PROBLEM/CONDITION: Autism spectrum disorder (ASD). PERIOD COVERED: 2022. DESCRIPTION OF SYSTEM: The Autism and Developmental Disabilities Monitoring Network is an active surveillance program that estimates prevalence and characteristics of ASD and monitors timing of ASD identification among children aged 4 and 8 years. In 2022, a total of 16 sites (located in Arizona, Arkansas, California, Georgia, Indiana, Maryland, Minnesota, Missouri, New Jersey, Pennsylvania, Puerto Rico, Tennessee, Texas [two sites: Austin and Laredo], Utah, and Wisconsin) conducted surveillance for ASD among children aged 4 and 8 years and suspected ASD among children aged 4 years. Surveillance included children who lived in the surveillance area at any time during 2022. Children were classified as having ASD if they ever received 1) an ASD diagnostic statement in a comprehensive developmental evaluation, 2) autism special education eligibility, or 3) an ASD International Classification of Diseases, Ninth Revision (ICD-9) code in the 299 range or International Classification of Diseases, Tenth Revision (ICD-10) code of F84.0, F84.3, F84.5, F84.8, or F84.9. Children aged 4 years were classified as having suspected ASD if they did not meet the case definition for ASD but had an evaluator's suspicion of ASD documented in a comprehensive developmental evaluation. RESULTS: Among children aged 8 years in 2022, ASD prevalence was 32.2 per 1,000 children (one in 31) across the 16 sites, ranging from 9.7 in Texas (Laredo) to 53.1 in California. The overall observed prevalence estimate was similar to estimates calculated using Bayesian hierarchical and random effects models. ASD was 3.4 times as prevalent among boys (49.2) than girls (14.3). Overall, ASD prevalence was lower among non-Hispanic White (White) children (27.7) than among Asian or Pacific Islander (A/PI) (38.2), American Indian or Alaska Native (AI/AN) (37.5), non-Hispanic Black or African American (Black) (36.6), Hispanic or Latino (Hispanic) (33.0), and multiracial children (31.9). No association was observed between ASD prevalence and neighborhood median household income (MHI) at 11 sites; higher ASD prevalence was associated with lower neighborhood MHI at five sites.Record abstraction was completed for 15 of the 16 sites for 8,613 children aged 8 years who met the ASD case definition. Of these 8,613 children, 68.4% had a documented diagnostic statement of ASD, 67.3% had a documented autism special education eligibility, and 68.9% had a documented ASD ICD-9 or ICD-10 code. All three elements of the ASD case definition were present for 34.6% of children aged 8 years with ASD.Among 5,292 (61.4% of 8,613) children aged 8 years with ASD with information on cognitive ability, 39.6% were classified as having an intellectual disability. Intellectual disability was present among 52.8% of Black, 50.0% of AI/AN, 43.9% of A/PI, 38.8% of Hispanic, 32.7% of White, and 31.2% of multiracial children with ASD. The median age of earliest known ASD diagnosis was 47 months and ranged from 36 months in California to 69.5 months in Texas (Laredo).Cumulative incidence of ASD diagnosis or eligibility by age 48 months was higher among children born in 2018 (aged 4 years in 2022) than children born in 2014 (aged 8 years in 2022) at 13 of the 15 sites that were able to abstract records. Overall cumulative incidence of ASD diagnosis or eligibility by age 48 months was 1.7 times as high among those born in 2018 compared with those born in 2014 and ranged from 1.4 times as high in Arizona and Georgia to 3.1 times as high in Puerto Rico. Among children aged 4 years, for every 10 children meeting the case definition of ASD, one child met the definition of suspected ASD.Children with ASD who were born in 2018 had more evaluations and identification during ages 0-4 years than children with ASD who were born in 2014 during the 0-4 years age window, with an interruption in the pattern in early 2020 coinciding with onset of the COVID-19 pandemic.Overall, 66.5% of children aged 8 years with ASD had a documented autism test. Use of autism tests varied widely across sites: 24.7% (New Jersey) to 93.5% (Puerto Rico) of children aged 8 years with ASD had a documented autism test in their records. The most common tests documented for children aged 8 years were the Autism Diagnostic Observation Schedule, Autism Spectrum Rating Scales, Childhood Autism Rating Scale, Gilliam Autism Rating Scale, and Social Responsiveness Scale. INTERPRETATION: Prevalence of ASD among children aged 8 years was higher in 2022 than previous years. ASD prevalence was higher among A/PI, Black, and Hispanic children aged 8 years than White children aged 8 years, continuing a pattern first observed in 2020. A/PI, Black, and Hispanic children aged 8 years with ASD were also more likely than White or multiracial children with ASD to have a co-occurring intellectual disability. Identification by age 48 months was higher among children born in 2018 compared with children born in 2014, suggesting increased early identification consistent with historical patterns. PUBLIC HEALTH ACTION: Increased identification of autism, particularly among very young children and previously underidentified groups, underscores the increased demand and ongoing need for enhanced planning to provide equitable diagnostic, treatment, and support services for all children with ASD. The substantial variability in ASD identification across sites suggests opportunities to identify and implement successful strategies and practices in communities to ensure all children with ASD reach their potential.

Evolving technology and the development of new devices that can aerosolize water present a risk for new sources of Legionella bacteria growth and spread within industrial settings. We investigated a cluster of legionellosis among employees of a manufacturing facility in South Carolina, USA, and found 2 unique equipment sources of Legionella bacteria. The cluster of cases took place during August-November 2022; a total of 34 cases of legionellosis, including 15 hospitalizations and 2 deaths, were reported. Legionella pneumophila was isolated from 3 devices: 2 water jet cutters and 1 floor scrubber. L. pneumophila sequence type 36 was identified in environmental isolates and 1 patient specimen, indicating that those devices were the likely source of infection. Remediation was ultimately achieved through the development and implementation of a device-specific water management program. Manufacturing facilities that use aerosol-generating devices should consider maintaining updated Legionella water management programs to prevent Legionella bacterial infections.

