2020 Science Clips Banner

Issue 39, September 27, 2022

Related Pages

CDC Science Clips: Volume 14, Issue 39, September 27, 2022

Science Clips is produced weekly to enhance awareness of emerging scientific knowledge for the public health community. Each article features an Altmetric Attention score to track social and mainstream media mentions.

The report consists of these components:

  1. 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.
    • Antimicrobial Resistance and Antibiotic Stewardship
      1. Identifying context-specific domains for assessing antimicrobial stewardship programmes in Asia: protocol for a scoping review
        Vu HT, Hamers RL, Limato R, Limmathurotsakul D, Karkey A, Dodds Ashley E, Anderson D, Patel PK, Patel TS, Lessa FC, van Doorn HR.
        BMJ Open. 2022 Sep 15;12(9):e061286.
        INTRODUCTION: Antimicrobial stewardship (AMS) is an important strategy to control antimicrobial resistance. Resources are available to provide guidance for design and implementation of AMS programmes, however these may have limited applicability in resource-limited settings including those in Asia. This scoping review aims to identify context-specific domains and items for the development of a healthcare facility (HCF)-level tool to guide AMS implementation in Asia. METHODS AND ANALYSIS: This review is the first step in a larger project to assess AMS implementation, needs and gaps in Asia. We will employ a deductive qualitative approach to identify locally appropriate domains and items of AMS implementation guided by Nilsen and Bernhardsson's contextual dimensions. This process is also informed by discussions from a technical advisory group coordinated by the US Centers for Disease Control and Prevention to develop an AMS HCF-level assessment tool for low-income and middle-income countries. We will review English-language documents that discuss HCF-level implementation, including those describing frameworks, components/elements or recommendations for design, implementation or assessment globally and specific to Asia. We have performed the search in August-September 2021 including general electronic databases (MEDLINE, Embase, Web of Science and Google Scholar), region-specific databases, national action plans, grey literature sources and reference lists to identify eligible documents. Country-specific documents will be restricted to countries in three subregions: South Asia, East Asia and Southeast Asia. Codes and themes will be derived through a content analysis, classified following the predefined context dimensions and used for developing domains and items of the assessment tool. ETHICS AND DISSEMINATION: Results from this review will feed into our stepwise process for developing a context-specific HCF-level assessment tool for AMS programmes to assess the implementation status, identify intervention opportunities and monitor progress over time. The process will be done in consultation with local stakeholders, the end-users of the generated knowledge.

      2. Fatal fungicide-associated triazole-resistant aspergillus fumigatus infection, Pennsylvania, USA
        Bradley K, Le-Mahajan A, Morris B, Peritz T, Chiller T, Forsberg K, Nunnally NS, Lockhart SR, Gold JA, Gould JM.
        Emerg Infect Dis. 2022 Sep;28(9):1904-1905.
        We report a fatal infection in a 65-year-old immunocompromised male patient caused by pan-triazole-resistant Aspergillus fumigatus containing a TR(34)/L98H genetic mutation linked to agricultural fungicide use. Clinical and environmental surveillance of triazole-resistant A. fumigatus is needed in the United States to prevent spread and guide healthcare and agricultural practices.

      3. Temporal trends in molecular markers of drug resistance in Plasmodium falciparum in human blood and profiles of corresponding resistant markers in mosquito oocysts in Asembo, western Kenya
        Zhou Z, Gimnig JE, Sergent SB, Liu Y, Abong'o B, Otieno K, Chebore W, Shah MP, Williamson J, Ter Kuile FO, Hamel MJ, Kariuki S, Desai M, Samuels AM, Walker ED, Shi YP.
        Malar J. 2022 Sep 13;21(1):265.
        BACKGROUND: Over the last two decades, the scale-up of vector control and changes in the first-line anti-malarial, from chloroquine (CQ) to sulfadoxine-pyrimethamine (SP) and then to artemether-lumefantrine (AL), have resulted in significant decreases in malaria burden in western Kenya. This study evaluated the long-term effects of control interventions on molecular markers of Plasmodium falciparum drug resistance using parasites obtained from humans and mosquitoes at discrete time points. METHODS: Dried blood spot samples collected in 2012 and 2017 community surveys in Asembo, Kenya were genotyped by Sanger sequencing for markers associated with resistance to SP (Pfdhfr, Pfdhps), CQ, AQ, lumefantrine (Pfcrt, Pfmdr1) and artemisinin (Pfk13). Temporal trends in the prevalence of these markers, including data from 2012 to 2017 as well as published data from 1996, 2001, 2007 from same area, were analysed. The same markers from mosquito oocysts collected in 2012 were compared with results from human blood samples. RESULTS: The prevalence of SP dhfr/dhps quintuple mutant haplotype C(50)I(51)R(59)N(108)I(164)/S(436)G(437)E(540)A(581)A(613) increased from 19.7% in 1996 to 86.0% in 2012, while an increase in the sextuple mutant haplotype C(50)I(51)R(59)N(108)I(164)/H(436)G(437)E(540)A(581)A(613) containing Pfdhps-436H was found from 10.5% in 2012 to 34.6% in 2017. Resistant Pfcrt-76 T declined from 94.6% in 2007 to 18.3% in 2012 and 0.9% in 2017. Mutant Pfmdr1-86Y decreased across years from 74.8% in 1996 to zero in 2017, mutant Pfmdr1-184F and wild Pfmdr1-D1246 increased from 17.9% to 58.9% in 2007 to 55.9% and 90.1% in 2017, respectively. Pfmdr1 haplotype N(86)F(184)S(1034)N(1042)D(1246) increased from 11.0% in 2007 to 49.6% in 2017. No resistant mutations in Pfk13 were found. Prevalence of Pfdhps-436H was lower while prevalence of Pfcrt-76 T was higher in mosquitoes than in human blood samples. CONCLUSION: This study showed an increased prevalence of dhfr/dhps resistant markers over 20 years with the emergence of Pfdhps-436H mutant a decade ago in Asembo. The reversal of Pfcrt from CQ-resistant to CQ-sensitive genotype occurred following 19 years of CQ withdrawal. No Pfk13 markers associated with artemisinin resistance were detected, but the increased haplotype of Pfmdr1 N(86)F(184)S(1034)N(1042)D(1246) was observed. The differences in prevalence of Pfdhps-436H and Pfcrt-76 T SNPs between two hosts and the role of mosquitoes in the transmission of drug resistant parasites require further investigation.

      4. The second national anti-tuberculosis drug resistance survey in Tanzania, 2017-2018
        Mutayoba BK, Ershova J, Lyamuya E, Hoelscher M, Heinrich N, Kilale AM, Range NS, Ngowi BJ, Ntinginya NE, Mfaume SM, Nkiligi E, Doulla B, Lyimo J, Kisonga R, Kingalu A, Lema Y, Kondo Z, Pletschette M.
        Trop Med Int Health. 2022 Aug 17.
        OBJECTIVE: To determine the levels and patterns of resistance to first- and second-line anti-tuberculosis (TB) drugs among new and previously treated sputum smear positive pulmonary TB (PTB) patients. METHODS: We conducted a nationally representative cross-sectional facility-based survey in June 2017-July 2018 involving 45 clusters selected based on probability proportional to size. The survey aimed to determine the prevalence of anti-TB drug resistance and associated risk factors among smear positive PTB patients in Tanzania. Sputum samples were examined using smear microscopy, Xpert MTB/RIF, culture and drug susceptibility testing (DST). Logistic regression was used to account for missing data and sampling design effects on the estimates and their standard errors. RESULTS: We enrolled 1557 TB patients, including 1408 (90.4%) newly diagnosed and 149 (9.6%) previously treated patients. The prevalence of multidrug-resistant TB (MDR-TB) was 0.85% [95% confidence interval (CI): 0.4-1.3] among new cases and 4.6% (95% CI: 1.1-8.2) among previously treated cases. The prevalence of Mycobacterium tuberculosis strains resistant to any of the four first-line anti-TB drugs (isoniazid, rifampicin, streptomycin and ethambutol) was 1.7% among new TB patients and 6.5% among those previously treated. Drug resistance to all first-line drugs was similar (0.1%) in new and previously treated patients. None of the isolates displayed poly-resistance or extensively drug-resistant TB (XDR-TB). The only risk factor for MDR-TB was history of previous TB treatment (odds ratio = 5.7, 95% CI: 1.9-17.2). CONCLUSION: The burden of MDR-TB in the country was relatively low with no evidence of XDR-TB. Given the overall small number of MDR-TB cases in this survey, it will be beneficial focusing efforts on intensified case detection including universal DST.

    • Chronic Diseases and Conditions
      1. National prevalence of IC/BPS in women and men utilizing Veterans Health Administration data
        Anger JT, Dallas KB, Bresee C, De Hoedt AM, Barbour KE, Hoggatt KJ, Goodman MT, Kim J, Freedland SJ.
        Front Pain Res (Lausanne). 2022 ;3:925834.
        IMPORTANCE: Interstitial cystitis/bladder pain syndrome (IC/BPS) is an immense burden to both patients and the American healthcare system; it is notoriously difficult to diagnose. Prevalence estimates vary widely (150-fold range in women and >500-fold range in men). OBJECTIVES: We aimed to create accurate national IC/BPS prevalence estimates by employing a novel methodology combining a national population-based dataset with individual chart abstraction. STUDY DESIGN: In this epidemiological survey, all living patients, with ≥2 clinic visits from 2016 to 2018 in the Veterans Health Administration, with an ICD-9/10 code for IC/BPS (n = 9,503) or similar conditions that may represent undiagnosed IC/BPS (n = 124,331), were identified (other were controls n = 5,069,695). A detailed chart review of random gender-balanced samples confirmed the true presence of IC/PBS, which were then age- and gender-matched to the general US population. RESULTS: Of the 5,203,529 patients identified, IC/BPS was confirmed in 541 of 1,647 sampled charts with an IC/BPS ICD code, 10 of 382 charts with an ICD-like code, and 3 of 916 controls. After age- and gender-matching to the general US population, this translated to national prevalence estimates of 0.87% (95% CI: 0.32, 1.42), with female and male prevalence of 1.08% (95% CI: 0.03, 2.13) and 0.66% (95% CI: 0.44, 0.87), respectively. CONCLUSIONS: We estimate the prevalence of IC/BPS to be 0.87%, which is lower than prior estimates based on survey data, but higher than prior estimates based on administrative data. These potentially represent the most accurate estimates to date, given the broader and more heterogeneous population studied and our novel methodology of combining in-depth chart abstraction with administrative data.

      2. miRNA extracted from extracellular vesicles is a robust biomarker of amyotrophic lateral sclerosis
        Banack SA, Dunlop RA, Stommel EW, Mehta P, Cox PA.
        J Neurol Sci. 2022 Aug 30;442:120396.
        BACKGROUND AND OBJECTIVES: We examined miRNA biomarkers for ALS extracted from extracellular vesicles in blood samples using a large and diverse patient and control population. Different blood collection and storage protocols by different investigators could impact repeatability of miRNA analysis. We tested the hypotheses that miRNA extracted from extracellular vesicles using immunoaffinity purification techniques are robust and repeatable across investigators, laboratories and in a broad ALS population. METHODS: De-identified patient blood plasma samples obtained from the U.S. National ALS Biorepository were compared with plasma from non-ALS controls. Extracellular vesicles were extracted and isolated using L1CAM immunoaffinity purification. Total RNA was extracted, and miRNA quantified using qPCR following careful quality control measures. Gene fold expressions of eight miRNAs were compared using a Mann-Whitney two-tailed test. RESULTS: One hundred blinded, blood plasma samples were analyzed. Thirty-five men and 15 women with ALS were compared with controls consisting of 30 men and 20 women. None of the ALS patient cohort reported family members with ALS suggesting sporadic ALS. Five of the eight biomarkers previously published were found to significantly discriminate ALS patient samples from control samples. DISCUSSION: The methods used in this study provide a repeatable measure of miRNA biomarkers that statistically differentiate ALS patient samples from control samples. The broad inclusion criteria for both the ALS patient cohort and controls along with the collection of blood samples by different investigators suggest that these methods are robust and represent good candidates for further research and development aimed at clinical application.

      3. Geographic examination of COVID-19 test percent positivity and proportional change in cancer screening volume, National Breast and Cervical Cancer Early Detection Program
        Bermudez Y, Scott LC, Beckman M, DeGroff A, Kenney K, Sun J, Rockwell T, Helsel W, Kammerer W, Sheu A, Miller J, Richardson LC.
        Prev Chronic Dis. 2022 Sep 15;19:E59.
        INTRODUCTION: In 2020, the COVID-19 pandemic led to significant declines in cancer screening, including among women served by the National Breast and Cervical Cancer Early Detection Program (NBCCEDP). This study examined the spatial association between state-based COVID-19 test percent positivity and proportional change in NBCCEDP screening volume. METHODS: Using the COVID-19 Diagnostic Laboratory Testing dataset, we calculated state-based monthly COVID-19 test percent positivity from July through December 2020 and categorized rates into low, medium, and high groups. We used data from 48 NBCCEDP state awardees to calculate the state-based monthly proportional change in screening volume and compared data for July-December 2020 with the previous 5-year average for those months. We categorized changes in screening volume into large decrease, medium decrease, and minimal change and created maps of the associations between variable subgroups by using bivariate mapping in QGIS. RESULTS: Bivariate relationships between COVID-19 test percent positivity and proportional change in cancer screening volume varied over time and geography. In 5 of 6 months, 4 states had high COVID-19 test percent positivity and minimal change in breast or cervical cancer screening volume; 2 states had high COVID-19 test percent positivity and minimal change in breast and cervical cancer screening volume. CONCLUSION: Some states maintained pre-COVID-19 screening volumes despite high COVID-19 test percent positivity. Follow-up research will be conducted to determine how these states differ from those with consistent decreases in screening volume and identify factors that may have contributed to differences. This information could be useful for planning to maximize NBCCEDP awardees' ability to maintain screening volume during future public health emergencies.

