Low CD4 Count or Being Out of Care Increases the Risk for Mpox Hospitalization Among People With Human Immunodeficiency Virus and Mpox.

Human immunodeficiency virus (HIV)-associated immunosuppression may increase the risk of hospitalization with mpox. Among persons diagnosed with mpox in the state of Georgia, we characterized the association between hospitalization with mpox and HIV status. People with HIV and a CD4 count <350 cells/mm3 or who were not engaged in HIV care had an increased risk of hospitalization.

Public Health Response to Clusters of Rapid HIV Transmission Among Hispanic or Latino Gay, Bisexual, and Other Men Who Have Sex with Men - Metropolitan Atlanta, Georgia, 2021-2022.

During February 2021-June 2022, the Georgia Department of Public Health (GDPH) detected five clusters of rapid HIV transmission concentrated among Hispanic or Latino (Hispanic) gay, bisexual, and other men who have sex with men (MSM) in metropolitan Atlanta. The clusters were detected through routine analysis of HIV-1 nucleotide sequence data obtained through public health surveillance (1,2). Beginning in spring 2021, GDPH partnered with health districts with jurisdiction in four metropolitan Atlanta counties (Cobb, DeKalb, Fulton, and Gwinnett) and CDC to investigate factors contributing to HIV spread, epidemiologic characteristics, and transmission patterns. Activities included review of surveillance and partner services interview data,† medical chart reviews, and qualitative interviews with service providers and Hispanic MSM community members. By June 2022, these clusters included 75 persons, including 56% who identified as Hispanic, 96% who reported male sex at birth, 81% who reported male-to-male sexual contact, and 84% of whom resided in the four metropolitan Atlanta counties. Qualitative interviews identified barriers to accessing HIV prevention and care services, including language barriers, immigration- and deportation-related concerns, and cultural norms regarding sexuality-related stigma. GDPH and the health districts expanded coordination, initiated culturally concordant HIV prevention marketing and educational activities, developed partnerships with organizations serving Hispanic communities to enhance outreach and services, and obtained funding for a bilingual patient navigation program with academic partners to provide staff members to help persons overcome barriers and understand the health care system. HIV molecular cluster detection can identify rapid HIV transmission among sexual networks involving ethnic and sexual minority groups, draw attention to the needs of affected populations, and advance health equity through tailored responses that address those needs.

Barriers and Facilitators to HIV Service Access among Hispanic/Latino Gay, Bisexual, and Other Men Who Have Sex with Men in Metropolitan Atlanta-a Qualitative Analysis.

Hispanic/Latino persons are disproportionately impacted by HIV in the US, and HIV diagnoses among Hispanic/Latino men in Georgia have increased over the past decade, particularly in metropolitan Atlanta. In 2022, the Georgia Department of Public Health detected five clusters of rapid HIV transmission centered among Hispanic/Latino gay, bisexual, and other men who have sex with men (HLMSM) in metropolitan Atlanta. We conducted in-depth interviews with 65 service providers and 29 HLMSM to identify barriers and facilitators to HIV service access for HLMSM. Interviews were audio recorded, transcribed, and translated, if needed. Initial data analyses were conducted rapidly in the field to inform public health actions. We then conducted additional analyses including line-by-line coding of the interview transcripts using a thematic analytic approach. We identified four main themes. First, inequity in language access was a predominant barrier. Second, multiple social and structural barriers existed. Third, HLMSM encountered intersectional stigma. Finally, the HLMSM community is characterized by its diversity, and there is not a one-size-fits-all approach to providing appropriate care to this population. The collection of qualitative data during an HIV cluster investigation allowed us to quickly identity barriers experienced by HLMSM when accessing HIV and other medical care, to optimize public health response and action. Well-designed program evaluation and implementation research may help elucidate specific strategies and tools to reduce health disparities, ensure equitable service access for HLMSM, and reduce HIV transmission in this population.

