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Issue 6, February 8, 2022

CDC Science Clips: Volume 14, Issue 6, February 8, 2022

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.
    • Antimicrobial Resistance and Antibiotic Stewardship
      1. National Healthcare Safety Network 2018 baseline neonatal Standardized Antimicrobial Administration Ratiosexternal icon
        O'Leary EN, Edwards JR, Srinivasan A, Neuhauser MM, Soe MM, Webb AK, Edwards EM, Horbar JD, Soll RF, Roberts J, Hicks LA, Wu H, Zayack D, Braun D, Cali S, Edwards WH, Flannery DD, Fleming-Dutra KE, Guzman-Cottrill JA, Kuzniewicz M, Lee GM, Newland J, Olson J, Puopolo KM, Rogers SP, Schulman J, Septimus E, Pollock DA.
        Hosp Pediatr. 2022 Jan 24.
        BACKGROUND: The microbiologic etiologies, clinical manifestations, and antimicrobial treatment of neonatal infections differ substantially from infections in adult and pediatric patient populations. In 2019, the Centers for Disease Control and Prevention developed neonatal-specific (Standardized Antimicrobial Administration Ratios SAARs), a set of risk-adjusted antimicrobial use metrics that hospitals participating in the National Healthcare Safety Network's (NHSN's) antimicrobial use surveillance can use in their antibiotic stewardship programs (ASPs). METHODS: The Centers for Disease Control and Prevention, in collaboration with the Vermont Oxford Network, identified eligible patient care locations, defined SAAR agent categories, and implemented neonatal-specific NHSN Annual Hospital Survey questions to gather hospital-level data necessary for risk adjustment. SAAR predictive models were developed using 2018 data reported to NHSN from eligible neonatal units. RESULTS: The 2018 baseline neonatal SAAR models were developed for 7 SAAR antimicrobial agent categories using data reported from 324 neonatal units in 304 unique hospitals. Final models were used to calculate predicted antimicrobial days, the SAAR denominator, for level II neonatal special care nurseries and level II/III, III, and IV NICUs. CONCLUSIONS: NHSN's initial set of neonatal SAARs provides a way for hospital ASPs to assess whether antimicrobial agents in their facility are used at significantly higher or lower rates compared with a national baseline or whether an individual SAAR value is above or below a specific percentile on a given SAAR distribution, which can prompt investigations into prescribing practices and inform ASP interventions.

      2. OBJECTIVE: To evaluate hospital-level variation in using first-line antibiotics for Clostridioides difficile infection (CDI) based on the burden of laboratory-identified (LabID) CDI. METHODS: Using data on hospital-level LabID CDI events and antimicrobial use (AU) for CDI (oral/rectal vancomycin or fidaxomicin) submitted to the National Healthcare Safety Network in 2019, we assessed the association between hospital-level CDI prevalence (per 100 patient admissions) and rate of CDI AU (days of therapy per 1,000 days present) to generate a predicted value of AU based on CDI prevalence and CDI test type using negative binomial regression. The ratio of the observed to predicted AU was then used to identify hospitals with extreme discordance between CDI prevalence and CDI AU, defined as hospitals with a ratio outside of the intervigintile range. RESULTS: Among 963 acute-care hospitals, rate of CDI prevalence demonstrated a positive dose-response relationship with rate of CDI AU. Compared with hospitals without extreme discordance (n = 902), hospitals with lower-than-expected CDI AU (n = 31) had, on average, fewer beds (median, 106 vs 208), shorter length of stay (median, 3.8 vs 4.2 days), and higher proportion of undergraduate or nonteaching medical school affiliation (48% vs 39%). Hospitals with higher-than-expected CDI AU (n = 30) were similar overall to hospitals without extreme discordance. CONCLUSIONS: The prevalence rate of LabID CDI had a significant dose-response association with first-line antibiotics for treating CDI. We identified hospitals with extreme discordance between CDI prevalence and CDI AU, highlighting potential opportunities for data validation and improvements in diagnostic and treatment practices for CDI.

    • Communicable Diseases
      1. The Maricopa County Department of Public Health in Arizona investigated three COVID-19 outbreaks associated with club sports, two in tournaments and one in a hockey league. During September through November 2020, 195 team-associated and 69 secondary household contact cases were identified among 2093 athletes, coaches, and staff members; the team attack rate ranged from 6% to 72%. Outbreaks occurred during high community transmission periods in Maricopa County. Identification of contacts and characterization of prevention strategies were challenging because of limited cooperation from athletes, families, and staff. (Am J Public Health. 2022;112(2):216-219. https://doi.org/10.2105/AJPH.2021.306579).

      2. Enhancing and promoting data management and systematic monitoring for an improved HIV/AIDS programs in Addis Ababa, Ethiopiaexternal icon
        Habte D, Zemenfeskudus S, Endale M, Zeidan M, Getachew D, Woldemichael D, Wesene AS, Teklebirhan E, Eyayu F, Zewdie R, Yirga D, Amdino W, Melaku Z, Abayneh SA.
        BMC Health Serv Res. 2022 ;22(1).
        Background: Ethiopia Population-based HIV Impact Assessment findings showed that in Addis Ababa, only 65.2% of people living with HIV (PLHIV) know their status. We present the enhanced HIV/AIDS data management and systematic monitoring experience in Addis Ababa City Administration Health Bureau (AACAHB). Methods: AACAHB established a command-post with leadership and technical team members from the health bureau, 10 sub-city health offices, and non-governmental stakeholders. The command-post improved governance, standardized HIV program implementation, and established accountability mechanism. A web-based database was established at each health facility, sub-city, and AACAHB level. Performance was scored (green, ≥75%; yellow, 50–74%; red, < 50%). The command-post reviewed performance on weekly basis. A mentorship team provided a weekly site-level support at underperforming public and private health facilities. At facility level, quality of data on recording tools such as registers, and individual medical records were maintained through continued review, feedback mechanisms and regular consistency check of data. Percentage and 95% confidence interval were computed to compare the improvement in program performance over time. Results: After 6 months of intervention period, the monthly New HIV case finding in 47 health facilities increased from 422 to 734 (1.7 times) and treatment initiation increased from 302 to 616 (2 times). After 6 months, the aggregate scoring for HIV testing at city level improved from yellow to green, HIV case finding improved from red to green, and treatment initiation improved from red to yellow. An increasing trend was noted in HIV positive case finding with statistically significant improvement from 43.4% [95% Confidence Interval: 40.23–46.59%] in May 2019 to 74.9% [95% Confidence Interval: 72.03–77.6%] in September 2019. Similarly, significant improvement was recorded for new HIV treatment from 30.9% [95% Confidence Interval: 28.01–33.94%] in May 2019 to 62.5% [95% Confidence Interval: 59.38–65.6%] in September 2019. Conclusions: Regular data driven HIV program review was institutionalized at city, sub-city and health facility levels which further improved HIV program monitoring and performance. The performance of HIV case finding and treatment initiation improved significantly via using intensified monitoring, data driven performance review, targeted site-level support based on the gap, and standardized approaches. © 2022, The Author(s).

      3. Serial thromboelastography and the development of venous thromboembolism in critically ill patients with COVID-19external icon
        Marvi TK, Stubblefield WB, Tillman BF, Tenforde MW, Patel MM, Lindsell CJ, Self WH, Grijalva CG, Rice TW.
        Crit Care Explor. 2022 Jan;4(1):e0618.
        To test the hypothesis that relatively lower clot strength on thromboelastography maximum amplitude (MA) is associated with development of venous thromboembolism (VTE) in critically ill patients with COVID-19. DESIGN: Prospective, observational cohort study. SETTING: Tertiary care, academic medical center in Nashville, TN. PATIENTS: Patients with acute respiratory failure from COVID-19 pneumonia admitted to the adult medical ICU without known VTE at enrollment. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Ninety-eight consecutive critically ill adults with laboratory-confirmed COVID-19 were enrolled. Thromboelastography parameters and conventional coagulation parameters were measured on days 0 (within 48 hr of ICU admission), 3, 5, and 7 after enrollment. The primary outcome was diagnosis of VTE with confirmed deep venous thrombosis and/or pulmonary embolism by clinical imaging or autopsy. Twenty-six patients developed a VTE. Multivariable regression controlling for antiplatelet exposure and anticoagulation dose with death as a competing risk found that lower MA was associated with increased risk of VTE. Each 1 mm increase in enrollment and peak MA was associated with an 8% and 14% decrease in the risk of VTE, respectively (enrollment MA: subdistribution hazard ratio [SHR], 0.92; 95% CI, 0.87-0.97; p = 0.003 and peak MA: SHR, 0.86; 95% CI, 0.81-0.91; p < 0.001). Lower enrollment platelet counts and fibrinogen levels were also associated with increased risk of VTE (p = 0.002 and p = 0.01, respectively). Platelet count and fibrinogen level were positively associated with MA (multivariable model: adjusted R (2) = 0.51; p < 0.001). CONCLUSIONS: When controlling for the competing risk of death, lower enrollment and peak MA were associated with increased risk of VTE. Lower platelet counts and fibrinogen levels at enrollment were associated with increased risk of VTE. The association of diminished MA, platelet counts, and fibrinogen with VTE may suggest a relative consumptive coagulopathy in critically ill patients with COVID-19.

      4. Severe outcomes, readmission, and length of stay among COVID-19 patients with intellectual and developmental disabilitiesexternal icon
        Koyama AK, Koumans EH, Sircar K, Lavery A, Hsu J, Ryerson AB, Siegel DA.
        Int J Infect Dis. 2022 Jan 22.

      5. HIV incidence and prevalence among adults aged 15-64 years in Rwanda: Results from the Rwanda Population-based HIV Impact Assessment (RPHIA) and District-level Modeling, 2019external icon
        Nsanzimana S, Rwibasira G, Malamba SS, Musengimana G, Kayirangwa E, Jonnalagadda S, Fazito E, Eaton J, Mugisha V, Remera E, Semakula M, Mulindabigwi A, Omolo FJ, Wiesner L, Moore C, Patel H, Justman J.
        Int J Infect Dis. 2022 Jan 20.
        OBJECTIVES: The 2018-19 Rwanda Population-based HIV Impact Assessment (RPHIA) was conducted to measure national HIV incidence and prevalence. District-level estimates were modeled to inform resources allocation. METHODS: RPHIA was a nationally representative cross-sectional household survey. Consenting adults were interviewed and tested for HIV using the national diagnostic algorithm followed by laboratory-based confirmation of HIV status, and testing for viral load (VL), limiting antigen (LAg) avidity and presence of antiretrovirals. Incidence was calculated using normalized optical density ≤ 1•5, VL ≥ 1,000 copies/mL, and undetectable antiretrovirals. Survey and programmatic data were used to model district-level HIV incidence and prevalence. RESULTS: Of 31,028 eligible adults, 98•7% participated in RPHIA and 934 tested HIV positive. HIV prevalence among adults in Rwanda was 3•0% (95% CI:2•7-3•3). National HIV incidence was 0•08% (95% CI:0•02-0•14) and 0•11% (95% CI:0•00-0•26) in the City of Kigali (CoK). Based on district-level modeling, HIV incidence was greatest in the three CoK districts (0•11% to 0•15%) and varied across other districts (0•03% to 0•10%). CONCLUSIONS: HIV prevalence among adults in Rwanda is 3.0%; HIV incidence is low at 0.08%. District-level modeling has identified disproportionately affected urban hotspots: areas to focus resources.

