Volume 12, Issue 42, November 24, 2020

CDC Science Clips: Volume 12, Issue 42, November 24, 2020

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. 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. The Lancet Commission on diabetes: using data to transform diabetes care and patient livesexternal icon
        Chan JC, Lim LL, Wareham NJ, Shaw JE, Orchard TJ, Zhang P, Lau ES, Eliasson B, Kong AP, Ezzati M, Aguilar-Salinas CA, McGill M, Levitt NS, Ning G, So WY, Adams J, Bracco P, Forouhi NG, Gregory GA, Guo J, Hua X, Klatman EL, Magliano DJ, Ng BP, Ogilvie D, Panter J, Pavkov M, Shao H, Unwin N, White M, Wou C, Ma RC, Schmidt MI, Ramachandran A, Seino Y, Bennett PH, Oldenburg B, Gagliardino JJ, Luk AO, Clarke PM, Ogle GD, Davies MJ, Holman RR, Gregg EW.
        Lancet. 2020 Nov 12.

      2. Angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use among hypertensive US adults with albuminuriaexternal icon
        Chu CD, Powe NR, McCulloch CE, Banerjee T, Crews DC, Saran R, Bragg-Gresham J, Morgenstern H, Pavkov ME, Saydah SH, Tuot DS.
        Hypertension. 2020 Nov 16.
        Since 2003, US hypertension guidelines have recommended ACE (angiotensin-converting enzyme) inhibitors or ARBs (angiotensin receptor blockers) as first-line antihypertensive therapy in the presence of albuminuria (urine albumin/creatinine ratio ≥300 mg/g). To examine national trends in guideline-concordant ACE inhibitor/ARB utilization, we studied adults participating in the National Health and Nutrition Examination Surveys 2001 to 2018 with hypertension (defined by self-report of high blood pressure, systolic blood pressure ≥140 mm Hg or diastolic ≥90 mm Hg, or use of antihypertensive medications). Among 20 538 included adults, the prevalence of albuminuria ≥300 mg/g was 2.8% in 2001 to 2006, 2.8% in 2007 to 2012, and 3.2% in 2013 to 2018. Among those with albuminuria ≥300 mg/g, no consistent trends were observed for the proportion receiving ACE inhibitor/ARB treatment from 2001 to 2018 among persons with diabetes, without diabetes, or overall. In 2013 to 2018, ACE inhibitor/ARB usage in the setting of albuminuria ≥300 mg/g was 55.3% (95% CI, 46.8%-63.6%) among adults with diabetes and 33.4% (95% CI, 23.1%-45.5%) among those without diabetes. Based on US population counts, these estimates represent 1.6 million adults with albuminuria ≥300 mg/g currently not receiving ACE inhibitor/ARB therapy, nearly half of whom do not have diabetes. ACE inhibitor/ARB underutilization represents a significant gap in preventive care delivery for adults with hypertension and albuminuria that has not substantially changed over time.

    • Communicable Diseases
      1. Features of Streptococcus agalactiae strains recovered from pregnant women and newborns attending different hospitals in Ethiopiaexternal icon
        Ali MM, Woldeamanuel Y, Asrat D, Fenta DA, Beall B, Schrag S, McGee L.
        BMC Infect Dis. 2020 Nov 16;20(1):848.
        BACKGROUND: Streptococcus agalactiae (Group B Streptococcus, GBS) serotypes, sequence types, and antimicrobial resistance profile vary across different geographic locations affecting disease patterns in newborns. These differences are important considerations for vaccine development efforts and data from large countries in Africa is limited. The aim of this study was to determine serotypes and genotypes of GBS isolates from pregnant women and their newborns in Ethiopia. METHODS: A hospital based cross-sectional study was conducted at three hospitals in Ethiopia from June 2014 to September 2015. Out of 225 GBS isolates, 121 GBS were recovered, confirmed and characterized at CDC's Streptococcus Laboratory using conventional microbiology methods and whole genome sequencing. RESULTS: Of the 121 isolates, 87 were from rectovaginal samples of pregnant women, 32 from different body parts of their newborns and 2 from blood of newborns with suspected sepsis. There were 25 mother-infant pairs and 24 pairs had concordant strains. The most prevalent serotypes among mothers and/or their babies were II, Ia and V (41.5, 20.6, 19.5 and 40.6%, 25 and 15.6%, respectively). Multilocus sequence typing (MLST) on 83 isolates showed ST10 (24; 28.9%) and ST2 (12; 14.5%) as most predominant sequence types. All GBS strains were susceptible to penicillin, cefotaxime and vancomycin, which correlated to the presence of wildtype PBP2x types and the lack of known vancomycin-resistance genes. Tetracycline resistance was high (73; 88%, associated primarily with tetM, but also tetO and tetL). Five isolates (6%) were resistant to erythromycin and clindamycin and 3 isolates were fluoroquinolone-resistant, containing associated mutations in gyrA and parC genes. All isolates were positive for one of four homologous Alpha/Rib family determinants and 1-2 of the three main pilus types. CONCLUSIONS: Predominant serotypes were II, Ia, and V. A limited number of clonal types were identified with two STs accounting for about half of the isolates. All strains collected in this study were susceptible to beta-lactam antibiotics and vancomycin. Typical of most GBS, these isolates were positive for single alpha-like family protein, serine-rich repeat gene, as well as 1-2 pilus determinants.

      2. Vital Signs: Deaths among persons with diagnosed HIV infection, United States, 2010-2018external icon
        Bosh KA, Johnson AS, Hernandez AL, Prejean J, Taylor J, Wingard R, Valleroy LA, Hall HI.
        MMWR Morb Mortal Wkly Rep. 2020 Nov 20;69(46):1717-1724.
        BACKGROUND: Life expectancy for persons with human immunodeficiency virus (HIV) infection who receive recommended treatment can approach that of the general population, yet HIV remains among the 10 leading causes of death among certain populations. Using surveillance data, CDC assessed progress toward reducing deaths among persons with diagnosed HIV (PWDH). METHODS: CDC analyzed National HIV Surveillance System data for persons aged ≥13 years to determine age-adjusted death rates per 1,000 PWDH during 2010-2018. Using the International Classification of Diseases, Tenth Revision, deaths with a nonmissing underlying cause were classified as HIV-related or non-HIV-related. Temporal changes in total deaths during 2010-2018 and deaths by cause during 2010-2017 (2018 excluded because of delays in reporting), by demographic characteristics, transmission category, and U.S. Census region of residence at time of death were calculated. RESULTS: During 2010-2018, rates of death decreased by 36.6% overall (from 19.4 to 12.3 per 1,000 PWDH). During 2010-2017, HIV-related death rates decreased 48.4% (from 9.1 to 4.7), whereas non-HIV-related death rates decreased 8.6% (from 9.3 to 8.5). Rates of HIV-related deaths during 2017 were highest by race/ethnicity among persons of multiple races (7.0) and Black/African American persons (5.6), followed by White persons (3.9) and Hispanic/Latino persons (3.9). The HIV-related death rate was highest in the South (6.0) and lowest in the Northeast (3.2). CONCLUSION: Early diagnosis, prompt treatment, and maintaining access to high-quality care and treatment have been successful in reducing HIV-related deaths and remain necessary for continuing reductions in HIV-related deaths.

      3. A nationwide outbreak of invasive pneumococcal disease in Israel caused by Streptococcus pneumoniae serotype 2external icon
        Dagan R, Ben-Shimol S, Benisty R, Regev-Yochay G, Lo SW, Bentley SD, Hawkins PA, McGee L, Ron M, Givon-Lavi N, Valinsky L, Rokney A.
        Clin Infect Dis. 2020 Nov 17.
        BACKGROUND: Invasive pneumococcal disease (IPD) caused by Streptococcus pneumoniae serotype 2 (Sp2) is infrequent. Large scale outbreaks have not been reported following pneumococcal conjugate vaccine (PCV) implementation. We describe a Sp2 IPD outbreak in Israel, in the 13-valent PCV (PCV13) era, with focus on Sp2 population structure and evolutionary dynamics. METHODS: The data derived from a population-based, nationwide active surveillance of IPD since 2009. 7-valent PCV (PCV7)/PCV13 vaccines were introduced in July 2009 and November 2010, respectively. Sp2 isolates were tested for antimicrobial susceptibility, Multilocus Sequence Typing (MLST) and Whole Genome Sequencing (WGS) analysis. RESULTS: Overall, 170 Sp2 IPD cases were identified during 2009-2019; Sp2 increased in 2015 and caused 6% of IPD during 2015-2019, a 7-fold increase compared with 2009-2014.The outbreak was caused by a previously unreported molecular type (ST-13578), initially observed in Israel in 2014. This clone caused 88% of Sp2 during 2015-2019. ST-13578 is a single-locus variant of ST-1504, previously reported globally, including in Israel. WGS analysis confirmed clonality among the ST-13578 population. Single-nucleotide polymorphisms-dense regions support a hypothesis that the ST-13578 outbreak clone evolved from ST-1504 by recombination.All tested strains were penicillin-susceptible (MIC <0.06 μg/mL). The ST-13578 clone was identified almost exclusively (99%) in the Jewish population and was mainly distributed in 3/7 Israeli districts. The outbreak is still ongoing, although declining since 2017.Conclusions: To the best of our knowledge, this is the first widespread Sp2 outbreak since PCV13 introduction worldwide, caused by the emerging ST-13578 clone.

      4. Remote household observation for non-influenza respiratory viral illnessexternal icon
        Emanuels A, Heimonen J, O'Hanlon J, Kim AE, Wilcox N, McCulloch DJ, Brandstetter E, Wolf CR, Logue JK, Han PD, Pfau B, Newman KL, Hughes JP, Jackson ML, Uyeki TM, Boeckh M, Starita LM, Nickerson DA, Bedford T, Englund JA, Chu HY.
        Clin Infect Dis. 2020 Nov 17.
        BACKGROUND: Non-influenza respiratory viruses are responsible for a substantial burden of disease in the United States. Household transmission is thought to contribute significantly to subsequent transmission through the broader community. In the context of the COVID-19 pandemic, contactless surveillance methods are of particular importance. METHODS: From November 2019 to April 2020, 303 households in the Seattle area were remotely monitored in a prospective longitudinal study for symptoms of respiratory viral illness. Enrolled participants reported weekly symptoms and submitted respiratory samples by mail in the event of an acute respiratory illness (ARI). Specimens were tested for fourteen viruses, including SARS-CoV-2, using RT-PCR. Participants completed all study procedures at home without physical contact with research staff. RESULTS: In total, 1171 unique participants in 303 households were monitored for ARI. Of participating households, 128 (42%) included a child aged <5 years and 202 (67%) included a child aged 5-12 years. Of the 678 swabs collected during the surveillance period, 237 (35%) tested positive for one or more non-influenza respiratory viruses. Rhinovirus, common human coronaviruses, and respiratory syncytial virus were the most common. Four cases of SARS-CoV-2 were detected in three households. CONCLUSIONS: This study highlights the circulation of respiratory viruses within households during the winter months during the emergence of the SARS-CoV-2 pandemic. Contactless methods of recruitment, enrollment and sample collection were utilized throughout this study, and demonstrate the feasibility of home-based, remote monitoring for respiratory infections.

