High-quality vaccine-preventable disease (VPD) surveillance data are critical for timely outbreak detection and response. In 2019, the World Health Organization (WHO) African Regional Office (AFRO) began transitioning from Epi Info, a free, CDC-developed statistical software package with limited capability to integrate with other information systems, affecting reporting timeliness and data use, to District Health Information Software 2 (DHIS2). DHIS2 is a free and open-source software platform for electronic aggregate Integrated Disease Surveillance and Response (IDSR) and case-based surveillance reporting. A national-level reporting system, which provided countries with the option to adopt this new system, was introduced. Regionally, the Epi Info database will be replaced with a DHIS2 regional data platform. This report describes the phased implementation from 2019 to the present. Phase one (2019-2021) involved developing IDSR aggregate and case-based surveillance packages, including pilots in the countries of Mali, Rwanda, and Togo. Phase two (2022) expanded national-level implementation to 27 countries and established the WHO AFRO DHIS2 regional data platform. Phase three (from 2023 to the present) activities have been building local capacity and support for country reporting to the regional platform. By February 2024, eight of 47 AFRO countries had adopted both the aggregate IDSR and case-based surveillance packages, and two had successfully transferred VPD surveillance data to the AFRO regional platform. Challenges included limited human and financial resources, the need to establish data-sharing and governance agreements, technical support for data transfer, and building local capacity to report to the regional platform. Despite these challenges, the transition to DHIS2 will support efficient data transmission to strengthen VPD detection, response, and public health emergencies through improved system integration and interoperability.

This cross-sectional study assesses the reliability and validity of methods used to capture gender identity in Adolescent Brain Cognitive Development (ABCD) Study participants. | eng

The 2017-2018 North American influenza season caused more hospitalizations and deaths than any year since the 2009 H1N1 pandemic. The majority of recorded influenza infections were caused by A(H3N2) viruses, with most of the virus’s North American diversity falling into the A2 clade. Within A2, we observe a subclade which we call A2/re that rose to comprise almost 70% of A(H3N2) viruses circulating in North America by early 2018. Unlike most fast-growing clades, however, A2/re contains no amino acid substitutions in the hemagglutinin (HA) segment. Moreover, HI assays did not suggest substantial antigenic differences between A2/re viruses and viruses sampled during the 2016-2017 season. Rather, we observe that the A2/re clade was the result of a reassortment event that occurred in late 2016 or early 2017 and involved the combination of the HA and PB1 segments of an A2 virus with neuraminidase (NA) and other segments a virus from the clade A1b. The success of this clade shows the need for antigenic analysis that targets NA in addition to HA. Our results illustrate the potential for non-HA drivers of viral success and necessitate the need for more thorough tracking of full viral genomes to better understand the dynamics of influenza epidemics.

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

The COVID-19 pandemic challenged countries to protect their populations from this emerging disease. One aspect of that challenge was to rapidly modify national surveillance systems or create new systems that would effectively detect new cases of COVID-19. Fifty-five countries leveraged past investments in District Health Information Software version 2 (DHIS2) to quickly adapt their national public health surveillance systems for COVID-19 case reporting and response activities. We provide background on DHIS2 and describe case studies from Sierra Leone, Sri Lanka, and Uganda to illustrate how the DHIS2 platform, its community of practice, long-term capacity building, and local autonomy enabled countries to establish an effective COVID-19 response. With these case studies, we provide valuable insights and recommendations for strategies that can be used for national electronic disease surveillance platforms to detect new and emerging pathogens and respond to public health emergencies.

BACKGROUND: Human adenoviruses typically cause self-limited respiratory, gastrointestinal, and conjunctival infections in healthy children. In late 2021 and early 2022, several previously healthy children were identified with acute hepatitis and human adenovirus viremia. METHODS: We used International Classification of Diseases, 10th Revision, codes to identify all children (<18 years of age) with hepatitis who were admitted to Children's of Alabama hospital between October 1, 2021, and February 28, 2022; those with acute hepatitis who also tested positive for human adenovirus by whole-blood quantitative polymerase chain reaction (PCR) were included in our case series. Demographic, clinical, laboratory, and treatment data were obtained from medical records. Residual blood specimens were sent for diagnostic confirmation and human adenovirus typing. RESULTS: A total of 15 children were identified with acute hepatitis - 6 (40%) who had hepatitis with an identified cause and 9 (60%) who had hepatitis without a known cause. Eight (89%) of the patients with hepatitis of unknown cause tested positive for human adenovirus. These 8 patients plus 1 additional patient referred to this facility for follow-up were included in this case series (median age, 2 years 11 months; age range, 1 year 1 month to 6 years 5 months). Liver biopsies indicated mild-to-moderate active hepatitis in 6 children, some with and some without cholestasis, but did not show evidence of human adenovirus on immunohistochemical examination or electron microscopy. PCR testing of liver tissue for human adenovirus was positive in 3 children (50%). Sequencing of specimens from 5 children showed three distinct human adenovirus type 41 hexon variants. Two children underwent liver transplantation; all the others recovered with supportive care. CONCLUSIONS: Human adenovirus viremia was present in the majority of children with acute hepatitis of unknown cause admitted to Children's of Alabama from October 1, 2021, to February 28, 2022, but whether human adenovirus was causative remains unclear. Sequencing results suggest that if human adenovirus was causative, this was not an outbreak driven by a single strain. (Funded in part by the Centers for Disease Control and Prevention.).

