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Issue 29, July 19, 2022

CDC Science Clips: Volume 14, Issue 29, July 19, 2022

Welcome to CDC Science Clips, CDC’s weekly scientific digest.

This week, Science Clips is pleased to feature articles related to the new CDC Vital Signs on Drug Overdose Deaths Rise, Disparities Widen: Differences Grew by Race, Ethnicity, and Other Factors

Drug overdose data, reported in this week's CDC's Vital Signs, show troubling trends and widening disparities between different population groups. From 2019 to 2020, overdose death rates (number of drug overdose deaths per 100,000 people) increased 44% for Black people and 39% for American Indian and Alaska Native (AI/AN) people. Most people who died by overdose had no evidence of substance use treatment before their deaths. In fact, a lower proportion of people from racial and ethnic minority groups received treatment, compared with White people. In addition, areas with greater income inequality—a larger income gap between the rich and the poor—have higher rates of overdose deaths. Comprehensive, community-based prevention and response efforts and culturally responsive actions can address disparities in drug overdose deaths and the inequities that contribute to them.

  • Increasing access to proven treatment for all people who have substance use disorder(s) is a critical part of their care and recovery.
  • Harm reduction services can further reduce overdoses and save lives. Harm reduction services can include naloxone, fentanyl test strips, and referral to substance use disorder treatment. Syringe services programs can serve as a valuable way to reach people who inject drugs and provide them with overdose prevention education and opportunities to link to substance use disorder treatment.

Drug overdose death disparities are widening at the same time as a record-breaking 92,000 lives were lost to drug overdoses during 2020. More must be done to prevent overdoses and deaths.

  1. CDC Vital Signs
    • Drug Overdose Deaths Rise, Disparities Widen
      1. Drug overdose deaths involving cocaine and psychostimulants with abuse potential among racial and ethnic groups - United States, 2004-2019
        Kariisa M, Seth P, Scholl L, Wilson N, Davis NL.
        Drug Alcohol Depend. 2021 Oct 1;227:109001.
        BACKGROUND: Drug overdose deaths involving stimulants, including cocaine and psychostimulants with abuse potential (e.g., methamphetamine), have been increasing, partly because of co-involvement with opioids. Stimulant-involved overdose deaths have disproportionately increased among non-Hispanic Black (Black) and non-Hispanic American Indian/Alaskan Native (AI/AN) persons; however, the role of opioids in exacerbating disproportionate stimulant-involved death rates is unclear. METHODS: Analysis of National Vital Statistics System multiple cause-of-death mortality files examined age-adjusted cocaine- and psychostimulant-involved death rates. Analyses of death rates stratified by racial and ethnic group and opioid co-involvement included: 1) Joinpoint regression of 2004-2019 trends, 2) changes in rates from 2018 to 2019, and 3) demographic and geographic characteristics of 2019 deaths. RESULTS: From 2004 to 2019, cocaine and psychostimulant-involved death rates were higher for Black and AI/AN persons, respectively. Among all groups, increases in cocaine-involved overdose rates were largely driven by opioid co-involvement, particularly after 2013. From 2004 to 2019, rates for psychostimulant-involved deaths increased with and without opioid co-involvement. Rates for overdoses co-involving cocaine and synthetic opioids increased from 2018 to 2019 for Hispanic, non-Hispanic White (White), and Black persons. Psychostimulant-involved overdose rates with and without synthetic opioid co-involvement increased among Hispanic, White, and Black persons. In 2019, Black and AI/AN persons continued to experience higher cocaine- and psychostimulant-involved death rates, respectively. CONCLUSIONS: Stimulant-involved deaths continue to increase, and the role of opioids in driving these deaths varies by race and ethnicity. Ensuring equitable access to proven prevention and treatment interventions and incorporating social determinants of health into future research around effective pharmacotherapies may help reduce stimulant-involved overdose deaths.

      2. The evolving overdose epidemic: Synthetic opioids and rising stimulant-related harms
        Jones CM, Bekheet F, Park JN, Alexander GC.
        Epidemiol Rev. 2020 Jan 31;42(1):154-166.
        The opioid overdose epidemic is typically described as having occurred in 3 waves, with morbidity and mortality accruing over time principally from prescription opioids (1999-2010), heroin (2011-2013), and illicit fentanyl and other synthetic opioids (2014-present). However, the increasing presence of synthetic opioids mixed into the illicit drug supply, including with stimulants such as cocaine and methamphetamine, as well as rising stimulant-related deaths, reflects the rapidly evolving nature of the overdose epidemic, posing urgent and novel public health challenges. We synthesize the evidence underlying these trends, consider key questions such as where and how concomitant exposure to fentanyl and stimulants is occurring, and identify actions for key stakeholders regarding how these emerging threats, and continued evolution of the overdose epidemic, can best be addressed.

      3. The opioid crisis in black communities
        James K, Jordan A.
        J Law Med Ethics. 2018 Jun;46(2):404-421.
        While much of the social and political attention surrounding the nationwide opioid epidemic has focused on the dramatic increase in overdose deaths among white, middle-class, suburban and rural users, the impact of the epidemic in Black communities has largely been unrecognized. Though rates of opioid use at the national scale are higher for whites than they are for Blacks, rates of increase in opioid deaths have been rising more steeply among Blacks (43%) than whites (22%) over the last five years. Moreover, the rate of opioid overdose deaths among Blacks already exceeds that of whites in several states. The lack of discussion of Black overdose deaths in the national opioid discourse further marginalizes Black people, and is highly consistent with a history of framing the addictions of people of color as deserving of criminal punishment, rather than worthy of medical treatment. This article argues that, because racial inequalities are embedded in American popular and political cultures as well as in medicine, the federal and state governments should develop more culturally targeted programs to benefit Black communities in the opioid crisis. Such programs include the use of faith-based organizations to deliver substance use prevention and treatment services, the inclusion of racial impact assessments in the implementation of drug policy proposals, and the formal consideration of Black people's interaction with the criminal justice system in designing treatment options.

      4. Integrating motivational interviewing and traditional practices to address alcohol and drug use among urban American Indian/Alaska Native youth
        Dickerson DL, Brown RA, Johnson CL, Schweigman K, D'Amico EJ.
        J Subst Abuse Treat. 2016 Jun;65:26-35.
        American Indians/Alaska Natives (AI/AN) exhibit high levels of alcohol and drug (AOD) use and problems. Although approximately 70% of AI/ANs reside in urban areas, few culturally relevant AOD use programs targeting urban AI/AN youth exist. Furthermore, federally-funded studies focused on the integration of evidence-based treatments with AI/AN traditional practices are limited. The current study addresses a critical gap in the delivery of culturally appropriate AOD use programs for urban AI/AN youth, and outlines the development of a culturally tailored AOD program for urban AI/AN youth called Motivational Interviewing and Culture for Urban Native American Youth (MICUNAY). We conducted focus groups among urban AI/AN youth, providers, parents, and elders in two urban communities in northern and southern California aimed at 1) identifying challenges confronting urban AI/AN youth and 2) obtaining feedback on MICUNAY program content. Qualitative data were analyzed using Dedoose, a team-based qualitative and mixed methods analysis software platform. Findings highlight various challenges, including community stressors (e.g., gangs, violence), shortage of resources, cultural identity issues, and a high prevalence of AOD use within these urban communities. Regarding MICUNAY, urban AI/AN youth liked the collaborative nature of the motivational interviewing (MI) approach, especially with regard to eliciting their opinions and expressing their thoughts. Based on feedback from the youth, three AI/AN traditional practices (beading, AI/AN cooking, and prayer/sage ceremony) were chosen for the workshops. To our knowledge, MICUNAY is the first AOD use prevention intervention program for urban AI/AN youth that integrates evidence-based treatment with traditional practices. This program addresses an important gap in services for this underserved population.

      5. This cross-sectional study evaluates trends in increased drug overdose mortality rates in the US by race and ethnicity before and during the COVID-19 pandemic.

      6. Buprenorphine treatment divide by race/ethnicity and payment
        Lagisetty PA, Ross R, Bohnert A, Clay M, Maust DT.
        JAMA Psychiatry. 2019 Sep 1;76(9):979-981.
        This study reports the seeming disparity in access to buprenorphine prescriptions among racial/ethnic minorities and individuals with lower income.

      7. Situating the continuum of overdose risk in the social determinants of health: A new conceptual framework
        Park JN, Rouhani S, Beletsky L, Vincent L, Saloner B, Sherman SG.
        Milbank Q. 2020 Sep;98(3):700-746.
        Policy Points This article reconceptualizes our understanding of the opioid epidemic and proposes six strategies that address the epidemic's social roots. In order to successfully reduce drug-related mortality over the long term, policymakers and public health leaders should develop partnerships with people who use drugs, incorporate harm reduction interventions, and reverse decades of drug criminalization policies. CONTEXT: Drug overdose is the leading cause of injury-related death in the United States. Synthetic opioids, predominantly illicit fentanyl and its analogs, surpassed prescription opioids and heroin in associated mortality rates in 2016. Unfortunately, interventions fail to fully address the current wave of the opioid epidemic and often omit the voices of people with lived experiences regarding drug use. Every overdose death is a culmination of a long series of policy failures and lost opportunities for harm reduction. METHODS: In this article, we conducted a scoping review of the opioid literature to propose a novel framework designed to foreground social determinants more directly into our understanding of this national emergency. The "continuum of overdose risk" framework is our synthesis of the global evidence base and is grounded in contemporary theories, models, and policies that have been successfully applied both domestically and internationally. FINDINGS: De-escalating overdose risk in the long term will require scaling up innovative and comprehensive solutions that have been designed through partnerships with people who use drugs and are rooted in harm reduction. CONCLUSIONS: Without recognizing the full drug-use continuum and the role of social determinants, the current responses to drug overdose will continue to aggravate the problem they are trying to solve.

      8. Trends in and characteristics of drug overdose deaths involving illicitly manufactured fentanyls - United States, 2019-2020
        O'Donnell J, Tanz LJ, Gladden RM, Davis NL, Bitting J.
        MMWR Morb Mortal Wkly Rep. 2021 Dec 17;70(50):1740-1746.
        During May 2020-April 2021, the estimated number of drug overdose deaths in the United States exceeded 100,000 over a 12-month period for the first time, with 64.0% of deaths involving synthetic opioids other than methadone (mainly illicitly manufactured fentanyls [IMFs], which include both fentanyl and illicit fentanyl analogs).* Introduced primarily as adulterants in or replacements for white powder heroin east of the Mississippi River (1), IMFs are now widespread in white powder heroin markets, increasingly pressed into counterfeit pills resembling oxycodone, alprazolam, or other prescription drugs, and are expanding into new markets, including in the western United States(†) (2). This report describes trends in overdose deaths involving IMFs (IMF-involved deaths) during July 2019-December 2020 (29 states and the District of Columbia [DC]), and characteristics of IMF-involved deaths during 2020 (39 states and DC) using data from CDC's State Unintentional Drug Overdose Reporting System (SUDORS). During July 2019-December 2020, IMF-involved deaths increased sharply in midwestern (33.1%), southern (64.7%), and western (93.9%) jurisdictions participating in SUDORS. Approximately four in 10 IMF-involved deaths also involved a stimulant. Highlighting the need for timely overdose response, 56.1% of decedents had no pulse when first responders arrived. Injection drug use was the most frequently reported individual route of drug use (24.5%), but evidence of snorting, smoking, or ingestion, but not injection drug use was found among 27.1% of decedents. Adapting and expanding overdose prevention, harm reduction, and response efforts is urgently needed to address the high potency (3), and various routes of use for IMFs. Enhanced treatment for substance use disorders is also needed to address the increased risk for overdose (4) and treatment complications (5) associated with using IMFs with stimulants.

      9. BACKGROUND: Understanding relationships between individual-level demographic, socioeconomic status (SES) and U.S. opioid fatalities can inform interventions in response to this crisis. METHODS: The Mortality Disparities in American Community Study (MDAC) links nearly 4 million 2008 American Community Survey responses to the 2008-2015 National Death Index. Univariate and multivariable models were used to estimate opioid overdose fatality hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: Opioid overdose was an overrepresented cause of death among people 10 to 59 years of age. In multivariable analysis, compared to Hispanics, Whites and American Indians/Alaska Natives had elevated risk (HR = 2.52, CI:2.21-2.88) and (HR = 1.88, CI:1.35-2.62), respectively. Compared to women, men were at-risk (HR = 1.61, CI:1.50-1.72). People who were disabled were at higher risk than those who were not (HR = 2.80, CI:2.59-3.03). Risk was higher among widowed than married (HR = 2.44, CI:2.03-2.95) and unemployed than employed individuals (HR = 2.46, CI:2.17-2.79). Compared to adults with graduate degrees, those with high school only were at-risk (HR = 2.48, CI:2.00-3.06). Citizens were more likely than noncitizens to die from this cause (HR = 4.62, CI:3.48-6.14). Compared to people who owned homes with mortgages, those who rented had higher HRs (HR = 1.36, CI:1.25-1.48). Non-rural residents had higher risk than rural residents (HR = 1.46, CI:1.34, 1.59). Compared to respective referent groups, people without health insurance (HR = 1.30, CI:1.20-1.41) and people who were incarcerated were more likely to die from opioid overdoses (HR = 2.70, CI:1.91-3.81). Compared to people living in households at least five-times above the poverty line, people who lived in poverty were more likely to die from this cause (HR = 1.36, CI:1.20-1.54). Compared to people living in West North Central states, HRs were highest among those in South Atlantic (HR = 1.29, CI:1.11, 1.50) and Mountain states (HR = 1.58, CI:1.33, 1.88). DISCUSSION: Opioid fatality was associated with indicators of low SES. The findings may help to target prevention, treatment and rehabilitation efforts to vulnerable groups.