      5. Factors associated with typical enteropathogenic Escherichia coli infection among children <5 years old with moderate-to-severe diarrhoea in rural western Kenya, 2008-2012external icon
        Fagerli K, Omore R, Kim S, Ochieng JB, Ayers TL, Juma J, Farag TH, Nasrin D, Panchalingam S, Robins-Browne RM, Nataro JP, Kotloff KL, Levine MM, Oundo J, Parsons MB, Laserson KF, Mintz ED, Breiman RF, O'Reilly CE.
        Epidemiol Infect. 2020 Nov 16:1-37.

      6. Progress toward poliomyelitis eradication - Pakistan, January 2019-September 2020external icon
        Hsu CH, Rehman MS, Bullard K, Jorba J, Kader M, Young H, Safdar M, Jafari HS, Ehrhardt D.
        MMWR Morb Mortal Wkly Rep. 2020 Nov 20;69(46):1748-1752.
        Pakistan and Afghanistan are the only countries where wild poliovirus type 1 (WPV1) is endemic (1,2). In 2019, Pakistan reported 147 WPV1 cases, approximately 12 times the number reported in 2018. As of September 15, 72 cases had been reported in 2020. Since 2019, WPV1 transmission has also spread from Pakistan's core poliovirus reservoirs (Karachi, Peshawar, and Quetta block) to southern districts of Khyber Pakhtunkhwa (KP), Punjab, and Sindh provinces. Further, an outbreak of circulating vaccine-derived poliovirus type 2 (cVDPV2), first detected in July 2019, has caused 22 paralytic cases in 2019 and 59 as of September 15, 2020, throughout the country. The coronavirus disease 2019 (COVID-19) pandemic has substantially reduced delivery of polio vaccines through essential immunization (formerly routine immunization) and prevented implementation of polio supplementary immunization activities (SIAs)* during March-July 2020. This report describes Pakistan's progress in polio eradication during January 2019-September 2020 and updates previous reports (1,3,4). The Pakistan polio program has reinitiated SIAs and will need large, intensive, high-quality campaigns with strategic use of available oral poliovirus vaccines (OPVs)(†) to control the surge and widespread transmission of WPV1 and cVDPV2.

      7. Few studies have assessed providers' intent of prescribing PrEP in the future. We analyzed cross-sectional web-based surveys to estimate trends from 2016 to 2020 in PrEP awareness and prescribing behaviors in the United States among primary care providers. Multivariable logistic regression was used to estimate prevalence of PrEP awareness, prescribing behaviors, and likelihood of prescribing PrEP in the next 12 months. The adjusted prevalence for PrEP awareness was significantly higher in 2019 (93.7%, 95% CI 91.9%, 95.2%) compared to 2018 (88.1%, 95% CI 85.5%, 90.3%). The adjusted prevalence for prescribing PrEP was significantly higher in 2019 (16.4%, 95% CI 13.6%, 19.6%) and 2020 (15.6%, 95% CI 13.0%, 18.7%) compared to 2018 (12.2%, 95% CI 10.0%, 14.7%). Practicing in the West and regularly screening for HIV were associated with higher PrEP awareness and provision. Studies should examine factors associated with PrEP provision for groups with increased risk for HIV.

      8. Persistence of positive RT-PCR results for over 70 days in two travelers with COVID-19external icon
        Kandetu TB, Dziuban EJ, Sikuvi K, Beard RS, Nghihepa R, van Rooyen G, Shiningavamwe A, Katjitae I.
        Disaster Med Public Health Prep. 2020 Nov 19:1-7.
        The relation of continuing to test positive for SARS-CoV-2 by reverse transcription real-time polymerase chain reaction (RT-PCR) to infectivity remains unclear, with numerous consequences. This report describes two patients with persistent viral detection by RT-PCR for 77 and 72 days, longer than other reported cases who were otherwise healthy.

      9. Enterovirus D68-associated acute flaccid myelitis, United States, 2020external icon
        Kidd S, Lopez AS, Konopka-Anstadt JL, Nix WA, Routh JA, Oberste MS.
        Emerg Infect Dis. 2020 Oct;26(10).
        Acute flaccid myelitis (AFM) is a serious neurologic condition that causes limb weakness or paralysis in previously healthy children. Since clusters of cases were first reported in 2014, nationwide surveillance has demonstrated sharp increases in AFM cases in the United States every 2 years, most occurring during late summer and early fall. Given this current biennial pattern, another peak AFM season is expected during fall 2020 in the United States. Scientific understanding of the etiology and the factors driving the biennial increases in AFM has advanced rapidly in the past few years, although areas of uncertainty remain. The Centers for Disease Control and Prevention and AFM partners are focused on answering key questions about AFM epidemiology and mechanisms of disease. This article summarizes the current understanding of AFM etiology and outlines priorities for surveillance and research as we prepare for a likely surge in cases in 2020.

      10. Household transmission of SARS-CoV-2 in the United Statesexternal icon
        Lewis NM, Chu VT, Ye D, Conners EE, Gharpure R, Laws RL, Reses HE, Freeman BD, Fajans M, Rabold EM, Dawson P, Buono S, Yin S, Owusu D, Wadhwa A, Pomeroy M, Yousaf A, Pevzner E, Njuguna H, Battey KA, Tran CH, Fields VL, Salvatore P, O'Hegarty M, Vuong J, Chancey R, Gregory C, Banks M, Rispens JR, Dietrich E, Marcenac P, Matanock AM, Duca L, Binder A, Fox G, Lester S, Mills L, Gerber SI, Watson J, Schumacher A, Pawloski L, Thornburg NJ, Hall AJ, Kiphibane T, Willardson S, Christensen K, Page L, Bhattacharyya S, Dasu T, Christiansen A, Pray IW, Westergaard RP, Dunn AC, Tate JE, Nabity SA, Kirking HL.
        Clin Infect Dis. 2020 Aug 16.
        BACKGROUND: Although many viral respiratory illnesses are transmitted within households, the evidence base for SARS-CoV-2 is nascent. We sought to characterize SARS-CoV-2 transmission within US households and estimate the household secondary infection rate (SIR) to inform strategies to reduce transmission. METHODS: We recruited laboratory-confirmed COVID-19 patients and their household contacts in Utah and Wisconsin during March 22-April 25, 2020. We interviewed patients and all household contacts to obtain demographics and medical histories. At the initial household visit, 14 days later, and when a household contact became newly symptomatic, we collected respiratory swabs from patients and household contacts for testing by SARS-CoV-2 rRT-PCR and sera for SARS-CoV-2 antibodies testing by enzyme-linked immunosorbent assay (ELISA). We estimated SIR and odds ratios (OR) to assess risk factors for secondary infection, defined by a positive rRT-PCR or ELISA test. RESULTS: Thirty-two (55%) of 58 households had evidence of secondary infection among household contacts. The SIR was 29% (n = 55/188; 95% confidence interval [CI]: 23-36%) overall, 42% among children (<18 years) of the COVID-19 patient and 33% among spouses/partners. Household contacts to COVID-19 patients with immunocompromised conditions had increased odds of infection (OR: 15.9, 95% CI: 2.4-106.9). Household contacts who themselves had diabetes mellitus had increased odds of infection (OR: 7.1, 95% CI: 1.2-42.5). CONCLUSIONS: We found substantial evidence of secondary infections among household contacts. People with COVID-19, particularly those with immunocompromising conditions or those with household contacts with diabetes, should take care to promptly self-isolate to prevent household transmission.

      11. Coronavirus disease 2019 (COVID-19) in a patient with disseminated histoplasmosis and HIV - a case report from Argentina and literature reviewexternal icon
        Messina FA, Marin E, Caceres DH, Romero M, Depardo R, Priarone MM, Rey L, Vázquez M, Verweij PE, Chiller TM, Santiso G.
        J Fungi (Basel). 2020 Nov 10;6(4).
        The disease caused by the new SARS-CoV-2, known as Coronavirus disease 2019 (COVID-19), was first identified in China in December 2019 and rapidly spread around the world. Coinfections with fungal pathogens in patients with COVID-19 add challenges to patient care. We conducted a literature review on fungal coinfections in patients with COVID-19. We describe a report of a patient with disseminated histoplasmosis who was likely infected with SARS-CoV-2 and experienced COVID-19 during hospital care in Buenos Aires, Argentina. This patient presented with advanced HIV disease, a well-known factor for disseminated histoplasmosis; on the other hand, we suspected that COVID-19 was acquired during hospitalization but there is not enough evidence to support this hypothesis. Clinical correlation and the use of specific Histoplasma and COVID-19 rapid diagnostics assays were key to the timely diagnosis of both infections, permitting appropriate treatment and patient care.

      12. Travel-related hepatitis E: a two-decade GeoSentinel analysisexternal icon
        Nicolini LA, Stoney RJ, Della Vecchia A, Grobusch M, Gautret P, Angelo KM, van Genderen PJ, Bottieau E, Leder K, Asgeirsson H, Leung DT, Connor B, Pandey P, Toscanini F, Gobbi F, Castelli F, Bassetti M, Hamer DH.
        J Travel Med. 2020 Nov 9;27(7).
        BACKGROUND: Hepatitis E virus (HEV) is widely distributed worldwide and is endemic in developing countries. Travel-related HEV infection has been reported at national levels, but global data are missing. Moreover, the global availability of HEV diagnostic testing has not been explored so far. The aim of this study is to describe the epidemiology of HEV infections in returning travellers and availability of HEV diagnostic testing in the GeoSentinel surveillance network. METHODS: This was a multicentre retrospective cross-sectional study. All confirmed and probable HEV travel-related infections reported in the GeoSentinel Network between 1999 and 2018 were evaluated. GeoSentinel sites were asked to complete a survey in 2018 to assess the availability and accessibility of HEV diagnostic procedures (i.e. serology and molecular tests) throughout the study period. RESULTS: Overall, 165 travel-related HEV infections were reported, mainly since 2010 (60%) and in tourists (50%). Travellers were exposed to hepatitis E in 27 countries; most travellers (62%) were exposed to HEV in South Asia. One patient was pregnant at the time of HEV infection and 14 had a concomitant gastrointestinal infection. No deaths were reported. In the 51% of patients with information available, there was no pre-travel consultation. Among 44 GeoSentinel sites that responded to the survey, 73% have access to HEV serology at a local level, while 55% could perform (at a local or central level) molecular diagnostics. CONCLUSION: Reported access to HEV diagnostic testing is suboptimal among sites that responded to the survey; this could negatively affect diagnosing HEV. Pre-travel consultations before travel to South Asia and other low-income and high-prevalence areas with a focus on food and water precautions could be helpful in preventing hepatitis E infection. Improved HEV diagnostic capacity should be implemented to prevent and correctly diagnose travel-related HEV infection.

