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 to 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 (aOR) were calculated using logistic regression. Etiologic 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 was 74.5%; mortality was 3.9%, similar to RSV-positive (2.4%) and lower than other cases (9.6%). CONCLUSIONS: HMPV-associated severe pediatric 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.

After introducing pneumococcal conjugate vaccines (PCVs), serotype replacement occurred in Streptococcus pneumoniae. Predicting which pneumococcal strains will become common in carriage after vaccination can enhance vaccine design, public health interventions, and understanding of pneumococcal evolution. Invasive pneumococcal isolates were collected during 1998-2018 by the Active Bacterial Core surveillance (ABCs). Carriage data from Massachusetts (MA) and Southwest United States were used to calculate weights. Using pre-vaccine data, serotype-specific inverse-invasiveness weights were defined as the ratio of the proportion of the serotype in carriage to the proportion in invasive data. Genomic data were processed under bioinformatic pipelines to define genetically similar sequence clusters (i.e., strains), and accessory genes (COGs) present in 5-95% of isolates. Weights were applied to adjust observed strain proportions and COG frequencies. The negative frequency-dependent selection (NFDS) model predicted strain proportions by calculating the post-vaccine strain composition in the weighted invasive disease population that would best match pre-vaccine COG frequencies. Inverse-invasiveness weighting increased the correlation of COG frequencies between invasive and carriage data in linear or logit scale for pre-vaccine, post-PCV7, and post-PCV13; and between different epochs in the invasive data. Weighting the invasive data significantly improved the NFDS model's accuracy in predicting strain proportions in the carriage population in the post-PCV13 epoch, with the adjusted R(2) increasing from 0.254 before weighting to 0.545 after weighting. The weighting system adjusted invasive disease data to better represent the pneumococcal carriage population, allowing the NFDS mechanism to predict strain proportions in carriage in the post-PCV13 epoch. Our methods enrich the value of genomic sequences from invasive disease surveillance.IMPORTANCEStreptococcus pneumoniae, a common colonizer in the human nasopharynx, can cause invasive diseases including pneumonia, bacteremia, and meningitis mostly in children under 5 years or older adults. The PCV7 was introduced in 2000 in the United States within the pediatric population to prevent disease and reduce deaths, followed by PCV13 in 2010, PCV15 in 2022, and PCV20 in 2023. After the removal of vaccine serotypes, the prevalence of carriage remained stable as the vacated pediatric ecological niche was filled with certain non-vaccine serotypes. Predicting which pneumococcal clones, and which serotypes, will be most successful in colonization after vaccination can enhance vaccine design and public health interventions, while also improving our understanding of pneumococcal evolution. While carriage data, which are collected from the pneumococcal population that is competing to colonize and transmit, are most directly relevant to evolutionary studies, invasive disease data are often more plentiful. Previously, evolutionary models based on negative frequency-dependent selection (NFDS) on the accessory genome were shown to predict which non-vaccine strains and serotypes were most successful in colonization following the introduction of PCV7. Here, we show that an inverse-invasiveness weighting system applied to invasive disease surveillance data allows the NFDS model to predict strain proportions in the projected carriage population in the post-PCV13/pre-PCV15 and pre-PCV20 epoch. The significance of our research lies in using a sample of invasive disease surveillance data to extend the use of NFDS as an evolutionary mechanism to predict post-PCV13 population dynamics. This has shown that we can correct for biased sampling that arises from differences in virulence and can enrich the value of genomic data from disease surveillance and advance our understanding of how NFDS impacts carriage population dynamics after both PCV7 and PCV13 vaccination.

There is an unmet need for developing drugs for the treatment of gonorrhea, due to rapidly evolving resistance of Neisseria gonorrhoeae against antimicrobial drugs used for empiric therapy, an increase in globally reported multidrug resistant cases, and the limited available therapeutic options. Furthermore, few drugs are under development. Development of antimicrobials is hampered by challenges in clinical trial design, limitations of available diagnostics, changes in and varying standards of care, lack of robust animal models, and clinically relevant pharmacodynamic targets. On April 23, 2021, the U.S. Food and Drug Administration; Centers for Disease Control and Prevention; and National Institute of Allergy and Infectious Diseases, National Institutes of Health co-sponsored a workshop with stakeholders from academia, industry, and regulatory agencies to discuss the challenges and strategies, including potential collaborations and incentives, to facilitate the development of drugs for the treatment of gonorrhea. This article provides a summary of the workshop.

INTRODUCTION: During emergencies, breastfeeding protects infants by providing essential nutrients, food security, comfort, and protection and is a priority lifesaving intervention. On February 24, 2022, the war in Ukraine escalated, creating a humanitarian catastrophe. The war has resulted in death, injuries, and mass internal displacement of over 5 million people. A further 8.2 million people have taken refuge in neighboring countries, including Poland. Among those impacted are infants and young children and their mothers. We conducted a study to explore the infant feeding challenges and needs of Ukrainian women affected by the war. METHODS: We conducted a qualitative descriptive study involving in-depth interviews (IDIs) with 75 war-affected Ukrainian mothers who had at least one infant aged less than 12 months at the time of the interview. Eligible mothers were either (1) living as Ukrainian refugees in Poland, having crossed the border from Ukraine on or after February 24, 2022, when the war started (n = 30) or (2) living in Ukraine as internally displaced persons or as residents in the community (n = 45). All interviews were audio-recorded (either transcribed or had responses summarized as expanded notes) and analyzed using qualitative thematic analysis using a two-step rapid analysis process. RESULTS: Participants in Ukraine who wanted to initiate breastfeeding right after birth faced opposition from healthcare workers at maternity hospitals. Ukrainian refugees who gave birth in Poland faced language barriers when seeking breastfeeding support. Half of the participants in Ukraine received commercial milk formula (CMF) donations even if they said they did not need them. Most respondents stated that breastfeeding information and support were urgently needed. CONCLUSION: Our data suggests that healthcare workers in Ukrainian maternity hospitals require additional training and motivation on delivering breastfeeding support. In addition, lactation consultants in maternity ward are needed in Ukraine, and interpretation support is needed for refugees to overcome language barriers. There is a need to control the indiscriminate donations of commercial milk formula and to ensure that complementary foods and commercial milk formula are available to those that need it. This study confirms the need for actions to ensure infant and young child feeding (IYCF) support is provided during emergencies.