  2. CDC Authored Publications
    The names of CDC authors are indicated in bold text.
    Articles published in the past 6-8 weeks authored by CDC or ATSDR staff.
    • Chronic Diseases and Conditions
      1. Factors impacting survival in those transplanted for NASH cirrhosis: Data from the NailNASH Consortium
        Rinella ME, Satapathy SK, Brandman D, Smith C, Elwir S, Xia J, Gibson M, Figueredo C, Angirekula M, Vanatta JM, Sarwar R, Jiang Y, Gregory D, Agostini T, Ko J, Podila P, Gallo G, Watt KD, Siddiqui MS.
        Clin Gastroenterol Hepatol. 2022 Feb 18.
        BACKGROUND & AIMS: Nonalcoholic steatohepatitis (NASH) is the leading indication for liver transplant (LT) in women and the elderly. Granular details into factors impacting survival in this population are needed to optimize management and improve outcomes. METHODS: Patients receiving LT for NASH cirrhosis from 1997 to 2017 across 7 transplant centers (NailNASH consortium) were analyzed. The primary outcome was all-cause mortality, and causes of death were enumerated. All outcomes were cross referenced with United Network for Organ Sharing and adjudicated at each individual center. Cox regression models were constructed to elucidate clinical factors impacting mortality. RESULTS: Nine hundred thirty-eight patients with a median follow-up of 3.8 years (interquartile range, 1.60-7.05 years) were included. The 1-, 3-, 5-, 10-, and 15-year survival of the cohort was 93%, 88%, 83%, 69%, and 46%, respectively. Of 195 deaths in the cohort, the most common causes were infection (19%), cardiovascular disease (18%), cancer (17%), and liver-related (11%). Inferior survival was noted in patients >65 years. On multivariable analysis, age >65 (hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.04-2.77; P = .04), end-stage renal disease (HR, 1.55; 95% CI, 1.04-2.31; P = .03), black race (HR, 5.25; 95% CI, 2.12-12.96; P = .0003), and non-calcineurin inhibitors-based regimens (HR, 2.05; 95% CI, 1.19-3.51; P = .009) were associated with increased mortality. Statin use after LT favorably impacted survival (HR, 0.38; 95% CI, 0.19-0.75; P = .005). CONCLUSIONS: Despite excellent long-term survival, patients transplanted for NASH at >65 years or with type 2 diabetes mellitus at transplant had higher mortality. Statin use after transplant attenuated risk and was associated with improved survival across all subgroups, suggesting that careful patient selection and implementation of protocol-based management of metabolic comorbidities may further improve clinical outcomes.

      2. Geospatial perspectives on the intersection of chronic disease and COVID-19
        Mennis J, Matthews KA, Huston SL.
        Prev Chronic Dis. 2022 Jun 30;19:E39.

      3. Assessing the impact of multicomponent interventions on colorectal cancer screening through simulation: What would it take to reach national screening targets in North Carolina?
        Hicklin K, O'Leary MC, Nambiar S, Mayorga ME, Wheeler SB, Davis MM, Richardson LC, Tangka FK, Lich KH.
        Prev Med. 2022 Jul 1:107126.
        Healthy People 2020 and the National Colorectal Cancer Roundtable established colorectal cancer (CRC) screening targets of 70.5% and 80%, respectively. While evidence-based interventions (EBIs) have increased CRC screening, the ability to achieve these targets at the population level remains uncertain. We simulated the impact of multicomponent interventions in North Carolina over 5 years to assess the potential for meeting national screening targets. Each intervention scenario is described as a core EBI with additional components indicated by the "+" symbol: patient navigation for screening colonoscopy (PN-for-Col+), mailed fecal immunochemical testing (MailedFIT+), MailedFIT+ targeted to Medicaid enrollees (MailedFIT + forMd), and provider assessment and feedback (PAF+). Each intervention was simulated with and without Medicaid expansion and at different levels of exposure (i.e., reach) for targeted populations. Outcomes included the percent up-to-date overall and by sociodemographic subgroups and number of CRC cases and deaths averted. Each multicomponent intervention was associated with increased CRC screening and averted both CRC cases and deaths; three had the potential to reach screening targets. PN-for-Col + achieved the 70.5% target with 97% reach after 1 year, and the 80% target with 78% reach after 5 years. MailedFIT+ achieved the 70.5% target with 74% reach after 1 year and 5 years. In the Medicaid population, assuming Medicaid expansion, MailedFIT + forMd reached the 70.5% target after 5 years with 97% reach. This study clarifies the potential for states to reach national CRC screening targets using multicomponent EBIs, but decision-makers also should consider tradeoffs in cost, reach, and ability to reduce disparities when selecting interventions.

    • Communicable Diseases
      1. A risk measurement tool for targeted HIV prevention measures amongst young pregnant and lactating women in South Africa
        Ramraj T, Abdelatif N, Chirinda W, Abdullah F, Kindra G, Goga A.
        BMC Public Health. 2022 Jun 30;22(1):1277.
        BACKGROUND: We aimed to develop and validate a tool to identify which pregnant/lactating young South African women (≤ 24 years) are at risk of HIV infection. METHODS: Data from three national South African Prevention of Mother-to-Child Transmission (PMTCT) evaluations were used to internally validate three HIV acquisition risk models for young postpartum women. We used univariate and multivariable logistic regression analysis to determine which risk factors were significant. Model coefficients were rounded and stratified into risk groups and the area under the receiver operating curve (AUROC) was computed. Models were developed to determine which risk factors provided the most predictive accuracy whilst remining clinically meaningful. RESULTS: Data from 9 456 adult and 4 658 young pregnant and lactating women were included in the development and validation data sets, respectively. The optimal model included the following risk factors: age (20-24 years old), informal house structure, two or more pregnancies, mothers who had knowledge of when they received their last HIV test result, no knowledge of the infant's father's HIV status, no knowledge of breastfeeding as a mode of MTCT and knowledge of PMTCT programme. The mean AUROC was 0.71 and 0.72 in the development and validation datasets respectively. The optimum cut off score was ≥ 27, having 84% sensitivity, 44% specificity, and identifying 44% of high-risk women eligible for PrEP. CONCLUSION: The optimal model to be used as a possible risk scoring tool to allow for early identification of those pregnant/lactating women most at-risk of HIV acquisition included both statistically as well as clinically meaningful risk factors. A field-based study is needed to test and validate the effectiveness of this targeted approach.

      2. Magnitude and determinants of SARS-CoV-2 household transmission: a longitudinal cohort study
        Daniel Kelly J, Lu S, Anglin K, Garcia-Knight M, Pineda-Ramirez J, Goldberg SA, Tassetto M, Zhang A, Donohue K, Davidson MC, Romero M, Sanchez RD, Djomaleu M, Mathur S, Chen JY, Forman CA, Servellita V, Montejano RD, Shak JR, Rutherford GW, Deeks SG, Abedi GR, Rolfes MA, Saydah S, Briggs-Hagen M, Peluso MJ, Chiu C, Midgley CM, Andino R, Martin JN.
        Clin Infect Dis. 2022 Jul 5.
        BACKGROUND: Households have emerged as important venues for SARS-CoV-2 transmission. Little is known, however, regarding the magnitude and determinants of household transmission in increasingly vaccinated populations. METHODS: From September 2020 to January 2022, symptomatic non-hospitalized individuals with SARS-CoV-2 infection by RNA detection were identified within 5 days of symptom onset; all individuals resided with at least one other SARS-CoV-2-uninfected household member. These infected persons (cases) and their household members (contacts) were subsequently followed with questionnaire-based measurement and serial nasal specimen collection. The primary outcome was SARS-CoV-2 infection among contacts. RESULTS: We evaluated 42 cases and their 74 household contacts. Among the contacts, 32 (43%) became infected, of whom 5/32 (16%) were asymptomatic; 81% of transmissions occurred by 5 days after the case's symptom onset. From 21 unvaccinated cases, 14-day cumulative incidence of SARS-CoV-2 infection among contacts was 18/40 (45%; 95% CI: 29, 62), most of whom were unvaccinated. From 21 vaccinated cases, 14-day cumulative incidence of SARS-CoV-2 infection was 14/34 (41%; 95% CI: 25, 59) among all contacts and 12/29 (41%; 95% CI: 24, 61) among vaccinated contacts. At least one co-morbid condition among cases and 10 or more days of RNA detection in cases were associated with increased risk of infection among contacts. CONCLUSIONS: Among households including individuals with symptomatic SARS-CoV-2 infection, both vaccinated-to-vaccinated and unvaccinated-to-unvaccinated transmission of SARS-CoV-2 to household contacts was common. Because vaccination alone did not notably reduce risk of infection, household contacts will need to employ additional interventions to avoid infection.

      3. SARS-CoV-2 infections and reinfections among fully vaccinated and unvaccinated university athletes - 15 states, January - November 2021
        Good MK, Czarnik M, Harmon KG, Aukerman D, O'Neal CS, Day C, Goerl K, Sifre K, Fink S, Riggs MA.
        Clin Infect Dis. 2022 Jun 30.
        BACKGROUND: Limited data currently exist on SARS-CoV-2 infections among fully vaccinated persons or reinfections in college-aged populations. CDC partnered with National Collegiate Athletic Association (NCAA) institutions to analyze retrospective data and present characteristics of positive COVID-19 cases among student athletes 18 years of age and older. METHODS: De-identified, individual-level data contributed by 21 universities on 1378 student athletes who tested positive for SARS-CoV-2 from January through November 2021 (pre-Omicron) were examined to determine percentages of infection among unvaccinated, partially vaccinated, and fully vaccinated individuals (breakthrough infections) as well as reinfections. Comparisons by demographic characteristics and regions were also made to further characterize these infections. RESULTS: Among the 1378 student athletes positive for SARS-CoV-2, 1070 (77.6%) were infected when unvaccinated and 22.4% (N = 308) were infected after full vaccination. There was a significant difference between Black (14.7%, n = 40) and White (23.9%, n = 168) student athletes who experienced a COVID-19 infection after being fully vaccinated (p < 0.01). Proportions of infections among fully vaccinated individuals did not differ statistically by sex (p = 0.06). CONCLUSIONS: This paper adds to the knowledge of COVID-19 infections among fully vaccinated individuals in college-aged populations. The level of infections among fully vaccinated student athletes indicates the need for maintaining precautions to prevent infection. Further study of COVID-19 vaccination, infection, and reinfection among the well-resourced and diverse population of student athletes might contribute further understanding of factors that play a role in health equity among young adults.

      4. Utility of a test to return strategy to identify individuals with COVID-19 in the pre-kindergarten through grade 12 school setting - District of Columbia, January 2022
        Samson ME, Still WL, Mark-Carew M, Jarris DK, Idris A, van Zyl A, Addo D, Ashley P, Ike OJ, Thomas ES, Mangla AT, Nesbitt LS.
        Clin Infect Dis. 2022 Jul 1.
        The highly transmissible SARS-CoV-2 Omicron variant led to increased hospitalizations, staffing shortages, and increased school closures. To reduce spread in school-aged children during the Omicron peak, the District of Columbia implemented a test-to-return strategy in public and public charter schools after a two-week break from in-person learning.