      13. Optimal allocation of societal HIV prevention resources to reduce HIV incidence in the United Statesexternal icon
        Sansom SL, Hicks KA, Carrico J, Jacobson EU, Shrestha RK, Green TA, Purcell DW.
        Am J Public Health. 2020 Nov 19:e1-e8.
        Objectives. To optimize combined public and private spending on HIV prevention to achieve maximum reductions in incidence.Methods. We used a national HIV model to estimate new infections from 2018 to 2027 in the United States. We estimated current spending on HIV screening, interventions that move persons with diagnosed HIV along the HIV care continuum, pre-exposure prophylaxis, and syringe services programs. We compared the current funding allocation with 2 optimal scenarios: (1) a limited-reach scenario with expanded efforts to serve eligible persons and (2) an ideal, unlimited-reach scenario in which all eligible persons could be served.Results. A continuation of the current allocation projects 331 000 new HIV cases over the next 10 years. The limited-reach scenario reduces that number by 69%, and the unlimited reach scenario by 94%. The most efficient funding allocations resulted in prompt diagnosis and sustained viral suppression through improved screening of high-risk persons and treatment adherence support for those infected.Conclusions. Optimal allocations of public and private funds for HIV prevention can achieve substantial reductions in new infections. Achieving reductions of more than 90% under current funding will require that virtually all infected receive sustained treatment. (Am J Public Health. Published online ahead of print November 19, 2020: e1-e8.

      14. Evaluation of the National Sexually Transmitted Disease Curriculum: Reach, utilization, and engagementexternal icon
        Snoeyenbos Newman G, Bauer K, Karpenko A, Unruh KT, Johnston C, Marrazzo JM, Workowski KA, Spach DH.
        Sex Transm Dis. 2020 Jun;47(6):412-418.
        BACKGROUND: With increasing rates of sexually transmitted infections in the United States, there is a critical need to educate health professionals on the prevention, diagnosis, and treatment of sexually transmitted infections. The National Sexually Transmitted Disease Curriculum (NSTDC, is a free, online curriculum, funded by the Centers for Disease Control and Prevention. The purpose of this article is to evaluate the reach, utilization, and engagement of users with the curriculum. METHODS: Data on NSTDC utilization was collected for 24 months after the February 1, 2017 launch. For all users, Google Analytics was used to determine total number of users, geographic location, age and sex, and average session duration. For registered users, additional data analysis included work-role, demographics, and completion of self-study modules, check-on-learning questions, and question banks. User satisfaction was measured on a 5-point Likert scale. RESULTS: During the evaluation period, 136,270 individual users accessed the NSTDC, including 24,652 registered users. Among all registered users, 10,660 (43.2%) were registered nurses, 2810 (11.4%) physicians, 4942 (20.1%) Advanced Practice Nurses and Physician Assistants, and 6213 (25.2%) nonclinicians. Among registered users, 18,533 (75.2%) completed at least 1 module, 7898 (32.0%) completed all 7 modules, and 19,804 (80.4%) answered optional check-on-learning questions. Median satisfaction with the content was (5) very satisfied (interquartile range, 4-5). CONCLUSIONS: The NSTDC is a free, guideline-based, online curriculum with novel dual functionality that has achieved extensive reach with a broad array of health professionals who engage deeply with the material. The wide usage of NSTDC demonstrates the need for high-quality, unbiased, free content in user-focused formats.

      15. Nowcasting (short-term forecasting) of influenza epidemics in local settings, Sweden, 2008-2019external icon
        Spreco A, Eriksson O, Dahlström Ö, Cowling BJ, Biggerstaff M, Ljunggren G, Jöud A, Istefan E, Timpka T.
        Emerg Infect Dis. 2020 Nov;26(11):2669-2677.
        The timing of influenza case incidence during epidemics can differ between regions within nations and states. We conducted a prospective 10-year evaluation (January 2008-February 2019) of a local influenza nowcasting (short-term forecasting) method in 3 urban counties in Sweden with independent public health administrations by using routine health information system data. Detection-of-epidemic-start (detection), peak timing, and peak intensity were nowcasted. Detection displayed satisfactory performance in 2 of the 3 counties for all nonpandemic influenza seasons and in 6 of 9 seasons for the third county. Peak-timing prediction showed satisfactory performance from the influenza season 2011-12 onward. Peak-intensity prediction also was satisfactory for influenza seasons in 2 of the counties but poor in 1 county. Local influenza nowcasting was satisfactory for seasonal influenza in 2 of 3 counties. The less satisfactory performance in 1 of the study counties might be attributable to population mixing with a neighboring metropolitan area.

      16. Burkholderia pseudomallei in soil, US Virgin Islands, 2019external icon
        Stone NE, Hall CM, Browne AS, Sahl JW, Hutton SM, Santana-Propper E, Celona KR, Guendel I, Harrison CJ, Gee JE, Elrod MG, Busch JD, Hoffmaster AR, Ellis EM, Wagner DM.
        Emerg Infect Dis. 2020 Nov;26(11):2773-2775.
        The distribution of Burkholderia pseudomallei in the Caribbean is poorly understood. We isolated B. pseudomallei from US Virgin Islands soil. The soil isolate was genetically similar to other isolates from the Caribbean, suggesting that B. pseudomallei might have been introduced to the islands multiple times through severe weather events.

      17. Characterization of COVID-19 in assisted living facilities - 39 states, October 2020external icon
        Yi SH, See I, Kent AG, Vlachos N, Whitworth JC, Xu K, Gouin KA, Zhang S, Slifka KJ, Sauer AG, Kutty PK, Perz JF, Stone ND, Stuckey MJ.
        MMWR Morb Mortal Wkly Rep. 2020 Nov 20;69(46):1730-1735.
        The coronavirus disease 2019 (COVID-19) pandemic has highlighted the vulnerability of residents and staff members in long-term care facilities (LTCFs) (1). Although skilled nursing facilities (SNFs) certified by the Centers for Medicare & Medicaid Services (CMS) have federal COVID-19 reporting requirements, national surveillance data are less readily available for other types of LTCFs, such as assisted living facilities (ALFs) and those providing similar residential care. However, many state and territorial health departments publicly report COVID-19 surveillance data across various types of LTCFs. These data were systematically retrieved from health department websites to characterize COVID-19 cases and deaths in ALF residents and staff members. Limited ALF COVID-19 data were available for 39 states, although reporting varied. By October 15, 2020, among 28,623 ALFs, 6,440 (22%) had at least one COVID-19 case among residents or staff members. Among the states with available data, the proportion of COVID-19 cases that were fatal was 21.2% for ALF residents, 0.3% for ALF staff members, and 2.5% overall for the general population of these states. To prevent the introduction and spread of SARS-CoV-2, the virus that causes COVID-19, in their facilities, ALFs should 1) identify a point of contact at the local health department; 2) educate residents, families, and staff members about COVID-19; 3) have a plan for visitor and staff member restrictions; 4) encourage social (physical) distancing and the use of masks, as appropriate; 5) implement recommended infection prevention and control practices and provide access to supplies; 6) rapidly identify and properly respond to suspected or confirmed COVID-19 cases in residents and staff members; and 7) conduct surveillance of COVID-19 cases and deaths, facility staffing, and supply information (2).

    • Disease Reservoirs and Vectors
      1. The changing triad of plague in Uganda: invasive black rats (Rattus rattus), indigenous small mammals, and their fleasexternal icon
        Enscore RE, Babi N, Amatre G, Atiku L, Eisen RJ, Pepin KM, Vera-Tudela R, Sexton C, Gage KL.
        J Vector Ecol. 2020 Dec;45(2):333-355.
        Rattus rattus was first reported from the West Nile Region of Uganda in 1961, an event that preceded the appearance of the first documented human plague outbreak in 1970. We investigated how invasive R. rattus and native small mammal populations, as well as their fleas, have changed in recent decades. Over an 18-month period, a total of 2,959 small mammals were captured, sampled, and examined for fleas, resulting in the identification of 20 small mammal taxa that were hosts to 5,109 fleas (nine species). Over three-fourths (75.8%) of captured mammals belonged to four taxa: R. rattus, which predominated inside huts, and Arvicanthis niloticus, Mastomys sp., and Crocidura sp., which were more common outside huts. These mammals were hosts for 85.8% of fleas collected, including the efficient plague vectors Xenopsylla cheopis and X. brasiliensis, as well as likely enzootic vectors, Dinopsyllus lypusus and Ctenophthalmus bacopus. Flea loads on small mammals were higher in certain environments in villages with a recent history of plague compared to those that lacked such a history. The significance of these results is discussed in relation to historical data, the initial spread of plague in the WNR and the continuing threat posed by the disease.

    • Environmental Health
      1. Internships are an essential component of preparing prospective college graduates for entering the practice-based field of environmental health (EH). EH professionals continually encounter events or hazards of high complexity and impact, and many experienced EH professionals are expected to retire within the next several years. Efforts are needed to ensure a supply of highly qualified and prepared graduates is available to sustain and strengthen the EH workforce. The National Environmental Public Health Internship Program (NEPHIP) addresses this need by supporting health department internships for EH students of academic programs accredited by the National Environmental Health Science and Protection Accreditation Council. We conducted an assessment to examine former NEPHIP intern and mentor experiences and perspectives on 1) how well the internships prepared interns for careers in EH and 2) to what extent the internships provided value to the host health department. Overall, the internships appeared to provide EH students with a well-rounded professional and practice-based experience, while health departments benefited from hosting interns with a foundational knowledge and college education in EH. Promoting the value of public health department EH internships could encourage more students and graduates to seek internship or employment opportunities with health departments, ultimately strengthening the EH workforce.

    • Epidemiology and Surveillance
      1. Modelling airport catchment areas to anticipate the spread of infectious diseases across land and air travelexternal icon
        Huber C, Watts A, Grills A, Yong JH, Morrison S, Bowden S, Tuite A, Nelson B, Cetron M, Khan K.
        Spat Spatio-temporal Epidemiol. 2021 ;36.
        Air travel is an increasingly important conduit for the worldwide spread of infectious diseases. However, methods to identify which airports an individual may use to initiate travel, or where an individual may travel to upon arrival at an airport is not well studied. This knowledge gap can be addressed by estimating airport catchment areas: the geographic extent from which the airport derives most of its patronage. While airport catchment areas can provide a simple decision-support tool to help delineate the spatial extent of infectious disease spread at a local scale, observed data for airport catchment areas are rarely made publicly available. Therefore, we evaluated a probabilistic choice behavior model, the Huff model, as a potential methodology to estimate airport catchment areas in the United States in data-limited scenarios. We explored the impact of varying input parameters to the Huff model on estimated airport catchment areas: distance decay exponent, distance cut-off, and measures of airport attractiveness. We compared Huff model catchment area patterns for Miami International Airport (MIA) and Harrisburg International Airport (MDT). We specifically compared our model output to observed data sampled for MDT to align model parameters with an established, observed catchment area. Airport catchment areas derived using the Huff model were highly sensitive to changes in model parameters. We observed that a distance decay exponent of 2 and a distance cut-off of 500 km represented the most realistic spatial extent and heterogeneity of the MIA catchment area. When these parameters were applied to MDT, the Huff model produced similar spatial patterns to the observed MDT catchment area. Finally, our evaluation of airport attractiveness showed that travel volume to the specific international destinations of interest for infectious disease importation risks (i.e., Brazil) had little impact on the predicted choice of airport when compared to all international travel. Our work is a proof of concept for use of the Huff model to estimate airport catchment areas as a generalizable decision-support tool in data-limited scenarios. While our work represents an initial examination of the Huff model as a method to approximate airport catchment areas, an essential next step is to conduct a quantitative calibration and validation of the model based on multiple airports, possibly leveraging local human mobility data such as call detail records or online social network data collected from mobile devices. Ultimately, we demonstrate how the Huff model could be potentially helpful to improve the precision of early warning systems that anticipate infectious disease spread, or to incorporate when local public health decision makers need to identify where to mobilize screening infrastructure or containment strategies at a local level.