      6. Hepatitis D-associated hospitalizations in the United States: 2010-2018external icon
        Wasuwanich P, Striley CW, Kamili S, Teshale EH, Seaberg EC, Karnsakul W.
        J Viral Hepat. 2022 Jan 25.
        In the U.S., hepatitis D is not a reportable condition, leading to gaps in epidemiological and clinical knowledge. We aim to estimate the incidence of hepatitis D-associated hospitalizations in the U.S. and describe the clinical, demographic, and geographic characteristics of those hospitalizations.We utilized hospitalization data from the 2010-2018 National Inpatient Sample fro m the Healthcare Cost and Utilization Project. Hepatitis D and hepatitis B only (HBV only) hospitalizations were identified by ICD-9 and ICD-10 codes. We identified 3,825 hepatitis D-associated hospitalizations. The hospitalization rate of hepatitis D was between 6.9 to 20.7 per 10,000,000 but did not change significantly over time. Compared to HBV only, the hepatitis D cohort had a greater proportion of males, Hispanics, hospitalizations in the Northeast region. The hepatitis D-associated hospitalizations also had significantly greater frequencies of liver failure, non-alcoholic cirrhosis, portal hypertension, ascites, and thrombocytopenia. While mortality in hepatitis D was similar to that of HBV only, age >65 years (OR=3.79; p=0.020) and having a diagnosis of alcoholic cirrhosis (OR=3.37; p=0.044) increased the odds of mortality within the hepatitis D cohort. Although the hepatitis D-associated hospitalizations were relatively uncommon, they were associated with severe complications.

      7. Trends in disease severity and health care utilization during the early Omicron variant period compared with previous SARS-COV-2 high transmission periods - United States, December 2020-January 2022external icon
        Iuliano AD, Brunkard JM, Boehmer TK, Peterson E, Adjei S, Binder AM, Cobb S, Graff P, Hidalgo P, Panaggio MJ, Rainey JJ, Rao P, Soetebier K, Wacaster S, Ai C, Gupta V, Molinari NM, Ritchey MD.
        MMWR Morb Mortal Wkly Rep. 2022 Jan 28;71(4):146-152.
        The B.1.1.529 (Omicron) variant of SARS-CoV-2, the virus that causes COVID-19, was first clinically identified in the United States on December 1, 2021, and spread rapidly. By late December, it became the predominant strain, and by January 15, 2022, it represented 99.5% of sequenced specimens in the United States* (1). The Omicron variant has been shown to be more transmissible and less virulent than previously circulating variants (2,3). To better understand the severity of disease and health care utilization associated with the emergence of the Omicron variant in the United States, CDC examined data from three surveillance systems and a large health care database to assess multiple indicators across three high-COVID-19 transmission periods: December 1, 2020-February 28, 2021 (winter 2020-21); July 15-October 31, 2021 (SARS-CoV-2 B.1.617.2 [Delta] predominance); and December 19, 2021-January 15, 2022 (Omicron predominance). The highest daily 7-day moving average to date of cases (798,976 daily cases during January 9-15, 2022), emergency department (ED) visits (48,238), and admissions (21,586) were reported during the Omicron period, however, the highest daily 7-day moving average of deaths (1,854) was lower than during previous periods. During the Omicron period, a maximum of 20.6% of staffed inpatient beds were in use for COVID-19 patients, 3.4 and 7.2 percentage points higher than during the winter 2020-21 and Delta periods, respectively. However, intensive care unit (ICU) bed use did not increase to the same degree: 30.4% of staffed ICU beds were in use for COVID-19 patients during the Omicron period, 0.5 percentage points lower than during the winter 2020-21 period and 1.2 percentage points higher than during the Delta period. The ratio of peak ED visits to cases (event-to-case ratios) (87 per 1,000 cases), hospital admissions (27 per 1,000 cases), and deaths (nine per 1,000 cases [lagged by 3 weeks]) during the Omicron period were lower than those observed during the winter 2020-21 (92, 68, and 16 respectively) and Delta (167, 78, and 13, respectively) periods. Further, among hospitalized COVID-19 patients from 199 U.S. hospitals, the mean length of stay and percentages who were admitted to an ICU, received invasive mechanical ventilation (IMV), and died while in the hospital were lower during the Omicron period than during previous periods. COVID-19 disease severity appears to be lower during the Omicron period than during previous periods of high transmission, likely related to higher vaccination coverage,(†) which reduces disease severity (4), lower virulence of the Omicron variant (3,5,6), and infection-acquired immunity (3,7). Although disease severity appears lower with the Omicron variant, the high volume of ED visits and hospitalizations can strain local health care systems in the United States, and the average daily number of deaths remains substantial.(§) This underscores the importance of national emergency preparedness, specifically, hospital surge capacity and the ability to adequately staff local health care systems. In addition, being up to date on vaccination and following other recommended prevention strategies are critical to preventing infections, severe illness, or death from COVID-19.

      8. HIV prevalence and incidence among men who have sex with men and transgender women in Bangkok, 2014-2018: Outcomes of a consensus development initiativeexternal icon
        van Griensven F, Phanuphak N, Manopaiboon C, Dunne EF, Colby DJ, Chaiphosri P, Ramautarsing R, Mock PA, Guadamuz TE, Rangsin R, Benjamaneepairoj K, Na Nakorn P, Vannakit R, de Lind van Wijngaarden JW, Avery M, Mills S.
        PLoS One. 2022 ;17(1):e0262694.
        To reach its goal of ending AIDS by 2030, Thailand has adopted antiretroviral treatment as prevention and HIV pre-exposure prophylaxis for men who have sex with men (MSM) and transgender women (TGW) as its core HIV control strategy. However, in the absence of reliable epidemiologic indicators, the impact of these policies on the course of the HIV epidemic in these groups remains unknown. To help answer this question, we formulated an HIV epidemic consensus initiative for Bangkok, Thailand, to analyze epidemiologic and program data and reach agreement between experts and stakeholders on the evolving state of the HIV epidemic among MSM and TGW. A customized Delphi process was used to consult and consolidate viewpoints of experts and stakeholders. Experts presented and discussed HIV prevalence and incidence data from recent and ongoing studies among MSM and TGW in Bangkok (2014 to 2018) during a meeting with stakeholders representing government, donors, and civil society. Agreement about the course of the HIV epidemic among MSM and TGW was attained by voting consensus. Based on presented data, meeting participants agreed that HIV prevalence and incidence had decreased among Bangkok MSM from 2014 to 2018. Despite these declines, HIV prevalence and incidence were found to remain high. This was particularly the case among younger MSM. Participants agreed that there was no evidence for a decrease in HIV prevalence and incidence among Bangkok TGW. Introduction of antiretroviral treatment as prevention and HIV pre-exposure prophylaxis may have contributed to these declines. However, HIV prevalence and incidence remained high, and no signs of a decrease were reported among Bangkok TGW. At the current rate of new HIV infections in MSM and TGW, Thailand will not reach its goal of ending AIDS by 2030. This HIV consensus initiative may serve as a model for building agreement and advocacy on epidemiologic and program data and their implications for a large metropolitan city.

      9. Combining information to estimate adherence in studies of pre-exposure prophylaxis for HIV prevention: Application to HPTN 067external icon
        Hughes JP, Williamson BD, Krakauer C, Chau G, Ortiz B, Wakefield J, Hendrix C, Amico KR, Holtz TH, Bekker LG, Grant R.
        Stat Med. 2022 Jan 25.
        In trials of oral HIV pre-exposure prophylaxis (PrEP), multiple approaches have been used to measure adherence, including self-report, pill counts, electronic dose monitoring devices, and biological measures such as drug levels in plasma, peripheral blood mononuclear cells, hair, and/or dried blood spots. No one of these measures is ideal and each has strengths and weaknesses. However, accurate estimates of adherence to oral PrEP are important as drug efficacy is closely tied to adherence, and secondary analyses of trial data within identified adherent/non-adherent subgroups may yield important insights into real-world drug effectiveness. We develop a statistical approach to combining multiple measures of adherence and show in simulated data that the proposed method provides a more accurate measure of true adherence than self-report. We then apply the method to estimate adherence in the ADAPT study (HPTN 067) in South African women.

    • Community Health Services
      1. Impact of coronavirus disease 2019 (COVID-19) on US hospitals and patients, April-July 2020external icon
        Sapiano MR, Dudeck MA, Soe M, Edwards JR, O'Leary EN, Wu H, Allen-Bridson K, Amor A, Arcement R, Chernetsky Tejedor S, Dantes R, Gross C, Haass K, Konnor R, Kroop SR, Leaptrot D, Lemoine K, Nkwata A, Peterson K, Wattenmaker L, Weiner-Lastinger LM, Pollock D, Benin AL.
        Infect Control Hosp Epidemiol. 2022 Jan;43(1):32-39.
        OBJECTIVE: The rapid spread of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) throughout key regions of the United States in early 2020 placed a premium on timely, national surveillance of hospital patient censuses. To meet that need, the Centers for Disease Control and Prevention's National Healthcare Safety Network (NHSN), the nation's largest hospital surveillance system, launched a module for collecting hospital coronavirus disease 2019 (COVID-19) data. We present time-series estimates of the critical hospital capacity indicators from April 1 to July 14, 2020. DESIGN: From March 27 to July 14, 2020, the NHSN collected daily data on hospital bed occupancy, number of hospitalized patients with COVID-19, and the availability and/or use of mechanical ventilators. Time series were constructed using multiple imputation and survey weighting to allow near-real-time daily national and state estimates to be computed. RESULTS: During the pandemic's April peak in the United States, among an estimated 431,000 total inpatients, 84,000 (19%) had COVID-19. Although the number of inpatients with COVID-19 decreased from April to July, the proportion of occupied inpatient beds increased steadily. COVID-19 hospitalizations increased from mid-June in the South and Southwest regions after stay-at-home restrictions were eased. The proportion of inpatients with COVID-19 on ventilators decreased from April to July. CONCLUSIONS: The NHSN hospital capacity estimates served as important, near-real-time indicators of the pandemic's magnitude, spread, and impact, providing quantitative guidance for the public health response. Use of the estimates detected the rise of hospitalizations in specific geographic regions in June after they declined from a peak in April. Patient outcomes appeared to improve from early April to mid-July.