      5. The HIV epidemic in South Africa: Key findings from 2017 national population-based survey
        Zuma K, Simbayi L, Zungu N, Moyo S, Marinda E, Jooste S, North A, Nadol P, Aynalem G, Igumbor E, Dietrich C, Sigida S, Chibi B, Makola L, Kondlo L, Porter S, Ramlagan S.
        Int J Environ Res Public Health. 2022 ;19(13).
        South Africa has the largest number of people living with HIV worldwide. South Africa has implemented five population-based HIV prevalence surveys since 2002 aimed at understanding the dynamics and the trends of the epidemic. This paper presents key findings from the fifth HIV prevalence, incidence, and behaviour survey conducted in 2017 following policy, programme, and epidemic change since the prior survey was conducted in 2012. A cross-sectional population-based household survey collected behavioural and biomedical data on all members of the eligible households. A total of 39,132 respondents from 11,776 households were eligible to participate, of whom 93.6% agreed to be interviewed, and 61.1% provided blood specimens. The provided blood specimens were used to determine HIV status, HIV incidence, viral load, exposure to antiretroviral treatment, and HIV drug resistance. Overall HIV incidence among persons aged 2 years and above was 0.48% which translates to an estimated 231,000 new infections in 2017. HIV prevalence was 14.0% translating to 7.9 million people living with HIV. Antiretroviral (ARV) exposure was 62.3%, with the lowest exposure among those aged 15 to 24 years (39.9%) with 10% lower ARV coverage among males compared to females. Viral suppression among those on treatment was high (87.3%), whilst HIV population viral load suppression was much lower (62.3%). In terms of risk behaviours, 13.6% of youth reported having had an early sexual debut (first sex before the age of 15 years), with more males reporting having done so (19.5%) than females (7.6%). Age-disparate relationships, defined as having a sexual partner 5+ years different from oneself,) among adolescents were more common among females (35.8%) than males (1.5%). Self-reported multiple sexual partnerships (MSPs), defined as having more than one sexual partner in the previous 12 months, were more commonly reported by males (25.5%) than females (9.0%). Condom use at last sexual encounter was highest among males than females. Three quarters (75.2%) of people reported they had ever been tested for HIV, with more females (79.3%) having had done so than males (70.9%). Two-thirds of respondents (66.8%) self-reported having tested for HIV in the past 12 months. Finally, 61.6% of males in the survey self-reported as having been circumcised, with circumcision being more common among youth aged 15–24 years (70.2%), Black Africans (68.9%), and those living in both rural informal (tribal) areas (65%) and urban areas (61.9%). Slightly more (51.2%) male circumcisions were reported to have occurred in a medical setting than in traditional settings (44.8%), with more young males aged 15–24 (62.6%) and men aged 25–49 (51.5%) reporting to have done so compared to most men aged 50 and older (57.1%) who reported that they had undergone circumcision in a traditional setting. The results of this survey show that strides have been made in controlling the HIV epidemic, especially in the reduction of HIV incidence, HIV testing, and treatment. Although condom use at last sex act remains unchanged, there continue to be some challenges with the lack of significant behaviour change as people, especially youth, continue to engage in risky behaviour and delay treatment initiation. Therefore, there is a need to develop or scale up targeted intervention programmes to increase HIV testing further and put more people living with HIV on treatment as well as prevent risky behaviours that put young people at risk of HIV infection. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

      6. Point prevalence estimates of activity-limiting long-term symptoms among U.S. adults ≥1 month after reported SARS-CoV-2 infection, November 1, 2021
        Tenforde MW, Devine OJ, Reese HE, Silk BJ, Iuliano AD, Threlkel R, Vu QM, Plumb ID, Cadwell BL, Rose C, Steele MK, Briggs-Hagen M, Ayoubkhani D, Pawelek P, Nafilyan V, Saydah SH, Bertolli J.
        J Infect Dis. 2022 Jul 1.
        BACKGROUND: Although most adults infected with SARS-CoV-2 fully recover, a proportion have ongoing symptoms, or post-COVID conditions (PCC), after infection. The objective of this analysis was to estimate the number of US adults with activity-limiting PCC on November 1, 2021. METHODS: We modeled the prevalence of PCC using reported infections occurring from February 1, 2020 - September 30, 2021, and population-based, household survey data on new activity-limiting symptoms ≥1 month following SARS-CoV-2 infection. From these data sources, we estimated the number and proportion of US adults with activity-limiting PCC on November 1, 2021, as 95% uncertainty intervals, stratified by sex and age. Sensitivity analyses adjusted for under-ascertainment of infections and uncertainty about symptom duration. RESULTS: On November 1, 2021, at least 3.0-5.0 million US adults were estimated to have activity-limiting PCC of ≥1 month duration, or 1.2%-1.9% of US adults. Population prevalence was higher in females (1.4%-2.2%) than males. The estimated prevalence after adjusting for under-ascertainment of infections was 1.7%-3.8%. CONCLUSION: Millions of US adults were estimated to have activity-limiting PCC. These estimates can support future efforts to address the impact of PCC on the U.S. population.

      7. Perinatal COVID-19 maternal and neonatal outcomes at two academic birth hospitals
        Flannery DD, Zevallos Barboza A, Pfeifer MR, Hudak ML, Barnette K, Getzlaff TR, Ellington SR, Woodworth KR, Dhudasia MB, Mukhopadhyay S, Weinberg DD, Foglia EE, Puopolo KM.
        J Perinatol. 2022 Jul 1:1-8.
        OBJECTIVE: Describe 1-month outcomes among newborns of persons with perinatal COVID-19. STUDY DESIGN: Prospective observational study of pregnant persons who tested positive for SARS-CoV-2 between 14 days before and 3 days after delivery and their newborns, from 3/2020 to 3/2021 at two urban high-risk academic hospitals. Phone interviews were conducted to determine 1-month newborn outcomes. RESULTS: Among 9748 pregnant persons, 209 (2.1%) tested positive for perinatal SARS-CoV-2. Symptomatically infected persons were more likely to have a preterm delivery due to worsening maternal condition and their newborns were more likely to test positive for SARS-CoV-2 compared with asymptomatic persons. Six of 191 (3.1%) infants tested were positive for SARS-CoV-2; none had attributable illness before discharge. Of 169 eligible families, 132 (78.1%) participated in post-discharge interviews; none reported their newborn tested positive for SARS-CoV-2 by 1 month of age. CONCLUSION: Symptomatic perinatal COVID-19 had a substantial effect on maternal health but no apparent short-term effect on newborns.

      8. Estimated number of COVID-19 infections, hospitalizations, and deaths prevented among vaccinated persons in the US, December 2020 to September 2021
        Steele MK, Couture A, Reed C, Iuliano D, Whitaker M, Fast H, Hall AJ, MacNeil A, Cadwell B, Marks KJ, Silk BJ.
        JAMA Netw Open. 2022 Jul 1;5(7):e2220385.
        IMPORTANCE: The number of SARS-CoV-2 infections and COVID-19-associated hospitalizations and deaths prevented among vaccinated persons, independent of the effect of reduced transmission, is a key measure of vaccine impact. OBJECTIVE: To estimate the number of SARS-CoV-2 infections and COVID-19-associated hospitalizations and deaths prevented among vaccinated adults in the US. DESIGN, SETTING, AND PARTICIPANTS: In this modeling study, a multiplier model was used to extrapolate the number of SARS-CoV-2 infections and COVID-19-associated deaths from data on the number of COVID-19-associated hospitalizations stratified by state, month, and age group (18-49, 50-64, and ≥65 years) in the US from December 1, 2020, to September 30, 2021. These estimates were combined with data on vaccine coverage and effectiveness to estimate the risks of infections, hospitalizations, and deaths. Risks were applied to the US population 18 years or older to estimate the expected burden in that population without vaccination. The estimated burden in the US population 18 years or older given observed levels of vaccination was subtracted from the expected burden in the US population 18 years or older without vaccination (ie, counterfactual) to estimate the impact of vaccination among vaccinated persons. EXPOSURES: Completion of the COVID-19 vaccination course, defined as 2 doses of messenger RNA (BNT162b2 or mRNA-1273) vaccines or 1 dose of JNJ-78436735 vaccine. MAIN OUTCOMES AND MEASURES: Monthly numbers and percentages of SARS-CoV-2 infections and COVID-19-associated hospitalizations and deaths prevented were estimated among those who have been vaccinated in the US. RESULTS: COVID-19 vaccination was estimated to prevent approximately 27 million (95% uncertainty interval [UI], 22 million to 34 million) infections, 1.6 million (95% UI, 1.4 million to 1.8 million) hospitalizations, and 235 000 (95% UI, 175 000-305 000) deaths in the US from December 1, 2020, to September 30, 2021, among vaccinated adults 18 years or older. From September 1 to September 30, 2021, vaccination was estimated to prevent 52% (95% UI, 45%-62%) of expected infections, 56% (95% UI, 52%-62%) of expected hospitalizations, and 58% (95% UI, 53%-63%) of expected deaths in adults 18 years or older. CONCLUSIONS AND RELEVANCE: These findings indicate that the US COVID-19 vaccination program prevented a substantial burden of morbidity and mortality through direct protection of vaccinated individuals.

      9. Interim analysis of acute hepatitis of unknown etiology in children aged <10 years - United States, October 2021-June 2022
        Cates J, Baker JM, Almendares O, Kambhampati AK, Burke RM, Balachandran N, Burnett E, Potts CC, Reagan-Steiner S, Kirking HL, Sugerman D, Parashar UD, Tate JE.
        MMWR Morb Mortal Wkly Rep. 2022 Jul 1;71(26):852-858.
        On April 21, 2022, CDC issued a health advisory(†) encouraging U.S. clinicians to report all patients aged <10 years with hepatitis of unknown etiology to public health authorities, after identification of similar cases in both the United States (1) and Europe.(§) A high proportion of initially reported patients had adenovirus detected in whole blood specimens, thus the health advisory encouraged clinicians to consider requesting adenovirus testing, preferentially on whole blood specimens. For patients meeting the criteria in the health advisory (patients under investigation [PUIs]), jurisdictional public health authorities abstracted medical charts and interviewed patient caregivers. As of June 15, 2022, a total of 296 PUIs with hepatitis onset on or after October 1, 2021, were reported from 42 U.S. jurisdictions. The median age of PUIs was 2 years, 2 months. Most PUIs were hospitalized (89.9%); 18 (6.1%) required a liver transplant, and 11 (3.7%) died. Adenovirus was detected in a respiratory, blood, or stool specimen of 100 (44.6%) of 224 patients.(¶) Current or past infection with SARS-CoV-2 (the virus that causes COVID-19) was reported in 10 of 98 (10.2%) and 32 of 123 (26.0%) patients, respectively. No common exposures (e.g., travel, food, or toxicants) were identified. This nationwide investigation is ongoing. Further clinical data are needed to understand the cause of hepatitis in these patients and to assess the potential association with adenovirus.

    • Disaster Preparedness and Emergency Services
      1. Operational challenges and considerations for COVID-19 research in humanitarian settings: A qualitative study of a project in Eastern Democratic Republic of the Congo and South Sudan
        Majer J, Udoh K, Beleke A, Ahmed D, Kumar D, Summers A, Ververs M, Bollemeijer I, Doocy S.
        PLoS One. 2022 ;17(6):e0267822.
        Since the beginning of the COVID-19 pandemic, much research has been conducted globally, but relatively few studies have been carried out in complex emergency settings that pose numerous operational challenges. We conducted a qualitative study to explore the barriers and enablers of a COVID-19 cohort study conducted in South Sudan and Eastern Democratic Republic of the Congo, to inform future research on COVID-19 and infectious diseases in humanitarian settings. We used a case study design embedded within the original prospective cohort study. Qualitative data was collected through four health facility assessments, 28 key informant interviews, and a focus group discussion. Data were analyzed using a manual thematic analysis approach and summarized against four primary themes: testing challenges and enablers, perceptions and attitudes towards COVID-19, national health system considerations, and study management considerations. Findings suggest most of the challenges affecting the cohort study were not specific to COVID-19 research but have been a feature of previous infectious disease research carried out in complex emergencies. However, the pandemic has exacerbated certain problems. The high proportion of travellers enrolled due to testing mandates, stigmatization of infected individuals linked to the heavy global focus on COVID-19, strained resources during waves of increasing infections, and remote management requirements all negatively impacted the cohort study. Factors that facilitated the research included proactive management, data quality oversight procedures, and strong collaboration with national health stakeholders. The global impact of COVID-19, its high public profile, and specific pandemic policies pose further operational challenges for research in already complex humanitarian settings. Future studies could plan mitigation measures that include flexibility in staffing and budgets, strategies to expand testing, and early partnerships with local organizations and health authorities.

