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.

Seroprevalence studies play an important role in estimating the number of children infected with SARS-CoV-2. We report SARS-CoV-2 seroprevalence in children seeking medical care for any reason at a free-standing pediatric hospital in Seattle, WA over a 2.5-year period and four distinct pandemic waves. We randomly selected residual serum samples from children and young adults seeking medical care as inpatients and outpatients at Seattle Children's Hospital between June 2020 and December 2022 to test for the presence of anti-nucleocapsid (N) antibodies. Samples were categorized into four distinct pandemic waves based on Washington State epidemiology: Wave 1 (June 2020-October 2020), Wave 2 (November 2020-June 2021), Wave 3 (July 2021-November 2021), and Wave 4 (December 2021-December 2022). Patient characteristics and COVID-19 vaccine status were obtained, and zip codes were used to ascertain the Social Vulnerability Index (SVI). Multivariable Poisson regression models with robust variance estimates were used to examine the relationship between patient characteristics and anti-N-positivity for each wave. Among 8,040 samples from 7,102 patients included in the analyses, seroprevalence rose from 2.4% (95% CI, 2.0%-3.1%) in Wave 1 to 25.5% (95% CI 23.3%-27.8%) in Wave 4 (following the Omicron surge). High SVI, Hispanic ethnicity, or use of government insurance was associated with increased anti-N positivity in most waves. We observed a steady increase in anti-N seroprevalence followed by a sharp increase after the Omicron surge in early 2022. Our data demonstrate the burden of COVID-19 on specific groups with health disparities within our region throughout the pandemic.IMPORTANCEOur results highlight the importance of seropositivity studies as essential tools to provide information on the incidence and prevalence of SARS-CoV-2 seropositivity. Our results also reinforce other reports demonstrating the inequitable burden of COVID-19 on groups with health disparities and that this inequitable burden continued to persist throughout the pandemic, even in a region with high adherence to COVID-19 mitigation efforts. It also highlights SVI's value in identifying communities that must be part of pandemic research, and public health and vaccination strategies.

BACKGROUND: To better establish the value of vaccination against influenza viruses, we estimated vaccine-averted influenza illnesses among young children and older adults in Chile, Guyana, and Paraguay. METHODS: We gathered country- and target population-specific data on monthly influenza hospitalizations, vaccine coverage, and vaccine effectiveness from surveillance records and immunization registries during 2013-2018. We applied a static compartmental model to estimate differences in the number influenza-associated respiratory disease events (symptomatic nonhospitalized illnesses, medically attended illnesses, hospitalizations) in the presence and absence of influenza vaccination programs. RESULTS: Between 2013 and 2018, vaccinating 68% of children aged 6-23 months in Chile averted an annual mean of 14 617 nonhospitalized, 9426 medically attended, and 328 hospitalized influenza illnesses; vaccinating 28% of children aged 6-23 months in Paraguay averted 1115 nonhospitalized, 719 medically attended, and 25 hospitalized influenza illnesses. Vaccinating 59% of older adults in Chile averted an annual mean of 83 429 nonhospitalized, 37 079 medically attended, and 1390 hospitalized influenza illnesses; vaccinating 36% of older adults in Paraguay averted an annual mean of 3932 nonhospitalized, 1748 medically attended, and 66 hospitalized influenza illnesses. In Guyana, a hypothetical campaign vaccinating 30% of children aged <5 years could have prevented an annual 1496 nonhospitalized, 971 medically attended, and 10 hospitalized influenza illnesses. Vaccinating 30% of adults aged ≥65 years could have prevented 568 nonhospitalized, 257 medically attended, and 10 hospitalized influenza illnesses. CONCLUSIONS: Influenza vaccination averted tens of thousands of illnesses and thousands of hospitalizations in Chile and Paraguay; influenza vaccination could have had a proportional benefit in Guyana.

People who inject drugs (PWID) account for the majority of hepatitis C virus (HCV) infections in the United States. The injection-equipment-sharing network likely plays an important role in shaping the dynamics of HCV transmission. Recognizing the emerging HCV epidemic in rural communities, we developed an agent-based network simulation model of HCV transmission via injection-equipment-sharing and used data on rural PWID networks to inform model parameterization and calibration. We then simulated an array of networks that varied key network properties to understand their impact on the magnitude and distribution of HCV incidence. The results show substantial heterogeneity in HCV acquisition risks across the network, summarized using the Ghyaini coefficient. In addition, although PWID with fewer injection partners had lower incidence, they collectively acquired more infections due to their larger population size. Higher prevalence, average number of partners, and homophily in HCV infection were associated with lower heterogeneity in infection risk across the network and higher overall incidence; other network properties including population size did not have a substantial impact. Our findings illustrate the heterogeneity of HCV transmission among PWID and suggest key network properties that could be measured, evaluated, or considered in the design of interventions for PWID in future studies.