    • Food Safety
      1. Shiga toxin-producing Escherichia coli infections associated with romaine lettuce - United States, 2018external icon
        Bottichio L, Keaton A, Thomas D, Fulton T, Tiffany A, Frick A, Mattioli M, Kahler A, Murphy J, Otto M, Tesfai A, Fields A, Kline K, Fiddner J, Higa J, Barnes A, Arroyo F, Salvatierra A, Holland A, Taylor W, Nash J, Morawski BM, Correll S, Hinnenkamp R, Havens J, Patel K, Schroeder MN, Gladney L, Martin H, Whitlock L, Dowell N, Newhart C, Watkins LF, Hill V, Lance S, Harris S, Wise M, Williams I, Basler C, Gieraltowski L.
        Clin Infect Dis. 2020 Nov 5;71(8):e323-e330.
        BACKGROUND: Produce-associated outbreaks of Shiga toxin-producing Escherichia coli (STEC) were first identified in 1991. In April 2018, New Jersey and Pennsylvania officials reported a cluster of STEC O157 infections associated with multiple locations of a restaurant chain. The Centers for Disease Control and Prevention (CDC) queried PulseNet, the national laboratory network for foodborne disease surveillance, for additional cases and began a national investigation. METHODS: A case was defined as an infection between 13 March and 22 August 2018 with 1 of the 22 identified outbreak-associated E. coli O157:H7 or E. coli O61 pulsed-field gel electrophoresis pattern combinations, or with a strain STEC O157 that was closely related to the main outbreak strain by whole-genome sequencing. We conducted epidemiologic and traceback investigations to identify illness subclusters and common sources. A US Food and Drug Administration-led environmental assessment, which tested water, soil, manure, compost, and scat samples, was conducted to evaluate potential sources of STEC contamination. RESULTS: We identified 240 case-patients from 37 states; 104 were hospitalized, 28 developed hemolytic uremic syndrome, and 5 died. Of 179 people who were interviewed, 152 (85%) reported consuming romaine lettuce in the week before illness onset. Twenty subclusters were identified. Product traceback from subcluster restaurants identified numerous romaine lettuce distributors and growers; all lettuce originated from the Yuma growing region. Water samples collected from an irrigation canal in the region yielded the outbreak strain of STEC O157. CONCLUSIONS: We report on the largest multistate leafy greens-linked STEC O157 outbreak in several decades. The investigation highlights the complexities associated with investigating outbreaks involving widespread environmental contamination.

      2. Lessons learned from a decade of investigations of shiga toxin-producing Escherichia coli outbreaks linked to leafy greens, United States and Canadaexternal icon
        Marshall KE, Hexemer A, Seelman SL, Fatica MK, Blessington T, Hajmeer M, Kisselburgh H, Atkinson R, Hill K, Sharma D, Needham M, Peralta V, Higa J, Blickenstaff K, Williams IT, Jhung MA, Wise M, Gieraltowski L.
        Emerg Infect Dis. 2020 Oct;26(10):2319-2328.
        Shiga toxin-producing Escherichia coli (STEC) cause substantial and costly illnesses. Leafy greens are the second most common source of foodborne STEC O157 outbreaks. We examined STEC outbreaks linked to leafy greens during 2009-2018 in the United States and Canada. We identified 40 outbreaks, 1,212 illnesses, 77 cases of hemolytic uremic syndrome, and 8 deaths. More outbreaks were linked to romaine lettuce (54%) than to any other type of leafy green. More outbreaks occurred in the fall (45%) and spring (28%) than in other seasons. Barriers in epidemiologic and traceback investigations complicated identification of the ultimate outbreak source. Research on the seasonality of leafy green outbreaks and vulnerability to STEC contamination and bacterial survival dynamics by leafy green type are warranted. Improvements in traceability of leafy greens are also needed. Federal and state health partners, researchers, the leafy green industry, and retailers can work together on interventions to reduce STEC contamination.

    • Health Disparities
      1. "We deserve care and we deserve competent care": Qualitative perspectives on health care from transgender youth in the Southeast United Statesexternal icon
        Pampati S, Andrzejewski J, Steiner RJ, Rasberry CN, Adkins SH, Lesesne CA, Boyce L, Grose RG, Johns MM.
        J Pediatr Nurs. 2020 Nov 10;56:54-59.
        PURPOSE: Transgender populations experience health inequities that underscore the importance of ensuring access to high quality care. We thematically summarize the health care experiences of transgender youth living in the southeast United States to identify potential barriers and facilitators to health care. DESIGN AND METHODS: Transgender youth recruited from community settings in an urban area of the southeast United States participated in individual interviews (n = 33) and focus groups (n = 9) about protective factors. We conducted a thematic analysis of data from 42 participants who described their experiences seeking and receiving health care. RESULTS: Participants reported a wide range of gender identities. The individual interview sample was majority Black (54.5%) and the mean age was 21.7 years and focus group participants were all white and the mean age was 16.8 years. Participants described numerous barriers to health care, including limited availability of gender affirming care, logistical challenges, such as gatekeeping and cost, concerns about confidentiality in relation to sexual behavior and gender identity, and inadequate cultural competency among providers regarding gender-affirming care. Facilitators included intake procedures collecting chosen pronouns and names and consistent use of them by providers, and open communication, including active listening. CONCLUSIONS: Findings underscore the need for a multi-component approach to ensure both transgender- and youth-friendly care. PRACTICE IMPLICATIONS: Providers and office staff may benefit from transgender cultural competency trainings. In addition, clinic protocols relating to confidentiality and chosen name and pronoun use may help facilitate access to and receipt of quality care.

    • Healthcare Associated Infections
      1. Mitochondrial genome sequences of the emerging fungal pathogen Candida aurisexternal icon
        Misas E, Chow NA, Gómez OM, Muñoz JF, McEwen JG, Litvintseva AP, Clay OK.
        Front Microbiol. 2020 ;11:560332.
        Candida auris is an emerging fungal pathogen capable of causing invasive infections in humans. Since its first appearance around 1996, it has been isolated in countries spanning five continents. C. auris is a yeast that has the potential to cause outbreaks in hospitals, can survive in adverse conditions, including dry surfaces and high temperatures, and has been frequently misidentified by traditional methods. Furthermore, strains have been identified that are resistant to two and even all three of the main classes of antifungals currently in use. Several nuclear genome assemblies of C. auris have been published representing different clades and continents, yet until recently, the mitochondrial genomes (mtDNA chromosomes) of this species and the closely related species of C. haemulonii, C. duobushaemulonii, and C. pseudohaemulonii had not been analyzed in depth. We used reads from PacBio and Illumina sequencing to obtain a de novo reference assembly of the mitochondrial genome of the C. auris clade I isolate B8441 from Pakistan. This assembly has a total size of 28.2 kb and contains 13 core protein-coding genes, 25 tRNAs and the 12S and 16S ribosomal subunits. We then performed a comparative analysis by aligning Illumina reads of 129 other isolates from South Asia, Japan, South Africa, and South America with the B8441 reference. The clades of the phylogenetic tree we obtained from the aligned mtDNA sequences were consistent with those derived from the nuclear genome. The mitochondrial genome revealed a generally low genetic variation within clades, although the South Asian clade displayed two sub-branches including strains from both Pakistan and India. In particular, the 86 isolates from Colombia and Venezuela had mtDNA sequences that were all identical at the base level, i.e., a single conserved haplotype or mitochondrial background that exhibited characteristic differences from the Pakistan reference isolate B8441, such as a unique 25-nt insert that may affect function.

    • Immunity and Immunization
      1. Declining gonococcal susceptibility to ceftriaxone and azithromycin has raised the possibility of untreatable gonorrhea in the future and re-ignited interest in gonococcal vaccine development. Despite decades of research, previous gonococcal vaccine candidates have been ineffective. A growing body of data suggest that meningococcal group B outer membrane vaccines (MenB OMV) may be cross-protective against Neisseria gonorrhoeae. Clinical trials of a licensed vaccine against N. meningitidis serogroup B containing an OMV component are underway to determine its efficacy against N. gonorrhoeae. Other experimental gonococcal vaccine candidates are in the preclinical phases. Population impact of future gonococcal vaccines with different levels of efficacy and duration of protection in various populations are being evaluated using modeling studies. Despite recent progress, gaps in gonococcal vaccine research remain. Research is needed to evaluate vaccine efficacy in preventing gonococcal infections acquired via various anatomic routes and among patients co-infected with other sexually transmitted infections. Studies that model the impact of a future vaccine on high-burden populations such as men who have sex with men and estimate both vaccine cost-effectiveness and the incremental cost-effectiveness ratio of vaccination to antimicrobial resistance and treatment costs are warranted. This narrative review examines the current state of gonococcal vaccine research, the possible impact of a gonococcal vaccine on gonorrhea rates based on modeling studies, gaps in the gonococcal vaccine literature, and public health implications of a future gonococcal vaccine on reducing the gonorrhea burden in the United States.