BACKGROUND: Artemisinin-based combination therapy (ACT) has been a major contributor to the substantial reductions in global malaria morbidity and mortality over the last decade. In Tanzania, artemether-lumefantrine (AL) was introduced as the first-line treatment for uncomplicated Plasmodium falciparum malaria in 2006. The World Health Organization (WHO) recommends regular assessment and monitoring of the efficacy of the first-line treatment, specifically considering that artemisinin resistance has been confirmed in the Greater Mekong sub-region. This study's main aim was to assess the efficacy and safety of AL for treating uncomplicated P. falciparum malaria in Tanzania. METHODS: This was a single-arm prospective antimalarial drug efficacy trial conducted in four of the eight National Malaria Control Programme (NMCP) sentinel sites in 2019. The trial was carried out in outpatient health facilities in Karume-Mwanza region, Ipinda-Mbeya region, Simbo-Tabora region, and Nagaga-Mtwara region. Children aged six months to 10 years with microscopy confirmed uncomplicated P. falciparum malaria who met the inclusion criteria were recruited based on the WHO protocol. The children received AL (a 6-dose regimen of AL twice daily for three days). Clinical and parasitological parameters were monitored during follow-up over 28 days to evaluate drug efficacy. RESULTS: A total of 628 children were screened for uncomplicated malaria, and 349 (55.6%) were enrolled between May and September 2019. Of the enrolled children, 343 (98.3%) completed the 28-day follow-up or attained the treatment outcomes. There were no early treatment failures; recurrent infections during follow-up were common at two sites (Karume 29.5%; Simbo 18.2%). PCR-corrected adequate clinical and parasitological response (ACPR) by survival analysis to AL on day 28 of follow-up varied from 97.7% at Karume to 100% at Ipinda and Nagaga sites. The commonly reported adverse events were cough, skin pallor, and abdominal pain. The drug was well tolerated, and no serious adverse event was reported. CONCLUSION: This study showed that AL had adequate efficacy and safety for the treatment of uncomplicated falciparum malaria in Tanzania in 2019. The high recurrent infections were mainly due to new infections, highlighting the potential role of introducing alternative artemisinin-based combinations that offer improved post-treatment prophylaxis, such as artesunate-amodiaquine (ASAQ).

BACKGROUND: The use of artemisinin-based combination therapy (ACT) is recommended by the World Health Organization for the treatment of uncomplicated falciparum malaria. Artemether-lumefantrine (AL) is the most widely adopted first-line ACT for uncomplicated malaria in sub-Saharan Africa (SSA), including mainland Tanzania, where it was introduced in December 2006. The WHO recommends regular assessment to monitor the efficacy of the first-line treatment specifically considering that artemisinin partial resistance was reported in Greater Mekong sub-region and has been confirmed in East Africa (Rwanda and Uganda). The main aim of this study was to assess the efficacy and safety of AL for the treatment of uncomplicated falciparum malaria in mainland Tanzania. METHODS: A single-arm prospective anti-malarial drug efficacy trial was conducted in Kibaha, Mlimba, Mkuzi, and Ujiji (in Pwani, Morogoro, Tanga, and Kigoma regions, respectively) in 2018. The sample size of 88 patients per site was determined based on WHO 2009 standard protocol. Participants were febrile patients (documented axillary temperature ≥ 37.5 °C and/or history of fever during the past 24 h) aged 6 months to 10 years. Patients received a 6-dose AL regimen by weight twice a day for 3 days. Clinical and parasitological parameters were monitored during 28 days of follow-up to evaluate the drug efficacy and safety. RESULTS: A total of 653 children were screened for uncomplicated malaria and 349 (53.7%) were enrolled between April and August 2018. Of the enrolled children, 345 (98.9%) completed the 28 days of follow-up or attained the treatment outcomes. There were no early treatment failures, but recurrent infections were higher in Mkuzi (35.2%) and Ujiji (23%). By Kaplan-Meier analysis of polymerase chain reaction (PCR) uncorrected adequate clinical and parasitological response (ACPR) ranged from 63.4% in Mkuzi to 85.9% in Mlimba, while PCR-corrected ACPR on day 28 varied from 97.6% in Ujiji to 100% in Mlimba. The drug was well tolerated; the commonly reported adverse events were cough, runny nose, and abdominal pain. No serious adverse event was reported. CONCLUSION: This study showed that AL had adequate efficacy and safety for the treatment of uncomplicated falciparum malaria. The high number of recurrent infections were mainly due to new infections, indicating the necessity of utilizing alternative artemisinin-based combinations, such as artesunate amodiaquine, which provide a significantly longer post-treatment prophylactic effect.

BACKGROUND: Housing is a major social determinant of health that affects health status and outcomes across the lifespan. OBJECTIVES: An interagency portfolio analysis assessed the level of funding invested in "health and housing research" from fiscal years (FY) 2016-2020 across the National Institutes of Health (NIH), the United States Department of Housing and Urban Development (HUD), and the Centers for Disease Control and Prevention (CDC) to characterize the existing health and housing portfolio and identify potential areas for additional research and collaboration. METHODS/RESULTS: We identified NIH, HUD, and CDC research projects that were relevant to both health and housing and characterized them by housing theme, health topic, population, and study design. We organized the assessment of the individual housing themes by four overarching housing-to-health pathways. From FY 2016-2020, NIH, HUD, and CDC funded 565 health and housing projects combined. The Neighborhood pathway was most common, followed by studies of the Safety and Quality pathway. Studies of the Affordability and Stability pathways were least common. Health topics such as substance use, mental health, and cardiovascular disease were most often studied. Most studies were observational (66%); only a little over one fourth (27%) were intervention studies. DISCUSSION: This review of the research grant portfolios of three major federal funders of health and housing research in the United States describes the diversity and substantial investment in research at the intersection between housing and health. Analysis of the combined portfolio points to gaps in studies on causal pathways linking housing to health outcomes. The findings highlight the need for research to better understand the causal pathways from housing to health and prevention intervention research, including rigorous evaluation of housing interventions and policies to improve health and well-being.