BACKGROUND: There is paucity of information on the role of cytomegalovirus (CMV) infection as a cause of stillbirths or childhood deaths in low-and middle-income countries (LMICs). We investigated attribution of CMV-disease in the causal pathway to stillbirths and deaths in children <5 years of age in seven LMICs participating in the Child Health and Mortality Prevention Surveillance (CHAMPS) network. METHODS: We analyzed stillbirths and decedents enrolled between December 2016 and July 2023. Deaths were investigated using post-mortem minimally invasive tissue sampling with histopathology and molecular diagnostic investigations of tissues and body fluids, along with review of clinical records. Multi-disciplinary expert panels reviewed findings and reported on the causal pathway to death. RESULTS: CMV was detected in 19.5%(1140/5841) of all evaluated deaths, including 5.0% (111/2204), 6.2% (139/2229), 41.2% (107/260), 68.1%(323/474) and 68.2%(460/674) of stillbirths, neonates (deaths 0-<28 days postnatal), young infants (28-<90 days), older infants (90-<365 days) and children (12-<60 months), respectively. CMV-disease was attributed in the causal pathway to death in 0.9%(20/2204) of stillbirths, 0.8%(17/2229) of neonates, 13.1% (34/260) of young infants, 9.7%(46/474) of older infants and 3.3%(22/674) of children. Decedents with CMV-disease compared with those without CMV-disease in the causal pathway, were more likely to have severe microcephaly (38.2% vs. 21.1%; aOR 2.2, 95%CI: 1.3-3.6) and HIV-infected (36.9% vs. 6.2%; aOR: 10.9, 95%CI: 6.5-18.5). CONCLUSIONS: CMV-disease is an important contributor to deaths during infancy and childhood and is often associated with severe microcephaly and HIV-infection. Improving management of CMV in HIV-infected children and a vaccine to prevent CMV are needed interventions.

Young People Living with HIV (YPLHIV, 15-24 years) are an important demographic of Persons Living with HIV (PLHIV) globally and in Southern Africa. However, YPLHIV experience poor outcomes across the HIV diagnostic and treatment cascade due to multiple factors. We estimated the prevalence and determinants of HIV viral suppression in YPLHIV on antiretroviral therapy (ART) in selected Southern African countries. We used publicly available data from Malawi, Zimbabwe, Mozambique, Lesotho, and Eswatini collected during the Population-based HIV Impact Assessments (PHIAs) of 2020 to 2021. Weighted proportions, and 95% confidence intervals (CI) were computed to estimate the prevalence of viral suppression (< 1000c/ml) and bivariate and multivariate analyses were conducted to identify determinants of viral suppression. A total of 855 records of YPLHIV on ART were included in the analysis. The prevalence of viral suppression in YPLHIV on ART was 82.4% (95% CI: 76.7, 86.9). Residing in Mozambique and duration on ART were inversely associated with viral suppression; adjusted odds ratios (AORs) of 0.37 (95% CI: 0.14, 0.95), and 0.87 (95% CI: 0.80, 0.94), respectively. A negative result in the depression screen, being married/cohabitating, and ever switching an ART regimen were positively associated with viral suppression: AORs of 5.78 (95% CI: 2.21, 15.11), 3.72 (95% CI: 1.44, 9.63), and 3.44 (95% CI: 1.69, 7), respectively. YPLHIV had suboptimal viral suppression lower than the UNAIDS 95% targets and may benefit from further research and tailored interventions addressing modifiable factors associated with viral suppression such as depression.

In 2006, human papillomavirus (HPV) vaccine was first recommended in the United States to prevent cancers and other diseases caused by HPV; vaccination coverage increased steadily through 2021, and increasing numbers of young women had received HPV vaccine as children or adolescents. Since 2008, CDC has monitored incidence of precancerous lesions (cervical intraepithelial neoplasia [CIN] grades 2-3 and adenocarcinoma in situ [AIS], collectively CIN2+), which are detected through cervical cancer screening and can be used as an intermediate outcome for monitoring vaccination impact, via the five-site Human Papillomavirus Vaccine Impact Monitoring Project. This analysis describes trends in incidence of CIN2+ and CIN3+ (i.e., CIN grade 3 and AIS) lesions during 2008-2022. Among women aged 20-24 years who were screened for cervical cancer, rates during 2008-2022 decreased for CIN2+ by 79%, and for CIN3+ by 80%. In the same period, CIN3+ rates among screened women aged 25-29 years decreased by 37%. These data are consistent with considerable impact of HPV vaccination for preventing cervical precancers among women in the age groups most likely to have been vaccinated, and support existing recommendations to vaccinate children at the routinely recommended ages as a cancer prevention measure.