      2. Safety and immunogenicity of inactivated poliovirus vaccine schedules for the post-eradication era: a randomised open-label, multicentre, phase 3, non-inferiority trialexternal icon
        Bandyopadhyay AS, Gast C, Rivera L, Saez-Llorens X, Oberste MS, Weldon WC, Modlin J, Clemens R, Costa Clemens SA, Jimeno J, Ruttimann R.
        Lancet Infect Dis. 2020 .
        Background: Following the global eradication of wild poliovirus, countries using live attenuated oral poliovirus vaccines will transition to exclusive use of inactivated poliovirus vaccine (IPV) or fractional doses of IPV (f-IPV; a f-IPV dose is one-fifth of a normal IPV dose), but IPV supply and cost constraints will necessitate dose-sparing strategies. We compared immunisation schedules of f-IPV and IPV to inform the choice of optimal post-eradication schedule. Method(s): This randomised open-label, multicentre, phase 3, non-inferiority trial was done at two centres in Panama and one in the Dominican Republic. Eligible participants were healthy 6-week-old infants with no signs of febrile illness or known allergy to vaccine components. Infants were randomly assigned (1:1:1:1, 1:1:1:2, 2:1:1:1), using computer-generated blocks of four or five until the groups were full, to one of four groups and received: two doses of intradermal f-IPV (administered at 14 and 36 weeks; two f-IPV group); or three doses of intradermal f-IPV (administered at 10, 14, and 36 weeks; three f-IPV group); or two doses of intramuscular IPV (administered at 14 and 36 weeks; two IPV group); or three doses of intramuscular IPV (administered at 10, 14, and 36 weeks; three IPV group). The primary outcome was seroconversion rates based on neutralising antibodies for poliovirus type 1 and type 2 at baseline and at 40 weeks (4 weeks after the second or third vaccinations) in the per-protocol population to allow non-inferiority and eventually superiority comparisons between vaccines and regimens. Three co-primary outcomes concerning poliovirus types 1 and 2 were to determine if seroconversion rates at 40 weeks of age after a two-dose regimen (administered at weeks 14 and 36) of intradermally administered f-IPV were non-inferior to a corresponding two-dose regimen of intramuscular IPV; if seroconversion rates at 40 weeks of age after a two-dose IPV regimen (weeks 14 and 36) were non-inferior to those after a three-dose IPV regimen (weeks 10, 14, and 36); and if seroconversion rates after a two-dose f-IPV regimen (weeks 14 and 36) were non-inferior to those after a three-dose f-IPV regimen (weeks 10, 14, and 36). The non-inferiority boundary was set at -10% for the lower bound of the two-sided 95% CI for the seroconversion rate difference. Safety was assessed as serious adverse events and important medical events. This study is registered on, NCT03239496. Finding(s): From Oct 23, 2017, to Nov 13, 2018, we enrolled 773 infants (372 [48%] girls) in Panama and the Dominican Republic (two f-IPV group n=217, three f-IPV group n=178, two IPV group n=178, and three IPV group n=200). 686 infants received all scheduled vaccine doses and were included in the per-protocol analysis. We observed non-inferiority for poliovirus type 1 seroconversion rate at 40 weeks for the two f-IPV dose schedule (95.9% [95% CI 92.0-98.2]) versus the two IPV dose schedule (98.7% [95.4-99.8]), and for the three f-IPV dose schedule (98.8% [95.6-99.8]) versus the three IPV dose schedule (100% [97.9-100]). Similarly, poliovirus type 2 seroconversion rate at 40 weeks for the two f-IPV dose schedule (97.9% [94.8-99.4]) versus the two IPV dose schedule (99.4% [96.4-100]), and for the three f-IPV dose schedule (100% [97.7-100]) versus the three IPV dose schedule (100% [97.9-100]) were non-inferior. Seroconversion rate for the two f-IPV regimen was statistically superior 4 weeks after the last vaccine dose in the 14 and 36 week schedule (95.9% [92.0-98.2]) compared with the 10 and 14 week schedule (83.2% [76.5-88.6]; p=0.0062) for poliovirus type 1. Statistical superiority of the 14 and 36 week schedule was also found for poliovirus type 2 (14 and 36 week schedule 97.9% [94.8-99.4] vs 10 and 14 week schedule 83.9% [77.2-89.2]; p=0.0062), and poliovirus type 3 (14 and 36 week schedule 84.5% [78.7-89.3] vs 10 and 14 week schedule 73.3% [65.8-79.9]; p=0.0062). For IPV, a two dose regimen administered at 14 and 36 weeks (99.4% [96.4-100]) was superior a 10 and 14 week schedule (88.9% [83.4-93.1]; p<0.0001) for poliovirus type 2, but not for type 1 (14 and 36 week schedule 98.7% [95.4-99.8] vs 10 and 14 week schedule 95.6% [91.4-98.1]), or type 3 (14 and 36 week schedule 97.4% [93.5-99.3] vs 10 and 14 week schedule 93.9% [89.3-96.9]). There were no related serious adverse events or important medical events reported in any group showing safety was unaffected by administration route or schedule. Interpretation(s): Our observations suggest that adequate immunity against poliovirus type 1 and type 2 is provided by two doses of either IPV or f-IPV at 14 and 36 weeks of age, and broad immunity is provided with three doses of f-IPV, enabling substantial savings in cost and supply. These novel clinical data will inform global polio immunisation policy for the post-eradication era. Funding(s): Bill & Melinda Gates Foundation.

      3. Durability of humoral immune responses to rubella following MMR vaccinationexternal icon
        Crooke SN, Riggenbach MM, Ovsyannikova IG, Warner ND, Chen MH, Hao L, Icenogle JP, Poland GA, Kennedy RB.
        Vaccine. 2020 Nov 12.
        BACKGROUND: While administration of the measles-mumps-rubella (MMR-II®) vaccine has been effective at preventing rubella infection in the United States, the durability of humoral immunity to the rubella component of MMR vaccine has not been widely studied among older adolescents and adults. METHODS: In this longitudinal study, we sought to assess the durability of rubella virus (RV)-specific humoral immunity in a healthy population (n = 98) of adolescents and young adults at two timepoints: ~7 and ~17 years after two doses of MMR-II® vaccination. Levels of circulating antibodies specific to RV were measured by ELISA and an immune-colorimetric neutralization assay. RV-specific memory B cell responses were also measured by ELISpot. RESULTS: Rubella-specific IgG antibody titers, neutralizing antibody titers, and memory B cell responses declined with increasing time since vaccination; however, these decreases were relatively moderate. Memory B cell responses exhibited a greater decline in men compared to women. CONCLUSIONS: Collectively, rubella-specific humoral immunity declines following vaccination, although subjects' antibody titers remain well above the currently recognized threshold for protective immunity. Clinical correlates of protection based on neutralizing antibody titer and memory B cell ELISpot response should be defined.

      4. Maternal anti-rotavirus IgG antibodies persist in the post-rotavirus vaccine eraexternal icon
        Payne DC, McNeal M, Staat MA, Piasecki AM, Cline A, DeFranco E, Goveia MG, Parashar UD, Burke RM, Morrow AL.
        J Infect Dis. 2020 Nov 19.
        To assess whether titers of anti-rotavirus IgG persist during the post-rotavirus vaccine era, the PREVAIL Cohort analyzed sera collected from Cincinnati-area mothers and young infants in 2017-18. Rotavirus-specific antibodies continue to be transferred from US mothers to offspring in the post-rotavirus vaccine era, despite dramatic decreases in childhood rotavirus gastroenteritis.

    • Informatics

    • Injury and Violence
      1. Taking action to prevent violence against adolescents in the time of COVID-19external icon
        Chiang L, Howard A, Butchart A.
        J Adolesc Health. 2020 Nov 9.

      2. Texting while driving: A discrete choice experimentexternal icon
        Foreman AM, Friedel JE, Hayashi Y, Wirth O.
        Accid Anal Prev. 2020 Nov 13;149:105823.
        Texting while driving is one of the most dangerous types of distracted driving and contributes to a large number of transportation incidents and fatalities each year. Drivers text while driving despite being aware of the risks. Although some factors related to the decision to text while driving have been elucidated, more remains to be investigated in order to better predict and prevent texting while driving. To study decision making involved in reading a text message while driving, we conducted a discrete choice experiment with 345 adult participants recruited from Amazon's Mechanical Turk. Participants were presented with multiple choice sets, each involving two different scenarios, and asked to choose the scenario in which they would be more likely to text while driving. The attributes of the scenarios were the relationship to the text-message sender, the road conditions, and the importance of the message. The attributes varied systematically across the choice sets. Participants were more likely to read a text message while driving if the sender of the message was a significant other, the message was perceived to be very important, and the participant was driving on rural roads. Discrete choice experiments offer a promising approach to studying decision making in drivers and other populations because they allow for an analysis of multiple factors simultaneously and the trade-offs among different choices.

      3. Teen dating violence (TDV) affects millions of young people in the USA each year (Basile et al. 2020) and is associated with a myriad of negative consequences across the lifespan, including placing individuals at greater risk for experiencing intimate partner violence (IPV) in their more permanent relationships in adulthood (Exner-Cortens et al. Pediatrics 131(1):71-78 Exner-Cortens et al. 2013; Exner-Cortens et al. Journal of Adolescent Health 60(2):176-183 Exner-Cortens et al. 2017). The CDC developed the Dating Matters®: Strategies to Promote Healthy Teen Relationships comprehensive prevention model to prevent TDV and its consequences among young people, and it was found to be effective at reducing TDV perpetration and victimization compared with another evidence-based program (Niolon et al. American Journal of Preventive Medicine 57(1):13-23 Niolon et al. 2019). Dating Matters addresses multiple risk and protective factors for TDV through its multiple components, many of which are shared risk and protective factors for other forms of violence and risk behaviors among adolescents. This article introduces this special section, which includes three papers examining these secondary outcomes of the Dating Matters comparative effectiveness, multi-site, longitudinal cluster randomized controlled trial and concludes with an invited commentary by Debman and Temple (in press). This introduction briefly discusses the Dating Matters comprehensive prevention model, the comparative effectiveness trial used to evaluate effectiveness, the outcomes examined by the three papers included in this special section and the commentary from external reviewers. This special section makes an important contribution to the field of violence prevention, highlighting a preventive intervention for TDV that addresses a constellation of risk and protective factors and demonstrating its effects on multiple adolescent risk and violence outcomes.

    • Laboratory Sciences
      1. Development and assessment of a pooled serum as candidate standard to measure influenza a virus group 1 hemagglutinin stalk-reactive antibodiesexternal icon
        Carreño JM, McDonald JU, Hurst T, Rigsby P, Atkinson E, Charles L, Nachbagauer R, Behzadi MA, Strohmeier S, Coughlan L, Aydillo T, Brandenburg B, García-Sastre A, Kaszas K, Levine MZ, Manenti A, McDermott AB, Montomoli E, Muchene L, Narpala SR, Perera R, Salisch NC, Valkenburg SA, Zhou F, Engelhardt OG, Krammer F.
        Vaccines (Basel). 2020 Nov 9;8(4).
        The stalk domain of the hemagglutinin has been identified as a target for induction of protective antibody responses due to its high degree of conservation among numerous influenza subtypes and strains. However, current assays to measure stalk-based immunity are not standardized. Hence, harmonization of assay readouts would help to compare experiments conducted in different laboratories and increase confidence in results. Here, serum samples from healthy individuals (n = 110) were screened using a chimeric cH6/1 hemagglutinin enzyme-linked immunosorbent assay (ELISA) that measures stalk-reactive antibodies. We identified samples with moderate to high IgG anti-stalk antibody levels. Likewise, screening of the samples using the mini-hemagglutinin (HA) headless construct #4900 and analysis of the correlation between the two assays confirmed the presence and specificity of anti-stalk antibodies. Additionally, samples were characterized by a cH6/1N5 virus-based neutralization assay, an antibody-dependent cell-mediated cytotoxicity (ADCC) assay, and competition ELISAs, using the stalk-reactive monoclonal antibodies KB2 (mouse) and CR9114 (human). A "pooled serum" (PS) consisting of a mixture of selected serum samples was generated. The PS exhibited high levels of stalk-reactive antibodies, had a cH6/1N5-based neutralization titer of 320, and contained high levels of stalk-specific antibodies with ADCC activity. The PS, along with blinded samples of varying anti-stalk antibody titers, was distributed to multiple collaborators worldwide in a pilot collaborative study. The samples were subjected to different assays available in the different laboratories, to measure either binding or functional properties of the stalk-reactive antibodies contained in the serum. Results from binding and neutralization assays were analyzed to determine whether use of the PS as a standard could lead to better agreement between laboratories. The work presented here points the way towards the development of a serum standard for antibodies to the HA stalk domain of phylogenetic group 1.