Sexual health education experienced by lesbian, gay, and bisexual (LGB) youth varies widely in relevancy and representation. However, associations among sexual orientation, type of sex education, and exposure to affirming or disaffirming content have yet to be examined. Understanding these patterns can help to address gaps in LGB-sensitive sex education. Our goal in this study was to examine the prevalence and associations among abstinence-only until marriage (AOUM) and comprehensive sex education with LGB-affirming and -disaffirming content sought/received before age 18 (from 1999 to 2014) by sexual orientation (completely heterosexual with same-sex contact, completely heterosexual with no same-sex contact, mostly heterosexual, bisexual, gay/lesbian) in a sample of 12,876 US young adults from the Growing Up Today Study. Compared to completely heterosexual referents, LGB participants who received AOUM sex education were more likely to encounter LGB-disaffirming content, and this effect was largest among sexual minority participants. Conversely, exposure to comprehensive sex education was associated with receipt of LGB-affirming information. Overall, participants commonly reported receiving AOUM sex education, which may lead to deficits and potential harm to sexual minorities. 2022 Informa UK Limited, trading as Taylor & Francis Group.

During October-November 2021, clinicians at a children's hospital in Alabama identified five pediatric patients with severe hepatitis and adenovirus viremia upon admission. In November 2021, hospital clinicians, the Alabama Department of Public Health, the Jefferson County Department of Health, and CDC began an investigation. This activity was reviewed by CDC and conducted consistent with applicable federal law and CDC policy.

The Adolescent Brain Cognitive Development(SM) (ABCD) study is a longitudinal study of adolescent brain development and health that includes over 11,800 youth in the United States. The ABCD study includes broad developmental domains, and gender and sexuality are two of these with noted changes across late childhood and early adolescence. The Gender Identity and Sexual Health (GISH) workgroup recommends measures of gender and sexuality for the ABCD study, prioritizing those that are developmentally sensitive, capture individual differences in the experience of gender and sexuality, and minimize participant burden. This manuscript describes the gender and sexuality measures used in ABCD and provides guidance for researchers using these data. Data showing the utility of these measures and longitudinal trends are presented. Including assessment of gender and sexuality in ABCD allows for characterization of developmental trajectories of gender and sexuality, and the broad scope of ABCD data collection allows examination of identity development in an intersectional manner.

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

BACKGROUND: Human papillomavirus (HPV) vaccine effectiveness (VE) evaluations provide important information for vaccination programs. We established a linkage between statewide central registries in Michigan to estimate HPV VE against in situ and invasive cervical lesions (CIN3+). METHODS: We linked females in Michigan's immunization and cancer registries using birth records to establish a cohort of 773,193 women with known vaccination history, of whom 3,838 were diagnosed with CIN3+. Residential address histories from a stratified random sample were used to establish a subcohort of 1,374 women without CIN3+ and 2,900 with CIN3+ among continuous Michigan residents. VE and 95% confidence intervals (CI) were estimated using cohort and case-cohort methods for up-to-date (UTD) vaccination and incomplete vaccination with 1 and 2 doses, and stratified by age at vaccination. RESULTS: Both analytic approaches demonstrated lower CIN3+ risk with UTD and non-UTD vaccination vs. no vaccination. The cohort analysis yielded VE estimates of 66% (95% CI 60-71%) for UTD, 33% (95% CI 18-46%) for 2 doses-not UTD, and 40% (95% CI 27-50%) for 1 dose. The case-cohort analysis yielded VE estimates of 72% (95% CI 64-79%) for UTD, 39% (95% CI 10-58%) for 2 doses-not UTD, and 48% (95% CI 25-63%) for 1 dose. VE was higher for vaccination at age <20 than {greater than or equal to}20 years. CONCLUSIONS: The statewide registry linkage found significant VE against CIN3+ with incomplete HPV vaccination, and an even higher VE with UTD vaccination. IMPACT: Future VE evaluations by number of doses for women vaccinated at younger ages may further clarify dose-related effectiveness.