      2. Prevention research centers and COVID-19: Models of a community-engaged response to a public health emergencyexternal icon
        Busse KR, Lemon SC, Comerford BP, Islam NS, Ulin BF, Eriksen MP, Ammerman AS.
        Public Health Rep. 2022 Jan 21:333549211059491.
        For more than 30 years, the network of Centers for Disease Control and Prevention (CDC)-funded Prevention Research Centers (PRCs) has worked with local communities and partners to implement and evaluate public health interventions and policies for the prevention of disease and promotion of health. The COVID-19 pandemic tested the PRC network's ability to rapidly respond to multiple, simultaneous public health crises. On April 28, 2020, to assess the network's engagement with activities undertaken in response to the early phase of the pandemic, PRC network leadership distributed an online survey to the directors of 34 currently or formerly funded PRCs, asking them to report their PRCs' engagement with predetermined activities across 9 topical areas and provide case studies exemplifying that engagement. We received responses from 24 PRCs, all of which reported engagement with at least 1 of the 9 topical areas (mean, 5). The topical areas with which the greatest number of PRCs reported engagement were support of frontline agencies (21 of 24, 88%) and support of activities related to health care (21 of 24, 88%). The mean number of activities with which PRCs reported engagement was 11. The PRCs provided more than 90 case studies exemplifying their work. The results of the survey indicated that the PRCs mobilized their personnel and resources to support the COVID-19 response in less than 6 weeks. We posit that the speed of this response was due, in part, to the broad and diverse expertise of PRC personnel and long-standing partnerships between PRCs and the communities in which they work.

    • Environmental Health
      1. Areas of rural Alabama may be at risk for re-emergence of soil-transmitted helminthiasis (STH) where environmental conditions are favorable for STH transmission, including in the agricultural Black Belt region. We describe pediatric Medicaid STH visits in Alabama and compare STH visit rates in Black Belt counties with those of non-Black Belt counties. Alabama Medicaid visit claims among children aged 0-18 years who received an STH diagnosis during January 2010-December 2018 were examined. STH-related pediatric visits were uncommon, but several counties with higher STH rates were identified. Visit rates did not differ meaningfully when comparing Black Belt with non-Black Belt region counties (rate ratio: 1.10; 95% CI: 0.73-1.64). Additional studies examining STH prevalence among children living in communities at risk for STH in Alabama can further clarify STH burden and identify communities experiencing environmental and sanitation conditions favorable to STH endemicity.

    • Epidemiology and Surveillance
      1. OBJECTIVE: Administrative claims are commonly relied upon to identify hypoglycemia. We assessed validity of 14 International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis code assignments to identify medication-related hypoglycemia leading to acute care encounters. RESEARCH DESIGN AND METHODS: A multisite, retrospective medical record review study was conducted in a sample of Medicare beneficiaries prescribed outpatient diabetes medications and who received hospital care between January 1, 2016 and September 30, 2017. Diagnosis codes were validated with structured medical record review using prespecified criteria (clinical presentation, blood glucose values, and treatments for hypoglycemia). Sensitivity, specificity, and positive and negative predictive value (PPV, NPV) were calculated and adjusted using sampling weights to correct for partial verification bias. RESULTS: Among 990 encounters (496 cases, 494 controls), hypoglycemia codes demonstrated moderate PPV (69.2%; 95% confidence interval: 65.0-73.0) and moderate sensitivity (83.9%; 95% confidence interval: 70.0-95.5). Codes performed better at identifying hypoglycemic events among emergency department/observation encounters compared with hospitalizations (PPV 92.9%, sensitivity 100.0% vs. PPV 53.7%, sensitivity 71.0%). Accuracy varied by diagnosis position, especially for hospitalizations, with PPV of 95.6% versus 46.5% with hypoglycemia in primary versus secondary positions. Use of adverse event/poisoning codes did not improve accuracy; reliance on these codes alone would have missed 97% of true hypoglycemic events. CONCLUSIONS: Accuracy of International Classification of Diseases, Tenth Revision codes in administrative claims to identify medication-related hypoglycemia varied substantially by encounter type and diagnosis position. Consideration should be given to the trade-off between PPV and sensitivity when selecting codes, encounter types, and diagnosis positions to identify hypoglycemia.

      2. Notes from the field: Early evidence of the SARS-COV-2 B.1.1.529 (Omicron) variant in community wastewater - United States, November-December 2021external icon
        Kirby AE, Welsh RM, Marsh ZA, Yu AT, Vugia DJ, Boehm AB, Wolfe MK, White BJ, Matzinger SR, Wheeler A, Bankers L, Andresen K, Salatas C, Gregory DA, Johnson MC, Trujillo M, Kannoly S, Smyth DS, Dennehy JJ, Sapoval N, Ensor K, Treangen T, Stadler LB, Hopkins L.
        MMWR Morb Mortal Wkly Rep. 2022 Jan 21;71(3):103-105.

      3. Disease surveillance among U.S.-bound immigrants and refugees - Electronic Disease Notification System, United States, 2014-2019external icon
        Phares CR, Liu Y, Wang Z, Posey DL, Lee D, Jentes ES, Weinberg M, Mitchell T, Stauffer W, Self JL, Marano N.
        MMWR Surveill Summ. 2022 Jan 21;71(2):1-21.
        PROBLEM/CONDITION: Each year, approximately 500,000 immigrants and tens of thousands of refugees (range: 12,000-85,000 during 2001-2020) move to the United States. While still abroad, immigrants, refugees, and others who apply for admission to live permanently in the United States must undergo a medical examination. This examination identifies persons with class A or B conditions. Applicants with class A conditions are inadmissible. Infectious conditions that cause an applicant to be inadmissible include infectious tuberculosis (TB) disease (class A TB), infectious syphilis, gonorrhea, and infectious Hansen's disease. Applicants with class B conditions are admissible but might require treatment or follow-up. Class B TB includes persons who completed successful treatment overseas for TB disease (class B0), those with signs or symptoms suggestive of TB but whose overseas laboratory tests and clinical examinations ruled out current infectious TB disease (class B1), those with a diagnosis of latent TB infection (LTBI) (class B2), and the close contacts of persons known to have TB disease (class B3). Voluntary public health interventions might also be offered during the overseas examination. After arriving in the United States, a follow-up TB examination is recommended for persons with class B TB. PERIOD COVERED: This report summarizes health information that was reported to CDC's Electronic Disease Notification (EDN) system for refugees, immigrants, and eligible others who arrived in the United States during 2014-2019. Eligible others are persons who although not classified as refugees (e.g., certain parolees, special immigrant visa holders, and follow-to-join asylees) are eligible for the same services and benefits as refugees. DESCRIPTION OF SYSTEM: The EDN system has both surveillance and programmatic components. The surveillance component is a centralized database that collects 1) health-related data from the overseas medical examination for immigrants with class A or B conditions and for all refugees and eligible others and 2) TB-related data from the postarrival TB examination. The programmatic component is a reporting system that sends arrival notifications to state and local health agencies in the jurisdiction where newly arriving persons have reported intending to live and provides state and local health agencies and other authorized users with medical data from overseas examinations. RESULTS: During 2014-2019, approximately 3.5 million persons moved to the United States from abroad, including 3.2 million immigrants, 313,890 refugees, and 95,993 eligible others. Among these, the overseas examination identified 139,683 persons (3,903 per 100,000 persons examined) with class B TB, 54 with primary or secondary syphilis (30 per 100,000 persons tested), 761 with latent syphilis (415 per 100,000 persons tested), and, after laboratory testing for gonorrhea was added in 2016, a total of 131 with gonorrhea (374 per 100,000 persons tested). Refugees were offered additional, voluntary interventions, including vaccinations and presumptive treatment for parasites. By 2019, first- and second-dose coverage with measles-containing vaccine were 96% and 80%, respectively. In refugee populations for whom presumptive treatment is recommended, up to 96% of refugees, depending on the specific regimen, were offered and accepted treatment. For the 139,683 persons identified overseas with class B TB, EDN sent arrival notifications and overseas medical data to the appropriate state or local health agency to facilitate postarrival TB examinations. Among 101,119 persons identified overseas as having class B0 TB (6,586) or class B1 TB (94,533), a total of 67,432 (67%) had a complete postarrival examination reported to EDN. Among 35,814 children aged 2-14 years identified overseas with class B2 TB, 20,758 (58%) had a complete postarrival examination reported to EDN. (Adults are not routinely tested for immune reactivity to Mycobacterium tuberculosis during the overseas medical examination.) Among those with a complete postarrival examination reported to EDN, the number with a diagnosis of culture-positive TB disease within the first year of arrival was 464 (688 cases per 100,000 persons examined) for those with class B0 or B1 TB and was 11 (53 cases per 100,000 persons examined) for children with class B2 TB. INTERPRETATION: During 2014-2019, the overseas medical examination system prevented importation of 6,586 cases of infectious TB, 815 cases of syphilis, and 131 cases of gonorrhea. When the examination is used to offer public health interventions, most refugees (up to 96%) accept the intervention. Postarrival follow-up examinations, which were completed for 88,190 persons and identified 475 cases of culture-positive TB, represent an important opportunity to further limit spread of TB disease in the United States by identifying and providing, if needed, preventive care for those with LTBI or treatment for those with disease. PUBLIC HEALTH ACTION: Federal, state, and local health departments and agencies should continue to use EDN data to monitor, evaluate, and improve health-related programs and policies aimed at U.S.-bound or recently arrived immigrants, refugees, and eligible others. Additional public health interventions that could be offered during the overseas medical examination should be considered (e.g., treatment for LTBI). Finally, for persons with class B TB, measures should be taken to identify and remove barriers to completing postarrival examinations to reduce risk for TB disease and community transmission, along with measures to encourage reporting of completed examinations for better data-driven decision-making.

      4. Risk factors and genotype distribution of hepatitis C virus in Georgia: A nationwide population-based surveyexternal icon
        Baliashvili D, Averhoff F, Kasradze A, Salyer SJ, Kuchukhidze G, Gamkrelidze A, Imnadze P, Alkhazashvili M, Chanturia G, Chitadze N, Sukhiashvili R, Blanton C, Drobeniuc J, Morgan J, Hagan LM.
        PLoS One. 2022 ;17(1):e0262935.
        In preparation for the National Hepatitis C Elimination Program in the country of Georgia, a nationwide household-based hepatitis C virus (HCV) seroprevalence survey was conducted in 2015. Data were used to estimate HCV genotype distribution and better understand potential sex-specific risk factors that contribute to HCV transmission. HCV genotype distribution by sex and reported risk factors were calculated. We used explanatory logistic regression models stratified by sex to identify behavioral and healthcare-related risk factors for HCV seropositivity, and predictive logistic regression models to identify additional variables that could help predict the presence of infection. Factors associated with HCV seropositivity in explanatory models included, among males, history of injection drug use (IDU) (aOR = 22.4, 95% CI = 12.7, 39.8) and receiving a blood transfusion (aOR = 3.6, 95% CI = 1.4, 8.8), and among females, history of receiving a blood transfusion (aOR = 4.0, 95% CI 2.1, 7.7), kidney dialysis (aOR = 7.3 95% CI 1.5, 35.3) and surgery (aOR = 1.9, 95% CI 1.1, 3.2). The male-specific predictive model additionally identified age, urban residence, and history of incarceration as factors predictive of seropositivity and were used to create a male-specific exposure index (Area under the curve [AUC] = 0.84). The female-specific predictive model had insufficient discriminatory performance to support creating an exposure index (AUC = 0.61). The most prevalent HCV genotype (GT) nationally was GT1b (40.5%), followed by GT3 (34.7%) and GT2 (23.6%). Risk factors for HCV seropositivity and distribution of HCV genotypes in Georgia vary substantially by sex. The HCV exposure index developed for males could be used to inform targeted testing programs.

