INTRODUCTION: Differentiated service delivery (DSD) models aim to tailor health services delivery to clients' preferences and clinical characteristics while reducing the burden on health systems. In Uganda, DSD models developed for HIV care were adapted to the tuberculosis (TB) services context to mitigate disruptions from the COVID-19 pandemic and inform national efforts to improve TB care. METHODS: Beginning in April 2021, four facility-based and five community-based DSD models were implemented in 28 TB clinics in Kampala and Soroti Regions. All clients in the intensive (months 1-2) and continuation (months 3-6) phases of treatment were eligible. Client preference and clinician concurrence determined model choice. All models allowed TB medication dispensing intervals ranging from biweekly to multi-month dispensing (MMD; ≥ 2 months). Data abstracted in December 2022 from TB registers and DSD enrolment tracking tools at 21 of 28 implementing facilities were used to evaluate the intervention. The TB treatment success rate (i.e. proportion cured or who completed treatment, vs. those who died, failed, were lost-to-follow-up or had no recorded outcome) in the DSD cohort was compared to facilities' 2018-2019 results using Fischer's exact test. RESULTS: Most facilities offered one (Kampala) or two (Soroti) facility-based models and one community-based model. Among 1864 TB clients enrolled between April 2021 and March 2022, 1822 (97.7%) used ≥ 1 DSD models; 210/1822 (11.5%) ever switched models. Overall, 70.5% (1284/1822) of clients enrolled in ≥ 1 facility-based model and 40.5% (737/1822) in ≥ 1 community-based model. The use of community-based models increased during the continuation phase. Facility-Based Individual Management and Home Delivery were the most-used models. In the intensive phase, the longest medication dispensation interval was biweekly for 50.0% of patients, monthly for 41.3% and MMD for 8.8%. During the continuation phase, the longest interval was biweekly for 0.6%, monthly for 71.7% and MMD for 27.6%. Overall, 1582/1864 (84.9%) clients were successfully treated, compared to 858/1177 (72.9%) in 2018-2019 (p < 0.001). Seven (0.4%) patients failed treatment, 32 (1.7%) were lost to follow-up, 101 (5.4%) died and 142 (7.6%) were not evaluated. CONCLUSIONS: TB DSD models were successfully implemented. TB treatment outcomes under DSD compared favourably to historical outcomes. Investigating factors affecting MMD use and model choice could further inform programme design.

Several essential vitamins and minerals whose deficiencies are associated with metabolic and functional disorders, including increased morbidity and mortality from both communicable and non-communicable diseases, are not being adequately addressed by large-scale, public health nutrition programs worldwide. These neglected micronutrients include thiamine, riboflavin, niacin, pyridoxine, vitamin B(12), vitamin D, vitamin K, calcium, selenium, and possibly others. In this narrative review, our objectives are to describe briefly the health implications of each of these deficiencies, summarize the limited available information on their epidemiology, and suggest possible approaches to address them. We conclude that more information, based on dietary assessments, nutritional biomarker surveys, and systematic surveillance of associated health conditions, is needed. Appropriate intervention programs, including changes in food systems to provide wider access to nutrient-rich foods, food fortification and targeted supplementation, should be implemented in settings where these deficiencies are confirmed.

The purpose of this study was to determine the feasibility of facility-level wastewater surveillance in the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in skilled nursing facility (SNF) wastewater using three concentration methods, as well as a proof-of-concept for antimicrobial resistance (AR) genes/organisms detection. Wastewater effluent samples were collected from an SNF over an 8-week period. Wastewater was concentrated using electronegative membrane filtration (enMF), polyethylene glycol precipitation, and Nanotrap(®) magnetic virus particles (NP). Quantification of the genome copy concentration from SARS-CoV-2 and bovine respiratory syncytial virus (BRSV), a SARS-CoV-2 surrogate spiked into all samples, was performed with droplet digital polymerase chain reaction (ddPCR). Wastewater sample aliquots were also enriched in microbiological culture media and screened for organisms with AR phenotypes on selective and differential agars. Multiplex real-time PCR was used to detect a broad array of carbapenem resistance genes. SARS-CoV-2 was detected and quantified from a single enMF-concentrated wastewater sample. The highest concentration of BRSV came from enMF-concentrated samples. Klebsiella, Enterobacter, Citrobacter, and Escherichia coli exhibiting AR phenotypes were successfully detected using culture-dependent approaches. Culture-independent, multiplex PCR indicated that bla(KPC) was the main carbapenemase gene detected in wastewater samples. Facility-level wastewater surveillance could be a useful strategy for SNFs.

Preliminary experimentation has suggested that a research-use-only real-time transcription-mediated amplification assay for Treponema pallidum (RUO T. pallidum TMA) yields instances of T. pallidum nucleic acid detection that coincide with non-treponemal serology in men who have sex with men (MSM) at increased risk for sexually transmitted infection. To further characterize the specificity of RUO T. pallidum TMA testing, 3,586 rectal swab specimens reported as "not detected" by the assay generated a mean endpoint FAM fluorescence of 637.5 units. Introduction of Treponema denticola, Treponema phagedenis, and Treponema refringens nucleic acid into matrices generated mean endpoint FAM fluorescence ranging from 620.7 to 633.5 units (P ≥ 0.15 versus control). Introduction of lubricant to a pooled rectal swab matrix did not result in elevated FAM fluorescence (mean endpoint value 628.3 units [95% CI 612.0, 644.6]; P = 0.67). Introduction of talcum powder, urine, seminal fluid, and blood also failed to generate increased FAM fluorescence (P ≥ 0.20). Analytic sensitivity assessment was measured by serial 10-fold dilution of T. pallidum whole organism or in vitro 23S rRNA transcript in specimen transport medium or pooled rectal swab matrix and interrogation by the assay. Probit analysis estimated sensitivity (95% detection) of RUO T. pallidum TMA at 421-5,707 in vitro transcript copies/mL and 9-48 T. pallidum cells/mL, depending on dilution matrix. These results support RUO T. pallidum TMA as a highly sensitive method for T. pallidum detection that is not impacted by potentially cross-reactive organisms or interfering substances and may have adjunctive diagnosis capability for syphilis in MSM. IMPORTANCE: Research-use-only Treponema pallidum transcription-mediated amplification (RUO T. pallidum TMA) has the potential to improve laboratory diagnosis of syphilis, particularly in patients at increased risk for sexually transmitted infection. The high analytic sensitivity and lack of cross-reactivity of the assay can facilitate other laboratories exploring the use of the test in a research setting.