The radiation-attenuated Plasmodium falciparum sporozoite (PfSPZ) vaccine provides protection against P. falciparum infection in malaria-naïve adults. Preclinical studies show that T cell-mediated immunity is required for protection and is readily induced in humans after vaccination. However, previous malaria exposure can limit immune responses and vaccine efficacy (VE) in adults. We hypothesized that infants with less previous exposure to malaria would have improved immunity and protection. We conducted a multi-arm, randomized, double-blind, placebo-controlled trial in 336 infants aged 5-12 months to determine the safety, tolerability, immunogenicity and efficacy of the PfSPZ Vaccine in infants in a high-transmission malaria setting in western Kenya ( NCT02687373 ). Groups of 84 infants each received 4.5 × 10(5), 9.0 × 10(5) or 1.8 × 10(6) PfSPZ Vaccine or saline three times at 8-week intervals. The vaccine was well tolerated; 52 (20.6%) children in the vaccine groups and 20 (23.8%) in the placebo group experienced related solicited adverse events (AEs) within 28 d postvaccination and most were mild. There was 1 grade 3-related solicited AE in the vaccine group (0.4%) and 2 in the placebo group (2.4%). Seizures were more common in the highest-dose group (14.3%) compared to 6.0% of controls, with most being attributed to malaria. There was no significant protection against P. falciparum infection in any dose group at 6 months (VE in the 9.0 × 10(5) dose group = -6.5%, P = 0.598, the primary statistical end point of the study). VE against clinical malaria 3 months after the last dose in the highest-dose group was 45.8% (P = 0.027), an exploratory end point. There was a dose-dependent increase in antibody responses that correlated with VE at 6 months in the lowest- and highest-dose groups. T cell responses were undetectable across all dose groups. Detection of Vδ2(+)Vγ9(+) T cells, which have been correlated with induction of PfSPZ Vaccine T cell immunity and protection in adults, were infrequent. These data suggest that PfSPZ Vaccine-induced T cell immunity is age-dependent and may be influenced by Vδ2(+)Vγ9(+) T cell frequency. Since there was no significant VE at 6 months in these infants, these vaccine regimens will likely not be pursued further in this age group.

INTRODUCTION: Limited research exists about how receiving/seeking sexual and reproductive health (SRH) information differs by sexual orientation. Our goal was to identify how sources and topics of SRH information differed by sexual orientation during adolescence in a sample of U.S. women. METHODS: A sample of 8,541 U.S. women ages 22-35 years from two cohorts of the Growing Up Today Study completed a 2016 questionnaire measure about receiving/seeking SRH information before age 18 years. Adjusted log-linear models assessed differences in SRH information topics and sources by reported sexual orientation (completely heterosexual with no same-sex partners [reference]; completely heterosexual with same-sex partners; mostly heterosexual; bisexual; lesbian). RESULTS: Compared to the referent, most sexual minority subgroups were more likely to receive/seek information from peers, media, and other sources (e.g., community centers). With the exception of lesbians, sexual minority subgroups were more likely to receive/seek information about contraception, and mostly heterosexual and bisexual women were more likely to receive information about sexually transmitted infections. Conclusions: Findings indicate women of diverse sexual orientations need access to SRH information from sources like schools, peers, and media. Sexual minority women receive/seek information about many SRH topics, which indicates that opportunities to tailor educational resources within and outside of schools are needed so SRH benefits to these populations are maximized. POLICY IMPLICATIONS: Specifying sexual minority-sensitive educational materials in sex education policy can meet information needs and aid sexual minority women in making informed sexual health decisions.

BACKGROUND: The Core Elements of Outpatient Antibiotic Stewardship provide a framework to improve antibiotic use, but evidence supporting safety are limited. We report the impact of Core Elements implementation within Veterans Health Administration sites. METHODS: A quasi-experimental controlled study assessed the effects of an intervention targeting antibiotic prescription for uncomplicated acute respiratory tract infections (ARI). Outcomes included per-visit antibiotic prescribing, treatment appropriateness, potential benefits and complications of reduced antibiotic treatment, and change in ARI diagnoses over a 3-year pre-implementation and 1-year post implementation period. Logistic regression adjusted for covariates [OR (95% CI)] and a difference-in-differences analysis compared outcomes between intervention and control sites. RESULTS: From 2014-2019, there were 16,712 and 51,275 patient-visits in 10 intervention and 40 control sites, respectively. Antibiotic prescribing rates pre-post implementation in intervention sites were 59.7% and 41.5%, respectively; in control sites they were 73.5% and 67.2%, respectively [difference-in-differences p<0.001]. The intervention site pre-post implementation odds ratio to receive appropriate therapy increased [1.67 (1.31, 2.14)] which remained unchanged within control sites [1.04 (0.91, 1.19)]. There was no difference in ARI-related return visits post-implementation [(-1.3% vs. -2.0%; difference-in-differences p=0.76] but all-cause hospitalization was lower within intervention sites [(-0.5% vs. -0.2%); difference-in-differences p=0.02]. The odds ratio to diagnose upper respiratory tract infection not otherwise specified compared to other non-ARI diagnosis increased post-implementation for intervention [1.27(1.21,1.34)] but not control [0.97(0.94,1.01)] sites. CONCLUSIONS: Implementation of the Core Elements was associated with reduced antibiotic prescribing for uncomplicated ARIs and a reduction in hospitalizations. ARI diagnostic coding changes were observed.