      5. Leading causes of death and high mortality rates in an HIV endemic setting (Kisumu county, Kenya, 2019)external icon
        Waruru A, Onyango D, Nyagah L, Sila A, Waruiru W, Sava S, Oele E, Nyakeriga E, Muuo SW, Kiboye J, Musingila PK, van der Sande MA, Massawa T, Rogena EA, DeCock KM, Young PW.
        PLoS One. 2022 ;17(1):e0261162.
        BACKGROUND: In resource-limited settings, underlying causes of death (UCOD) often are not ascertained systematically, leading to unreliable mortality statistics. We reviewed medical charts to establish UCOD for decedents at two high volume mortuaries in Kisumu County, Kenya, and compared ascertained UCOD to those notified to the civil registry. METHODS: Medical experts trained in COD certification examined medical charts and ascertained causes of death for 456 decedents admitted to the mortuaries from April 16 through July 12, 2019. Decedents with unknown HIV status or who had tested HIV-negative >90 days before the date of death were tested for HIV. We calculated annualized all-cause and cause-specific mortality rates grouped according to global burden of disease (GBD) categories and separately for deaths due to HIV/AIDS and expressed estimated deaths per 100,000 population. We compared notified to ascertained UCOD using Cohen's Kappa (κ) and assessed for the independence of proportions using Pearson's chi-squared test. FINDINGS: The four leading UCOD were HIV/AIDS (102/442 [23.1%]), hypertensive disease (41/442 [9.3%]), other cardiovascular diseases (23/442 [5.2%]), and cancer (20/442 [4.5%]). The all-cause mortality rate was 1,086/100,000 population. The highest cause-specific mortality was in GBD category II (noncommunicable diseases; 516/100,000), followed by GBD I (communicable, perinatal, maternal, and nutritional; 513/100,000), and III (injuries; 56/100,000). The HIV/AIDS mortality rate was 251/100,000 population. The proportion of deaths due to GBD II causes was higher among females (51.9%) than male decedents (42.1%; p = 0.039). Conversely, more men/boys (8.6%) than women/girls (2.1%) died of GBD III causes (p = 0.002). Most of the records with available recorded and ascertained UCOD (n = 236), 167 (70.8%) had incorrectly recorded UCOD, and agreement between notified and ascertained UCOD was poor (29.2%; κ = 0.26). CONCLUSIONS: Mortality from infectious diseases, especially HIV/AIDS, is high in Kisumu County, but there is a shift toward higher mortality from noncommunicable diseases, possibly reflecting an epidemiologic transition and improving HIV outcomes. The epidemiologic transition suggests the need for increased focus on controlling noncommunicable conditions despite the high communicable disease burden. The weak agreement between notified and ascertained UCOD could lead to substantial inaccuracies in mortality statistics, which wholly depend on death notifications.

      6. Expanding data to care programs to improve HIV care continuum among men who have sex with men and transgender persons: Key processes and outcomes from Project PrIDE, 2015-2019external icon
        Mulatu MS, Carter JW, Flores SA, Benton S, Galindo CA, Johnson WD, Wilkes AL, Mbaka CK, Prather C.
        Public Health Rep. 2022 Jan 21:333549211058175.
        OBJECTIVES: During 2015-2019, five local and state health department jurisdictions implemented Data to Care (D2C) programs supported by Project PrIDE (Pre-exposure prophylaxis, Implementation, Data to Care, and Evaluation) to improve linkage or reengagement in HIV medical care among persons with HIV (PWH) who had gaps in care, particularly among men who have sex with men (MSM) and transgender persons. We describe findings from the cross-jurisdiction evaluation of the project. METHODS: We conducted a qualitative analysis of the final progress reports submitted by PrIDE jurisdictions to the Centers for Disease Control and Prevention to identify key D2C activities implemented and challenges encountered. We also conducted descriptive analysis on aggregate quantitative data to summarize key D2C program outcomes. RESULTS: PrIDE jurisdictions implemented multiple activities to build their D2C capacity, identify PWH who were not in care or virally suppressed, provide linkage/reengagement services, and monitor outcomes. Overall, 11 463 PWH were selected for follow-up, 45% of whom were MSM or transgender persons. Investigations were completed for 8935 (77.9%) PWH. Only 2323 (26.0%) PWH were confirmed not in care or virally suppressed; 1194 (51.4%) were subsequently linked/reengaged in care; among those, 679 (56.9%) were virally suppressed at last test. PrIDE jurisdictions identified data-related (eg, incomplete or delayed laboratory results), program capacity (eg, insufficient staff), and social and structural (eg, unstable housing) challenges that affected their D2C implementation. CONCLUSIONS: PrIDE jurisdictions successfully enhanced their D2C capacity, reached priority populations who were not in care or virally suppressed, and improved their engagement in care and health outcomes. Data-related and non-data-related challenges limited the efficiency of D2C programs. Findings can help inform other D2C programs and contribute to national HIV prevention goals.

    • Genetics and Genomics
      1. The Latin American Epidemiology Network for ALS (Laenals)external icon
        Hardiman O, Heverin M, Rooney J, Lillo P, Godoy G, Sáez D, Valenzuela D, Hughes R, Perna A, Ketzoian CN, Vazquez C, Gutierrez Gil J, Arias Morales A, Lara Fernandez G, Zaldivar T, Horton K, Mehta P, Logroscino G.
        Amyotroph Lateral Scler Frontotemporal Degener. 2022 Jan 21:1-6.
        Background: There is evolving evidence of non-uniform distribution of ALS worldwide, with apparently lower incident and prevalent rates outside populations of European origin. However, the phenotype, survival and environmental risk in populations of mixed ancestral origin have not been well established. Large scale population based studies of incidence, prevalence, phenotype and risk factors in admixed populations are necessary to determine the true demography of ALS, and to test the hypothesis of differential risk and phenotype in populations of mixed ancestry. Methods: The Latin American Epidemiological Network of ALS (LAENALS) has been established to perform a comparative analysis of ALS epidemiology between three different Latin American populations (Cuba, Uruguay and Chile), and to test the hypothesis that the demographics, phenotype and outcome of ALS are influenced by ancestral origin, and that environmental and occupational risk factors differ across different ethnicities due to subtle differences in gene- environmental interactions. Recognition and interrogation of these differences is an important step toward novel therapeutic approaches and personalized medicine for all ALS both in the US, and worldwide. Discussion: This work will enable direct and detailed comparative studies between different ancestral populations with varying degrees of admixture, with facility for comparison with a large European reference dataset for ALS, and will provide a unique and rich dataset of admixed populations for later comparative genomic studies.

      2. Evaluating a cluster and the overall trend of invasive haemophilus influenzae serotype b in Alaska 2005-2019external icon
        Nolen LD, Topaz N, Miernyk K, Bressler S, Massay SC, Geist M, Zulz T, Singleton R.
        Pediatr Infect Dis J. 2022 Jan 21.
        BACKGROUND: In 2019, 5 cases of invasive Haemophilus influenzae serotype b (Hib) occurred in the Anchorage region of Alaska over a period of 16 days. No cases had occurred in Alaska in the preceding 26 months. METHODS: Alaska Hib isolates from 2005 through 2019 were analyzed using whole-genome sequencing (WGS). Rates were compared to the CDC's Active Bacterial Core surveillance (ABCs) data. RESULTS: A total of 33 cases of invasive Hib occurred in Alaska from 2005 through 2019. Of the 5 cases associated with the cluster, 2 (40%) occurred in adults and all occurred in the Anchorage region. In contrast, only 14% (4/28) of the noncluster cases occurred in this region (P < 0.01). Two cluster cases were linked epidemiologically and the bacteria were nearly identical. The other 3 cluster cases were caused by 3 genetically distinct bacteria. When the full period was evaluated, the unadjusted rate of invasive Hib disease in Alaska was 15.5 times higher in Alaska Native (AN) people than non-AN people [1.3/100,000 vs. 0.07/100,000, 95% confidence intervals (CI): 10.2-22.5). The age-adjusted rate of invasive Hib disease in Alaska was 9.4 times higher than the ABCs rate (95% CI: 6.3-14.1). CONCLUSIONS: While clustered in time and space, the 5 cases in 2019 were not due to a single bacterial strain. AN people continue to have elevated rates of invasive Hib infection compared to both non-AN people in Alaska and the ABCs population.

      3. COVID-19 and sickle cell disease-related deaths reported in the United Statesexternal icon
        Payne AB, Schieve LA, Abe K, Hulihan M, Hooper WC, Hsu LL.
        Public Health Rep. 2022 Jan 21:333549211063518.
        Sickle cell disease (SCD) is associated with increased risk of poor health outcomes from respiratory infections, including COVID-19 illness. We used US death data to investigate changes in SCD-related mortality before and during the COVID-19 pandemic. We estimated annual age- and quarter-adjusted SCD-related mortality rates for 2014-2020. We estimated the number of excess deaths in 2020 compared with 2019 using the standardized mortality ratio (SMR). We found 1023 SCD-related deaths reported in the United States during 2020, of which 86 (8.4%) were associated with COVID-19. SCD-related deaths, both associated and not associated with COVID-19, occurred most frequently among adults aged 25-59 years. The SCD-related mortality rate changed <5% year to year from 2014 to 2019 but increased 12% in 2020; the sharpest increase was among adults aged ≥60 years. The SMR comparing 2020 with 2019 was 1.12 (95% CI, 1.06-1.19). Overall, 113 (95% CI, 54-166) excess SCD-related deaths occurred in 2020.