      4. Efforts in the US to prevent and treat cardiovascular disease (CVD) contributed to large decreases in death rates for decades; however, in the last decade, progress has stalled, and in many counties, CVD death rates have increased. Because of these increases, there is heightened urgency to disseminate high-quality data on the temporal trends in CVD mortality. The Local Trends in Heart Disease and Stroke Mortality Dashboard is an online, interactive visualization of US county-level death rates and trends for several CVD outcomes across stratifications of age, race and ethnicity, and sex. This powerful visualization tool generates national maps of death rates and trends, state maps of death rates and trends, county-level line plots of annual death rates, and bar charts of percentage changes. County-level death rates and trends were estimated by applying a Bayesian spatiotemporal model to data obtained from the National Vital Statistics System of the National Center for Health Statistics and US Census bridged-race intercensal estimates for the years 1999 through 2019. The Local Trends in Heart Disease and Stroke Mortality Dashboard makes it easy for public health practitioners, health care providers, and community leaders to monitor county-level spatiotemporal trends in CVD mortality by age group, race and ethnicity, and sex and provides key information for identifying and addressing local health inequities in CVD mortality trends.

    • Communicable Diseases
      1. Impact of the coronavirus disease 2019 pandemic on prescriptions for antiretroviral drugs for HIV treatment in the United States, 2019-2021
        Zhu W, Huang YA, Wiener J, Neblett-Fanfair R, Kourtis AP, Hall HI, Hoover KW.
        AIDS. 2022 Oct 1;36(12):1697-1705.
        OBJECTIVE: To assess disruption in healthcare services for HIV treatment by national emergency in response to the coronavirus disease 2019 (COVID-19) pandemic in the United States. DESIGN: Time-series analysis. METHODS: We analyzed the IQVIA Real World Data-Longitudinal Prescriptions Database and calculated time trends in the weekly number of persons with active antiretroviral prescriptions for HIV treatment, and of persons who obtained antiretroviral prescriptions during January 2017-March 2021. We used interrupted time-series models to estimate the impact of the COVID-19 pandemic on antiretroviral therapy (ART) use between March 2020 and March 2021. RESULTS: We found that the weekly number of persons with active antiretroviral prescriptions decreased by an average 2.5% (95% confidence interval [CI]: -3.8% to -1.1%), compared to predicted use, during March 2020 through March 2021. The weekly number of persons who obtained antiretroviral prescriptions decreased 4.5% (95% CI: -6.0% to -3.0%), compared to the predicted number. Men, persons aged ≤34 years, privately insured persons, and persons in medication assistance programs had greater decreases than other groups. CONCLUSIONS: We demonstrated a decrease in the number of persons with active antiretroviral prescriptions during the first year of the COVID-19 pandemic and the number did not return to levels expected in the absence of the pandemic. Disruptions in HIV care and decreased ART may lead to lower levels of viral suppression and immunologic control, and increased HIV transmission in the community.

      2. PrEP use and adherence among transgender persons in Chicago, IL (SHIPP Study, 2014-2018, USA)
        Townes A, Pyra M, Smith DK, Babu AS, Williams T, Wiener J, Henny KD, Schneider J.
        AIDS Behav. 2022 Sep 12.
        Few studies investigating daily oral preexposure prophylaxis (PrEP) focus on transgender persons. The Sustainable Health Center Implementation PrEP Pilot (SHIPP) Study included a large observational cohort of transgender persons with implications for PrEP in the United States. We examined data from SHIPP's observational cohort and its Medication Adherence Substudy (MAS) to understand adherence among transgender participants in Chicago, IL. We assessed adherence by the proportion of days covered (PDC) for PrEP medication prescriptions, self-reported interview data, and concentrations of intracellular tenofovir diphosphate (TFV-DP) in dried blood spot (DBS) samples. Between 2014 and 2018, there were 510 transgender participants, 349 (68.4%) transgender women and 152 (29.8%) transgender men. Forty-five of these participants were enrolled in the MAS, 31 (68.9%) transgender women and 9 (20.0%) transgender men. By the 3-month follow up, 100% of MAS participants who completed an interview reported taking 4 or more doses of PrEP in the previous week. At 6, 9, and 12 months, taking 4 or more doses in the past week was reported by 81.0%, 94.1%, and 83.3% of participants, respectively. Results from TFV-DP DBS indicated that fewer participants reached the same level of adherence (4 or more doses/week) at clinical visits compared to self-report and even fewer participants reached this level of adherence based on the calculated PDC. Among participants who remained on PrEP throughout the study, DBS adherence levels declined after the first three months. There remains a critical need to develop strategies to address barriers and interventions that support PrEP adherence among transgender people.

      3. Objectives. To evaluate COVID-19 disparities among non-Hispanic American Indian/Alaska Native (AI/AN) and non-Hispanic White persons in urban areas. Methods. Using COVID-19 case surveillance data, we calculated cumulative incidence rates and risk ratios (RRs) among non-Hispanic AI/AN and non-Hispanic White persons living in select urban counties in the United States by age and sex during January 22, 2020, to October 19, 2021. We separated cases into prevaccine (January 22, 2020-April 4, 2021) and postvaccine (April 5, 2021-October 19, 2021) periods. Results. Overall in urban areas, the COVID-19 age-adjusted rate among non-Hispanic AI/AN persons (n = 47 431) was 1.66 (95% confidence interval [CI] = 1.36, 2.01) times that of non-Hispanic White persons (n = 2 301 911). The COVID-19 prevaccine age-adjusted rate was higher (8227 per 100 000; 95% CI = 6283, 10 770) than was the postvaccine rate (3703 per 100 000; 95% CI = 3235, 4240) among non-Hispanic AI/AN compared with among non-Hispanic White persons (2819 per 100 000; 95% CI = 2527, 3144; RR = 1.31; 95% CI = 1.17, 1.48). Conclusions. This study highlights disparities in COVID-19 between non-Hispanic AI/AN and non-Hispanic White persons in urban areas. These findings suggest that COVID-19 vaccination and other public health efforts among urban AI/AN communities can reduce COVID-19 disparities in urban AI/AN populations. (Am J Public Health. 2022;112(10):1489-1497. https://doi.org/10.2105/AJPH.2022.306966).

      4. A bicyclist's tale
        Min Z, Alvarez G, Rao S, Khoury F, Cheema T, Bhanot N, Bishop HS, Qvarnstrom Y, Sapp SG, Cantey PT.
        Clin Infect Dis. 2022 Sep 10;75(4):729-731.

      5. Efavirenz pharmacokinetics and human immunodeficiency virus type 1 (HIV-1) viral suppression among patients receiving tuberculosis treatment containing daily high-dose rifapentine
        Podany AT, Pham M, Sizemore E, Martinson N, Samaneka W, Mohapi L, Badal-Faesen S, Dawson R, Johnson JL, Mayanja H, Lalloo U, Whitworth WC, Pettit A, Campbell K, Phillips PP, Bryant K, Scott N, Vernon A, Kurbatova EV, Chaisson RE, Dorman SE, Nahid P, Swindells S, Dooley KE, Fletcher CV.
        Clin Infect Dis. 2022 Sep 10;75(4):560-566.
        BACKGROUND: A 4-month regimen containing rifapentine and moxifloxacin has noninferior efficacy compared to the standard 6-month regimen for drug-sensitive tuberculosis. We evaluated the effect of regimens containing daily, high-dose rifapentine on efavirenz pharmacokinetics and viral suppression in patients with human immunodeficiency virus (HIV)-associated tuberculosis (TB). METHODS: In the context of a Phase 3 randomized controlled trial, HIV-positive individuals already virally suppressed on efavirenz--containing antiretroviral therapy (ART) (EFV1), or newly initiating efavirenz (EFV2) received TB treatment containing rifapentine (1200 mg), isoniazid, pyrazinamide, and either ethambutol or moxifloxacin. Mid-interval efavirenz concentrations were measured (a) during ART and TB cotreatment (Weeks 4, 8, 12, and 17, different by EFV group) and (b) when ART was taken alone (pre- or post-TB treatment, Weeks 0 and 22). Apparent oral clearance (CL/F) was estimated and compared. Target mid-interval efavirenz concentrations were > 1 mg/L. Co-treatment was considered acceptable if > 80% of participants had mid-interval efavirenz concentrations meeting this target. RESULTS: EFV1 and EFV2 included 70 and 41 evaluable participants, respectively. The geometric mean ratio comparing efavirenz CL/F with vs without TB drugs was 0.79 (90% confidence interval [CI] .72-.85) in EFV1 and 0.84 [90% CI .69-.97] in EFV2. The percent of participants with mid-interval efavirenz concentrations > 1mg/L in EFV1 at Weeks 0, 4, 8, and 17 was 96%, 96%, 88%, and 89%, respectively. In EFV2, at approximately 4 and 8 weeks post efavirenz initiation, the value was 98%. CONCLUSIONS: TB treatment containing high-dose daily rifapentine modestly decreased (rather than increased) efavirenz clearance and therapeutic targets were met supporting the use of efavirenz with these regimens, without dose adjustment. CLINICAL TRIALS REGISTRATION: NCT02410772.

      6. Increasing incidence of invasive group A streptococcus disease, Idaho, USA, 2008-2019
        Dunne EM, Hutton S, Peterson E, Blackstock AJ, Hahn CG, Turner K, Carter KK.
        Emerg Infect Dis. 2022 Sep;28(9):1785-1795.
        We investigated invasive group A Streptococcus epidemiology in Idaho, USA, during 2008-2019 using surveillance data, medical record review, and emm (M protein gene) typing results. Incidence increased from 1.04 to 4.76 cases/100,000 persons during 2008-2019. emm 1, 12, 28, 11, and 4 were the most common types, and 2 outbreaks were identified. We examined changes in distribution of clinical syndrome, patient demographics, and risk factors by comparing 2008-2013 baseline with 2014-2019 data. Incidence was higher among all age groups during 2014-2019. Streptococcal toxic shock syndrome increased from 0% to 6.4% of cases (p = 0.02). We identified no differences in distribution of demographic or risk factors between periods. Results indicated that invasive group A Streptococcus is increasing among the general population of Idaho. Ongoing surveillance of state-level invasive group A Streptococcus cases could help identify outbreaks, track regional trends in incidence, and monitor circulating emm types.

      7. Primary resistance against integrase strand transfer inhibitors in integrase strand transfer inhibitor-naive patients failing first- and second-line ART in Tanzania
        Henerico S, Lyimo E, Makubi AN, Magesa D, Desderius B, Mueller A, Changalucha J, Kalluvya SE, Van Zyl G, Preiser W, Mshana SE, Kasang C.
        J Antimicrob Chemother. 2022 Sep 14.
        INTRODUCTION: Sub-Saharan African countries are introducing integrase strand transfer inhibitors (INSTIs) in their ART programmes as the preferred first-line regimen, and dolutegravir is the INSTI of choice due to its potency, tolerability and high genetic barrier to resistance. Dolutegravir was introduced into the first-line ART regimen in Tanzania in 2019. However, there is a paucity of data on the occurrence of mutations in HIV lineages circulating in Tanzania. This study aimed to determine the prevalence of INSTI primary resistance mutations in Tanzanian patients exposed to ART but not INSTIs. METHODS: Plasma samples from 50 INSTI-naive patients failing first- or second-line ART [median (IQR) age: 40 (21.93-46.41) years; 68% women] were subjected to Sanger sequencing of the HIV integrase gene. Participants had been on ART for a median (IQR) duration of 7.32 (4.73-9.29) years, with 80% and 20% failing first- and second-line ART, respectively. RESULTS: No major INSTI mutations were found, but 2 (4%) participants had the accessory mutation T97A. Using the REGA HIV-1 subtyping tool, HIV subtype A1 (53.1%) was found to be dominant, followed by subtypes C (30.6%) and D (16.3%). CONCLUSIONS: This study found no current evidence for transmitted resistance against INSTIs among unexposed patients failing ART and supports the scale-up of INSTI-based regimens. However, the presence of accessory mutations calls for the surveillance of INSTI resistance mutations to ensure that the anticipated long-term desired outcomes are achieved.

