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Issue 22, June 29, 2021

CDC Science Clips: Volume 13, Issue 22, June 29, 2021

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

  1. Top Articles of the Week
    Selected weekly by a senior CDC scientist from the standard sections listed below.
    The names of CDC authors are indicated in bold text.
    • Chronic Diseases and Conditions
      • Case-control study in ALS using the National ALS Registry: lead and agricultural chemicals are potential risk factorsexternal icon
        Mitsumoto H, Garofalo DC, Gilmore M, Andrews L, Santella RM, Andrews H, McElhiney M, Murphy J, Nieves JW, Rabkin J, Hupf J, Horton DK, Mehta P, Factor-Litvak P.
        Amyotroph Lateral Scler Frontotemporal Degener. 2021 Jun 17:1-13.
        Objective: To identify occupational risk factors for ALS using well-characterized participants with ALS (P-ALS), sibling controls (S-controls), and matched population controls (P-controls) within the National ALS Registry. We also compared oxidative stress (OS) biomarkers between groups. Methods: P-ALS were recruited over 4 years. Demographic, socioeconomic, and medical data were ascertained from medical records and structured interviews. P-ALS were followed prospectively for 2 years or until death, whichever came sooner. S-controls and age-, sex-, race/ethnicity-, and residential location-matched P-controls were recruited over 3 years. Occupational exposure to lead and agricultural chemicals (ACs) were assigned by an occupational hygienist, blinded to case status. OS biomarkers in urine were measured. Results: P-ALS (mean age 62.8 years; 63% males) resided across the United States. Demographic and socioeconomic variables did not differ among P-ALS, S-controls, and P-controls. P-ALS were more likely to report occupations with exposure to lead (adjusted OR (aOR)=2.3, 95% CI 1.1, 4.6) and ACs (aOR = 2.4, 95% CI 1.2, 4.6) compared to pooled controls. Among those with occupations with exposure to both lead and ACs, aOR was 7.2 (95% CI 2.0, 26.1). Urinary 8-oxo-dG was significantly elevated among P-ALS (11.07 ± 5.42 ng/mL) compared to S-controls, P-controls, or pooled controls (pooled 7.43 ± 5.42 ng/mL; p < 0.0001) but was not associated with occupational exposure to either lead or ACs. Conclusions: Findings reveal increased risk of ALS diagnosis among those with occupational exposure to lead and ACs and increased OS biomarkers among cases compared to controls. OS may be an important pathogenic mechanism in ALS.

    • Communicable Diseases
      • Antibodies to SARS-CoV-2 in All of Us Research Program Participants, January 2-March 18, 2020external icon
        Althoff KN, Schlueter DJ, Anton-Culver H, Cherry J, Denny JC, Thomsen I, Karlson EW, Havers FP, Cicek MS, Thibodeau SN, Pinto LA, Lowy D, Malin BA, Ohno-Machado L, Williams C, Goldstein D, Kouame A, Ramirez A, Roman A, Sharpless NE, Gebo KA, Schully SD.
        Clin Infect Dis. 2021 Jun 15.
        BACKGROUND: With limited SARS-CoV-2 testing capacity in the US at the start of the epidemic (January - March), testing was focused on symptomatic patients with a travel history throughout February, obscuring the picture of SARS-CoV-2 seeding and community transmission. We sought to identify individuals with SARS-CoV-2 antibodies in the early weeks of the US epidemic. METHODS: All of Us study participants in all 50 US states provided blood specimens during study visits from January 2 to March 18, 2020. A participant was considered seropositive if they tested positive for SARS-CoV-2 immunoglobulin G (IgG) antibodies on the Abbott Architect SARS-CoV-2 IgG ELISA and the EUROIMMUN SARS-CoV-2 ELISA in a sequential testing algorithm. Sensitivity and specificity of the Abbott and EUROIMMUNE ELISAs and the net sensitivity and specificity of the sequential testing algorithm were estimated with 95% confidence intervals. RESULTS: The estimated sensitivity of Abbott and EUROIMMUN was 100% (107/107 [96.6%, 100%]) and 90.7% (97/107 [83.5%, 95.4%]), respectively. The estimated specificity of Abbott and EUROIMMUN was 99.5% (995/1,000 [98.8%, 99.8%]) and 99.7% (997/1,000 [99.1%, 99.9%), respectively. The net sensitivity and specificity of our sequential testing algorithm was 90.7% (97/107 [83.5%, 95.4%]) and 100.0% (1,000/1,000 [99.6%, 100%]), respectively. Of the 24,079 study participants with blood specimens from January 2 to March 18, 2020, 9 were seropositive, 7 of whom were seropositive prior to the first confirmed case in the states of Illinois, Massachusetts, Wisconsin, Pennsylvania, and Mississippi. CONCLUSIONS: Our findings indicate SARS-CoV-2 infections weeks prior to the first recognized cases in 5 US states.

      • Serologic Testing of US Blood Donations to Identify Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-Reactive Antibodies: December 2019-January 2020external icon
        Basavaraju SV, Patton ME, Grimm K, Rasheed MA, Lester S, Mills L, Stumpf M, Freeman B, Tamin A, Harcourt J, Schiffer J, Semenova V, Li H, Alston B, Ategbole M, Bolcen S, Boulay D, Browning P, Cronin L, David E, Desai R, Epperson M, Gorantla Y, Jia T, Maniatis P, Moss K, Ortiz K, Park SH, Patel P, Qin Y, Steward-Clark E, Tatum H, Vogan A, Zellner B, Drobeniuc J, Sapiano MR, Havers F, Reed C, Gerber S, Thornburg NJ, Stramer SL.
        Clin Infect Dis. 2021 Jun 15;72(12):e1004-e1009.
        BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), was first identified in Wuhan, China, in December 2019, with subsequent worldwide spread. The first US cases were identified in January 2020. METHODS: To determine if SARS-CoV-2-reactive antibodies were present in sera prior to the first identified case in the United States on 19 January 2020, residual archived samples from 7389 routine blood donations collected by the American Red Cross from 13 December 2019 to 17 January 2020 from donors resident in 9 states (California, Connecticut, Iowa, Massachusetts, Michigan, Oregon, Rhode Island, Washington, and Wisconsin) were tested at the Centers for Disease Control and Prevention for anti-SARS-CoV-2 antibodies. Specimens reactive by pan-immunoglobulin (pan-Ig) enzyme-linked immunosorbent assay (ELISA) against the full spike protein were tested by IgG and IgM ELISAs, microneutralization test, Ortho total Ig S1 ELISA, and receptor-binding domain/ACE2 blocking activity assay. RESULTS: Of the 7389 samples, 106 were reactive by pan-Ig. Of these 106 specimens, 90 were available for further testing. Eighty-four of 90 had neutralizing activity, 1 had S1 binding activity, and 1 had receptor-binding domain/ACE2 blocking activity >50%, suggesting the presence of anti-SARS-CoV-2-reactive antibodies. Donations with reactivity occurred in all 9 states. CONCLUSIONS: These findings suggest that SARS-CoV-2 may have been introduced into the United States prior to 19 January 2020.

    • Environmental Health
      • Maternal phthalate and phthalate alternative metabolites and urinary biomarkers of estrogens and testosterones across pregnancyexternal icon
        Pacyga DC, Gardiner JC, Flaws JA, Li Z, Calafat AM, Korrick SA, Schantz SL, Strakovsky RS.
        Environ Int. 2021 Jun 8;155:106676.
        BACKGROUND/OBJECTIVES: Pregnant women are ubiquitously exposed to phthalates from food packaging materials and personal care products. Phthalates alter estrogen and testosterone concentrations in experimental models, but their ability to impact these hormones in human pregnancy is not well characterized. METHODS: We recruited women ages 18-40 into the Illinois Kids Development Study (I-KIDS) in early pregnancy. Participants provided up to 5 first-morning urine samples across pregnancy (8-40 weeks gestation) that we pooled for quantification of 19 phthalate or phthalate alternative metabolites. Either individual (ng/mL) or molar sums (nmol/mL) of metabolites were used as exposure biomarkers. We summed urinary concentrations (ng/mL) of eight major estrogen (SumEstrogens) and two major testosterone (SumTestosterones) metabolites measured at median 13, 28, and 34 weeks gestation. We also estimated the ratio of estrogens-to-androgens. Linear mixed-effects models assessed relationships of phthalates/alternatives as continuous measures or as concentration quartiles with SumEstrogens, SumTestosterones, and the Estrogen/Androgen ratio in 434 women. In our models, we controlled for age, race, education, parity, smoking in the first trimester, pre-pregnancy body mass index, diet quality, conception season, fetal sex, and gestational age at hormone assessment. We also explored whether gestational age at hormone assessment or fetal sex modified these associations. All biomarkers and outcomes were specific gravity-adjusted, and continuous exposures and outcomes were also natural log-transformed. RESULTS: Most participants were non-Hispanic white (80.9%), college educated (82.2%), and had urinary phthalate/alternative metabolite concentrations similar to those of reproductive-aged U.S. women. Overall, select phthalate metabolites were positively associated with SumEstrogens and SumTestosterones, but negatively associated with the Estrogen/Androgen ratio. For example, SumEstrogens was 5.1% (95%CI: 1.8, 8.5) higher with every 2-fold increase in sum of di(2-ethylhexyl) phthalate metabolites, while SumTestosterones was 7.9% (95%CI: 1.0, 15.3) higher and Estrogen/Androgen ratio was -7.7% (95%CI: -13.6, -1.4) lower with every 2-fold increase in monoethyl phthalate. However, phthalate alternatives were only positively associated with SumEstrogens, which was 2.4% (95%CI: 0.4, 4.5) and 3.2% (95%CI: 0.7, 5.8) higher with every 2-fold increase in sum of di(isononyl) cyclohexane-1,2-dicarboxylate metabolites and sum of di(2-ethylhexyl) terephthalate metabolites, respectively. Gestational age- and fetal sex-specific associations were only consistently observed for associations of phthalates/alternatives with SumEstrogens, where associations were strongest in mid-to-late pregnancy in women carrying females. CONCLUSION: Phthalates/alternatives may impact gestational hormones, with potential for gestational age- and fetal sex-specific associations. Whether maternal urinary estrogens and testosterones mediate associations of phthalates/alternatives with pregnancy and fetal outcomes merits further investigation.

    • Health Economics
    • Healthcare Associated Infections
    • Immunity and Immunization
      • American College of Rheumatology Guidance for COVID-19 Vaccination in Patients With Rheumatic and Musculoskeletal Diseases: Version 2external icon
        Curtis JR, Johnson SR, Anthony DD, Arasaratnam RJ, Baden LR, Bass AR, Calabrese C, Gravallese EM, Harpaz R, Kroger A, Sadun RE, Turner AS, Williams EA, Mikuls TR.
        Arthritis Rheumatol. 2021 Jun 15.
        OBJECTIVE: To provide guidance to rheumatology providers on the use of coronavirus disease 2019 (COVID-19) vaccines for patients with rheumatic and musculoskeletal diseases (RMDs). METHODS: A task force was assembled that included 9 rheumatologists/immunologists, 2 infectious disease specialists, and 2 public health physicians. After agreeing on scoping questions, an evidence report was created that summarized the published literature and publicly available data regarding COVID-19 vaccine efficacy and safety, as well as literature for other vaccines in RMD patients. Task force members rated their agreement with draft consensus statements on a 9-point numerical scoring system, using a modified Delphi process and the RAND/University of California Los Angeles Appropriateness Method, with refinement and iteration over 2 sessions. Consensus was determined based on the distribution of ratings. RESULTS: Despite a paucity of direct evidence, 74 draft guidance statements were developed by the task force and agreed upon with consensus to provide guidance for use of the COVID-19 vaccines in RMD patients and to offer recommendations regarding the use and timing of immunomodulatory therapies around the time of vaccination. CONCLUSION: These guidance statements, made in the context of limited clinical data, are intended to provide direction to rheumatology health care providers on how to best use COVID-19 vaccines and to facilitate implementation of vaccination strategies for RMD patients.

    • Injury and Violence
      • Substance use and deaths by suicide: A latent class analysis of the National Violent Death Reporting Systemexternal icon
        Culbreth R, Swahn MH, Osborne M, Brandenberger K, Kota K.
        Prev Med. 2021 Jun 10:106682.
        Substance use is strongly associated with suicide completions. However, little is known about the patterns of substances used in suicide deaths. The purpose of this analysis is to determine latent classes of toxicology-reported substances among individuals who completed suicide. The sample consists of suicide victims in the National Violent Death Reporting System (NVDRS) during years 2003-2017 (n = 202,838). Toxicology reports were used to construct latent class analyses of substance use among suicide victims. Correlates for latent class membership included sex, race/ethnicity, previous experiences of child abuse, homelessness, and intimate partner violence (IPV) victimization. The majority of suicide victims were male (77.7%), straight/heterosexual (99.5%) and white (88.3%). The final unconditional model yielded a four-class model, including a "No substance/single substance use" class, an "Alcohol and other substance" class, a "Marijuana and other substance" class, and an "Opiate use" class. Compared to the reference class of "No substance/single substance," females were more likely than males to be classified in the "Alcohol and other substance" class, the "Multi-substance use" class, and the "Opiate use" class. Homelessness was associated with classification in the "Marijuana and other substance" class and the "Opiate use" class compared to the "No substance/single substance" class. IPV was associated with both polysubstance use classes ("Alcohol plus other substance" and "Marijuana plus other substance") along with the "Opiate use" class compared to the "No substance/single substance" class. These classes highlight profiles of suicide descendants and emphasize the importance of polysubstance use prevention among females, homeless individuals, and those who experience IPV.