Background. Despite use of highly effective conjugate vaccines, invasive pneumococcal disease (IPD) remains a leading cause of morbidity and mortality and disproportionately affects Indigenous populations. Although included in the 13-valent pneumococcal conjugate vaccine (PCV13), which was introduced in 2010, serotype 3 continues to cause disease among Indigenous communities in the Southwest USA. In the Navajo Nation, serotype 3 IPD incidence increased among adults (3.8/100 000 in 2001-2009 and 6.2/100 000 in 2011-2019); in children the disease persisted although the rates dropped from 5.8/100 000 to 2.3/100 000.Methods. We analysed the genomic epidemiology of serotype 3 isolates collected from 129 adults and 63 children with pneumococcal carriage (n=61) or IPD (n=131) from 2001 to 2018 of the Navajo Nation. Using whole-genome sequencing data, we determined clade membership and assessed changes in serotype 3 population structure over time.Results. The serotype 3 population structure was characterized by three dominant subpopulations: clade II (n=90, 46.9 %) and clade Iα (n=59, 30.7 %), which fall into Clonal Complex (CC) 180, and a non-CC180 clade (n=43, 22.4 %). The proportion of clade II-associated IPD cases increased significantly from 2001 to 2010 to 2011-2018 among adults (23.1-71.8 %; P<0.001) but not in children (27.3-33.3 %; P=0.84). Over the same period, the proportion of clade II-associated carriage increased; this was statistically significant among children (23.3-52.6 %; P=0.04) but not adults (0-50.0 %, P=0.08).Conclusions. In this setting with persistent serotype 3 IPD and carriage, clade II has increased since 2010. Genomic changes may be contributing to the observed trends in serotype 3 carriage and disease over time.

INTRODUCTION: In 2012, the World Health Organization revised treatment guidelines for childhood pneumonia with lower chest wall indrawing (LCWI) but no 'danger signs', to recommend home-based treatment. We analysed data from children hospitalized with LCWI pneumonia in the Pneumonia Etiology Research for Child Health (PERCH) study to identify sub-groups with high odds of mortality, who might continue to benefit from hospital management but may not be admitted by staff implementing the 2012 guidelines. We compare the proportion of deaths identified using the criteria in the 2012 guidelines, and the proportion of deaths identified using an alternative set of criteria from our model. METHODS: PERCH enrolled a cohort of 2189 HIV-negative children aged 2-59 months who were admitted to hospital with LCWI pneumonia (without obvious cyanosis, inability to feed, vomiting, convulsions, lethargy or head nodding) between 2011-2014 in Kenya, Zambia, South Africa, Mali, The Gambia, Bangladesh, and Thailand. We analysed risk factors for mortality among these cases using predictive logistic regression. Malnutrition was defined as mid-upper-arm circumference <125mm or weight-for-age z-score <-2. RESULTS: Among 2189 cases, 76 (3·6%) died. Mortality was associated with oxygen saturation <92% (aOR 3·33, 1·99-5·99), HIV negative but exposed status (4·59, 1·81-11·7), moderate or severe malnutrition (6·85, 3·22-14·6) and younger age (infants compared to children 12-59 months old, OR 2·03, 95%CI 1·05-3·93). At least one of three risk factors: hypoxaemia, HIV exposure, or malnutrition identified 807 children in this population, 40% of LCWI pneumonia cases and identified 86% of the children who died in hospital (65/76). Risk factors identified using the 2012 WHO treatment guidelines identified 66% of the children who died in hospital (n = 50/76). CONCLUSIONS: Although it focuses on treatment failure in hospital, this study supports the proposal for better risk stratification of children with LCWI pneumonia. Those who have hypoxaemia, any malnutrition or those who were born to HIV positive mothers, experience poorer outcomes than other children with LCWI pneumonia. Consistent identification of these risk factors should be prioritised and children with at least one of these risk factors should not be managed in the community.

INTRODUCTION: Racial and ethnic minority groups and individuals with limited educational attainment experience a disproportionate burden of diabetes. Prediabetes represents a high-risk state for developing type 2 diabetes, but most adults with prediabetes are unaware of having the condition. Uncovering whether racial, ethnic, or educational disparities also occur in the prediabetes stage could help inform strategies to support health equity in preventing type 2 diabetes and its complications. We examined the prevalence of prediabetes and prediabetes awareness, with corresponding prevalence ratios according to race, ethnicity, and educational attainment. METHODS: This study was a pooled cross-sectional analysis of the National Health and Nutrition Examination Survey data from 2011 to March 2020. The final sample comprised 10,262 U.S. adults who self-reported being Asian, Black, Hispanic, or White. Prediabetes was defined using hemoglobin A1c and fasting plasma glucose values. Those with prediabetes were classified as "aware" or "unaware" based on survey responses. We calculated prevalence ratios (PR) to assess the relationship between race, ethnicity, and educational attainment with prediabetes and prediabetes awareness, controlling for sociodemographic, health and healthcare-related, and clinical characteristics. RESULTS: In fully adjusted logistic regression models, Asian, Black, and Hispanic adults had a statistically significant higher risk of prediabetes than White adults (PR:1.26 [1.18,1.35], PR:1.17 [1.08,1.25], and PR:1.10 [1.02,1.19], respectively). Adults completing less than high school and high school had a significantly higher risk of prediabetes compared to those with a college degree (PR:1.14 [1.02,1.26] and PR:1.12 [1.01,1.23], respectively). We also found that Black and Hispanic adults had higher rates of prediabetes awareness in the fully adjusted model than White adults (PR:1.27 [1.07,1.50] and PR:1.33 [1.02,1.72], respectively). The rates of prediabetes awareness were consistently lower among those with less than a high school education relative to individuals who completed college (fully-adjusted model PR:0.66 [0.47,0.92]). DISCUSSION: Disparities in prediabetes among racial and ethnic minority groups and adults with low educational attainment suggest challenges and opportunities for promoting health equity in high-risk groups and expanding awareness of prediabetes in the United States.