      8. CONTEXT: The Centers for Disease Control and Prevention recommends that all persons aged 13 to 64 years are tested for human immunodeficiency virus (HIV). However, results from US surveys show that 50% of persons and less had ever tested for HIV. PROGRAM: The Centers for Disease Control and Prevention annually funds 60 health departments to conduct comprehensive HIV prevention and surveillance activities that include HIV testing. IMPLEMENTATION: We selected the 31 health departments with quality data (ie, ≤20% missing or invalid values for variables to verify linkage to HIV medical care and new HIV diagnoses) in 2019. Main outcomes were new HIV diagnoses, linkage, and pre-exposure prophylaxis (PrEP) awareness and referrals. We used SAS 9.4 to conduct descriptive, chi-square, and multivariate regression analyses. Our objectives were to determine outcomes and characteristics of persons in non-health care settings who tested for HIV for the first time. EVALUATION: Compared with persons who previously tested for HIV, persons who tested for the first time were more likely to be aged 13 to 29 years than aged 30 years and older (62.0% [24 295/39 192] vs 42.1% [61 911/147 087], P < .001) and have a higher percentage of new HIV diagnoses (0.6% [242/39 320] vs 0.5% [667/147 475], P < .001). Among persons who tested for the first time, overall percentages of linkage, PrEP awareness, and PrEP referral were 73.4%, 33.3%, and 30.8%, respectively. Compared with referent groups, persons who tested for the first time in the South and had a new HIV diagnosis were less likely to be linked (adjusted prevalence ratio [aPR] = 0.72, 95% confidence interval [CI]: 0.59-0.89); persons who inject drugs were less likely to be aware of PrEP (aPR = 0.84, 95% CI: 0.77-0.91); and persons in the Northeast were less likely to receive PrEP referrals (aPR = 0.28, 95% CI: 0.26-0.31). DISCUSSION: Non-health care sites should consider increasing HIV testing, PrEP awareness, and prompt referrals to PrEP and HIV treatment services for persons who have never previously tested.

      9. HIV and sexually transmitted infections among persons with Monkeypox - eight U.S. Jurisdictions, May 17-July 22, 2022
        Curran KG, Eberly K, Russell OO, Snyder RE, Phillips EK, Tang EC, Peters PJ, Sanchez MA, Hsu L, Cohen SE, Sey EK, Yin S, Foo C, Still W, Mangla A, Saafir-Callaway B, Barrineau-Vejjajiva L, Meza C, Burkhardt E, Smith ME, Murphy PA, Kelly NK, Spencer H, Tabidze I, Pacilli M, Swain CA, Bogucki K, DelBarba C, Rajulu DT, Dailey A, Ricaldi J, Mena LA, Daskalakis D, Bachmann LH, Brooks JT, Oster AM.
        MMWR Morb Mortal Wkly Rep. 2022 Sep 9;71(36):1141-1147.
        High prevalences of HIV and other sexually transmitted infections (STIs) have been reported in the current global monkeypox outbreak, which has affected primarily gay, bisexual, and other men who have sex with men (MSM) (1-5). In previous monkeypox outbreaks in Nigeria, concurrent HIV infection was associated with poor monkeypox clinical outcomes (6,7). Monkeypox, HIV, and STI surveillance data from eight U.S. jurisdictions* were matched and analyzed to examine HIV and STI diagnoses among persons with monkeypox and assess differences in monkeypox clinical features according to HIV infection status. Among 1,969 persons with monkeypox during May 17-July 22, 2022, HIV prevalence was 38%, and 41% had received a diagnosis of one or more other reportable STIs in the preceding year. Among persons with monkeypox and diagnosed HIV infection, 94% had received HIV care in the preceding year, and 82% had an HIV viral load of <200 copies/mL, indicating HIV viral suppression. Compared with persons without HIV infection, a higher proportion of persons with HIV infection were hospitalized (8% versus 3%). Persons with HIV infection or STIs are disproportionately represented among persons with monkeypox. It is important that public health officials leverage systems for delivering HIV and STI care and prevention to reduce monkeypox incidence in this population. Consideration should be given to prioritizing persons with HIV infection and STIs for vaccination against monkeypox. HIV and STI screening and other recommended preventive care should be routinely offered to persons evaluated for monkeypox, with linkage to HIV care or HIV preexposure prophylaxis (PrEP) as appropriate.

      10. Orthopoxvirus testing challenges for persons in populations at low risk or without known epidemiologic link to Monkeypox - United States, 2022
        Minhaj FS, Petras JK, Brown JA, Mangla AT, Russo K, Willut C, Lee M, Beverley J, Harold R, Milroy L, Pope B, Gould E, Beeler C, Schneider J, Mostafa HH, Godfred-Cato S, Click ES, Borah BF, Galang RR, Cash-Goldwasser S, Wong JM, McCormick DW, Yu PA, Shelus V, Carpenter A, Schatzman S, Lowe D, Townsend MB, Davidson W, Wynn NT, Satheshkumar PS, O'Connor SM, O'Laughlin K, Rao AK, McCollum AM, Negrón ME, Hutson CL, Salzer JS.
        MMWR Morb Mortal Wkly Rep. 2022 Sep 9;71(36):1155-1158.
        Since May 2022, approximately 20,000 cases of monkeypox have been identified in the United States, part of a global outbreak occurring in approximately 90 countries and currently affecting primarily gay, bisexual, and other men who have sex with men (MSM) (1). Monkeypox virus (MPXV) spreads from person to person through close, prolonged contact; a small number of cases have occurred in populations who are not MSM (e.g., women and children), and testing is recommended for persons who meet the suspected case definition* (1). CDC previously developed five real-time polymerase chain reaction (PCR) assays for detection of orthopoxviruses from lesion specimens (2,3). CDC was granted 510(k) clearance for the nonvariola-orthopoxvirus (NVO)-specific PCR assay by the Food and Drug Administration. This assay was implemented within the Laboratory Response Network (LRN) in the early 2000s and became critical for early detection of MPXV and implementation of public health action in previous travel-associated cases as well as during the current outbreak (4-7). PCR assays (NVO and other Orthopoxvirus laboratory developed tests [LDT]) represent the primary tool for monkeypox diagnosis. These tests are highly sensitive, and cross-contamination from other MPXV specimens being processed, tested, or both alongside negative specimens can occasionally lead to false-positive results. This report describes three patients who had atypical rashes and no epidemiologic link to a monkeypox case or known risk factors; these persons received diagnoses of monkeypox based on late cycle threshold (Ct) values ≥34, which were false-positive test results. The initial diagnoses were followed by administration of antiviral treatment (i.e., tecovirimat) and JYNNEOS vaccine postexposure prophylaxis (PEP) to patients' close contacts. After receiving subsequent testing, none of the three patients was confirmed to have monkeypox. Knowledge gained from these and other cases resulted in changes to CDC guidance. When testing for monkeypox in specimens from patients without an epidemiologic link or risk factors or who do not meet clinical criteria (or where these are unknown), laboratory scientists should reextract and retest specimens with late Ct values (based on this report, Ct ≥34 is recommended) (8). CDC can be consulted for complex cases including those that appear atypical or questionable cases and can perform additional viral species- and clade-specific PCR testing and antiorthopoxvirus serologic testing.

      11. Detection of higher cycle threshold values in culturable SARS-CoV-2 Omicron BA.1 sublineage compared with pre-Omicron variant specimens - San Francisco Bay area, California, July 2021-March 2022
        Tassetto M, Garcia-Knight M, Anglin K, Lu S, Zhang A, Romero M, Pineda-Ramirez J, Sanchez RD, Donohue KC, Pfister K, Chan C, Saydah S, Briggs-Hagen M, Peluso MJ, Martin JN, Andino R, Midgley CM, Kelly JD.
        MMWR Morb Mortal Wkly Rep. 2022 Sep 9;71(36):1151-1154.
        Before emergence in late 2021 of the highly transmissible B.1.1.529 (Omicron) variant of SARS-CoV-2, the virus that causes COVID-19 (1,2), several studies demonstrated that SARS-CoV-2 was unlikely to be cultured from specimens with high cycle threshold (Ct) values(§) from real-time reverse transcription-polymerase chain reaction (RT-PCR) tests (suggesting low viral RNA levels) (3). Although CDC and others do not recommend attempting to correlate Ct values with the amount of infectious virus in the original specimen (4,5), low Ct values are sometimes used as surrogate markers for infectiousness in clinical, public health, or research settings without access to virus culture (5). However, the consistency in reliability of this practice across SARS-CoV-2 variants remains uncertain because Omicron-specific data on infectious virus shedding, including its relationship with RNA levels, are limited. In the current analysis, nasal specimens collected from an ongoing longitudinal cohort(¶) (6,7) of nonhospitalized participants with positive SARS-CoV-2 test results living in the San Francisco Bay Area** were used to generate Ct values and assess for the presence of culturable SARS-CoV-2 virus; findings were compared between specimens from participants infected with pre-Omicron variants and those infected with the Omicron BA.1 sublineage. Among specimens with culturable virus detected, Ct values were higher (suggesting lower RNA levels) during Omicron BA.1 infections than during pre-Omicron infections, suggesting variant-specific differences in viral dynamics. Supporting CDC guidance, these data show that Ct values likely do not provide a consistent proxy for infectiousness across SARS-CoV-2 variants.

    • Community Health Services
      1. HIV testing services outcomes in CDC-funded health departments during COVID-19
        Patel D, Williams WO, Wright C, Taylor-Aidoo N, Song W, Marandet A, DiNenno EA.
        J Acquir Immune Defic Syndr. 2022 Oct 1;91(2):117-121.
        BACKGROUND: Organizations offering HIV prevention services have reported interruptions during the COVID-19 pandemic. The national extent of these interruptions and their public health impact remain largely unexplored. METHODS: Using data from 60 state and local health departments, we compared HIV testing services outcomes in calendar years 2019 and 2020, including the number of Centers for Disease Control and Prevention (CDC)-funded HIV tests conducted, the percentage of persons with newly diagnosed HIV infection (ie, HIV positivity), and the percentage linked to HIV medical care within 30 days after new diagnoses (ie, linkage to care) using χ2 and robust Poisson models. We also assessed the independent associations between the pandemic period (ie, March-December 2020) and the number of COVID-19 cases with monthly HIV testing services outcomes using multivariable robust Poisson models. RESULTS: There was a 46.0% (P < 0.001) reduction in the number of CDC-funded HIV tests conducted in 2020 (n = 1,255,895) compared with 2019 (n = 2,324,421). Although there were fewer persons with newly diagnosed HIV in 2020 (n = 5581 vs. n = 7739 in 2019), HIV positivity was greater in 2020 (0.4% vs. 0.3% in 2019; adjusted prevalence ratio [aPR] = 1.33, 95% confidence interval [CI]: 1.05 to 1.69). When adjusting for the monthly number of COVID-19 cases, the pandemic period was associated with a 56% reduction in the number of monthly CDC-funded HIV tests (adjusted rate ratio = 0.44, 95% CI: 0.37 to 0.52) but 28% higher monthly HIV positivity (aPR = 1.28 95% CI: 1.16 to 1.41) and 10% higher linkage to care (aPR = 1.10, 95% CI: 1.02 to 1.18). DISCUSSION: Despite increased HIV positivity, a drastic reduction in the number of CDC-funded HIV tests was observed in 2020, affecting the ability to identify persons with newly diagnosed HIV. CDC and health departments will need to expand testing strategies to cover tests not conducted in 2020 while adapting to the continuing pandemic.A visual abstract is available for this article at: http://links.lww.com/QAI/B941.

      2. Health care usage among adolescents with congenital heart defects at 5 sites in the United States, 2011 to 2013
        Lui GK, Sommerhalter K, Xi Y, Botto LD, Crume T, Farr S, Feldkamp ML, Glidewell J, Hsu D, Khanna A, Krikov S, Li J, Raskind-Hood C, Sarno L, Van Zutphen AR, Zaidi A, Soim A, Book WM.
        J Am Heart Assoc. 2022 Sep 14:e026172.
        Background We sought to characterize health care usage for adolescents with congenital heart defects (CHDs) using population-based multisite surveillance data. Methods and Results Adolescents aged 11 to 18 years with ≥1 CHD-related diagnosis code and residing in 5 US sites were identified in clinical and administrative data sources for the years 2011 to 2013. Sites linked data on all inpatient, emergency department (ED), and outpatient visits. Multivariable log-binomial regression models including age, sex, unweighted Charlson comorbidity index, CHD severity, cardiology visits, and insurance status, were used to identify associations with inpatient, ED, and outpatient visits. Of 9626 eligible adolescents, 26.4% (n=2543) had severe CHDs and 21.4% had Charlson comorbidity index >0. At least 1 inpatient, ED, or outpatient visit was reported for 21%, 25%, and 96% of cases, respectively. Cardiology visits, cardiac imaging, cardiac procedures, and vascular procedures were reported for 38%, 73%, 10%, and 5% of cases, respectively. Inpatient, ED, and outpatient visits were consistently higher for adolescents with severe CHDs compared with nonsevere CHDs. Adolescents with severe and nonsevere CHDs had higher health care usage compared with the 2011 to 2013 general adolescent US population. Adolescents with severe CHDs versus nonsevere CHDs were twice as likely to have at least 1 inpatient visit when Charlson comorbidity index was low (Charlson comorbidity index =0). Adolescents with CHDs and public insurance, compared with private insurance, were more likely to have inpatient (adjusted prevalence ratio, 1.5 [95% CI, 1.3-1.7]) and ED (adjusted prevalence ratio, 1.6 [95% CI, 1.4-1.7]) visits. Conclusions High resource usage by adolescents with CHDs indicates a substantial burden of disease, especially with public insurance, severe CHDs, and more comorbidities.