OBJECTIVES: We investigated causes of fever in the primary levels of care in Southeast Asia, and evaluated whether C-reactive protein (CRP) could distinguish bacterial from viral pathogens. METHODS: Blood and nasopharyngeal swab specimens were taken from children and adults with fever (>37.5 C) or history of fever (<14 days) in Thailand and Myanmar. RESULTS: Of 773 patients with at least one blood or nasopharyngeal swab specimen collected, 227 (29.4%) had a target organism detected. Influenza virus type A was detected in 85/227 cases (37.5%), followed by dengue virus (30 cases, 13.2%), respiratory syncytial virus (24 cases, 10.6%) and Leptospira spp. (9 cases, 4.0%). Clinical outcome was similar between patients with a bacterial or a viral organism, regardless of antibiotic prescription. CRP was higher among patients with a bacterial organism compared to those with a viral organism (median 18mg/L, interquartile range [10-49] versus 10mg/L [</=8-22], p-value 0.003), with an area under the curve of 0.65, 95% confidence interval (0.55-0.75). CONCLUSIONS: Serious bacterial infections requiring antibiotics are exceptions rather than the rule in the first lines of care. CRP-testing could assist in ruling out such cases in settings where diagnostic uncertainty is high and routine antibiotic prescription is common. The original CRP randomised-controlled trial (RCT) was registered with ClinicalTrials.gov, number NCT02758821.

An infant or toddler can begin the process of receiving Part C early intervention services by having a diagnosed condition with a high probability of developmental delay (Individuals with Disabilities Education Improvement Act, 2004). How states define those diagnosed conditions that begin the initiation process varies widely. Lists of diagnosed conditions were collected from state Part C websites and Part C coordinators for a descriptive analysis. Across 49 states, the District of Columbia, and 4 territories, a final list of 620 unique conditions was compiled. No single condition was listed by all jurisdictions. Hearing impairment was the condition listed by the most states (n = 38), followed by fetal alcohol syndrome (n = 34). Of the 620 conditions, 168 (27%) were listed by only 1 state, 554 (89%) were listed by fewer than 10 states, and 66 (11%) were listed by 10 or more states. Of these 66 conditions, 47 (71%) were listed by fewer than 20 states. Most of these 66 conditions (n = 48; 72.7%) had a prevalence of "very rare or rare," 8 (12%) were "common," 6 (9%) were "very common," and 4 (6.1%) were "unknown." The wide heterogeneity in the number and type of diagnostic conditions listed across states should be further investigated as it may represent imbalances in children with diagnosed conditions gaining access to Part C evaluations and individualized family service plans and potentially the services themselves across states. In addition, providing ready access to lists of diagnosed conditions is a simple step that could help states and Part C programs facilitate access to services.

BACKGROUND: Despite strong evidence and national policy supporting type 2 diabetes prevention, little is known about type 2 diabetes prevention in the primary care setting. OBJECTIVE: Our objective was to assess primary care physicians' knowledge and practice regarding perceived barriers and potential interventions to improving management of prediabetes. DESIGN: Cross-sectional mailed survey. PARTICIPANTS: Nationally representative random sample of US primary care physicians (PCPs) identified from the American Medical Association Physician Masterfile. MAIN MEASURES: We assessed PCP knowledge, practice behaviors, and perceptions related to prediabetes. We performed chi-square and Fisher's exact tests to evaluate the association between PCP characteristics and the main survey outcomes. KEY RESULTS: In total, 298 (33%) eligible participants returned the survey. PCPs had limited knowledge of risk factors for prediabetes screening, laboratory diagnostic criteria for prediabetes, and management recommendations for patients with prediabetes. Only 36% of PCPs refer patients to a diabetes prevention lifestyle change program as their initial management approach, while 43% discuss starting metformin for prediabetes. PCPs believed that barriers to type 2 diabetes prevention are both at the individual level (e.g., patients' lack of motivation) and at the system level (e.g., lack of weight loss resources). PCPs reported that increased access to and insurance coverage of type 2 diabetes prevention programs and coordination of referral of patients to these resources would facilitate type 2 diabetes preventive efforts. CONCLUSIONS: Addressing gaps in PCP knowledge may improve the identification and management of people with prediabetes, but system-level changes are necessary to support type 2 diabetes prevention in the primary care setting.

BACKGROUND: The World Health Organization recommends regular therapeutic efficacy studies (TES) to monitor the performance of first and second-line anti-malarials. In 2016, efficacy and safety of artemether-lumefantrine (AL) for the treatment of uncomplicated falciparum malaria were assessed through a TES conducted between April and October 2016 at four sentinel sites of Kibaha, Mkuzi, Mlimba, and Ujiji in Tanzania. The study also assessed molecular markers of artemisinin and lumefantrine (partner drug) resistance. METHODS: Eligible patients were enrolled at the four sites, treated with standard doses of AL, and monitored for 28 days with clinical and laboratory assessments. The main outcomes were PCR corrected cure rates, day 3 positivity rates, safety of AL, and prevalence of single nucleotide polymorphisms in Plasmodium falciparum kelch 13 (Pfk13) (codon positions: 440-600) and P. falciparum multi-drug resistance 1 (Pfmdr1) genes (codons: N86Y, Y184F and D1246Y), markers of artemisinin and lumefantrine resistance, respectively. RESULTS: Of 344 patients enrolled, three withdrew, six were lost to follow-up; and results were analysed for 335 (97.4%) patients. Two patients had treatment failure (one early treatment failure and one recrudescent infection) after PCR correction, yielding an adequate clinical and parasitological response of > 98%. Day 3 positivity rates ranged from 0 to 5.7%. Common adverse events included cough, abdominal pain, vomiting, and diarrhoea. Two patients had serious adverse events; one died after the first dose of AL and another required hospitalization after the second dose of AL (on day 0) but recovered completely. Of 344 samples collected at enrolment (day 0), 92.7% and 100% were successfully sequenced for Pfk13 and Pfmdr1 genes, respectively. Six (1.9%) had non-synonymous mutations in Pfk13, none of which had been previously associated with artemisinin resistance. For Pfmdr1, the NFD haplotype (codons N86, 184F and D1246) was detected in 134 (39.0%) samples; ranging from 33.0% in Mlimba to 45.5% at Mkuzi. The difference among the four sites was not significant (p = 0.578). All samples had a single copy of the Pfmdr1 gene. CONCLUSION: The study indicated high efficacy of AL and the safety profile was consistent with previous reports. There were no known artemisinin-resistance Pfk13 mutations, but there was a high prevalence of a Pfmdr1 haplotype associated with reduced sensitivity to lumefantrine (but no reduced efficacy was observed in the subjects). Continued TES and monitoring of markers of resistance to artemisinin and partner drugs is critical for early detection of resistant parasites and to inform evidence-based malaria treatment policies. Trial Registration ClinicalTrials.gov NCT03387631.