    • Laboratory Sciences
    • Maternal and Child Health
      • Maternal Psychiatric Conditions, Treatment With Selective Serotonin Reuptake Inhibitors, and Neurodevelopmental Disordersexternal icon
        Ames JL, Ladd-Acosta C, Fallin MD, Qian Y, Schieve LA, DiGuiseppi C, Lee LC, Kasten EP, Zhou G, Pinto-Martin J, Howerton EM, Eaton CL, Croen LA.
        Biol Psychiatry. 2021 Apr 14.
        BACKGROUND: This study aims to clarify relationships of maternal psychiatric conditions and selective serotonin reuptake inhibitor (SSRI) use during preconception and pregnancy with risk of neurodevelopmental disorders in offspring. METHODS: We used data from the Study to Explore Early Development, a multisite case-control study conducted in the United States among children born between 2003 and 2011. Final study group classifications of autism spectrum disorder (ASD) (n = 1367), developmental delays or disorders (DDs) (n = 1750), and general population controls (n = 1671) were determined by an in-person standardized developmental assessment. Maternal psychiatric conditions and SSRI use during pregnancy were ascertained from both self-report and medical records. We used logistic regression to evaluate associations of ASD and DDs (vs. population controls) with maternal psychiatric conditions and SSRI treatment in pregnancy. To reduce confounding by indication, we also examined SSRI associations in analyses restricted to mothers with psychiatric conditions during pregnancy. RESULTS: Psychiatric conditions and SSRI use during pregnancy were significantly more common among mothers of children with either ASD or DDs than among population controls. Odds of ASD were similarly elevated among mothers with psychiatric conditions who did not use SSRIs during pregnancy (adjusted odds ratio 1.81, 95% confidence interval 1.44-2.27) as in mothers who did use SSRIs (adjusted odds ratio 2.05, 95% confidence interval 1.50-2.80). Among mothers with psychiatric conditions, SSRI use was not significantly associated with ASD in offspring (adjusted odds ratio 1.14, 95% confidence interval 0.80-1.62). Primary findings for DDs exhibited similar relationships to those observed with ASD. CONCLUSIONS: Maternal psychiatric conditions but not use of SSRIs during pregnancy were associated with increased risk of neurodevelopmental disorders in offspring.

    • Occupational Safety and Health
      • Characterizing exposures to flame retardants, dioxins, and furans among firefighters responding to controlled residential firesexternal icon
        Mayer AC, Fent KW, Chen IC, Sammons D, Toennis C, Robertson S, Kerber S, Horn GP, Smith DL, Calafat AM, Ospina M, Sjodin A.
        Int J Hyg Environ Health. 2021 Jun 10;236:113782.
        Firefighters may encounter items containing flame retardants (FRs), including organophosphate flame retardants (OPFRs) and polybrominated diphenyl ethers (PBDEs), during structure fires. This study utilized biological monitoring to characterize FR exposures in 36 firefighters assigned to interior, exterior, and overhaul job assignments, before and after responding to controlled residential fire scenarios. Firefighters provided four urine samples (pre-fire and 3-h, 6-h, and 12-h post-fire) and two serum samples (pre-fire and approximately 23-h post-fire). Urine samples were analyzed for OPFR metabolites, while serum samples were analyzed for PBDEs, brominated and chlorinated furans, and chlorinated dioxins. Urinary concentrations of diphenyl phosphate (DPhP), a metabolite of triphenyl phosphate (TPhP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP), a metabolite of tris(1,3-dichloro-2-propyl) phosphate (TDCPP), and bis(2-chloroethyl) phosphate (BCEtP), a metabolite of tris(2-chloroethyl) phosphate (TCEP), increased from pre-fire to 3-hr and 6-hr post-fire collection, but only the DPhP increase was statistically significant at a 0.05 level. The 3-hr and 6-hr post-fire concentrations of DPhP and BDCPP, as well as the pre-fire concentration of BDCPP, were statistically significantly higher than general population levels. BDCPP pre-fire concentrations were statistically significantly higher in firefighters who previously participated in a scenario (within the past 12 days) than those who were responding to their first scenario as part of the study. Similarly, firefighters previously assigned to interior job assignments had higher pre-fire concentrations of BDCPP than those previously assigned to exterior job assignments. Pre-fire serum concentrations of 2,3,4,7,8-pentachlorodibenzofuran (23478-PeCDF), a known human carcinogen, were also statistically significantly above the general population levels. Of the PBDEs quantified, only decabromodiphenyl ether (BDE-209) pre- and post-fire serum concentrations were statistically significantly higher than the general population. These results suggest firefighters absorbed certain FRs while responding to fire scenarios.

    • Parasitic Diseases
      • Detecting Malaria Hotspots in Haiti, a Low-Transmission Settingexternal icon
        Dismer AM, Lemoine JF, Baptiste MJ, Mace KE, Impoinvil D, Vanden Eng J, Chang MA.
        Am J Trop Med Hyg. 2021 Apr 19;104(6):2108-16.
        In 2006, Haiti committed to malaria elimination when the transmission was thought to be low, but before robust national parasite prevalence estimates were available. In 2011, the first national population-based survey confirmed the national malaria parasite prevalence was < 1%. In both 2014 and 2015, Haiti reported approximately 17,000 malaria cases identified passively at health facilities. To detect malaria transmission hotspots for targeting interventions, the National Malaria Control Program (NMCP) piloted an enhanced geographic information surveillance system in three departments with relatively high-, medium-, and low-transmission areas. From October 2014-September 2015, NMCP staff abstracted health facility records of confirmed malaria cases from 59 health facilities and geo-located patients' households. Household locations were aggregated to 1-km2 grid cells to calculate cumulative incidence rates (CIRs) per 1,000 persons. Spatial clustering of CIRs were tested using Getis-Ord Gi* analysis. Space-time permutation models searched for clusters up to 6 km in distance using a 1-month malaria transmission window. Of the 2,462 confirmed cases identified from health facility records, 58% were geo-located. Getis-Ord Gi* analysis identified 43 1-km2 hotspots in coastal and inland areas that overlapped primarily with 13 space-time clusters (size: 0.26-2.97 km). This pilot describes the feasibility of detecting malaria hotspots in resource-poor settings. More data from multiple years and serological household surveys are needed to assess completeness and hotspot stability. The NMCP can use these pilot methods and results to target foci investigations and malaria interventions more accurately.


  2. CDC Authored Publications
    The names of CDC authors are indicated in bold text.
    Articles published in the past 6-8 weeks authored by CDC or ATSDR staff.
    • Chronic Diseases and Conditions
      1. COVID-19 and Chronic Disease: The Impact Now and in the Futureexternal icon
        Hacker KA, Briss PA, Richardson L, Wright J, Petersen R.
        Prev Chronic Dis. 2021 Jun 17;18:E62.

      2. Differences in U.S. Rural-Urban Trends in Diabetes ABCS, 1999-2018external icon
        Mercado CI, McKeever Bullard K, Gregg EW, Ali MK, Saydah SH, Imperatore G.
        Diabetes Care. 2021 Jun 14.
        OBJECTIVE: To examine changes in and the relationships between diabetes management and rural and urban residence. RESEARCH DESIGN AND METHODS: Using National Health and Nutrition Examination Survey (1999-2018) data from 6,372 adults aged ≥18 years with self-reported diagnosed diabetes, we examined poor ABCS: A1C >9% (>75 mmol/mol), Blood pressure (BP) ≥140/90 mmHg, Cholesterol (non-HDL) ≥160 mg/dL (≥4.1 mmol/L), and current Smoking. We compared odds of urban versus rural residents (census tract population size ≥2,500 considered urban, otherwise rural) having poor ABCS across time (1999-2006, 2007-2012, and 2013-2018), overall and by sociodemographic and clinical characteristics. RESULTS: During 1999-2018, the proportion of U.S. adults with diabetes residing in rural areas ranged between 15% and 19.5%. In 1999-2006, there were no statistically significant rural-urban differences in poor ABCS. However, from 1999-2006 to 2013-2018, there were greater improvements for urban adults with diabetes than for rural for BP ≥140/90 mmHg (relative odds ratio [OR] 0.8, 95% CI 0.6-0.9) and non-HDL ≥160 mg/dL (≥4.1 mmol/L) (relative OR 0.45, 0.4-0.5). These differences remained statistically significant after adjustment for race/ethnicity, education, poverty levels, and clinical characteristics. Yet, over the 1999-2018 time period, minority race/ethnicity, lower education attainment, poverty, and lack of health insurance coverage were factors associated with poorer A, B, C, or S in urban adults compared with their rural counterparts. CONCLUSIONS: Over two decades, rural U.S. adults with diabetes have had less improvement in BP and cholesterol control. In addition, rural-urban differences exist across sociodemographic groups, suggesting that efforts to narrow this divide may need to address both socioeconomic and clinical aspects of care.

      3. Potential Strategies to Increase Gynecologic Oncologist Treatment for Ovarian Cancerexternal icon
        Stewart SL, Mezzo JL, Nielsen D, Rim SH, Moore AR, Bhalakia A, House M.
        J Womens Health (Larchmt). 2021 Jun;30(6):769-781.
        Evidence shows that treatment by gynecologic oncologists (GOs) increases overall survival among women with ovarian cancer. However, specific strategies for institutions and community-based public health programs to promote treatment by GOs are lacking. To address this, we conducted a literature review to identify evidence-based and promising system- and environmental-change strategies for increasing treatment by GOs, in effort to ensure that all women with ovarian cancer receive the standard of care. We searched for English-language literature published from 2008 to 2018. We used PubMed, PubMed Central, OVID, and EBSCO for peer-reviewed literature and Google and Google Scholar for gray literature related to increasing receipt of care by GOs among ovarian cancer patients. Numerous suggested and proposed strategies that have potential to increase treatment by GOs were discussed in several articles. We grouped these approaches into five strategic categories: increasing knowledge/awareness of role and importance of GOs, improving models of care, improving payment structures, improving/increasing insurance coverage for GO care, and expanding or enhancing the GO workforce. We identified several strategies with the potential for increasing GO care among ovarian cancer patients, although currently there is little evidence regarding their effectiveness across US populations. Public health programs and entities that measure delivery of quality health care may pilot the strategies in their populations. Certain strategies may work better in certain environments and a combination of strategies may be necessary for any one entity to increase GO ovarian cancer care. Findings, lessons learned, and recommendations from implementation projects would inform community and public health practice.

      4. Cancer Incidence Projections in the United States Between 2015 and 2050external icon
        Weir HK, Thompson TD, Stewart SL, White MC.
        Prev Chronic Dis. 2021 Jun 10;18:E59.
        INTRODUCTION: The number of adults entering the age groups at greatest risk for being diagnosed with cancer is increasing. Projecting cancer incidence can help the cancer control community plan and evaluate prevention strategies aimed at reducing the growing number of cancer cases. METHODS: We used data from the Surveillance, Epidemiology, and End Results Program and the US Census Bureau to estimate average, annual, age-standardized cancer incidence rates and case counts (for all sites combined and top 22 invasive cancers) in the US for 2015 and to project cancer rates and counts to 2050. We used age, period, and cohort models to inform projections. RESULTS: Between 2015 and 2050, we predict the overall age-standardized incidence rate (proxy for population risk for being diagnosed with cancer) to stabilize in women (1%) and decrease in men (-9%). Cancers with the largest change in risk include a 34% reduction for lung and bronchus and a 32% increase for corpus uterine (32%). Because of the growth and aging of the US population, we predict that the annual number of cancer cases will increase 49%, from 1,534,500 in 2015 to 2,286,300 in 2050, with the largest percentage increase among adults aged ≥75 years. Cancers with the largest projected absolute increase include female breast, colon and rectum, and prostate. DISCUSSION: By 2050, we predict the total number of incident cases to increase by almost 50% as a result of the growth and aging of the US population. A greater emphasis on cancer risk reduction is needed to counter these trends.

    • Communicable Diseases
      1. Epidemiology of reported HIV and other sexually transmitted infections during the COVID-19 pandemic, New York Cityexternal icon
        Braunstein SL, Slutsker JS, Lazar R, Shah D, Hennessy RR, Chen S, Pathela P, Daskalakis DC, Schillinger JA.
        J Infect Dis. 2021 Jun 16.
        Early in the COVID-19 crisis, a statewide executive order ("PAUSE") severely restricted the movement of New Yorkers from March 23-June 7, 2020. We used NYC surveillance data for HIV, chlamydia, gonorrhea, and syphilis to describe trends in diagnosis and reporting surrounding PAUSE. During PAUSE, the volume of positive HIV/STI tests, and diagnoses of HIV, chlamydia, gonorrhea, and syphilis declined substantially, reaching a nadir in April before rebounding. Some shifts in characteristics of reported cases were identified.