The 2017-2018 North American influenza season caused more hospitalizations and deaths than any year since the 2009 H1N1 pandemic. The majority of recorded influenza infections were caused by A(H3N2) viruses, with most of the virus's North American diversity falling into the A2 clade. Within A2, we observe a subclade which we call A2/re that rose to comprise almost 70 per cent of A(H3N2) viruses circulating in North America by early 2018. Unlike most fast-growing clades, however, A2/re contains no amino acid substitutions in the hemagglutinin (HA) segment. Moreover, hemagglutination inhibition assays did not suggest substantial antigenic differences between A2/re viruses and viruses sampled during the 2016-2017 season. Rather, we observe that the A2/re clade was the result of a reassortment event that occurred in late 2016 or early 2017 and involved the combination of the HA and PB1 segments of an A2 virus with neuraminidase (NA) and other segments a virus from the clade A1b. The success of this clade shows the need for antigenic analysis that targets NA in addition to HA. Our results illustrate the potential for non-HA drivers of viral success and necessitate the need for more thorough tracking of full viral genomes to better understand the dynamics of influenza epidemics.

BACKGROUND: VZV vasculopathy is characterized by persistent arterial inflammation leading to stroke. Studies show that VZV induces amyloid formation that may aggravate vasculitis. Thus, we determined if VZV central nervous system (CNS) infection produces amyloid. METHODS: Aβ peptides, amylin, and amyloid were measured in CSF from 16 VZV vasculopathy subjects and 36 stroke controls. To determine if infection induced amyloid deposition, mock- and VZV-infected quiescent primary human perineurial cells (qHPNCs), present in vasculature, were analyzed for intracellular amyloidogenic transcripts/proteins and amyloid. Supernatants were assayed for amyloidogenic peptides and ability to induce amyloid formation. To determine amylin's function during infection, amylin was knocked down with siRNA and viral cDNA quantitated. RESULTS: Compared to controls, VZV vasculopathy CSF had increased amyloid that positively correlated with amylin and anti-VZV antibody levels; Aβ40 was reduced and Aβ42 unchanged. Intracellular amylin, Aβ42, and amyloid were seen only in VZV-infected qHPNCs. VZV-infected supernatant formed amyloid fibrils following addition of amyloidogenic peptides. Amylin knockdown decreased viral cDNA. CONCLUSIONS: VZV infection increased levels of amyloidogenic peptides and amyloid in CSF and qHPNCs, indicating that VZV-induced amyloid deposition may contribute to persistent arterial inflammation in VZV vasculopathy. In addition, we identified a novel proviral function of amylin.

BACKGROUND: There are known associations between mental health symptoms and transgender identity among adults. Whether this relationship extends to early adolescents and to gender domains other than identity is unclear. This study measured dimensions of gender in a large, diverse, sample of youth, and examined associations between diverse gender experiences and mental health. METHODS: The ABCD study is an ongoing, longitudinal, US cohort study. Baseline data (release 2.0) include 11,873 youth age 9/10 (48% female); and the 4,951 1-year follow-up visits (age 10/11; 48% female) completed prior to data release. A novel gender survey at the 1-year visit assessed felt-gender, gender noncontentedness, and gender nonconformity using a 5-point scale. Mental health measures included youth- and parent-reports. RESULTS: Roughly half a percent of 9/10-year-olds (n = 58) responded 'yes' or 'maybe' when asked, 'Are you transgender' at baseline. Recurrent thoughts of death were more prevalent among these youth compared to the rest of the cohort (19.6% vs. 6.4%, chi(2) = 16.0, p < .001). At the 1-year visit, when asked about the three dimensions of gender on a 5-point scale, 33.2% (n = 1,605) provided responses that were not exclusively and totally aligned with one gender. Significant relationships were observed between mental health symptoms and gender diversity for all dimensions assessed. CONCLUSIONS: Similar to adult studies, early adolescents identifying as transgender reported increased mental health symptoms. Results also point to considerable diversity in other dimensions of gender (felt-gender, gender noncontentedness, gender nonconformity) among 10/11-year-olds, and find this diversity to be related to critical mental health symptoms. These findings add to our limited understanding of the relationship between dimensions of gender and wellness for youth.