Background: Proper nutrition during infancy and toddlerhood is crucial for supporting healthy growth and development, including bone health. Complementary feeding is the process that starts when human milk or infant formula is complemented by other foods and beverages, beginning during late infancy and continuing to 24 mo of age. Objectives: This article aims to describe systematic reviews (SRs) conducted by the Nutrition Evidence Systematic Review team for the USDA and the Department of Health and Human Services Pregnancy and Birth to 24 Months Project to answer these questions: what is the relationship between 1) timing of introduction of complementary foods and beverages (CFBs) or 2) types and/or amounts of CFBs consumed and bone health? Methods: The literature was searched with the use of 4 databases (CINAHL, Cochrane, Embase, and PubMed) to identify articles published from January 1980 to July 2016 that addressed these topics and met predetermined criteria for inclusion. For each study, data were extracted and risk of bias was assessed. The evidence was qualitatively synthesized to develop a conclusion statement, and the strength of the evidence was graded. Results: Three articles addressed the timing of introduction of CFBs and bone health during childhood (through 18 y of age), and 2 addressed the types and/or amounts of CFBs consumed relative to bone health. Conclusions: Insufficient evidence was available to draw conclusions about the relationships between the timing of CFB introduction and types and/or amounts of CFBs consumed and bone health. Therefore, a grade was not assignable for these SRs. The ability to draw conclusions was limited by an overall lack of research, failure to adjust for several key confounding factors, and heterogeneity in studies with regard to methodology, subject populations, and results. Additional research is needed that addresses these gaps and limitations.

BACKGROUND: In 2013, the World Health Organization recommended distribution through schools, health facilities, community health workers, and mass campaigns to maintain coverage with insecticide-treated nets (ITNs). We piloted school distribution in 3 local government areas (LGAs) of Cross River State, Nigeria. METHODS: From January to March 2011, all 3 study sites participated in a mass ITN campaign. Baseline data were collected in June 2012 (N=753 households) and school distribution began afterward. One ITN per student was distributed to 4 grades once a year in public schools. Obubra LGA distributed ITNs in 2012, 2013, and 2014 and Ogoja LGA in 2013 and 2014 while Ikom LGA served as a comparison site. Pregnant women in all sites were eligible to receive ITNs through standard antenatal care (ANC). Endline survey data (N=1,450 households) were collected in March 2014. Data on ITN ownership, population access to an ITN, and ITN use were gathered and analyzed. Statistical analysis used contingency tables and chi-squared tests for univariate analysis, and a concentration index was calculated to assess equity in ITN ownership. RESULTS: Between baseline and endline, household ownership of at least 1 ITN increased in the intervention sites, from 50% (95% confidence interval [CI]: 44.7, 54.3) to 76% (95% CI: 71.2, 81.0) in Ogoja and from 51% (95% CI: 35.3, 66.7) to 78% (95% CI: 71.5, 83.1) in Obubra, as did population access to ITN, from 36% (95% CI: 32.0, 39.5) to 53% (95% CI: 48.0, 58.0) in Ogoja and from 34% (95% CI: 23.2, 45.6) to 55% in Obubra (95% CI: 48.4, 60.9). In contrast, ITN ownership declined in the comparison site, from 64% (95% CI: 56.4, 70.8) to 43% (95% CI: 37.4, 49.4), as did population ITN access, from 47% (95% CI: 40.0, 53.7) to 26% (95% CI: 21.9, 29.9). Ownership of school ITNs was nearly as equitable (concentration index 0.06 [95% CI: 0.02, 0.11]) as for campaign ITNs (-0.03 [95% CI: -0.08, 0.02]), and there was no significant oversupply or undersupply among households with ITNs. Schools were the most common source of ITNs at endline and very few households (<2%) had nets from both school and ANC. CONCLUSION: ITN distribution through schools and ANC provide complementary reach and can play an effective role in achieving and maintaining universal coverage. More research is needed to evaluate the cost-effectiveness of such continuous distribution channels in combination with, or as a potential replacement for, subsequent mass campaigns.

BACKGROUND: Norovirus is the leading cause of epidemic and sporadic acute gastroenteritis (AGE) in the United States. Widespread prevalence necessitates implementation of accurate norovirus detection assays in clinical diagnostic laboratories. OBJECTIVE: To evaluate RIDA((R))GENE norovirus GI/GII real-time RT-PCR assay (RGN RT-PCR) using stool samples from patients with sporadic AGE. STUDY DESIGN: Patients between 14days to 101 years of age with symptoms of AGE were enrolled prospectively at four sites across the United States during 2014-2015. Stool specimens were screened for the presence of norovirus RNA by the RGN RT-PCR assay. Results were compared with a reference method that included conventional RT-PCR and sequencing of a partial region of the 5'end of the norovirus ORF2 gene. RESULTS: A total of 259 (36.0%) of 719 specimens tested positive for norovirus by the reference method. The RGN RT-PCR assay detected norovirus in 244 (94%) of these 259 norovirus positive specimens. The sensitivity and specificity (95% confidence interval) of the RGN RT-PCR assay for detecting norovirus genogroup (G) I was 82.8% (63.5-93.5) and 99.1% (98.0-99.6) and for GII was 94.8% (90.8-97.2) and 98.6% (96.9-99.4), respectively. Seven specimens tested positive by the RGN-RT PCR that were negative by the reference method. The fifteen false negative samples were typed as GII.4 Sydney, GII.13, GI.3, GI.5, GI.2, GII.1, and GII.3 in the reference method. CONCLUSIONS: The RGN RT-PCR assay had a high sensitivity and specificity for the detection of norovirus in stool specimens from patients with sporadic AGE.