    • Disease Reservoirs and Vectors
      1. Predicting distributions of blacklegged ticks (Ixodes scapularis), Lyme disease spirochetes (Borrelia burgdorferi sensu stricto) and human Lyme disease cases in the eastern United States
        Burtis JC, Foster E, Schwartz AM, Kugeler KJ, Maes SE, Fleshman AC, Eisen RJ.
        Ticks Tick Borne Dis. 2022 Jun 30;13(5):102000.
        Lyme disease is the most commonly reported vector-borne disease in the United States (US), with approximately 300,000 -to- 40,000 cases reported annually. The blacklegged tick, Ixodes scapularis, is the primary vector of the Lyme disease-causing spirochete, Borrelia burgdorferi sensu stricto, in high incidence regions in the upper midwestern and northeastern US. Using county-level records of the presence of I. scapularis or presence of B. burgdorferi s.s. infected host-seeking I. scapularis, we generated habitat suitability consensus maps based on an ensemble of statistical models for both acarological risk metrics. Overall accuracy of these suitability models was high (AUC = 0.76 for I. scapularis and 0.86 for B. burgdorferi s.s. infected-I. scapularis). We sought to compare which acarological risk metric best described the distribution of counties reporting high Lyme disease incidence (≥10 confirmed cases/100,000 population) by setting the models to a fixed omission rate (10%). We compared the percent of high incidence counties correctly classified by the two models. The I. scapularis consensus map correctly classified 53% of high and low incidence counties, while the B. burgdorferi s.s. infected-I. scapularis consensus map classified 83% correctly. Counties classified as suitable by the B. burgdorferi s.s. map showed a 91% overlap with high Lyme disease incidence counties with over a 38-fold difference in Lyme disease incidence between high- and low-suitability counties. A total of 288 counties were classified as highly suitable for B. burgdorferi s.s., but lacked records of infected-I. scapularis and were not classified as high incidence. These counties were considered to represent a leading edge for B. burgdorferi s.s. infection in ticks and humans. They clustered in Illinois, Indiana, Michigan, and Ohio. This information can aid in targeting tick surveillance and prevention education efforts in counties where Lyme disease risk may increase in the future.

    • Environmental Health
      1. Study of "ALS reversals": LifeTime environmental exposures (StARLiTE)
        Crayle J, Lutz M, Raymond J, Mehta P, Bedlack R.
        Amyotroph Lateral Scler Frontotemporal Degener. 2022 Jul 1:1-9.
        We previously reported on a series of patients diagnosed with ALS whom had an extraordinary course defined by substantial and sustained improvement in weakness and function. For this study, twenty-five of these "ALS Reversals" completed extensive environmental exposure questionnaires. These responses were then compared to a large database of prior responses from patients with typically progressive ALS (n = 6187). The results demonstrated that the "Reversal" participants have had a diverse number of exposures with substantial heterogeneity. In general, this was similar to the control group; however, there were a few specific differences that could be further explored in future research.

    • Genetics and Genomics
      1. Effect of childhood vaccination and antibiotic use on pneumococcal populations and genome-wide associations with disease among children in Nepal: An observational study
        Kandasamy R, Lo S, Gurung M, Carter MJ, Gladstone R, Lees J, Shrestha S, Thorson S, Bijukchhe S, Gautam MC, Shrestha R, Gurung S, Khadka B, McGee L, Breiman RF, Murdoch DR, Kelly DF, Shrestha S, Bentley SD, Pollard AJ.
        Lancet Microbe. 2022 Jul;3(7):e503-e511.
        BACKGROUND: Pneumococcal disease is a leading cause of bacterial pneumonia and invasive bacterial disease among children globally. The reason some strains of pneumococci are more likely to cause disease, and how interventions such as vaccines and antibiotics affect pneumococcal strains is poorly understood. We aimed to identify genetic regions under selective pressure and those associated with disease through the analysis of pneumococcal whole-genome sequences. METHODS: Whole-genome sequencing was performed on pneumococcal isolates collected between January, 2005, and May, 2018, in Kathmandu, Nepal, which included programmatic ten-valent pneumococcal conjugate vaccine (PCV10) introduction in 2015. Isolates were from three distinct cohorts: nasopharyngeal swabs of healthy community-based children, nasopharyngeal swabs of children admitted to hospital with pneumonia, and sterile-site cultures from children admitted to hospital. Across these cohorts we examined serotype distribution, antibiotic resistance, strain distribution, and regions of recombination to determine genes that were undergoing diversifying selection. Genome-wide association studies comparing pneumonia and sterile-site isolates with healthy carriage were used to determine novel variants associated with disease. FINDINGS: After programmatic introduction of PCV10, there was a decline in vaccine covered serotypes; however, strains that had expressed these serotypes continued to exist in the post-PCV population. We identified GPSC9 to be a strain of concern due to its high prevalence in disease, multidrug resistance, and ability to switch to an unencapsulated phenotype via insertion of virulence factor pspC into the cps locus. Antibiotic resistance loci to co-trimoxazole were found to be prevalent (pre-PCV10 78% vs post-PCV10 81%; p=0·27) and increasingly prevalent to penicillin (pre-PCV10 15% vs post-PCV10 32%; p<0·0001). Regions with multiple recombinations were identified spanning the surface protein virulence factors pspA and pspC and antibiotic targets pbpX, folA, folC, folE, and folP. Furthermore, we identified variants in lacE2 to be strongly associated with isolates from children with pneumonia and PRIP to be strongly associated with isolates from sterile sites. INTERPRETATION: Our work highlights the effect of pneumococcal conjugate vaccines, antibiotics, and host-pathogen interaction in pneumococcal variation, and the pathogen's capability of adapting to these factors at both population-wide and strain-specific levels. Ongoing surveillance of disease-associated strains and further investigation of lacE2 and PRIP as serotype-independent targets for therapeutic interventions is required. FUNDING: Gavi, The Vaccine Alliance; WHO; Bill & Melinda Gates Foundation; Wellcome Sanger Institute; and US Centers for Disease Control and Prevention.

    • Health Behavior and Risk
      1. Behaviors and attitudes of college students during an academic semester at two Wisconsin universities during the COVID-19 pandemic
        Rosenblum HG, Segaloff HE, Cole D, Lee CC, Currie DW, Abedi GR, Remington PL, Kelly GP, Pitts C, Langolf K, Kahrs J, Leibold K, Westergaard RP, Hsu CH, Kirking HL, Tate JE.
        J Am Coll Health. 2022 Jul 1:1-8.
        OBJECTIVE: Characterize college student COVID-19 behaviors and attitudes during the early pandemic. Participants: Students on two university campuses in Wisconsin. METHODS: Surveys administered in September and November 2020. RESULTS: Few students (3-19%) participated in most in-person activities during the semester, with eating at restaurants as the exception (72-80%) and attending work (35%) and parties (33%) also reported more frequently. The majority wore masks in public (94-99%), but comparatively fewer (42%) did so at parties. Mask-wearing at parties decreased from September to November (p < 0.05). Students attending parties, or consuming more alcohol, were less concerned and more likely to take COVID-19-associated risks. CONCLUSIONS: Students were motivated to adhere to COVID-19 prevention measures but gathered socially. Though there was frequent public masking, mask-wearing at parties declined in November and may represent pandemic fatigue. High-yield strategies for decreasing viral spread may include changing masking social norms and engaging with students about creative risk-reduction strategies.

      2. Effectiveness of personal protection measures against Lyme disease: A review of epidemiologic studies from the United States
        Schwartz AM, Mackeprang JM, Mead PS, Hinckley AF.
        Zoonoses Public Health. 2022 Jul 5.
        Lyme disease, the most commonly reported vector-borne disease in the United States, is caused by the bacteria Borrelia burgdorferi and is transmitted through the bite of an infected blacklegged tick. In the absence of a licensed vaccine, the prevention of Lyme disease relies heavily on limiting tick exposure. Methods for limiting tick exposure include personal protection measures such as repellent use, wearing protective clothing, avoiding areas where ticks may be present, bathing after exposure to tick habitat and performing regular tick checks. Public health officials typically recommend all these personal protection measures; however, there is limited evidence to promote one behaviour or practice over another. The focus of this article is to review available literature that examines the effectiveness of recommended personal protection measures to prevent Lyme and other Ixodes-transmitted diseases in humans. Articles included in this review were identified through Google Scholar and PubMed searches using specific search terms. We identified over 56,000 articles using Google Scholar and PubMed searches. Of those, 16 studies fit our criteria for inclusion and were reviewed in their entirety. Among the personal protection measures evaluated, no intervention was predominantly or consistently effective across studies, demonstrating that, currently, there is no single best method for primary prevention of Ixodes-transmitted diseases in the United States. Frequently recommended practices such as tick checks, repellent use and protective clothing had mixed results across studies. Study design differences limited comparability among studies, and sample sizes for these studies may have been too small to detect statistically significant results even if a prevention method was effective. Though many of the reviewed personal protection measures are frequently recommended to the public, limited evidence demonstrates their ability to prevent tick-borne disease. Additional standardized studies are needed to evaluate personal protection measures.

    • Health Economics
      1. Health economics research in primary prevention of cancer: Assessment, current challenges, and future directions
        Ekwueme DU, Halpern MT, Chesson HW, Ashok M, Drope J, Hong YR, Maciosek M, Pesko MF, Kenkel DS.
        J Natl Cancer Inst Monogr. 2022 Jul 5;2022(59):28-41.
        In the past 2 decades, the demand for information on health economics research to guide health care decision making has substantially increased. Studies have provided evidence that eliminating or reducing tobacco use; eating a healthy diet, including fruit and vegetables; being physically active; reducing alcohol consumption; avoiding ultraviolet radiation; and minimizing exposure to environmental and occupational carcinogenic agents should substantially reduce cancer incidence in the population. The benefits of these primary prevention measures in reducing cancer incidence are not instantaneous. Therefore, health economics research has an important role to play in providing credible information to decision makers on the health and economic benefits of primary prevention. This article provides an overview of health economics research related to primary prevention of cancer. We addressed the following questions: 1) What are the gaps and unmet needs for performing health economics research focused on primary prevention of cancer? 2) What are the challenges and opportunities to conducting health economics research to evaluate primary prevention of cancer? and 3) What are the future directions for enhancing health economics research on primary prevention of cancer? Modeling primary prevention of cancer is often difficult given data limitations, long delays before the policy or intervention is effective, possible unintended effects of the policy or intervention, and the necessity of outside expertise to understand key inputs or outputs to the modeling. Despite these challenges, health economics research has an important role to play in providing credible information to decision makers on the health and economic benefits of primary prevention of cancer.

      2. The differential impact of reopening states with and without COVID-19 face mask mandates on county-level consumer spending
        Dunphy C, Miller GF, Sunshine G, McCord R, Howard-Williams M, Proia K, Stephens J.
        Public Health Rep. 2022 Jul 6:333549221103816.
        OBJECTIVES: By the end of 2020, 38 states and the District of Columbia had issued requirements that people wear face masks when in public settings to counter SARS-CoV-2 transmission. To examine the role face mask mandates played in economic recovery, we analyzed the interactive effect of having a state face mask mandate in place on county-level consumer spending after state reopening, adjusting for county rates of new COVID-19 cases and deaths, time trends, and county-specific effects. METHODS: We collected county-specific data from state executive orders, consumer spending data from the Opportunity Insights Economic Tracker, and COVID-19 case and death data from the Centers for Disease Control and Prevention COVID-19 tracker. Using an event study approach, we compared county-level changes in consumer spending before and after state-issued closure orders were lifted and assessed the interactive effect of state-issued face mask mandates. RESULTS: The lifting of state-issued closures was associated with an average increase in consumer spending across all counties studied within 1 month. However, the increase was 1.2-1.7 percentage points higher in counties with a state face mask mandate in place than in counties without a state face mask mandate. CONCLUSIONS: In addition to their public health benefits, face mask mandates may have assisted economic recovery during the COVID-19 pandemic, suggesting they are a strong public health strategy for policy makers to consider now and for potential future pandemics arising from airborne viruses.

    • Health Equity and Health Disparities
      1. US government health agencies' efforts to address HIV-related intersectional stigma
        Gaist PA, Greenwood GL, Wilson A, Dempsey A, Harrison TP, Haverkate RT, Koenig LJ, McCree DH, Palmieri J, Phillips HJ.
        Am J Public Health. 2022 Jun;112(S4):S401-s404.

      2. Getting critical information during the COVID-19 pandemic: Experiences of Spanish and Chinese speakers with limited English proficiency
        SteelFisher GK, Caporello HL, Lubell KM, Ben-Porath EN, Green AR, Luo F, Briseno L, Lane L, Sheff SE, Taillepierre JD, Espino L, Boyea A.
        Health Secur. 2022 Jun 30.
        People with limited English proficiency in the United States have suffered disproportionate negative health outcomes during the COVID-19 pandemic. Effective communications are critical tools in addressing inequities insofar as they can motivate adoption of protective behaviors and reduce incidence of disease; however, little is known about experiences of communities with limited English proficiency receiving relevant information during COVID-19 or other outbreaks. To address this gap and provide inputs for communication strategies, we completed a study based on 2 novel and nationally representative surveys conducted between June and August 2020 among Spanish and Chinese speakers with limited English proficiency (n = 764 and n = 355, respectively). Results first showed that Spanish and Chinese speakers did not consistently receive information about protective behaviors from key public health and government institutions early in the pandemic. Second, for such information, Spanish and Chinese speakers used a diverse set of information resources that included family and friends, social media, and traditional media from both inside and outside the United States. Third, Spanish and Chinese speakers faced challenges getting COVID-19 information, including receiving media messages that felt discriminatory toward Latinx or Chinese people. Together, these findings suggest gaps in effectively reaching Spanish and Chinese speakers. Data highlight the important role of bilingual materials to support sharing of information between Spanish or Chinese speakers and English speakers within their social networks, and the need for digital news content for traditional and social media. Finally, efforts are needed to address discriminatory messaging in media and to actively counter it in public health communications.