OBJECTIVE: Longer-acting pre-exposure prophylaxis (LA-PrEP) products have potential to increase PrEP uptake and continuation. This study sought to elicit preferences for LA-PrEP product and delivery program characteristics among populations disproportionately impacted by HIV to identify factors important to adoption and anticipate potential use challenges. DESIGN: Cross-sectional, online discrete choice experiment. METHODS: We recruited 940 men who have sex with men (MSM), people who inject drugs (PWID), and Black heterosexual men and women (BHMW) with PrEP indications. In a series of 10 tasks, participants chose between two hypothetical LA-PrEP options composed of 5 attributes (product type, side effects, clinic type, appointment duration, cost), or neither (their current HIV prevention method). Analysis used random-parameters logit models. RESULTS: Respondents chose an LA-PrEP method over their current HIV prevention option in 96.8% of tasks. Cost was the most important determinant of LA-PrEP choice for all populations (relative importance [RI] of 10]. Side effects and product type were 1/3 to 1/2 as important as cost (RI 3.5-5.1). MSM and PWID most preferred the 12-month implant followed by semiannual dual injections and least preferred the monthly oral pill and 2-month single injection. BHMW most preferred the monthly pill and semiannual injections and least preferred the 12-month implant and 2-month injection. Clinic type and appointment duration had minimal influence (RI 0.1-2.1). CONCLUSIONS: Results suggest high demand for LA-PrEP among populations with disproportionately high HIV incidence. To facilitate use, programs should offer a range of LA-PrEP products, minimize out-of-pocket costs, and counsel on side effects.

BACKGROUND: We calculated prevalences of birth defects among infants of participants in the Centers for Disease Control and Prevention's (CDC) COVID-19 Vaccine Pregnancy Registry (C19VPR). METHODS: C19VPR enrolled women receiving COVID-19 vaccines ≤ 30 days before the last menstrual period or during pregnancy from December 2020 through June 2021. We included 19,931 participants with singleton pregnancies ending ≥ 20 weeks' gestation who did not report COVID-19 illness during pregnancy. Clinicians identified birth defects from participant-reported infant health information up to 4 months after birth. We compared C19VPR birth defect prevalences to published pre-pandemic estimates. For seven defects originating during embryogenesis (cleft lip with/without cleft palate, atrial septal defect, coarctation of the aorta, ventricular septal defect, esophageal atresia or stenosis, hypospadias, kidney agenesis/hypoplasia/dysplasia), we estimated prevalence ratios comparing those vaccinated < 14 weeks' to those vaccinated ≥ 14 weeks' gestation. RESULTS: Participants reported receiving Pfizer-BioNTech vaccines (59.0%), Moderna (38.2%), and Janssen (2.8%) vaccines. Most (65.2%) participants received their first COVID-19 vaccine after the first trimester. The prevalence of major birth defects was 3.8%. Among defects with comparator estimates available (n = 50), 35 were below or within expected ranges. C19VPR prevalences were higher than the comparator confidence interval for 15 defects; however, C19VPR confidence intervals included comparator estimates. Prevalences did not differ by the timing of vaccination for seven defects examined. CONCLUSIONS: Birth defects prevalence estimates among infants born to women receiving COVID-19 vaccines during or just prior to pregnancy were generally similar to pre-pandemic estimates. While there was no strong evidence of associations between vaccination and specific defects, statistical power was low.

Advanced molecular detection (AMD) refers to the integration of next-generation sequencing, epidemiologic, and bioinformatics data to drive public health actions. As new AMD technologies emerge, it is critical to ensure those methods are used in communities that are most affected by disease-induced illness and death. We describe strategies and opportunities for using AMD approaches to improve health in those communities, which include improving access to pathogen sequencing, increasing data linkages, and using pathogen sequencing for those diseases where sequencing technologies can provide the best health outcome. Such strategies can help address and prevent differences in health outcomes in various populations, such as rural and tribal communities, persons with underlying health issues, and other populations that experience higher risks for infectious disease.