PROBLEM/CONDITION: Heart disease is the leading cause of death in the United States. In 2015, heart disease accounted for approximately 630,000 deaths, representing one in four deaths in the United States. Although heart disease death rates decreased 68% for the total population from 1968 to 2015, marked disparities in decreases exist by race and state. PERIOD COVERED: 1968-2015. DESCRIPTION OF SYSTEM: The National Vital Statistics System (NVSS) data on deaths in the United States were abstracted for heart disease using diagnosis codes from the eighth, ninth, and tenth revisions of the International Classification of Diseases (ICD-8, ICD-9, and ICD-10) for 1968-2015. Population estimates were obtained from NVSS files. National and state-specific heart disease death rates for the total population and by race for adults aged >/=35 years were calculated for 1968-2015. National and state-specific black-white heart disease mortality ratios also were calculated. Death rates were age standardized to the 2000 U.S. standard population. Joinpoint regression was used to perform time trend analyses. RESULTS: From 1968 to 2015, heart disease death rates decreased for the total U.S. population among adults aged >/=35 years, from 1,034.5 to 327.2 per 100,000 population, respectively, with variations in the magnitude of decreases by race and state. Rates decreased for the total population an average of 2.4% per year, with greater average decreases among whites (2.4% per year) than blacks (2.2% per year). At the national level, heart disease death rates for blacks and whites were similar at the start of the study period (1968) but began to diverge in the late 1970s, when rates for blacks plateaued while rates for whites continued to decrease. Heart disease death rates among blacks remained higher than among whites for the remainder of the study period. Nationwide, the black-white ratio of heart disease death rates increased from 1.04 in 1968 to 1.21 in 2015, with large increases occurring during the 1970s and 1980s followed by small but steady increases until approximately 2005. Since 2005, modest decreases have occurred in the black-white ratio of heart disease death rates at the national level. The majority of states had increases in black-white mortality ratios from 1968 to 2015. The number of states with black-white mortality ratios >1 increased from 16 (40%) to 27 (67.5%). INTERPRETATION: Although heart disease death rates decreased both for blacks and whites from 1968 to 2015, substantial differences in decreases were found by race and state. At the national level and in most states, blacks experienced smaller decreases in heart disease death rates than whites for the majority of the period. Overall, the black-white disparity in heart disease death rates increased from 1968 to 2005, with a modest decrease from 2005 to 2015. PUBLIC HEALTH ACTION: Since 1968, substantial increases have occurred in black-white disparities of heart disease death rates in the United States at the national level and in many states. These increases appear to be due to faster decreases in heart disease death rates for whites than blacks, particularly from the late 1970s until the mid-2000s. Despite modest decreases in black-white disparities at the national level since 2005, in 2015, heart disease death rates were 21% higher among blacks than among whites. This study demonstrates the use of NVSS data to conduct surveillance of heart disease death rates by race and of black-white disparities in heart disease death rates. Continued surveillance of temporal trends in heart disease death rates by race can provide valuable information to policy makers and public health practitioners working to reduce heart disease death rates both for blacks and whites and disparities between blacks and whites.

CONTEXT: Kalanchoe pinnata (Lam.) Pers. (Crassulaceae) is a succulent plant that is known for its traditional antivirus and antibacterial usage. OBJECTIVE: This work examines two compounds identified from the K. pinnata plant for their antivirus activity against human alphaherpesvirus (HHV) 1 and 2 and vaccinia virus (VACV). MATERIALS AND METHODS: Compounds KPB-100 and KPB-200 were isolated using HPLC and were identified using NMR and MS. Both compounds were tested in plaque reduction assay of HHV-2 wild type (WT) and VACV. Both compounds were then tested in virus spread inhibition and virus yield reduction (VYR) assays of VACV. KPB-100 was further tested in viral cytopathic effect (CPE) inhibition assay of HHV-2 TK-mutant and VYR assay of HHV-1 WT. RESULTS: KPB-100 and KPB-200 inhibited HHV-2 at IC50 values of 2.5 and 2.9 mug/mL, respectively, and VACV at IC50 values of 3.1 and 7.4 mug/mL, respectively, in plaque reduction assays. In virus spread inhibition assay of VACV KPB-100 and KPB-200 yielded IC50 values of 1.63 and 13.2 mug/mL, respectively, and KPB-100 showed a nearly 2-log reduction in virus in VYR assay of VACV at 20 mug/mL. Finally, KPB-100 inhibited HHV-2 TK- at an IC50 value of 4.5 mug/mL in CPE inhibition assay and HHV-1 at an IC90 of 3.0 mug/mL in VYR assay. DISCUSSION AND CONCLUSION: Both compounds are promising targets for synthetic optimization and in vivo study. KPB-100 in particular showed strong inhibition of all viruses tested.

On August 3, 2016, the Ohio Department of Health Laboratory reported to CDC that a respiratory specimen collected on July 28 from a male aged 13 years who attended an agricultural fair in Ohio during July 22-29, 2016, and subsequently developed a respiratory illness, tested positive by real-time reverse transcription-polymerase chain reaction (rRT-PCR) for influenza A(H3N2) variant* (H3N2v). The respiratory specimen was collected as part of routine influenza surveillance activities. The next day, CDC was notified of a child aged 9 years who was a swine exhibitor at an agricultural fair in Michigan who became ill on July 29, 2016, and tested positive for H3N2v virus at the Michigan Department of Health and Human Services Laboratory. Investigations by Michigan and Ohio health authorities identified 18 human infections linked to swine exhibits at agricultural fairs. To minimize transmission of influenza viruses from infected swine to visitors, agricultural fair organizers should consider prevention measures such as shortening the time swine are on the fairgrounds, isolating ill swine, maintaining a veterinarian on call, providing handwashing stations, and prohibiting food and beverages in animal barns. Persons at high risk for influenza-associated complications should be discouraged from entering swine barns.

Zika virus is a cause of microcephaly and brain abnormalities (1), and it is the first known mosquito-borne infection to cause congenital anomalies in humans. The establishment of a comprehensive surveillance system to monitor pregnant women with Zika virus infection will provide data to further elucidate the full range of potential outcomes for fetuses and infants of mothers with asymptomatic and symptomatic Zika virus infection during pregnancy. In February 2016, Zika virus disease and congenital Zika virus infections became nationally notifiable conditions in the United States (2). Cases in pregnant women with laboratory evidence of Zika virus infection who have either 1) symptomatic infection or 2) asymptomatic infection with diagnosed complications of pregnancy can be reported as cases of Zika virus disease to ArboNET* (2), CDC's national arboviral diseases surveillance system. Under existing interim guidelines from the Council for State and Territorial Epidemiologists (CSTE), asymptomatic Zika virus infections in pregnant women who do not have known pregnancy complications are not reportable. ArboNET does not currently include pregnancy surveillance information (e.g., gestational age or pregnancy exposures) or pregnancy outcomes. To understand the full impact of infection on the fetus and neonate, other systems are needed for reporting and active monitoring of pregnant women with laboratory evidence of possible Zika virus infection during pregnancy. Thus, in collaboration with state, local, tribal, and territorial health departments, CDC established two surveillance systems to monitor pregnancies and congenital outcomes among women with laboratory evidence of Zika virus infection(dagger) in the United States and territories: 1) the U.S. Zika Pregnancy Registry (USZPR),( section sign) which monitors pregnant women residing in U.S. states and all U.S. territories except Puerto Rico, and 2) the Zika Active Pregnancy Surveillance System (ZAPSS), which monitors pregnant women residing in Puerto Rico. As of May 12, 2016, the surveillance systems were monitoring 157 and 122 pregnant women with laboratory evidence of possible Zika virus infection from participating U.S. states and territories, respectively. Tracking and monitoring clinical presentation of Zika virus infection, all prenatal testing, and adverse consequences of Zika virus infection during pregnancy are critical to better characterize the risk for congenital infection, the performance of prenatal diagnostic testing, and the spectrum of adverse congenital outcomes. These data will improve clinical guidance, inform counseling messages for pregnant women, and facilitate planning for clinical and public health services for affected families.