Obesity negatively affects children's health because of its associations with cardiovascular disease risk factors, type 2 diabetes, asthma, fatty liver disease, victimization stemming from social stigma and bullying, and poor mental health (e.g., anxiety and depression) (1). Children who have overweight or obesity in early childhood are approximately four times as likely to have overweight or obesity in young adulthood as their normal weight peers (2). Obesity prevalence is especially high among children from low-income families (3). In 2010, the overall upward trend in obesity prevalence turned downward among children aged 2-4 years enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC), a program of the U.S. Department of Agriculture (USDA); prevalence decreased significantly in all racial/ethnic groups and in 34 of the 56 WIC state or territory agencies during 2010-2014 (4). A more recent study among young children enrolled in WIC reported that the overall obesity prevalence decreased from 15.9% in 2010 to 13.9% in 2016 and statistically significant decreases were observed in all age, sex, and racial/ethnic subgroups (3). However, this study did not provide obesity trends at the state level. In collaboration with USDA, CDC used data from the WIC Participant and Program Characteristics (WIC PC) to update state-specific trends through 2016. During 2010-2016, modest but statistically significant decreases in obesity prevalence among children aged 2-4 years enrolled in WIC occurred in 41 (73%) of 56 WIC state or territory agencies. Comprehensive approaches that create positive changes to promote healthy eating and physical activity for young children from all income levels,* strengthen nutrition education and breastfeeding support among young children enrolled in WIC, and encourage redemptions of healthy foods in WIC food packages could help maintain or accelerate these declining trends.

Prevalence of childhood obesity is high in the United States, especially among children from lower-income families.1 Among children aged 2 through 4 years enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC), obesity prevalence increased between 2000 and 2010 but declined through 2014.2 The decline was statistically significant among all racial/ethnic groups and in 34 of 56 state WIC agencies. The present study examines trends in overweight and obesity by age, sex, and race/ethnicity using WIC data from 2010 to 2016.

BACKGROUND: We describe early health services utilization for children diagnosed with medium-chain acyl-CoA dehydrogenase (MCAD) deficiency through newborn screening in Ontario, Canada, relative to a screen negative comparison cohort. METHODS: Eligible children were identified via newborn screening between April 1, 2006 and March 31, 2010. Age-stratified rates of physician encounters, emergency department (ED) visits and inpatient hospitalizations to March 31, 2012 were compared using incidence rate ratios (IRR) and incidence rate differences (IRD). We used negative binomial regression to adjust IRRs for sex, gestational age, birth weight, socioeconomic status and rural/urban residence. RESULTS: Throughout the first few years of life, children with MCAD deficiency (n = 40) experienced statistically significantly higher rates of physician encounters, ED visits, and hospital stays compared with the screen negative cohort. The highest rates of ED visits and hospitalizations in the MCAD deficiency cohort occurred from 6 months to 2 years of age (ED use: 2.1-2.5 visits per child per year; hospitalization: 0.5-0.6 visits per child per year), after which rates gradually declined. CONCLUSIONS: This study confirms that young children with MCAD deficiency use health services more frequently than the general population throughout the first few years of life. Rates of service use in this population gradually diminish after 24 months of age.