BACKGROUND: Split-hand/foot malformation (SHFM) is a rare, genetically heterogeneous, congenital limb defect. Some but not all associated genes are known; therefore, the aim was to identify genes underlying SHFM. METHODS: Buccal cell-derived DNA from 26 children with SHFM and their parents who participated in the National Birth Defects Prevention Study was exome sequenced. Family-based trio analyzes prioritized rare coding variants by inheritance patterns, predicted pathogenicity, and location within putative limb development genes. Copy-number variants in SHFM candidate genomic regions were also examined. Case-control analyzes compared coding variants between case children and 1191 controls (parents of children with non-limb birth defects). Variant validation was by Sanger sequencing or droplet digital polymerase chain reaction. RESULTS: In family-based analyzes, the prioritized and validated variants (each in a single family) included likely damaging variants that were heterozygous and de novo in speckle type BTB/POZ protein (SPOP) and ubiquitin-like modifier activating enzyme 2 (UBA2), X-linked recessive in fibroblast growth factor 13 (FGF13) and RNA binding motif protein 10 (RBM10), and compound heterozygous in interleukin enhancer binding factor 3 (ILF3). Validation assays did not confirm predicted de novo copy-number gains at chromosomes 10q24 and 19p13.11. Case-control analyzes did not identify statistically significant associations. CONCLUSION: Exome analysis nominated new susceptibility genes (FGF13, ILF3, RBM10, SPOP) and detected a variant in a known candidate gene (UBA2). Follow-up investigation is needed to ascertain damaging variants in these genes in additional cases with SHFM and evaluate the impact of the variants on gene expression, protein function, and limb development.

BACKGROUND: Brain infections pose substantial challenges in diagnosis and management and carry high mortality and morbidity, especially in low-income and middle-income countries. We aimed to improve the diagnosis and early management of patients admitted to hospital (adults aged 16 years and older and children aged >28 days) with suspected acute brain infections at 13 hospitals in Brazil, India, and Malawi. METHODS: With hospital stakeholders, policy makers, and patient and public representatives, we co-designed a multifaceted clinical and laboratory intervention, informed by an evaluation of routine practice. The intervention, tailored for each setting, included a diagnostic and management algorithm, a lumbar puncture pack, a testing panel, and staff training. We used multivariable logistic regression and interrupted time series analysis to compare the coprimary outcomes-the percentage of patients achieving a syndromic diagnosis and the percentage achieving a microbiological diagnosis before and after the intervention. The study was registered at ClinicalTrials.gov (NCT04190303) and is complete. FINDINGS: Between Jan 5, 2021, and Nov 30, 2022, we screened 10 462 patients and enrolled a total of 2233 patients at 13 hospital sites connected to the four study centres in Brazil, India, and Malawi. 1376 (62%) were recruited before the intervention and 857 (38%) were recruited after the intervention. 2154 patients (96%) had assessment of the primary outcome (1330 [62%] patients recruited pre-intervention and 824 [38%] recruited post-intervention). The median age across centres was 23 years (IQR 6-44), with 1276 (59%) being adults aged 16 years or older and 888 (41%) children aged between 29 days and 15 years; 1264 (59%) patients were male and 890 (41%) were female. Data on race and ethnicity were not recorded. 1020 (77%) of 1320 patients received a syndromic diagnosis before the intervention, rising to 701 (86%) of 813 after the intervention (adjusted odds ratio [aOR] 1·81 [95% CI 1·40-2·34]; p<0·0001). A microbiological diagnosis was made in 294 (22%) of 1330 patients pre-intervention, increasing to 250 (30%) of 824 patients post-intervention (aOR 1·46 [95% CI 1·18-1·79]; p=0·00040). Interrupted time series analysis confirmed that these increases exceeded a modest underlying trend of improvement over time. The percentage receiving a lumbar puncture, time to appropriate therapy, and functional outcome also improved. INTERPRETATION: Diagnosis and management of patients with suspected acute brain infections improved following introduction of a simple intervention package across a diverse range of hospitals on three continents. The intervention is now being implemented in other settings as part of the WHO Meningitis Roadmap and encephalitis control initiatives. FUNDING: UK National Institute for Health and Care Research.

Newborn screening (NBS) is one of the United States' largest, most successful preventative public health initiatives, improving outcomes for newborns with inborn errors of metabolism. Most disorders on the Recommended Uniform Screening Panel are screened using triple-quadrupole mass spectrometry and flow injection analysis. While these methods are sensitive and well suited for high-throughput quantitative applications, the breadth of measured analytes is limited to a relatively small number of biomarkers, which often have considerable overlaps between healthy and diseased populations. High-resolution liquid chromatography-mass spectrometry (LC-MS)-based metabolomics is now capable of profiling thousands of metabolites, making it well suited for exploratory and biomarker discovery studies. To this end, we developed a robust workflow for performing nontargeted LC-MS analysis on dried bloodspot (DBS) specimens with coverage across many metabolic pathways relevant to NBS. HILIC chromatography enabled quantitation of amino acid and acylcarnitine species while also retaining lipid species, such as lyso-phosphatidylcholines. We analyzed 810 newborn-derived DBS samples across a wide range of newborn birthweights, identifying correlations with metabolites that help to better account for the lower accuracy observed for some NBS markers (e.g., isovalerylcarnitine). Additionally, we leveraged this nontargeted workflow to capture new biomarkers and metabolic phenotypes in newborns associated with parenteral nutrition administration and maternal nicotine exposure. Two critical biomarkers were identified as useful additions to targeted screening panels: N-acetyltyrosine as a qualitative marker for parenteral nutrition administration and N-acetylputrescine as a quantitative marker for controlling birthweight variability.