      2. Outbreak of Acute Respiratory Illness Associated with Human Adenovirus Type 4 at the U.S. Coast Guard Academy, 2019external icon
        Chu VT, Simon E, Lu X, Rockwell P, Abedi GR, Gardner C, Kujawski SA, Schneider E, Gentile M, Ramsey LA, Liu R, Jones S, Janik C, Siniscalchi A, Landry ML, Christopher J, Lindstrom S, Steiner S, Thomas D, Gerber SI, Biggs HM.
        J Infect Dis. 2021 Jun 17.
        BACKGROUND: Although a human adenovirus (HAdV) vaccine is available for military use, officers-in-training are not routinely vaccinated. We describe an HAdV-associated respiratory outbreak among unvaccinated cadets at the U.S. Coast Guard Academy and its impact on cadet training. METHODS: We defined a case as a cadet with new onset cough or sore throat during August 1-October 4, 2019. We reviewed medical records and distributed a questionnaire to identify cases and to estimate impact on cadet training. We performed real-time PCR testing on patient and environmental samples and whole genome sequencing on a subset of positive patient samples. RESULTS: Among the 1,072 cadets, 378 (35%) cases were identified by medical records (n=230) or additionally by the questionnaire (n=148). Of the 230 cases identified from medical records, 138 (60%) were male and 226 (98%) had no underlying conditions. From questionnaire responses, 113/228 (50%) cases reported duty restrictions. Of cases with respiratory specimens, 36/50 (72%) were HAdV positive; all 14 sequenced specimens were HAdV-4a1. Sixteen (89%) of 18 environmental specimens from the cadet dormitory were HAdV-positive. CONCLUSIONS: The HAdV-4-associated outbreak infected a substantial number of cadets and significantly impacted cadet training. Routine vaccination could prevent HAdV respiratory outbreaks in this population.

      3. Comparison of Symptoms and RNA Levels in Children and Adults With SARS-CoV-2 Infection in the Community Settingexternal icon
        Chung E, Chow EJ, Wilcox NC, Burstein R, Brandstetter E, Han PD, Fay K, Pfau B, Adler A, Lacombe K, Lockwood CM, Uyeki TM, Shendure J, Duchin JS, Rieder MJ, Nickerson DA, Boeckh M, Famulare M, Hughes JP, Starita LM, Bedford T, Englund JA, Chu HY.
        JAMA Pediatr. 2021 Jun 11.
        IMPORTANCE: The association between COVID-19 symptoms and SARS-CoV-2 viral levels in children living in the community is not well understood. OBJECTIVE: To characterize symptoms of pediatric COVID-19 in the community and analyze the association between symptoms and SARS-CoV-2 RNA levels, as approximated by cycle threshold (Ct) values, in children and adults. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used a respiratory virus surveillance platform in persons of all ages to detect community COVID-19 cases from March 23 to November 9, 2020. A population-based convenience sample of children younger than 18 years and adults in King County, Washington, who enrolled online for home self-collection of upper respiratory samples for SARS-CoV-2 testing were included. EXPOSURES: Detection of SARS-CoV-2 RNA by reverse transcription-polymerase chain reaction (RT-PCR) from participant-collected samples. MAIN OUTCOMES AND MEASURES: RT-PCR-confirmed SARS-CoV-2 infection, with Ct values stratified by age and symptoms. RESULTS: Among 555 SARS-CoV-2-positive participants (mean [SD] age, 33.7 [20.1] years; 320 were female [57.7%]), 47 of 123 children (38.2%) were asymptomatic compared with 31 of 432 adults (7.2%). When symptomatic, fewer symptoms were reported in children compared with adults (mean [SD], 1.6 [2.0] vs 4.5 [3.1]). Symptomatic individuals had lower Ct values (which corresponded to higher viral RNA levels) than asymptomatic individuals (adjusted estimate for children, -3.0; 95% CI, -5.5 to -0.6; P = .02; adjusted estimate for adults, -2.9; 95% CI, -5.2 to -0.6; P = .01). The difference in mean Ct values was neither statistically significant between symptomatic children and symptomatic adults (adjusted estimate, -0.7; 95% CI, -2.2 to 0.9; P = .41) nor between asymptomatic children and asymptomatic adults (adjusted estimate, -0.6; 95% CI, -4.0 to 2.8; P = .74). CONCLUSIONS AND RELEVANCE: In this community-based cross-sectional study, SARS-CoV-2 RNA levels, as determined by Ct values, were significantly higher in symptomatic individuals than in asymptomatic individuals and no significant age-related differences were found. Further research is needed to understand the role of SARS-CoV-2 RNA levels and viral transmission.

      4. Making voluntary medical male circumcision services sustainable: Findings from Kenya's pilot models, baseline and year 1external icon
        Davis SM, Owuor N, Odoyo-June E, Wambua J, Omanga E, Lukobo M, Laube C, Mwandi Z, Suraratdecha C, Kioko UM, Rotich W, Kataka J, Ng'eno C, Mohan D, Toledo C, Aoko A, Anyango J, Oneya D, Orenjuro K, Mgamb E, Serrem K, Juma A.
        PLoS One. 2021 ;16(6):e0252725.
        Voluntary medical male circumcision is a crucial HIV prevention program for men in sub-Saharan Africa. Kenya is one of the first countries to achieve high population coverage and seek to transition the program to a more sustainable structure designed to maintain coverage while making all aspects of service provision domestically owned and implemented. Using pre-defined metrics, we created and evaluated three models of circumcision service delivery (static, mobile and mixed) to identify which had potential for sustaining high circumcision coverage among 10-14-year-olds group, a historically high-demand and accessible age group, at the lowest possible cost. We implemented each model in two distinct geographic areas, one in Siaya and the other in Migori county, and assessed multiple aspects of each model's sustainability. These included numerical achievements against targets designed to reach 80% coverage over two years; quantitative expenditure outcomes including unit expenditure plus its primary drivers; and qualitative community perception of program quality and sustainability based on Likert scale. Outcome values at baseline were compared with those for year one of model implementation using bivariate linear regression, unpaired t-tests and Wilcoxon rank tests as appropriate. Across models, numerical target achievement ranged from 45-140%, with the mixed models performing best in both counties. Unit expenditures varied from approximately $57 in both countries at baseline to $44-$124 in year 1, with the lowest values in the mixed and static models. Mean key informant perception scores generally rose significantly from baseline to year 1, with a notable drop in the area of community engagement. Consistently low scores were in the aspects of domestic financing for service provision. Sustainability-focused circumcision service delivery models can successfully achieve target volumes at lower unit expenditures than existing models, but strategies for domestic financing remain a crucial challenge to address for long-term maintenance of the program.

      5. Hepatitis A Virus Infections Among Men Who Have Sex with Men - Eight U.S. States, 2017-2018external icon
        Foster MA, Hofmeister MG, Albertson JP, Brown KB, Burakoff AW, Gandhi AP, Glenn-Finer RE, Gounder P, Ho PY, Kavanaugh T, Latash J, Lewis RL, Longmire AG, Myrick-West A, Perella DM, Reddy V, Stanislawski ES, Stoltey JE, Sullivan SM, Utah OF, Zipprich J, Teshale EH.
        MMWR Morb Mortal Wkly Rep. 2021 Jun 18;70(24):875-878.
        During 1995-2011, the overall incidence of hepatitis A decreased by 95% in the United States from 12 cases per 100,000 population during 1995 to 0.4 cases per 100,000 population during 2011, and then plateaued during 2012─2015. The incidence increased by 294% during 2016-2018 compared with the incidence during 2013-2015, with most cases occurring among populations at high risk for hepatitis A infection, including persons who use illicit drugs (injection and noninjection), persons who experience homelessness, and men who have sex with men (MSM) (1-3). Previous outbreaks among persons who use illicit drugs and MSM led to recommendations issued in 1996 by the Advisory Committee on Immunization Practices (ACIP) for routine hepatitis A vaccination of persons in these populations (4). Despite these long-standing recommendations, vaccination coverage rates among MSM remain low (5). In 2017, the New York City Department of Health and Mental Hygiene contacted CDC after public health officials noted an increase in hepatitis A infections among MSM. Laboratory testing* of clinical specimens identified strains of the hepatitis A virus (HAV) that subsequently matched strains recovered from MSM in other states. During January 1, 2017-October 31, 2018, CDC received reports of 260 cases of hepatitis A among MSM from health departments in eight states, a substantial increase from the 16 cases reported from all 50 states during 2013-2015. Forty-eight percent (124 of 258) of MSM patients were hospitalized for a median of 3 days. No deaths were reported. In response to these cases, CDC supported state and local health departments with public health intervention efforts to decrease HAV transmission among MSM populations. These efforts included organizing multistate calls among health departments to share information, providing guidance on developing targeted outreach and managing supplies for vaccine campaigns, and conducting laboratory testing of clinical specimens. Targeted outreach for MSM to increase awareness about hepatitis A infection and improve access to vaccination services, such as providing convenient locations for vaccination, are needed to prevent outbreaks among MSM.

      6. Population analysis of Vibrio cholerae in aquatic reservoirs reveals a novel sister species (Vibrio paracholerae sp. nov.) with a history of association with humansexternal icon
        Islam MT, Nasreen T, Kirchberger P, Liang KY, Orata FD, Johura FT, Hussain NA, Im MS, Tarr CL, Alam M, Boucher YF.
        Appl Environ Microbiol. 2021 Jun 16:Aem0042221.
        Most efforts to understand the biology of Vibrio cholerae have focused on a single group, the pandemic-generating lineage harbouring the strains responsible for all known cholera pandemics. Consequently, little is known about the diversity of this species in its native aquatic environment. To understand the differences in the V. cholerae populations inhabiting regions with a history of cholera cases and those lacking such a history, a comparative analysis of population composition was performed. Little overlap was found in lineage compositions between those in Dhaka (cholera endemic) located in the Ganges delta, and of Falmouth (no known history of cholera), a small coastal town on the United States east coast. The most striking difference was the presence of a group of related lineages at high abundance in Dhaka which was completely absent from Falmouth. Phylogenomic analysis revealed that these lineages form a cluster at the base of the phylogeny for the V. cholerae species, sufficiently differentiated genetically and phenotypically to form a novel species. A retrospective search revealed that strains from this species have been anecdotally found from around the world and were isolated as early as 1916 from a British soldier in Egypt suffering from choleraic diarrhoea. In 1935 Gardner and Venkatraman unofficially referred to a member of this group as Vibrio paracholerae. In recognition of this earlier designation, we propose the name Vibrio paracholerae sp. nov. for this bacterium. Genomic analysis suggests a link with human populations for this novel species and substantial interaction with its better-known sister species. Importance Cholera continues to remain a major public health threat around the globe. Understanding the ecology, evolution, and environmental adaptation of the causative agent Vibrio cholerae and tracking the emergence of novel lineages with pathogenic potential are essential to combat the problem. In this study, we investigated the population dynamics of Vibrio cholerae in an inland locality which is known as endemic for cholera and compared with that of a cholera free coastal location. We found the consistent presence of the pandemic generating V. cholerae in cholera-endemic Dhaka and an exclusive presence of a lineage phylogenetically distinct from other V. cholerae. Our study suggests that this lineage represents a novel species having pathogenic potential and a human link to its environmental abundance. The possible association with human population, co-existence and interaction with toxigenic V. cholerae in the natural environment make this potential human pathogen an important subject for future studies.

      7. Outbreaks of Adenovirus-associated Respiratory Illness on 5 College Campuses in the United States, 2018-2019external icon
        Kujawski SA, Lu X, Schneider E, Blythe D, Boktor S, Farrehi J, Haupt T, McBride D, Stephens E, Sakthivel SK, Bachaus B, Waller K, Bauman L, Marconi A, Lewis R, Dettinger L, Ernst R, Kinsey W, Lindstrom S, Gerber SI, Watson JT, Biggs HM.
        Clin Infect Dis. 2021 Jun 1;72(11):1992-1999.
        BACKGROUND: Human adenoviruses (HAdVs) are commonly associated with acute respiratory illness. HAdV outbreaks are well documented in congregate military training settings, but less is known about outbreaks on college campuses. During fall 2018 and spring 2019, 5 United States (US) colleges reported increases in HAdV-associated respiratory illness. Investigations were performed to better understand HAdV epidemiology in this setting. METHODS: A case was defined as a student at one of the 5 colleges, with acute respiratory illness and laboratory-confirmed HAdV infection during October 2018-December 2018 or March-May 2019. Available respiratory specimens were typed by HAdV type-specific real-time polymerase chain reaction assays, and for a subset, whole genome sequencing was performed. We reviewed available medical records and cases were invited to complete a questionnaire, which included questions on symptom presentation, social history, and absenteeism. RESULTS: We identified 168 HAdV cases. Median age was 19 (range, 17-22) years and 102 cases (61%) were male. Eleven cases were hospitalized, 10 with pneumonia; 2 cases died. Among questionnaire respondents, 80% (75/94) missed ≥ 1 day of class because of their illness. Among those with a type identified (79%), HAdV types 4 and 7 were equally detected, with frequency of each varying by site. Genome types 4a1 and 7d were identified, respectively, by whole genome sequence analysis. CONCLUSIONS: HAdV respiratory illness was associated with substantial morbidity and missed class time among young, generally healthy adults on 5 US college campuses. HAdVs should be considered a cause of respiratory illness outbreaks in congregate settings such as college campuses.