BACKGROUND: Phthalate exposures are ubiquitous during pregnancy and may contribute to racial and ethnic disparities in preterm birth. OBJECTIVES: We investigated race and ethnicity in the relationship between biomarkers of phthalate exposure and preterm birth by examining: a) how hypothetical reductions in racial and ethnic disparities in phthalate metabolites might reduce the probability of preterm birth; and b) exposure-response models stratified by race and ethnicity. METHODS: We pooled individual-level data on 6,045 pregnancies from 16 U.S. cohorts. We investigated covariate-adjusted differences in nine urinary phthalate metabolite concentrations by race and ethnicity [non-Hispanic White (White, 43%), non-Hispanic Black (Black, 13%), Hispanic/Latina (38%), and Asian/Pacific Islander (3%)]. Using g-computation, we estimated changes in the probability of preterm birth under hypothetical interventions to eliminate disparities in levels of urinary phthalate metabolites by proportionally lowering average concentrations in Black and Hispanic/Latina participants to be approximately equal to the averages in White participants. We also used race and ethnicity-stratified logistic regression to characterize associations between phthalate metabolites and preterm birth. RESULTS: In comparison with concentrations among White participants, adjusted mean phthalate metabolite concentrations were consistently higher among Black and Hispanic/Latina participants by 23%-148% and 4%-94%, respectively. Asian/Pacific Islander participants had metabolite levels that were similar to those of White participants. Hypothetical interventions to reduce disparities in metabolite mixtures were associated with lower probabilities of preterm birth for Black [13% relative reduction; 95% confidence interval (CI): - 34%, 8.6%] and Hispanic/Latina (9% relative reduction; 95% CI: - 19%, 0.8%) participants. Odds ratios for preterm birth in association with phthalate metabolites demonstrated heterogeneity by race and ethnicity for two individual metabolites (mono-n-butyl and monoisobutyl phthalate), with positive associations that were larger in magnitude observed among Black or Hispanic/Latina participants. CONCLUSIONS: Phthalate metabolite concentrations differed substantially by race and ethnicity. Our results show hypothetical interventions to reduce population-level racial and ethnic disparities in biomarkers of phthalate exposure could potentially reduce the probability of preterm birth. https://doi.org/10.1289/EHP12831.

BACKGROUND: Accreditation Council for Graduate Medical Education (ACGME) work-hour restrictions (WHRs) are intended to improve patient safety by reducing resident fatigue. Compliance with ACGME WHRs is not universal. PURPOSE: The purpose of this study was to identify factors that influence residents' decisions to take a postcall day (PCD) off according to ACGME WHRs. METHODS: Residents (N = 433) at one university were emailed a link to a survey in 2019. The survey included demographic details and a Discrete Choice Experiment examining influences on resident decisions to take a PCD off. RESULTS: One hundred seventy-five residents (40.4%) responded to the survey; 113 residents (26%) completed the survey. Positive feedback from attending physicians about taking PCDs off in the past had the greatest impact on respondents' decisions to take a PCD off, increasing the probability by 27.3%, followed by chief resident comments about the resident looking tired (16.6% increase), and having never heard their attendings comment about PCDs off as either positive or negative (13.9% increase). Factors that had the largest effect on decreasing the probability of taking a PCD were negative feedback about taking PCDs off (14.3% decrease), continuity of care concerns (10.8% decrease), and whether the resident was looking forward to an assignment (7.9% decrease). CONCLUSIONS: The most important influencer of residents' decisions to take a PCD off was related to feedback from their attending physicians, suggesting that compliance with WHRs can be improved by focusing on the residency program's safety culture.

The tragedy of transfusion-associated hepatitis and HIV spurred a decades-long overhaul of the regulatory oversight and practice of blood transfusion. Consequent to improved donor selection, testing, process control, clinical transfusion practice and post-transfusion surveillance, transfusion in the United States and other high-income countries is now a very safe medical procedure. Nonetheless, pathogens continue to emerge and threaten the blood supply, highlighting the need for a proactive approach to blood transfusion safety. Blood donor populations and the global transfusion infrastructure are under-utilized resources for the study of infectious diseases. Blood donors are large, demographically diverse subsets of general populations for whom cross-sectional and longitudinal samples are readily accessible for serological and molecular testing. Blood donor collection networks span diverse geographies, including in low- and middle-income countries, where agents, especially zoonotic pathogens, are able to emerge and spread, given limited tools for recognition, surveillance and control. Routine laboratory storage and transportation, coupled with data capture, afford access to rich epidemiological data to assess the epidemiology and pathogenesis of established and emerging infections. Subsequent to the State of the Science in Transfusion Medicine symposium in 2022, our working group (WG), "Emerging Infections: Impact on Blood Science, the Blood Supply, Blood Safety, and Public Health" elected to focus on "leveraging donor populations to study the epidemiology and pathogenesis of transfusion-transmitted and emerging infectious diseases." The 5 landmark studies span (1) the implication of hepatitis C virus in post-transfusion hepatitis, (2) longitudinal evaluation of plasma donors with incident infections, thus informing the development of a widely used staging system for acute HIV infection, (3) explication of the dynamics of early West Nile Virus infection, (4) the deployment of combined molecular and serological donor screening for Babesia microti, to characterize its epidemiology and infectivity and facilitate routine donor screening, and (5) national serosurveillance for SARS-CoV-2 during the COVID-19 pandemic. The studies highlight the interplay between infectious diseases and transfusion medicine, including the imperative to ensure blood transfusion safety and the broader application of blood donor populations to the study of infectious diseases.

INTRODUCTION: The American Diabetes Association (ADA) recommends screening for prediabetes and diabetes (dysglycemia) starting at age 35, or younger than 35 years among adults with overweight or obesity and other risk factors. Diabetes risk differs by sex, race, and ethnicity, but performance of the recommendation in these sociodemographic subgroups is unknown. METHODS: Nationally representative data from the National Health and Nutrition Examination Surveys (2015-March 2020) were analyzed from 5,287 nonpregnant US adults without diagnosed diabetes. Screening eligibility was based on age, measured body mass index, and the presence of diabetes risk factors. Dysglycemia was defined by fasting plasma glucose ≥100mg/dL (≥5.6 mmol/L) or haemoglobin A1c ≥5.7% (≥39mmol/mol). The sensitivity, specificity, and predictive values of the ADA screening criteria were examined by sex, race, and ethnicity. RESULTS: An estimated 83.1% (95% CI=81.2-84.7) of US adults were eligible for screening according to the 2023 ADA recommendation. Overall, ADA's screening criteria exhibited high sensitivity [95.0% (95% CI=92.7-96.6)] and low specificity [27.1% (95% CI=24.5-29.9)], which did not differ by race or ethnicity. Sensitivity was higher among women [97.8% (95% CI=96.6-98.6)] than men [92.4% (95% CI=88.3-95.1)]. Racial and ethnic differences in sensitivity and specificity among men were statistically significant (P=0.04 and P=0.02, respectively). Among women, guideline performance did not differ by race and ethnicity. DISCUSSION: The ADA screening criteria exhibited high sensitivity for all groups and was marginally higher in women than men. Racial and ethnic differences in guideline performance among men were small and unlikely to have a significant impact on health equity. Future research could examine adoption of this recommendation in practice and examine its effects on treatment and clinical outcomes by sex, race, and ethnicity.