      3. Associations between mobility, food insecurity, and transactional sex among women in cohabitating partnerships: An analysis from 6 African countries 2016-2017
        Khalifa A, Findley S, Gummerson E, Mantell JE, Hakim AJ, Philip NM, Ginindza C, Hassani AS, Hong SY, Jalloh MF, Kirungi WL, Maile L, Mgomella GS, Miller LA, Minchella P, Mutenda N, Njau P, Schwitters A, Ward J, Low A.
        J Acquir Immune Defic Syndr. 2022 Aug 1;90(4):388-398.
        BACKGROUND: Mobile women are at risk of HIV infection in sub-Saharan Africa, although we lack evidence for HIV risk among women in mobile partnerships, especially in the context of household food insecurity, a growing concern in the region. SETTING: Women aged 15-59 years with a cohabitating male partner who participated in population-based HIV impact assessment surveys in Eswatini, Lesotho, Namibia, Tanzania, Uganda, and Zambia. METHODS: We evaluated the association between women's and their partner's mobility (being away from home for more than 1 month or staying elsewhere) and transactional sex (selling sex or receiving money or goods in exchange for sex). We examined associations for effect measure modification by food insecurity level in the household in the past month. We used survey-weighted logistic regression, pooled and by country, adjusting for individual, partner, and household-level variables. RESULTS: Among women with a cohabitating male partner, 8.0% reported transactional sex, ranging from 2.7% in Lesotho to 13.4% in Uganda. Women's mobility [aOR 1.35 (95% CI: 1.08 to 1.68)], but not their partner's mobility [aOR 0.91 (0.74-1.12)], was associated with transactional sex. Food insecurity was associated with transactional sex independent of mobility [aOR 1.29 (1.10-1.52)]. Among those who were food insecure, mobility was not associated with increased odds of transactional sex. CONCLUSION: Food insecurity and women's mobility each increased the odds of transactional sex. Because transactional sex is associated with HIV risk, prevention programs can address the needs of mobile and food-insecure women, including those in cohabitating relationships.

      4. Trends in obesity disparities during childhood
        Ogden CL, Martin CB, Freedman DS, Hales CM.
        Pediatrics. 2022 Jul 5.

    • Healthcare Associated Infections
      1. Antibiotic resistant infections among COVID-19 inpatients in U.S. hospitals
        Baggs J, Rose AN, McCarthy NL, Wolford H, Srinivasan A, Jernigan JA, Reddy SC.
        Clin Infect Dis. 2022 Jul 2.
        We described bacterial/fungal co-infections and antibiotic resistant infections among inpatients diagnosed with COVID-19 and compared findings with inpatients diagnosed with influenza-like-illness. Less than 10% of COVID-19 inpatients had bacterial/fungal co-infection. Longer lengths of stay, critical care stay, and mechanical ventilation contribute to increased incidence of hospital-onset infections among COVID-19 inpatients.

    • Immunity and Immunization
      1. Primary care professionals' attitudes towards vaccination recommendation for patients with inflammatory bowel disease
        Xu F, deJong N, Kappelman MD, Greenlund KJ, Carlson SA.
        Inflamm Bowel Dis. 2022 Jul 2.
        BACKGROUND: Immunization among patients with inflammatory bowel disease (IBD) is suboptimal. We sought to characterize attitudes of US primary care professionals (PCPs) towards immunization practices for patients with IBD. METHODS: Using a web-based opt-in panel of PCPs (DocStyles survey, spring 2021, cross-sectional study), we assessed likelihood of PCPs' recommending influenza, pneumococcal disease, herpes zoster, and human papilloma virus vaccinations for IBD patients by PCP characteristics and availability of clinical tools. Reasons for unlikelihood of recommending vaccines and approaches to improve vaccine recommendation were examined. RESULTS: Among 1503 PCPs, 64% recommended all vaccines. Herpes zoster vaccine was most likely to be recommended (89.8%) and pneumococcal vaccine was least likely (74.0%). Clinical tools including decision support based on electronic health records (EHRs; 48.9%) and staff tracking of patients' vaccine needs (36.3%) were significantly associated with likelihood of recommending vaccines (P < .001). A greater likelihood of vaccine recommendation was observed for pediatricians vs other medical specialties, group outpatient clinic vs other worksites, and seeing >50 patients/week (P < .05). One-third of PCPs were unlikely to recommend ≥1 vaccine, and the top reason reported was unfamiliarity with vaccine guidelines for patients with IBD (48.0%). A review of guidelines or continued medical education (63.0%) and decision support from EHRs (51.2%) were the most frequently selected approaches identified to improve certainty of vaccine recommendation. CONCLUSIONS: There is room for improvement of vaccination recommendations by PCPs. Promoting continuing education and use of clinical tools may help support PCP immunization practices for patients with IBD. In a survey of 1503 primary care professionals, pneumococcal vaccines were the least likely to be recommended to patients with inflammatory bowel disease (IBD). Promoting continuing education and use of clinical practice tools may improve vaccination recommendations for IBD patients. eng

      2. Survey of physician practices, attitudes, and knowledge regarding recombinant zoster vaccine
        Hurley LP, O'Leary ST, Dooling K, Anderson TC, Crane LA, Cataldi JR, Brtnikova M, Beaty BL, Gorman C, Guo A, Lindley MC, Kempe A.
        J Gen Intern Med. 2022 Jul 6.
        BACKGROUND: Herpes zoster vaccination rates remain low despite longstanding national recommendations to vaccinate immunocompetent adults aged ≥ 50 years. The Advisory Committee on Immunization Practice (ACIP) updated its recommendations for recombinant zoster vaccine (RZV) in October 2021 to include immunocompromised adults aged ≥19 years. OBJECTIVE: To assess practices, attitudes, and knowledge about RZV, barriers to recommending RZV, and likelihood of recommending RZV to patients with various immunocompromising conditions. DESIGN: Mail and internet-based survey conducted from May through July 2020. PARTICIPANTS: General internists and family physicians throughout the USA. MAIN MEASURES: Survey responses. KEY RESULTS: The response rate was 66% (632/955). Many physicians were already recommending RZV to immunocompromised populations, including adults ≥50 years with HIV (67% of respondents) and on recombinant human immune modulator therapy (56%). Forty-seven percent of respondents both stocked/administered RZV and referred patients elsewhere, frequently a pharmacy, for vaccination; 42% did not stock RZV and only referred patients. The majority agreed pharmacies do not inform them when RZV has been given (64%). Physicians were generally knowledgeable about RZV; however, 25% incorrectly thought experiencing side effects from the first dose of RZV that interfere with normal activities was a reason to not receive the second dose. The top reported barrier to recommending RZV was experience with patients declining RZV due to cost concerns (67%). Most physicians reported they would be likely to recommend RZV to immunocompromised patients. CONCLUSION: Most primary care physicians welcome updated ACIP RZV recommendations for immunocompromised adults. Knowledge gaps, communication issues, and financial barriers need to be addressed to optimize vaccination delivery.

      3. COVID-19 vaccine uptake among patients with systemic lupus erythematosus in the American Midwest: The Lupus Midwest Network (LUMEN)
        Chevet B, Figueroa-Parra G, Yang JX, Hulshizer CA, Gunderson TM, Duong SQ, Putman MS, Barbour KE, Crowson CS, Duarte-García A.
        J Rheumatol. 2022 Jul 1.
        OBJECTIVE: Systemic lupus erythematosus (SLE) patients are at higher risk of poor outcomes from coronavirus disease 2019 (COVID-19). The vaccination rate among such patients is unknown. We aimed to assess COVID-19 vaccine uptake among SLE patients. METHODS: We included 342 SLE patients from the Lupus Midwest Network and 350 age, sex, race, and county matched comparators. Vaccination uptake for influenza, pneumococcal, and zoster vaccines before pandemic restrictions began (up to February 29, 2020) was assessed. First-dose COVID-19 vaccine uptake was electronically retrieved and manually ascertained (December 15, 2020, to July 31, 2021). Time to COVID-19 vaccination, demographics, lupus manifestations, medications, comorbidity index, area deprivation index, and rurality measures were compared. RESULTS: On July 31, 2021, 83.3% of SLE patients and 85.5% of comparators were vaccinated against COVID-19. The COVID-19 vaccination rates were similar among SLE and comparators (hazard ratio: 0.93; 95% CI: 0.79-1.10). Non-vaccinated SLE patients were more likely to be men (27.3% versus 14.1% vaccinated), younger (mean 54.1 versus 58.8 years in vaccinated), have a shorter SLE duration (median 7.3 versus 10.7 years in vaccinated), and be less frequently vaccinated with influenza and pneumococcal vaccine. CONCLUSION: SLE patients in the Lupus Midwest Network had similar COVID-19 vaccination uptake as matched comparators, most of whom were vaccinated early when the vaccine became available. One in six remain unvaccinated.

      4. COVID-19 vaccine provider availability and vaccination coverage among children aged 5-11 years - United States, November 1, 2021-April 25, 2022
        DeCuir J, Meng L, Pan Y, Vogt T, Chatham-Stevens K, Meador S, Shaw L, Black CL, Harris LQ.
        MMWR Morb Mortal Wkly Rep. 2022 Jul 1;71(26):847-851.
        COVID-19 can lead to severe outcomes in children, including multisystem inflammatory syndrome, hospitalization, and death (1,2). On November 2, 2021, the Advisory Committee on Immunization Practices issued an interim recommendation for use of the BNT162b2 (Pfizer-BioNTech) vaccine in children aged 5-11 years for the prevention of COVID-19; however, vaccination coverage in this age group remains low (3). As of June 7, 2022, 36.0% of children aged 5-11 years in the United States had received ≥1 of COVID-19 vaccine (3). Among factors that might influence vaccination coverage is the availability of vaccine providers (4). To better understand how provider availability has affected COVID-19 vaccination coverage among children aged 5-11 years, CDC analyzed data on active COVID-19 vaccine providers and county-level vaccine administration data during November 1, 2021-April 25, 2022. Among 2,586 U.S. counties included in the analysis, 87.5% had at least one active COVID-19 vaccine provider serving children aged 5-11 years. Among the five assessed active provider types, most counties had at least one pharmacy (69.1%) or public health clinic (61.3%), whereas fewer counties had at least one pediatric clinic (29.7%), family medicine clinic (29.0%), or federally qualified health center (FQHC)* (22.8%). Median county-level vaccination coverage was 14.5% (IQR = 8.9%-23.6%). After adjusting for social vulnerability index (SVI)(†) and urbanicity, the analysis found that vaccination coverage among children aged 5-11 years was higher in counties with at least one active COVID-19 vaccine provider than in counties with no active providers (adjusted rate ratio [aRR] = 1.66). For each provider type, presence of at least one provider in the county was associated with higher coverage; the largest difference in vaccination coverage was observed between counties with and without pediatric clinics (aRR = 1.37). Ensuring broad access to COVID-19 vaccines, in addition to other strategies to address vaccination barriers, could help increase vaccination coverage among children aged 5-11 years.

      5. Interim recommendations of the Advisory Committee on Immunization Practices for Use of Moderna and Pfizer-BioNTech COVID-19 vaccines in children aged 6 months-5 years - United States, June 2022
        Fleming-Dutra KE, Wallace M, Moulia DL, Twentyman E, Roper LE, Hall E, Link-Gelles R, Godfrey M, Woodworth KR, Anderson TC, Rubis AB, Shanley E, Jones JM, Morgan RL, Brooks O, Talbot HK, Lee GM, Bell BP, Daley M, Meyer S, Oliver SE.
        MMWR Morb Mortal Wkly Rep. 2022 Jul 1;71(26):859-868.
        On June 17, 2022, the Food and Drug Administration (FDA) issued Emergency Use Authorization (EUA) amendments for the mRNA-1273 (Moderna) COVID-19 vaccine for use in children aged 6 months-5 years, administered as 2 doses (25 µg [0.25 mL] each), 4 weeks apart, and BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine for use in children aged 6 months-4 years, administered as 3 doses (3 µg [0.2 mL] each), at intervals of 3 weeks between doses 1 and 2 and ≥8 weeks between doses 2 and 3. On June 18, 2022, the Advisory Committee on Immunization Practices (ACIP) issued separate interim recommendations for use of the Moderna COVID-19 vaccine in children aged 6 months-5 years and the Pfizer-BioNTech COVID-19 vaccine in children aged 6 months-4 years for the prevention of COVID-19.* Both the Moderna and Pfizer-BioNTech COVID-19 vaccines met the criteria for immunobridging, which is the comparison of neutralizing antibody levels postvaccination in young children with those in young adults in whom efficacy had been demonstrated. Descriptive efficacy analyses were also conducted for both Moderna and Pfizer-BioNTech COVID-19 vaccines during the period when the Omicron variant of SARS-CoV-2 (the virus that causes COVID-19) predominated. No specific safety concerns were identified among recipients of either vaccine. ACIP recommendations for the use of the Moderna COVID-19 vaccine and the Pfizer-BioNTech COVID-19 vaccine in children aged 6 months-5 years and 6 months-4 years, respectively, are interim and will be updated as additional information becomes available. Vaccination is important for protecting children aged 6 months-5 years against COVID-19.