      8. Transmission Dynamics and Microevolution of Neisseria meningitidis During Carriage and Invasive Disease in High School Students in Georgia and Maryland, 2006-2007external icon
        Mustapha MM, Marsh JW, Shutt KA, Schlackman J, Ezeonwuka C, Farley MM, Stephens DS, Wang X, Van Tyne D, Harrison LH.
        J Infect Dis. 2021 Jun 15;223(12):2038-2047.
        BACKGROUND: The mechanisms by which Neisseria meningitidis cause persistent human carriage and transition from carriage to invasive disease have not been fully elucidated. METHODS: Georgia and Maryland high school students were sampled for pharyngeal carriage of N. meningitidis during the 2006-2007 school year. A total of 321 isolates from 188 carriers and all 67 invasive disease isolates collected during the same time and from the same geographic region underwent whole-genome sequencing. Core-genome multilocus sequence typing was used to compare allelic profiles, and direct read mapping was used to study strain evolution. RESULTS: Among 188 N. meningitidis culture-positive students, 98 (52.1%) were N. meningitidis culture positive at 2 or 3 samplings. Most students who were positive at >1 sampling (98%) had persistence of a single strain. More than a third of students carried isolates that were highly genetically related to isolates from other students in the same school, and occasional transmission within the same county was also evident. The major pilin subunit gene, pilE, was the most variable gene, and no carrier had identical pilE sequences at different time points. CONCLUSION: We found strong evidence of local meningococcal transmission at both the school and county levels. Allelic variation within genes encoding bacterial surface structures, particularly pilE, was common.

      9. Impact of Social Distancing and Travel Restrictions on Non-Coronavirus Disease 2019 (Non-COVID-19) Respiratory Hospital Admissions in Young Children in Rural Alaskaexternal icon
        Nolen LD, Seeman S, Bruden D, Klejka J, Desnoyers C, Tiesinga J, Singleton R.
        Clin Infect Dis. 2021 Jun 15;72(12):2196-2198.
        Hospitalizations due to non-coronavirus disease 2019 (non-COVID-19) respiratory illnesses decreased dramatically after social distancing was implemented in a high-risk population in rural Alaska; an unprecedented decline compared to the past 10 respiratory seasons. This demonstrates the potential secondary benefits of implementing social distancing and travel restrictions on respiratory illnesses.

      10. Estimated Incidence of Coronavirus Disease 2019 (COVID-19) Illness and Hospitalization-United States, February-September 2020external icon
        Reese H, Iuliano AD, Patel NN, Garg S, Kim L, Silk BJ, Hall AJ, Fry A, Reed C.
        Clin Infect Dis. 2021 Jun 15;72(12):e1010-e1017.
        BACKGROUND: In the United States, laboratory-confirmed coronavirus disease 2019 (COVID-19) is nationally notifiable. However, reported case counts are recognized to be less than the true number of cases because detection and reporting are incomplete and can vary by disease severity, geography, and over time. METHODS: To estimate the cumulative incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, symptomatic illnesses, and hospitalizations, we adapted a simple probabilistic multiplier model. Laboratory-confirmed case counts that were reported nationally were adjusted for sources of underdetection based on testing practices in inpatient and outpatient settings and assay sensitivity. RESULTS: We estimated that through the end of September, 1 of every 2.5 (95% uncertainty interval [UI]: 2.0-3.1) hospitalized infections and 1 of every 7.1 (95% UI: 5.8-9.0) nonhospitalized illnesses may have been nationally reported. Applying these multipliers to reported SARS-CoV-2 cases along with data on the prevalence of asymptomatic infection from published systematic reviews, we estimate that 2.4 million hospitalizations, 44.8 million symptomatic illnesses, and 52.9 million total infections may have occurred in the US population from 27 February-30 September 2020. CONCLUSIONS: These preliminary estimates help demonstrate the societal and healthcare burdens of the COVID-19 pandemic and can help inform resource allocation and mitigation planning.

      11. Secretor status strongly influences the incidence of symptomatic norovirus infection in a genotype-dependent manner in a Nicaraguan birth cohortexternal icon
        Reyes Y, González F, Gutierrez L, Blandon P, Centeno E, Zepeda O, Toval-Ruíz C, Lindesmith LC, Baric RS, Vielot N, Diez-Valcarce M, Vinjé J, Svensson L, Becker-Dreps S, Nordgren J, Bucardo F.
        J Infect Dis. 2021 Jun 15.
        BACKGROUND: The role of histo-blood group on the burden and severity of norovirus gastroenteritis in young infants has not been well documented. METHODS: Norovirus gastroenteritis was assessed in 443 Nicaraguan children followed from birth until 3 years of age. Stool samples were tested for norovirus by RT-qPCR and histo-blood group antigens (HBGA) were determined by phenotyping of saliva and blood. Hazards ratios (95% CI) and predictors of norovirus AGE outcome stratified by HBGA were estimated using Cox proportional hazards models. RESULTS: Of 1,353 AGE episodes experienced by children, 229 (17%) tested positive for norovirus with an overall incidence of 21.9/100 child-years. Secretor children were infected as early as 2 months old and had a higher incidence of norovirus GII compared to non-secretor children (15.4 vs 4.1/100 child-years, P = 0.006). Furthermore, all GII.4 AGE episodes occurred in secretor children. Children infected with GI (adjusted OR=0.09, 95% CI 0.02-0.33) or non-GII.4 viruses (adjusted OR=0.2, 95% CI: 0.07-0.6) were less likely to have severe AGE compared to GII.4 infected children. CONCLUSION: Secretor status in children strongly influences the incidence of symptomatic norovirus infection in a genogroup or genotype-dependent manner and provides evidence that clinical severity in children depends on norovirus genotypes.

      12. Timing of Antiretroviral Therapy Initiation and Risk of Cancer Among Persons Living With Human Immunodeficiency Virusexternal icon
        Silverberg MJ, Leyden W, Hernández-Ramírez RU, Qin L, Lin H, Justice AC, Hessol NA, Achenbach CJ, D'Souza G, Engels EA, Althoff KN, Mayor AM, Sterling TR, Kitahata MM, Bosch RJ, Saag MS, Rabkin CS, Horberg MA, Gill MJ, Grover S, Mathews WC, Li J, Crane HM, Gange SJ, Lau B, Moore RD, Dubrow R, Neugebauer RS.
        Clin Infect Dis. 2021 Jun 1;72(11):1900-1909.
        BACKGROUND: Persons living with human immunodeficiency virus (HIV; PLWH) experience a high burden of cancer. It remains unknown which cancer types are reduced in PLWH with earlier initiation of antiretroviral therapy (ART). METHODS: We evaluated AIDS-free, ART-naive PLWH during 1996-2014 from 22 cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. PLWH were followed from first observed CD4 of 350-500 cells/µL (baseline) until incident cancer, death, lost-to-follow-up, or December 2014. Outcomes included 6 cancer groups and 5 individual cancers that were confirmed by chart review or cancer registry linkage. We evaluated the effect of earlier (in the first 6 months after baseline) versus deferred ART initiation on cancer risk. Marginal structural models were used with inverse probability weighting to account for time-dependent confounding and informative right-censoring, with weights informed by subject's age, sex, cohort, baseline year, race/ethnicity, HIV transmission risk, smoking, viral hepatitis, CD4, and AIDS diagnoses. RESULTS: Protective results for earlier ART were found for any cancer (adjusted hazard ratio [HR] 0.57; 95% confidence interval [CI], .37-.86), AIDS-defining cancers (HR 0.23; 95% CI, .11-.49), any virus-related cancer (HR 0.30; 95% CI, .16-.54), Kaposi sarcoma (HR 0.25; 95% CI, .10-.61), and non-Hodgkin lymphoma (HR 0.22; 95% CI, .06-.73). By 15 years, there was also an observed reduced risk with earlier ART for virus-related NADCs (0.6% vs 2.3%; adjusted risk difference -1.6; 95% CI, -2.8, -.5). CONCLUSIONS: Earlier ART initiation has potential to reduce the burden of virus-related cancers in PLWH but not non-AIDS-defining cancers (NADCs) without known or suspected viral etiology.

      13. Multisystem Inflammatory Syndrome in Children - Initial Therapy and Outcomesexternal icon
        Son MB, Murray N, Friedman K, Young CC, Newhams MM, Feldstein LR, Loftis LL, Tarquinio KM, Singh AR, Heidemann SM, Soma VL, Riggs BJ, Fitzgerald JC, Kong M, Doymaz S, Giuliano JS, Keenaghan MA, Hume JR, Hobbs CV, Schuster JE, Clouser KN, Hall MW, Smith LS, Horwitz SM, Schwartz SP, Irby K, Bradford TT, Maddux AB, Babbitt CJ, Rowan CM, McLaughlin GE, Yager PH, Maamari M, Mack EH, Carroll CL, Montgomery VL, Halasa NB, Cvijanovich NZ, Coates BM, Rose CE, Newburger JW, Patel MM, Randolph AG.
        N Engl J Med. 2021 Jun 16.
        BACKGROUND: The assessment of real-world effectiveness of immunomodulatory medications for multisystem inflammatory syndrome in children (MIS-C) may guide therapy. METHODS: We analyzed surveillance data on inpatients younger than 21 years of age who had MIS-C and were admitted to 1 of 58 U.S. hospitals between March 15 and October 31, 2020. The effectiveness of initial immunomodulatory therapy (day 0, indicating the first day any such therapy for MIS-C was given) with intravenous immune globulin (IVIG) plus glucocorticoids, as compared with IVIG alone, was evaluated with propensity-score matching and inverse probability weighting, with adjustment for baseline MIS-C severity and demographic characteristics. The primary outcome was cardiovascular dysfunction (a composite of left ventricular dysfunction or shock resulting in the use of vasopressors) on or after day 2. Secondary outcomes included the components of the primary outcome, the receipt of adjunctive treatment (glucocorticoids in patients not already receiving glucocorticoids on day 0, a biologic, or a second dose of IVIG) on or after day 1, and persistent or recurrent fever on or after day 2. RESULTS: A total of 518 patients with MIS-C (median age, 8.7 years) received at least one immunomodulatory therapy; 75% had been previously healthy, and 9 died. In the propensity-score-matched analysis, initial treatment with IVIG plus glucocorticoids (103 patients) was associated with a lower risk of cardiovascular dysfunction on or after day 2 than IVIG alone (103 patients) (17% vs. 31%; risk ratio, 0.56; 95% confidence interval [CI], 0.34 to 0.94). The risks of the components of the composite outcome were also lower among those who received IVIG plus glucocorticoids: left ventricular dysfunction occurred in 8% and 17% of the patients, respectively (risk ratio, 0.46; 95% CI, 0.19 to 1.15), and shock resulting in vasopressor use in 13% and 24% (risk ratio, 0.54; 95% CI, 0.29 to 1.00). The use of adjunctive therapy was lower among patients who received IVIG plus glucocorticoids than among those who received IVIG alone (34% vs. 70%; risk ratio, 0.49; 95% CI, 0.36 to 0.65), but the risk of fever was unaffected (31% and 40%, respectively; risk ratio, 0.78; 95% CI, 0.53 to 1.13). The inverse-probability-weighted analysis confirmed the results of the propensity-score-matched analysis. CONCLUSIONS: Among children and adolescents with MIS-C, initial treatment with IVIG plus glucocorticoids was associated with a lower risk of new or persistent cardiovascular dysfunction than IVIG alone. (Funded by the Centers for Disease Control and Prevention.).

      14. Retention in Medical Care Among Insured Adolescents and Young Adults With Diagnosed HIV Infection, United States, 2010-2014external icon
        Tanner MR, Bush T, Nesheim SR, Weidle PJ, Byrd KK.
        Public Health Rep. 2021 Jun 16:333549211023266.
        OBJECTIVES: Retention in care is a critical component of effective HIV treatment, and adolescents and young adults are at higher risk of inadequate retention than older adults. The objective of our study was to examine the patterns of retention in care among adolescents and young adults with HIV infection by analyzing Medicaid and commercial health insurance claims data. METHODS: We evaluated retention in care for HIV-diagnosed adolescents and young adults aged 13-24 using the 2010-2014 MarketScan Medicaid and MarketScan Commercial Claims health insurance databases. The study period extended 36 months from the date of the first claim with a code for HIV or AIDS. We determined the unweighted proportion retained in care for the Medicaid and Commercial Claims cohorts for months 0-24 and 25-36. We assessed associations between demographic characteristics and retention in care using logistic regression. RESULTS: A total of 378 adolescents and young adults were in the Medicaid cohort and 1028 in the Commercial Claims cohort. In the Medicaid and Commercial Claims cohorts, respectively, 186 (49%) and 591 (57%) adolescents and young adults were retained in care during months 0-24. In the Medicaid cohort, 113 (73%) people retained in care and 69 (45%) people not retained in care during months 0-24 were retained in care during months 25-36. In the Commercial Claims cohort, 313 (77%) and 94 (31%) retained and not retained people, respectively, were found to be in care during months 25-36. CONCLUSIONS: Notable proportions of HIV-diagnosed adolescents and young adults are not adequately retained in care; public health interventions tailored to this population are needed.

      15. Obesity and Mortality Among Patients Diagnosed With COVID-19external icon
        Tartof SY, Murali SB, Malden DE.
        Ann Intern Med. 2021 Jun;174(6):887-888.