      3. SARS-CoV-2 screening testing in schools: A comparison of school- vs home-based collection methods
        Chung E, Magedson A, Emanuels A, Luiten K, Pfau B, Truong M, Chow EJ, Hughes JP, Uyeki TM, Englund JA, Nickerson DA, Lockwood CM, Shendure J, Starita LM, Chu HY.
        J Pediatric Infect Dis Soc. 2022 Sep 9.

      4. Rapid COVID-19 testing and on-site case investigation and contact tracing in an underresourced area of Salt Lake City, Utah, December 2020-April 2021
        Gillwald K, Lee SH, Paegle A, Mead P, Acker T, Roberts NB, Dunn AC.
        Public Health Rep. 2022 Sep 8:333549221120807.
        This case study describes how we paired free SARS-CoV-2 rapid antigen testing with on-site case investigation and contact tracing at a drive-through site in an underresourced area of Salt Lake City. Residents of this area had lower rates of employment and health insurance and higher rates of poverty than in the Utah general population. People were given an option to remain on-site and wait until their test results were ready. If a vehicle occupant received a positive test result, the case investigation occurred on-site; contact tracing with the other vehicle occupants was also initiated. People were provided resources to support isolation and quarantine. Bilingual staff who spoke Spanish were incorporated into the workflow. From December 2020 through April 2021, public health staff administered 39 587 rapid tests; 4094 people received a positive test result and 1133 stayed for on-site case investigation. More than half (60.5%) of people with a positive test result who agreed to stay for on-site case investigation were Hispanic or self-reported belonging to a non-Hispanic racial minority group (American Indian/Alaska Native, Asian, Black or African American, Native Hawaiian or Other Pacific Islander, or other racial identities). Pairing rapid antigen testing with on-site case investigation and contact tracing is feasible and improved the timeliness of case investigation by ≥1 day. On-site vaccination services were later integrated. Future emergency responses might consider assisting underresourced communities with on-site services that provide convenient and accessible public health interventions. By providing dependable and reliable services, we were able to achieve buy-in and become a consistent resource for those in the community.

    • Disease Reservoirs and Vectors
      1. Abstract: Aedes aegypti (Linnaeus) is an invasive mosquito species and notable vector of several pathogens in the USA. Their cryptic and anthropophilic nature puts this species in close association with humans, where they can also be a nuisance. Mosquito control programs are the front line of defense for protecting the community from nuisance-biting and disease. However, the occurrence and prevalence of insecticide resistance in mosquitoes is a well-documented phenomenon that directly impacts the efficacy of insecticide applications. In Florida specifically, widespread resistance in Ae. aegypti has created a need for operational strategies that combat and, ideally, reverse resistance. Laboratory studies and the association between fitness costs and insecticide resistance indicate that this reversion is possible under the right conditions. For a 2.5-year period, the impact of varying operational treatment regimens on insecticide resistance in Ae. aegypti is evaluated using kdr genotyping and the CDC bottle bioassay. In an organophosphate treatment area, a decrease in frequency of a double homozygous resistant genotype was observed. CDC bottle bioassays did not reveal any clear trends in the data to indicate a reversion to insecticide susceptibility. However, the changes in genotype could indicate the first step back to insecticide susceptibility. This study provides preliminary data that has implications for resistance management in mosquito control operations. Article Highlights: Presented study represents the first field study to evaluate how changing insecticide pressures on resistant mosquitoes affects insecticide resistance.A decrease in the double homozygous resistance genotype was observed in Ae. aegypti from the organophosphate treatment area after a change in use patterns.Identifiable trends in phenotypic resistance as a result of the treatment regimens were not observed. © 2022, The Author(s).

    • Environmental Health
      1. Indoor dampness and mold are prevalent, and the exposure has been associated with various illnesses such as the exacerbation of existing asthma, asthma development, current asthma, ever-diagnosed asthma, bronchitis, respiratory infection, allergic rhinitis, dyspnea, wheezing, cough, upper respiratory symptoms, and eczema. However, assessing exposures or environments in damp and moldy buildings/rooms, especially by collecting and analyzing environmental samples for microbial agents, is complicated. Nonetheless, observational assessment (visual and olfactory inspection) has been demonstrated as an effective method for evaluating indoor dampness and mold. The National Institute for Occupational Safety and Health developed an observational assessment method called the Dampness and Mold Assessment Tool (DMAT). The DMAT uses a semi-quantitative approach to score the level of dampness and mold-related damage (mold odor, water damage/stains, visible mold, and wetness/dampness) by intensity or size for each of the room components (ceiling, walls, windows, floor, furnishings, ventilation system, pipes, and supplies and materials). Total or average room scores and factor-or component-specific scores can be calculated for data analysis. Because the DMAT uses a semi-quantitative scoring method, it better differentiates the level of damage compared to the binary (presence or absence of damage) approach. Thus, our DMAT provides useful information on identifying dampness and mold, tracking and comparing past and present damage by the scores, and prioritizing remediation to avoid potential adverse health effects in occupants. This protocol-type article describes the DMAT and demonstrates how to apply it to effectively manage indoor dampness and mold-related damage. © 2022 by the authors.

      2. Prenatal exposure to polybrominated diphenyl ethers and BMI Z-scores from 5 to 14 years
        Kupsco A, Sjödin A, Cowell W, Jones R, Oberfield S, Wang S, Hoepner LA, Gallagher D, Baccarelli AA, Goldsmith J, Rundle AG, Herbstman JB.
        Environ Health. 2022 Sep 8;21(1):82.
        BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are flame-retardant compounds widely used in household products until phase out in 2004. PBDEs are endocrine disruptors and are suggested to influence signaling related to weight control. Prenatal exposures to PBDEs may alter childhood adiposity, yet few studies have examined these associations in human populations. METHODS: Data were collected from a birth cohort of Dominican and African American mother-child pairs from New York City recruited from 1998 to 2006. PBDE congeners BDE-47, - 99, - 100, and - 153 were measured in cord plasma (ng/μL) and dichotomized into low (< 80th percentile) and high (>80th percentile) exposure categories. Height and weight were collected at ages 5, 7, 9, 11, and an ancillary visit from 8 to 14 years (n = 289). Mixed-effects models with random intercepts for participant were used to assess associations between concentrations of individual PBDE congeners or the PBDE sum and child BMI z-scores (BMIz). To assess associations between PBDEs and the change in BMIz over time, models including interactions between PBDE categories and child age and (child age)(2) were fit. Quantile g-computation was used to investigate associations between BMIz and the total PBDE mixture. Models were adjusted for baseline maternal covariates: ethnicity, age, education, parity, partnership status, and receipt of public assistance, and child covariates: child sex and cord cholesterol and triglycerides. RESULTS: The prevalence of children with obesity at age 5 was 24.2% and increased to 30% at age 11. Neither cord levels of individual PBDEs nor the total PBDE mixture were associated with overall BMIz in childhood. The changes in BMIz across childhood were not different between children with low or high PBDEs. Results were similar when adjusting for postnatal PBDE exposures. CONCLUSIONS: Prenatal PBDE exposures were not associated with child growth trajectories in a cohort of Dominican and African American children.

      3. Childhood urinary organophosphate esters and cognitive abilities in a longitudinal cohort study
        Percy Z, Chen A, Yang W, Braun JM, Lanphear B, Ospina M, Calafat AM, Xie C, Cecil K, Vuong AM, Xu Y, Yolton K.
        Environ Res. 2022 Sep 11:114265.
        The use of organophosphate esters (OPEs) as flame retardants, which has increased over the past two decades, raises concerns that OPEs may be harmful to humans, especially children. Animal studies and some human studies have reported that OPEs may adversely impact brain development, but few human studies evaluated OPE exposure during early childhood and neurodevelopmental outcomes. We aimed to fill this knowledge gap with the present study on urinary OPE metabolite concentrations at ages 1-5 years and cognitive abilities at 8 years. We used data of 223 children from the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort in Cincinnati, Ohio. The point estimates for bis-2-chloroethyl-phosphate (BCEP) and bis(1,3-dichloro-2-propyl)-phosphate (BDCIPP) in association with IQ tended to be small and positive, while the point estimates for diphenyl-phosphate (DPHP) were small and negative, with 95% CIs including the null. However, we did find that socioeconomic status (SES) variables modified associations between OPEs and child IQ, with adverse OPE-IQ associations being stronger in socioeconomically disadvantaged children than in others. We identified an additional 1- to 2-point decrease in Full Scale IQ for every log-unit increase in BDCIPP, BCEP, and DPHP among those with lower maternal education, non-white race, lower income, or living in more deprived neighborhoods. We observed similar results for the Perceptual Reasoning, Verbal Comprehension, and Working Memory Index Scores. We suspect that there is residual confounding related to socioeconomic disadvantage, which was not captured with the available SES variables typically used in epidemiologic studies.

      4. Environmental Public Health Tracking, an untapped resource for occupational health
        Namulanda G, Monti M, Werner A, Nogueira I, Solomon G, English P, Karlsson N, Cosser A, Bush K, Mitchell C.
        J Occup Environ Hyg. 2022 Sep 13:1-9.

      5. Associations between prenatal urinary biomarkers of phthalate exposure and preterm birth: A pooled study of 16 US cohorts
        Welch BM, Keil AP, Buckley JP, Calafat AM, Christenbury KE, Engel SM, O'Brien KM, Rosen EM, James-Todd T, Zota AR, Ferguson KK, Alshawabkeh AN, Cordero JF, Meeker JD, Barrett ES, Bush NR, Nguyen RH, Sathyanarayana S, Swan SH, Cantonwine DE, McElrath TF, Aalborg J, Dabelea D, Starling AP, Hauser R, Messerlian C, Zhang Y, Bradman A, Eskenazi B, Harley KG, Holland N, Bloom MS, Newman RB, Wenzel AG, Braun JM, Lanphear BP, Yolton K, Factor-Litvak P, Herbstman JB, Rauh VA, Drobnis EZ, Sparks AE, Redmon JB, Wang C, Binder AM, Michels KB, Baird DD, Jukic AM, Weinberg CR, Wilcox AJ, Rich DQ, Weinberger B, Padmanabhan V, Watkins DJ, Hertz-Picciotto I, Schmidt RJ.
        JAMA Pediatr. 2022 Sep 1;176(9):895-905.
        IMPORTANCE: Phthalate exposure is widespread among pregnant women and may be a risk factor for preterm birth. OBJECTIVE: To investigate the prospective association between urinary biomarkers of phthalates in pregnancy and preterm birth among individuals living in the US. DESIGN, SETTING, AND PARTICIPANTS: Individual-level data were pooled from 16 preconception and pregnancy studies conducted in the US. Pregnant individuals who delivered between 1983 and 2018 and provided 1 or more urine samples during pregnancy were included. EXPOSURES: Urinary phthalate metabolites were quantified as biomarkers of phthalate exposure. Concentrations of 11 phthalate metabolites were standardized for urine dilution and mean repeated measurements across pregnancy were calculated. MAIN OUTCOMES AND MEASURES: Logistic regression models were used to examine the association between each phthalate metabolite with the odds of preterm birth, defined as less than 37 weeks of gestation at delivery (n = 539). Models pooled data using fixed effects and adjusted for maternal age, race and ethnicity, education, and prepregnancy body mass index. The association between the overall mixture of phthalate metabolites and preterm birth was also examined with logistic regression. G-computation, which requires certain assumptions to be considered causal, was used to estimate the association with hypothetical interventions to reduce the mixture concentrations on preterm birth. RESULTS: The final analytic sample included 6045 participants (mean [SD] age, 29.1 [6.1] years). Overall, 802 individuals (13.3%) were Black, 2323 (38.4%) were Hispanic/Latina, 2576 (42.6%) were White, and 328 (5.4%) had other race and ethnicity (including American Indian/Alaskan Native, Native Hawaiian, >1 racial identity, or reported as other). Most phthalate metabolites were detected in more than 96% of participants. Higher odds of preterm birth, ranging from 12% to 16%, were observed in association with an interquartile range increase in urinary concentrations of mono-n-butyl phthalate (odds ratio [OR], 1.12 [95% CI, 0.98-1.27]), mono-isobutyl phthalate (OR, 1.16 [95% CI, 1.00-1.34]), mono(2-ethyl-5-carboxypentyl) phthalate (OR, 1.16 [95% CI, 1.00-1.34]), and mono(3-carboxypropyl) phthalate (OR, 1.14 [95% CI, 1.01-1.29]). Among approximately 90 preterm births per 1000 live births in this study population, hypothetical interventions to reduce the mixture of phthalate metabolite levels by 10%, 30%, and 50% were estimated to prevent 1.8 (95% CI, 0.5-3.1), 5.9 (95% CI, 1.7-9.9), and 11.1 (95% CI, 3.6-18.3) preterm births, respectively. CONCLUSIONS AND RELEVANCE: Results from this large US study population suggest that phthalate exposure during pregnancy may be a preventable risk factor for preterm delivery.