BACKGROUND: Mobile health (mHealth) apps provide easy and quick access for end users to monitor their health-related activities. Features such as medication reminders help end users adhere to their medication schedules and automatically record these actions, thereby helping manage their overall health. Due to insufficient mHealth tools tailored for HIV preventive care in young men who have sex with men (MSM), our study evaluated the usability of the mChoice app, a tool designed to enhance preexposure prophylaxis (PrEP) adherence and promote sexual health (eg, encouraging the use of condoms and being aware of the partner's HIV status and PrEP use). OBJECTIVE: This study aimed to apply systematic usability evaluations to test the mChoice app and to refine the visualizations to better capture and display patient-reported health information. METHODS: Usability testing involved heuristic evaluations conducted with 5 experts in informatics and user testing with 20 young MSM who were taking or were eligible to take PrEP. RESULTS: End users demonstrated satisfaction with the appearance of the mChoice app, reporting that the app has an intuitive interface to track PrEP adherence. However, participants highlighted areas needing improvement, including chart titles and the inclusion of "undo" and "edit" buttons to improve user control when recording PrEP use. CONCLUSIONS: Usability evaluations involving heuristic experts and end users provided valuable insights into the mChoice app's design. Areas for improvement were identified, such as enhancing chart readability and providing additional user controls. These findings will guide iterative refinements, ensuring that future versions of the app better address the needs of its target audience and effectively support HIV prevention.

BACKGROUND: Our objective was to characterize the education and employment history of young adults with congenital heart defects (CHD) living in the United States. METHODS: The 2016-2019 Congenital Heart Survey To Recognize Outcomes, Needs, and well-beinG collected data from young adults (ages 19-38) with CHD identified from active birth defect in Arkansas, Arizona, and Atlanta, Georgia. Educational attainment, employment history, and special education between kindergarten and 12th grade were self-/proxy-reported. Respondent percentages were standardized to the eligible population by CHD severity, birth year, site, sex, and maternal race/ethnicity and compared by CHD severity using p values from Z-scores. Log-binomial prevalence ratios (aPRs) assessed associations between respondent characteristics and outcomes, adjusting for CHD severity, age group, sex, race/ethnicity, and site. Employment models also adjusted for education. Point estimates were compared to the 2018 American Community Survey (ACS) 5-year general population estimates. RESULTS: Among 1438 respondents, 28.3% attained ≥ bachelor's degree and 22.1% were unemployed for ≥ 12 months. Estimates were comparable by CHD severity (aPRs ~1.0) and similar to general population estimates (in ACS, 21% attained ≥ bachelor's degree and 26% were unemployed). About 25.3% of adults with CHD received special education, more commonly adults with severe (32.9%) than nonsevere CHD (23.5%, p = 0.01). CONCLUSIONS: Among young adults with CHD, educational attainment and employment did not substantially differ by CHD severity or from general population rates. One in four used special education between kindergarten and 12th grade. Clinical guidelines recommend ongoing educational and vocational support to individuals with CHD as needed so this population continues to thrive.

INTRODUCTION: An estimated 800 000 children (<15 years) globally living with HIV remain undiagnosed. To reach these children with timely HIV testing services during infancy, we implemented a community-based differentiated care model using mobile point-of-care (POC) technology for early infant diagnosis (EID) of HIV, and assessed its effects on EID positivity, antiretroviral therapy (ART) initiation and 3-month retention in care. METHODS: Between 1 June 2019 and 31 May 2020 at six health facilities in Lusaka, Zambia, we enrolled mother-infant pairs (MIPs) at high risk for vertical transmission of HIV based on missing or late infant EID testing or other maternal risk factors. We offered these MIPs community POC EID testing (post-intervention), and compared their outcomes to historical high-risk controls at the same sites (1 June 2017-31 May 2018; pre-intervention). We used propensity score matched weighting and mixed effects regression modelling to estimate outcome differences pre-intervention and post-intervention, and to identify MIP characteristics predictive of vertical transmission of HIV. RESULTS: 2577 MIPs were included in the analysis: 1763 and 814 high-risk MIPs from the pre-intervention and post-intervention periods, respectively. Infant HIV positivity was significantly higher in the post-intervention (2.2%) vs pre-intervention (1.1%) period (p=0.038), however this difference was attenuated (0.83%, 95% CI: -0.50%, 2.15%) after adjusting for differences in maternal age, maternal antenatal care visits, infant birth month and facility. During the post-intervention period, MIPs where the mother disengaged from care were 12.97 (95% CI: 2.41, 69.98) times as likely to have an infant diagnosed with HIV vs those in which the infant received late EID testing without maternal care disengagement. Among 18 infants diagnosed with HIV by the intervention, 16 (88.9%) initiated same-day ART and all continued ART at 3-month follow-up. CONCLUSION: Community-based differentiated care employing POC EID technology increased testing positivity in unadjusted analyses, and resulted in high ART initiation and early care retention, suggesting it may be a promising approach for reaching infants and young children living with HIV being missed by current facility-based approaches. TRIAL REGISTRATION NUMBER: This trial is registered under the following Clinicaltrials.gov Identifier: NCT03133728.