Objective. Many cardiovascular deaths can be avoided through primary prevention to address cardiovascular disease (CVD) risk factors or better access to quality medical care. In this cross-sectional study, we examined the relationship between four county-level health factors and rates of avoidable death from CVD during 2006–2010. Methods. We defined avoidable deaths from CVD as deaths among U.S. residents younger than 75 years of age caused by the following underlying conditions, using International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) codes: ischemic heart disease (I20–I25), chronic rheumatic heart disease (I05–I09), hypertensive disease (I10–I15), or cerebrovascular disease (I60–I69). We stratified county-level death rates by race (non-Hispanic white or non-Hispanic black) and age-standardized them to the 2000 U.S. standard population. We used County Health Rankings data to rank county-level z scores corresponding to four health factors: health behavior, clinical care, social and economic factors, and physical environment. We used Poisson rate ratios (RRs) and 95% confidence intervals (CIs) to compare rates of avoidable death from CVD by health-factor quartile. Results. In a comparison of worst-ranked and best-ranked counties, social and economic factors had the strongest association with rates of avoidable death per 100,000 population from CVD for the total population (RR51.49; 95% CI 1.39, 1.60) and for each racial/ethnic group (non-Hispanic white: RR51.37; 95% CI 1.29, 1.45; non-Hispanic black: RR51.54; 95% CI 1.42, 1.67). Among the non-Hispanic white population, health behaviors had the next strongest association, followed by clinical care. Among the non-Hispanic black population, we observed a significant association with clinical care and physical environment in a comparison of worst-ranked and best-ranked counties. Conclusion. Social and economic factors have the strongest association with rates of avoidable death from CVD by county, which reinforces the importance of social and economic interventions to address geographic disparities in avoidable deaths from CVD.

BACKGROUND: Although many studies have documented the dramatic declines in heart disease mortality in the United States at the national level, little attention has been given to the temporal changes in the geographic patterns of heart disease mortality. METHODS AND RESULTS: Age-adjusted and spatially smoothed county-level heart disease death rates were calculated for 2-year intervals from 1973 to 1974 to 2009 to 2010 for those aged ≥35 years. Heart disease deaths were defined according to the International Classification of Diseases codes for diseases of the heart in the eighth, ninth, and tenth revisions of the International Classification of Diseases. A fully Bayesian spatiotemporal model was used to produce precise rate estimates, even in counties with small populations. A substantial shift in the concentration of high-rate counties from the Northeast to the Deep South was observed, along with a concentration of slow-decline counties in the South and a nearly 2-fold increase in the geographic inequality among counties. CONCLUSIONS: The dramatic change in the geographic patterns of heart disease mortality during 40 years highlights the importance of small-area surveillance to reveal patterns that are hidden at the national level, gives communities the historical context for understanding their current burden of heart disease, and provides important clues for understanding the determinants of the geographic disparities in heart disease mortality.

BACKGROUND: An estimated 100,000 cases of congenital rubella syndrome (CRS) occur worldwide each year. The reported mortality rate for infants with CRS is up to 33%. The cellular mechanisms responsible for the multiple congenital defects in CRS are presently unknown. Here we identify cell types positive for rubella virus (RV) in CRS infants. METHODS: Cells and organs involved in RV replication were identified in paraffin-embedded autopsy tissues from three fatal case-patients by histopathologic examination and immunohistochemical (IHC) staining using a rabbit polyclonal RV antibody. Normal rabbit antisera and RV antisera preabsorbed with highly purified RV served as negative controls. RESULTS: RV antigen was found in interstitial fibroblasts in the heart, adventitial fibroblasts of large blood vessels, alveolar macrophages, progenitor cells of the outer granular layer of the brain, and in capillary endothelium and basal plate in the placenta. The antibody specificity was verified by IHC staining of multiple tissue sections from other infectious disease cases. RV infection of each cell type is consistent with abnormalities which have been identified in patients with CRS, in the heart, large blood vessels, and brain. Antigen distribution was consistent with inflammatory response to vascular injury and systemic spread of RV. CONCLUSIONS: The identification of RV positive cell types in CRS is important to better understand the pathology and pathogenesis of CRS.

Neoplasms occur naturally in invertebrates but are not known to develop in tapeworms. We observed nests of monomorphic, undifferentiated cells in samples from lymph-node and lung biopsies in a man infected with the human immunodeficiency virus (HIV). The morphologic features and invasive behavior of the cells were characteristic of cancer, but their small size suggested a nonhuman origin. A polymerase-chain-reaction (PCR) assay targeting eukaryotes identified Hymenolepis nana DNA. Although the cells were unrecognizable as tapeworm tissue, immunohistochemical staining and probe hybridization labeled the cells in situ. Comparative deep sequencing identified H. nana structural genomic variants that are compatible with mutations described in cancer. Invasion of human tissue by abnormal, proliferating, genetically altered tapeworm cells is a novel disease mechanism that links infection and cancer.

Influenza viruses are pathogens of significant public health importance. The influence of nutritional status on severity of disease has become increasingly recognized. In particular, high dietary salt intake has been linked to cardiovascular disease, but the effects on infectious diseases have not been studied. This study investigated the impact on influenza-induced morbidity and mortality in mice fed isocaloric diets containing 10-fold increments of sodium by altering the salt levels. Following infection, despite higher levels of IFN-gamma cytokine in the lung as well as virus-neutralizing antibody in the serum of mice fed the lowest salt level, the amounts of dietary salt intake had no substantial impact on the disease severity or the ability to respond immunologically to the infection.