    • Epidemiology and Surveillance
      1. Question evaluation for real-time surveys: Lessons from COVID-19 data collection
        Willson S, Scanlon P, Miller K.
        SSM Qual Res Health. 2022 Dec;2:100164.
        The need for high-quality, real-time data has never presented itself as clearly as it did during the COVID-19 pandemic. Responding to the COVID-19 pandemic, from both a policy and a public health perspective, required timely, accurate data about the public's attitudes and behaviors from health surveillance, monitoring, and public opinion surveys. The uniqueness of the COVID-19 pandemic also created particular challenges for survey data collection, specifically, how to develop high quality survey questions on topics that had never been previously fielded. To account for this challenge, the National Center for Health Statistics adopted an iterative, two-component, mixed-method approach to question design and evaluation. The first, a cognitive interviewing study using virtual, online interviews was used to produce interpretative schemata of the response processes underlying the survey questions. The second, a two-round, mixed method survey using a statistically-sampled panel, was designed to further develop the interpretive schemata and to allow for detailed subgroup analyses. To increase the usefulness of the survey's second round, cognitive interview findings and results from the survey's first round were used to develop both open- and close-ended embedded probes. Taken together, the studies reveal the specific problems for question-design during such a novel, quickly-evolving event: 1) a lack of shared understanding of novel concepts and vocabulary, 2) the shifting reference period respondents use to think about attitudes and behaviors during a multi-year event, 3) the pervasive nature of the event that therefore frames how respondents conceptualize and process questions about unrelated topics. This iterative approach to understanding question-design problems not only allowed for the continuing improvement of COVID-19 survey items, going forward, it also provided a methodological foundation for question development for high quality, real-time data collection.

    • Genetics and Genomics
      1. Molecular epidemiology of blastomyces gilchristii clusters, Minnesota, USA
        Bagal UR, Ireland M, Gross A, Fischer J, Bentz M, Berkow EL, Litvintseva AP, Chow NA.
        Emerg Infect Dis. 2022 Sep;28(9):1924-1926.
        We characterized 2 clusters of blastomycosis cases in Minnesota, USA, using whole-genome sequencing and single-nucleotide polymorphism analyses. Blastomyces gilchristii was confirmed as the cause of infection. Genomic analyses corresponded with epidemiologic findings for cases of B. gilchristii infections, demonstrating the utility of genomic methods for future blastomycosis outbreak investigations.

    • Global Health
      1. Immune imprinting drives human norovirus potential for global spread
        Lindesmith LC, Boshier FA, Brewer-Jensen PD, Roy S, Costantini V, Mallory ML, Zweigart M, May SR, Conrad H, O'Reilly KM, Kelly D, Celma CC, Beard S, Williams R, Tutill HJ, Becker Dreps S, Bucardo F, Allen DJ, Vinjé J, Goldstein RA, Breuer J, Baric RS.
        mBio. 2022 Sep 14:e0186122.
        Understanding the complex interactions between virus and host that drive new strain evolution is key to predicting the emergence potential of variants and informing vaccine development. Under our hypothesis, future dominant human norovirus GII.4 variants with critical antigenic properties that allow them to spread are currently circulating undetected, having diverged years earlier. Through large-scale sequencing of GII.4 surveillance samples, we identified two variants with extensive divergence within domains that mediate neutralizing antibody binding. Subsequent serological characterization of these strains using temporally resolved adult and child sera suggests that neither candidate could spread globally in adults with multiple GII.4 exposures, yet young children with minimal GII.4 exposure appear susceptible. Antigenic cartography of surveillance and outbreak sera indicates that continued population exposure to GII.4 Sydney 2012 and antigenically related variants over a 6-year period resulted in a broadening of immunity to heterogeneous GII.4 variants, including those identified here. We show that the strongest antibody responses in adults exposed to GII.4 Sydney 2012 are directed to previously circulating GII.4 viruses. Our data suggest that the broadening of antibody responses compromises establishment of strong GII.4 Sydney 2012 immunity, thereby allowing the continued persistence of GII.4 Sydney 2012 and modulating the cycle of norovirus GII.4 variant replacement. Our results indicate a cycle of norovirus GII.4 variant replacement dependent upon population immunity. Young children are susceptible to divergent variants; therefore, emergence of these strains worldwide is driven proximally by changes in adult serological immunity and distally by viral evolution that confers fitness in the context of immunity. IMPORTANCE In our model, preepidemic human norovirus variants harbor genetic diversification that translates into novel antigenic features without compromising viral fitness. Through surveillance, we identified two viruses fitting this profile, forming long branches on a phylogenetic tree. Neither evades current adult immunity, yet young children are likely susceptible. By comparing serological responses, we demonstrate that population immunity varies by age/exposure, impacting predicted susceptibility to variants. Repeat exposure to antigenically similar variants broadens antibody responses, providing immunological coverage of diverse variants but compromising response to the infecting variant, allowing continued circulation. These data indicate norovirus GII.4 variant replacement is driven distally by virus evolution and proximally by immunity in adults.

    • Health Economics
      1. OBJECTIVE: To estimate medical costs associated with 17 major diabetes-related complications and treatment procedures among Medicare beneficiaries aged ≥65 years with type 2 diabetes. RESEARCH DESIGN AND METHODS: Claims data from 100% of Medicare beneficiaries enrolled in fee-for-service plans from 2006 to 2017 were analyzed. Records with type 2 diabetes and complications were identified using ICD-9, ICD-10, and diagnosis-related group codes. The index year was the year when a person was first identified as having diabetes with an inpatient claim or an outpatient claim plus another inpatient/outpatient claim in the 2 years following the first claim in Medicare. Included individuals were followed from index years until death, discontinuation of plan coverage, or 31 December 2017. Fixed-effects regression was used to estimate the cost in years when the complication event occurred and in subsequent years. The total cost for each complication was calculated for 2017 by multiplying the complication prevalence by the cost estimate. All costs were standardized to 2017 U.S. dollars. RESULTS: Our study included 10,982,900 beneficiaries with type 2 diabetes. Follow-up ranged from 3 to 10 years. The three costliest complications were kidney failure treated by transplant (occurring year $79,045, subsequent years $17,303), kidney failure treated by dialysis ($54,394, $38,670), and lower-extremity amputation ($38,982, $8,084). Congestive heart failure accounted for the largest share (18%) of total complication costs. CONCLUSIONS: Costs associated with diabetes complications were substantial. Our cost estimates provide essential information needed for conducting economic evaluation of treatment and programs to prevent and delay diabetes complications in Medicare beneficiaries.

      2. Estimated costs and quality-adjusted life-years lost due to N. gonorrhoeae infections acquired in 2015 in the United States: A modelling study of overall burden and disparities by age, race/ethnicity, and other factors
        Li Y, Rönn MM, Tuite AR, Chesson HW, Gift TL, Trikalinos TA, Testa C, Bellerose M, Hsu K, Berruti AA, Malyuta Y, Menzies NA, Salomon JA.
        Lancet Reg Health Am. 2022 ;16.
        Background: Disparities in the health and economic burden of gonorrhoea have not been systematically quantified. We estimated population-level health losses and costs associated with gonococcal infection and sequelae in the United States. Methods: We used probability-tree models to capture gonorrhoea sequelae and to estimate attributable disease burden in terms of the discounted lifetime costs and quality-adjusted life-years (QALYs) lost due to incident infections acquired during 2015 from the healthcare system perspective. Numbers of infections in 2015 were obtained from a published gonorrhoea transmission model. We evaluated population-level disease burden, disaggregated by sex, age, race/ethnicity, and for men who have sex with men (MSM). We conducted a multivariate sensitivity analysis for key parameters. Findings: Discounted lifetime QALYs lost per incident gonococcal infection were estimated as 0.093 (95% uncertainty interval [UI] 0.022-0.22) for women, 0.0020 (0.0015-0.0024) for heterosexual men, and 0.0015 (0.00070-0.0021) for MSM. Discounted lifetime costs per incident infection were USD 261 (109-480), 169 (88-263), and 133 (50-239), respectively. At the population level, total discounted lifetime QALYs lost due to infections acquired during 2015 were 53,293 (12,326-125,366) for women, 621 (430-872) for heterosexual men, and 1,078 (427-1,870) for MSM. Total discounted lifetime costs were USD 150 million (64-277 million), 54 million (25-92 million), and 97 million (34-197 million), respectively. The highest total burden of both QALYs and costs at the population-level was observed in Non-Hispanic Black women, and highest burden per 1,000 person-years was identified in MSM among men and American Indian/Alaska Native among women. Interpretation: Gonorrhoea causes substantial health losses and costs in the United States. These results can inform planning and prioritization of prevention services. Funding: Centers for Disease Control and Prevention, Charles A. King Trust. © 2022 The Author(s)

      3. Building the health-economic case for scaling up the WHO-HEARTS hypertension control package in low- and middle-income countries
        Moran AE, Farrell M, Cazabon D, Sahoo SK, Mugrditchian D, Pidugu A, Chivardi C, Walbaum M, Alemayehu S, Isaranuwatchai W, Ankurawaranon C, Choudhury SR, Pickersgill SJ, Watkins DA, Husain MJ, Rao KD, Matsushita K, Marklund M, Hutchinson B, Nugent R, Kostova D, Garg R.
        Rev Panam Salud Publica. 2022 ;46:e140.
        Generally, hypertension control programs are cost-effective, including in low- and middle-income countries, but country governments and civil society are not likely to support hypertension control programs unless value is demonstrated in terms of public health benefits, budget impact, and value-for-investment for the individual country context. The World Health Organization (WHO) and the Pan American Health Organization (PAHO) established a standard, simplified Global HEARTS approach to hypertension control, including preferred antihypertensive medicines and blood pressure measurement devices. The objective of this study is to report on health economic studies of HEARTS hypertension control package cost (especially medication costs), cost-effectiveness, and budget impact and describe mathematical models designed to translate hypertension control program data into the optimal approach to hypertension care service delivery and financing, especially in low- and middle-income countries. Early results suggest that HEARTS hypertension control interventions are either cost-saving or cost-effective, that the HEARTS package is affordable at between US$ 18-44 per person treated per year, and that antihypertensive medicines could be priced low enough to reach a global standard of an average <US$ 5 per patient per year in the public sector. This health economic evidence will make a compelling case for government ownership and financial support for national scale hypertension control programs.

    • Health Equity and Health Disparities
      1. Closing the information gap: Making COVID-19 information accessible for people with disabilities
        Anderson SM, Flores AL, Baldwin LZ, Phillips CP, Meunier J.
        Assist Technol Outcomes Benefits. 2022 ;16(Special Issue 2):86-103.
        It is essential that people with disabilities have equitable access to COVID-19 communication resources to protect themselves, their families, and their communities. The Accessible Materials and Culturally Relevant Messages for Individuals with Disabilities project aimed to deliver essential COVID-19 information in braille, American Sign Language (ASL), simplified text, and other alternative formats, along with providing additional tools and trainings that people with disabilities and organizations that serve them can use to apply the COVID-19 guidance. Lessons learned from this project can be implemented in future public health emergencies as well as in general public health messaging for people with disabilities. This project, led by Georgia Tech’s Center for Inclusive Design and Innovation (CIDI) and with technical assistance from the Centers for Disease Control and Prevention (CDC), was supported by the CDC Foundation, using funds from the CDC Foundation’s COVID-19 Emergency Response Fund. © ATIA 2022.

      2. “Include me”: Implementing inclusive and accessible communication in public health
        Flores AL, Meunier J, Peacock G.
        Assist Technol Outcomes Benefits. 2022 ;16(Special Issue 2):104-110.
        To ensure access to health communication, attention must be paid to the needs of all audiences. As scientists working in a highly technical organization, we often focus more on methods and findings without giving the same thought to how we convey messages and the communication needs of specific audiences. In this essay, we outline how we learned a great deal about communications during the planning and execution of a Public Health Grand Rounds (PHGR). This PHGR gave us a chance to pause and consider what was most important: our public health messages, making them relevant and understandable, ensuring they were informative and actionable, and maximizing accessible outlets and methods for disseminating our messages. © ATIA 2022.

      3. Choosing the emergency department as an alternative for STD care: Potential disparities in access
        Pearson WS, Tromble E, Jenkins WD, Solnick R, Gift TL.
        J Health Care Poor Underserved. 2022 ;33(3):1163-1168.
        This analysis was designed to determine if there existed differences by race in seeking sexually transmitted disease (STD) care in an emergency department (ED). Methods. Data were collected from 4,138 patients attending 26 STD clinics across the United States (U.S.). The questionnaire asked where the patient would have sought care if the STD clinic had not been available that day. Responses were stratified by race and differences were tested for statistical significance. Results. Black/African American patients chose hospital emergency room as an alternative for STD clinic care at a rate approximately 2.5 times that of White patients (15.5% v. 5.8%, p <.05). This difference persisted among Black/African American patients after controlling for demographic variables (adjusted OR 2.91; 2.21–3.82 95% CI). Discussion. Receiving appropriate care is key to stemming the increases in sexually transmitted infections in the U.S. These findings suggest that disparities in access to STD care exist for Black/African American people. © Meharry Medical College Journal of Health Care for the Poor and Underserved.