Treatment Guideline Nonadherence Pretransport Associated With Need for Higher Level of Care in Children Transferred to a Pediatric Tertiary Care Center for Status Epilepticus.

OBJECTIVES: We sought to investigate the association between adherence to the American Epilepsy Society (AES) 2016 guidelines for management of convulsive status epilepticus (SE) and clinical outcomes among children requiring interhospital transport for SE. We hypothesized that pretransport guideline nonadherence would be associated with needing higher level of care posttransfer. METHODS: This was a retrospective cohort study of children aged 30 days to 18 years transferred to our pediatric tertiary center from 2017 to 2019 for management of SE. Their care episodes were classified as 2016 American Epilepsy Society guideline adherent or nonadherent. There were 40 referring hospitals represented in this cohort. RESULTS: Of 260 care episodes, 55 (21%) were guideline adherent, 184 (71%) were guideline nonadherent, and 21 (8%) had insufficient data to determine guideline adherence. Compared with the adherent group, patients in the nonadherent care group had longer hospitalizations (32 hours [17-68] vs 21 hours [7-48], P = 0.006), were more likely to require intensive care unit admission (47% vs 31%), and less likely to be discharged home from the emergency department (16% vs 35%; χ 2 test, P = 0.01). Intubation rates did not differ significantly between groups (25% vs 18%, P = 0.37). When we fit a multivariable model to adjust for confounding variables, guideline nonadherence was associated with need for higher level of care (odds ratio, 2.04; 95% confidence interval, 1.04-3.99). Treatment guideline adherence did not improve over the 3-year study period (2017: 22%, 2018: 19%, 2019: 29% [χ 2 test for differences between any 2 years, P = 0.295]). CONCLUSIONS: Guideline nonadherence pretransport was associated with longer hospitalizations and need for higher level of care among children transferred for SE at our institution. These findings suggest a need to improve SE guideline adherence through multifaceted quality improvement efforts targeting both the prehospital and community hospital settings.

Epidemiologic and Clinical Characteristics of Monkeypox Cases - United States, May 17-July 22, 2022.

Monkeypox, a zoonotic infection caused by an orthopoxvirus, is endemic in parts of Africa. On August 4, 2022, the U.S. Department of Health and Human Services declared the U.S. monkeypox outbreak, which began on May 17, to be a public health emergency (1,2). After detection of the first U.S. monkeypox case), CDC and health departments implemented enhanced monkeypox case detection and reporting. Among 2,891 cases reported in the United States through July 22 by 43 states, Puerto Rico, and the District of Columbia (DC), CDC received case report forms for 1,195 (41%) cases by July 27. Among these, 99% of cases were among men; among men with available information, 94% reported male-to-male sexual or close intimate contact during the 3 weeks before symptom onset. Among the 88% of cases with available data, 41% were among non-Hispanic White (White) persons, 28% among Hispanic or Latino (Hispanic) persons, and 26% among non-Hispanic Black or African American (Black) persons. Forty-two percent of persons with monkeypox with available data did not report the typical prodrome as their first symptom, and 46% reported one or more genital lesions during their illness; 41% had HIV infection. Data suggest that widespread community transmission of monkeypox has disproportionately affected gay, bisexual, and other men who have sex with men and racial and ethnic minority groups. Compared with historical reports of monkeypox in areas with endemic disease, currently reported outbreak-associated cases are less likely to have a prodrome and more likely to have genital involvement. CDC and other federal, state, and local agencies have implemented response efforts to expand testing, treatment, and vaccination. Public health efforts should prioritize gay, bisexual, and other men who have sex with men, who are currently disproportionately affected, for prevention and testing, while addressing equity, minimizing stigma, and maintaining vigilance for transmission in other populations. Clinicians should test patients with rash consistent with monkeypox,† regardless of whether the rash is disseminated or was preceded by prodrome. Likewise, although most cases to date have occurred among gay, bisexual, and other men who have sex with men, any patient with rash consistent with monkeypox should be considered for testing. CDC is continually evaluating new evidence and tailoring response strategies as information on changing case demographics, clinical characteristics, transmission, and vaccine effectiveness become available.§.