Alzheimer’s disease and related dementias (ADRD) remain a public health priority, with prevalence of Alzheimer’s disease—the most common cause of dementia—among people aged 65 years and older living in the United States expected to grow to nearly 13.8 million people by 2060 (Alzheimer’s Association, 2023). ADRD are not normal aging; they impair memory and cognitive functioning, disrupting daily life. Over time, people with ADRD need increased assistance with basic activities of daily living and must rely on others for support, affecting family, friends, professional caregiving infrastructures, health and long-term care systems, and financial institutions designed to pay for care. In 2023, the formal cost of caring for people with ADRD to the health and long-term care systems in the United States is projected to total $345 billion (Alzheimer’s Association, 2023). Additionally, unpaid caregiving by family and friends was valued at nearly $339.5 billion in 2022 (Alzheimer’s Association, 2023). | | The lifetime cost of care for a person with Alzheimer’s disease was more than double the cost of care for a person without Alzheimer’s disease (Alzheimer’s Association, 2023). The total formal cost of ADRD care is projected to reach around $1 trillion in 2050 (Alzheimer’s Association, 2023; Zissimopoulos et al., 2014). These estimates do not consider the loss of quality of life for people with ADRD and their caregivers. It is imperative for the health of our systems and our population that public health address modifiable risk factors of ADRD.

Background The Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance (MORDOR) trial in Niger, Malawi, and Tanzania found that biannual mass distribution of azithromycin to children younger than 5 years led to a 13.5% reduction in all-cause mortality. Additional endpoints in the trial have attempted to elucidate the mechanisms for mortality reduction. In this pre-specified secondary analysis, we assessed the effect of azithromycin compared with placebo on IgG- based measures of infectious disease exposure with a multiplex bead assay that included antigens to malaria parasites (Plasmodium falciparum, P. vivax, P. malariae, P. ovale), bacterial pathogens (Campylobacter spp., enterotoxigenic Escherichia coli, Vibrio cholerae, Salmonella enterica, Streptococcus pyogenes) and protozoans (Cryptosporidium parvum, Giardia duodenales).Methods and Findings Thirty communities in rural Niger were randomized 1:1 to biannual distributions of azithromycin or placebo among children ages 1-59 months. The analysis included 5,642 blood specimens collected from 3,814 children ages 1-59 months, measured at 6, 12, 24, and 36 months of follow-up in a repeated cross-sectional design. Campylobacter spp. seroprevalence averaged over all study visits was lower in azithromycin communities compared to placebo (91% vs 94%, difference = –3%, 95% CI: –5%, –1%; P=0.03), which corresponded to a 29% lower seroconversion rate (1.30 versus 1.84 seroconversions per year, hazard ratio = 0.71, 95% CI: 0.56, 0.89; P=0.004). Antibody-based measures of infection with P. falciparum and group A streptococcus were consistently lower in azithromycin communities, but were not statistically different from placebo, and there were no other differences across pathogens. Strengths of the study included masking of participants, investigators, and analysts, high treatment coverage, large sample size, and objective outcomes. Principal limitations included the timing of blood collection with respect to treatment (approximately 6 months later, which could have missed transient effects in the weeks immediately following treatment), and the durability of IgG response following clearance of infection. Both limitations would lead the trial to under-estimate effects on antibody-based measures of infection.Conclusions The reduction in Campylobacter spp. despite these limitations suggests an effect on carriage, findings which align with an independent metagenomic analysis of rectal swabs collected in the same villages and with previously reported reductions in dysentery-associated mortality. Given significant sequelae of Campylobacter infection among preschool aged children, our results support at least one possible mechanism through which biannual mass distribution of azithromycin likely reduced mortality in this study population.Competing Interest StatementThis work was supported by the Bill &amp; Melinda Gates Foundation (award no. OPP1032340 to TML) and was supported in part by an unrestricted grant from Research to Prevent Blindness and by the National Institute of Allergy and Infectious Diseases (award no. K01-AI119180 to BFA). The Gates Foundation approved the study design, but had no role in data collection, data analysis, data interpretation, or writing of the report. The authors declare no competing interests. The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. Use of trade names is for identification only and does not imply endorsement by the Public Health Service or by the U.S. Department of Health and Human Services. Clinical TrialNCT02048007Funding StatementThis work was supported by the Bill &amp; Melinda Gates Foundation (award no. OPP1032340 to TML) and was supported in part by an unrestricted grant from Research to Prevent Blindness and by the National Institute of Allergy and Infectious Diseases (award no. K01-AI119180 to BFA). The Gates Foundation approved the study design, but had no role in data collection, data nalysis, data interpretation, or writing of the report.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:The trial protocol was reviewed and approved by the Committee on Human Research at the University of California, San Francisco, and the Niger Ministry of Health's Ethical Committee. Parents or guardians of enrolled children provided oral consent before each azithromycin or placebo treatment and at each specimen collection visit. Parents or guardians were instructed to report any adverse event within 7 days of treatment by contacting their village representative, who then reported events to the site coordinator and UCSF. An independent Data and Safety Monitoring Committee provided additional oversight. CDC researchers had access to de-identified samples for analysis (no personally identifying information).All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesData and computational notebooks used to conduct the analyses are available through the Open Science Framework (https://osf.io/954bt) and Dryad (xx DOI forthcoming xx). Analyses used R statistical software, version 4.0.2. https://osf.io/954bt

Candida auris is a multidrug-resistant yeast which has emerged in healthcare facilities worldwide, however little is known about identification methods, patient colonization, spread, environmental survival, and drug resistance. Colonization on both biotic and abiotic surfaces, along with travel, appear to be the major factors for the spread of this pathogen across the globe. In this investigation, we present laboratory findings from an ongoing C. auris outbreak in NY from August 2016 through 2018. A total of 540 clinical isolates, 11,035 patient surveillance specimens, and 3,672 environmental surveillance samples were analyzed. Laboratory methods included matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for yeast isolate identification, real-time PCR for rapid surveillance sample screening, culture on selective/non-selective media for recovery of C. auris and other yeasts from surveillance samples, antifungal susceptibility testing to determine the C. auris resistance profile, and Sanger sequencing of ribosomal genes for C. auris genotyping. Results included: a) identification and confirmation of C. auris in 413 clinical isolates and 931 patient surveillance isolates, as well as identification of 277 clinical cases and 350 colonized cases from 151 healthcare facilities including 59 hospitals, 92 nursing homes, 1 long-term acute care hospital (LTACH), and 2 hospices, b) successful utilization of an in-house developed C. auris real-time PCR assay for the rapid screening of patient and environmental surveillance samples, c) demonstration of relatively heavier colonization of C. auris in nares compared to the axilla/groin, and d) predominance of the South Asia Clade I with intrinsic resistance to fluconazole and elevated minimum inhibitory concentration (MIC) to voriconazole (81%), amphotericin B (61%), 5-FC (3%) and echinocandins (1%). These findings reflect greater regional prevalence and incidence of C. auris and the deployment of better detection tools in an unprecedented outbreak.