      4. Molecular epidemiology of rotavirus strains in symptomatic and asymptomatic children in Manhiça District, Southern Mozambique 2008-2019external icon
        Manjate F, João ED, Chirinda P, Garrine M, Vubil D, Nobela N, Kotloff K, Nataro JP, Nhampossa T, Acácio S, Tate JE, Parashar U, Mwenda JM, Alonso PL, Nyaga M, Cunha C, Mandomando I.
        Viruses. 2022 Jan 12;14(1).
        Group A rotaviruses remain the leading cause of diarrhoea in children aged <5 years. Mozambique introduced rotavirus vaccine (Rotarix(®)) in September 2015. We report rotavirus genotypes circulating among symptomatic and asymptomatic children in Manhiça District, Mozambique, pre- and post-vaccine introduction. Stool was collected from enrolled children and screened for rotavirus by enzyme-immuno-sorbent assay. Positive specimens were genotyped for VP7 (G genotypes) and VP4 (P genotypes) by the conventional reverse transcriptase polymerase chain reaction. The combination G12P[8] was more frequently observed in pre-vaccine than in post-vaccine introduction, in moderate to severe diarrhoea (34%, 61/177 vs. 0, p < 0.0001) and controls (23%, 26/113 vs. 0, p = 0.0013) and mixed genotypes (36%, 24/67 vs. 7% 4/58, p = 0.0003) in less severe diarrhoea. We observed changes in post-vaccine compared to pre-vaccine introduction, where G3P[4] and G3P[8] were prevalent in moderate to severe diarrhoea (10%, 5/49 vs. 0, p = 0.0002; and 14%, 7/49 vs. 1%, 1/177, p < 0.0001; respectively), and in less severe diarrhoea (21%, 12/58 vs. 0, p = 0.003; and 24%, 14/58 vs. 0, p < 0.0001; respectively). Our surveillance demonstrated the circulation of similar genotypes contemporaneously among cases and controls, as well as switching from pre- to post-vaccine introduction. Continuous surveillance is needed to evaluate the dynamics of the changes in genotypes following vaccine introduction.

    • Health Behavior and Risk
      1. Pregnancy Risk Assessment Monitoring System for Dads: A piloted randomized trial of public health surveillance of recent fathers' behaviors before and after infant birthexternal icon
        Garfield CF, Simon CD, Stephens F, Castro Román P, Bryan M, Smith RA, Kortsmit K, Salvesen von Essen B, Williams L, Kapaya M, Dieke A, Barfield W, Warner L.
        PLoS One. 2022 ;17(1):e0262366.
        BACKGROUND: Becoming a father impacts men's health and wellbeing, while also contributing to the health and wellbeing of mothers and children. There is no large-scale, public health surveillance system aimed at understanding the health and behaviors of men transitioning into fatherhood. The purpose of this study was to describe piloted randomized approaches of a state-based surveillance system examining paternal behaviors before and after their infant's birth to better understand the health needs of men and their families during the transition to parenthood. METHODS: During October 2018-July 2019, 857 fathers in Georgia were sampled 2-6 months after their infant's birth from birth certificates files and surveyed via mail, online or telephone, in English or Spanish, using two randomized approaches: Indirect-to-Dads and Direct-to-Dads. Survey topics included mental and physical health, healthcare, substance use, and contraceptive use. FINDINGS: Weighted response rates (Indirect-to-Dads, 33%; Direct-to-Dads, 31%) and population demographics did not differ by approach. Respondents completed the survey by mail (58%), online (28%) or telephone (14%). Among 266 fathers completing the survey, 55% had a primary care physician, and 49% attended a healthcare visit for themselves during their infant's mother's pregnancy or since their infant's birth. Most fathers were overweight or had obesity (70%) while fewer reported smoking cigarettes (19%), binge drinking (13%) or depressive symptoms (10%) since their infant's birth. CONCLUSIONS: This study tests a novel approach for obtaining population-based estimates of fathers' perinatal health behaviors, with comparable response rates from two pragmatic approaches. The pilot study results quantify a number of public health needs related to fathers' health and healthcare access.

    • Health Economics
      1. Global health impacts for economic models of climate change: A systematic review and meta-analysisexternal icon
        Cromar KR, Anenberg SC, Balmes JR, Fawcett AA, Ghazipura M, Gohlke JM, Hashizume M, Howard P, Lavigne E, Levy K, Madrigano J, Martinich JA, Mordecai EA, Rice MB, Saha S, Scovronick NC, Sekercioglu F, Svendsen ER, Zaitchik BF, Ewart G.
        Ann Am Thorac Soc. 2022 Jan 24.
        RATIONALE: Avoiding excess health damages attributable to climate change is a primary motivator for policy interventions to reduce greenhouse gas emissions. However, the health benefits of climate mitigation, as included in the policy assessment process, have been estimated without much input from health experts. OBJECTIVES: In accordance with recommendations from the National Academies in a 2017 report on approaches to update the social cost of greenhouse gases (SC-GHG), an expert panel of 26 health researchers and climate economists gathered for a virtual technical workshop in May 2021 to conduct a systematic review and meta-analysis and recommend improvements to the estimation of health impacts in economic-climate models. METHODS: Regionally-resolved effect estimates of unit increases in temperature on net all-cause mortality risk were generated through random-effects pooling of studies identified through a systematic review. RESULTS: Effect estimates, and associated uncertainties, varied by global region, but net increases in mortality risk associated with increased average annual temperatures (ranging from 0.1-1.1% per 1 degree C) was estimated for all global regions. Key recommendations for the development and utilization of health damage modules were provided by the expert panel, and include: not relying on individual methodologies in estimating health damages; incorporating a broader range of cause-specific mortality impacts; improving the climate parameters available in economic models; accounting for socio-economic trajectories and adaptation factors when estimating health damages; and carefully considering how air pollution impacts should be incorporated in economic-climate models. CONCLUSIONS: This work provides an example for how subject-matter experts can work alongside climate economists in making continued improvements to SC-GHG estimates.

      2. Health-related economic benefits of universal access to piped water in Arctic communities: Estimates for the Yukon-Kuskokwim Delta region of Alaskaexternal icon
        Fuente D, Mosites E, Bressler S, Eichelberger L, Lefferts B, January G, Singleton R, Thomas T.
        Int J Hyg Environ Health. 2022 Jan 17;240:113915.
        This paper presents estimates of the potential health-related economic benefits of providing universal access to in-home water and sanitation services to households in rural Alaska. In particular, we use data on disease incidence rates, health care costs, and local estimates of the impact of piped water on disease reduction to estimate the potential health-related economic benefits of providing universal access to piped water in the Yukon Kuskokwim (Y.K.) Delta region of Alaska. We include estimates of avoided treatment and diagnosis costs as well as private benefits associated with reduced morbidity and mortality associated with improved access to in-home piped water. To our knowledge, these are the first estimates of the economic benefits of improved access to water and sanitation in rural Alaska and the Arctic. Our analysis suggests increased access to in-home piped water in the region may yield substantial reductions in direct medical expenses incurred by public agencies and families, as well as reductions in time and travel costs associated with improved health outcomes. These benefits, along with the array of health and non-health-related benefits not included in our analysis, may provide new impetus to expanding access to high-quality water and sanitation services in the region.

      3. Financial navigation: Staff perspectives on patients' financial burden of cancer careexternal icon
        Yeager KA, Zahnd WE, Eberth JM, Vanderpool RC, Rohweder C, Teal R, Vu M, Stradtman L, Frost EL, Trapl E, Gonzalez SK, Vu T, Ko LK, Cole A, Farris PE, Shannon J, Askelson N, Seegmiller L, White A, Edward J, Davis M, Petermann V, Wheeler SB.
        J Cancer Surviv. 2022 Jan 26.
        PURPOSE: To describe perceptions of financial navigation staff concerning patients' cancer-related financial burden. METHODS: This qualitative descriptive study used a semi-structured interview guide to examine perceptions of financial navigation staff concerning patients' cancer-related financial burden. Staff who provided financial navigation support services to cancer patients were interviewed from different types of cancer programs across seven states representing rural, micropolitan, and urban settings. Interviews lasted approximately one hour, were audio recorded, and transcribed. Transcripts were double coded for thematic analysis. RESULTS: Thirty-five staff from 29 cancer centers were interviewed. The first theme involved communication issues related to patient and financial navigation staff expectations, timing and the sensitive nature of financial discussions. The second theme involved the multi-faceted impact of financial burden on patients, including stress, difficulty adhering to treatments, and challenges meeting basic, non-medical needs. CONCLUSIONS AND IMPLICATIONS FOR CANCER SURVIVORS: Cancer-related financial burden has a profound impact on cancer survivors' health and non-health outcomes. Discussions regarding cancer-related costs between cancer survivors and healthcare team members could help to normalize conversations and mitigate the multi-faceted determinants and effects of cancer-related financial burden. As treatment may span months and years and unexpected costs arise, having this discussion regularly and systematically is needed.

      4. Trends in pricing and out-of-pocket spending on Entecavir among commercially insured patients, 2014-2018external icon
        Alpern JD, Joo H, Link B, Ciaccia A, Stauffer WM, Bahr NC, Leventhal TM.
        JAMA Netw Open. 2022 Jan 4;5(1):e2144521.

      5. INTRODUCTION/AIMS: The multidisciplinary Duchenne muscular dystrophy (DMD) Care Considerations were developed to standardize care and improve outcomes. We provide cumulative cost estimates for selected key preventive (i.e., excluding new molecular therapies and acute care) elements of the care considerations in eight domains (neuromuscular, rehabilitation, respiratory, cardiac, orthopedic, gastrointestinal, endocrine, psychosocial management) independent of completeness of uptake or provision of non-preventive care. METHODS: We used de-identified insurance claims data from a large Midwestern commercial health insurer during 2018. We used Current Procedural Terminology and National Drug codes to extract unit costs for clinical encounters representing key preventive elements of the DMD Care Considerations. We projected per-patient cumulative costs from ages 5 to 25 years for these elements by multiplying a schedule of recommended frequencies of preventive services by unit costs in 2018 US dollars. RESULTS: Assuming a diagnosis at age 5 years, independent ambulation until age 11, and survival until age 25, we estimated 670 billable clinical events. The 20-year per-patient cumulative cost was $174,701 with prednisone ($2.3 million with deflazacort) and an expected total of $12,643 ($29,194) for out-of-pocket expenses associated with those events and medications. DISCUSSION: Standardized monitoring of disease progression and treatments may reduce overall costs of illness. Costs associated with these services would be needed to quantify potential savings. Our approach demonstrates a method to estimate costs associated with implementation of preventive care schedules.

    • Health Equity and Health Disparities
      1. Hospitalizations for COVID-19 Among American Indian and Alaska Native Adults (≥ 18 Years Old) - New Mexico, March-September 2020external icon
        Hicks JT, Burnett E, Matanock A, Khalil G, English K, Doman B, Murphy T.
        J Racial Ethn Health Disparities. 2022 Jan 21.
        To assess the presence of racial disparity during the COVID-19 pandemic, the New Mexico Department of Health (NMDOH) sought to compare the case rate and risk of hospitalization between persons of American Indian and Alaska Native (AI/AN) race and persons of other races in New Mexico from March 1 through September 30, 2020. Using NMDOH COVID-19 surveillance data, age-standardized COVID-19 case and hospitalization risks were compared between adults (≥ 18 years old) of AI/AN and other races. We compared age, sex, and comorbidities between hospitalized adults of AI/AN and other races. Among AI/AN persons, age-standardized COVID-19 case and hospitalization risks were 3.7 (95% CI 3.6-3.8) and 10.5 (95% CI 9.8-11.2) times as high as persons of other races. Hospitalized AI/AN patients had higher proportions of diabetes mellitus (48% vs. 33%, P < 0.0001) and chronic liver disease (8% vs. 5%, P = 0.0004) compared to hospitalized patients of other races. AI/AN populations have disproportionately higher risk of COVID-19 hospitalization compared to other races in New Mexico. By identifying etiologic factors that contribute to inequity, public health partners can implement culturally appropriate health interventions to mitigate disease severity within AI/AN communities.