Magnetic Ranking Cytometry: Profiling Rare Cells at the Single-Cell Level.

Cellular heterogeneity in biological systems presents major challenges in the diagnosis and treatment of disease and also complicates the deconvolution of complex cellular phenomena. Single-cell analysis methods provide information that is not masked by the intrinsic heterogeneity of the bulk population and can therefore be applied to gain insights into heterogeneity among different cell subpopulations with fine resolution. Over the last 5 years, an explosion in the number of single-cell measurement methods has occurred. However, most of these methods are applicable to pure populations of cultured cells and are not able to handle high levels of phenotypic heterogeneity or a large background of nontarget cells. Microfluidics is an attractive tool for single cell manipulation as it enables individual encasing of single cells, allowing for high-throughput analysis with precise control of the local environment. Our laboratory has developed a new microfluidics-based analytical strategy to meet this unmet need referred to as magnetic ranking cytometry (MagRC). Cells expressing a biomarker of interest are labeled with receptor-coated magnetic nanoparticles and isolated from nontarget cells using a microfluidic device. The device ranks the cells according to the level of bound magnetic nanoparticles, which corresponds to the expression level of a target biomarker. Over the last several years, two generations of MagRC devices have been developed for different applications. The first-generation MagRC devices are powerful tools for the quantitation and analysis of rare cells present in heterogeneous samples, such as circulating tumor cells, stem cells, and pathogenic bacteria. The second-generation MagRC devices are compatible with the efficient recovery of cells sorted on the basis of protein expression and can be used to analyze large populations of cells and perform phenotypic CRISPR screens. To improve analytical precision, newer iterations of the first-generation and second-generation MagRC devices have been integrated with electrochemical sensors and Hall effect sensors, respectively. Both generations of MagRC devices permit the isolation of viable cells, which sets the stage for a wide range of applications, such as generating cell lines from rare cells and in vitro screening for effective therapeutic interventions in cancer patients to realize the promise of personalized medicine. This Account summarizes the development and application of the MagRC and describes a suite of advances that have enabled single-cell tumor cell analysis and monitoring tumor response to therapy, stem cell analysis, and detection of pathogens.

Use of mid-upper arm circumference to screen for thinness among sub-Saharan African male detainees.

OBJECTIVE: BMI is a time-intensive measurement to assess nutritional status. Mid-upper arm circumference (MUAC) has been studied as a proxy for BMI in adults, but there is no consensus on its optimal use. DESIGN: We calculated sensitivity, specificity and area under receiver operating characteristic curve (AUROCC) of MUAC for BMI < 18·5, <17 and <16 kg/m2. We designed a system using two MUAC cut-offs, with a healthy (non-thin) 'green' group, a 'yellow' group requiring BMI measurement and a 'red' group who could proceed directly to treatment for thinness. SETTING: We retrospectively analysed monitoring data collected by the International Committee of the Red Cross in places of detention. PARTICIPANTS: 11 917 male detainees in eight African countries. RESULTS: MUAC had excellent discriminatory ability with AUROCC: 0·87, 0·90 and 0·92 for BMI < 18·5, BMI < 17 and BMI < 16 kg/m2, respectively. An upper cut-off of MUAC 25·5 cm to exclude healthy detainees would result in 64 % fewer detainees requiring BMI screening and had sensitivity 77 % (95 % CI 69·4, 84·7) and specificity 79·6 % (95 % CI 72·6, 86·5) for BMI < 18·5 kg/m2. A lower cut-off of MUAC < 21·0 cm had sensitivity 25·4 % (95 % CI 11·7, 39·1) and specificity 99·0 % (95 % CI 97·9, 100·0) for BMI < 16 kg/m2. An additional 50 kg weight requirement improved specificity to 99·6 % (95 % CI 99·0, 100·0) with similar sensitivity. CONCLUSIONS: A MUAC cut-off of 25·5 cm, above which detainees are classified as healthy and below receive further screening, would result in significant time savings. A cut-off of <21·0 cm and weight <50 kg can identify some detainees with BMI < 16 kg/m2 who require immediate treatment.