Streptococcus pneumoniae serotype 3 remains a significant cause of morbidity and mortality worldwide, despite inclusion in the 13-valent pneumococcal conjugate vaccine (PCV13). Serotype 3 increased in carriage since the implementation of PCV13 in the United States, while invasive disease rates remain unchanged. We investigated the persistence of serotype 3 in carriage and disease, through genomic analyses of a global sample of 301 serotype 3 isolates of the Netherlands3–31 (PMEN31) clone CC180, combined with associated patient data and PCV utilization among countries of isolate collection. We assessed phenotypic variation between dominant clades in capsule charge (zeta potential), capsular polysaccharide shedding, and susceptibility to opsonophagocytic killing, which have previously been associated with carriage duration, invasiveness, and vaccine escape. We identify a recent shift in the CC180 population attributed to a lineage termed Clade II, which was estimated by Bayesian coalescent analysis to have first appeared in 1968 [95% HPD: 1939–1989] and increased in prevalence and effective population size thereafter. Clade II isolates are divergent from the pre-PCV13 serotype 3 population in non-capsular antigenic composition, competence, and antibiotic susceptibility, the last resulting from the acquisition of a Tn916-like conjugative transposon. Differences in recombination rates among clades correlated with variations in the ATP-binding subunit of Clp protease as well as amino acid substitutions in the comCDE operon. Opsonophagocytic killing assays elucidated the low observed efficacy of PCV13 against serotype 3. Variation in PCV13 use among sampled countries was not independently correlated with the CC180 population shift; therefore, genotypic and phenotypic differences in protein antigens and, in particular, antibiotic resistance may have contributed to the increase of Clade II. Our analysis emphasizes the need for routine, representative sampling of isolates from disperse geographic regions, including historically under-sampled areas. We also highlight the value of genomics in resolving antigenic and epidemiological variations within a serotype, which may have implications for future vaccine development.Author Summary Streptococcus pneumoniae is a leading cause of bacterial pneumoniae, meningitis, and otitis media. Despite inclusion in the most recent pneumococcal conjugate vaccine, PCV13, serotype 3 remains epidemiologically important globally. We investigated the persistence of serotype 3 using whole-genome sequencing data form 301 isolates collected among 24 countries from 1993–2014. Through phylogenetic analysis, we identified three distinct lineages within a single clonal complex, CC180, and found one has recently emerged and grown in prevalence. We then compared genomic difference among lineages as well as variations in pneumococcal vaccine use among sampled countries. We found that the recently emerged lineage, termed Clade II, has a higher prevalence of antibiotic resistance compared to other lineages, diverse surface protein antigens, and a higher rate of recombination, a process by which bacteria can uptake and incorporate genetic material from its surroundings. Differences in vaccine use among sampled countries did not appear to be associated with the emergence of Clade II. We highlight the need to routine, representative sampling of bacterial isolates from diverse geographic areas and show the utility of genomic data in resolving epidemiological differences within a pathogen population.

INTRODUCTION: In 2021, the U.S. Preventive Services Task Force (USPSTF) recommended prediabetes and diabetes screening for asymptomatic adults aged 35-70 years with overweight/obesity, lowering the age from 40 years in its 2015 recommendation. The USPSTF suggested considering earlier screening in racial and ethnic groups with high diabetes risk at younger ages or lower BMI. This study examined the clinical performance of these USPSTF screening recommendations as well as alternative age and BMI cutoffs in the U.S. adult population overall, and separately by race and ethnicity. METHODS: Nationally representative data were collected from 3,243 nonpregnant adults without diagnosed diabetes in January 2017-March 2020 and analyzed from 2021 to 2022. Screening eligibility was based on age and measured BMI. Collectively, prediabetes and undiagnosed diabetes were defined by fasting plasma glucose ≥100 mg/dL or hemoglobin A(1c) ≥5.7%. The sensitivity, specificity, and predictive values of alternate screening criteria were examined overall, and by race and ethnicity. RESULTS: The 2021 criteria exhibited marginally higher sensitivity (58.6%, 95% CI=55.5, 61.6 vs 52.9%, 95% CI=49.7, 56.0) and lower specificity (69.3%, 95% CI=65.7, 72.2 vs 76.4%, 95% CI=73.3, 79.2) than the 2015 criteria overall, and within each racial and ethnic group. Screening at lower age and BMI thresholds resulted in even greater sensitivity and lower specificity, especially among Hispanic, non-Hispanic Black, and Asian adults. Screening all adults aged 35-70 years regardless of BMI yielded the most equitable performance across all racial and ethnic groups. CONCLUSIONS: The 2021 USPSTF screening criteria will identify more adults with prediabetes and diabetes in all racial and ethnic groups than the 2015 criteria. Screening all adults aged 35-70 years exhibited even higher sensitivity and performed most similarly by race and ethnicity, which may further improve early detection of prediabetes and diabetes in diverse populations.

BACKGROUND: Pneumonia is the leading cause of death among children younger than 5 years. In this study, we estimated causes of pneumonia in young African and Asian children, using novel analytical methods applied to clinical and microbiological findings. METHODS: We did a multi-site, international case-control study in nine study sites in seven countries: Bangladesh, The Gambia, Kenya, Mali, South Africa, Thailand, and Zambia. All sites enrolled in the study for 24 months. Cases were children aged 1-59 months admitted to hospital with severe pneumonia. Controls were age-group-matched children randomly selected from communities surrounding study sites. Nasopharyngeal and oropharyngeal (NP-OP), urine, blood, induced sputum, lung aspirate, pleural fluid, and gastric aspirates were tested with cultures, multiplex PCR, or both. Primary analyses were restricted to cases without HIV infection and with abnormal chest x-rays and to controls without HIV infection. We applied a Bayesian, partial latent class analysis to estimate probabilities of aetiological agents at the individual and population level, incorporating case and control data. FINDINGS: Between Aug 15, 2011, and Jan 30, 2014, we enrolled 4232 cases and 5119 community controls. The primary analysis group was comprised of 1769 (41·8% of 4232) cases without HIV infection and with positive chest x-rays and 5102 (99·7% of 5119) community controls without HIV infection. Wheezing was present in 555 (31·7%) of 1752 cases (range by site 10·6-97·3%). 30-day case-fatality ratio was 6·4% (114 of 1769 cases). Blood cultures were positive in 56 (3·2%) of 1749 cases, and Streptococcus pneumoniae was the most common bacteria isolated (19 [33·9%] of 56). Almost all cases (98·9%) and controls (98·0%) had at least one pathogen detected by PCR in the NP-OP specimen. The detection of respiratory syncytial virus (RSV), parainfluenza virus, human metapneumovirus, influenza virus, S pneumoniae, Haemophilus influenzae type b (Hib), H influenzae non-type b, and Pneumocystis jirovecii in NP-OP specimens was associated with case status. The aetiology analysis estimated that viruses accounted for 61·4% (95% credible interval [CrI] 57·3-65·6) of causes, whereas bacteria accounted for 27·3% (23·3-31·6) and Mycobacterium tuberculosis for 5·9% (3·9-8·3). Viruses were less common (54·5%, 95% CrI 47·4-61·5 vs 68·0%, 62·7-72·7) and bacteria more common (33·7%, 27·2-40·8 vs 22·8%, 18·3-27·6) in very severe pneumonia cases than in severe cases. RSV had the greatest aetiological fraction (31·1%, 95% CrI 28·4-34·2) of all pathogens. Human rhinovirus, human metapneumovirus A or B, human parainfluenza virus, S pneumoniae, M tuberculosis, and H influenzae each accounted for 5% or more of the aetiological distribution. We observed differences in aetiological fraction by age for Bordetella pertussis, parainfluenza types 1 and 3, parechovirus-enterovirus, P jirovecii, RSV, rhinovirus, Staphylococcus aureus, and S pneumoniae, and differences by severity for RSV, S aureus, S pneumoniae, and parainfluenza type 3. The leading ten pathogens of each site accounted for 79% or more of the site's aetiological fraction. INTERPRETATION: In our study, a small set of pathogens accounted for most cases of pneumonia requiring hospital admission. Preventing and treating a subset of pathogens could substantially affect childhood pneumonia outcomes. FUNDING: Bill & Melinda Gates Foundation.