OBJECTIVES: After respiratory syncytial virus (RSV), human metapneumovirus (hMPV) was the second-ranked pathogen attributed to severe pneumonia in the PERCH study. We sought to characterize hMPV-positive cases in high-burden settings, which have limited data, by comparing with RSV-positive and other cases. METHODS: Children aged 1-59 months hospitalized with suspected severe pneumonia and age/season-matched community controls in seven African and Asian countries had nasopharyngeal/oropharyngeal swabs tested by multiplex PCR for 32 respiratory pathogens, among other clinical and lab assessments at admission. Odds ratios adjusted for age and site (adjusted OR [aOR]) were calculated using logistic regression. Aetiologic probability was estimated using Bayesian nested partial latent class analysis. Latent class analysis identified syndromic constellations of clinical characteristics. RESULTS: hMPV was detected more frequently among cases (267/3887, 6.9%) than controls (115/4976, 2.3%), among cases with pneumonia chest X-ray findings (8.5%) than without (5.5%), and among controls with respiratory tract illness (3.8%) than without (1.8%; all p ≤ 0.001). HMPV-positive cases were negatively associated with the detection of other viruses (aOR, 0.18), especially RSV (aOR, 0.11; all p < 0.0001), and positively associated with the detection of bacteria (aORs, 1.77; p 0.03). No single clinical syndrome distinguished hMPV-positive from other cases. Among hMPV-positive cases, 65.2% were aged <1 year and 27.5% had pneumonia danger signs; positive predictive value for hMPV aetiology was 74.5%; mortality was 3.9%, similar to RSV-positive (2.4%) and lower than that among other cases (9.6%). DISCUSSION: HMPV-associated severe paediatric pneumonia in high-burden settings was predominantly in young infants and clinically indistinguishable from RSV. HMPV-positives had low case fatality, similar to that in RSV-positives.

BACKGROUND: The prevalence and risk factors for ongoing symptoms following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [SCV2]) or influenza infection are not well characterized. We conducted a prospective cohort study of households wherein ≥1 individual was infected with SCV2 or influenza to evaluate prevalence of and factors associated with ongoing symptoms at 90 days. METHODS: Index cases and their household contacts provided baseline health and sociodemographic information and collected daily respiratory specimens for 10 days following enrollment. Participants completed a follow-up survey 90 days after enrollment to characterize ongoing symptoms. RESULTS: We analyzed 1967 participants enrolled between December 2021 and May 2023. The risk of ongoing symptoms did not differ by infection status in SCV2 (SCV2-positive: 15.6%; SCV2-negative: 13.9%; odds ratio [OR]: 1.14; 95% CI: .7-1.69) or influenza (influenza-positive: 8.8%; influenza-negative: 10.0%; OR: .87; 95% CI: .45-1.72) households. However, among study participants with a documented infection, SCV2-positive participants had nearly twice the odds of ongoing symptoms as influenza-positive participants (OR: 1.92; 95% CI: 1.27-2.97). CONCLUSIONS: These results suggest that SCV2 households have a significantly higher prevalence of ongoing symptoms compared with influenza households (OR: 1.78; 95% CI: 1.28-2.47). Among participants with SCV2 infection, underlying conditions (adjusted OR [aOR]: 2.65; 95% CI: 1.80-3.90) and coronavirus disease 2019 (COVID-19)-like symptoms (aOR: 2.92; 95% CI: 1.15-7.43) during acute infection increased odds of ongoing symptoms at 90 days, whereas hybrid immunity reduced the odds of ongoing symptoms (aOR: 0.44; 95% CI: .22-.90).

BACKGROUND: In Zambia, the true extent of SARS-CoV-2 infections is unknown because initial surveillance focused on patients with symptoms or severe disease. Antenatal sentinel surveillance had not been used to assess infection trends. The ANC COVID-19 surveillance study sought to determine SARS-CoV-2 seroprevalence and COVID-19 vaccine uptake among pregnant women. We provide insight into the study implementation, challenges encountered, best practices, and lessons learned. METHODS: A repeated cross-sectional seroprevalence survey was implemented at 39 health facilities in four districts from September 2021 to September 2022. Pregnant women aged 15-49 years were enrolled at their first antenatal care visits. An electronic questionnaire gathered demographics and other COVID-19 related information from consenting participants. A dried blood sample was collected to detect IgG antibodies using a multiplex bead assay. Seropositive results were categorized as infection, infection and vaccination or infection based on anti-RBD and anti-nucleocapsid test results. Problems and their root causes were identified as they occurred. Practical problem-solving strategies were devised, implemented, and monitored to ensure that goals were accomplished. RESULTS: In the primary analysis, 7% of the 9,221 samples collected from participants were not tested because they were missing. COVID-19 vaccine uptake of 9,111 pregnant women was assessed. Approximately 64% of participants were cumulatively seropositive for SARS-CoV-2 antibodies. Seroprevalence increased from 27.8% in September 2021 to 56.6% in July 2022. We observed an increase in vaccine coverage (0.5-27%) over time. Women aged 40-49 years old, without education and with prior COVID-19 infection were associated with higher vaccine uptake. The Delta variant of COVID-19 and the reallocation of health facilities between two partners delayed surveillance activities and increased the cost of implementation (e.g., the purchase of additional calibration and validation kits and DBS cards). Protocol deviations were attributed to the lack of experience in conducting research but, the district RAs repeatedly trained health facility staff to enhance their research knowledge. CONCLUSIONS: Incorporating SARS-CoV-2 surveillance into routine antenatal care is feasible and potentially sustainable when existing health system infrastructure, human resources, and surveillance systems are leveraged. Yet, careful planning is needed to anticipate implementation challenges and ensure high-quality data collection.

The 2015-16 Zika virus epidemic emerged in the Americas and rapidly spread throughout the region and beyond, showing the epidemic potential of this mosquito-borne Orthoflavivirus and its capacity to cause severe congenital malformations and neurological sequelae. WHO declared the Zika virus epidemic a public health emergency of international concern in 2016. Despite this declaration, there are no licensed Zika virus vaccines, therapeutics, or diagnostic tests appropriate for routine antenatal screening. To address this absence of essential tools to detect and mitigate the threat of future Zika virus outbreaks, a group of global experts developed a priority agenda for Zika virus research and development. This Series paper summarises crucial challenges and knowledge gaps and outlines a comprehensive strategy to advance research, surveillance, global capacity, policy, and investment for Zika virus preparedness and response.