Acute and Delayed Deaths after West Nile Virus Infection, Texas, USA, 2002-2012.

Infection with West Nile virus (WNV) has a well-characterized acute disease process. However, long-term consequences are less understood. We searched death records for 4,142 residents of Texas, USA, infected with WNV during 2002-2012 and identified 557 (13%) deaths. We analyzed all-cause and cause-specific deaths after WNV infection by calculating standardized mortality ratios and using statewide mortality data. Acute-phase deaths (<90 days after symptom onset) occurred in 289 (7%) of case-patients; of those deaths, 289 (92%) were cases of West Nile neuroinvasive disease (WNND). Convalescent-phase deaths (>90 days after symptom onset) occurred in 268 (7%) of the remaining 3,853 case-patients; 210 (78%) of these deaths occurred in patients with WNND. Convalescent-phase WNND case-patients showed excess deaths from infectious and renal causes; case-patients <60 years of age had increased risk for all-cause death, specifically from renal, infectious, digestive, and circulatory causes. We provide population-level evidence of increased risk for death after WNV infection resulting in WNND.

Maternal, fetal, and perinatal outcomes among pregnant women admitted to an Ebola treatment center in the Democratic Republic of Congo, 2018-2020.

OBJECTIVE: This study aims to investigate maternal, fetal, and perinatal outcomes during the 2018-2020 Ebola outbreak in Democratic Republic of Congo (DRC). METHODS: Mortality between pregnant and non-pregnant women of reproductive age admitted to DRC's Mangina Ebola treatment center (ETC) were compared using propensity score matching. Propensity scores were calculated using age, initial Ebola viral load, Ebola vaccination status, and investigational therapeutic. Additionally, fetal and perinatal outcomes of pregnancies were also described. RESULTS: Twenty-seven pregnant women were admitted to the Mangina ETC during December 2018-January 2020 among 162 women of childbearing age. We found no evidence of increase mortality among pregnant women compared to non-pregnant women (relative risk:1.0, 95%CI: 0.58-1.72). Among surviving mothers, pregnancy outcomes were poor with at least 58% (11/19) experiencing loss of pregnancy while 16% (3/19) were discharged with viable pregnancy. Two mothers with viable pregnancies were vaccinated, and all received investigational therapeutics. Two live births occurred, with one infant surviving after the infant and mother received an investigational post-exposure prophylaxis and Ebola therapeutic respectively. CONCLUSIONS: Pregnancy was not associated with increased mortality among women with EVD in the Mangina ETC. Fetal and perinatal outcomes remained poor in pregnancies complicated by EVD, though novel therapeutics may have potential for improving these outcomes.

Perceived Benefits and Barriers of a COVID-19 Test to Stay Program in a School District Serving Black or African American People With Low Income, December 2021.