Meningococcal disease is rare but serious, often striking previously healthy adolescents or young adults, with substantial morbidity and mortality. The incidence of meningococcal disease in the USA declined even prior to the issuance of routine recommendations for vaccination, although an uptick in incidence has occurred since 2022. Routine recommendations for adolescent MenACWY vaccination were issued in 2005, and recommendations for adolescent MenB vaccination based on shared clinical decision-making (SCDM) were issued in 2015. Although meningococcal vaccines are safe and effective, their limited duration of protection coupled with low disease incidence result in a high cost per case averted by vaccination, most notably with MenB vaccines. The low cost-effectiveness raises ethical concerns about resource use and the role of economic analyses in policy decisions. However, the potential for substantial public health impact remains. Outer membrane vesicle (OMV)-containing MenB vaccines provide some protection against gonorrhea infections. The recent development of pentavalent ABCWY vaccines provide the opportunity to reduce the number of injections and simplify implementation, provided MenACWY and MenB vaccine schedules are harmonized. Vaccine attributes, implementation issues, and resource utilization will be important considerations in optimization of the US adolescent meningococcal vaccination strategy.

OBJECTIVE: Using an innovative data sharing model, we assessed the impacts of the COVID-19 pandemic on the health of people who inject drugs (PWID). DESIGN: The PWID Data Collaborative was established in 2021 to promote data sharing across PWID studies in North America. Contributing studies submitted aggregate data on 23 standardized indicators during four time periods: prepandemic (March 2019 to February 2020), early-pandemic (March 2020 to February 2021), mid-pandemic (March 2021 to February 2022), and late pandemic (March 2022 to February 2023). METHODS: We present study-specific and meta-analyzed estimates for the percentage of PWID who took medications for opioid use disorder, received substance use treatment, shared syringes or injection equipment, had a mental health condition, had been incarcerated, or had experienced houselessness. To examine change over time across indicators, we fit a random effects meta-regression model to prevalence estimates using time as a moderator. RESULTS: Thirteen studies contributed estimates to the Data Collaborative on these indicators, representing 6213 PWID interviews. We observed minimal change across prevalence of the six indicators between the prepandemic (March 2019 to February 2020) and three subsequent time periods, overall or within individual studies. Considerable heterogeneity was observed across study-specific and time-specific estimates. CONCLUSION: Limited pandemic-related change observed in indicators of PWID health is likely a result of policy and supportive service-related changes and may also reflect resilience among service providers and PWID themselves. The Data Collaborative is an unprecedented data sharing model with potential to greatly improve the quality and timeliness of data on the health of PWID.

To understand how coronavirus disease 2019 vaccines impact infection risk in children &lt;5 years, we assessed risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from September 2022 to April 2023 in 3 cohort studies. There was no difference in risk by vaccination status. While vaccines reduce severe disease, they may not reduce SARS-CoV-2 infections in naïve young children.

BACKGROUND: Mozambique introduced 10-valent-pneumococcal conjugate vaccine (PCV10) in 2013. We aimed to evaluate the indirect effect of PCV10 on invasive pneumococcal disease (IPD) and clinical severe pneumonia (CSP) in infants aged less than 10 weeks. METHODS: Routine surveillance data for IPD and CSP among admitted infants less than 10 weeks of age were analyzed to compare IPD and CSP incidence using demographic surveillance data from pre- and post-PCV10 periods. IPD was defined as isolation of pneumococcus from blood or cerebrospinal fluid, and CSP according to World Health Organization criteria. RESULTS: The incidence of IPD and CSP among infants less than 10 weeks decreased by 87% [incidence rate ratio (IRR): 0.13; 95% confidence interval (CI): 0.02-0.95] from 283/100,000 in the pre-PCV to 36/100,000 children year at risk (CYAR) post-PCV, and by 62% (IRR: 0.38; 95% CI: 0.27-0.52) from 4100/100,000 pre-PCV to 1550/100,000 CYAR post-PCV periods, respectively. Vaccine-type IPD incidence declined by 92% (IRR: 0.18; 95% CI: 0.02-1.34) from 205/100,000 pre-PCV to 36/100,000 CYAR post-PCV, though the reduction was not statistically significant. The mortality rate due to IPD among infants less than 10 weeks declined from 47/100,000 CYAR in the pre-PCV to 0 in the post-PCV period. Mortality due to CSP declined by 29% (IRR: 0.71; 95% CI: 0.34-1.50), from 457/100,000 CYAR in the pre-PCV to 324/100,000 in the post-PCV periods. CONCLUSIONS: PCV10 introduction led to substantial declines in the incidence of IPD, CSP and associated mortality in infants too young to be vaccinated (less than 10 weeks) in Mozambique, suggesting indirect protection.