      2. The role of the gut microbiome in resisting norovirus infection as revealed by a human challenge studyexternal icon
        Patin NV, Peña-Gonzalez A, Hatt JK, Moe C, Kirby A, Konstantinidis KT.
        mBio. 2020 Nov 17;11(6).
        Norovirus infections take a heavy toll on worldwide public health. While progress has been made toward understanding host responses to infection, the role of the gut microbiome in determining infection outcome is unknown. Moreover, data are lacking on the nature and duration of the microbiome response to norovirus infection, which has important implications for diagnostics and host recovery. Here, we characterized the gut microbiomes of subjects enrolled in a norovirus challenge study. We analyzed microbiome features of asymptomatic and symptomatic individuals at the genome (population) and gene levels and assessed their response over time in symptomatic individuals. We show that the preinfection microbiomes of subjects with asymptomatic infections were enriched in Bacteroidetes and depleted in Clostridia relative to the microbiomes of symptomatic subjects. These compositional differences were accompanied by differences in genes involved in the metabolism of glycans and sphingolipids that may aid in host resilience to infection. We further show that microbiomes shifted in composition following infection and that recovery times were variable among human hosts. In particular, Firmicutes increased immediately following the challenge, while Bacteroidetes and Proteobacteria decreased over the same time. Genes enriched in the microbiomes of symptomatic subjects, including the adenylyltransferase glgC, were linked to glycan metabolism and cell-cell signaling, suggesting as-yet unknown roles for these processes in determining infection outcome. These results provide important context for understanding the gut microbiome role in host susceptibility to symptomatic norovirus infection and long-term health outcomes.IMPORTANCE The role of the human gut microbiome in determining whether an individual infected with norovirus will be symptomatic is poorly understood. This study provides important data on microbes that distinguish asymptomatic from symptomatic microbiomes and links these features to infection responses in a human challenge study. The results have implications for understanding resistance to and treatment of norovirus infections.

      3. Characterization of reference materials for spinal muscular atrophy genetic testing: A GeT-RM Collaborative Projectexternal icon
        Prior TW, Bayrak-Toydemir P, Lynnes TC, Mao R, Metcalf JD, Muralidharan K, Iwata-Otsubo A, Pham HT, Pratt VM, Qureshi S, Requesens D, Shen J, Vetrini F, Kalman L.
        J Mol Diagn. 2020 Nov 13.
        Spinal muscular atrophy (SMA) is an autosomal recessive disorder predominately caused by bi-allelic loss of the SMN1 gene. Increased copies of SMN2, a low functioning nearly identical paralog, is associated with a less severe phenotype. SMA was recently recommended for inclusion in newborn screening. Clinical laboratories must accurately measure SMN1 and SMN2 copy number to identify SMA patients, carriers, and to identify individuals likely to benefit from therapeutic interventions. Having publicly available and appropriately characterized reference materials with various combinations of SMN1 and SMN2 copy number variants is critical to assure accurate SMA clinical testing. To address this need, the Centers for Disease Control and Prevention based Genetic Testing Reference Material Coordination Program (GeT-RM), in collaboration with members of the genetic testing community and the Coriell Institute for Medical Research, have characterized 15 SMA reference materials derived from publicly available cell lines. DNA samples were distributed to four volunteer testing laboratories for genotyping using 3 different methods. The characterized samples had 0-4 copies of SMN1 and 0-5 copies SMN2. The samples also contained clinically important allele combinations (eg. 0 copies SMN1, 3 copies SMN2), and several had markers indicative of a SMA carrier. These and other reference materials characterized by the GeT-RM will support the quality of clinical laboratory testing and are available from the Coriell Institute.

      4. Do i have HIV or not? Lack of RNA detection and the case for sensitive DNA testingexternal icon
        Springer SA, Masciotra S, Johnson JA, Campbell S.
        Open Forum Infect Dis. 2020 Nov;7(11):ofaa478.
        We present a case of a 20-year-old male who had ambiguous HIV test results after entering new provider care and whose status was later complicated by undetectable viral RNA off antiretroviral therapy (ART). Verifying HIV infection status may occasionally require sensitive DNA testing that might need to be considered in diagnostic guidelines to resolve diagnosis and ensure appropriate ART management.

      5. Functional characterization of circulating mumps viruses with stop codon mutations in the small hydrophobic proteinexternal icon
        Stinnett RC, Beck AS, Lopareva EN, McNall RJ, Latner DR, Hickman CJ, Rota PA, Bankamp B.
        mSphere. 2020 Nov 18;5(6).
        Between 2015 and 2017, routine molecular surveillance in the United States detected multiple mumps viruses (MuVs) with mutations in the small hydrophobic (SH) gene compared to a reference virus of the same genotype. These mutations include an unusual pattern of uracil-to-cytosine hypermutations and other mutations resulting in the generation of premature stop codons or disruption of the canonical stop codon. The mumps virus SH protein may serve as a virulence factor, based on evidence that it inhibits apoptosis and innate immune signaling in vitro and that recombinant viruses that do not express the SH protein are attenuated in an animal model. In this study, mumps viruses bearing variant SH sequences were isolated from contemporary outbreak samples to evaluate the impact of the observed mutations on SH protein function. All isolates with variant SH sequences replicated in interferon-competent cells with no evidence of attenuation. Furthermore, all SH-variant viruses retained the ability to abrogate induction of NF-κB-mediated innate immune signaling in infected cells. Ectopic expression of variant mumps SH genes is consistent with findings from infection experiments, indicating that the observed abrogation of signaling was not mediated by other viral factors that may modulate innate immune signaling. Molecular surveillance is an important public health tool for monitoring the diversity of circulating mumps viruses and can provide insights into determinants of disease. These findings, in turn, will inform studies employing reverse genetics to elucidate the specific mechanisms of MuV pathogenesis and potential impacts of observed sequence variants on infectivity, fitness, and virulence.IMPORTANCE Mumps virus (MuV) outbreaks occur in the United States despite high coverage with measles, mumps, rubella (MMR) vaccine. Routine genotyping of laboratory-confirmed mumps cases has been practiced in the United States since 2006 to enhance mumps surveillance. This study reports the detection of unusual mutations in the small hydrophobic (SH) protein of contemporary laboratory-confirmed mumps cases and is the first to describe the impact of such mutations on SH protein function. These mutations are predicted to profoundly alter the amino acid sequence of the SH protein, which has been shown to antagonize host innate immune responses; however, they were neither associated with defects in virus replication nor attenuated protein function in vitro, consistent with detection in clinical specimens. A better understanding of the forces governing mumps virus sequence diversity and of the functional consequences of mutations in viral proteins is important for maintaining robust capacity for mumps detection and disease control.

      6. Measuring 226Ra in urine at low levels is critical for both biomonitoring and radiological emergency response. Here we report a new analytical method to quantify 226Ra, as developed and validated by a simple dilute-and-shoot procedure, followed by Inductively Coupled Plasma-triple quadrupole-mass spectrometry detection using 'No Gas MS-MS' mode. The method provides rapid and accurate results for 226Ra with a limit of detection (LOD) down to 0.007 ng/l (0.26 Bq/l). This LOD is well below the recommended action levels for 226Ra detection in children and pregnant women (C/P) set by the Clinical Decision Guide (NCRP Report #161). Results for 226Ra obtained by this method are within ±7.0% of the target values of standard reference materials spiked in the urine.

    • Maternal and Child Health
      1. BACKGROUND: Little is known regarding risk for co-occurring mental health conditions among pediatric patients with congenital adrenal hyperplasia (CAH). The objective of the current study was to investigate the prevalence of medically managed attention-deficit/hyperactivity disorder (ADHD) in 2 large administrative samples of insured children and adolescents with and without CAH in the United States. METHODS: We assessed the prevalence of CAH and of medically managed ADHD using algorithms defined from diagnosis codes and filled prescriptions data using the IBM MarketScan Commercial and Multi-State Medicaid claims databases. We evaluated subjects who were continuously enrolled for ≥ 12 months with a first claim during October 2015 through December 2017 when they were 5 to 18 years old. RESULTS: The administrative prevalence of CAH in the Commercial (N = 3 685 127) and Medicaid (N = 3 434 472) samples was 10.1 per 100 000 (n = 372) and 7.2 per 100 000 (n = 247), respectively. The prevalence of medically managed ADHD in the non-CAH population was 8.4% in the Commercial sample and 15.1% in the Medicaid sample. Among children with CAH, there was no increased prevalence of ADHD in the Commercial (9.2%, prevalence ratio [PR] = 1.1; 95% confidence interval [CI], 0.82-1.54; P = 0.48) or Medicaid (13.8%; PR = 0.91; 95% CI, 0.67-1.24; P = 0.55) samples compared with the general population. CONCLUSIONS: Using 2 large samples of insured children and adolescents in the United States, we found similar prevalence of medically managed ADHD among those with CAH and the general population. Future research to assess the validity of our claims algorithm for identifying pediatric CAH cases is warranted.

    • Nutritional Sciences
      1. Background: Ensuring the quality of anthropometry data is paramount for getting accurate estimates of malnutrition prevalence among children aged 6–59 months in humanitarian and refugee settings. Previous reports based on data from Demographic and Health Surveys suggested systematic differences in anthropometric data quality between the younger and older groups of preschool children. Methods: We analyzed 712 anthropometric population-representative field surveys from humanitarian and refugee settings conducted during 2011–2018. We examined and compared the quality of five anthropometric indicators in children aged 6–23 months and children aged 24–59 months: weight for height, weight for age, height for age, body mass index for age and mid-upper arm circumference (MUAC) for age. Using the z-score distribution of each indicator, we calculated the following parameters: standard deviation (SD), percentage of outliers, and measures of distribution normality. We also examined and compared the quality of height, weight, MUAC and age measurements using missing data and rounding criteria. Results: Both SD and percentage of flags were significantly smaller on average in older than in younger age group for all five anthropometric indicators. Differences in SD between age groups did not change meaningfully depending on overall survey quality or on the quality of age ascertainment. Over 50% of surveys overall did not deviate significantly from normality. The percentage of non-normal surveys was higher in older than in the younger age groups. Digit preference score for weight, height and MUAC was slightly higher in younger age group, and for age slightly higher in the older age group. Children with reported exact date of birth (DOB) had much lower digit preference for age than those without exact DOB. SD, percentage flags and digit preference scores were positively correlated between the two age groups at the survey level, such as those surveys showing higher anthropometry data quality in younger age group also tended to show higher quality in older age group. Conclusions: There should be an emphasis on increased rigor of training survey measurers in taking anthropometric measurements in the youngest children. Standardization test, a mandatory component of the pre-survey measurer training and evaluation, of 10 children should include at least 4–5 children below 2 years of age.

      2. Most national, mandatory flour fortification standards do not align with international recommendations for iron, zinc, and vitamin B12 levelsexternal icon
        Bobrek KS, Broersen B, Aburto NJ, Garg A, Serdula M, Beltrán Velázquez F, Wong EC, Pachón H.
        Food Policy. 2020 .
        As national flour fortification standards are one of the policy documents developed to guide food fortification, the objective was to compare national, mandatory wheat and maize flour fortification standards to World Health Organization (WHO) fortification guidelines. For each nutrient in 72 countries’ standards, the type of compound was noted as ‘yes’ if it was included in international guidelines or ‘no’ if it was not. Nutrient levels in standards were classified as lower than, equal to, or higher than those suggested by WHO. If another food (i.e. rice, oil, milk) was mass fortified with a nutrient categorized as “lower than,” the classification was changed to “less than recommendation and included in other mass fortified food”. At least 61% of standards included one or more recommended compounds for all nutrients in standards for wheat flour alone (iron, folic acid, vitamin A, zinc, vitamin B12,), wheat and maize flour together (iron, folic acid, vitamin A, zinc, vitamin B12) and maize flour alone (thiamin, riboflavin, niacin, pyridoxine); no country included pantothenic acid in its maize flour standard. For folic acid, vitamin A, thiamin, riboflavin, niacin and pyridoxine, at least 50% of standards (1) met or exceeded WHO suggested levels, or (2) were lower than suggested levels and another food was mass fortified with the specific nutrient in the country. For iron, zinc and vitamin B12, less than 50% of standards met (1) or (2). In conclusion, iron, zinc and vitamin B12 may require the most attention in national fortification standards.