After the emergence of SARS-CoV-2 in late 2019, transmission expanded globally, and on January 30, 2020, COVID-19 was declared a public health emergency of international concern.* Analysis of the early Wuhan, China outbreak (1), subsequently confirmed by multiple other studies (2,3), found that 80% of deaths occurred among persons aged ≥60 years. In anticipation of the time needed for the global vaccine supply to meet all needs, the World Health Organization (WHO) published the Strategic Advisory Group of Experts on Immunization (SAGE) Values Framework and a roadmap for prioritizing use of COVID-19 vaccines in late 2020 (4,5), followed by a strategy brief to outline urgent actions in October 2021.(†) WHO described the general principles, objectives, and priorities needed to support country planning of vaccine rollout to minimize severe disease and death. A July 2022 update to the strategy brief(§) prioritized vaccination of populations at increased risk, including older adults,(¶) with the goal of 100% coverage with a complete COVID-19 vaccination series** for at-risk populations. Using available public data on COVID-19 mortality (reported deaths and model estimates) for 2020 and 2021 and the most recent reported COVID-19 vaccination coverage data from WHO, investigators performed descriptive analyses to examine age-specific mortality and global vaccination rollout among older adults (as defined by each country), stratified by country World Bank income status. Data quality and COVID-19 death reporting frequency varied by data source; however, persons aged ≥60 years accounted for >80% of the overall COVID-19 mortality across all income groups, with upper- and lower-middle-income countries accounting for 80% of the overall estimated excess mortality. Effective COVID-19 vaccines were authorized for use in December 2020, with global supply scaled up sufficiently to meet country needs by late 2021 (6). COVID-19 vaccines are safe and highly effective in reducing severe COVID-19, hospitalizations, and mortality (7,8); nevertheless, country-reported median completed primary series coverage among adults aged ≥60 years only reached 76% by the end of 2022, substantially below the WHO goal, especially in middle- and low-income countries. Increased efforts are needed to increase primary series and booster dose coverage among all older adults as recommended by WHO and national health authorities.

AIMS: Recent USPSTF and ADA guidelines expanded criteria of whom to test to identify prediabetes and diabetes. We described which Americans are eligible and report receiving glucose testing by USPSTF 2015 and 2021 as well as ADA 2003 and 2022 recommendations, and performance of each guideline. METHODS: We analyzed cross-sectional data from 6,007 non-pregnant U.S. adults without diagnosed diabetes in the 2013-2018 National Health and Nutrition Examination Surveys. We reported proportions of adults who met each guideline's criteria for glucose testing and reported receiving glucose testing in the past three years, overall and by key population subgroups,. Defining prediabetes (FPG 100-125mg/dL and/or HbA1c 5.7-6.4%) or previously undiagnosed diabetes (FPG≥126mg/dL and/or HbA1c≥6.5%), we assessed sensitivity and specificity. RESULTS: During 2013-2018, 76.7 million, 90.4 million, 157.7 million, and 169.5 million US adults met eligibility for glucose testing by USPSTF 2015, 2021, and ADA 2003 and 2022 guidelines, respectively. On average, 52% of adults reported receiving glucose testing within the past 3 years. Likelihood of receiving glucose testing was lower among younger adults, men, Hispanic adults, those with less than high school completion, those living in poverty, and those without health insurance or a usual place of care than their respective counterparts. ADA recommendations were most sensitive (range: 91.0% to 100.0%) and least specific (range: 18.3% to 35.3%); USPSTF recommendations exhibited lower sensitivity (51.9% to 66.6%), but higher specificity (56.6% to 74.5%). CONCLUSIONS: An additional 12-14 million US adults are eligible for diabetes screening. USPSTF 2021 criteria provide balanced sensitivity and specificity while ADA 2022 criteria maximize sensitivity. Glucose testing does not align with guidelines and disparities remain.

In November 2020, the Seventy-Third World Health Assembly endorsed the Immunization Agenda 2030: A Global Strategy to Leave No One Behind (IA2030) in decision WHA73/(9). IA2030 defines what needs to happen to achieve the global vision of a world where everyone, everywhere, at every age fully benefits from vaccines for good health and well-being. | | IA2030 is a global strategy created for the global community and requiring broad ownership by all immunization and non-immunization stakeholders, including those involved in health system strengthening and disease-specific initiatives. While WHO was asked to lead the development of IA2030, all stakeholders co-created, co-developed and now co-own it. IA2030 has been designed to respond to the interests of each and every country, regardless of income level or geography. Recognizing that the most important actions for success must be taken by individual Member States, IA2030 aims to reinforce country ownership for planning and implementing effective and comprehensive vaccination programmes.