    • Disaster Control and Emergency Services
      1. The World Trade Center Health Program: Petitions for adding qualifying health conditionsexternal icon
        Daniels RD, Carreón T, Bilics JA, Reissman DB, Howard J.
        Am J Ind Med. 2021 Jun 15.
        The federally mandated World Trade Center Health Program provides limited health benefits for qualifying health conditions related to the 9/11 terrorist attacks. A qualifying health condition is an illness or health condition for which the member's exposure to airborne toxins, any other hazard, or any other adverse condition resulting from the 9/11 terrorist attacks is considered substantially likely to be a significant factor in aggravating, contributing to, or causing the illness or health condition. These qualifying health conditions are listed in federal regulations. The regulations also provide a process for amending this list. This commentary describes the methods developed for adding health conditions to the list of qualifying health conditions and discusses changes to the list that have occurred during the Program's 2011-2020 period.

    • Disease Reservoirs and Vectors
      1. Comparison of four outdoor mosquito trapping methods as potential replacements for human landing catches in western Kenyaexternal icon
        Abong'o B, Gimnig JE, Longman B, Odongo T, Wekesa C, Webwile A, Oloo B, Nduta M, Muchoki M, Omoke D, Wacira D, Opondo K, Ochomo E, Munga S, Donnelly MJ, Oxborough RM.
        Parasit Vectors. 2021 Jun 12;14(1):320.
        INTRODUCTION: Longitudinal monitoring of outdoor-biting malaria vector populations is becoming increasingly important in understanding the dynamics of residual malaria transmission. However, the human landing catch (HLC), the gold standard for measuring human biting rates indoors and outdoors, is costly and raises ethical concerns related to increased risk of infectious bites among collectors. Consequently, routine data on outdoor-feeding mosquito populations are usually limited because of the lack of a scalable tool with similar sensitivity to outdoor HLC. METHODOLOGY: The Anopheles trapping sensitivity of four baited proxy outdoor trapping methods-Furvela tent trap (FTT), host decoy trap (HDT), mosquito electrocuting traps (MET) and outdoor CDC light traps (OLT)-was assessed relative to HLC in a 5 × 5 replicated Latin square conducted over 25 nights in two villages of western Kenya. Indoor CDC light trap (ILT) was run in one house in each of the compounds with outdoor traps, while additional non-Latin square indoor and outdoor HLC collections were performed in one of the study villages. RESULTS: The MET, FTT, HDT and OLT sampled approximately 4.67, 7.58, 5.69 and 1.98 times more An. arabiensis compared to HLC, respectively, in Kakola Ombaka. Only FTT was more sensitive relative to HLC in sampling An. funestus in Kakola Ombaka (RR = 5.59, 95% CI 2.49-12.55, P < 0.001) and Masogo (RR = 4.38, 95% CI 1.62-11.80, P = 0.004) and in sampling An. arabiensis in Masogo (RR = 5.37, 95% CI 2.17-13.24, P < 0.001). OLT sampled significantly higher numbers of An. coustani in Kakola Ombaka (RR = 3.03, 95% CI 1.65-5.56, P < 0.001) and Masogo (RR = 2.88, 95% CI 1.15-7.22, P = 0.02) compared to HLC. OLT, HLC and MET sampled mostly An. coustani, FTT had similar proportions of An. funestus and An. arabiensis, while HDT sampled predominantly An. arabiensis in both villages. FTT showed close correlation with ILT in vector abundance for all three species at both collection sites. CONCLUSION: FTT and OLT are simple, easily scalable traps and are potential replacements for HLC in outdoor sampling of Anopheles mosquitoes. However, the FTT closely mirrored indoor CDC light trap in mosquito indices and therefore may be more of an indoor mimic than a true outdoor collection tool. HDT and MET show potential for sampling outdoor host-seeking mosquitoes. However, the traps as currently designed may not be feasible for large-scale, longitudinal entomological monitoring. Therefore, the baited outdoor CDC light trap may be the most appropriate tool currently available for assessment of outdoor-biting and malaria transmission risk.

    • Environmental Health
      1. Harmful algal blooms (HABs) are the rapid growth of algae that can produce toxic or harmful effects in people and animals. Potential health effects include respiratory illness, gastrointestinal illness, skin and eye irritation, and sometimes more severe toxic effects such as liver damage. Defining HAB exposure and related illness is challenging for many reasons, including characterizing the exposure. Large electronic health record databases present an opportunity to study health encounters specifically related to HAB exposure through querying medical diagnostic codes. We queried the MarketScan Research Databases between January 2009 and April 2019 for use of the International Classification of Diseases (ICD) codes for HAB exposure. We found a total of 558 records that used either the ICD-9 or ICD-10 code for HAB exposure. Respiratory illness was most commonly reported along with the HAB exposure code. Use of HAB exposure codes showed seasonal fluctuations during 2012–2019. We found that although the HAB-related ICD-9 and ICD-10 codes were used infrequently, they were most often recorded during bloom seasons in warmer months. This analysis is the first that utilizes a large-scale national database of de-identified health records to understand the use of medical diagnostic codes related to algae exposure. © 2021, National Environmental Health Association. All rights reserved.


    • Health Disparities
      1. During 1999-2019, a total of 81,947 unintentional drowning deaths occurred in the United States (1). Drowning is one of the three leading causes of unintentional injury death among persons aged ≤29 years and results in more deaths among children aged 1-4 years than any other cause except birth defects (2). Drowning death rates have decreased since 1990 (declining by 57% worldwide and by 32% in the United States) (3). However, because of racial/ethnic disparities in drowning risk, rates remain high among certain racial/ethnic groups, particularly American Indian or Alaska Native (AI/AN) persons and Black or African-American (Black) persons (4). To assess whether decreasing drowning death rates have been accompanied by reductions in racial/ethnic disparities, and to further describe these disparities by age group and setting, CDC analyzed U.S. mortality data during 1999-2019. The drowning death rate among persons aged ≤29 years was 1.3 per 100,000 population. The rate per 100,000 among AI/AN persons (2.5) and Black persons (1.8) was higher than among all other racial/ethnic groups and was 2.0 and 1.5 times higher than among White persons (1.2). Racial/ethnic disparities in drowning death rates did not significantly decline for most groups, and the disparity in rates among Black persons compared with White persons increased significantly from 2005-2019. Drowning death rates are associated with persistent and concerning racial/ethnic disparities. A better understanding of the factors that contribute to drowning disparities is needed. Implementing and evaluating community-based interventions, including those promoting basic swimming and water safety skills, among disproportionately affected racial/ethnic groups could help reduce drowning disparities.

    • Healthcare Associated Infections
      1. Feasibility and acceptance of a cloud-based mobile app for antimicrobial stewardship and infection control in Colombian hospitalsexternal icon
        Ketcherside WJ, Olson JB, Hunt LN, Mehta JM, Gutiérrez CP, Coy LM, Pradera IP, Rivera AD, Cano JA, Saeed A, Sapiro V, Park BJ, Malpiedi P, Botero MV.
        Int J Infect Control. 2020 Jul 23;16(3):1-6.
        Infection control and antimicrobial stewardship programs (ICASPs) are essential to reduce the emergence and spread of antimicrobial resistance. The primary objective of this study was to assess the feasibility of extending a commercial off-the-shelf (COTS) software for ICASPs in low- and middle-income countries (LMICs). This project involved three hospitals in Colombia, including Centro Médico Imbanaco, Clínica San Francisco, and DIME Clínica Neurocardiovascular. A COTS platform (ILÚM Health Solutions(™) Kenilworth, NJ) was extended to function in a range of technology settings, and translatable to almost any language. ICASP features were added, including clinical practice guidelines, hand hygiene (HH) documentation, and isolation precaution (IP) documentation. The platform was delivered as a smartphone mobile application ("app") for both iOS and Android. The app was successfully implemented at all sites, however, full back-end data integration was not feasible at any site. In contrast to the United States, a suite of surveillance tools and physician-focused decision support without patient data proved to be valuable. Language translation processing occurred quickly and incurred minimal costs. HH and IP compliance tracking were the most used features among ICASP staff; treatment guidelines were most often used by physicians. Use of the app streamlined activities and reduced the time spent on ICASP tasks. Users consistently reported positive impressions including simplicity of design, ease of navigation, and improved efficiency. This ICASP app was feasible in limited-resource settings, highly acceptable to users, and represents an innovative approach to antimicrobial resistance prevention.

    • Immunity and Immunization
      1. Rotavirus Vaccine Is Effective Against Rotavirus Gastroenteritis Resulting in Outpatient Care: Results From the Medically Attended Acute Gastroenteritis (MAAGE) Studyexternal icon
        Burke RM, Groom HC, Naleway AL, Katz EM, Salas B, Mattison CP, Donald J, Tsaknaridis L, Biggs C, Bowen MD, Tate JE, Parashar UD, Schmidt M, Hall AJ.
        Clin Infect Dis. 2021 Jun 1;72(11):2000-2005.
        BACKGROUND: Rotavirus is a common cause of severe pediatric acute gastroenteritis. Two vaccines are licensed in the United States and have demonstrated high effectiveness against moderate to severe disease. However, fewer data are available on rotavirus vaccine effectiveness (VE) against milder disease. METHODS: We leveraged active surveillance data from Kaiser Permanente Northwest to calculate rotavirus VE against medically attended rotavirus illness among age-eligible children. We utilized a test-negative case-control design and applied 4 distinct case definitions based on reverse transcription-quantitative real-time PCR (qRT-PCR) assay and enzyme immunoassay (EIA) test results. VE was calculated as 100 × (1 - odds ratio), and models were adjusted for age group. RESULTS: The VE analysis population comprised 842 children, 799 (95%) of whom had mild disease requiring at most a clinic visit and 698 (83%) of whom were fully vaccinated against rotavirus. Age-adjusted VE was 70% (95% confidence interval [CI], 37-86%) against disease defined solely by qRT-PCR results, 72% (95% CI, 31-89%) against disease as defined by qRT-PCR with a quantification cycle (C q ) value <27, 73% (95% CI, 32-90%) against disease that was qRT-PCR positive but EIA negative, and 62% (95% CI, -20-88%) against disease defined solely by EIA. Results were similar when restricting to disease resulting in at most an ambulatory clinic or emergency department visit. CONCLUSIONS: These results support the effectiveness of rotavirus vaccination in protecting US children from mild to moderate and severe disease. Our findings are also useful to show the effectiveness of rotavirus vaccination against qRT-PCR-defined illness.

      2. Live, oral rotavirus vaccines are more effective at preventing rotavirus disease in countries with low child mortality compared to high child mortality. Among several hypotheses, poorer protection in malnourished children, who are more prevalent in countries with high child mortality, may partially explain this difference. We conducted a literature search to identify articles with a laboratory-confirmed rotavirus endpoint that evaluated differences by malnutrition status in rotavirus vaccine effectiveness and vaccine efficacy (VE) or the prevalence of rotavirus infection or illness among children <5 years old. We identified 7 analyses from 11 countries published from 2007 to 2019 that stratified rotavirus VE by malnutrition status. Among well-nourished children, VE point estimates ranged from 71% to 84% in observational studies and 26% to 61% in clinical trials. Among malnourished children, they ranged from -28% to 45% in observational studies and -3% to 61% in clinical trials. The relative difference between VE in well-nourished and malnourished children by length-for-age ranged from 37% to 64%, by weight-for-age ranged from 0% to 107%, and by weight-for-height ranged from -65% to 137%. We identified 3 cohort and 6 cross-sectional studies of natural rotavirus infection and illness and none reported that malnourished children were more susceptible to rotavirus infection or illness than well-nourished children. Overall, rotavirus vaccines may offer less protection to children with malnutrition than well-nourished children. As malnourished children often have worse outcomes from diarrhea, high rotavirus vaccine coverage and a better understanding of the performance of oral rotavirus vaccines in this population is important, though our finding that malnourished children may be less susceptible to rotavirus provides important context and information for vaccine evaluation design.

      3. Cost effectiveness and impact of a targeted age- and incidence-based West Nile virus vaccine strategyexternal icon
        Curren EJ, Shankar MB, Fischer M, Meltzer MI, Staples JE, Gould CV.
        Clin Infect Dis. 2021 Jun 12.
        BACKGROUND: West Nile virus (WNV) is the leading cause of arboviral disease in the United States and is associated with significant morbidity and mortality. A previous analysis found that a vaccination program targeting persons aged ≥60 years was more cost effective than universal vaccination, but costs remained high. METHODS: We used a mathematical Markov model to evaluate cost-effectiveness of an age- and incidence-based WNV vaccination program. We grouped states and large counties (≥100,000 persons aged ≥60 years) by median annual WNV incidence rates from 2004 to 2017 for persons aged ≥60 years. We defined WNV incidence thresholds, in increments of 0.5 cases per 100,000 persons ≥60 years. We calculated potential cost per WNV vaccine-prevented case and per quality adjusted life years (QALYs) saved. RESULTS: Vaccinating persons aged ≥60 years in states with an annual incidence of WNV neuroinvasive disease of ≥0.5 per 100,000 resulted in approximately half the cost per health outcome averted compared to vaccinating persons aged ≥60 years in all the contiguous United States. This approach could potentially prevent 37% of all neuroinvasive disease cases and 63% of WNV-related deaths nationally. Employing such a threshold at a county-level further improved cost-effectiveness ratios while preventing 19% and 30% of WNV-related neuroinvasive disease cases and deaths, respectively. CONCLUSIONS: An age- and incidence-based WNV vaccination program could be a more cost-effective strategy than an age-based program while still having a substantial impact on lowering WNV-related morbidity and mortality.