      4. Investigating health disparities associated with multisystem inflammatory syndrome in children after SARS-CoV-2 infection
        Zambrano LD, Ly KN, Link-Gelles R, Newhams MM, Akande M, Wu MJ, Feldstein LR, Tarquinio KM, Sahni LC, Riggs BJ, Singh AR, Fitzgerald JC, Schuster JE, Giuliano JS, Englund JA, Hume JR, Hall MW, Osborne CM, Doymaz S, Rowan CM, Babbitt CJ, Clouser KN, Horwitz SM, Chou J, Patel MM, Hobbs C, Randolph AG, Campbell AP.
        Pediatr Infect Dis J. 2022 Sep 7.
        BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a postinfectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related complication that has disproportionately affected racial/ethnic minority children. We conducted a pilot study to investigate risk factors for MIS-C aiming to understand MIS-C disparities. METHODS: This case-control study included MIS-C cases and SARS-CoV-2-positive outpatient controls aged less than 18 years frequency-matched 4:1 to cases by age group and site. Patients hospitalized with MIS-C were admitted between March 16 and October 2, 2020, across 17 pediatric hospitals. We evaluated race, ethnicity, social vulnerability index (SVI), insurance status, weight-for-age and underlying medical conditions as risk factors using mixed effects multivariable logistic regression. RESULTS: We compared 241 MIS-C cases to 817 outpatient SARS-CoV-2-positive at-risk controls. Cases and controls had similar sex, age and U.S. census region distribution. MIS-C patients were more frequently previously healthy, non-Hispanic Black, residing in higher SVI areas, and in the 95th percentile or higher for weight-for-age. In the multivariable analysis, the likelihood of MIS-C was higher among non-Hispanic Black children [adjusted odds ratio (aOR): 2.07; 95% CI: 1.23-3.48]. Additionally, SVI in the 2nd and 3rd tertiles (aOR: 1.88; 95% CI: 1.18-2.97 and aOR: 2.03; 95% CI: 1.19-3.47, respectively) were independent factors along with being previously healthy (aOR: 1.64; 95% CI: 1.18-2.28). CONCLUSIONS: In this study, non-Hispanic Black children were more likely to develop MIS-C after adjustment for sociodemographic factors, underlying medical conditions, and weight-for-age. Investigation of the potential contribution of immunologic, environmental, and other factors is warranted.


    • Healthcare Associated Infections
      1. Hospital-onset bacteremia and fungemia: An evaluation of predictors and feasibility of benchmarking comparing two risk-adjusted models among 267 hospitals
        Yu KC, Ye G, Edwards JR, Gupta V, Benin AL, Ai C, Dantes R.
        Infect Control Hosp Epidemiol. 2022 Sep 9:1-9.
        OBJECTIVES: To evaluate the prevalence of hospital-onset bacteremia and fungemia (HOB), identify hospital-level predictors, and to evaluate the feasibility of an HOB metric. METHODS: We analyzed 9,202,650 admissions from 267 hospitals during 2015-2020. An HOB event was defined as the first positive blood-culture pathogen on day 3 of admission or later. We used the generalized linear model method via negative binomial regression to identify variables and risk markers for HOB. Standardized infection ratios (SIRs) were calculated based on 2 risk-adjusted models: a simple model using descriptive variables and a complex model using descriptive variables plus additional measures of blood-culture testing practices. Performance of each model was compared against the unadjusted rate of HOB. RESULTS: Overall median rate of HOB per 100 admissions was 0.124 (interquartile range, 0.00-0.22). Facility-level predictors included bed size, sex, ICU admissions, community-onset (CO) blood culture testing intensity, and hospital-onset (HO) testing intensity, and prevalence (all P < .001). In the complex model, CO bacteremia prevalence, HO testing intensity, and HO testing prevalence were the predictors most associated with HOB. The complex model demonstrated better model performance; 55% of hospitals that ranked in the highest quartile based on their raw rate shifted to a lower quartile when the SIR from the complex model was applied. CONCLUSIONS: Hospital descriptors, aggregate patient characteristics, community bacteremia and/or fungemia burden, and clinical blood-culture testing practices influence rates of HOB. Benchmarking an HOB metric is feasible and should endeavor to include both facility and clinical variables.

      2. Comparison of the risk of recurrent Clostridioides difficile infections among patients in 2018 versus 2013
        Guh AY, Yi SH, Baggs J, Winston L, Parker E, Johnston H, Basiliere E, Olson D, Fridkin SK, Mehta N, Wilson L, Perlmutter R, Holzbauer SM, D'Heilly P, Phipps EC, Flores KG, Dumyati GK, Hatwar T, Pierce R, Ocampo VL, Wilson CD, Watkins JJ, Korhonen L, Paulick A, Adamczyk M, Gerding DN, Reddy SC.
        Open Forum Infect Dis. 2022 Sep;9(9):ofac422.
        Among persons with an initial Clostridioides difficile infection (CDI) across 10 US sites in 2018 compared with 2013, 18.3% versus 21.1% had ≥1 recurrent CDI (rCDI) within 180 days. We observed a 16% lower adjusted risk of rCDI in 2018 versus 2013 (P < .0001).

    • Immunity and Immunization
      1. COVID-19 vaccine effectiveness during a prison outbreak when Omicron was the dominant circulating variant-Zambia, December 2021
        Simwanza J, Hines JZ, Sinyange D, Sinyange N, Mulenga C, Hanyinza S, Sakubita P, Langa N, Nowa H, Gardner P, Saasa N, Chitempa G, Simpungwe J, Malambo W, Hamainza B, Chipimo PJ, Kapata N, Kapina M, Musonda K, Liwewe M, Mwale C, Fwoloshi S, Mulenga LB, Agolory S, Mukonka V, Chilengi R.
        Am J Trop Med Hyg. 2022 Sep 12.
        During a COVID-19 outbreak in a prison in Zambia from December 14 to 19, 2021, a case-control study was done to measure vaccine effectiveness (VE) against infection and symptomatic infection, when the Omicron variant was the dominant circulating variant. Among 382 participants, 74.1% were fully vaccinated, and the median time since full vaccination was 54 days. There were no hospitalizations or deaths. COVID-19 VE against any SARS-CoV-2 infection was 64.8%, and VE against symptomatic SARS-CoV-2 infection was 72.9%. COVID-19 vaccination helped protect incarcerated persons against SARS-CoV-2 infection during an outbreak while Omicron was the dominant variant in Zambia. These findings provide important local evidence that might be used to increase COVID-19 vaccination in Zambia and other countries in Africa.

      2. Fecal shedding of 2 novel live attenuated oral poliovirus type 2 vaccine candidates by healthy infants administered bivalent oral poliovirus vaccine/inactivated poliovirus vaccine: 2 randomized clinical trials
        Gast C, Bandyopadhyay AS, Sáez-Llorens X, De Leon T, DeAntonio R, Jimeno J, Aguirre G, McDuffie LM, Coffee E, Mathis DL, Oberste MS, Weldon WC, Konopka-Anstadt JL, Modlin J, Bachtiar NS, Fix A, Konz J, Clemens R, Costa Clemens SA, Rüttimann R.
        J Infect Dis. 2022 Sep 13;226(5):852-861.
        BACKGROUND: Primary intestinal immunity through viral replication of live oral vaccine is key to interrupt poliovirus transmission. We assessed viral fecal shedding from infants administered Sabin monovalent poliovirus type 2 vaccine (mOPV2) or low and high doses of 2 novel OPV2 (nOPV2) vaccine candidates. METHODS: In 2 randomized clinical trials in Panama, a control mOPV2 study (October 2015 to April 2016) and nOPV2 study (September 2018 to October 2019), 18-week-old infants vaccinated with bivalent oral poliovirus vaccine/inactivated poliovirus vaccine received 1 or 2 study vaccinations 28 days apart. Stools were assessed for poliovirus RNA by polymerase chain reaction (PCR) and live virus by culture for 28 days postvaccination. RESULTS: Shedding data were available from 621 initially reverse-transcription PCR-negative infants (91 mOPV2, 265 nOPV2-c1, 265 nOPV2-c2 recipients). Seven days after dose 1, 64.3% of mOPV2 recipients and 31.3%-48.5% of nOPV2 recipients across groups shed infectious type 2 virus. Respective rates 7 days after dose 2 decreased to 33.3% and 12.9%-22.7%, showing induction of intestinal immunity. Shedding of both nOPV2 candidates ceased at similar or faster rates than mOPV2. CONCLUSIONS: Viral shedding of either nOPV candidate was similar or decreased relative to mOPV2, and all vaccines showed indications that the vaccine virus was replicating sufficiently to induce primary intestinal mucosal immunity.

      3. COVID-19-associated hospitalizations among vaccinated and unvaccinated adults 18 years or older in 13 US States, January 2021 to April 2022
        Havers FP, Pham H, Taylor CA, Whitaker M, Patel K, Anglin O, Kambhampati AK, Milucky J, Zell E, Moline HL, Chai SJ, Kirley PD, Alden NB, Armistead I, Yousey-Hindes K, Meek J, Openo KP, Anderson EJ, Reeg L, Kohrman A, Lynfield R, Como-Sabetti K, Davis EM, Cline C, Muse A, Barney G, Bushey S, Felsen CB, Billing LM, Shiltz E, Sutton M, Abdullah N, Talbot HK, Schaffner W, Hill M, George A, Hall AJ, Bialek SR, Murthy NC, Murthy BP, McMorrow M.
        JAMA Intern Med. 2022 Sep 8.
        IMPORTANCE: Understanding risk factors for hospitalization in vaccinated persons and the association of COVID-19 vaccines with hospitalization rates is critical for public health efforts to control COVID-19. OBJECTIVE: To determine characteristics of COVID-19-associated hospitalizations among vaccinated persons and comparative hospitalization rates in unvaccinated and vaccinated persons. DESIGN, SETTING, AND PARTICIPANTS: From January 1, 2021, to April 30, 2022, patients 18 years or older with laboratory-confirmed SARS-CoV-2 infection were identified from more than 250 hospitals in the population-based COVID-19-Associated Hospitalization Surveillance Network. State immunization information system data were linked to cases, and the vaccination coverage data of the defined catchment population were used to compare hospitalization rates in unvaccinated and vaccinated individuals. Vaccinated and unvaccinated patient characteristics were compared in a representative sample with detailed medical record review; unweighted case counts and weighted percentages were calculated. EXPOSURES: Laboratory-confirmed COVID-19-associated hospitalization, defined as a positive SARS-CoV-2 test result within 14 days before or during hospitalization. MAIN OUTCOMES AND MEASURES: COVID-19-associated hospitalization rates among vaccinated vs unvaccinated persons and factors associated with COVID-19-associated hospitalization in vaccinated persons were assessed. RESULTS: Using representative data from 19 509 hospitalizations (see Table 1 for demographic information), monthly COVID-19-associated hospitalization rates ranged from 3.5 times to 17.7 times higher in unvaccinated persons than vaccinated persons regardless of booster dose status. From January to April 2022, when the Omicron variant was predominant, hospitalization rates were 10.5 times higher in unvaccinated persons and 2.5 times higher in vaccinated persons with no booster dose, respectively, compared with those who had received a booster dose. Among sampled cases, vaccinated hospitalized patients with COVID-19 were older than those who were unvaccinated (median [IQR] age, 70 [58-80] years vs 58 [46-70] years, respectively; P < .001) and more likely to have 3 or more underlying medical conditions (1926 [77.8%] vs 4124 [51.6%], respectively; P < .001). CONCLUSIONS AND RELEVANCE: In this cross-sectional study of US adults hospitalized with COVID-19, unvaccinated adults were more likely to be hospitalized compared with vaccinated adults; hospitalization rates were lowest in those who had received a booster dose. Hospitalized vaccinated persons were older and more likely to have 3 or more underlying medical conditions and be long-term care facility residents compared with hospitalized unvaccinated persons. The study results suggest that clinicians and public health practitioners should continue to promote vaccination with all recommended doses for eligible persons.

      4. Infectious viral shedding of SARS-CoV-2 Delta following vaccination: A longitudinal cohort study
        Garcia-Knight M, Anglin K, Tassetto M, Lu S, Zhang A, Goldberg SA, Catching A, Davidson MC, Shak JR, Romero M, Pineda-Ramirez J, Diaz-Sanchez R, Rugart P, Donohue K, Massachi J, Sans HM, Djomaleu M, Mathur S, Servellita V, McIlwain D, Gaudiliere B, Chen J, Martinez EO, Tavs JM, Bronstone G, Weiss J, Watson JT, Briggs-Hagen M, Abedi GR, Rutherford GW, Deeks SG, Chiu C, Saydah S, Peluso MJ, Midgley CM, Martin JN, Andino R, Kelly JD.
        PLoS Pathog. 2022 Sep 12;18(9):e1010802.
        The impact of vaccination on SARS-CoV-2 infectiousness is not well understood. We compared longitudinal viral shedding dynamics in unvaccinated and fully vaccinated adults. SARS-CoV-2-infected adults were enrolled within 5 days of symptom onset and nasal specimens were self-collected daily for two weeks and intermittently for an additional two weeks. SARS-CoV-2 RNA load and infectious virus were analyzed relative to symptom onset stratified by vaccination status. We tested 1080 nasal specimens from 52 unvaccinated adults enrolled in the pre-Delta period and 32 fully vaccinated adults with predominantly Delta infections. While we observed no differences by vaccination status in maximum RNA levels, maximum infectious titers and the median duration of viral RNA shedding, the rate of decay from the maximum RNA load was faster among vaccinated; maximum infectious titers and maximum RNA levels were highly correlated. Furthermore, amongst participants with infectious virus, median duration of infectious virus detection was reduced from 7.5 days (IQR: 6.0-9.0) in unvaccinated participants to 6 days (IQR: 5.0-8.0) in those vaccinated (P = 0.02). Accordingly, the odds of shedding infectious virus from days 6 to 12 post-onset were lower among vaccinated participants than unvaccinated participants (OR 0.42 95% CI 0.19-0.89). These results indicate that vaccination had reduced the probability of shedding infectious virus after 5 days from symptom onset.