    • Occupational Safety and Health
      1. Safe patient handling and mobility (SPHM) for increasingly bariatric patient populations: Factors related to caregivers' self-reported pain and injuryexternal icon
        Galinsky T, Deter L, Krieg E, Feng HA, Battaglia C, Bell R, Haddock KS, Hilton T, Lynch C, Matz M, Moscatel S, Riley FD, Sampsel D, Shaw S.
        Appl Ergon. 2020 Nov 12;91:103300.
        This study was conducted at 5 Veterans Administration Medical Centers (VAMCs). A cross sectional survey was administered to 134 workers who routinely lift and mobilize patients within their workplaces' safe patient handling and mobility (SPHM) programs, which are mandated in all VAMCs. The survey was used to examine a comprehensive list of SPHM and non-SPHM variables, and their associations with self-reported musculoskeletal injury and pain. Previously unstudied variables distinguished between "bariatric" (≥300 lb or 136 kg) and "non-bariatric" (<300 lb or 136 kg) patient handling. Significant findings from stepwise and logistic regression provide targets for workplace improvements, predicting: lower injury odds with more frequently having sufficient time to use equipment, higher back pain odds with more frequent bariatric handling, lower back pain odds with greater ease in following SPHM policies, and lower odds of upper extremity pain with more bariatric equipment, and with higher safety climate ratings.

      2. Radiographic screening reveals high burden of silicosis among workers at an engineered stone countertop fabrication facility in Californiaexternal icon
        Heinzerling A, Cummings KJ, Flattery J, Weinberg JL, Materna B, Harrison R.
        Am J Respir Crit Care Med. 2020 Nov 18.

      3. The declaration of coronavirus disease 2019 (COVID-19) as a public health emergency in the United States immediately changed the way we work and live, and intensified feelings of stress and uncertainty about the future. New routines and behaviors such as adhering to stay-at-home orders, wearing masks, and social distancing, along with frequent messaging about handwashing, cleaning, and not touching our faces, are constant reminders of our new normal and have been shown to increase anxiety. Exposure to an abundance of news coverage, some of which is conflicting or has changed over time, has fueled feelings of uncertainty and fear. The closure of many businesses has led to job loss and financial instability for millions for an undetermined period. Essential service occupations- some of which might not have been previously recognized for exposure to infectious diseases- are now perceived as more dangerous due to the increased infection risk associated with working among the general public. Worries about the health and wellbeing of ourselves and loved ones have further affected our emotional health and added to fatigue. New terms such as caution fatigue and quarantine fatigue have emerged to describe the weariness we feel about our new restrictive circumstances as a result of the COVID-19 pandemic. ... The only certain thing during these uncertain times is the need to work together to navigate through uncharted territories. Recognizing that worker fatigue can be attributed to a variety of sources stemmfog from individual concerns, changes in work routines and schedules, and varying degrees of stress due to adversities related to COVID-19 can aid in the development of targeted, efficient mitigation strategies. A holistic approach with shared responsibility and open communication among employers and employees is needed to ensure worker safety, health. and well-being and a successful return to regular operations. As the economy reopens, addressing changes in work hours and routines, organizational practices, and the physical and psychosocial work environment due to COVID-19 will help mitigate worker fatigue and can support healthy behaviors and practices as workers adjust to the new normal.

    • Parasitic Diseases
      1. Association of malnutrition with subsequent malaria parasitemia among children younger than three years in Kenya: A secondary data analysis of the Asembo Bay Cohort Studyexternal icon
        Donovan CV, McElroy P, Adair L, Pence BW, Oloo AJ, Lal A, Bloland P, Nahlen B, Juliano JJ, Meshnick S.
        Am J Trop Med Hyg. 2020 Nov 16.
        Malaria and malnutrition remain primary causes of morbidity and mortality among children younger than 5 years in Africa. Studies investigating the association between malnutrition and subsequent malaria outcomes are inconsistent. We studied the effects of malnutrition on incidence and prevalence of malaria parasitemia in data from a cohort studied in the 1990s. Data came from the Asembo Bay cohort study, which collected malaria and health information on children from 1992 to 1996 in western Kenya. Infants were enrolled at birth and followed up until loss to follow-up, death, end of study, or 5 years old. Anthropometric measures and blood specimens were obtained monthly. Nutritional exposures included categorized Z-scores for height-for-age, weight-for-age, and weight-for-height. Febrile parasitemia and afebrile parasitemia were assessed with thick and thin blood films. Multiply imputed and weighted multinomial generalized estimating equation models estimated odds ratios (OR) for the association between exposures and outcomes. The sample included 1,182 children aged 0-30 months who contributed 18,028 follow-up visits. There was no significant association between malnutrition and either incident febrile parasitemia or prevalent febrile parasitemia. Prevalence ORs for afebrile parasitemia increased from 1.07 (95% CI: 0.89, 1.29) to 1.35 (1.03, 1.76) as stunting severity increased from mild to severe, and from 1.16 (1.02, 1.33) to 1.35 (1.09, 1.66) as underweight increased from mild to moderate. Stunting and underweight did not show a significant association with subsequent febrile parasitemia infections, but they did show a modest association with subsequent afebrile parasitemia. Consideration should be given to testing malnourished children for malaria, even if they present without fever.

      2. The risk of Plasmodium vivax parasitaemia after P. falciparum malaria: An individual patient data meta-analysis from the WorldWide Antimalarial Resistance Networkexternal icon
        Hossain MS, Commons RJ, Douglas NM, Thriemer K, Alemayehu BH, Amaratunga C, Anvikar AR, Ashley EA, Asih PB, Carrara VI, Lon C, D'Alessandro U, Davis TM, Dondorp AM, Edstein MD, Fairhurst RM, Ferreira MU, Hwang J, Janssens B, Karunajeewa H, Kiechel JR, Ladeia-Andrade S, Laman M, Mayxay M, McGready R, Moore BR, Mueller I, Newton PN, Thuy-Nhien NT, Noedl H, Nosten F, Phyo AP, Poespoprodjo JR, Saunders DL, Smithuis F, Spring MD, Stepniewska K, Suon S, Suputtamongkol Y, Syafruddin D, Tran HT, Valecha N, Van Herp M, Van Vugt M, White NJ, Guerin PJ, Simpson JA, Price RN.
        PLoS Med. 2020 Nov;17(11):e1003393.
        BACKGROUND: There is a high risk of Plasmodium vivax parasitaemia following treatment of falciparum malaria. Our study aimed to quantify this risk and the associated determinants using an individual patient data meta-analysis in order to identify populations in which a policy of universal radical cure, combining artemisinin-based combination therapy (ACT) with a hypnozoitocidal antimalarial drug, would be beneficial. METHODS AND FINDINGS: A systematic review of Medline, Embase, Web of Science, and the Cochrane Database of Systematic Reviews identified efficacy studies of uncomplicated falciparum malaria treated with ACT that were undertaken in regions coendemic for P. vivax between 1 January 1960 and 5 January 2018. Data from eligible studies were pooled using standardised methodology. The risk of P. vivax parasitaemia at days 42 and 63 and associated risk factors were investigated by multivariable Cox regression analyses. Study quality was assessed using a tool developed by the Joanna Briggs Institute. The study was registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42018097400). In total, 42 studies enrolling 15,341 patients were included in the analysis, including 30 randomised controlled trials and 12 cohort studies. Overall, 14,146 (92.2%) patients had P. falciparum monoinfection and 1,195 (7.8%) mixed infection with P. falciparum and P. vivax. The median age was 17.0 years (interquartile range [IQR] = 9.0-29.0 years; range = 0-80 years), with 1,584 (10.3%) patients younger than 5 years. 2,711 (17.7%) patients were treated with artemether-lumefantrine (AL, 13 studies), 651 (4.2%) with artesunate-amodiaquine (AA, 6 studies), 7,340 (47.8%) with artesunate-mefloquine (AM, 25 studies), and 4,639 (30.2%) with dihydroartemisinin-piperaquine (DP, 16 studies). 14,537 patients (94.8%) were enrolled from the Asia-Pacific region, 684 (4.5%) from the Americas, and 120 (0.8%) from Africa. At day 42, the cumulative risk of vivax parasitaemia following treatment of P. falciparum was 31.1% (95% CI 28.9-33.4) after AL, 14.1% (95% CI 10.8-18.3) after AA, 7.4% (95% CI 6.7-8.1) after AM, and 4.5% (95% CI 3.9-5.3) after DP. By day 63, the risks had risen to 39.9% (95% CI 36.6-43.3), 42.4% (95% CI 34.7-51.2), 22.8% (95% CI 21.2-24.4), and 12.8% (95% CI 11.4-14.5), respectively. In multivariable analyses, the highest rate of P. vivax parasitaemia over 42 days of follow-up was in patients residing in areas of short relapse periodicity (adjusted hazard ratio [AHR] = 6.2, 95% CI 2.0-19.5; p = 0.002); patients treated with AL (AHR = 6.2, 95% CI 4.6-8.5; p < 0.001), AA (AHR = 2.3, 95% CI 1.4-3.7; p = 0.001), or AM (AHR = 1.4, 95% CI 1.0-1.9; p = 0.028) compared with DP; and patients who did not clear their initial parasitaemia within 2 days (AHR = 1.8, 95% CI 1.4-2.3; p < 0.001). The analysis was limited by heterogeneity between study populations and lack of data from very low transmission settings. Study quality was high. CONCLUSIONS: In this meta-analysis, we found a high risk of P. vivax parasitaemia after treatment of P. falciparum malaria that varied significantly between studies. These P. vivax infections are likely attributable to relapses that could be prevented with radical cure including a hypnozoitocidal agent; however, the benefits of such a novel strategy will vary considerably between geographical areas.