OBJECTIVES: To evaluate how postmortem anthropometric malnutrition (PAM) measures align with expert panel attribution of malnutrition as a causal or significant condition in under-5 mortality (U5M). DESIGN: Cohort study using data from the Child Health and Mortality Prevention Surveillance network, incorporating clinical records, postmortem anthropometrics, minimally invasive tissue sampling, clinical abstraction and verbal autopsy to determine multiple causes of death. SETTING/PARTICIPANTS: 1405 deaths of children aged 1-59 months from six African countries between 2016 and 2023. PRIMARY AND SECONDARY OUTCOME MEASURES: PAM was determined using z-scores from the WHO Child Growth Standards: underweight (weight-for-age<(-2)), wasting (arm circumference-for-age or weight-for-length<(-2)) and stunting (length-for-age <(-2)). Performance metrics (sensitivity (SE), specificity (SP) and positive predictive values (PPV)) were calculated to determine the alignment between PAM and expert panel attribution of malnutrition as a causal or significant condition to death. RESULTS: Nearly 75% of cases demonstrated moderate-to-severe malnutrition by PAM, while expert panels attributed malnutrition in 41% of cases. Performance metrics varied across anthropometric indices: underweight exhibited the highest SE (89.7%), while wasting based on arm circumference had the highest SP (81.9%) and PPV (76.8%). Discrepancies between PAM classification and expert panel attribution differed significantly by site, age, location of death and preventability of death (p<0.05). Adjusted multivariate regression showed that expert panel attribution was more likely with increasing severity of PAM. CONCLUSIONS: The proportion of U5M attributable to malnutrition ranged between 41% (expert panel attribution) and 74% (PAM). Variability in classification underscores the need for monitoring and quality improvement measures to address discrepancies. Improved alignment between PAM and panel assessments is essential for accurately identifying malnutrition-related deaths and designing effective interventions to reduce U5M.

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.

BACKGROUND: Almost half of individuals born with Down syndrome (DS) have congenital heart defects (CHDs). Yet, little is known about the health and healthcare needs of adults with CHDs and DS. Therefore, we examined comorbidities and healthcare utilization of this population. METHODS: Data were from the 2016-2019 Congenital Heart Survey to Recognize Outcomes, Needs, and well-beinG (CH STRONG), a survey of 19-38-year-olds with CHDs identified through birth defects registries in Arkansas, Arizona, and Atlanta. Outcome estimates were standardized to the CH STRONG eligible population. Multivariable Poisson regression generated adjusted prevalence ratios (aPRs) for associations between DS and each outcome, adjusting for covariates, including CHD severity. RESULTS: Among 1500 respondents, 9.1% had DS. Compared to those without DS, respondents with DS were more commonly male (55.5% vs. 45.0%), < 25 years old (51.8% vs. 42.7%), non-Hispanic White (72.3% vs. 69.3%), and publicly insured (77.4% vs. 22.8%; all p < 0.05). Of adults with CHDs and DS, 5.5% had cardiac comorbidities, 19.3% had emergency room (ER) visits, 6.2% had hospital admissions, and 1.2% had cost-related delays in care in the last year; 0.1 to 0.6 times lower than adults with CHDs without DS. Additionally, 26.7% had non-cardiac comorbidities (aPR = 1.25 [0.92-1.72]), most commonly sleep apnea (13.7% vs. 3.2%, aPR = 3.67 [2.02-6.67]). Receipt of cardiology care in the last 2 years was similarly low (52.7% vs. 44.7%). CONCLUSIONS: Adults with CHDs and DS comprise a substantial percentage of adults with CHDs and have unique health and healthcare needs. Half of adults with CHDs and DS are not receiving recommended routine cardiac care.

BACKGROUND: In Uganda, adolescent girls', and young women's (AGYW-15-24 years) current HIV prevalence is fourfold compared with their male counterparts due to compounded social, economic, and environmental factors. Using the Protective Motivation Theory (PMT), we explored HIV-acquisition risk sources and perceived protective factors from AGYW and caregivers' perspective. MATERIALS AND METHODS: During 2018, we conducted a qualitative study guided by PMT to explore factors influencing HIV acquisition among AGYW. We purposively sampled two groups of key informants, AGYW at high-risk for HIV acquisition (uninfected) and AGYW living with HIV, varied by age and place of residence (urban/rural). We conducted 34 focus group discussions with AGYW, nine with AGYW parents, and 25 key informant interviews. Data were analyzed using the framework method based on the PMT and developed from participants' narratives. RESULTS: AGYW were knowledgeable about HIV, HIV acquisition risk factors, and HIV prevention interventions. Nonetheless, few AGYW knew about pre-exposure prophylaxis (PrEP). Imbalance in power relations between the genders explained inability of AGYW making safe healthy decisions, with social norms giving men power over women. Parents modelling positively influenced HIV risk behavior. Many AGYW viewed staying in school a protective factor both while at school and further for life. AGYW identified alcohol use, desire for material possessions, discounting HIV disease severity, social norms, and poverty as barriers to engaging in self-protective behaviors. Several AGYW believed that access to AGYW-focused programs would facilitate healthy sex-positive, protective behaviors. DISCUSSION: While PMT focuses on individual factors confirmed by our findings, we found HIV risk behavior to be influenced by complex contextual factors including poverty, gender inequality and cultural norms. Distinct HIV risk factors among AGYW require policy and comprehensive targeted interventions addressing violence, alcohol consumption, increased economic opportunities, educational opportunities, safe-sex practices, and PrEP scale-up which may prevent HIV in AGYW and facilitate HIV epidemic control.