In the era of genomic characterization of strains for public health microbiology, whole genome sequencing (WGS)-enabled subtyping of Salmonella provides superior discrimination of strains compared to traditional methods such as serotyping. Nonetheless, serotypes are still very useful; they maintain historical continuity and facilitate clear communication. Genetic determination of serotypes from WGS data is now routine. Genetic determination of rarer serotypes can be problematic due to a lack of sequences for rare antigen types and alleles, a lack of understanding of the genetic basis for some antigens, or some inconsistencies in the White-Kauffmann-Le Minor (WKL) Scheme for Salmonella serotype designation. Here, we present a simplified interpretation of serotypes to address the shortcomings of genetic methods, which will allow the streamlined integration of serotype determination into the WGS workflow. The simplification represents a consensus perspective among major U.S. public health agencies and serves as a WGS-oriented interpretation of the WKL Scheme. We also present SeqSero2S, a bioinformatics tool for WGS-based serotype prediction using the simplified interpretation.IMPORTANCEThe utility of Salmonella serotyping has evolved from a primary subtyping method, where the need for strain discrimination justified its complexity, to a supplemental subtyping scheme and nomenclature convention, where clarity and simplicity in communication have become important for its continued use. Compared to phenotypic methods like serotyping, whole genome sequencing (WGS)-based subtyping methods excel in recognizing natural populations, which avoids grouping together strains from different genetic backgrounds or splitting genetically related strains into different groups. This simplified interpretation of serotypes addresses a shortcoming of the original scheme by combining some serotypes that are known to be genetically related. Our simplified interpretation of the White-Kauffmann-Le Minor (WKL) Scheme facilitates a complete and smooth transition of serotyping's role, especially from the public health perspective that has been shaped by the routine use of WGS.

BACKGROUND: Although many factors are associated with gastroschisis risk, studies have not systematically explored whether they account for its increasing frequency over the past decades or its inverse association with maternal age. We examined whether previously reported risk factors for gastroschisis from the National Birth Defects Prevention Study (NBDPS) explain the association with increasing temporal prevalence or young maternal age. METHODS: Using data from the NBDPS (1997-2011), crude odds ratios (ORs) were calculated for birth years 2005-2011 versus 1997-2004 and maternal age < 25 versus 25+ years. We then adjusted for 16 factors separately with logistic regression (paternal age, interpregnancy interval, parity, alcohol, cigarettes, illicit drugs, oral contraceptives, cold/flu with fever, genitourinary infection, polycyclic aromatic hydrocarbons, diet quality, prepregnancy body mass index, parental race and ethnicity, language spoken at home, years lived in the United States, and household income). RESULTS: The birth year OR (1.28; 95% CI: 1.14, 1.44) was attenuated by 16% after adjustment for polycyclic aromatic hydrocarbon exposure (OR 1.08; 95 CI: 0.92, 1.26). The young maternal age OR (7.76; 95% CI: 6.71, 8.97) was attenuated by 30% after adjustment for paternal age (OR 5.43; 95% CI: 4.55, 6.48) and separately for interpregnancy interval (OR 5.45; 95% CI: 4.43, 6.69). CONCLUSION: Some evidence suggests that risk factors for gastroschisis account for small amounts of the time trend and maternal age associations. However, it remains unclear what factors underlie the complete calendar time or maternal age associations.

Larval source management (LSM) has a long history of advocacy and successes but is rarely adopted where funds are limited. The World Health Organization (WHO) guidelines on malaria prevention recommend the use of LSM as a supplementary intervention to the core vector control methods (insecticide-treated nets and indoor residual spraying), arguing that its feasibility in many settings can be limited by larval habitats being numerous, transient, and difficult to find or treat. Another key argument is that there is insufficient high-quality evidence for its effectiveness to support wide-scale implementation. However, the stagnation of progress towards malaria elimination demands that we consider additional options to the current emphasis on insecticidal commodities targeting adult mosquitoes inside homes. This letter is the result of a global, crossdisciplinary collaboration comprising: (a) detailed online expert discussions, (b) a narrative review of countries that have eliminated local malaria transmission, and (c) a mathematical modeling exercise using two different approaches. Together, these efforts culminated in seven key recommendations for elevating larval source management as a strategy for controlling malaria and other mosquito-borne diseases in Africa (Box 1). LSM encompasses the use of larvicide (a commodity) as well as various environmental sanitation measures. Together, these efforts lead to the long-term reduction of mosquito populations, which benefits the entire community by controlling both disease vector and nuisance mosquitoes. In this paper, we argue that the heavy reliance on large-scale cluster-randomized controlled trials (CRTs) to generate evidence on epidemiological endpoints restricts the recommendation of approaches to only those interventions that can be measured by functional units and deliver relatively uniform impact and, therefore, are more likely to receive financial support for conducting these trials. The explicit impacts of LSM may be better captured by using alternative evaluation approaches, especially high-quality operational data and a recognition of locally distinct outcomes and tailored strategies. LSM contributions are also evidenced by the widespread use of LSM strategies in nearly all countries that have successfully achieved malaria elimination. Two modelling approaches demonstrate that a multifaceted strategy, which incorporates LSM as a central intervention alongside other vector control methods, can effectively mitigate key biological threats such as insecticide resistance and outdoor biting, leading to substantial reductions in malaria cases in representative African settings. This argument is extended to show that the available evidence is sufficient to establish the link between LSM approaches and reduced disease transmission of mosquito-borne illnesses. What is needed now is a significant boost in the financial resources and public health administration structures necessary to train, employ and deploy local-level workforces tasked with suppressing mosquito populations in scientifically driven and ecologically sensitive ways. In conclusion, having WHO guidelines that recognize LSM as a key intervention to be delivered in multiple contextualized forms would open the door to increased flexibility for funding and aid countries in implementing the strategies that they deem appropriate. Financially supporting the scale-up of LSM with high-quality operations monitoring for vector control in combination with other core tools can facilitate better health. The global health community should reconsider how evidence and funding are used to support LSM initiatives.