      2. Racial and ethnic disparities in receipt of medications for treatment of COVID-19 - United States, March 2020-August 2021external icon
        Wiltz JL, Feehan AK, Molinari NM, Ladva CN, Truman BI, Hall J, Block JP, Rasmussen SA, Denson JL, Trick WE, Weiner MG, Koumans E, Gundlapalli A, Carton TW, Boehmer TK.
        MMWR Morb Mortal Wkly Rep. 2022 Jan 21;71(3):96-102.
        The COVID-19 pandemic has magnified longstanding health care and social inequities, resulting in disproportionately high COVID-19-associated illness and death among members of racial and ethnic minority groups (1). Equitable use of effective medications (2) could reduce disparities in these severe outcomes (3). Monoclonal antibody (mAb) therapies against SARS-CoV-2, the virus that causes COVID-19, initially received Emergency Use Authorization (EUA) from the Food and Drug Administration (FDA) in November 2020. mAbs are typically administered in an outpatient setting via intravenous infusion or subcutaneous injection and can prevent progression of COVID-19 if given after a positive SARS-CoV-2 test result or for postexposure prophylaxis in patients at high risk for severe illness.(†) Dexamethasone, a commonly used steroid, and remdesivir, an antiviral drug that received EUA from FDA in May 2020, are used in inpatient settings and help prevent COVID-19 progression(§) (2). No large-scale studies have yet examined the use of mAb by race and ethnicity. Using COVID-19 patient electronic health record data from 41 U.S. health care systems that participated in the PCORnet, the National Patient-Centered Clinical Research Network,(¶) this study assessed receipt of medications for COVID-19 treatment by race (White, Black, Asian, and Other races [including American Indian or Alaska Native, Native Hawaiian or Other Pacific Islander, and multiple or Other races]) and ethnicity (Hispanic or non-Hispanic). Relative disparities in mAb** treatment among all patients(††) (805,276) with a positive SARS-CoV-2 test result and in dexamethasone and remdesivir treatment among inpatients(§§) (120,204) with a positive SARS-CoV-2 test result were calculated. Among all patients with positive SARS-CoV-2 test results, the overall use of mAb was infrequent, with mean monthly use at 4% or less for all racial and ethnic groups. Hispanic patients received mAb 58% less often than did non-Hispanic patients, and Black, Asian, or Other race patients received mAb 22%, 48%, and 47% less often, respectively, than did White patients during November 2020-August 2021. Among inpatients, disparities were different and of lesser magnitude: Hispanic inpatients received dexamethasone 6% less often than did non-Hispanic inpatients, and Black inpatients received remdesivir 9% more often than did White inpatients. Vaccines and preventive measures are the best defense against infection; use of COVID-19 medications postexposure or postinfection can reduce morbidity and mortality and relieve strain on hospitals but are not a substitute for COVID-19 vaccination. Public health policies and programs centered around the specific needs of communities can promote health equity (4). Equitable receipt of outpatient treatments, such as mAb and antiviral medications, and implementation of prevention practices are essential to reducing existing racial and ethnic inequities in severe COVID-19-associated illness and death.

    • Healthcare Associated Infections
      1. Implementation of the comprehensive unit-based safety program to improve infection prevention and control practices in four neonatal intensive care units in Pune, Indiaexternal icon
        Johnson J, Latif A, Randive B, Kadam A, Rajput U, Kinikar A, Malshe N, Lalwani S, Parikh TB, Vaidya U, Malwade S, Agarkhedkar S, Curless MS, Coffin SE, Smith RM, Westercamp M, Colantuoni E, Robinson ML, Mave V, Gupta A, Manabe YC, Milstone AM.
        Front Pediatr. 2021 ;9:794637.
        Objective: To implement the Comprehensive Unit-based Safety Program (CUSP) in four neonatal intensive care units (NICUs) in Pune, India, to improve infection prevention and control (IPC) practices. Design: In this quasi-experimental study, we implemented CUSP in four NICUs in Pune, India, to improve IPC practices in three focus areas: hand hygiene, aseptic technique for invasive procedures, and medication and intravenous fluid preparation and administration. Sites received training in CUSP methodology, formed multidisciplinary teams, and selected interventions for each focus area. Process measures included fidelity to CUSP, hand hygiene compliance, and central line insertion checklist completion. Outcome measures included the rate of healthcare-associated bloodstream infection (HA-BSI), all-cause mortality, patient safety culture, and workload. Results: A total of 144 healthcare workers and administrators completed CUSP training. All sites conducted at least 75% of monthly meetings. Hand hygiene compliance odds increased 6% per month [odds ratio (OR) 1.06 (95% CI 1.03-1.10)]. Providers completed insertion checklists for 68% of neonates with a central line; 83% of checklists were fully completed. All-cause mortality and HA-BSI rate did not change significantly after CUSP implementation. Patient safety culture domains with greatest improvement were management support for patient safety (+7.6%), teamwork within units (+5.3%), and organizational learning-continuous improvement (+4.7%). Overall workload increased from a mean score of 46.28 ± 16.97 at baseline to 65.07 ± 19.05 at follow-up (p < 0.0001). Conclusion: CUSP implementation increased hand hygiene compliance, successful implementation of a central line insertion checklist, and improvements in safety culture in four Indian NICUs. This multimodal strategy is a promising framework for low- and middle-income country healthcare facilities to reduce HAI risk in neonates.

      2. Donor-derived tuberculosis among solid organ transplant recipients in the United States - 2008-2018external icon
        Malinis M, LaHoz RM, Vece G, Annambhotla P, Aslam S, Basavaraju SV, Bucio J, Danziger-Isakov L, Florescu DF, Jones JM, Rana M, Wolfe CR, Michaels MG.
        Transpl Infect Dis. 2022 Jan 22.
        Mycobacterium tuberculosis can be transmitted via organ donation and result in severe outcomes. To better understand donor-derived tuberculosis (DDTB), all potential transmissions reported to the Organ Procurement and Transplantation Network (OPTN) Ad Hoc Disease Transmission Advisory Committee between 2008-2018 were analyzed. Among 51 total reports, nine (17%) (9 donors/35 recipients) had ≥1 recipient with proven/probable disease transmission. Of these, eight were reported due to recipient disease, and one was reported due to a positive donor result. Proven/probable DDTB transmissions were reported in six lung and five non-lung recipients. The median time to diagnosis was 104 days post-transplant (range 0-165 days). Pulmonary TB, extrapulmonary TB, pulmonary plus extrapulmonary TB, and asymptomatic TB infection with positive interferon-gamma release assay were present in five, three, one, and two recipients, respectively. All recipients received treatment and survived except for one whose death was not attributed to TB. All donors associated with proven/probable DDTB had ≥1 TB risk factor. Six were born in a TB-endemic country, five had traveled to a TB-endemic country, 3 had been incarcerated, and 3 had latent TB infection. These cases highlight the importance of evaluating donors for TB based on risk factors. Early post-transplant TB in organ recipients of donors with TB risk factors requires prompt reporting to OPTN to identify other potential affected recipients and implement timely treatment interventions. This article is protected by copyright. All rights reserved.

    • Immunity and Immunization
      1. Recent studies have provided key information about SARS-CoV-2 vaccines' efficacy and effectiveness (VE). One important question that remains is whether the protection conferred by vaccines wanes over time. However, estimates over time are subject to bias from differential depletion of susceptibles between vaccinated and unvaccinated groups. Here we examine the extent to which biases occur under different scenarios and assess whether serologic testing has the potential to correct this bias. By identifying non-vaccine antibodies, these tests could identify individuals with prior infection. We find in scenarios with high baseline VE, differential depletion of susceptibles creates minimal bias in VE estimates, suggesting that any observed declines are likely not due to spurious waning alone. However, if baseline VE is lower, the bias for leaky vaccines (that reduce individual probability of infection given contact) is larger and should be corrected by excluding individuals with past infection if the mechanism is known to be leaky. Conducting analyses both unadjusted and adjusted for past infection could give lower and upper bounds for the true VE. Studies of VE should therefore enroll individuals regardless of prior infection history but also collect information, ideally through serologic testing, on this critical variable.

      2. The structure and immune regulatory implications of the ubiquitin-like tandem domain within an avian 2'-5' oligoadenylate synthetase-like proteinexternal icon
        Shepard JD, Freitas BT, Rodriguez SE, Scholte FE, Baker K, Hutchison MR, Longo JE, Miller HC, O'Boyle BM, Tandon A, Zhao P, Grimsey NJ, Wells L, Bergeron É, Pegan SD.
        Front Immunol. 2021 ;12:794664.
        Post-translational modification of host and viral proteins by ubiquitin and ubiquitin-like proteins plays a key role in a host's ability to mount an effective immune response. Avian species lack a ubiquitin-like protein found in mammals and other non-avian reptiles; interferon stimulated gene product 15 (ISG15). ISG15 serves as a messenger molecule and can be conjugated to both host and viral proteins leading them to be stabilized, degraded, or sequestered. Structurally, ISG15 is comprised of a tandem ubiquitin-like domain (Ubl), which serves as the motif for post-translational modification. The 2'-5' oligoadenylate synthetase-like proteins (OASL) also encode two Ubl domains in series near its C-terminus which binds OASL to retinoic acid inducible gene-I (RIG-I). This protein-protein interaction increases the sensitivity of RIG-I and results in an enhanced production of type 1 interferons and a robust immune response. Unlike human and other mammalian OASL homologues, avian OASLs terminate their tandem Ubl domains with the same LRLRGG motif found in ubiquitin and ISG15, a motif required for their conjugation to proteins. Chickens, however, lack RIG-I, raising the question of structural and functional characteristics of chicken OASL (chOASL). By investigating chOASL, the evolutionary history of viruses with deubiquitinases can be explored and drivers of species specificity for these viruses may be uncovered. Here we show that the chOASL tandem Ubl domains shares structural characteristics with mammalian ISG15, and that chOASL can oligomerize and conjugate to itself. In addition, the ISG15-like features of avian OASLs and how they impact interactions with viral deubiquitinases and deISGylases are explored.