      6. Safety of live-attenuated vaccines in children exposed to biologic response modifiers in utero
        Zerbo O, Modaressi S, Goddard K, Lewis E, Getahun D, Palmsten KK, Fuller CC, Crane B, Donahue JG, Daley MF, Jackson LA, Wodi AP, McNeil MM, Klein NP.
        Pediatrics. 2022 Jul 1;150(1).

      7. Methodology for a correlate of protection for group B Streptococcus: Report from the Bill & Melinda Gates Foundation workshop held on 10 and 11 February 2021
        Gilbert PB, Isbrucker R, Andrews N, Goldblatt D, Heath PT, Izu A, Madhi SA, Moulton L, Schrag SJ, Shang N, Siber G, Sobanjo-Ter Meulen A.
        Vaccine. 2022 Jun 29.
        Worldwide, childhood mortality has declined significantly, with improvements in hygiene and vaccinations against common childhood illnesses, yet newborn mortality remains high. Group B Streptococcus (GBS) disease significantly contributes to newborn mortality and is the leading cause of meningitis in infants. Many years of research have demonstrated the potential for maternal vaccination against GBS to confer protection to the infant, and at least three vaccine candidates are currently undergoing clinical trials. Given the relatively low disease incidence, any clinical vaccine efficacy study would need to include at least 40,000 to 60,000 participants. Therefore, a path to vaccine licensure based on a correlate of protection (CoP) would be the preferred route, with post-approval effectiveness studies demonstrating vaccine impact on reduction of disease burden likely to be required as part of conditional marketing approval. This workshop, hosted by the Bill & Melinda Gates Foundation on 10 and 11 February 2021, discussed considerations and potential statistical methodologies for establishing a CoP for GBS disease. Consensus was reached that an antibody marker with global threshold predictive of a high level of vaccine protection would be most beneficial for licensure assessments. IgG binding antibody in cord blood would likely serve as the CoP, with additional studies needed to confirm a high correlation with functional antibody and to demonstrate comparable kinetics of natural versus vaccine-induced antibody. Common analyses of ongoing seroepidemiological studies include estimation of absolute and relative disease risk as a function of infant antibody concentration, with adjustment for confounders of the impact of antibody concentration on infant GBS disease including gestational age and maternal age. Estimation of an antibody concentration threshold indicative of high protection should build in margin for uncertainties from sources including unmeasured confounders, imperfect causal mediation, and variability in point and confidence interval estimates across regions and/or serotypes.

      8. Association of caregiver attitudes with adolescent HPV vaccination in 13 southern US states
        Vasudevan L, Ostermann J, Wang Y, Harrison SE, Yelverton V, Fish LJ, Williams C, Walter EB.
        Vaccine X. 2022 Aug;11:100181.
        BACKGROUND AND OBJECTIVES:  HPV vaccination coverage is lower than that of other adolescent vaccines in the southern US. This study sought to characterize caregiver attitudes associated with adolescent HPV vaccination in the southern US and to inform interventions to promote HPV vaccination. METHODS: From December 2019 - January 2020, caregivers of adolescents (ages 9-17 years) living in thirteen southern US states were recruited from a nationally-representative online survey panel. Caregivers (N = 1,105) completed a cross-sectional survey that assessed general adolescent vaccine attitudes as well as those associated with the HPV vaccine and HPV vaccination decision-making. The primary study outcome was adolescents' receipt of at least one dose of the HPV vaccine. RESULTS: Caregivers with vaccinated adolescents had greater positive attitudes towards adolescent vaccines compared to caregivers of unvaccinated adolescents. Top three areas of concern among caregivers were related to vaccine ingredients, perceptions that adolescents receive too many vaccines, and worry about vaccine side effects. In multivariable regression models, positive attitudes towards the HPV vaccine and HPV vaccination decision-making strongly associated with HPV vaccination in addition to general adolescent vaccination attitudes. Caregivers' reported discomfort with discussing the topic of sex was predictive of lower vaccination uptake for older adolescents. CONCLUSIONS: Public health messaging in the southern US should be tailored to reduce concerns about vaccine safety and to communicate the importance of timely HPV vaccination. Campaigns that deliver information specific to the HPV vaccine and to support vaccination decision-making may be more effective than those delivering only general adolescent vaccination information at promoting on-time HPV vaccination.

    • Informatics
      1. Using machine learning techniques and national tuberculosis surveillance data to predict excess growth in genotyped tuberculosis clusters
        Althomsons SP, Winglee K, Heilig CM, Talarico S, Silk B, Wortham J, Hill AN, Navin TR.
        Am J Epidemiol. 2022 Jul 2.
        The early identification of clusters of persons with tuberculosis (TB) that will grow to become outbreaks creates an opportunity for intervention in preventing future TB cases. We used surveillance data (2009-2018) from the United States, statistically derived definitions of unexpected growth, and machine learning techniques to predict which clusters of genotype-matched TB cases are most likely to continue accumulating cases above expected growth within a 1-year follow-up period. We developed a model to predict which clusters are likely to grow on a training and testing dataset that was generalizable to a validation dataset. Our model shows that characteristics of clusters were more important than the social, demographic, and clinical characteristics of the patients in those clusters. For instance, the time between cases before unexpected growth was identified as the most important of our predictors. A faster accumulation of cases increased the probability of excess growth being predicted during the follow-up period. We demonstrated that combining the characteristics of clusters and cases with machine learning can add to existing tools to help prioritize which clusters may benefit most from public health interventions. For example, consideration of an entire cluster, not only an individual patient, may assist in interrupting ongoing transmission.

      2. Using latent class analysis to inform the design of an EHR-based national chronic disease surveillance model
        Nasuti L, Andrews B, Li W, Wiltz J, Hohman KH, Patanian M.
        Chronic Illn. 2022 May 3:17423953221099043.
        The Multi-state EHR-based Network for Disease Surveillance (MENDS) developed a pilot electronic health record (EHR) surveillance system capable of providing national chronic disease estimates. To strategically engage partner sites, MENDS conducted a latent class analysis (LCA) and grouped states by similarities in socioeconomics, demographics, chronic disease and behavioral risk factor prevalence, health outcomes, and health insurance coverage. Three latent classes of states were identified, which inform the recruitment of additional partner sites in conjunction with additional factors (e.g. partner site capacity and data availability, information technology infrastructure). This methodology can be used to inform other public health surveillance modernization efforts that leverage timely EHR data to address gaps, use existing technology, and advance surveillance.

      3. Comparing trained and untrained probabilistic ensemble forecasts of COVID-19 cases and deaths in the United States
        Ray EL, Brooks LC, Bien J, Biggerstaff M, Bosse NI, Bracher J, Cramer EY, Funk S, Gerding A, Johansson MA, Rumack A, Wang Y, Zorn M, Tibshirani RJ, Reich NG.
        Int J Forecast. 2022 Jul 1.
        The U.S. COVID-19 Forecast Hub aggregates forecasts of the short-term burden of COVID-19 in the United States from many contributing teams. We study methods for building an ensemble that combines forecasts from these teams. These experiments have informed the ensemble methods used by the Hub. To be most useful to policy makers, ensemble forecasts must have stable performance in the presence of two key characteristics of the component forecasts: (1) occasional misalignment with the reported data, and (2) instability in the relative performance of component forecasters over time. Our results indicate that in the presence of these challenges, an untrained and robust approach to ensembling using an equally weighted median of all component forecasts is a good choice to support public health decision makers. In settings where some contributing forecasters have a stable record of good performance, trained ensembles that give those forecasters higher weight can also be helpful.

      4. Metamodeling for policy simulations with multivariate outcomes
        Zhong H, Brandeau ML, Yazdi GE, Wang J, Nolen S, Hagan L, Thompson WW, Assoumou SA, Linas BP, Salomon JA.
        Med Decis Making. 2022 Jun 23:272989x221105079.
        PURPOSE: Metamodels are simplified approximations of more complex models that can be used as surrogates for the original models. Challenges in using metamodels for policy analysis arise when there are multiple correlated outputs of interest. We develop a framework for metamodeling with policy simulations to accommodate multivariate outcomes. METHODS: We combine 2 algorithm adaptation methods-multitarget stacking and regression chain with maximum correlation-with different base learners including linear regression (LR), elastic net (EE) with second-order terms, Gaussian process regression (GPR), random forests (RFs), and neural networks. We optimize integrated models using variable selection and hyperparameter tuning. We compare the accuracy, efficiency, and interpretability of different approaches. As an example application, we develop metamodels to emulate a microsimulation model of testing and treatment strategies for hepatitis C in correctional settings. RESULTS: Output variables from the simulation model were correlated (average ρ = 0.58). Without multioutput algorithm adaptation methods, in-sample fit (measured by R(2)) ranged from 0.881 for LR to 0.987 for GPR. The multioutput algorithm adaptation method increased R(2) by an average 0.002 across base learners. Variable selection and hyperparameter tuning increased R(2) by 0.009. Simpler models such as LR, EE, and RF required minimal training and prediction time. LR and EE had advantages in model interpretability, and we considered methods for improving the interpretability of other models. CONCLUSIONS: In our example application, the choice of base learner had the largest impact on R(2); multioutput algorithm adaptation and variable selection and hyperparameter tuning had a modest impact. Although advantages and disadvantages of specific learning algorithms may vary across different modeling applications, our framework for metamodeling in policy analyses with multivariate outcomes has broad applicability to decision analysis in health and medicine.

    • Injury and Violence
      1. Motor vehicle crash deaths - United States and 28 other high-income countries, 2015 and 2019
        Yellman MA, Sauber-Schatz EK.
        MMWR Morb Mortal Wkly Rep. 2022 Jul 1;71(26):837-843.
        Motor vehicle crashes are preventable, yet they continue to be a leading cause of death in the United States. An average of 36,791 crash deaths occurred each year (101 deaths each day) during 2015-2019 in the United States. To measure progress in reducing motor vehicle crash deaths, CDC calculated population-based, distance-based, and vehicle-based death rates in 2015 and 2019, as well as average rates and average percent changes from 2015 to 2019, for the United States and 28 other high-income countries for which data were available. In 2019, the population-based death rate in the United States (11.1 per 100,000 population; 36,355 deaths) was the highest among the 29 high-income countries and was 2.3 times the average rate of the 28 other high-income countries (4.8). The 2019 U.S. distance-based death rate (1.11 per 100 million vehicle miles traveled) was higher than the average rate among 20 other high-income countries (0.92), and the 2019 U.S. vehicle-based death rate (1.21 per 10,000 registered vehicles) was higher than the average rate among 27 other high-income countries (0.78). The population-based death rate in the United States increased 0.1% from 2015 to 2019, whereas the average change among 27 other high-income countries was -10.4%. Widespread implementation of proven strategies and the Safe System approach, which accounts for human error and works to protect everyone on the road, (1) can help reduce motor vehicle crash deaths in the United States.

      2. The measurement of intimate partner violence using International Classification of Diseases diagnostic codes: A systematic review
        Rebbe R, Adhia A, Eastman AL, Chen M, Winn J.
        Trauma Violence Abuse. 2022 May 4:15248380221090977.
        Intimate partner violence (IPV) is challenging to measure yet systematic surveillance of IPV is critical to informing public health prevention and response efforts. Administrative medical data provide opportunities for such surveillance, and often use the International Classification of Diseases (ICD). The primary purpose of this systematic review was to document which ICD codes have been used in empirical literature to identify IPV, understand the justification used to select specific codes to develop IPV case definitions, and identify the data sources and types of research questions addressed by the existing literature. We searched 11 databases and of the initial 2182 results, 21 empirical studies from 2000 to 2020 met the study inclusion criteria including using ICD codes to measure IPV. The majority of these studies (90.5%) used either national samples of data or population-based administrative data from emergency departments (52.4%) or inpatient hospitalizations (38.1%). We found wide variation of ICD diagnostic codes to measure IPV and categorized the sets of codes used based on the number of codes. The most commonly used ICD-9 codes were E967.3, 995.81, 995.80, 995.85 and the most common ICD-10 codes were T74.1 and Z63.0. Few studies validated the ICD codes used to measure IPV. Most included studies (81.0%) answered epidemiological research questions. The current study provides suggestions for future research, including justifying the selection of ICD codes and providing a range of estimates based on narrow and broad sets of codes. Implications for policy and practice, including enhanced training for healthcare professionals in documenting IPV, are discussed.