BACKGROUND: This study aimed to assess how knee savers (KSs) and knee pads (KPs) alleviate risks of knee musculoskeletal disorders (MSDs) among roofers during various phases of shingle installation. These phases encompass (1) reaching for shingles, (2) placing shingles, (3) grabbing a nail gun, (4) moving to the first nailing position, (5) nailing shingles, (6) replacing the nail gun, and (7) returning to an upright position. METHODS: In a laboratory setting, nine male participants simulated the shingle installation task on a slope-adjustable roof platform (0°, 15°, and 30° slopes) under four intervention conditions: no intervention (NO); with KPs only (KP); with KSs only (KS); and with both KPs and KSs (BO). Knee flexion, abduction, adduction, and internal/external rotations were measured to assess intervention impact through statistical analysis. RESULTS: Phase 5 (nailing shingles), one of the riskiest phases, saw reduced knee rotations, with BO and KP interventions being the most effective. Phase 6 (replacing the nail gun) exhibited notable reductions in all knee rotations, primarily due to BO intervention. Significant improvements in certain knee angles for other phases were noted, particularly with BO intervention. CONCLUSIONS: BO and KP can lower knee strain by minimizing extreme knee postures and thereby reducing the risk of MSDs during the installation of shingles, especially at critical periods and on steeper slopes. This study highlights the importance of applying focused ergonomic techniques in the roofing sector to improve workers' musculoskeletal health.

INTRODUCTION: We assessed the risk of adverse pregnancy and birth outcomes and birth defects among women living with HIV (WLHIV) on antiretroviral therapy (ART) and HIV-negative women. METHODS: We analyzed data on live births, stillbirths, and spontaneous abortions during 2015-2021 from a hospital-based birth defects surveillance system in Kampala, Uganda. ART regimens were recorded from hospital records and maternal self-reports. Using a log-binomial regression model, we compared the prevalence of 16 major external birth defects and other adverse birth outcomes among WLHIV on ART and HIV-negative women. RESULTS: A total of 203,092 births were included from 196,373 women of which 15,020 (7.6%) were WLHIV on ART. During pregnancy, 15,566 infants were primarily exposed to non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART (n=13,614; 87.5%). After adjusting for maternal age, parity, and number of antenatal care (ANC) visits, WLHIV on NNRTI were more likely than HIV-negative women to deliver preterm (adjusted prevalence ratio [aPR]=1.27, 95% confidence interval [CI]: 1.21,1.32), post-term (aPR=1.23, 95% CI: 1.16,1.32), or small for gestational age infants (aPR=1.35, 95% CI: 1.30,1.40). Spina bifida was more prevalent among infants born to WLHIV on ART periconceptionally compared to HIV-negative women (aPR=2.45, 95% CI 1.27,4.33). The prevalence of the other selected birth defects were similar between infants from WLHIV on ART and HIV-negative women. CONCLUSION: In Uganda, WLHIV on ART were more likely than HIV-negative women to experience selected adverse birth outcomes. Further surveillance of maternal ART exposure, including by drug class and ART regimen, is needed to monitor and prevent adverse birth outcomes in WLHIV.

BACKGROUND: Reports from China describe an increase in the frequency of fetal situs inversus in 2023 after the country's "zero-Covid" policy was lifted, suggesting an association with maternal SARS-CoV-2 infection. However, a report of birth defects surveillance data from Scandinavia observed no sustained increase during the SARS-CoV-2 pandemic (2020-2022 vs. 2018-2019). We examined birth defects surveillance data to assess any increase in situs inversus in the U.S. during the SARS-CoV-2 pandemic. METHODS: We combined data from four population-based birth defects programs in Massachusetts, Minnesota, North Carolina, and Atlanta, Georgia, to compare the prevalence of situs inversus among infants and fetuses delivered before (2017-2019) and during (2021-2022) the SARS-CoV-2 pandemic. We defined situs inversus as mirror-image transposition of the heart and/or other organs, or primary ciliary dyskinesis with situs inversus, excluding isolated dextrocardia. The programs varied in the pregnancy outcomes included (live births ± non-live births); all included both prenatal and postnatal diagnoses. RESULTS: We identified 294 infants and fetuses with situs inversus (6.8% non-live births). We estimated the combined prevalence per 10,000 live births as 1.72 during the pandemic versus 1.71 before the pandemic (OR = 1.005; 95% CI: 0.778-1.297). The estimated annual prevalence ranged from 1.41 in 2017 to 2.21 in 2019 with no significant trend across the study period (p = 0.39). CONCLUSIONS: We did not observe an increase in situs inversus during the SARS-CoV-2 pandemic. Because information about SARS-CoV-2 infection among individual pregnancies was not available from all programs, we could not assess a specific association with maternal infection.