BACKGROUND: Sulfadoxine-pyrimethamine resistance threatens efficacy of intermittent preventive treatment of malaria during pregnancy, and alternative regimens need to be identified. With the return of chloroquine efficacy in southern Africa, we postulated that chloroquine either as an intermittent therapy or as weekly chemoprophylaxis would be more efficacious than intermittent sulfadoxine-pyrimethamine for prevention of malaria in pregnancy and associated maternal and newborn adverse outcomes. METHODS: We did an open-label, single-centre, randomised controlled trial at Ndirande Health Centre, Blantyre, in southern Malawi. We enrolled pregnant women (first or second pregnancy) at 20-28 weeks' gestation who were HIV negative. Participants were randomly assigned in a 1:1:1 ratio using a computer-generated list to either intermittent sulfadoxine-pyrimethamine (two doses of 1500 mg sulfadoxine and 75 mg pyrimethamine, 4 weeks apart), intermittent chloroquine (two doses of 600 mg on day 1, 600 mg on day 2, and 300 mg on day 3), or chloroquine prophylaxis (600 mg on day 1 then 300 mg every week). The primary endpoint was placental malaria in the modified intent-to-treat population, which consisted of participants who contributed placental histopathology data at birth. Secondary outcomes included clinical malaria, maternal anaemia, low birthweight, and safety. This trial is registered with ClinicalTrials.gov, number NCT01443130. FINDINGS: Between February, 2012, and May, 2014, we enrolled and randomly allocated 900 women, of whom 765 contributed histopathological data and were included in the primary analysis. 108 (14%) women had placental malaria, which was lower than the anticipated prevalence of placental malaria infection. Protection from placental malaria was not improved by chloroquine as either prophylaxis (30 [12%] of 259 had positive histopathology; relative risk [RR] 0.75, 95% CI 0.48-1.17) or intermittent therapy (39 [15%] of 253; RR 1.00, 0.67-1.50) compared with intermittent sulfadoxine-pyrimethamine (39 [15%] of 253). In protocol-specified analyses adjusted for maternal age, gestational age at enrolment, bednet use the night before enrolment, anaemia at enrolment, and malaria infection at enrolment, women taking chloroquine as prophylaxis had 34% lower placental infections than did those allocated intermittent sulfadoxine-pyrimethamine (RR 0.66, 95% CI 0.46-0.95). Clinical malaria was reported in nine women assigned intermittent sulfadoxine-pyrimethamine, four allocated intermittent chloroquine (p=0.26), and two allocated chloroquine prophylaxis (p=0.063). Maternal anaemia was noted in five women assigned intermittent sulfadoxine-pyrimethamine, 15 allocated intermittent chloroquine (p=0.038), and six assigned chloroquine prophylaxis (p>0.99). Low birthweight was recorded for 31 babies born to women allocated intermittent sulfadoxine-pyrimethamine, 29 assigned intermittent chloroquine (p=0.78), and 41 allocated chloroquine prophylaxis (p=0.28). Four women assigned intermittent sulfadoxine-pyrimethamine had adverse events possibly related to study product compared with 94 women allocated intermittent chloroquine (p<0.0001) and 26 allocated chloroquine prophylaxis (p<0.0001). Three women had severe or life-threatening adverse events related to study product, of whom all were assigned intermittent chloroquine (p=0.25). INTERPRETATION: Chloroquine administered as intermittent therapy did not provide better protection from malaria and related adverse effects compared with intermittent sulfadoxine-pyrimethamine in a setting of high resistance to sulfadoxine-pyrimethamine. Chloroquine chemoprophylaxis might provide benefit in protecting against malaria during pregnancy, but studies with larger sample sizes are needed to confirm these results. FUNDING: US National Institutes of Health.

Given the potential for human exposure to silver nanoparticles from spray disinfectants and dietary supplements, we characterized the silver-containing nanoparticles in 22 commercial products that advertised the use of silver or colloidal silver as the active ingredient. Characterization parameters included: total silver, fractionated silver (particulate and dissolved), primary particle size distribution, hydrodynamic diameter, particle number, and plasmon resonance absorbance. A high degree of variability between claimed and measured values for total silver was observed. Only 7 of the products showed total silver concentrations within 20% of their nominally reported values. In addition, significant variations in the relative percentages of particulate vs. soluble silver were also measured in many of these products reporting to be colloidal. Primary silver particle size distributions by transmission electron microscopy (TEM) showed two populations of particles - smaller particles (< 5 nm) and larger particles between 20 and 40 nm. Hydrodynamic diameter measurements using nanoparticle tracking analysis (NTA) correlated well with TEM analysis for the larger particles. Z-average (Z-Avg) values measured using dynamic light scattering (DLS); however, were typically larger than both NTA or TEM particle diameters. Plasmon resonance absorbance signatures (peak absorbance at around 400 nm indicative of metallic silver nanoparticles) were only noted in 4 of the 9 yellow-brown colored suspensions. Although the total silver concentrations were variable among products, ranging from 0.54 mg/L to 960 mg/L, silver containing nanoparticles were identified in all of the product suspensions by TEM.

BACKGROUND: Concerns regarding vaccine safety and pain have prompted certain parents to limit the number of shots their child receives per visit. We estimated the prevalence of shot-limited children in Michigan, described their characteristics, assessed whether shot-limited children were up-to-date on recommended vaccinations, and investigated possible intervention points for vaccination education. METHODS: We analyzed vaccination registry and birth record data of children born in Michigan during 2012 who had 2 vaccination visits, with 1 visits after age 5months. Shot-limited was defined as receiving 2 shots at all visits through age 24months. Nonlimited children received >2 shots at 1 visits. Up-to-date vaccination was based on receipt of a seven-vaccine series and was determined at ages 24months and 35months. Risk ratios (RR) were calculated using risk regression. RESULTS: Of 101,443 children, a total of 2,967 (3%) children were shot-limited. Mothers of shot-limited children were more likely to be white (RR: 1.2; 95% confidence interval [CI]: 1.2-1.2), college graduate (RR: 1.9; 95% CI: 1.9-2.0), and married (RR: 1.5; 95% CI: 1.5-1.5). Compared with nonlimited children, shot-limited children were more likely to be born in a nonhospital setting (RR: 11.7; 95% CI: 9.4-14.6) and have a midwife attendant (RR: 1.9; 95% CI: 1.7-2.1). Shot-limited children were less likely to be up-to-date on recommended vaccinations (RR: 0.2; 95% CI: 0.2-0.3); this association was stronger for those with a midwife birth attendant (RR: 0.1; 95% CI: 0.1-0.2) rather than a medical doctor (RR: 0.3; 95% CI: 0.2-0.3). CONCLUSIONS: Shot-limited children are less likely to be up-to-date on vaccinations, possibly leading to increased risk for vaccine-preventable diseases. This association was stronger for those with a midwife birth attendant. This analysis should prompt targeted education, such as to midwives, concerning risks associated with shot-limiting behavior.