    • Laboratory Sciences
      1. Updated U.S. Public Health Service guideline for testing of transplant candidates aged <12 years for infection with HIV, hepatitis B virus, and hepatitis C virus - United States, 2022
        Free RJ, Levi ME, Bowman JS, Bixler D, Brooks JT, Buchacz K, Moorman A, Berger J, Basavaraju SV.
        MMWR Morb Mortal Wkly Rep. 2022 Jul 1;71(26):844-846.
        The U.S. Public Health Service (PHS) has periodically published recommendations about reducing the risk for transmission of HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV) through solid organ transplantation (1-4). Updated guidance published in 2020 included the recommendation that all transplant candidates receive HIV, HBV, and HCV testing during hospital admission for transplant surgery to more accurately assess their pretransplant infection status and to better identify donor transmitted infection (4). In 2021, CDC was notified that this recommendation might be unnecessary for pediatric organ transplant candidates because of the low likelihood of infection after the perinatal period and out of concern that the volume of blood drawn for testing could negatively affect critically ill children.* CDC and other partners reviewed surveillance data from CDC on estimates of HIV, HBV, and HCV infection rates in the United States and data from the Organ Procurement & Transplantation Network (OPTN)(†) on age and weight distributions among U.S. transplant recipients. Feedback from the transplant community was also solicited to understand the impact of changes to the existing policy on organ transplantation. The 2020 PHS guideline was accordingly updated to specify that solid organ transplant candidates aged <12 years at the time of transplantation who have received postnatal infectious disease testing are exempt from the recommendation for HIV, HBV, and HCV testing during hospital admission for transplantation.

      2. Influenza A virus infection and pathology in nasal and periocular tissues after ocular inoculation in ferrets
        Gary JM, Ritter JM, Sun X, Maines TR, Belser JA.
        Vet Pathol. 2022 Jul 4:3009858221109103.
        Influenza A viruses (IAV) cause mammalian infections following several transmission routes. Considering the anatomic proximity and connection between the nasopharynx and periocular tissues, there is a need to understand the dynamics of virus spread between these sites following both respiratory and nonrespiratory viral transmission. We examined virus distribution and associated inflammation within nasal and periocular tissues during the acute phase of H1N1 IAV infection in ferrets following intranasal or ocular inoculation. Ocular and intranasal inoculations with IAV caused comparable viral antigen distribution and inflammation in the nasal passages, though infection kinetics and magnitude differed by inoculation route. Ocular inoculation was associated with inflammation in the conjunctiva and lacrimal glands. Although intranasal inoculation was also associated with periocular inflammation, the onset was delayed relative to ocular inoculation. This work underscores the importance of investigating extrapulmonary tissues following mammalian infection with respiratory pathogens, even after intranasal inoculation.

    • Nutritional Sciences
      1. Changes in spina bifida lesion level after folic acid fortification in the United States
        Mai CT, Evans J, Alverson CJ, Yue X, Flood T, Arnold K, Nestoridi E, Denson L, Adisa O, Moore CA, Nance A, Zielke K, Rice S, Shan X, Dean JH, Ethen M, Hansen B, Isenburg J, Kirby RS.
        J Pediatr. 2022 Jun 27.
        OBJECTIVE: To assess whether the severity of cases of spina bifida changed after mandatory folic acid fortification in the United States. STUDY DESIGN: Six active population-based birth defects programs provided data on cases of spina bifida for 1992-1996 (pre-fortification) and 1999-2016 (post-fortification); programs contributed varying years of data. Case information included both medical record verbatim text description of the spina bifida diagnosis and spina bifida codes (International Classification of Diseases, Clinical Modification, or a modified birth defects surveillance coding system). Comparing pre- with post-fortification periods, adjusted odds ratios (aOR) for case severity [upper-level (cervical, thoracic) to lower-level (lumbar, sacral) lesion cases] and prevalence ratios (PR) were estimated. RESULTS: A total of 2,593 cases of spina bifida (7,816,062 live births) met inclusion criteria, with 573 and 2,020 cases from the pre- and post-fortification periods respectively. Case severity decreased 70% (aOR: 0.30; 95% confidence interval [CI] 0.26, 0.35) between the fortification periods. The decrease was most pronounced for non-Hispanic white mothers. Overall spina bifida prevalence declined 23% (PR=0.77, 95% CI=0.71, 0.85), with similar reduction seen across early, mid, and recent post-fortification periods. A statistically significant decrease in upper-level lesions occurred in the post-fortification compared with pre-fortification periods (PR=0.28, 95% CI=0.22, 0.34), while prevalence of lower-level lesions remained relatively similar (PR: 0.94, 95% CI: 0.84, 1.05). CONCLUSIONS: Severity of cases of spina bifida decreased after mandatory folic acid fortification in the United States. Further examination is warranted to understand better the potential effect of folic acid on spina bifida severity.

    • Occupational Safety and Health
      1. COVID-19 test positivity by occupation using the Delphi US COVID-19 trends and impact survey, September-November 2020
        Cox-Ganser JM, Henneberger PK, Weissman DN, Guthrie G, Groth CP.
        Am J Ind Med. 2022 Jul 5.
        BACKGROUND: The potential for work to be a risk factor for coronavirus disease 2019 (COVID-19) was recognized early in the pandemic based on the likelihood of work-related differences in exposures to COVID-19 in different occupations. Due to intense demands of the pandemic, implementation of recommendations to collect information on occupation in relation to COVID-19 has been uneven across the United States. The objective of this study was to investigate COVID-19 test positivity by occupation. METHODS: We analyzed data collected from September 8 to November 30, 2020, by the Delphi Group at Carnegie Mellon University US COVID-19 Trends and Impact Survey, offered daily to a random sample of US-based Facebook users aged 18 years or older, who were invited via a banner in their news feed. Our focus was ever testing positive for COVID-19 in respondents working outside the home for pay in the past 4 weeks. RESULTS: The major occupational groups of "Production", "Building and grounds cleaning and maintenance," "Construction and extraction," "Healthcare support," and "Food preparation and serving" had the five highest test positivity percentages (16.7%-14.4%). Highest detailed occupational categories (28.6%-19.1%) were "Massage therapist," "Food processing worker," "Bailiff, correctional officer, or jailer," "Funeral service worker," "First-line supervisor of production and operating workers," and "Nursing assistant or psychiatric aide." Differences in test positivity by occupation remained after adjustment for age, gender, and pre-existing medical conditions. CONCLUSION: Information on differences in test positivity by occupation can aid targeting of messaging for vaccination and testing and mitigation strategies for the current and future respiratory infection epidemics and pandemics. These results, obtained before availability of COVID-19 vaccines, can form a basis for comparison to evaluate impacts of vaccination and subsequent emergence of viral variants.

      2. The Continuous NHANES Survey provides detailed health and environmental chemical burden information on the U.S. population. As of 2012, there were data for 72,000 participants. Based on single biomarker determinations, cumulative burdens were estimated. Because age distributions would differ comparing ambient environmental and occupational exposures, a procedure to distinguish ambient from likely occupational exposures was applied. Associations are reported for osteoporosis and kidney disease-related outcomes with cadmium, lead, and other metals. Cumulative cadmium burden (from blood cadmium, ambient and occupational) was a strong predictor of bone fracture risk and ambient tungsten also had a positive association. Cumulative lead (ambient and occupational) had a negative ("protective") association with fractures as did mercury (occupational). Bone mineral density was statistically significant and similarly predicted by metal exposures. Kidney disease was significantly associated with cumulative lead burdens from both the estimated ambient and occupational sources and with ambient blood cadmium but was most strongly associated with cumulative occupational uranium burden. Systolic blood pressure statistically significantly increased with cumulative ambient and occupational lead (blood) burden and with ambient cadmium and cobalt. Diastolic blood pressure was significantly associated with several cadmium and cobalt metrics along with ambient and occupational cumulative burdens for lead. For environmental substances with burden half-lives measured in years, NHANES offers opportunities for hypothesis generation and confirmation.

    • Parasitic Diseases
      1. Evaluation of the residual efficacy and physical durability of five long-lasting insecticidal nets (LLINs) in Senegal
        Diouf EH, Diouf M, Dieme C, Swamidoss I, Ngom EH, Senghor MW, Mbaye M, Konaté A, Coulibaly Y, Tine D, Dia I, Dotson EM, Faye O, Konaté L.
        Malar J. 2022 Jul 2;21(1):210.
        BACKGROUND: The preventive and curative strategies of malaria are based on promoting the use of long-lasting insecticidal nets (LLINs) and treating confirmed cases with artemisinin-based combination therapy. These strategies have led to a sharp decline in the burden of malaria, which remains a significant public health problem in sub-Saharan countries. The objective of this study was to determine and compare the residual efficacy of LLINs recommended by the World Health Organization. METHODS: The study was conducted in six villages in two sites in Senegal located in the Sahelo-Sudanian area of the Thiès region, 70 km from Dakar and in Mbagame, a semi-urban zone in the Senegal River Valley. A census was conducted of all sleeping places in each household to be covered by LLINs. Five brands of LLIN were distributed, and every six months, retention rates, net use, maintenance, physical integrity, insecticide chemical content, and biological efficacy were examined for each type of LLIN. RESULTS: A total of 3012 LLINs were distributed in 1249 households in both sites, with an average coverage rate of 94% (95% CI 92.68-95.3). After 36 months, the average retention rate was 12.5% and this rate was respectively 20.5%, 15.1%, 10%, 7%, and 3% for Olyset Net(®), Dawa Plus(®) 2.0, PermaNet(®) 2.0, NetProtect(®) and Life Net(®), respectively. The proportion of LLINs with holes and the average number of holes per mosquito net increased significantly during each follow-up, with a large predominance of size 1 (small) holes for all types of LLINs distributed. During the three-year follow-up, bioassay mortality rates of a susceptible strain of insectary reared Anopheles coluzzii decreased in the following net types: in Dawa Plus(®) 2.0 (100% to 51.7%), PermaNet(®) 2.0 (96.6% to 83%), and Olyset Net(®) (96.6% to 33.3%). Mortality rates remained at 100% in Life Net(®) over the same time period. After 36 months, the average insecticide content per brand of LLIN decreased by 40.9% for Dawa Plus(®) 2.0, 31% for PermaNet(®) 2.0, 39.6% for NetProtect(®) and 51.9% for Olyset Net(®) and 40.1% for Life Net. CONCLUSIONS: Although some net types retained sufficient insecticidal activity, based on all durability parameters measured, none of the net types survived longer than 2 years.

      2. Identification of a rapidly-spreading triple mutant for high-level metabolic insecticide resistance in Anopheles gambiae provides a real-time molecular diagnostic for anti-malarial intervention deployment
        Njoroge H, Van't Hof A, Oruni A, Pipini D, Nagi SC, Lynd A, Lucas ER, Tomlinson S, Grau-Bove X, McDermott D, Wat'senga FT, Manzambi EZ, Agossa FR, Mokuba A, Irish S, Kabula B, Mbogo C, Bargul J, Paine MJ, Weetman D, Donnelly MJ.
        Mol Ecol. 2022 Jul 1.
        Studies of insecticide resistance provide insights into the capacity of populations to show rapid evolutionary responses to contemporary selection. Malaria control remains heavily dependent on pyrethroid insecticides, primarily in long lasting insecticidal nets (LLINs). Resistance in the major malaria vectors has increased in concert with the expansion of LLIN distributions. Identifying genetic mechanisms underlying high-level resistance is crucial for the development and deployment of resistance-breaking tools. Using the Anopheles gambiae 1000 genomes (Ag1000g) data we identified a very recent selective sweep in mosquitoes from Uganda which localized to a cluster of cytochrome P450 genes. Further interrogation revealed a haplotype involving a trio of mutations, a nonsynonymous point mutation in Cyp6p4 (I236M), an upstream insertion of a partial Zanzibar-like transposable element (TE) and a duplication of the Cyp6aa1 gene. The mutations appear to have originated recently in An. gambiae from the Kenya-Uganda border, with stepwise replacement of the double-mutant (Zanzibar-like TE and Cyp6p4-236M) with the triple-mutant haplotype (including Cyp6aa1 duplication), which has spread into the Democratic Republic of Congo and Tanzania. The triple-mutant haplotype is strongly associated with increased expression of genes able to metabolise pyrethroids and is strongly predictive of resistance to pyrethroids most notably deltamethrin. Importantly, there was increased mortality in mosquitoes carrying the triple-mutation when exposed to nets co-treated with the synergist piperonyl butoxide (PBO). Frequencies of the triple-mutant haplotype remain spatially variable within countries, suggesting an effective marker system to guide deployment decisions for limited supplies of PBO-pyrethroid co-treated LLINs across African countries.