Transgender youth are disproportionately affected by HIV, particularly minoritized youth in the US south. To understand HIV service use among transgender youth, we interviewed 25 young racial and ethnic minority clients of four southern community-based HIV service organizations (CBOs), and CBO staff (n = 12), about service access and use. Participants were assigned male at birth and identified as female (n = 8), transgender (n = 11) or gender-fluid or nonbinary (n = 6). The majority were Black/African American or mixed race; four were Hispanic or Latino/a. Most were unemployed; nearly half were unstably housed or homeless during the prior year. Four service types were each used by approximately two-thirds of participants: counseling/support, HIV/STD testing/education, pre-exposure prophylaxis education/prescriptions, and transgender-related medical services (primarily hormone provision). Just over a quarter used social services (e.g., housing, employment). Key facilitators to service use included a non-stigmatizing CBO atmosphere, and easy and convenient access. Poor access (e.g., inconvenient hours, location), lack of transportation or parking, social service needs, and lack of money were barriers. Qualitative reports highlighted unmet social service needs, particularly housing, especially for those without HIV. To reduce disparities, HIV prevention for racial and ethnic minoritized transgender youth should simultaneously address hormone provision, HIV risk reduction and social service needs.

IMPORTANCE: The degree that in-home cannabis smoking can be detected in the urine of resident children is unclear. OBJECTIVE: Test association of in-home cannabis smoking with urinary cannabinoids in children living at home. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used baseline data from Project Fresh Air, a 2012-2016 randomized clinical trial to reduce fine particulate matter levels. Eligible participants were recruited from households in San Diego County, California, with children under age 14 years and an adult tobacco smoker in residence. Children's urine samples were analyzed in 2022. EXPOSURES: In-home cannabis smoking, measured by: parent or guardian report of in-home cannabis smoking; number of daily nonspecific smoking events computed via an air particle count algorithm; and number of daily cannabis smoking events ascertained by residualization, adjusting for air nicotine, tobacco smoking, and other air particle generating or ventilating activities. MAIN OUTCOMES AND MEASURES: Levels of the cannabis biomarker Δ9-tetrahydrocannabinol (THC) and its major metabolites, 11-hydroxy-Δ9-tetrahydrocannabinol and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol. Biomarker molar equivalents were summed to represent total THC equivalents (TTE) in urine. Logistic regression assessed whether in-home smoking was associated with cannabis biomarker detection. For children with detectable urinary cannabinoids, linear regression assessed in-home smoking association with quantity of urinary TTE. RESULTS: A total of 275 children were included in analysis (mean [SD] age, 3.6 [3.6] years; 144 male [52.4%]; 38 Black [13.8%], 132 Hispanic [48.0%], and 52 White [18.9%]). Twenty-nine households (10.6%) reported in-home cannabis smoking in the past 7 days; 75 children [27.3%] had detectable urinary cannabinoids. Odds of detectable TTE in children's urine were significantly higher in households with reported in-home cannabis smoking than households without (odds ratio [OR], 5.0; 95% CI, 2.4-10.4) and with each additional ascertained daily cannabis smoking event (OR, 2.5; 95% CI, 1.6-3.9). Although the point estimate for TTE levels was higher among children with detectable urinary cannabinoids and exposure to more daily cannabis smoking events (increase per event, 35.68%; 95% CI, -7.12% to 98.21%), the difference was not statistically significant. CONCLUSIONS AND RELEVANCE: In this cross-sectional study, in-home cannabis smoking was associated with significantly increased odds of child exposure to cannabis smoke, as assessed by urinary cannabinoid biomarkers. As young children spend most of their time at home, reducing in-home cannabis smoking could substantially reduce their exposure to the toxic and carcinogenic chemicals found in cannabis smoke.

Background: The World Health Organization (WHO) has developed guidance for community health workers (CHWs) in identifying sick young infants based on clinical signs. We conducted a prospective, observational cohort study to characterise mortality risk of young infants based on their clinical signs. Methods: We conducted a population-based, prospective observational cohort study at five sites in Bangladesh (Sylhet, November 01, 2011–December 31, 2013), India (Vellore and Odisha, September 01, 2013–February 28, 2015), and Pakistan (Karachi, January 01, 2012–December 31, 2013; Matiari, March 01, 2012–December 31, 2013) to identify newborn infants who were followed-up by CHWs through 10 scheduled home visits over the first 60 completed days after birth to identify signs of possible serious bacterial infection (PSBI). We determined the frequency of signs and conducted Cox regression to investigate the association of signs with mortality risk within 7 days of identification of the signs. Findings: CHWs made 522,309 visits to assess 63,017 young infants and found ≥1 sign(s) of PSBI at 14,245 visits (2.7%), including 5.8% (5568 of 96,390) and 1.8% (6635 of 365,769) of visits of infants 0–<3 and 7–<60 days of age, respectively. Each of the seven signs of PSBI when found alone was associated with significantly (p < 0.0001) increased risk for mortality, which increased further if any other additional sign of PSBI was found concurrently. Over the young infant period (days 0–<60) CHW identification of no movement or movement only on stimulation was associated with the highest risk for mortality [adjusted hazard ratio (aHR) 73.0, 95% confidence interval (CI) 44.4–119.9] followed by poor feeding (aHR 31.9, 95% CI 24.1–42.3) and hypothermia (<35.5 °C) (aHR 31.4, 95% CI 23.5–41.9). Hypothermia had particularly high risk for mortality during days 7–<60 (HR 45.1, 95% CI 27.6–73.4). Interpretation: WHO reconsideration of hypothermia as a sign of critical illness is warranted. Implementation research is urgently needed to reduce infant mortality by ensuring immediate referrals and interventions for children identified early by CHWs with no movement or movement only on stimulation, hypothermia, or poor feeding, especially in resource-poor settings. Funding: Bill and Melinda Gates Foundation, New Venture Fund for Global Policy and Advocacy. © 2025 The Author(s)