INTRODUCTION: The Accreditation Council for Graduate Medical Education (ACGME), which sets the standards for residency training, instituted work-hour restrictions in 2003. Our purpose was to assess residents' perceptions of fatigue and local safety climate specific to these duty-hour restrictions. METHODS:  All residents (N=433) at one university were emailed a link to a survey in 2019. The survey included demographic details, on-call descriptors, an 18-point climate survey (CS), and the 33-point Chalder Fatigue Questionnaire (CFQ). The CS was adapted from a commonly used safety climate scale and intended to measure the respondent's perceptions of their program's attitudes and practices around resident duty-hour compliance. A Pearson correlational analysis was used to determine if there were associations between the variables. RESULTS:  Mean CS score was 12.89 (95% confidence interval, CI 12.32-13.46, N=164, 48.5%). Respondents were most likely to disagree with "Residents are told when they are at risk of working beyond ACGME duty-hour restrictions," where 57 (34.7%) disagreed or strongly disagreed. Mean CFQ score was 16.02 (95% CI 14.87-17.17, N=113, 26.1%). As the CS score improved, CFQ scores decreased indicating an inverse relationship between duty-hour climate and fatigue (r=-0.328, p<0.05). Having a protected post-call day off, and having either the Program Director, Chief Resident, or Senior Resident decide that a resident takes a post-call day off were all associated with higher CS scores.  Conclusion: We found that the CS had good internal consistency and evidence of construct validity. An inverse relationship between CS score and fatigue suggests that the level of fatigue is higher among residents in programs where residents perceived that ACGME duty-hour compliance was less important.

In a report on the rise of emergency department visits for opioid overdoses, the US Centers for Disease Control and Prevention (CDC) described the importance of coordinated, informed efforts with public safety, including first responders and law enforcement.2 Since 2015, CDC has awarded millions in funding to support overdose prevention and surveillance efforts through Overdose Data to Action, the Overdose Response Strategy, and the Opioid Rapid Response Program.3,4 Improving partnerships between PH/PS to reduce drug overdose deaths is a core component of these signature CDC programs.5–7

CONTEXT: Public health and public safety collaborations can strengthen and improve efforts to address the worsening drug overdose crisis. PROGRAM: The Overdose Response Strategy is addressing this need through a national public health and public safety program designed to foster the cross-sector sharing of timely data, pertinent intelligence, and evidence-based and innovative strategies to prevent and respond to drug overdose. IMPLEMENTATION: Since 2015, the Overdose Response Strategy has been implemented by state-based public health and public safety teams who work together to prevent and respond to drug overdoses within and across sectors, states, and territories. The public health and public safety teams share data systems to inform rapid and effective community overdose prevention efforts; support immediate, evidence-based response efforts that can directly reduce overdose deaths; design and use promising strategies at the intersection of public health and public safety; and use effective and efficient primary prevention strategies that can reduce substance use and overdose long term. Implementation of the Overdose Response Strategy aligns with the US Centers for Disease Control and Prevention's Strategic Partnering Framework. EVALUATION: The evaluation of the Overdose Response Strategy, which is currently underway, is based on 2 evaluation approaches: Collective Impact and Organizational Network Analysis. These approaches provide a way to look at the strength of the relationship between public health and public safety and the way the relationship is leveraged to advance program goals and objectives. DISCUSSION: The Overdose Response Strategy serves as a strategic partnership model that can potentially be applied to other issues, such as gun violence, that may benefit from public health and public safety collaboration.

Monkeypox virus (MPXV) is an orthopoxvirus in the Poxviridae family. The current multinational monkeypox outbreak has now spread to 96 countries that have not historically reported monkeypox, with most cases occurring among gay, bisexual, and other men who have sex with men (1,2). The first monkeypox case in the United States associated with this outbreak was identified in May 2022 in Massachusetts (1); monkeypox has now been reported in all 50 states, the District of Columbia (DC), and one U.S. territory. MPXV is transmitted by close contact with infected persons or animals; infection results in a febrile illness followed by a diffuse vesiculopustular rash and lymphadenopathy. However, illness in the MPXV current Clade II outbreak has differed: the febrile prodrome is frequently absent or mild, and the rash often involves genital, anal, or oral regions (3,4). Although neuroinvasive disease has been previously reported with MPXV infection (5,6), it appears to be rare. This report describes two cases of encephalomyelitis in patients with monkeypox disease that occurred during the current U.S. outbreak. Although neurologic complications of acute MPXV infections are rare, suspected cases should be reported to state, tribal, local, or territorial health departments to improve understanding of the range of clinical manifestations of and treatment options for MPXV infections during the current outbreak.

IMPORTANCE: Phthalate exposure is widespread among pregnant women and may be a risk factor for preterm birth. OBJECTIVE: To investigate the prospective association between urinary biomarkers of phthalates in pregnancy and preterm birth among individuals living in the US. DESIGN, SETTING, AND PARTICIPANTS: Individual-level data were pooled from 16 preconception and pregnancy studies conducted in the US. Pregnant individuals who delivered between 1983 and 2018 and provided 1 or more urine samples during pregnancy were included. EXPOSURES: Urinary phthalate metabolites were quantified as biomarkers of phthalate exposure. Concentrations of 11 phthalate metabolites were standardized for urine dilution and mean repeated measurements across pregnancy were calculated. MAIN OUTCOMES AND MEASURES: Logistic regression models were used to examine the association between each phthalate metabolite with the odds of preterm birth, defined as less than 37 weeks of gestation at delivery (n=539). Models pooled data using fixed effects and adjusted for maternal age, race and ethnicity, education, and prepregnancy body mass index. The association between the overall mixture of phthalate metabolites and preterm birth was also examined with logistic regression. G-computation, which requires certain assumptions to be considered causal, was used to estimate the association with hypothetical interventions to reduce the mixture concentrations on preterm birth. RESULTS: The final analytic sample included 6045 participants (mean [SD] age, 29.1 [6.1] years). Overall, 802 individuals (13.3%) were Black, 2323 (38.4%) were Hispanic/Latina, 2576 (42.6%) were White, and 328 (5.4%) had other race and ethnicity (including American Indian/Alaskan Native, Native Hawaiian, >1 racial identity, or reported as other). Most phthalate metabolites were detected in more than 96% of participants. Higher odds of preterm birth, ranging from 12% to 16%, were observed in association with an interquartile range increase in urinary concentrations of mono-n-butyl phthalate (odds ratio [OR], 1.12 [95% CI, 0.98-1.27]), mono-isobutyl phthalate (OR, 1.16 [95% CI, 1.00-1.34]), mono(2-ethyl-5-carboxypentyl) phthalate (OR, 1.16 [95% CI, 1.00-1.34]), and mono(3-carboxypropyl) phthalate (OR, 1.14 [95% CI, 1.01-1.29]). Among approximately 90 preterm births per 1000 live births in this study population, hypothetical interventions to reduce the mixture of phthalate metabolite levels by 10%, 30%, and 50% were estimated to prevent 1.8 (95% CI, 0.5-3.1), 5.9 (95% CI, 1.7-9.9), and 11.1 (95% CI, 3.6-18.3) preterm births, respectively. CONCLUSIONS AND RELEVANCE: Results from this large US study population suggest that phthalate exposure during pregnancy may be a preventable risk factor for preterm delivery.