PURPOSE: To demonstrate the implications of choosing analytical methods for quantifying spatiotemporal trends, we compare the assumptions, implementation, and outcomes of popular methods using county-level heart disease mortality in the United States between 1973 and 2010. METHODS: We applied four regression-based approaches (joinpoint regression, both aspatial and spatial generalized linear mixed models, and Bayesian space-time model) and compared resulting inferences for geographic patterns of local estimates of annual percent change and associated uncertainty. RESULTS: The average local percent change in heart disease mortality from each method was -4.5%, with the Bayesian model having the smallest range of values. The associated uncertainty in percent change differed markedly across the methods, with the Bayesian space-time model producing the narrowest range of variance (0.0-0.8). The geographic pattern of percent change was consistent across methods with smaller declines in the South Central United States and larger declines in the Northeast and Midwest. However, the geographic patterns of uncertainty differed markedly between methods. CONCLUSIONS: The similarity of results, including geographic patterns, for magnitude of percent change across these methods validates the underlying spatial pattern of declines in heart disease mortality. However, marked differences in degree of uncertainty indicate that Bayesian modeling offers substantially more precise estimates.

Ebola viruses and Marburg viruses include some of the most virulent and fatal pathogens known to humans. These viruses cause severe haemorrhagic fevers, with case fatality rates in the range 25-90%. The diagnosis of filovirus using formalin-fixed tissues from fatal cases poses a significant challenge. The most characteristic histopathological findings are seen in the liver; however, the findings overlap with many other viral and non-viral haemorrhagic diseases. The need to distinguish filovirus infections from other haemorrhagic fevers, particularly in areas with multiple endemic viral haemorrhagic agents, is of paramount importance. In this review we discuss the current state of knowledge of filovirus infections and their pathogenesis, including histopathological findings, epidemiology, modes of transmission and filovirus entry and spread within host organisms. The pathogenesis of filovirus infections is complex and involves activation of the mononuclear phagocytic system, with release of pro-inflammatory cytokines, chemokines and growth factors, endothelial dysfunction, alterations of the innate and adaptive immune systems, direct organ and endothelial damage from unrestricted viral replication late in infection, and coagulopathy. Although our understanding of the pathogenesis of filovirus infections has rapidly increased in the past few years, many questions remain unanswered.

Despite declines in mortality from cardiovascular diseases (CVD) and many CVD risk factors, CVD remains the leading cause of death in the US and racial and ethnic disparities persist. In 2010, rates of CVD mortality per 100,000 were: 192.2 for White women; 260.5 for Black women; 278.4 for White men; and 369.2 for Black men1. In 2009-2010, metrics of ideal cardiovascular health factors (i.e., blood pressure, physical activity, healthy diet, healthy weight, smoking status, and glucose) were noted to be lower for Blacks and Mexican Americans than for Whites or other racial groups. In 2012, the following age-adjusted prevalence estimates among non-White adult populations were noted in comparison to the White population: (1) the prevalence of heart disease and coronary heart disease (CHD) was similar in Black, lower in Hispanic and Asian, and higher in American Indians/Alaska Native, and Native Hawaiian or Other Pacific Islander populations; (2) the prevalence of hypertension was higher in Black, similar or lower in Hispanic and Asian, and higher in American Indians/Alaska Native, and Native Hawaiian or Other Pacific Islander populations; and (3) the prevalence of having had a stroke was higher in Black, lower in Hispanic, and lower in Asian populations.

INTRODUCTION: High sodium intake and low potassium intake, which can contribute to hypertension and risk of cardiovascular disease, may be related to the availability of healthful food in neighborhood stores. Despite evidence linking food environment with diet quality, this relationship has not been evaluated in the United States. The modified retail food environment index (mRFEI) provides a composite measure of the retail food environment and represents the percentage of healthful-food vendors within a 0.5 mile buffer of a census tract. METHODS: We analyzed data from 8,779 participants in the National Health and Nutrition Examination Survey, 2005-2008. By using linear regression, we assessed the relationship between mRFEI and sodium intake, potassium intake, and the sodium-potassium ratio. Models were stratified by region (South and non-South) and included participant and neighborhood characteristics. RESULTS: In the non-South region, higher mRFEI scores (indicating a more healthful food environment) were not associated with sodium intake, were positively associated with potassium intake (P [trend] = .005), and were negatively associated with the sodium-potassium ratio (P [trend] = .02); these associations diminished when neighborhood characteristics were included, but remained close to statistical significance for potassium intake (P [trend] = .05) and sodium-potassium ratio (P [trend] = .07). In the South, mRFEI scores were not associated with sodium intake, were negatively associated with potassium intake (P [trend] = < .001), and were positively associated with sodium-potassium ratio (P [trend] = .01). These associations also diminished after controlling for neighborhood characteristics for both potassium intake (P [trend] = .03) and sodium-potassium ratio (P [trend] = .40). CONCLUSION: We found no association between mRFEI and sodium intake. The association between mRFEI and potassium intake and the sodium-potassium ratio varied by region. National strategies to reduce sodium in the food supply may be most effective to reduce sodium intake. Strategies aimed at the local level should consider regional context and neighborhood characteristics.

Melioidosis is caused by the soil-borne pathogen Burkholderia pseudomallei. To investigate whether the distinct phenotypic and virulent characteristics result from environmental adaptations in the soil or from the host body, two pairs of isogenic strains were generated by passages in soil or mice. After cultivation in soil, the levels of 3-hydroxytetradecanoic acid, biofilm formation, flagellar expression, and ultrastructure were altered in the bacteria. Uniformly fatal melioidosis developed as a result of infection with mouse-derived strains; however, the survival rates of mice infected with soil-derived strains prolonged. After primary infection or reinfection with soil-derived strains, the mice developed a low degree of bacterial hepatitis and bacterial colonization in the liver and bone marrow compared with mice that were infected with isogenic or heterogenic mouse-derived strains. We suggest that specific phenotypic and pathogenic patterns can be induced through infection with B. pseudomallei that has been cultured in different (soil versus mouse) environments.