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: Persons aged 13-24 years are a priority population in the National HIV/AIDS Strategy. Young adults with HIV have poorer health outcomes-including not being retained in care, antiretroviral nonadherence, and not being virally suppressed-than other persons with HIV. SETTING: Centers for Disease Control and Prevention's Medical Monitoring Project data collected June 2018 through May 2022. METHODS: We compared demographic characteristics, social determinants of health (SDOH), and mental health between persons aged 18-24 years with HIV versus persons aged ≥25 years with HIV. Among those aged 18-24 years, we analyzed total and unmet needs for ancillary services, defined as those that support care engagement, viral suppression, and overall health and well-being among people with HIV. RESULTS: Persons aged 18-24 years were more likely to have a household income <100% of the federal poverty level (48% vs. 39%), and experience unstable housing or homelessness (37% vs. 18%) or hunger/food insecurity (29% vs. 18%) than those aged ≥25 years. Persons aged 18-24 years had higher median HIV stigma scores (40 vs. 29) and were more likely to experience symptoms of generalized anxiety disorder (21% vs. 15%) than those aged ≥25 years. Of persons aged 18-24 years, 96% had a need for ≥1 ancillary service, of whom 56% had ≥1 unmet need; unmet needs were highest for subsistence services (53%) and non-HIV medical services (41%). CONCLUSIONS: Addressing unmet needs for subsistence and non-HIV medical services could help reduce disparities in SDOH and mental health that drive inequities in health outcomes among persons with HIV aged 18-24 years.

BACKGROUND: Measures of diagnostic test accuracy provide evidence of how well a test correctly identifies or rules-out disease. Commonly used diagnostic accuracy measures (DAMs) include sensitivity and specificity, predictive values, likelihood ratios, area under the receiver operator characteristic curve (AUROC), area under precision-recall curves (AUPRC), diagnostic effectiveness (accuracy), disease prevalence, and diagnostic odds ratio (DOR) etc. Most available analysis tools perform accuracy testing for a single diagnostic test using summarized data. We developed a SAS macro for evaluating multiple diagnostic tests using individual-level data that creates a 2 × 2 summary table, AUROC and AUPRC as part of output. METHODS: The SAS macro presented here is automated to reduce analysis time and transcription errors. It is simple to use as the user only needs to specify the input dataset, "standard" and "test" variables and threshold values. It creates a publication-quality output in Microsoft Word and Excel showing more than 15 different accuracy measures together with overlaid AUROC and AUPRC graphics to help the researcher in making decisions to adopt or reject diagnostic tests. Further, it provides for additional variance estimation methods other than the normal distribution approximation. RESULTS: We tested the macro for quality control purposes by reproducing results from published work on evaluation of multiple types of dried blood spots (DBS) as an alternative for human immunodeficiency virus (HIV) viral load (VL) monitoring in resource-limited settings compared to plasma, the gold-standard. Plasma viral load reagents are costly, and blood must be prepared in a reference laboratory setting by a qualified technician. On the other hand, DBS are easy to prepare without these restrictions. This study evaluated the suitability of DBS from venous, microcapillary and direct spotting DBS, hence multiple diagnostic tests which were compared to plasma specimen. We also used the macro to reproduce results of published work on evaluating performance of multiple classification machine learning algorithms for predicting coronary artery disease. CONCLUSION: The SAS macro presented here is a powerful analytic tool for analyzing data from multiple diagnostic tests. The SAS programmer can modify the source code to include other diagnostic measures and variance estimation methods. By automating analysis, the macro adds value by saving analysis time, reducing transcription errors, and producing publication-quality outputs.