      4. OBJECTIVE: To maintain acceptable response rates, the cost has grown for vaccination surveys that use traditional data collection modes, such as face-to-face and telephone interviews. Conducting a web or internet survey could be a low-cost alternative. However, because the internet is not used by everyone, we need to study how prevalence estimates in web surveys for vaccination surveillance could be affected by internet non-use. METHOD: We analyzed data from the 2013-2017 Behavioral Risk Factor Surveillance System to assess undercoverage biases from internet non-use by partitioning into proportion of internet non-users and difference in prevalence of influenza and pneumococcal vaccinations between internet and internet non-users, respectively. RESULTS: The proportion of internet non-users decreased monotonically from 43.3% in 2013 to 35.4% in 2017; however, the undercoverage bias from internet use for pneumococcal vaccination increased from 0.8 to 1.5 percentage points at the same time. Overall, the undercoverage bias was -1.1 and 1.5 percentage points for influenza vaccination and pneumococcal vaccination in 2017, respectively. For both vaccinations, we found large absolute and relative biases among certain demographic subgroups. CONCLUSIONS: Although the proportion of internet non-users decreased in recent years, undercoverage bias of hybrid internet survey for influenza and pneumococcal vaccinations did not decrease. Despite a small overall undercoverage bias, the bias in subpopulation groups was not negligible.

      5. Estimating the number of averted illnesses and deaths as a result of vaccination against an influenza pandemic in nine low- and middle-income countriesexternal icon
        Lutz CS, Biggerstaff M, Rolfes MA, Lafond KE, Azziz-Baumgartner E, Porter RM, Reed C, Bresee JS.
        Vaccine. 2021 Jun 9.
        BACKGROUND: During the 2009 influenza A(H1N1)pdm09 pandemic, 77 countries received donated monovalent A(H1N1)pdm09 vaccine through the WHO Pandemic Influenza A(H1N1) Vaccine Deployment Initiative. However, 47% did not receive their first shipment until after the first wave of virus circulation, and 8% did not receive their first shipment until after the WHO declared the end of the pandemic. Arguably, these shipments were too late into the pandemic to have a substantial effect on virus transmission or disease burden during the first waves of the pandemic. OBJECTIVES: In order to evaluate the potential benefits of earlier vaccine availability, we estimated the number of illnesses and deaths that could be averted during a 2009-like influenza pandemic under five different vaccine-availability timing scenarios. METHODS: We adapted a model originally developed to estimate annual influenza morbidity and mortality burden averted through US seasonal vaccination and ran it for five vaccine availability timing scenarios in nine low- and middle-income countries that received donated vaccine. RESULTS: Among nine study countries, we estimated that the number of averted cases was 61-216,197 for actual vaccine receipt, increasing to 2,914-283,916 had vaccine been available simultaneously with the United States. CONCLUSIONS: Earlier delivery of vaccines can reduce influenza case counts during a simulated 2009-like pandemic in some low- and middle-income countries. For others, increasing the number of cases and deaths prevented through vaccination may be dependent on factors other than timely initiation of vaccine administration, such as distribution and administration capacity.

      6. Low Influenza Vaccine Effectiveness Against A(H3N2)-Associated Hospitalizations in 2016-2017 and 2017-2018 of the Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN)external icon
        Martin ET, Cheng C, Petrie JG, Alyanak E, Gaglani M, Middleton DB, Ghamande S, Silveira FP, Murthy K, Zimmerman RK, Monto AS, Trabue C, Talbot HK, Ferdinands JM.
        J Infect Dis. 2021 Jun 15;223(12):2062-2071.
        BACKGROUND: The 2016-2017 and 2017-2018 influenza seasons were notable for the high number of hospitalizations for influenza A(H3N2) despite vaccine and circulating strain match. METHODS: We evaluated vaccine effectiveness (VE) against hospitalization in the test-negative HAIVEN study. Nasal-throat swabs were tested by quantitative reverse transcription polymerase chain reaction (RT-PCR) for influenza and VE was determined based on odds of vaccination by generalized estimating equations. Vaccine-specific antibody was measured in a subset of enrollees. RESULTS: A total of 6129 adults were enrolled from 10 hospitals. Adjusted VE against A(H3N2) was 22.8% (95% confidence interval [CI], 8.3% to 35.0%), pooled across both years and 49.4% (95% CI, 34.3% to 61.1%) against B/Yamagata. In 2017-2018, the A(H3N2) VE point estimate for the cell-based vaccine was 43.0% (95% CI, -36.3% to 76.1%; 56 vaccine recipients) compared to 24.0% (95% CI, 3.9% to 39.9%) for egg-based vaccines. Among 643 with serology data, hemagglutinin antibodies against the egg-based A(H3N2) vaccine strain were increased in influenza-negative individuals. CONCLUSIONS: Low VE for the A/Hong Kong/4801/2014 vaccine virus in both A(H3N2) seasons emphasizes concerns for continued changes in H3N2 antigenic epitopes, including changes that may impact glycosylation and ultimately reduce VE.

      7. Estimates of Inactivated Influenza Vaccine Effectiveness Among Children in Senegal: Results From 2 Consecutive Cluster-Randomized Controlled Trials in 2010 and 2011external icon
        Niang MN, Sugimoto JD, Diallo A, Diarra B, Ortiz JR, Lewis KD, Lafond KE, Halloran ME, Widdowson MA, Neuzil KM, Victor JC.
        Clin Infect Dis. 2021 Jun 15;72(12):e959-e969.
        BACKGROUND: We report results of years 2 and 3 of consecutive cluster-randomized controlled trials of trivalent inactivated influenza vaccine (IIV3) in Senegal. METHODS: We cluster-randomized (1:1) 20 villages to annual vaccination with IIV3 or inactivated poliovirus vaccine (IPV) of age-eligible residents (6 months-10 years). The primary outcome was total vaccine effectiveness against laboratory-confirmed influenza illness (LCI) among age-eligible children (modified intention-to-treat population [mITT]). Secondary outcomes were indirect (herd protection) and population (overall community) vaccine effectiveness. RESULTS: We vaccinated 74% of 12 408 age-eligible children in year 2 (June 2010-April 11) and 74% of 11 988 age-eligible children in year 3 (April 2011-December 2011) with study vaccines. Annual cumulative incidence of LCI was 4.7 (year 2) and 4.2 (year 3) per 100 mITT child vaccinees of IPV villages. In year 2, IIV3 matched circulating influenza strains. The total effectiveness was 52.8% (95% confidence interval [CI], 32.3-67.0), and the population effectiveness was 36.0% (95% CI, 10.2-54.4) against LCI caused by any influenza strain. The indirect effectiveness against LCI by A/H3N2 was 56.4% (95% CI, 39.0-68.9). In year 3, 74% of influenza detections were vaccine-mismatched to circulating B/Yamagata and 24% were vaccine-matched to circulating A/H3N2. The year 3 total effectiveness against LCI was -14.5% (95% CI, -81.2-27.6). Vaccine effectiveness varied by type/subtype of influenza in both years. CONCLUSIONS: IIV3 was variably effective against influenza illness in Senegalese children, with total and indirect vaccine effectiveness present during the year when all circulating strains matched the IIV3 formulation. CLINICAL TRIALS REGISTRATION: NCT00893906.

      8. Evaluation of post-introduction COVID-19 vaccine effectiveness: Summary of interim guidance of the World Health Organizationexternal icon
        Patel MK, Bergeri I, Bresee JS, Cowling BJ, Crowcroft NS, Fahmy K, Hirve S, Kang G, Katz MA, Lanata CF, L'Azou Jackson M, Joshi S, Lipsitch M, Mwenda JM, Nogareda F, Orenstein WA, Ortiz JR, Pebody R, Schrag SJ, Smith PG, Srikantiah P, Subissi L, Valenciano M, Vaughn DW, Verani JR, Wilder-Smith A, Feikin DR.
        Vaccine. 2021 Jun 1.
        Phase 3 randomized-controlled trials have provided promising results of COVID-19 vaccine efficacy, ranging from 50 to 95% against symptomatic disease as the primary endpoints, resulting in emergency use authorization/listing for several vaccines. However, given the short duration of follow-up during the clinical trials, strict eligibility criteria, emerging variants of concern, and the changing epidemiology of the pandemic, many questions still remain unanswered regarding vaccine performance. Post-introduction vaccine effectiveness evaluations can help us to understand the vaccine's effect on reducing infection and disease when used in real-world conditions. They can also address important questions that were either not studied or were incompletely studied in the trials and that will inform evolving vaccine policy, including assessment of the duration of effectiveness; effectiveness in key subpopulations, such as the very old or immunocompromised; against severe disease and death due to COVID-19; against emerging SARS-CoV-2 variants of concern; and with different vaccination schedules, such as number of doses and varying dosing intervals. WHO convened an expert panel to develop interim best practice guidance for COVID-19 vaccine effectiveness evaluations. We present a summary of the interim guidance, including discussion of different study designs, priority outcomes to evaluate, potential biases, existing surveillance platforms that can be used, and recommendations for reporting results.

      9. COVID-19 Vaccination Coverage Among Pregnant Women During Pregnancy - Eight Integrated Health Care Organizations, United States, December 14, 2020-May 8, 2021external icon
        Razzaghi H, Meghani M, Pingali C, Crane B, Naleway A, Weintraub E, Kenigsberg TA, Lamias MJ, Irving SA, Kauffman TL, Vesco KK, Daley MF, DeSilva M, Donahue J, Getahun D, Glenn S, Hambidge SJ, Jackson L, Lipkind HS, Nelson J, Zerbo O, Oduyebo T, Singleton JA, Patel SA.
        MMWR Morb Mortal Wkly Rep. 2021 Jun 18;70(24):895-899.
        COVID-19 vaccines are critical for ending the COVID-19 pandemic; however, current data about vaccination coverage and safety in pregnant women are limited. Pregnant women are at increased risk for severe illness and death from COVID-19 compared with nonpregnant women of reproductive age, and are at risk for adverse pregnancy outcomes, such as preterm birth (1-4). Pregnant women are eligible for and can receive any of the three COVID-19 vaccines available in the United States via Emergency Use Authorization.* Data from Vaccine Safety Datalink (VSD), a collaboration between CDC and multiple integrated health systems, were analyzed to assess receipt of ≥1 dose (first or second dose of the Pfizer-BioNTech or Moderna vaccines or a single dose of the Janssen [Johnson & Johnson] vaccine) of any COVID-19 vaccine during pregnancy, receipt of first dose of a 2-dose COVID-19 vaccine (initiation), or completion of a 1- or 2-dose COVID-19 vaccination series. During December 14, 2020-May 8, 2021, a total of 135,968 pregnant women were identified, 22,197 (16.3%) of whom had received ≥1 dose of a vaccine during pregnancy. Among these 135,968 women, 7,154 (5.3%) had initiated and 15,043 (11.1%) had completed vaccination during pregnancy. Receipt of ≥1 dose of COVID-19 vaccine during pregnancy was highest among women aged 35-49 years (22.7%) and lowest among those aged 18-24 years (5.5%), and higher among non-Hispanic Asian (Asian) (24.7%) and non-Hispanic White (White) women (19.7%) than among Hispanic (11.9%) and non-Hispanic Black (Black) women (6.0%). Vaccination coverage increased among all racial and ethnic groups over the analytic period, likely because of increased eligibility for vaccination(†) and increased availability of vaccine over time. These findings indicate the need for improved outreach to and engagement with pregnant women, especially those from racial and ethnic minority groups who might be at higher risk for severe health outcomes because of COVID-19 (4). In addition, providing accurate and timely information about COVID-19 vaccination to health care providers, pregnant women, and women of reproductive age can improve vaccine confidence and coverage by ensuring optimal shared clinical decision-making.

      10. The future of Japanese encephalitis vaccination: expert recommendations for achieving and maintaining optimal JE controlexternal icon
        Vannice KS, Hills SL, Schwartz LM, Barrett AD, Heffelfinger J, Hombach J, Letson GW, Solomon T, Marfin AA.
        NPJ Vaccines. 2021 Jun 15;6(1):82.