      3. Population-based prevalence of Chlamydia trachomatis infection and antibodies in four districts with varying levels of trachoma endemicity in Amhara, Ethiopiaexternal icon
        Nash SD, Astale T, Nute AW, Bethea D, Chernet A, Sata E, Zerihun M, Gessese D, Ayenew G, Ayele Z, Melak B, Haile M, Zeru T, Tadesse Z, Arnold BF, Callahan EK, Martin DL.
        Am J Trop Med Hyg. 2020 Oct 26.
        The Trachoma Control Program in Amhara region, Ethiopia, scaled up the surgery, antibiotics, facial cleanliness, and environmental improvement (SAFE) strategy in all districts starting in 2007. Despite these efforts, many districts still require additional years of SAFE. In 2017, four districts were selected for the assessment of antibody responses against Chlamydia trachomatis antigens and C. trachomatis infection to better understand transmission. Districts with differing endemicity were chosen, whereby one had a previous trachomatous inflammation-follicular (TF) prevalence of > 30% (Andabet), one had a prevalence between 10% and 29.9% (Dera), one had a prevalence between 5% and 10% (Woreta town), and one had a previous TF prevalence of < 5% (Alefa) and had not received antibiotic intervention for 2 years. Survey teams assessed trachoma clinical signs and took conjunctival swabs and dried blood spots (DBS) to measure infection and antibody responses. Trachomatous inflammation-follicular prevalence among children aged 1-9 years was 37.0% (95% CI: 31.1-43.3) for Andabet, 14.7% (95% CI: 10.0-20.5) for Dera, and < 5% for Woreta town and Alefa. Chlamydia trachomatis infection was only detected in Andabet (11.3%). Within these districts, 2,195 children provided DBS. The prevalence of antibody responses to the antigen Pgp3 was 36.9% (95% CI: 29.0-45.6%) for Andabet, 11.3% (95% CI: 5.9-20.6%) for Dera, and < 5% for Woreta town and Alefa. Seroconversion rate for Pgp3 in Andabet was 0.094 (95% CI: 0.069-0.128) events per year. In Andabet district, where SAFE implementation has occurred for 11 years, the antibody data support the finding of persistently high levels of trachoma transmission.

    • Public Health Leadership and Management
      1. Reading between the lines: A qualitative case study of national public health institute functions and attributes in the Joint External Evaluationexternal icon
        Clemente J, Rhee S, Miller B, Bronner E, Whitney E, Bratton S, Carnevale C.
        J Public Health Afr. 2020 Apr 29;11(1):1329.
        National Public Health Institutes (NPHIs) are national-level institutions that can lead and coordinate a country's public health system. The Africa Centres for Disease Control and Prevention (Africa CDC) considers NPHI development critical to strengthening public health systems in Africa. This paper describes how Joint External Evaluation (JEE) reports demonstrate the role NPHIs can play in supporting the goals of IHR compliance and global health security. This study is a secondary document-based qualitative analysis of JEE reports from 11 countries in the WHO AFRO region (Botswana, Ethiopia, Liberia, Mozambique, Namibia, Nigeria, Rwanda, Sierra Leone, South Africa, Uganda, and Zambia). Researchers found three distinct thematic areas: i) core public health functions, ii) governance, and iii) coordination, collaboration, and communication. These themes and their interlinkages, both in pairs and all three, were of importance in displaying the roles that NPHIs could play in the strengthening of health systems. The data suggests that NPHIs, though not always explicitly mentioned in the data, may have a vital role in strengthening health systems across Africa and their governments' goals of achieving IHR compliance.

      2. Zambia field epidemiology training program: strengthening health security through workforce developmentexternal icon
        Kumar R, Kateule E, Sinyange N, Malambo W, Kayeye S, Chizema E, Chongwe G, Minor P, Kapina M, Baggett HC, Yard E, Mukonka V.
        Pan Afr Med J. 2020 ;36:323.
        The Zambia Field Epidemiology Training Program (ZFETP) was established by the Ministry of Health (MoH) during 2014, in order to increase the number of trained field epidemiologists who can investigate outbreaks, strengthen disease surveillance, and support data-driven decision making. We describe the ZFETP´s approach to public health workforce development and health security strengthening, key milestones five years after program launch, and recommendations to ensure program sustainability. Program description: ZFETP was established as a tripartite arrangement between the Zambia MoH, the University of Zambia School of Public Health, and the U.S. Centers for Disease Control and Prevention. The program runs two tiers: Advanced and Frontline. To date, ZFETP has enrolled three FETP-Advanced cohorts (training 24 residents) and four Frontline cohorts (training 71 trainees). In 2016, ZFETP moved organizationally to the newly established Zambia National Public Health Institute (ZNPHI). This re-positioning raised the program´s profile by providing residents with increased opportunities to lead high-profile outbreak investigations and analyze national surveillance data-achievements that were recognized on a national stage. These successes attracted investment from the Government of Republic of Zambia (GRZ) and donors, thus accelerating field epidemiology workforce capacity development in Zambia. In its first five years, ZFETP achieved early success due in part to commitment from GRZ, and organizational positioning within the newly formed ZNPHI, which have catalyzed ZFETP´s institutionalization. During the next five years, ZFETP seeks to sustain this momentum by expanding training of both tiers, in order to accelerate the professional development of field epidemiologists at all levels of the public health system.

    • Reproductive Health
      1. The role of public-private partnerships to increase access to contraception in an emergency response setting: The Zika Contraception Access Network Programexternal icon
        Romero L, Mendoza ZV, Croft L, Bhakta R, Sidibe T, Bracero N, Malave C, Suarez A, Sanchez L, Cordero D, Lathrop E, Monroe J.
        J Womens Health (Larchmt). 2020 Nov;29(11):1372-1380.
        The Zika Contraception Access Network (Z-CAN) program was a short-term emergency response intervention that used contraception to prevent unintended pregnancies to reduce Zika-related adverse birth outcomes during the 2016-2017 Zika virus outbreak in Puerto Rico. The Centers for Disease Control and Prevention (CDC) reported that a collaborative and coordinated response was needed from governments and private-sector partners to improve access to contraception during the Zika outbreak in Puerto Rico. In response, the National Foundation for the CDC, with technical assistance from CDC, established the Z-CAN program, a network of 153-trained physicians, that provided client-centered contraceptive counseling and same-day access to the full range of the Food and Drug Administration-approved reversible contraceptive methods at no cost for women who chose to prevent pregnancy. From May 2016 to September 2017, 29,221 women received Z-CAN services. Through Z-CAN, public-private partnerships provided a broad range of opportunities for partners to come together to leverage technical expertise, experience, and resources to remove barriers to access contraception that neither the public nor the private sector could address alone. Public-private partnerships focused on three areas: (1) the coordination of efforts among federal and territorial agencies to align strategies, leverage resources, and address sustainability; (2) the mobilization of private partnerships to secure resources from private corporations, domestic philanthropic organizations, and nonprofit organizations for contraceptive methods, physician reimbursement, training and proctoring resources, infrastructure costs, and a health communications campaign; and (3) the engagement of key stakeholders to understand context and need, and to identify strategies to reach the target population. Public-private partnerships provided expertise, support, and awareness, and could be used to help guide programs to other settings for which access to contraception could improve health outcomes.

    • Substance Use and Abuse
      1. Tobacco product use among adults - United States, 2019external icon
        Cornelius ME, Wang TW, Jamal A, Loretan CG, Neff LJ.
        MMWR Morb Mortal Wkly Rep. 2020 Nov 20;69(46):1736-1742.
        Cigarette smoking remains the leading cause of preventable disease and death in the United States (1). The prevalence of current cigarette smoking among U.S. adults has declined over the past several decades, with a prevalence of 13.7% in 2018 (2). However, a variety of combustible, noncombustible, and electronic tobacco products are available in the United States (1,3). To assess recent national estimates of tobacco product use among U.S. adults aged ≥18 years, CDC analyzed data from the 2019 National Health Interview Survey (NHIS). In 2019, an estimated 50.6 million U.S. adults (20.8%) reported currently using any tobacco product, including cigarettes (14.0%), e-cigarettes (4.5%), cigars (3.6%), smokeless tobacco (2.4%), and pipes* (1.0%).(†) Most current tobacco product users (80.5%) reported using combustible products (cigarettes, cigars, or pipes), and 18.6% reported using two or more tobacco products.(§) The prevalence of any current tobacco product use was higher among males; adults aged ≤65 years; non-Hispanic American Indian/Alaska Native (AI/AN) adults; those whose highest level of educational attainment was a General Educational Development (GED) certificate; those with an annual household income <$35,000; lesbian, gay, or bisexual (LGB) adults; uninsured adults and those with Medicaid; those with a disability; or those with mild, moderate, or severe generalized anxiety disorder. E-cigarette use was highest among adults aged 18-24 years (9.3%), with over half (56.0%) of these young adults reporting that they had never smoked cigarettes. Implementing comprehensive, evidence-based, population level interventions (e.g., tobacco price increases, comprehensive smoke-free policies, high-impact antitobacco media campaigns, and barrier-free cessation coverage), in coordination with regulation of the manufacturing, marketing, and sale of all tobacco products, can reduce tobacco-related disease and death in the United States (1,4). As part of a comprehensive approach, targeted interventions are also warranted to reach subpopulations with the highest prevalence of use, which might vary by tobacco product type.

    • Zoonotic and Vectorborne Diseases
      1. 2018 Zika Health Brigade: Delivering critical health screening in the U.S. Virgin Islandsexternal icon
        Godfred-Cato S, Fehrenbach SN, Reynolds MR, Galang RR, Schoelles D, Brown-Shuler L, Hillman B, DeWilde L, Prosper A, Hudson A, Moore CA, Ellis EM.
        Trop Med Infect Dis. 2020 Nov 9;5(4).
        In 2017, Hurricanes Irma and Maria caused significant damage to the United States Virgin Islands (USVI), heightening the challenges many residents faced in accessing adequate healthcare and receiving recommended Zika virus screening services. To address this challenge, the USVI Department of Health (DOH) requested technical assistance from the Centers for Disease Control and Prevention (CDC), the Health Resources and Services Administration (HRSA), and the American Academy of Pediatrics (AAP) to organize a health brigade to bring needed medical care to an underserved population. It also established the development of important partnerships between federal and private partners as well as between clinical providers and public health entities such as the Epidemiology & Disease Reporting, Maternal Child Health (MCH), and Infant and Toddlers Programs within the DOH, and local clinicians. This health brigade model could be replicated to ensure recommended evaluations are delivered to populations that may have unmet medical needs due to the complexity of the conditions and/or rural location.

      2. Targeted metagenomics for clinical detection and discovery of bacterial tick-borne pathogensexternal icon
        Kingry L, Sheldon S, Oatman S, Pritt B, Anacker M, Bjork J, Neitzel D, Strain A, Berry J, Sloan L, Respicio-Kingry L, Dietrich E, Bloch K, Moncayo A, Srinivasamoorthy G, Hu B, Hinckley A, Mead P, Kugeler K, Petersen J.
        J Clin Microbiol. 2020 Oct 21;58(11).
        Tick-borne diseases, due to a diversity of bacterial pathogens, represent a significant and increasing public health threat throughout the Northern Hemisphere. A high-throughput 16S V1-V2 rRNA gene-based metagenomics assay was developed and evaluated using >13,000 residual samples from patients suspected of having tick-borne illness and >1,000 controls. Taxonomic predictions for tick-borne bacteria were exceptionally accurate, as independently validated by secondary testing. Overall, 881 specimens were positive for bacterial tick-borne agents. Twelve tick-borne bacterial species were detected, including two novel pathogens, representing a 100% increase in the number of tick-borne bacteria identified compared to what was possible by initial PCR testing. In three blood specimens, two tick-borne bacteria were simultaneously detected. Seven bacteria, not known to be tick transmitted, were also confirmed to be unique to samples from persons suspected of having tick-borne illness. These results indicate that 16S V1-V2 metagenomics can greatly simplify diagnosis and accelerate the discovery of bacterial tick-borne pathogens.

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

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