      3. The burden of influenza among Kenyan pregnant and postpartum women and their infants, 2015-2020external icon
        Otieno NA, Nyawanda BO, McMorrow M, Oneko M, Omollo D, Lidechi S, Widdowson MA, Flannery B, Chaves SS, Azziz-Baumgartner E, Emukule GO.
        Influenza Other Respir Viruses. 2022 Jan 23.
        BACKGROUND: In tropical Africa, data about influenza-associated illness burden are needed to assess potential benefits of influenza vaccination among pregnant women. We estimated the incidence of influenza among pregnant women and their infants in Siaya County, Kenya. METHODS: We enrolled women at <31 weeks of gestation and conducted weekly follow-up until 6-month postpartum to identify acute respiratory illnesses (ARIs). We defined ARI among mothers as reported cough, rhinorrhoea or sore throat and among infants as maternal-reported cough, difficulty breathing, rhinorrhoea or clinician diagnosis of respiratory illness. We collected nasal/nasopharyngeal and oropharyngeal swabs from mothers/infants with ARI and tested for influenza A and B using molecular assays. We calculated antenatal incidence of laboratory-confirmed influenza among mothers and postnatal incidence among mothers and infants. RESULTS: During June 2015 to May 2020, we analysed data from 3,026 pregnant women at a median gestational age of 16 weeks (interquartile range [IQR], 13, 18) and followed 2,550 infants. Incidence of laboratory-confirmed influenza during pregnancy (10.3 episodes per 1,000 person-months [95% confidence interval {CI} 8.6-11.8]) was twofold higher than in the postpartum period (4.0 [95% CI 2.6-5.5]; p < 0.01). Incidence was significantly higher among human immunodeficiency virus (HIV)-infected pregnant women (15.6 [95% CI 11.0-20.6] vs. 9.1 [95% CI 7.5-10.8]; p < 0.01). Incidence among young infants was 4.4 (95% CI 3.0-5.9) and similar among HIV-exposed and HIV-unexposed infants. CONCLUSION: Our findings suggest a substantial burden of influenza illnesses during pregnancy, with a higher burden among HIV-infected mothers. Kenyan authorities should consider the value of vaccinating pregnant women, especially if HIV infected.

      4. Advances in understanding of the innate immune response to human norovirus infection using organoid modelsexternal icon
        Mboko WP, Chhabra P, Valcarce MD, Costantini V, Vinjé J.
        J Gen Virol. 2022 Jan;103(1).
        Norovirus is the leading cause of epidemic and endemic acute gastroenteritis worldwide and the most frequent cause of foodborne illness in the United States. There is no specific treatment for norovirus infections and therapeutic interventions are based on alleviating symptoms and limiting viral transmission. The immune response to norovirus is not completely understood and mechanistic studies have been hindered by lack of a robust cell culture system. In recent years, the human intestinal enteroid/human intestinal organoid system (HIE/HIO) has enabled successful human norovirus replication. Cells derived from HIE have also successfully been subjected to genetic manipulation using viral vectors as well as CRISPR/Cas9 technology, thereby allowing studies to identify antiviral signaling pathways important in controlling norovirus infection. RNA sequencing using HIE cells has been used to investigate the transcriptional landscape during norovirus infection and to identify antiviral genes important in infection. Other cell culture platforms such as the microfluidics-based gut-on-chip technology in combination with the HIE/HIO system also have the potential to address fundamental questions on innate immunity to human norovirus. In this review, we highlight the recent advances in understanding the innate immune response to human norovirus infections in the HIE system, including the application of advanced molecular technologies that have become available in recent years such as the CRISPR/Cas9 and RNA sequencing, as well as the potential application of single cell transcriptomics, viral proteomics, and gut-on-a-chip technology to further elucidate innate immunity to norovirus.

      5. Association between 3 doses of mRNA COVID-19 vaccine and symptomatic infection caused by the SARS-cov-2 Omicron and Delta variantsexternal icon
        Accorsi EK, Britton A, Fleming-Dutra KE, Smith ZR, Shang N, Derado G, Miller J, Schrag SJ, Verani JR.
        JAMA. 2022 Jan 21.
        IMPORTANCE: Assessing COVID-19 vaccine performance against the rapidly spreading SARS-CoV-2 Omicron variant is critical to inform public health guidance. OBJECTIVE: To estimate the association between receipt of 3 doses of Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273 vaccine and symptomatic SARS-CoV-2 infection, stratified by variant (Omicron and Delta). DESIGN, SETTING, AND PARTICIPANTS: A test-negative case-control analysis among adults 18 years or older with COVID-like illness tested December 10, 2021, through January 1, 2022, by a national pharmacy-based testing program (4666 COVID-19 testing sites across 49 US states). EXPOSURES: Three doses of mRNA COVID-19 vaccine (third dose ≥14 days before test and ≥6 months after second dose) vs unvaccinated and vs 2 doses 6 months or more before test (ie, eligible for a booster dose). MAIN OUTCOMES AND MEASURES: Association between symptomatic SARS-CoV-2 infection (stratified by Omicron or Delta variants defined using S-gene target failure) and vaccination (3 doses vs unvaccinated and 3 doses vs 2 doses). Associations were measured with multivariable multinomial regression. Among cases, a secondary outcome was median cycle threshold values (inversely proportional to the amount of target nucleic acid present) for 3 viral genes, stratified by variant and vaccination status. RESULTS: Overall, 23 391 cases (13 098 Omicron; 10 293 Delta) and 46 764 controls were included (mean age, 40.3 [SD, 15.6] years; 42 050 [60.1%] women). Prior receipt of 3 mRNA vaccine doses was reported for 18.6% (n = 2441) of Omicron cases, 6.6% (n = 679) of Delta cases, and 39.7% (n = 18 587) of controls; prior receipt of 2 mRNA vaccine doses was reported for 55.3% (n = 7245), 44.4% (n = 4570), and 41.6% (n = 19 456), respectively; and being unvaccinated was reported for 26.0% (n = 3412), 49.0% (n = 5044), and 18.6% (n = 8721), respectively. The adjusted odds ratio for 3 doses vs unvaccinated was 0.33 (95% CI, 0.31-0.35) for Omicron and 0.065 (95% CI, 0.059-0.071) for Delta; for 3 vaccine doses vs 2 doses the adjusted odds ratio was 0.34 (95% CI, 0.32-0.36) for Omicron and 0.16 (95% CI, 0.14-0.17) for Delta. Median cycle threshold values were significantly higher in cases with 3 doses vs 2 doses for both Omicron and Delta (Omicron N gene: 19.35 vs 18.52; Omicron ORF1ab gene: 19.25 vs 18.40; Delta N gene: 19.07 vs 17.52; Delta ORF1ab gene: 18.70 vs 17.28; Delta S gene: 23.62 vs 20.24). CONCLUSIONS AND RELEVANCE: Among individuals seeking testing for COVID-like illness in the US in December 2021, receipt of 3 doses of mRNA COVID-19 vaccine (compared with unvaccinated and with receipt of 2 doses) was less likely among cases with symptomatic SARS-CoV-2 infection compared with test-negative controls. These findings suggest that receipt of 3 doses of mRNA vaccine, relative to being unvaccinated and to receipt of 2 doses, was associated with protection against both the Omicron and Delta variants, although the higher odds ratios for Omicron suggest less protection for Omicron than for Delta.

      6. Myocarditis cases reported after mRNA-based COVID-19 vaccination in the US from December 2020 to August 2021external icon
        Oster ME, Shay DK, Su JR, Gee J, Creech CB, Broder KR, Edwards K, Soslow JH, Dendy JM, Schlaudecker E, Lang SM, Barnett ED, Ruberg FL, Smith MJ, Campbell MJ, Lopes RD, Sperling LS, Baumblatt JA, Thompson DL, Marquez PL, Strid P, Woo J, Pugsley R, Reagan-Steiner S, DeStefano F, Shimabukuro TT.
        JAMA. 2022 Jan 25;327(4):331-340.
        IMPORTANCE: Vaccination against COVID-19 provides clear public health benefits, but vaccination also carries potential risks. The risks and outcomes of myocarditis after COVID-19 vaccination are unclear. OBJECTIVE: To describe reports of myocarditis and the reporting rates after mRNA-based COVID-19 vaccination in the US. DESIGN, SETTING, AND PARTICIPANTS: Descriptive study of reports of myocarditis to the Vaccine Adverse Event Reporting System (VAERS) that occurred after mRNA-based COVID-19 vaccine administration between December 2020 and August 2021 in 192 405 448 individuals older than 12 years of age in the US; data were processed by VAERS as of September 30, 2021. EXPOSURES: Vaccination with BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna). MAIN OUTCOMES AND MEASURES: Reports of myocarditis to VAERS were adjudicated and summarized for all age groups. Crude reporting rates were calculated across age and sex strata. Expected rates of myocarditis by age and sex were calculated using 2017-2019 claims data. For persons younger than 30 years of age, medical record reviews and clinician interviews were conducted to describe clinical presentation, diagnostic test results, treatment, and early outcomes. RESULTS: Among 192 405 448 persons receiving a total of 354 100 845 mRNA-based COVID-19 vaccines during the study period, there were 1991 reports of myocarditis to VAERS and 1626 of these reports met the case definition of myocarditis. Of those with myocarditis, the median age was 21 years (IQR, 16-31 years) and the median time to symptom onset was 2 days (IQR, 1-3 days). Males comprised 82% of the myocarditis cases for whom sex was reported. The crude reporting rates for cases of myocarditis within 7 days after COVID-19 vaccination exceeded the expected rates of myocarditis across multiple age and sex strata. The rates of myocarditis were highest after the second vaccination dose in adolescent males aged 12 to 15 years (70.7 per million doses of the BNT162b2 vaccine), in adolescent males aged 16 to 17 years (105.9 per million doses of the BNT162b2 vaccine), and in young men aged 18 to 24 years (52.4 and 56.3 per million doses of the BNT162b2 vaccine and the mRNA-1273 vaccine, respectively). There were 826 cases of myocarditis among those younger than 30 years of age who had detailed clinical information available; of these cases, 792 of 809 (98%) had elevated troponin levels, 569 of 794 (72%) had abnormal electrocardiogram results, and 223 of 312 (72%) had abnormal cardiac magnetic resonance imaging results. Approximately 96% of persons (784/813) were hospitalized and 87% (577/661) of these had resolution of presenting symptoms by hospital discharge. The most common treatment was nonsteroidal anti-inflammatory drugs (589/676; 87%). CONCLUSIONS AND RELEVANCE: Based on passive surveillance reporting in the US, the risk of myocarditis after receiving mRNA-based COVID-19 vaccines was increased across multiple age and sex strata and was highest after the second vaccination dose in adolescent males and young men. This risk should be considered in the context of the benefits of COVID-19 vaccination.