Racial residential segregation has been associated with an increased risk for heart disease and stroke deaths. However, there has been little research into the role that candidate mediating pathways may play in the relationship between segregation and heart disease or stroke deaths. In this study, we examined the relationship between metropolitan statistical area (MSA)-level segregation and heart disease and stroke mortality rates, by age and race, and also estimated the effects of various educational, economic, social, and health-care indicators (which we refer to as pathways) on this relationship. We used Poisson mixed models to assess the relationship between the isolation index in 265 U.S. MSAs and county-level (heart disease, stroke) mortality rates. All models were stratified by race (non-Hispanic black, non-Hispanic white), age group (35-64 years, ≥65 years), and cause of death (heart disease, stroke). We included each potential pathway in the model separately to evaluate its effect on the segregation-mortality association. Among blacks, segregation was positively associated with heart disease mortality rates in both age groups but only with stroke mortality rates in the older age group. Among whites, segregation was marginally associated with heart disease mortality rates in the younger age group and was positively associated with heart disease mortality rates in the older age group. Three of the potential pathways we explored attenuated relationships between segregation and mortality rates among both blacks and whites: percentage of female-headed households, percentage of residents living in poverty, and median household income. Because the percentage of female-headed households can be seen as a proxy for the extent of social disorganization, our finding that it has the greatest attenuating effect on the relationship between racial segregation and heart disease and stroke mortality rates suggests that social disorganization may play a strong role in the elevated rates of heart disease and stroke found in racially segregated metropolitan areas.

September 2012 marked the beginning of the largest reported outbreak of infections associated with epidural and intra-articular injections. Contamination of methylprednisolone acetate with the black mold, Exserohilum rostratum, was the primary cause of the outbreak, with >13,000 persons exposed to the potentially contaminated drug, 741 confirmed drug-related infections, and 55 deaths. Fatal meningitis and localized epidural, paraspinal, and peripheral joint infections occurred. Tissues from 40 laboratory-confirmed cases representing these various clinical entities were evaluated by histopathological analysis, special stains, and IHC to characterize the pathological features and investigate the pathogenesis of infection, and to evaluate methods for detection of Exserohilum in formalin-fixed, paraffin-embedded (FFPE) tissues. Fatal cases had necrosuppurative to granulomatous meningitis and vasculitis, with thrombi and abundant angioinvasive fungi, with extensive involvement of the basilar arterial circulation of the brain. IHC was a highly sensitive method for detection of fungus in FFPE tissues, demonstrating both hyphal forms and granular fungal antigens, and PCR identified Exserohilum in FFPE and fresh tissues. Our findings suggest a pathogenesis for meningitis involving fungal penetration into the cerebrospinal fluid at the injection site, with transport through cerebrospinal fluid to the basal cisterns and subsequent invasion of the basilar arteries. Further studies are needed to characterize Exserohilum and investigate the potential effects of underlying host factors and steroid administration on the pathogenesis of infection.

OBJECTIVE: The purpose of this analysis was to determine whether there is an association between type of emergency medical services (EMS) medical direction and local EMS agency practices and characteristics specifically related to emergency response for acute cardiovascular events. METHODS: We surveyed 1,292 EMS agencies in nine states. For each cardiovascular prehospital procedure or practice, we compared the proportion of agencies that employed paid (full- or part-time) medical directors with the proportion of agencies that employed volunteer medical directors. We also compared the proportion of EMS agencies who reported direct interaction between emergency medical technicians (EMTs) and their medical director within the previous four weeks with the proportion of agencies who reported no direct interaction. Chi-square tests were used to assess statistical differences in proportion of agencies with a specific procedure by medical director employment status and medical director interaction. We repeated these comparisons using t-tests to evaluate mean differences in call volume. RESULTS: The EMS agencies with prehospital cardiovascular response policies were more likely to report employment of a paid medical director and less likely to report employment of a volunteer medical director. Similarly, agencies with prehospital cardiovascular response practices were more likely to report recent medical director interaction and less likely to report absence of recent medical director interaction. Mean call volumes for chest pain, cardiac arrest, and stroke were higher among agencies having paid medical directors (compared with agencies having volunteer medical directors) and agencies having recent medical director interaction (compared with agencies not having recent medical director interaction). CONCLUSIONS: Our study demonstrated that EMS agencies with a paid medical director and agencies with medical director interaction with EMTs in the previous four weeks were more likely to have prehospital cardiovascular procedures in place. Given the strong relationship that both employment status and direct interaction have with the presence of these practices, agencies with limited resources to provide a paid medical director or a medical director that can be actively involved with EMTs should be supported through partnerships and other interventions to ensure that they receive the necessary levels of medical director oversight.

OBJECTIVES: To examine prehospital emergency medical services (EMS) scope of practice for acute cardiovascular events and characteristics that may affect scope of practice; and to describe variations in EMS scope of practice for these events and the characteristics associated with that variability. METHODS: In 2008, we conducted a telephone survey of 1,939 eligible EMS providers in nine states to measure EMS agency characteristics, medical director involvement, and 18 interventions authorized for prehospital care of acute cardiovascular events by three levels of emergency medical technician (EMT) personnel. RESULTS: A total of 1,292 providers responded to the survey, for a response rate of 67%. EMS scope of practice interventions varied by EMT personnel level, with the proportion of authorized interventions increasing as expected from EMT-Basic to EMT-Paramedic. Seven of eight statistically significant associations indicated that EMS agencies in urban settings were less likely to authorize interventions (odds ratios <0.7) for any level of EMS personnel. Based on the subset of six statistically significant associations, fire department-based EMS agencies were two to three times more likely to authorize interventions for EMT-Intermediate personnel. Volunteer EMS agencies were more than twice as likely as nonvolunteer agencies to authorize interventions for EMT-Basic and EMT-Intermediate personnel but were less likely to authorize any one of the 11 interventions for EMT-Paramedics. Greater medical director involvement was associated with greater likelihood of authorization of seven of the 18 interventions for EMT-Basic and EMT-Paramedic personnel but had no association with EMT-Intermediate personnel. CONCLUSIONS: We noted statistically significant variations in scope of practice by rural vs. urban setting, medical director involvement, and type of EMS service (fire department-based/non-fire department-based; volunteer/paid). These variations highlight local differences in the composition and capacity of EMS providers and offer important information for the transition towards the implementation of a national scope of practice model.