OBJECTIVES: Quarantine after exposure to COVID-19 has resulted in substantial loss of in-person learning in schools from prekindergarten through grade 12. Test to Stay (TTS), a strategy that limits the spread of SARS-CoV-2 while prioritizing in-person learning, requires substantial investment in resources. The objective of this study was to assess the perceived benefits, barriers, and facilitators of implementing TTS in an urban school district in the Midwest serving primarily Black or African American people with low income. METHODS: In December 2021, we used a concurrent mixed-methods approach to understand perceived benefits, barriers, and facilitators of implementing TTS by combining quantitative analysis of telephone surveys conducted with parents (n = 124) and a qualitative inquiry involving key informants from the school district and local health department (n = 22). We analyzed quantitative data using descriptive statistics. We used thematic analysis to analyze qualitative data. RESULTS: Quantitative findings showed that parents supported TTS because it was convenient (n = 83, 97%) and effective (n = 82, 95%) in keeping students learning in person (n = 82, 95%) and preventing the spread of COVID-19 (n = 80, 93%). Qualitative interviews with informants found that having a clear protocol and assigning staff to specified tasks allowed for successful TTS implementation. However, insufficient staffing and testing resources, parent mistrust of testing, and lack of communication from schools were perceived barriers. CONCLUSION: The school community strongly supported TTS despite the many implementation challenges faced. This study emphasized the importance of ensuring resources for equitable implementation of COVID-19 prevention strategies and the critical role of communication.

A traumatic pandemic: High acuity pediatric trauma in the COVID19 era.

OBJECTIVE: Gaps remain in our understanding on how COVID19 affects trends in pediatric trauma, the leading cause of mortality and morbidity during childhood and adolescence. METHODS: We compared high acuity trauma visits (requiring admission, surgery, or fatality) presenting between March through February 2021 to corresponding months in 2017-2019. We evaluated the differences in mechanisms of injury, age, and Area Deprivation Index (ADI), a measure of socioeconomic disadvantage, during this time period. Data were analyzed using longitudinal time series analyses and t-tests. RESULTS: Of 687 traumas presenting from March 2020 through February 2021, 322 were high acuity traumas. High acuity traumas declined significantly to a nadir of 16 in April 2020. High acuity traumas increased and surpassed previous years to a peak of 40 visits in August 2020 and from October through December 2020. There were more visits for high acuity assaults and confirmed or suspected physical child abuse but fewer for falls, drownings, and motor vehicle accidents from March to August 2020 and from October through December 2020 compared to prior years. High acuity assaults and physical child abuse cases on average were from the most disadvantaged areas, and physical child abuse patients were younger during the peak of the Pandemic compared to Pre-Pandemic months. CONCLUSION: This analysis provides insight into how the COVID19 pandemic has affected high acuity trauma in an inner-city pediatric population. Findings may be used to guide public health measures on safety and injury prevention as the pandemic continues.

Ultrathroughput immunomagnetic cell sorting platform.

High-throughput phenotypic cell sorting is critical to the development of cell-based therapies and cell screening discovery platforms. However, current cytometry platforms are limited by throughput, number of fractionated populations that can be isolated, cell viability, and cost. We present an ultrathroughput microfluidic cell sorter capable of processing hundreds of millions of live cells per hour per device based on protein expression. This device, a next-generation microfluidic cell sorter (NG-MICS), combines multiple technologies, including 3D printing, reversible clamp sealing, and superhydrophobic treatments to create a reusable and user-friendly platform ready for deployment. The utility of such a platform is demonstrated through the rapid isolation of mature natural killer cells from peripheral blood mononuclear cells, for use in CAR-NK therapies at clinically-relevant scale.

Rapid On-Cell Selection of High-Performance Human Antibodies.

Phage display is a critical tool for developing antibodies. However, existing approaches require many time-consuming rounds of biopanning and screening of potential candidates due to a high rate of failure during validation. Herein, we present a rapid on-cell phage display platform which recapitulates the complex in vivo binding environment to produce high-performance human antibodies in a short amount of time. Selection is performed in a highly stringent heterogeneous mixture of cells to quickly remove nonspecific binders. A microfluidic platform then separates antigen-presenting cells with high throughput and specificity. An unsupervised machine learning algorithm analyzes sequences of phage from all pools to identify the structural trends that contribute to affinity and proposes ideal candidates for validation. In a proof-of-concept screen against human Frizzled-7, a key ligand in the Wnt signaling pathway, antibodies with picomolar affinity were discovered in two rounds of selection that outperformed current gold-standard reagents. This approach, termed µCellect, is low cost, high throughput, and compatible with a wide variety of cell types, enabling widespread adoption for antibody development.

