine the interaction of two important and common ecosystem management priorities in estuaries: limiting eutrophication and restoration of submerged aquatic vegetation (SAV). Rates of benthic nitrogen processing can vary by habitat type and there is need for more complete data on the contribution of SAV to overall nitrogen cycling in estuaries, as well as a need to examine nitrogen cycling in situ to better characterize the role of SAV areal coverage in mediating estuarine eutrophication. We compare nitrogen cycling between two common and adjacent habitat types (SAV and adjacent bare sediment [BS]) in an index coastal estuary using an in situ chamber-based approach to better capture realized habitat differences. We also examined genomic community structure of sediment bacteria and archaea to identify biological indicators of nitrogen exchange. Both mean sediment–water exchange of dissolved N2 and microbial functional community structure differed between SAV and BS. Habitat differences were more consistent with lower variability at locations with low salinity and when sediment organic content was highest, which aligns with findings in other studies. Habitat types differed significantly in microbial composition, including functional groups and genes, like nifH, that may contribute to observed differences in nitrogen cycling. Overall, habitat type appeared most important to nitrogen cycling near the river mouth where sediment nitrogen was higher, and this information has implications for integrated management of habitat restoration/conservation and nutrient loading.

Age-related cognitive decline, a common component of the brain aging process, is associated with significant impairment in daily functioning and quality of life among geriatric adults. While the complexity of mechanisms underlying cognitive aging are still being elucidated, microbial exposure and the multifactorial inflammatory cascades associated with systemic infections are emerging as potential drivers of neurological senescence. The negative cognitive and neurobiological consequences of a single pathogen-associated inflammatory experience, such as that modeled through treatment with lipopolysaccharide (LPS), are well documented. Yet, the brain aging impacts of repeated, intermittent inflammatory challenges are less well studied. To extend the emerging literature assessing the impact of infection burden on cognitive function among normally aging mice, here, we repeatedly exposed adult mice to intermittent LPS challenges during the aging period. Male 10-month-old C57BL6 mice were systemically administered escalating doses of LPS once every two weeks for 2.5 months. We evaluated cognitive consequences using the non-spatial step-through inhibitory avoidance task, and both spatial working and reference memory versions of the Morris water maze. We also probed several potential mechanisms, including cortical and hippocampal cytokine/chemokine gene expression, as well as hippocampal neuronal function via extracellular field potential recordings. Though there was limited evidence for an ongoing inflammatory state in cortex and hippocampus, we observed impaired learning and memory and a disruption of hippocampal long-term potentiation. These data suggest that a history of intermittent exposure to LPS-induced inflammation is associated with subtle but significantly impaired cognition among normally aging mice. The broader impact of these findings may have important implications for standard of care involving infections in aging individuals or populations at-risk for dementia.

BACKGROUND: Children with congenital heart defects have an increased risk of neurodevelopmental disability. The impact of environmental chemical exposures during daily life on neurodevelopmental outcomes in toddlers with congenital heart defects is unknown. METHODS: This prospective study investigated the impacts of early childhood exposure to mixtures of environmental chemicals on neurodevelopmental outcomes after cardiac surgery. Outcomes were assessed at 18 months of age using The Bayley Scales of Infant and Toddler Development-III. Urinary concentrations of exposure biomarkers of pesticides, phenols, parabens, and phthalates, and blood levels of lead, mercury, and nicotine were measured at the same time point. Bayesian profile regression and weighted quantile sum regression were utilized to assess associations between mixtures of biomarkers and neurodevelopmental scores. RESULTS: One-hundred and forty infants were enrolled, and 110 (79%) returned at 18 months of age. Six biomarker exposure clusters were identified from the Bayesian profile regression analysis; and the pattern was driven by 15 of the 30 biomarkers, most notably 13 phthalate biomarkers. Children in the highest exposure cluster had significantly lower adjusted language scores by -9.41 points (95%CI: -17.2, -1.7) and adjusted motor scores by -4.9 points (-9.5, -0.4) compared to the lowest exposure. Weighted quantile sum regression modeling for the overall exposure-response relationship showed a significantly lower adjusted motor score ( = -2.8 points [2.5th and 97.5th percentile: -6.0, -0.6]). The weighted quantile sum regression index weights for several phthalates, one paraben, and one phenol suggest their relevance for poorer neurodevelopmental outcomes. CONCLUSIONS: Like other children, infants with congenital heart defects are exposed to complex mixtures of environmental chemicals in daily life. Higher exposure biomarker concentrations were associated with significantly worse performance for language and motor skills in this population.