Influenza surveillance is important for monitoring influenza virus circulation and disease burden to inform influenza prevention and control measures. The aim of this study was to describe the epidemiology and to estimate the incidence of influenza in two communities in West Java, Indonesia, before and after the 2009 H1N1 pandemic. A population-based surveillance study in the community health care setting was conducted to estimate the annual incidence of influenza. A real-time reverse transcription polymerase chain reaction (RT-PCR) assay was used for influenza case ascertainment. A population census was implemented to calculate the population at risk and estimate community health care utilization rate. The mean annual incidence of influenza A and B, adjusted for healthcare utilization, was 1.6 (95%CI: 1.3–2.0) and 0.7 (95%CI: 0.5–1.0) per 1000 persons, respectively, with the most affected group being young and school-age children. The annual cumulative incidence of influenza A for children under five in 2009, 2010, and 2011 was 7.0 (95%CI: 4.4–11.2), 10.6 (95%CI: 7.3–15.4), and 6.3 (95%CI: 3.8– 10.2). For influenza B was 4.3 (95%CI: 2.4–7.8), 2.0 (95%CI: 0.8–4.7), and 0.4 (95%CI: 0.1–2.8), respectively. This study highlights that the incidence of influenza among young and school-age children is consistently higher compared to adults and the elderly throughout these periods. These populations are potential targets for influenza vaccination in Indonesia. © 2024, Narra Sains Indonesia. All rights reserved.

Young Black women in the southern US face a high HIV burden. While daily oral HIV pre-exposure prophylaxis (PrEP) can effectively prevent HIV, its use is low among Black women. The acceptability of and perceived intention to use emerging PrEP products among young Black women in the southern US are not well understood. Non-oral PrEP alternatives could address challenges to PrEP uptake and reduce health disparities. We conducted virtual semi-structured interviews with Black women aged 18-34 in Atlanta, GA; Baton Rouge, LA; and Jackson, MS, to explore their perspectives on three emerging PrEP products: a long-acting injection, a subdermal implant, and a dual-purpose contraception and HIV prevention intravaginal ring. Seventy-five interviews were conducted from January to October 2021 and analyzed using inductive thematic analysis with NVivo software. Most participants were open to using medication to prevent HIV. The intravaginal ring was the most preferred, primarily due to its dual-purpose function, although it was also frequently rejected. The long-acting injection was the second most preferred and least rejected, perceived as the least invasive. The skin implant was the least preferred and most rejected, viewed as the most invasive. Our findings highlight the need for multiple PrEP options to meet individual preferences. Detailed descriptions, instructions, and experiential learning methods are crucial for choosing non-oral PrEP modalities. Practitioners should address questions and offer peer-based learning opportunities. Designing and promoting PrEP strategies for young Black women should involve close consultation with these consumers.

More than 60 percent of US adults report that they had adverse childhood experiences (ACEs). For this study of 930,000 children born during the period 1999-2003, we used linked administrative, survey, and criminal justice data to measure the association between ACEs (parental death; separation; incarceration; or criminal charge for intimate partner violence, substance use disorder, or child sexual or nonsexual abuse) and socioeconomic disadvantages at ages 18-22 during 2017-21. After childhood socioeconomic status was controlled for, young adults with ACEs were more likely to have been charged with felonies, have become teenage parents, live in a household with poverty or housing assistance, be enrolled in Medicaid, and be employed, and were less likely to be enrolled in an educational institution. These outcomes were most likely among young adults with multiple ACEs or lower childhood socioeconomic status. Using new linked data opportunities, this study provides large-scale, person-level longitudinal evidence of the long-lasting and substantial societal cost of ACEs.

This study examines trends in buprenorphine dispensing from retail pharmacies to adolescents and young adults aged 10 to 24 years in the US from 2020 to 2023. | eng

BACKGROUND: Adolescent girls and young women (AGYW) aged 15-24 years are more likely to acquire HIV than their male counterparts, and well-targeted prevention interventions are needed. We developed a method to quantify the risk of HIV acquisition based on individual risk factors and population viral load (PVL) to improve targeting of prevention interventions. SETTING: This study is based on household health survey data collected in 13 sub-Saharan African countries, 2015-2019. METHODS: We developed a Bayesian spatial model which jointly estimates district-level PVL and the probability of infection among individual AGYW, aged 15-24 years, based on individual behavioral/demographic risk factors and area-level PVL. The districts (second subnational level) typically comprise the areas of estimation. The model borrows strength across countries by incorporating random effects which quantify country-level differences in HIV prevalence among AGYW. RESULTS: The combined survey data provided 52,171 questionnaire responses and blood tests from AGYW, and 280,323 blood samples from all respondents from which PVL was estimated. PVL was-by far-the most important predictor of test positivity (aOR = 70.6; 0.95-probability credible interval 20.7‒240.5). Having a partner with HIV increased the odds of testing positive among AGYW who were never (aOR = 12.1; 7.5‒19.6) and ever pregnant (aOR = 32.1; 23.7-43.4). The area under the cross-validated receiver-operating characteristic curve for classification of test positivity was 82%. CONCLUSION: The fitted model provides a statistically principled basis for priority enrollment in HIV prevention interventions of those AGYW most at risk of HIV infection and geographic placement of prevention services.

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.