    • Injury and Violence
      1. Emergency Department Visits for Suspected Suicide Attempts Among Persons Aged 12-25 Years Before and During the COVID-19 Pandemic - United States, January 2019-May 2021external icon
        Yard E, Radhakrishnan L, Ballesteros MF, Sheppard M, Gates A, Stein Z, Hartnett K, Kite-Powell A, Rodgers L, Adjemian J, Ehlman DC, Holland K, Idaikkadar N, Ivey-Stephenson A, Martinez P, Law R, Stone DM.
        MMWR Morb Mortal Wkly Rep. 2021 Jun 18;70(24):888-894.
        Beginning in March 2020, the COVID-19 pandemic and response, which included physical distancing and stay-at-home orders, disrupted daily life in the United States. Compared with the rate in 2019, a 31% increase in the proportion of mental health-related emergency department (ED) visits occurred among adolescents aged 12-17 years in 2020 (1). In June 2020, 25% of surveyed adults aged 18-24 years reported experiencing suicidal ideation related to the pandemic in the past 30 days (2). More recent patterns of ED visits for suspected suicide attempts among these age groups are unclear. Using data from the National Syndromic Surveillance Program (NSSP),* CDC examined trends in ED visits for suspected suicide attempts(†) during January 1, 2019-May 15, 2021, among persons aged 12-25 years, by sex, and at three distinct phases of the COVID-19 pandemic. Compared with the corresponding period in 2019, persons aged 12-25 years made fewer ED visits for suspected suicide attempts during March 29-April 25, 2020. However, by early May 2020, ED visit counts for suspected suicide attempts began increasing among adolescents aged 12-17 years, especially among girls. During July 26-August 22, 2020, the mean weekly number of ED visits for suspected suicide attempts among girls aged 12-17 years was 26.2% higher than during the same period a year earlier; during February 21-March 20, 2021, mean weekly ED visit counts for suspected suicide attempts were 50.6% higher among girls aged 12-17 years compared with the same period in 2019. Suicide prevention measures focused on young persons call for a comprehensive approach, that is adapted during times of infrastructure disruption, involving multisectoral partnerships (e.g., public health, mental health, schools, and families) and implementation of evidence-based strategies (3) that address the range of factors influencing suicide risk.

    • Laboratory Sciences
      1. CDC designed a rapid HPGe Bioassay Method for (137)Cs, (60)Co, and (192)Ir that is suitable for a public health response to a radiological incident where people may ingest or inhale radionuclides. The method uses a short count time, small sample volume, and a large volume detector and well size. It measures a patient's urine sample collected post-incident. The levels of concern are directly related to the Clinical Decision Guide levels recommended in the National Council of Radiation Protection 161.

      2. Database of ab initio L-edge X-ray absorption near edge structureexternal icon
        Chen Y, Chen C, Zheng C, Dwaraknath S, Horton MK, Cabana J, Rehr J, Vinson J, Dozier A, Kas JJ, Persson KA, Ong SP.
        Sci Data. 2021 Jun 11;8(1):153.
        The L-edge X-ray Absorption Near Edge Structure (XANES) is widely used in the characterization of transition metal compounds. Here, we report the development of a database of computed L-edge XANES using the multiple scattering theory-based FEFF9 code. The initial release of the database contains more than 140,000 L-edge spectra for more than 22,000 structures generated using a high-throughput computational workflow. The data is disseminated through the Materials Project and addresses a critical need for L-edge XANES spectra among the research community.

      3. Investigation of particle transfer to sampler covers during the transportation of samplesexternal icon
        Erekaife G, Park HD, Kashon ML, Chisholm WP, Lee EG.
        J Occup Environ Hyg. 2021 Jun 15:1-10.
        This study investigated the effects of particle transfer to the covers of aerosol samplers during transportation of wood dust and welding fume samples. Wood dust samples were collected in a sanding chamber using four sampler types: closed-face cassettes (CFC), CFC with Accu-CAP inserts, disposable inhalable samplers (DIS), and Institute of Occupational Medicine (IOM). Welding fumes were collected in a walk-in chamber using the same samplers, with Solu-Sert replacing Accu-CAP. The samples were divided into two groups, with one group transported by air and the other by land. They were returned in the same manner and analyzed gravimetrically for wood dust and chemically for welding fumes. For wood dust, IOM showed a significantly higher percentage of particles transferred to the covers compared with the other samplers regardless of the transportation mode (p < 0.0001; 64% by air and 15% by land), while other samplers showed less than or close to 10% (3.5-12%). When the percentages of particle transfer to the covers were compared between the air and land transportation, both IOM and CFC samples showed differences between modes of transportation, while others did not. For welding fumes, most samples (61% of samples for copper [Cu] and 76% of samples for manganese [Mn]) showed nondetectable amounts of the analyte on the covers. For all samplers, the particle transfer to the covers for both transportation modes ranged from 0.2-33% for Cu and less than 4.5% for Mn. Overall, this study confirms that particle transfer to sampler covers during transport highly depends upon the transportation mode and sampler type for wood dust, whereas particle transfer seems minimal for welding fumes. The findings of this study are based on two materials and limited sample sizes. Further investigation considering different industry types and tasks, particle size ranges, and materials might be necessary. Nevertheless, occupational professionals should account for this transfer when handling and analyzing samples in practice.

      4. Managing biological variation data: modern approaches for study design and clinical applicationexternal icon
        Johnson PR, Shahangian S, Astles JR.
        Crit Rev Clin Lab Sci. 2021 Jun 15:1-20.
        For more than one half-century, variability observed in clinical test result measurements has been ascribed to three major independent factors: (i) pre-analytical variation, occurring at sample collection and processing steps; (ii) analytical variation of the test method for which measurements are taken, and; (iii) biological variation (BV). Appreciation of this last source of variability is the major goal of this review article. Several recent advances have been made to generate, collate, and utilize BV data of biomarker tests within the clinical laboratory setting. Consideration of both prospective and retrospective study designs will be addressed. The prospective/direct study design will be described in accordance with recent recommendations discussed in the framework of a newly-developed system of checklist items. Potential value of retrospective/indirect study design, modeled on data mining from cohort studies or pathology laboratory information systems (LIS), offers an alternative approach to obtain BV estimates for clinical biomarkers. Moreover, updates to BV databases have made these data more current and widely accessible. Principal aims of this review are to provide the clinical laboratory scientist with a historical framework of BV concepts, to highlight useful applications of BV data within the clinical laboratory environment, and to discuss key terms and concepts related to statistical treatment of BV data.

      5. High-throughput quantitation of SARS-CoV-2 antibodies in a single-dilution homogeneous assayexternal icon
        Kainulainen MH, Bergeron E, Chatterjee P, Chapman AP, Lee J, Chida A, Tang X, Wharton RE, Mercer KB, Petway M, Jenks HM, Flietstra TD, Schuh AJ, Satheshkumar PS, Chaitram JM, Owen SM, McMullan LK, Flint M, Finn MG, Goldstein JM, Montgomery JM, Spiropoulou CF.
        Sci Rep. 2021 Jun 10;11(1):12330.
        SARS-CoV-2 emerged in late 2019 and has since spread around the world, causing a pandemic of the respiratory disease COVID-19. Detecting antibodies against the virus is an essential tool for tracking infections and developing vaccines. Such tests, primarily utilizing the enzyme-linked immunosorbent assay (ELISA) principle, can be either qualitative (reporting positive/negative results) or quantitative (reporting a value representing the quantity of specific antibodies). Quantitation is vital for determining stability or decline of antibody titers in convalescence, efficacy of different vaccination regimens, and detection of asymptomatic infections. Quantitation typically requires two-step ELISA testing, in which samples are first screened in a qualitative assay and positive samples are subsequently analyzed as a dilution series. To overcome the throughput limitations of this approach, we developed a simpler and faster system that is highly automatable and achieves quantitation in a single-dilution screening format with sensitivity and specificity comparable to those of ELISA.

      6. Comparative potency analysis of whole smoke solutions in the bacterial reverse mutation testexternal icon
        Meng F, Mei N, Yan J, Guo X, Richter PA, Chen T, De M.
        Mutagenesis. 2021 Jun 16.
        Short-term in vitro genotoxicity assays are useful tools to assess whether new and emerging tobacco products potentially have reduced toxicity. We previously demonstrated that potency ranking by benchmark dose (BMD) analysis quantitatively identifies differences among several known carcinogens and toxic chemicals representing different chemical classes found in cigarette smoke. In this study, six whole smoke solution (WSS) samples containing both the particulate and gas phases of tobacco smoke were generated from two commercial cigarette brands under different smoking-machine regimens. Sixty test cigarettes of each brand were machine-smoked according to the International Organization for Standardization (ISO) puffing protocol. In addition, either 60 or 20 test cigarettes of each brand were machine-smoked with the Canadian Intense (CI) puffing protocol. All six WSSs were evaluated in the bacterial reverse mutation (Ames) test using Salmonella typhimurium strains, in the presence or absence of S9 metabolic activation. The resulting S9-mediated mutagenic concentration-responses for the four WSSs from 60 cigarettes were then compared using BMD modeling analysis and the mutagenic potency expressed as number of revertants per μl of the WSS. The quantitative approaches resulted in a similar rank order of mutagenic potency for the Ames test in both TA98 and TA100. Under the conditions of this study, these results indicate that quantitative analysis of the Ames test data can discriminate between the mutagenic potencies of WSSs on the basis of smoking-machine regimen (ISO vs. CI), and cigarette product (differences in smoke chemistry).

      7. Responding to a radiological or nuclear incident may require assessing tens to hundreds of thousands of people for possible radionuclide contamination. The measurement of radioactive Sr is important because of its impact on people’s health. The existing analytical method for urine Sr-90 analysis using crown ethers is laborious and involves possible exposure to concentrated acids; therefore, this work is devoted to the development of the automated Sr-90 separation process, which became possible with the prepFast pre-analytical system (Elemental Scientific, Inc). © 2021, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

      8. RPAcan3990: an ultrasensitive recombinase polymerase assay to detect Angiostrongylus cantonensis DNAexternal icon
        Sears WJ, Qvarnstrom Y, Nutman TB.
        J Clin Microbiol. 2021 Jun 16:Jcm0118521.
        Angiostrongylus cantonensis (Ac) is one of the leading causes of eosinophilic meningitis worldwide. A field deployable molecular detection method could enhance both environmental surveillance and clinical diagnosis of this emerging pathogen. Accordingly, RPAcan3990, a recombinase polymerase assay (RPA) was developed to target a region predicted to be highly repeated in the Ac genome. The assay was then adapted to produce a visually interpretable fluorescent readout using an orange camera lens filter and a blue light. Using Ac genomic DNA, the limit of detection was found to be 1fg/μl by both fluorometer measurement and visual reading. All clinical samples known to be positive for Ac from various areas of the globe were positive by RPAcan3990. Cerebrospinal fluid samples from other etiologies of eosinophilic meningitis (i.e. Toxocara sp., Gnathostoma sp.) were negative in the RPAcan3990 assay. The optimal incubation temperature range for the reaction was between 35-40°C. The assay successfully detected 1fg/μl of Ac genomic DNA after incubation at human body temperature (in a shirt pocket). In conclusion, these data suggest RPAcan3990 is potentially a point of contact molecular assay capable of sensitively detecting Ac by producing visually interpretable results with minimal instrumentation.

      9. The United States experienced an outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI) that began in August 2019. Patient diagnosis and treatment sometimes involved bronchoscopy and collection of the bronchoalveolar lavage (BAL) fluid. Although this matrix has been useful for understanding some chemical exposures in the lungs, no methods existed for measuring the nicotine content. Therefore, we developed a simple and sensitive method for measuring nicotine in the BAL fluid. Nicotine was extracted from the BAL fluid using acetone precipitation in a 96-well plate format to increase the sample throughput (200 samples/day). We optimized liquid chromatography column conditions (e.g., mobile phase, column temperature) and mass spectrometry parameters to improve the signal-to-noise ratio and lower limits of detection (LOD) for measuring nicotine in the BAL fluid. The LOD for nicotine in the BAL fluid was 0.050 ng/mL at a sample volume of 40 μL of the BAL fluid. The within-day and between-day imprecision and bias were less than 10%. This method detected nicotine in 15 of 43 BAL fluids from EVALI case patients. This method is useful for understanding recent inhalational exposure to nicotine as part of characterizing EVALI or similar illnesses.

      10. The characterization of the metabolism of lower chlorinated PCB, such as 4-chlorobiphenyl (PCB3), is challenging because of the complex metabolite mixtures formed in vitro and in vivo. We performed parallel metabolism studies with PCB3 and its hydroxylated metabolites to characterize the metabolism of PCB3 in HepG2 cells using nontarget high-resolution mass spectrometry (Nt-HRMS). Briefly, HepG2 cells were exposed for 24 h to 10 μM PCB3 or its seven hydroxylated metabolites in DMSO or DMSO alone. Six classes of metabolites were identified with Nt-HRMS in the culture medium exposed to PCB3, including monosubstituted metabolites at the 3'-, 4'-, 3-, and 4- (1,2-shift product) positions and disubstituted metabolites at the 3',4'-position. 3',4'-Di-OH-3 (4'-chloro-3,4-dihydroxybiphenyl), which can be oxidized to a reactive and toxic PCB3 quinone, was a central metabolite that was rapidly methylated. The resulting hydroxylated-methoxylated metabolites underwent further sulfation and, to a lesser extent, glucuronidation. Metabolomic analyses revealed an altered tryptophan metabolism in HepG2 cells following PCB3 exposure. Some PCB3 metabolites were associated with alterations of endogenous metabolic pathways, including amino acid metabolism, vitamin A (retinol) metabolism, and bile acid biosynthesis. In-depth studies are needed to investigate the toxicities of PCB3 metabolites, especially the 3',4'-di-OH-3 derivatives identified in this study.