      5. BACKGROUND: New strategies to increase measles and rubella vaccine coverage, particularly in low- and middle-income countries, are needed if elimination goals are to be achieved. With this regard, measles and rubella vaccine microneedle patches (MRV-MNP), in which the vaccine is embedded in dissolving microneedles, offer several potential advantages over subcutaneous delivery. These include ease of administration, increased thermostability, an absence of sharps waste, reduced overall costs and pain-free administration. This trial will provide the first clinical trial data on MRV-MNP use and the first clinical vaccine trial of MNP technology in children and infants. METHODS: This is a phase 1/2, randomized, active-controlled, double-blind, double-dummy, age de-escalation trial. Based on the defined eligibility criteria for the trial, including screening laboratory investigations, 45 adults [18-40 years] followed by 120 toddlers [15-18 months] and 120 infants [9-10 months] will be enrolled in series. To allow double-blinding, participants will receive either the MRV-MNP and a placebo (0.9% sodium chloride) subcutaneous (SC) injection or a placebo MNP and the MRV by SC injection (MRV-SC). Local and systemic adverse event data will be collected for 14 days following study product administration. Safety laboratories will be repeated on day 7 and, in the adult cohort alone, on day 14. Unsolicited adverse events including serious adverse events will be collected until the final study visit for each participant on day 180. Measles and rubella serum neutralizing antibodies will be measured at baseline, on day 42 and on day 180. Cohort progression will be dependent on review of the unblinded safety data by an independent data monitoring committee. DISCUSSION: This trial will provide the first clinical data on the use of a MNP to deliver the MRV and the first data on the use of MNPs in a paediatric population. It will guide future product development decisions for what may be a key technology for future measles and rubella elimination. TRIAL REGISTRATION: Pan-African Clinical Trials Registry 202008836432905 . CLINICALTRIALS: gov NCT04394689.

    • Informatics
      1. Objectives. To examine the impact of racial/ethnic coding strategies on the esti-mated prevalence of risk behaviors among American Indian/Alaska Native (AI/AN) high school students. Methods. Data from the national Youth Risk Behavior Survey (2017 and 2019) were analyzed (N=28,422). Racial/ethnic data were coded to identify “Multiracial/ ethnic AI/AN students” and “AI/AN alone students.” The prevalence of persistent feelings of sadness or hopelessness, suicidality, and violence victimization were compared across the coding schemes and with non-Hispanic White students. Results. Of students who self-identified as AI/AN, one in six (18%) were AI/AN alone. The prevalence of many health risk behaviors was significantly higher among AI/AN students than non-Hispanic/Latino White students. The precision of the risk behavior prevalence estimates, however, varied considerably. Conclusion. How racial/ethnic data were coded affected the precision of calculations of risk behavior prevalence among AI/AN students, who are often multiracial and of Hispanic/ Latino ethnicity. © Meharry Medical College.

      2. Benchmark datasets for SARS-CoV-2 surveillance bioinformatics
        Xiaoli L, Hagey JV, Park DJ, Gulvik CA, Young EL, Alikhan NF, Lawsin A, Hassell N, Knipe K, Oakeson KF, Retchless AC, Shakya M, Lo CC, Chain P, Page AJ, Metcalf BJ, Su M, Rowell J, Vidyaprakash E, Paden CR, Huang AD, Roellig D, Patel K, Winglee K, Weigand MR, Katz LS.
        PeerJ. 2022 ;10:e13821.
        BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), has spread globally and is being surveilled with an international genome sequencing effort. Surveillance consists of sample acquisition, library preparation, and whole genome sequencing. This has necessitated a classification scheme detailing Variants of Concern (VOC) and Variants of Interest (VOI), and the rapid expansion of bioinformatics tools for sequence analysis. These bioinformatic tools are means for major actionable results: maintaining quality assurance and checks, defining population structure, performing genomic epidemiology, and inferring lineage to allow reliable and actionable identification and classification. Additionally, the pandemic has required public health laboratories to reach high throughput proficiency in sequencing library preparation and downstream data analysis rapidly. However, both processes can be limited by a lack of a standardized sequence dataset. METHODS: We identified six SARS-CoV-2 sequence datasets from recent publications, public databases and internal resources. In addition, we created a method to mine public databases to identify representative genomes for these datasets. Using this novel method, we identified several genomes as either VOI/VOC representatives or non-VOI/VOC representatives. To describe each dataset, we utilized a previously published datasets format, which describes accession information and whole dataset information. Additionally, a script from the same publication has been enhanced to download and verify all data from this study. RESULTS: The benchmark datasets focus on the two most widely used sequencing platforms: long read sequencing data from the Oxford Nanopore Technologies platform and short read sequencing data from the Illumina platform. There are six datasets: three were derived from recent publications; two were derived from data mining public databases to answer common questions not covered by published datasets; one unique dataset representing common sequence failures was obtained by rigorously scrutinizing data that did not pass quality checks. The dataset summary table, data mining script and quality control (QC) values for all sequence data are publicly available on GitHub: https://github.com/CDCgov/datasets-sars-cov-2. DISCUSSION: The datasets presented here were generated to help public health laboratories build sequencing and bioinformatics capacity, benchmark different workflows and pipelines, and calibrate QC thresholds to ensure sequencing quality. Together, improvements in these areas support accurate and timely outbreak investigation and surveillance, providing actionable data for pandemic management. Furthermore, these publicly available and standardized benchmark data will facilitate the development and adjudication of new pipelines.

    • Injury and Violence
      1. Violence exposure among adolescent boys and young men in Colombia with a lifetime history of transactional sex
        Meinhart M, Seff I, Villaveces A, Roa AH, Stark L.
        J Adolesc Health. 2022 Sep 7.
        PURPOSE: There is a paucity of research examining the contextual factors that shape the violence experienced by those engaged in transactional sex, particularly among adolescent boys and young men. Recognizing the acute vulnerability among youth engaged in transactional sex, this analysis examined the associations between lifetime transactional sex and experience of violence among 13- to 24-year-old males. METHODS: Using data from two strata of the 2018 Violence Against Children and Youth Survey from Colombia, logistic regressions were used to estimate the association between engagement in transactional sex and violence exposure. Three groups of violence outcomes were examined: violence victimization, violence perpetration, and witnessing violence. RESULTS: Violence victimization and witnessing violence were widespread. Adolescent boys and young men with a lifetime history of transactional sex were significantly more likely to experience violence victimization than those without a lifetime history of transactional sex, particularly intimate partner violence (adjusted odds ratio [aOR]: 5.23 and 5.41) and caregiver emotional violence (aOR: 7.23 and 8.74). In the national and priority samples respectively, those with a lifetime history of transactional sex were also significantly more likely to witness violence within the home (aOR: 4.42 and 4.99) and outside of the home (aOR: 7.24 and 28.32). DISCUSSION: Although research is needed to determine causal pathways, our findings highlight the ubiquity of violence and the criticality of supporting this group of adolescent boys and young men. Interventions for those with a history of transactional sex should address factors that may contribute to drivers of violence and transactional sex.

      2. The impact of the COVID-19 pandemic on the needs and lived experiences of intimate partner violence survivors in the United States: Advocate perspectives
        Ragavan MI, Risser L, Duplessis V, DeGue S, Villaveces A, Hurley TP, Chang J, Miller E, Randell KA.
        Violence Against Women. 2022 Oct;28(12-13):3114-3134.
        We explored the challenges and lived experiences of intimate partner violence (IPV) survivors during the COVID-19 pandemic by interviewing 53 U.S.-based IPV advocates between June and November 2020. Advocates described how the COVID-19 pandemic limited survivors' abilities to meet their basic needs. The pandemic was also described as being used by abusive partners to perpetrate control and has created unique safety and harm reduction challenges. IPV survivors experienced compounding challenges due to structural inequities. IPV must be considered by local, state, and federal governments when developing disaster planning policies and practices, including in the context of pandemics.

    • Laboratory Sciences
      1. Comparative analysis of three multiplex platforms for the detection of respiratory viral pathogens
        Banerjee D, Hassan F, Avadhanula V, Piedra PA, Boom J, Sahni LC, Weinberg GA, Lindstrom S, Rha B, Harrison CJ, Selvarangan R.
        J Clin Virol. 2022 Aug 31;156:105274.
        BACKGROUND: Acute viral respiratory infections are a major health burden in children worldwide. In recent years, rapid and sensitive multiplex nucleic acid amplification tests (NAATs) have replaced conventional methods for routine virus detection in the clinical laboratory. OBJECTIVE/STUDY DESIGN: We compared BioFire® FilmArray® Respiratory Panel (FilmArray V1.7), Luminex NxTag® Respiratory Pathogen Panel (NxTag RPP) and Applied Biosystems TaqMan Array Card (TAC) for the detection of eight viruses in pediatric respiratory specimens. Results from the three platforms were analyzed with a single-plex real-time RT-PCR (rRT-PCR) assay for each virus. RESULTS: Of the 170/210 single-plex virus-positive samples, FilmArray detected a virus in 166 (97.6%), TAC in 163 (95.8%) and NxTag RPP in 160 (94.1%) samples. The Positive Percent Agreement (PPA) of FilmArray, NxTag RPP and TAC was highest for influenza B (100%, 100% and 95.2% respectively) and lowest for seasonal coronaviruses on both FilmArray (90.2%) and NxTag RPP (81.8%), and for parainfluenza viruses 1- 4 on TAC (84%). The Negative Percent Agreement (NPA) was lowest for rhinovirus/enterovirus (92.9%, 96.7% and 97.3%) on FilmArray, NxTag RPP and TAC respectively. NPA for all three platforms was highest (100%) for both parainfluenza viruses 1- 4 and influenza A and B, and 100% for human metapneumovirus with TAC as well. CONCLUSION: All three multiplex platforms displayed high overall agreement (>90%) and high NPA (>90%), while PPA was pathogen dependent and varied among platforms; high PPA (>90%) was observed for FilmArray for all eight viruses, TAC for six viruses and NxTag RPP for 4 viruses.

      2. Inductively coupled plasma mass spectrometry (ICP-MS) has proven to be an excellent analytical technique with high sensitivity for detecting low levels of long-lived radionuclides, such as thorium. However, the high-sensitivity technique increases the memory effect of thorium. This study developed a rapid, high-throughput, simple method for measuring thorium in urine using quadrupole inductively coupled plasma mass spectrometry (Q-ICP-MS). Replacing the commonly used hazardous hydrofluoric acid with a rinse solution of 0.025 mol/L oxalic acid and 5% (v/v) nitric acid eliminated the memory effect of thorium. 233U was used as internal standard in this study. The limit of detection (LOD) for thorium in this study is 0.77 ng/L, which is comparable to those of reported methods using more sophisticated and expensive sector field inductively coupled plasma mass spectrometry (SF-ICP-MS). This proposed method can determine thorium concentrations in urine in both occupationally exposed workers and populations that live in areas with high background levels of thorium. © 2022, Akadémiai Kiadó, Budapest, Hungary.

    • Occupational Safety and Health
      1. Self-reported exposure to hazards and mitigation strategies among oil and gas extraction workers in 3 U.S. states
        Wingate KC, Scott KA, Pratt S, King B, Esswein EJ, Ramirez-Cardenas A, Snawder J, Hagan-Haynes K.
        J Occup Environ Hyg. 2022 Sep 12:1-22.
        Numerous health and safety hazards exist at U.S. onshore oil and gas extraction worksites. Higher fatal injury rates have been reported among drilling and servicing companies, which are more likely to employ workers in construction and extraction occupations, compared to operators that employ more workers in management and office and administrative support roles. However, there is little information describing the extent to which workers encounter these hazards, are provided hazard mitigation strategies by their employers, or use personal protective equipment (PPE). A cross-sectional survey of 472 U.S. oil and gas extraction workers was conducted to identify and characterize factors related to on-the-job fatalities, injuries, and illnesses and determine the health and safety concerns of workers. Workers were employed by servicing companies (271/472, 57.4%), drilling contractors (106/472, 22.5%), and operators (95/472, 20.1%). The likelihood of contact with hazardous substances varied by substance and company type. Drilling and servicing employees had significantly higher odds of self-reported contact with pipe dope (OR(drilling)=10.07, 95% CI: 1.74-63.64; OR(servicing)=5.95, 95% CI: 2.18-18.34), diesel exhaust (OR(drilling)=2.28, 95% CI: 1.15-5.05; OR(servicing)=4.93, 95% CI: 2.73-10.32), and drilling mud (OR(drilling)=24.36, 95% CI: 4.45-144.69; OR(servicing)=3.48, 95% CI: 1.24-12.20), compared to operators. Safety policies, programs, and trainings were commonly reported by workers, although substance-specific training (e.g., respirable crystalline silica hazards) was less common. Differences in self-reported employer PPE requirements and worker use of PPE when needed or required for safety highlight a need for novel strategies to improve use of PPE. Overall, this study highlights differences in work conditions by company type and uncovers gaps in employer administrative controls and PPE use.