IMPORTANCE: Because transmission of ocular strains of Chlamydia trachomatis is greatest among preschool-aged children, limiting azithromycin distributions to this age group may conserve resources and result in less antimicrobial resistance, which is a potential advantage in areas with hypoendemic trachoma and limited resources. OBJECTIVE: To determine the efficacy of mass azithromycin distributions to preschool-aged children as a strategy for trachoma elimination in areas with hypoendemic disease. DESIGN, SETTING, AND PARTICIPANTS: In this cluster randomized clinical trial performed from November 23, 2014, until July 31, 2017, thirty rural communities in Niger were randomized at a 1:1 ratio to biannual mass distributions of either azithromycin or placebo to children aged 1 to 59 months. Participants and study personnel were masked to treatment allocation. Data analyses for trachoma outcomes were performed from October 19, 2021, through June 10, 2022. INTERVENTIONS: Every 6 months, a single dose of either oral azithromycin (20 mg/kg using height-based approximation for children who could stand or weight calculation for small children) or oral placebo was provided to all children aged 1 to 59 months. MAIN OUTCOMES AND MEASURES: Trachoma was a prespecified outcome of the trial, assessed as the community-level prevalence of trachomatous inflammation-follicular and trachomatous inflammation-intense through masked grading of conjunctival photographs from a random sample of 40 children per community each year during the 2-year study period. A secondary outcome was the seroprevalence of antibodies to C trachomatis antigens. RESULTS: At baseline, 4726 children in 30 communities were included; 1695 children were enrolled in 15 azithromycin communities and 3031 children were enrolled in 15 placebo communities (mean [SD] proportions of boys, 51.8% [4.7%] vs 52.0% [4.2%]; mean [SD] age, 30.8 [2.8] vs 30.6 [2.6] months). The mean coverage of study drug for the 4 treatments was 79% (95% CI, 75%-83%) in the azithromycin group and 82% (95% CI, 79%-85%) in the placebo group. The mean prevalence of trachomatous inflammation-follicular at baseline was 1.9% (95% CI, 0.5%-3.5%) in the azithromycin group and 0.9% (95% CI, 0-1.9%) in the placebo group. At 24 months, trachomatous inflammation-follicular prevalence was 0.2% (95% CI, 0-0.5%) in the azithromycin group and 0.8% (95% CI, 0.2%-1.6%) in the placebo group (incidence rate ratio adjusted for baseline: 0.18 [95% CI, 0.01-1.20]; permutation P = .07). CONCLUSIONS AND RELEVANCE: The findings of this trial do not show that biannual mass azithromycin distributions to preschool-aged children were more effective than placebo, although the underlying prevalence of trachoma was low. The sustained absence of trachoma even in the placebo group suggests that trachoma may have been eliminated as a public health problem in this part of Niger. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02048007.

OBJECTIVE: Although geographically specific data can help target HIV prevention and treatment strategies, Nigeria relies on national- and state-level estimates for policymaking and intervention planning. We calculated sub-state estimates along the HIV continuum of care in Nigeria. DESIGN: Using data from the Nigeria HIV/AIDS Indicator and Impact Survey (NAIIS) (July-December 2018), we conducted a geospatial analysis estimating three key programmatic indicators: prevalence of HIV infection among adults (aged 15-64 years); antiretroviral therapy (ART) coverage among adults living with HIV; and viral load suppression (VLS) rate among adults living with HIV. METHODS: We used an ensemble modeling method called stacked generalization to analyze available covariates and a geostatistical model to incorporate the output from stacking as well as spatial autocorrelation in the modeled outcomes. Separate models were fitted for each indicator. Finally, we produced raster estimates of each indicator on an approximately 5×5-km grid and estimates at the sub-state/local government area (LGA) and state level. RESULTS: Estimates for all three indicators varied both within and between states. While state-level HIV prevalence ranged from 0.3% (95% uncertainty interval [UI]: 0.3%-0.5%]) to 4.3% (95% UI: 3.7%-4.9%), LGA prevalence ranged from 0.2% (95% UI: 0.1%-0.5%) to 8.5% (95% UI: 5.8%-12.2%). Although the range in ART coverage did not substantially differ at state level (25.6%-76.9%) and LGA level (21.9%-81.9%), the mean absolute difference in ART coverage between LGAs within states was 16.7 percentage points (range, 3.5-38.5 percentage points). States with large differences in ART coverage between LGAs also showed large differences in VLS-regardless of level of effective treatment coverage-indicating that state-level geographic targeting may be insufficient to address coverage gaps. CONCLUSION: Geospatial analysis across the HIV continuum of care can effectively highlight sub-state variation and identify areas that require further attention in order to achieve epidemic control. By generating local estimates, governments, donors, and other implementing partners will be better positioned to conduct targeted interventions and prioritize resource distribution.

In this issue of the Journal, we highlight the problem of violence against children globally. We conceptualized this process and the thematic focus and widely disseminated an invitation to submit manuscripts. Each of us took the lead editorial role in a group of manuscripts submitted for this issue. Dr. Viswanathan led the review process for manuscripts submitted by Moe et. al, Seff et. al., Couture et. al, Osborne et. al, Khan et. al., and Friedman et. al. Dr Villaveces led the reviews of Pendharkar et. al, Tang et. al, Ryan et. al, Bravo Sanzana et. al, Flynn O'Brien et. al., Silverman et. al., and Taliep et.al. We hope that readers will see the complexities related to violence against children and get a better sense of the global implications of this problem.

The MORDOR trial in Niger, Malawi, and Tanzania found that biannual mass distribution of azithromycin to children younger than 5 years led to a 13.5% reduction in all-cause mortality (NCT02048007). To help elucidate the mechanism for mortality reduction, we report IgG responses to 11 malaria, bacterial, and protozoan pathogens using a multiplex bead assay in pre-specified substudy of 30 communities in the rural Niger placebo-controlled trial over a three-year period (n = 5642 blood specimens, n = 3814 children ages 1-59 months). Mass azithromycin reduces Campylobacter spp. force of infection by 29% (hazard ratio = 0.71, 95% CI: 0.56, 0.89; P = 0.004) but serological measures show no significant differences between groups for other pathogens against a backdrop of high transmission. Results align with a recent microbiome study in the communities. Given significant sequelae of Campylobacter infection among preschool aged children, our results support an important mechanism through which biannual mass distribution of azithromycin likely reduces mortality in Niger.