    • Occupational Safety and Health
      1. Risk assessment for o-toluidine and bladder cancer incidenceexternal icon
        Park RM, Carreón T, Hanley KW.
        Am J Ind Med. 2021 Jun 10.
        BACKGROUND: Elevated bladder cancer incidence has been reported in a cohort of 1875 workers manufacturing chemicals used in the rubber industry and employed any time during 1946-2006. o-Toluidine (OT), an aromatic amine, was the prime suspect agent. Using the available environmental data and process characterization, previous investigators assigned ranks to volatile chemical air concentrations across time in departments and jobs, reflecting probabilities of exposure and use of personal protective equipment for airborne and dermal exposures. Aniline, another aromatic amine, was present at comparable concentrations and is known to be an animal carcinogen but produced lower levels in post-shift urine and of hemoglobin adducts than OT in a group of workers. METHODS: A quantitative risk assessment was performed based on this same population. In this study, cumulative OT exposures were estimated (a) based on previously assigned ranks of exposure intensity and reported actual exposures in jobs with the highest assigned rank, and (b) directly from the historical environmental sampling for OT. Models of bladder cancer incidence were evaluated taking into account possible healthy worker survivor effects. RESULTS: Under various assumptions regarding workforce turnover, the excess lifetime risk of bladder cancer from OT exposure at 1 ppb was estimated to be in the range 1-7 per thousand. CONCLUSIONS: The current ACGIH TLV and OSHA standards for OT are 2 and 5 ppm, respectively, 1000-fold higher than the exposure estimated here for 1-7 per thousand excess lifetime risk.

    • Parasitic Diseases
      1. Impact of Community-Based Mass Testing and Treatment on Malaria Infection Prevalence in a High-Transmission Area of Western Kenya: A Cluster Randomized Controlled Trialexternal icon
        Samuels AM, Odero NA, Odongo W, Otieno K, Were V, Shi YP, Sang T, Williamson J, Wiegand R, Hamel MJ, Kachur SP, Slutsker L, Lindblade KA, Kariuki SK, Desai MR.
        Clin Infect Dis. 2021 Jun 1;72(11):1927-1935.
        BACKGROUND: Global gains toward malaria elimination have been heterogeneous and have recently stalled. Interventions targeting afebrile malaria infections may be needed to address residual transmission. We studied the efficacy of repeated rounds of community-based mass testing and treatment (MTaT) on malaria infection prevalence in western Kenya. METHODS: Twenty clusters were randomly assigned to 3 rounds of MTaT per year for 2 years or control (standard of care for testing and treatment at public health facilities along with government-sponsored mass long-lasting insecticidal net [LLIN] distributions). During rounds, community health volunteers visited all households in intervention clusters and tested all consenting individuals with a rapid diagnostic test. Those positive were treated with dihydroartemisinin-piperaquine. Cross-sectional community infection prevalence surveys were performed in both study arms at baseline and each year after 3 rounds of MTaT. The primary outcome was the effect size of MTaT on parasite prevalence by microscopy between arms by year, adjusted for age, reported LLIN use, enhanced vegetative index, and socioeconomic status. RESULTS: Demographic and behavioral characteristics, including LLIN usage, were similar between arms at each survey. MTaT coverage across the 3 annual rounds ranged between 75.0% and 77.5% in year 1, and between 81.9% and 94.3% in year 2. The adjusted effect size of MTaT on the prevalence of parasitemia between arms was 0.93 (95% confidence interval [CI], .79-1.08) and 0.92 (95% CI, .76-1.10) after year 1 and year 2, respectively. CONCLUSIONS: MTaT performed 3 times per year over 2 years did not reduce malaria parasite prevalence in this high-transmission area. CLINICAL TRIALS REGISTRATION: NCT02987270.

      2. Urogenital schistosomiasis infection prevalence targets to determine elimination as a public health problem based on microhematuria prevalence in school-age childrenexternal icon
        Wiegand RE, Fleming FM, Straily A, Montgomery SP, de Vlas SJ, Utzinger J, Vounatsou P, Secor WE.
        PLoS Negl Trop Dis. 2021 Jun 11;15(6):e0009451.
        BACKGROUND: Recent research suggests that schistosomiasis targets for morbidity control and elimination as a public health problem could benefit from a reanalysis. These analyses would define evidence-based targets that control programs could use to confidently assert that they had controlled or eliminated schistosomiasis as a public health problem. We estimated how low Schistosoma haematobium infection levels diagnosed by urine filtration in school-age children should be decreased so that microhematuria prevalence was at, or below, a "background" level of morbidity. METHODOLOGY: Data obtained from school-age children in Burkina Faso, Mali, Niger, Tanzania, and Zambia who participated in schistosomiasis monitoring and evaluation cohorts were reanalyzed before and after initiation of preventive chemotherapy. Bayesian models estimated the infection level prevalence probabilities associated with microhematuria thresholds ≤10%, 13%, or 15%. PRINCIPAL FINDINGS: An infection prevalence of 5% could be a sensible target for urogenital schistosomiasis morbidity control in children as microhematuria prevalence was highly likely to be below 10% in all surveys. Targets of 8% and 11% infection prevalence were highly likely to result in microhematuria levels less than 13% and 15%, respectively. By contrast, measuring heavy-intensity infections only achieves these thresholds at impractically low prevalence levels. CONCLUSIONS/SIGNIFICANCE: A target of 5%, 8%, or 11% urogenital schistosomiasis infection prevalence in school-age children could be used to determine whether a geographic area has controlled or eliminated schistosomiasis as a public health problem depending on the local background threshold of microhematuria.

    • Reproductive Health
      1. Exploring experience of and engagement in coercive pregnancy behaviors among sexually active young men from five clinics in Baltimore, MDexternal icon
        Dimenstein NB, Lindberg LD, Sanders R, Jennings JM, Frohwirth LF, Dittus PJ, Marcell AV.
        Contraception. 2021 Jun 9.
        OBJECTIVES: To explore young men's perceived experience of coercive pregnancy behaviors by female partners, and engagement in and behavioral overlap of these occurrences in this sample. STUDY DESIGN: Heterosexually active young men aged 15-24 (n=39), recruited from three primary care and two sexually transmitted disease clinics in Baltimore, MD city over a two-week period, were surveyed on their perceived experience of and engagement in coercive pregnancy behaviors, attitudes about women, and background characteristics. RESULTS: Of 130 invited, sixty-six (51%) agreed to participate, 39 of whom were heterosexual young men; 87% were non-Hispanic Black and 59% were aged 20-24. Eleven (28%) perceived one or more coercive pregnancy behaviors by a partner and nine (23%) engaged in one or more coercive behavior. Most (58%) agreed women are responsible for birth control decisions, but 55% believed women could not be trusted to tell the truth about contraceptive use and 68% believe women would like to get pregnant. CONCLUSIONS: Over one-third of young men perceived experience of coercive pregnancy behaviors by partners and/or engaged in these behaviors. Findings have implications for promoting healthy relationships among young people.

      2. Factors Associated with Contraceptive Use in Sub-Saharan Africaexternal icon
        Kraft JM, Serbanescu F, Schmitz MM, Mwanshemele Y, Ruiz AG, Maro G, Chaote P.
        J Womens Health (Larchmt). 2021 Jun 14.
        Background: Globally 10% of women have an unmet need for contraception, with higher rates in sub-Saharan Africa. Programs to improve family planning (FP) outcomes require data on how service characteristics (e.g., geographic access, quality) and women's characteristics are associated with contraceptive use. Materials and Methods: We combined data from health facility assessments (2018 and 2019) and a population-based regional household survey (2018) of married and in-union women ages 15-49 in the Kigoma Region of Tanzania. We assessed the associations between contraceptive use and service (i.e., distance, methods available, personnel) and women's (e.g., demographic characteristics, fertility experiences and intentions, attitudes toward FP) characteristics. Results: In this largely rural sample (n = 4,372), 21.7% of women used modern reversible contraceptive methods. Most variables were associated with contraceptive use in bivariate analyses. In multivariate analyses, access to services located <2 km of one's home that offered five methods (adjusted odds ratio [aOR] = 1.57, confidence interval [CI] = 1.18-2.10) and had basic amenities (aOR = 1.66, CI = 1.24-2.2) increased the odds of contraceptive use. Among individual variables, believing that FP benefits the family (aOR = 3.65, CI = 2.18-6.11) and believing that contraception is safe (aOR = 2.48, CI = 1.92-3.20) and effective (aOR = 3.59, CI = 2.63-4.90) had strong associations with contraceptive use. Conclusions: Both service and individual characteristics were associated with contraceptive use, suggesting the importance of coordination between efforts to improve access to services and social and behavior change interventions that address motivations, knowledge, and attitudes toward FP.

    • Social and Behavioral Sciences
      1. Mental Health Among Parents of Children Aged <18 Years and Unpaid Caregivers of Adults During the COVID-19 Pandemic - United States, December 2020 and February-⁠March 2021external icon
        Czeisler M, Rohan EA, Melillo S, Matjasko JL, DePadilla L, Patel CG, Weaver MD, Drane A, Winnay SS, Capodilupo ER, Robbins R, Wiley JF, Facer-Childs ER, Barger LK, Czeisler CA, Howard ME, Rajaratnam SM.
        MMWR Morb Mortal Wkly Rep. 2021 Jun 18;70(24):879-887.
        Early during the COVID-19 pandemic, nearly two thirds of unpaid caregivers of adults reported adverse mental or behavioral health symptoms, compared with approximately one third of noncaregivers(†) (1). In addition, 27% of parents of children aged <18 years reported that their mental health had worsened during the pandemic (2). To examine mental health during the COVID-19 pandemic among U.S. adults on the basis of their classification as having a parenting role (i.e., unpaid persons caring for children and adolescents aged <18 years, referred to as children in this report) or being an unpaid caregiver of adults (i.e., persons caring for adults aged ≥18 years),(§) CDC analyzed data from cross-sectional surveys that were administered during December 2020 and February-March 2021 for The COVID-19 Outbreak Public Evaluation (COPE) Initiative.(¶) Respondents were categorized as parents only, caregivers of adults only, parents-caregivers (persons in both roles), or nonparents/noncaregivers (persons in neither role). Adjusted odds ratios (aORs) for any adverse mental health symptoms, particularly suicidal ideation, were higher among all respondents who were parents, caregivers of adults, or both compared with respondents who were nonparents/noncaregivers and were highest among persons in both roles (parents-caregivers) (any adverse mental health symptoms: aOR = 5.1, 95% confidence interval [CI] = 4.1-6.2; serious suicidal ideation: aOR = 8.2, 95% CI = 6.5-10.4). These findings highlight that parents and caregivers, especially those balancing roles both as parents and caregivers, experienced higher levels of adverse mental health symptoms during the COVID-19 pandemic than adults without these responsibilities. Caregivers who had someone to rely on for support had lower odds of experiencing any adverse mental health symptoms. Additional measures are needed to improve mental health among parents, caregivers, and parents-caregivers.

    • Substance Use and Abuse

    • Zoonotic and Vectorborne Diseases
      1. The urgency of resuming disrupted dog rabies vaccination campaigns: a modeling and cost-effectiveness analysisexternal icon
        Kunkel A, Jeon S, Joseph HC, Dilius P, Crowdis K, Meltzer MI, Wallace R.
        Sci Rep. 2021 Jun 14;11(1):12476.
        Dog vaccination is a cost-effective approach to preventing human rabies deaths. In Haiti, the last nation-wide dog vaccination campaign occurred in 2018. We estimated the number of human lives that could be saved by resuming dog vaccination in 2021 compared to 2022 and compared the cost-effectiveness of these two scenarios. We modified a previously published rabies transmission and economic model to estimate trends in dog and human rabies cases in Haiti from 2005 to 2025, with varying assumptions about when dog vaccinations resume. We compared model outputs to surveillance data on human rabies deaths from 2005 to 2020 and animal rabies cases from 2018 to 2020. Model predictions and surveillance data both suggest a 5- to 8-fold increase in animal rabies cases occurred in Haiti's capital city between Fall 2019 and Fall 2020. Restarting dog vaccination in Haiti in 2021 compared to 2022 could save 285 human lives and prevent 6541 human rabies exposures over a five-year period. It may also decrease program costs due to reduced need for human post-exposure prophylaxis. These results show that interruptions in dog vaccination campaigns before elimination is achieved can lead to significant human rabies epidemics if not promptly resumed.

      2. Spatiotemporal Heterogeneity of Zika Virus Transmission in Indonesia: Serosurveillance Data from a Pediatric Populationexternal icon
        Sasmono RT, Johar E, Yohan B, Ma'roef CN, Pronyk P, Hadinegoro SR, Soepardi EJ, Bouckenooghe A, Hawley WA, Rosenberg R, Powers AM, Soebandrio A, Myint KS.
        Am J Trop Med Hyg. 2021 May 3;104(6):2220-3.
        The presence of Zika virus (ZIKV) in Indonesia has been recognized since the 1970s, but its transmission dynamics there have been poorly understood. To understand more fully the geographic distribution and burden of ZIKV disease, we performed retrospective serological tests on specimens collected from asymptomatic children age 5 to 9 years old living at 30 sites in 14 provinces. Of 870 serum samples tested, 9.2% were found to be positive for anti-ZIKV antibodies, as confirmed by plaque reduction neutralization assays. This was the same overall prevalence reported previously for 1- to 4-year-old children collected at the same sites at the same time. Together with geographic differences in seroprevalence between the age groups, these data suggest that, although ZIKV might be endemic in Indonesia, its occurrence has been focal and episodic.


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