    • Physical Activity
      1. Changes in physical activity and sedentary time in United States adults in response to COVID-19
        Matthews CE, Saint-Maurice P, Fulton JE, Patel S, Loftfield E, Sampson JN, Keadle SK, Berrigan D.
        PLoS One. 2022 ;17(9):e0273919.
        Physical activity is associated lower risk for a broad range of non-communicable diseases and early mortality, and even small changes in daily activity levels could have a profound effect on public health at the population level. The COVID-19 pandemic reshaped daily life for United States (US) adults resulting in reductions in physical activity early in the pandemic, but its longer-term effects on daily activities are unknown. To examine the longer-term impact of the pandemic on daily activity levels, we conducted a nationwide longitudinal study of 1,635 adults (20-75 years) in AmeriSpeak. Previous-day recalls of time-use, sedentary time, and physical activity were completed on randomly selected days in Fall 2019 (pre-pandemic) and Fall 2020. Overall, US adults reported less time in transportation (-0.47 hrs/d), more total discretionary time (0.40 hrs/d), but no changes in total sedentary time (0.10 hrs/d) or leisure-time physical activity (-0.06 hrs/d). Women reported significantly less total activity (-0.36 hrs/d) and participants with children < 13 yrs reported more sedentary time (0.60 to 0.82 hrs/d) and less moderate-to-vigorous intensity activity (-0.84 to -0.72 hrs/d). Adults without children reported no changes in sedentary time (0.02 hrs/d) or moderate-vigorous intensity activity (-0.06 hrs/d). Adults who started working from home reported no changes in physical activity, but they were among the most sedentary and least active population groups at both timepoints. Our findings describe the complex inter-play between competing behaviors as time-use demands have changed in response to the pandemic, particularly for adults with younger children. Many US adults are likely to continue working from home; therefore, implementation of evidence-based approaches to increase physical activity and reduce sedentary time in this growing population subgroup appears warranted.

    • Substance Use and Abuse
      1. Impact of Massachusetts law prohibiting flavored tobacco products sales on cross-border cigarette sales
        Ali FR, King BA, Seaman EL, Vallone D, Schillo B.
        PLoS One. 2022 ;17(9):e0274022.
        BACKGROUND: In June 2020, Massachusetts implemented a law prohibiting the sale of all flavored tobacco products, including menthol cigarettes. This law was associated with significant declines in overall cigarette and menthol cigarette sales in Massachusetts, however it is unknown whether the law has increased cross-border sales in neighboring states where menthol cigarettes are still sold. METHODS: U.S. cigarette retail scanner data were licensed from the IRi Company. Cigarette pack sales were summed in 4-week periods during January 2020-December 2021 (n = 832). Outcomes were state-level pack sales per 1000 population, overall and by flavor status (menthol and non-flavored). A difference-in-differences analysis was used to examine adjusted sales for Massachusetts border states (New Hampshire, Connecticut, Vermont, and Rhode Island) before (January 2020-May 2020) and after (June 2020-December 2021) the Massachusetts's law, compared to 28 non-border states. Control variables included state and time fixed effects; real price per pack; tobacco control policies; COVID-19 cases and deaths, and related statewide closure; and state sociodemographic characteristics. RESULTS: Following the law, unadjusted sales of menthol, non-flavored, and overall cigarettes trended upward in border states; however, these increases were not statistically significant or different from sales patterns in non-border states. This finding persisted after accounting for product prices, tobacco control policies, the COVID-19 pandemic, sociodemographic factors, and fixed effects. CONCLUSION: Laws prohibiting the sale of flavored tobacco products, including menthol products, reduce access to these products, while having no significant impact on cross-border sales in neighboring states where menthol cigarettes are sold.

    • Zoonotic and Vectorborne Diseases
      1. Prevalence of microcephaly and Zika virus infection in a pregnancy cohort in Kenya, 2017-2019
        Osoro E, Inwani I, Mugo C, Hunsperger E, Verani JR, Omballa V, Wamalwa D, Rhee C, Nduati R, Kinuthia J, Jin H, Okutoyi L, Mwaengo D, Maugo B, Otieno NA, Mirieri H, Shabibi M, Munyua P, Njenga MK, Widdowson MA.
        BMC Med. 2022 Sep 14;20(1):291.
        BACKGROUND: Zika virus (ZIKV), first discovered in Uganda in 1947, re-emerged globally in 2013 and was later associated with microcephaly and other birth defects. We determined the incidence of ZIKV infection and its association with adverse pregnancy and fetal outcomes in a pregnancy cohort in Kenya. METHODS: From October 2017 to July 2019, we recruited and followed up women aged ≥ 15 years and ≤ 28 weeks pregnant in three hospitals in coastal Mombasa. Monthly follow-up included risk factor questions and a blood sample collected for ZIKV serology. We collected anthropometric measures (including head circumference), cord blood, venous blood from newborns, and any evidence of birth defects. Microcephaly was defined as a head circumference (HC) < 2 standard deviations (SD) for sex and gestational age. Severe microcephaly was defined as HC < 3 SD for sex and age. We tested sera for anti-ZIKV IgM antibodies using capture enzyme-linked immunosorbent assay (ELISA) and confirmed positives using the plaque reduction neutralization test (PRNT(90)) for ZIKV and for dengue (DENV) on the samples that were ZIKV neutralizing antibody positive. We collected blood and urine from participants reporting fever or rash for ZIKV testing. RESULTS: Of 2889 pregnant women screened for eligibility, 2312 (80%) were enrolled. Of 1916 recorded deliveries, 1816 (94.6%) were live births and 100 (5.2%) were either stillbirths or spontaneous abortions (< 22 weeks of gestation). Among 1236 newborns with complete anthropometric measures, 11 (0.9%) had microcephaly and 3 (0.2%) had severe microcephaly. A total of 166 (7.2%) participants were positive for anti-ZIKV IgM, 136 of whom became seropositive during follow-up. Among the 166 anti-ZIKV IgM positive, 3 and 18 participants were further seropositive for ZIKV and DENV neutralizing antibodies, respectively. Of these 3 and 18 pregnant women, one and 13 (72.2%) seroconverted with antibodies to ZIKV and DENV, respectively. All 308 samples (serum and urine samples collected during sick visits and samples that were anti-ZIKV IgM positive) tested by RT-PCR were negative for ZIKV. No adverse pregnancy or neonatal outcomes were reported among the three participants with confirmed ZIKV exposure. Among newborns from pregnant women with DENV exposure, four (22.2%) were small for gestational age and one (5.6%) had microcephaly. CONCLUSIONS: The prevalence of severe microcephaly among newborns in coastal Kenya was high relative to published estimates from facility-based studies in Europe and Latin America, but little evidence of ZIKV transmission. There is a need for improved surveillance for microcephaly and other congenital malformations in Kenya.

      2. Severe arboviral neuroinvasive disease in patients on rituximab therapy: A review
        Kapadia RK, Staples JE, Gill CM, Fischer M, Khan E, Laven JJ, Panella A, Velez JO, Hughes HR, Brault A, Pastula DM, Gould CV.
        Clin Infect Dis. 2022 Sep 14.
        With increasing use of rituximab and other B-cell depleting monoclonal antibodies for multiple indications, infectious complications are being recognized. We summarize clinical findings of patients on rituximab with arboviral diseases identified through literature review or consultation with the Centers for Disease Control and Prevention. We identified 21 patients on recent rituximab therapy who were diagnosed with an arboviral disease caused by West Nile, tick-borne encephalitis, eastern equine encephalitis, Cache Valley, Jamestown Canyon, and Powassan viruses. All reported patients had neuroinvasive disease. The diagnosis of arboviral infection required molecular testing in 20 (95%) patients. Median illness duration was 36 days (range, 12 days-1 year) and 15/19 (79%) patients died from their illness. Patients on rituximab with arboviral disease can have a severe or prolonged course with an absence of serologic response. Patients should be counseled about mosquito and tick bite prevention when receiving rituximab and other B-cell depleting therapies.

      3. Pathogenesis and transmissibility of North American highly pathogenic avian influenza a(H5N1) virus in ferrets
        Pulit-Penaloza JA, Belser JA, Brock N, Thakur PB, Tumpey TM, Maines TR.
        Emerg Infect Dis. 2022 Sep;28(9):1913-1915.
        Highly pathogenic avian influenza A(H5N1) viruses have spread rapidly throughout North American flyways in recent months, affecting wild birds in over 40 states. We evaluated the pathogenicity and transmissibility of a representative virus using a ferret model and examined replication kinetics of this virus in human respiratory tract cells.

      4. A forty-year review of Rocky Mountain spotted fever cases in California shows clinical and epidemiologic changes
        Kjemtrup AM, Padgett K, Paddock CD, Messenger S, Hacker JK, Feiszli T, Melgar M, Metzger ME, Hu R, Kramer VL.
        PLoS Negl Trop Dis. 2022 Sep 15;16(9):e0010738.
        Rocky Mountain spotted fever (RMSF) is a life-threatening tick-borne disease documented in North, Central, and South America. In California, RMSF is rare; nonetheless, recent fatal cases highlight ecological cycles of the two genera of ticks, Dermacentor and Rhipicephalus, known to transmit the disease. These ticks occur in completely different habitats (sylvatic and peridomestic, respectively) resulting in different exposure risks for humans. This study summarizes the demographic, exposure, and clinical aspects associated with the last 40 years of reported RMSF cases to the California Department of Public Health (CDPH). Seventy-eight RMSF cases with onsets from 1980 to 2019 were reviewed. The incidence of RMSF has risen in the last 20 years from 0.04 cases per million to 0.07 cases per million (a two-fold increase in reports), though the percentage of cases that were confirmed dropped significantly from 72% to 25% of all reported cases. Notably, Hispanic/Latino populations saw the greatest rise in incidence. Cases of RMSF in California result from autochthonous and out-of-state exposures. During the last 20 years, more cases reported exposure in Southern California or Mexico than in the previous 20 years. The driver of these epidemiologic changes is likely the establishment and expansion of Rhipicephalus sanguineus sensu lato ticks in Southern California and on-going outbreaks of RMSF in northern Mexico. Analysis of available electronically reported clinical data from 2011 to 2019 showed that 57% of reported cases presented with serious illness requiring hospitalization with a 7% mortality. The difficulty in recognizing RMSF is due to a non-specific clinical presentation; however, querying patients on the potential of tick exposure in both sylvatic and peridomestic environments may facilitate appropriate testing and treatment.

      5. Pathology and epidemiology of fatal toxoplasmosis in free-ranging marmosets (Callithrix spp.) from the Brazilian Atlantic forest
        Rodrigues Oliveira A, Ritter JM, Oliveira Dos Santos D, Pizzolato de Lucena F, Aquino de Mattos S, Parente de Carvalho T, Bullock H, Giannini Alves Moreira L, Magalhães Arthuso Vasconcelos I, Barroso Costa F, Alves da Paixão T, Santos RL.
        PLoS Negl Trop Dis. 2022 Sep 15;16(9):e0010782.
        Toxoplasmosis is an important zoonotic disease that affects a wide range of warm-blooded host species. Neotropical primates (New World Primates; NWP) are highly susceptible, developing a lethal acute systemic disease. Toxoplasmosis in free-ranging NWP is poorly described, with only a few studies based on serosurveys. Herein we performed a retrospective study focusing on the epidemiology and pathology of toxoplasmosis among 1,001 free-ranging marmoset (Callithrix spp.) deaths from the Brazilian Atlantic Forest. This study included marmosets necropsied at the Instituto Municipal de Medicina Veterinária Jorge Vaitsman (IJV) from January 2017 to July 2019, which were found dead from all regions in the State of Rio de Janeiro. Histopathology, immunohistochemistry, and transmission electron microscopy were performed to better characterize toxoplasmosis in this free-ranging population. All samples were also tested for Yellow Fever Virus (YFV) RT-qPCR by the official diagnostic service. A total of 1,001 free-ranging marmosets were included in this study, with 16 (1.6%) cases of lethal Toxoplasma gondii infections identified both as individual cases and in outbreaks. Presence of infection was not associated with sex, age, geographical distribution, or year of death, and no co-infection with YFV was observed. The main pathological feature in these cases was random necrotizing hepatitis with detection of intralesional T. gondii zoites in all infected cases. Interstitial pneumonia rich in alveolar foamy macrophages and fibrin deposition, necrotizing myocarditis and necrotizing splenitis were also pathological features in affected marmosets. Therefore, toxoplasmosis was considered the cause of death in 1.6% of free-ranging marmosets in this retrospective series, including some cases associated with outbreaks. Necrotizing random hepatitis was a consistent pathological finding in affected cases and sampling of liver should be ensured from Callitrichid post mortem cases.


DISCLAIMER: Articles listed in the CDC Science Clips are selected by the Stephen B. Thacker CDC Library to provide current awareness of the public health literature. An article's inclusion does not necessarily represent the views of the Centers for Disease Control and Prevention nor does it imply endorsement of the article's methods or findings. CDC and DHHS assume no responsibility for the factual accuracy of the items presented. The selection, omission, or content of items does not imply any endorsement or other position taken by CDC or DHHS. Opinion, findings and conclusions expressed by the original authors of items included in the Clips, or persons quoted therein, are strictly their own and are in no way meant to represent the opinion or views of CDC or DHHS. References to publications, news sources, and non-CDC Websites are provided solely for informational purposes and do not imply endorsement by CDC or DHHS.