Genome-wide in vivo screen of circulating tumor cells identifies SLIT2 as a regulator of metastasis.

Circulating tumor cells (CTCs) break free from primary tumors and travel through the circulation system to seed metastatic tumors, which are the major cause of death from cancer. The identification of the major genetic factors that enhance production and persistence of CTCs in the bloodstream at a whole genome level would enable more comprehensive molecular mechanisms of metastasis to be elucidated and the identification of novel therapeutic targets, but this remains a challenging task due to the heterogeneity and extreme rarity of CTCs. Here, we describe an in vivo genome-wide CRISPR knockout screen using CTCs directly isolated from a mouse xenograft. This screen elucidated SLIT2-a gene encoding a secreted protein acting as a cellular migration cue-as the most significantly represented gene knockout in the CTC population. SLIT2 knockout cells are highly metastatic with hypermigratory and mesenchymal phenotype, resulting in enhanced cancer progression in xenograft models.

Epilepsy related multimorbidity, polypharmacy and risks in adults with intellectual disabilities: a national study.

BACKGROUND: A quarter of people with Intellectual Disability (ID) in the UK have epilepsy compared to 0.6% in the general population and die much younger. Epilepsy is associated with two-fifths of all deaths with related polypharmacy and multi-morbidity. Epilepsy research on this population has been poor. This study describes real-world clinical and risk characteristics of a large cohort across England and Wales. METHODS: A retrospective multi-centre cohort study was conducted. Information on seizure characteristics, ID severity, relevant co-morbidities, psychotropic and antiseizure drugs (ASDs), SUDEP and other risk factors was collected across a year. RESULTS: Of 904 adults across 10 centres (male:female, 1.5:1), 320 (35%) had mild ID and 584 (65%) moderate-profound (M/P) ID. The mean age was 39.9 years (SD 15.0). Seizures were more frequent in M/P ID (p < 0.001). Over 50% had physical health co-morbidities, more in mild ID (p < 0.01). A third had psychiatric co-morbidity and a fifth had an underlying genetic disorder. Autism Spectrum Disorder was seen in over a third (37%). Participants were on median two ASDs and overall, five medications. Over quarter were on anti-psychotics. Over 90% had an epilepsy review in the past year but 25% did not have an epilepsy care plan, particularly those with mild ID (p < 0.001). Only 61% had a documented discussion of SUDEP, again less likely with mild ID or their care stakeholders (p < 0.001). CONCLUSIONS: Significant levels of multi-morbidity, polypharmacy and a lack of systemised approach to treatment and risk exist. Addressing these concerns is essential to reduce premature mortality.

High-throughput genome-wide phenotypic screening via immunomagnetic cell sorting.

Genome-scale functional genetic screens are used to identify key genetic regulators of a phenotype of interest. However, the identification of genetic modifications that lead to a phenotypic change requires sorting large numbers of cells, which increases operational times and costs and limits cell viability. Here, we introduce immunomagnetic cell sorting facilitated by a microfluidic chip as a rapid and scalable high-throughput method for loss-of-function phenotypic screening using CRISPR-Cas9. We used the method to process an entire genome-wide screen containing more than 108 cells in less than 1 h-considerably surpassing the throughput achieved by fluorescence-activated cell sorting, the gold-standard technique for phenotypic cell sorting-while maintaining high levels of cell viability. We identified modulators of the display of CD47, which is a negative regulator of phagocytosis and an important cell-surface target for immuno-oncology drugs. The top hit of the screen, the glutaminyl cyclase QPCTL, was validated and shown to modify the N-terminal glutamine of CD47. The method presented could bridge the gap between fluorescence-activated cell sorting and less flexible yet higher-throughput systems such as magnetic-activated cell sorting.