BACKGROUND AND OBJECTIVES: Many neonatal intensive care units (NICUs) do not give rotavirus vaccines to inpatients due to a theoretical risk of horizontal transmission of vaccine strains. We aimed to determine incidence and clinical significance of vaccine-strain transmission to unvaccinated infants in a NICU that routinely administers pentavalent rotavirus vaccine (RV5). METHODS: This prospective cohort study included all patients admitted to a 100-bed NICU for 1 year. Stool specimens were collected weekly; real-time quantitative reverse-transcription polymerase chain reaction was used to detect any RV5 strain. Incidence of transmission to unvaccinated infants was calculated assuming each unvaccinated patient's stool contributed 1 patient-day at risk for transmission. Investigations and geospatial analyses were conducted for suspected transmission events. RESULTS: Of 1238 infants admitted, 560 (45%) were premature and 322 (26%) had gastrointestinal pathology. During observation, 226 RV5 doses were administered. Overall, 3448 stool samples were tested, including 2252 from 686 unvaccinated patients. Most (681, 99.3%) unvaccinated patients never tested positive for RV5 strain. Five (<1%) tested RV5 strain positive. The estimated rate of transmission to unvaccinated infants was 5/2252 stools or 2.2/1000 patient-days at risk (95% CI: 0.7-5.2). No gastroenteritis symptoms were identified in transmission cases within 7 days of collection of RV5-positive stool. Of 126 patients for whom the RV5 series was initiated before the discharge date, 55% would have become age-ineligible to start the series if vaccination was allowed only at discharge. CONCLUSIONS: Transmission of RV5 strain was infrequent and without clinical consequences. Benefits of allowing vaccine-induced protection against rotavirus disease in infants through in-NICU RV5 vaccination appear to have outweighed risks from vaccine-strain transmission.

BACKGROUND: The Federal Retail Pharmacy Program (FRPP) integrated pharmacies as partners in the national effort to maximize vaccination during the COVID-19 public health emergency. OBJECTIVES: The objective of this study was to quantify the contribution of pharmacies participating in FRPP to COVID-19 vaccination efforts during December 2020-September 2023 across sociodemographic groups in the United States. METHODS: Data on COVID-19 vaccine doses administered reported to CDC by FRPP and jurisdictional immunization information systems (IIS) of all 50 states, the District of Columbia, and U.S. territories were analyzed to estimate FRPP contributions. RESULTS: Approximately 314.9 million COVID-19 vaccine doses were administered by FRPP throughout this period, constituting 48.9% of all COVID-19 vaccine doses administered. FRPP contributions to COVID-19 vaccination ranged from 12.9% to 56.8% for persons aged 6 months-4 years and 12-17 years, respectively. FRPP made the highest contribution to administering COVID-19 doses to Non-Hispanic Asian (48.7%) and Hispanic/Latino (49.8%) persons. The proportion of COVID-19 doses given by FRPP pharmacies was found to be higher in urban areas (57%) compared with rural areas (45%). CONCLUSION: FRPP administered a substantial proportion of COVID-19 vaccine doses in the United States and provided vaccine access for persons across a wide range of groups. Pharmacies can complement vaccination efforts during public health emergency situations and in routine vaccination programs.

Endurance exercise training (ExT) induces metabolic, structural, and functional adaptations via lipidomic modifications, yet the systematic elucidation of lipidome alterations in response to ExT remains incomplete. As a part of the Molecular Transducers of Physical Activity Consortium (MoTrPAC), we leveraged non-targeted and targeted lipidomics for the systematic discovery of lipid alterations in the brown adipose tissue, heart, hippocampus, kidney, liver, lung, skeletal muscle gastrocnemius, subcutaneous white adipose tissue, and plasma in response to 1, 2, 4 or 8 weeks of ExT in 6-month-old male and female Fischer-344 rats. This study demonstrates that these tissues, each with distinct lipidomic features, underwent dynamic, sexually dimorphic lipid remodeling. Exercise trained animals showed reduced whole-body adiposity and improved cardiorespiratory fitness, along with enhanced utilization of lipid stores and dynamic triacylglycerol remodeling compared to sedentary controls in all tissues except hippocampus. They also showed modifications in phospholipids, lysophospholipids, oxylipins, and ceramides in several tissues. Coordinated changes across tissues reflect systemic tissue communication, with liver-plasma-heart connection potentially playing a key role in systemic lipid metabolism during ExT. These data will improve our understanding of lipid-associated biological processes underlying the health-promoting benefits of ExT.

Using data from the US population-based, multisite Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet), we describe respiratory testing and insufficiency among people with facioscapulohumeral muscular dystrophy (FSHD) diagnosed during 2008-2016. We calculated frequencies and proportions for selected outpatient respiratory assessments (pulmonary function tests [PFTs], forced vital capacity (FVC), inspiratory/expiratory pressure, and polysomnograms) and abnormal test results. We examined frequencies by disease characteristics (FSHD type, ages of onset, non-ambulatory status, scoliosis, lordosis), obesity, and number of health encounters. Of 170 people with FSHD, 20.0% underwent PFTs during 2008-2016. Polysomnograms were infrequent (14.1%). FVC <80% predicted was recorded for 64.7% of people tested; additional respiratory outcomes were rare (<5%). Frequency of evaluations and respiratory insufficiency were higher among those with known risk factors and longer follow-up. We observed low proportions of respiratory testing among all confirmed cases of FSHD, but relatively high proportions of mild respiratory insufficiency among those tested. The higher proportions of testing among people with conditions that increase risk of respiratory complications suggest targeted monitoring. Broad implementation of the FSHD guidelines recommending all individuals receive baseline respiratory evaluation at diagnosis could identify respiratory insufficiency as a complication of FSHD.