Three human clinical isolates (X1654, X1655, and W9944) were recovered from the sputum and bronchial washings of two patients with pulmonary infections. The 16S rRNA gene sequence analysis of the isolates showed that they share 100 % sequence similarity with each other and belong to the genus Nocardia. Close phylogenetic neighbours are Nocardia brevicatena ATCC 15333T (98.6 %) and Nocardia paucivorans ATCC BAA-278T (98.4 %). The in silico DNA-DNA relatedness between the isolates ranges from 96.8 to 100 % suggesting that they belong to the same genomic species. The DNA-DNA relatedness between X1654 and N. brevicatena ATCC 15333T is 13.3 +/- 2.3 % and N. paucivorans ATCC BAA-278T is 18.95 +/- 1.1 % suggesting that they do not belong to the same genomic species. Believed to represent a novel species, these isolates were further characterised to establish their taxonomic standing within the genus. Chemotaxonomic data for isolate X1654 are consistent with those described for the genus Nocardia: this isolate produced saturated and unsaturated fatty acids, tuberculostearic acid (15.9 %), the major menaquinone was MK-8 (H4cyclic), mycolic acid chain lengths ranged from 38 to 58 carbons, produced meso-diaminopimelic acid with arabinose, glucose, and galactose as the whole cell sugars. The polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, and phosphatidylinositol mannosides. The DNA G+C content is 66.7 mol %. Based on the combination of phenotypic, chemotaxonomic, and genotypic data for X1654, X1655, and W9944, we conclude that these isolates represent a novel species within the genus Nocardia for which we propose the name Nocardia donostiensis sp. nov. with X1654T (=DSM 46814T = CECT 8839T) as the type strain.

BACKGROUND: There is no consensus in the literature regarding the impact of false positive newborn screening results on early health care utilization patterns. We evaluated the impact of false positive newborn screening results for medium-chain acyl-CoA dehydrogenase deficiency (MCADD) in a cohort of Ontario infants. METHODS: The cohort included all children who received newborn screening in Ontario between April 1, 2006 and March 31, 2010. Newborn screening and diagnostic confirmation results were linked to province-wide health care administrative datasets covering physician visits, emergency department visits, and inpatient hospitalizations, to determine health service utilization from April 1, 2006 through March 31, 2012. Incidence rate ratios (IRRs) were used to compare those with false positive results for MCADD to those with negative newborn screening results, stratified by age at service use. RESULTS: We identified 43 infants with a false positive newborn screening result for MCADD during the study period. These infants experienced significantly higher rates of physician visits (IRR: 1.42) and hospitalizations (IRR: 2.32) in the first year of life relative to a screen negative cohort in adjusted analyses. Differences in health services use were not observed after the first year of life. CONCLUSIONS: The higher use of some health services among false positive infants during the first year of life may be explained by a psychosocial impact of false positive results on parental perceptions of infant health, and/or by differences in underlying health status. Understanding the impact of false positive newborn screening results can help to inform newborn screening programs in designing support and education for families. This is particularly important as additional disorders are added to expanded screening panels, yielding important clinical benefits for affected children but also a higher frequency of false positive findings.

BACKGROUND: Improvements in health care for children with chronic diseases must be informed by research that emphasizes outcomes of importance to patients and families. To support a program of research in the field of rare inborn errors of metabolism (IEM), we conducted a broad scoping review of primary studies that: (i) focused on chronic pediatric diseases similar to IEM in etiology or manifestations and in complexity of management; (ii) reported patient- and/or family-oriented outcomes; and (iii) measured these outcomes using self-administered tools. METHODS: We developed a comprehensive review protocol and implemented an electronic search strategy to identify relevant citations in Medline, EMBASE, DARE and Cochrane. Two reviewers applied pre-specified criteria to titles/abstracts using a liberal accelerated approach. Articles eligible for full-text review were screened by two independent reviewers with discrepancies resolved by consensus. One researcher abstracted data on study characteristics, patient- and family-oriented outcomes, and self-administered measures. Data were validated by a second researcher. RESULTS: 4,118 citations were screened with 304 articles included. Across all included reports, the most-represented diseases were diabetes (35%), cerebral palsy (23%) and epilepsy (18%). We identified 43 unique patient- and family-oriented outcomes from among five emergent domains, with mental health outcomes appearing most frequently. The studies reported the use of 405 independent self-administered measures of these outcomes. CONCLUSIONS: Patient- and family-oriented research investigating chronic pediatric diseases emphasizes mental health and appears to be relatively well-developed in the diabetes literature. Future research can build on this foundation while identifying additional outcomes that are priorities for patients and families.