    • Public Health Leadership and Management

      1. Implementation of a nationwide knowledge-based COVID-19 contact tracing training program, 2020
        Ruebush E, Dennison A, Lane JT, Harper-Hardy P, Poulin A, Prather B, Wright S, Harvey D, Fraser MR.
        Public Health Rep. 2022 Jul 4:333549221101327.
        In the United States, the public health response to control COVID-19 required rapid expansion of the contact tracing workforce from approximately 2200 personnel prepandemic to more than 100 000 during the pandemic. We describe the development and implementation of a free nationwide training course for COVID-19 contact tracers that launched April 28, 2020, and summarize participant characteristics and evaluation findings through December 31, 2020. Uptake of the online asynchronous training was substantial: 90 643 registrants completed the course during the first 8 months. In an analysis of a subset of course participants (n = 13 697), 7724 (56.4%) reported having no prepandemic public health experience and 7178 (52.4%) reported currently serving as case investigators, contact tracers, or both. Most participants who completed a course evaluation reported satisfaction with course utility (94.8%; 59 497 of 62 753) and improved understanding of contact tracing practice (93.0%; 66 107 of 71 048). These findings suggest that the course successfully reached the intended audience of new public health practitioners. Lessons learned from this implementation indicate that an introductory course level is appropriate for a national knowledge-based training that aims to complement jurisdiction-specific training. In addition, offering a range of implementation options can promote course uptake among public health agency staff. This course supported the emerging needs of the public health practice community by training a workforce to fill an important gap during the COVID-19 pandemic and could serve as a feasible model for enhancing workforce knowledge for future and ongoing public health threats.

    • Reproductive Health
      1. Assisted reproductive technology cycles involving male factor infertility in the United States, 2017-2018: data from the National Assisted Reproductive Technology Surveillance System
        Jewett A, Warner L, Kawwass JF, Mehta A, Eisenberg ML, Nangia AK, Dupree JM, Honig S, Hotaling JM, Kissin DM.
        F S Rep. 2022 Jun;3(2):124-130.
        OBJECTIVE: To describe the prevalence and treatment characteristics of assisted reproductive technology (ART) cycles involving specific male factor infertility diagnoses in the United States. DESIGN: Cross-sectional analysis of ART cycles in the National ART Surveillance System (NASS). SETTING: Clinics that reported patient ART cycles performed in 2017 and 2018. PATIENTS: Patients who visited an ART clinic and the cycles were reported in the NASS. The ART cycles included all autologous and donor cycles that used fresh or frozen embryos. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Analyses used new, detailed reporting of male factor infertility subcategories, treatment characteristics, and male partner demographics available in the NASS. RESULTS: Among 399,573 cycles started with intent to transfer an embryo, 30.4% (n = 121,287) included a male factor infertility diagnosis as a reason for using ART. Of these, male factor only was reported in 16.5% of cycles, and both male and female factors were reported in 13.9% of cycles; 21.8% of male factor cycles had >1 male factor. Abnormal sperm parameters were the most commonly reported diagnoses (79.7%), followed by medical condition (5.3%) and genetic or chromosomal abnormalities (1.0%).Males aged ≤40 years comprised 59.6% of cycles with male factor infertility. Intracytoplasmic sperm injection was the primary method of fertilization (81.7%). Preimplantation genetic testing was used in 26.8%, and single embryo transfer was used in 66.8% of cycles with male factor infertility diagnosis. CONCLUSIONS: Male factor infertility is a substantial contributor to infertility treatments in the United States. Continued assessment of the prevalence and characteristics of ART cycles with male factor infertility may inform treatment options and improve ART outcomes. Future studies are necessary to further evaluate male factor infertility.

      2. Examining the ratio of obstetric beds to births, 2000-2019
        DeSisto CL, Goodman DA, Brantley MD, Menard MK, Declercq E.
        J Community Health. 2022 Jun 30.
        The number of U.S. births has been declining. There is also concern about rural obstetric units closing. To better understand the relationship between births and obstetric beds during 2000-2019, we examined changes over time in births, birth hospital distributions (i.e., hospital birth volume, ownership, and urban-rural designation), and the ratio of births to obstetric beds. We analyzed American Hospital Association Annual Survey data from 2000 to 2019. We included U.S. hospitals with at least 25 reported births during the year and at least 1 reported obstetric bed. We categorized birth volume to identify and describe hospitals with maternity services using seven categories. We calculated ratios of number of births to number of obstetric beds overall, by annual birth volume category, by three categories of hospital ownership, and by six urban-rural categories. The ratio of births to obstetric beds, which may represent need for maternity services, has stayed relatively consistent at 65 over the past two decades, despite the decline in births and changes in birth hospital distributions. The ratios were smallest in hospitals with < 250 annual births and largest in hospitals with ≥ 7000 annual births. The largest ratios of births to obstetric beds were in large metro areas and the smallest ratios were in noncore areas. At a societal level, the reduction in obstetric beds corresponds with the drop in the U.S. birth rate. However, consistency in the overall ratio can mask important differences that we could not discern, such as the impact of closures on distances to closest maternity care.

    • Substance Use and Abuse
      1. Pulmonary and critical care considerations for e-cigarette, or vaping, product use-associated lung injury
        Hayes D, Board A, Calfee CS, Ellington S, Pollack LA, Kathuria H, Eakin MN, Weissman DN, Callahan SJ, Esper AM, Crotty Alexander LE, Sharma NS, Meyer NJ, Smith LS, Novosad S, Evans ME, Goodman AB, Click ES, Robinson RT, Ewart G, Twentyman E.
        Chest. 2022 Mar 5.
        BACKGROUND: In 2019, the United States experienced a nationwide outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI). More than one-half of these patients required admission to an ICU. RESEARCH QUESTION: What are the recent literature and expert opinions which inform the diagnosis and management of patients with critical illness with EVALI? STUDY DESIGN AND METHODS: To synthesize information critical to pulmonary/critical care specialists in the care of patients with EVALI, this study examined data available from patients hospitalized with EVALI between August 2019 and January 2020; reviewed the clinical course and critical care experience with those patients admitted to the ICU; and compiled opinion of national experts. RESULTS: Of the 2,708 patients with confirmed or probable EVALI requiring hospitalization as of January 21, 2020, a total of 1,604 (59.2%) had data available on ICU admission; of these, 705 (44.0%) were admitted to the ICU and are included in this analysis. The majority of ICU patients required respiratory support (88.5%) and in severe cases required intubation (36.1%) or extracorporeal membrane oxygenation (6.7%). The majority (93.0%) of these ICU patients survived to discharge. Review of the clinical course and expert opinion provided insight into: imaging; considerations for bronchoscopy; medical treatment, including use of empiric antibiotics, antiviral agents, and corticosteroids; respiratory support, including considerations for intubation, positioning maneuvers, and extracorporeal membrane oxygenation; and patient outcomes. INTERPRETATION: Review of the clinical course of patients with EVALI requiring ICU admission and compilation of expert opinion provided critical insight into pulmonary/critical care-specific considerations for this patient population. Because a large proportion of patients hospitalized with EVALI required ICU admission, it is important to remain prepared to care for patients with EVALI.

      2. Estimated number of people who inject drugs in the United States
        Bradley H, Hall E, Asher A, Furukawa N, Jones CM, Shealey J, Buchacz K, Handanagic S, Crepaz N, Rosenberg ES.
        Clin Infect Dis. 2022 Jul 6.
        BACKGROUND: Public health data signal increases in the number of people who inject drugs (PWID) in the United States during the past decade. An updated PWID population size estimate is critical for informing interventions and policies aiming to reduce injection-associated infections and overdose, as well as to provide a baseline for assessments of pandemic-related changes in injection drug use. METHODS: We used a modified multiplier approach to estimate the number of adults who injected drugs in the United States in 2018. We deduced the estimated number of non-fatal overdose events among PWID from two of our previously published estimates: the number of injection-involved overdose deaths and the meta-analyzed ratio of non-fatal to fatal overdose. The number of non-fatal overdose events was divided by prevalence of non-fatal overdose among current PWID for a population size estimate. RESULTS: There were an estimated 3,694,500 (95% CI: 1,872,700-7,273,300) PWID in the U.S. in 2018, representing 1.46% (95% CI: 0.74% - 2.87%) of the adult population. The estimated prevalence of injection drug use was highest among male persons (2.1%; 95% CI: 1.1-4.2%), non-Hispanic White persons (1.8%; 95% CI: 0.9-3.6%), and adults aged 18-39 years (1.8%; 0.9-3.6%). CONCLUSIONS: Using transparent, replicable methods and largely publicly available data, we provide the first update to the number of people who inject drugs in the U.S. in nearly ten years. Findings suggest the population size of PWID has substantially grown in the past decade and that prevention services for PWID should be proportionally increased.

    • Zoonotic and Vectorborne Diseases
      1. Sympatric recombination in zoonotic cryptosporidium leads to emergence of populations with modified host preference
        Wang T, Guo Y, Roellig DM, Li N, Santín M, Lombard J, Kváč M, Naguib D, Zhang Z, Feng Y, Xiao L.
        Mol Biol Evol. 2022 Jul 1.
        Genetic recombination plays a critical role in the emergence of pathogens with phenotypes such as drug resistance, virulence, and host adaptation. Here, we tested the hypothesis that recombination between sympatric ancestral populations leads to the emergence of divergent variants of the zoonotic parasite Cryptosporidium parvum with modified host ranges. Comparative genomic analyses of 101 isolates have identified seven subpopulations isolated by distance. They appear to be descendants of two ancestral populations, IIa in northwestern Europe and IId from southwestern Asia. Sympatric recombination in areas with both ancestral subtypes and subsequent selective sweeps have led to the emergence of new subpopulations with mosaic genomes and modified host preference. Subtelomeric genes could be involved in the adaptive selection of subpopulations, while copy number variations of genes encoding invasion-associated proteins are potentially associated with modified host ranges. These observations reveal ancestral origins of zoonotic C. parvum and suggest that pathogen import through modern animal farming might promote the emergence of divergent subpopulations of C. parvum with modified host preference.

      2. Etiology of acute febrile illnesses in Southern China: Findings from a two-year sentinel surveillance project, 2017-2019
        Rainey JJ, Siesel C, Guo X, Yi L, Zhang Y, Wu S, Cohen AL, Liu J, Houpt E, Fields B, Yang Z, Ke C.
        PLoS One. 2022 ;17(6):e0270586.
        BACKGROUND: Southern China is at risk for arborvirus disease transmission, including Zika virus and dengue. Patients often present to clinical care with non-specific acute febrile illnesses (AFI). To better describe the etiology of AFI, we implemented a two-year AFI surveillance project at five sentinel hospitals in Yunnan and Guangdong Provinces. METHODS: Between June 2017 and August 2019, we enrolled patients between 2 and 65 years of age presenting at one sentinel hospital in Mengla County, Yunnan, and four in Jiangmen City, Guangdong, with symptoms of AFI (acute onset of fever ≥ 37.5°C within the past 7 days) without respiratory symptoms or diarrhea. Demographic, epidemiologic, and clinical information was obtained and entered into a web-based AFI surveillance database. A custom TaqMan Array card (TAC) was used to test patients' whole blood specimens for 27 different pathogens using real-time polymerase chain reaction assays. RESULTS: During the two-year project period, 836 patients were enrolled; 443 patients from Mengla County and 393 patients from Jiangmen City. The median age was 33 years [range: 2-65], and most were hospitalized [641, 77%]. Of 796 patients with valid TAC results, 341 (43%) were positive for at least one of the 10 unique pathogens detected. This included 205 (26%) patients positive for dengue virus, 60 (8%) for Orientia tsutsugamushi, and 42 (5%) for Coxiella burnetii. Ten patients (1%) in Jiangmen City tested positive for malaria, 8 of whom reported recent travel outside of China. TAC results were negative for 455 (57%) patients. None of the patients had a positive TAC detection for Zika virus. CONCLUSIONS: The project detected variability in the etiology of AFI in Southern China and highlighted the importance of differential diagnosis. Dengue, O. tsutsugamushi, and C. burnetii were the most frequently identified pathogens among enrolled AFI patients. As a non-notifiable disease, the frequent detection of C. burnetii is noteworthy and warrants additional investigation. The project provided a framework for routine surveillance for persons presenting with AFI.

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