Hurricane Ida, a Category 4 hurricane, made landfall in southern Louisiana in August of 2021, causing widespread wind damage and flooding. The objective of this study was to investigate knowledge, attitudes, and practices related to post-hurricane mold exposure and cleanup among residents and workers in areas of Louisiana affected by Hurricane Ida and assess changes in knowledge, attitudes, and practices that have occurred over the past 16 years since Hurricane Katrina. We conducted in-person interviews with 238 residents and 68 mold-remediation workers in areas in and around New Orleans to ask about their mold cleanup knowledge and practices, personal protective equipment use, and risk perceptions related to mold. Knowledge of recommended safety measures increased since the post-Katrina survey but adherence to recommended safety measures did not. Many residents and some workers reported using insufficient personal protective equipment when cleaning up mold despite awareness of the potential negative health effects of mold exposure.

Common methods to collect data include quantitative, qualitative, and mixed method approaches. Although it is common to complete data collection in-person, the onset of COVID-19 has resulted in the increased use of online modalities. Qualitative research is commonly gathered through individual or focus group interviews. However, best practices outlining strategies when conducting online focus groups and approaches to address issues specific to online research (i.e., scammers) are limited. Due to the growing use of data collection through such means, it is imperative to draw out specific strategies that could regulate data quality and reduce the chances of scamming. The current article addresses this practical gap by providing a synthesis of the available literature on online focus groups that document best practices and suggestions to deal with scammers which is currently missing from the literature. The goal was to provide initial suggestions to improve data quality of online focus groups by examining the available literature that outlines best practices, addresses the issues of scammers, and to provide a concise and comprehensive overview of identified literature The article is organized beginning with a review of the literature. The research is then synthesized including an outline of best practices and strategies to address scammers when engaging in online focus groups. The article closes with a discussion of the significance of the review, limitations, and article summary. Scammers are prevalent in online spaces. Although this article provides a preliminary outline of suggestions from the literature, more research is necessary that provides specific examples of how challenges have been addressed and the impact of including the recommended strategies on the research process and outcomes. © 2024, Ludomedia EN. All rights reserved.

INTRODUCTION: Exposure to unfavorable environmental conditions during pregnancy, such as extreme heat and air pollution, has been linked to increased risk of stillbirth, defined as fetal mortality at or after 20 weeks' gestation, however no studies have examined its association with social vulnerability. We examined associations between county-level stillbirth rates, environmental risk factors for stillbirth, and social vulnerability in the United States. METHODS: This ecologic study linked county-level data from three nationwide datasets on stillbirths (National Vital Statistics System), environmental conditions (North American Land Data Assimilation System and Environmental Protection Agency), and social vulnerability (Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry Social Vulnerability Index). Poisson and negative binomial models were fit to the variables and produced rate ratios to estimate associations among stillbirth rates, environmental risk factors, and social vulnerability. RESULTS: Social vulnerability was positively associated withn stillbirth rates, annual average number of extreme heat days, and ambient concentration of particulate matter ≤ 2.5 μm in diameter (PM2.5). The average number of days that ozone and PM2.5 each exceeded regulatory standards were not associated with stillbirth rates or social vulnerability. A positive association between average annual PM2.5 concentration and stillbirth rates was detected; no other significant associations between environmental risk factors and stillbirth rates were observed. DISCUSSION: We found evidence of associations between social vulnerability and stillbirth rates, and between social vulnerability and environmental risk factors for stillbirth at the county level. Further research could inform understanding of how social vulnerability impacts the relationship between environmental exposures and stillbirth risk.

Adolescent mental health and suicide risk remain substantial public health concerns. High pre-COVID rates of poor mental health and suicide-related behaviors have continued to rise, highlighting the need to identify factors that might foster positive mental health outcomes and reduce suicide-related behaviors at population levels. Using CDC's 2023 Youth Risk Behavior Survey, CDC analyzed the prevalence of mental health and suicide risk indicators and their associations with individual-, family-, and school- or community-level protective factors. Prevalence estimates were calculated for each of the mental health and suicide risk indicators by demographic characteristic. Prevalence ratios adjusted for sex, sexual identity, grade, and race and ethnicity were calculated to examine the association between protective factors and mental health and suicide risk indicators. Overall, 39.7% of students experienced persistent feelings of sadness and hopelessness, 28.5% experienced poor mental health, 20.4% seriously considered attempting suicide, and 9.5% had attempted suicide. Mental health and suicide risk indicators differed by sex, sexual identity, grade, and race and ethnicity. All protective factors were associated with lower prevalence of one or more risk indicators. Findings from this report can serve as a foundation for the advancement of research on protective factors and for the development and implementation of programs, practices, and policies that protect and promote mental health and emotional well-being among youth.

Social media has become a pervasive presence in everyday life, including among youths. In 2023, for the first time, CDC's nationally representative Youth Risk Behavior Survey included an item assessing U.S. high school students' frequency of social media use. Data from this survey were used to estimate the prevalence of frequent social media use (i.e., used social media at least several times a day) among high school students and associations between frequent social media use and experiences with bullying victimization, persistent feelings of sadness or hopelessness, and suicide risk. All prevalence estimates and measures of association used Taylor series linearization. Prevalence ratios were calculated using logistic regression with predicted marginals. Overall, 77.0% of students reported frequent social media use, with observed differences by sex, sexual identity, and racial and ethnic identity. Frequent social media use was associated with a higher prevalence of bullying victimization at school and electronically, persistent feelings of sadness or hopelessness, and some suicide risk among students (considering attempting suicide and having made a suicide plan), both overall and in stratified models. This analysis characterizes the potential harms of frequent social media use for adolescent health among a nationally representative sample of U.S. high school students. Findings might support multisectoral efforts to create safer digital environments for youths, including decision-making about social media policies, practices, and protections.