State immunization and cancer registries contain data that, if linked, could be used to monitor the impact of human papillomavirus (HPV) vaccine on cervical cancer and precancer. Michigan is uniquely positioned to examine these outcomes using two population-based resources: the state-wide cancer registry and immunization information system (IIS). We assessed the feasibility of identifying females in the IIS who had continuous Michigan residence and linking them to the cancer registry. We considered continuous residence necessary for future studies of vaccine impact to avoid misclassifying those who may have been immunized while residing out-of-state and whose immunization therefore may not have been reported in Michigan. We identified females with 1976-1996 birthdates in the IIS and used probabilistic linkage software to match them with Michigan birth records. A stratified random sample of IIS-birth matches was provided to a commercial locator service to identify females with continuous Michigan residence. Cervical carcinoma in situ cases diagnosed in 2006 among females aged 10 through 30 years were also matched with the birth records; cancer registry-birth matches were merged with the IIS-birth matches using the birth record identifier. Overall, 68% of the 1274,282 IIS and 61% of the 1358 cancer registry records could be matched with birth records. Among the sample of IIS-birth matches, most (86%) were continuous residents. Seventy percent or more of cancer registry-birth matches merged with IIS-birth matches for cases born after 1984. This is the first effort in the U.S. to show that linking records across IIS and cancer registries is practical and reasonably efficient. The increasing proportion of matches between the registries and live birth file with birth year, and the use of population-based data, strengthen the utility of this approach. Future steps include use of this method to examine incidence of cervical cancer precursors in HPV immunization-eligible females.

In October 2011, the Advisory Committee on Immunization Practices (ACIP) first recommended the routine administration of a tetanus, diphtheria, and acellular pertussis vaccine (Tdap) during pregnancy as a strategy to protect infants from pertussis (also known as whooping cough). This recommendation applied to women previously unvaccinated with Tdap and specified the optimal vaccination time as late second or third trimester (after 20 weeks' gestation). By vaccinating pregnant women, infants, who are at highest risk for mortality and morbidity from pertussis, gain passive immunity from maternal antibodies transferred to them in utero (2-4). Since this recommendation was made, little has been published on the percentage of women receiving Tdap during pregnancy. In Michigan, Medicaid pays for costs of pregnancy for approximately 40% of births. Infants enrolled in Medicaid are a particularly vulnerable population; in Michigan, their all-cause mortality is higher than that of privately insured infants. To assess vaccination coverage among pregnant women enrolled in a publicly funded insurance program in Michigan, Medicaid administrative claims data and statewide immunization information system data for mothers of infants born during November 2011-February 2013 were analyzed. This report describes the results of that analysis, which indicated that only 14.3% of these women received Tdap during pregnancy, with rates highest (17.6%) among non-Hispanic, non-Arab whites and lowest (6.8%) among Arab women. Vaccination was related to maternal age and gestational age at birth, but not to adequacy of prenatal care. In 2013, recognizing the importance of Tdap for every pregnancy, ACIP revised its guidelines to include a Tdap dose during every pregnancy. Ensuring that all infants receive the protection against pertussis afforded by maternal vaccination will require enhanced efforts to vaccinate pregnant women.

OBJECTIVES: We evaluated the use of a statewide immunization information system (IIS) to target influenza vaccine reminders to high-risk children during a pandemic. METHODS: We used Michigan's IIS to identify high-risk children (i.e., those with ≥ 1 chronic condition) aged 6 months to 18 years with no record of pH1N1 vaccination among children currently or previously enrolled in Medicaid (n = 202 133). Reminders were mailed on December 7, 2009. We retrospectively assessed children's eligibility for evaluation and compared influenza vaccination rates across 3 groups on the basis of their high-risk and reminder status. RESULTS: Of the children sent reminders, 53 516 were ineligible. Of the remaining 148 617 children, vaccination rates were higher among the 142 383 high-risk children receiving reminders than among the 6234 high-risk children with undeliverable reminders and the 142 383 control group children without chronic conditions who were not sent reminders. CONCLUSIONS: Midseason reminders to parents of unvaccinated high-risk children with current or past Medicaid enrollment were associated with increased pH1N1 and seasonal influenza vaccination rates. Future initiatives should consider strategies to expand targeting of high-risk groups and improve IIS reporting during pandemic events.