      7. Use of recombinant zoster vaccine in immunocompromised adults aged ≥19 years: Recommendations of the Advisory Committee on Immunization Practices - United States, 2022external icon
        Anderson TC, Masters NB, Guo A, Shepersky L, Leidner AJ, Lee GM, Kotton CN, Dooling KL.
        MMWR Morb Mortal Wkly Rep. 2022 Jan 21;71(3):80-84.
        Zoster Vaccine Recombinant, Adjuvanted (Shingrix, GlaxoSmithKline [GSK]) is a 2-dose (0.5 mL each) subunit vaccine containing recombinant glycoprotein E in combination with adjuvant (AS01(B)) that was licensed in the United States for prevention of herpes zoster for adults aged ≥50 years by the Food and Drug Administration (FDA) and recommended for immunocompetent adults aged ≥50 years by the Advisory Committee on Immunization Practices (ACIP) in 2017* (1). On July 23, 2021, the FDA expanded the indication for recombinant zoster vaccine (RZV) to include adults aged ≥18 years who are or will be at increased risk for herpes zoster because of immunodeficiency or immunosuppression caused by known disease or therapy (2). On October 20, 2021, ACIP recommended 2 doses of RZV for the prevention of herpes zoster and related complications in adults aged ≥19 years(†) who are or will be immunodeficient or immunosuppressed because of disease or therapy. RZV is the first herpes zoster vaccine approved for use in immunocompromised persons. With moderate to high vaccine efficacy and an acceptable safety profile, RZV has the potential to prevent considerable herpes zoster incidence and related complications. This report updates previous ACIP recommendations for the prevention of herpes zoster (1,3).

      8. Use of the Janssen (Johnson & Johnson) COVID-19 Vaccine: Updated Interim Recommendations from the Advisory Committee on Immunization Practices - United States, December 2021external icon
        Oliver SE, Wallace M, See I, Mbaeyi S, Godfrey M, Hadler SC, Jatlaoui TC, Twentyman E, Hughes MM, Rao AK, Fiore A, Su JR, Broder KR, Shimabukuro T, Lale A, Shay DK, Markowitz LE, Wharton M, Bell BP, Brooks O, McNally V, Lee GM, Talbot HK, Daley MF.
        MMWR Morb Mortal Wkly Rep. 2022 Jan 21;71(3):90-95.
        On February 27, 2021, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for the adenovirus-vectored COVID-19 vaccine (Janssen Biotech, Inc., a Janssen Pharmaceutical company, Johnson & Johnson), and on February 28, 2021, the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation for its use as a single-dose primary vaccination in persons aged ≥18 years (1,2). On April 13, 2021, CDC and FDA recommended a pause in the use of Janssen COVID-19 vaccine after reports of thrombosis with thrombocytopenia syndrome (TTS), a rare condition characterized by low platelets and thrombosis, including at unusual sites such as the cerebral venous sinus (cerebral venous sinus thrombosis [CVST]), after receipt of the vaccine.* ACIP rapidly convened two emergency meetings to review reported cases of TTS, and 10 days after the pause commenced, ACIP reaffirmed its interim recommendation for use of the Janssen COVID-19 vaccine in persons aged ≥18 years, but included a warning regarding rare clotting events after vaccination, primarily among women aged 18-49 years (3). In July, after review of an updated benefit-risk assessment accounting for risks of Guillain-Barré syndrome (GBS) and TTS, ACIP concluded that benefits of vaccination with Janssen COVID-19 vaccine outweighed risks. Through ongoing safety surveillance and review of reports from the Vaccine Adverse Event Reporting System (VAERS), additional cases of TTS after receipt of Janssen COVID-19 vaccine, including deaths, were identified. On December 16, 2021, ACIP held an emergency meeting to review updated data on TTS and an updated benefit-risk assessment. At that meeting, ACIP made a recommendation for preferential use of mRNA COVID-19 vaccines over the Janssen COVID-19 vaccine, including both primary and booster doses administered to prevent COVID-19, for all persons aged ≥18 years. The Janssen COVID-19 vaccine may be considered in some situations, including for persons with a contraindication to receipt of mRNA COVID-19 vaccines.

      9. Progress toward poliomyelitis eradication - Afghanistan, January 2020-November 2021external icon
        Sadigh KS, Akbar IE, Wadood MZ, Shukla H, Jorba J, Chaudhury S, Martinez M.
        MMWR Morb Mortal Wkly Rep. 2022 Jan 21;71(3):85-89.
        Wild poliovirus types 2 and 3 were declared eradicated in 2015 and 2019, respectively, and, since 2017, transmission of wild poliovirus type 1 (WPV1) has been detected only in Afghanistan and Pakistan. In 2020, these countries reported their highest number of WPV1 cases since 2014 and experienced outbreaks of type 2 circulating vaccine-derived poliovirus (cVDPV2)* (1); in Afghanistan, the number of WPV1 cases reported increased 93%, from 29 in 2019 to 56 in 2020, with 308 cVDPV2 cases reported. This report describes the activities and progress toward polio eradication in Afghanistan during January 2020-November 2021 and updates previous reports (2-4). Despite restrictions imposed by antigovernment elements since 2018, disruption of polio eradication efforts by the COVID-19 pandemic, and civil and political instability, eradication activities have resumed. During January-November 2021, four WPV1 cases and 43 cVDPV2 cases were detected, representing decreases of 93% from 56 and 85% from 281, respectively, during the same period in 2020. After the assumption of nationwide control by the current de facto government of Afghanistan during August 2021, health officials committed to oral poliovirus vaccine (OPV) campaigns nationwide, with the potential to vaccinate approximately 2.5 million children against poliovirus who were previously not accessible for ≥2 years. Although challenges remain, vigorous, sustained polio eradication efforts in Afghanistan could result in substantial progress toward eradication during 2022-2023.

      10. Assessment of COVID-19 vaccination practices for 16 vaccination providers in Puerto Rico, 2021external icon
        Sánchez-González L, Wong JM, Conde A, Alicea M, Soto-Gomez E, Feliciano C, Rivera Á, Martínez M, Paz-Bailey G, Cardona I.
        P R Health Sci J. 2021 Dec;40(4):185-187.
        OBJECTIVE: To assess COVID-19 vaccine providers' adherence to best practices and identify knowledge and practice gaps to guide corrective actions and retraining activities in Puerto Rico. METHODS: A CDC supportive evaluation tool was modified to collect information on vaccine storage, handling, preparation, administration, and post-vaccination care. Assessment visits to COVID-19 vaccine providers in Puerto Rico were conducted a month after the availability of COVID-19 vaccines in the island. RESULTS: A total 16 vaccine providers were visited, 12 (75%) administering Pfizer-BioNTech vaccine and 4 (25%) administering Moderna vaccine. All providers adhered to correct handling practices after vaccine thawing. Required resources for managing anaphylaxis on site were available in all sites. Few instances of incorrect use of retractable-needle syringes, unapproved temperature monitoring devices, and lack of recorded temperature data were observed. Corrective actions were taken during the evaluation visit. CONCLUSION: No major deficiencies that could jeopardize vaccine viability or patient safety were found. The use of a supportive evaluation tool during assessment visits is helpful to determine needs for vaccine providers retraining and to continue the safe administration of COVID-19 vaccines in Puerto Rico.

    • Injury and Violence
      1. While there is strong evidence that the experience of intimate partner violence (IPV) shapes PrEP use among heterosexual women, evidence for similar relationships among gay, bisexual and other men who have sex with men (GBMSM) is scant. In this paper we analyze baseline data from a large randomized controlled trial (RCT) of an HIV prevention intervention for GBMSM recruited from three cities (Atlanta, Detroit and New York City) to examine how the recent experience of IPV shapes their rankings of PrEP delivery options. Men were asked to rank from 1 to 8 PrEP taken by daily pill, event-based pill, injection, anal suppository (before sex), suppository (after sex), gel (penile or rectal) (before sex), and gel (after sex) and condoms. The analysis sample is 694 HIV-negative, sexually active GBMSM. Analysis considers an ordinal outcome measuring participant's ranked preferences for their future use of eight HIV prevention options. Men who experienced physical IPV preferred PrEP in pill form, while men who experienced partners monitoring their behaviors (monitoring IPV) preferred PrEP by injection. Men who experienced emotional IPV ranked PrEP by pill lower than other methods. Sexual and controlling IPV were not significantly associated with PrEP modality ranking. As more modes of PrEP delivery become available, providers should be encouraged to screen GBMSM seeking PrEP for IPV, and to provide men with the necessary information to facilitate an informed choice when deciding on a PrEP modality that will work for them and their relationship context.

      2. Progress toward the UNAIDS 90-90-90 targets among female sex workers and sexually exploited female adolescents in Juba and Nimule, South Sudanexternal icon
        Hakim AJ, Bolo A, Coy KC, Achut V, Katoro J, Caesar G, Lako R, Taban AI, Sleeman K, Wesson J, Okiria AG.
        BMC Public Health. 2022 Jan 19;22(1):132.
        BACKGROUND: Little is known about HIV in South Sudan and even less about HIV among female sex workers (FSW). We characterized progress towards UNAIDS 90-90-90 targets among female sex workers (FSW) and sexually exploited female adolescents in Juba and Nimule, South Sudan. METHODS: We conducted a biobehavioral survey of FSW and sexually exploited female adolescents using respondent-driven sampling (RDS) in Juba (November 2015-March 2016) and in Nimule (January-March 2017) to estimate achievements toward the UNAIDS 90-90-90 targets (90% of HIV-positive individuals know their status; of these, 90% are receiving antiretroviral therapy [ART]; and of these, 90% are virally suppressed). Eligibility criteria were girls and women who were aged ≥15 years; spoke English, Juba Arabic, or Kiswahili; received money, goods, or services in exchange for sex in the past 6 months; and resided, worked, or socialized in the survey city for ≥1 month. Data were weighted for RDS methods. RESULTS: We sampled 838 FSW and sexually exploited female adolescents in Juba (HIV-positive, 333) and 409 in Nimule (HIV-positive, 108). Among HIV-positive FSW and sexually exploited female adolescents living in Juba, 74.8% self-reported being aware of their HIV status; of these, 73.3% self-reported being on ART; and of these, 62.2% were virally suppressed. In Nimule, 79.5% of FSW and sexually exploited female adolescents living with HIV self-reported being aware of their HIV status; of these, 62.9% self-reported being on ART; and of these, 75.7% were virally suppressed. CONCLUSIONS: Although awareness of HIV status is the lowest of the 90-90-90 indicators in many countries, treatment uptake and viral suppression were lowest among FSW and sexually exploited female adolescents in South Sudan. Differentiated service delivery facilitate linkage to and retention on treatment in support of attainment of viral suppression.

      3. Intimate partner violence (IPV) during pregnancy presents a risk for maternal mental health problems, preterm birth, and having a low birthweight infant. We assessed the prevalence of self-reported physical, emotional, and sexual violence during pregnancy by a current partner among women with a recent live birth. We analyzed data from the 2016–2018 Pregnancy Risk Assessment Monitoring System in six states to calculate weighted prevalence estimates and 95% confidence intervals for experiences of violence by demographic characteristics, health care utilization, and selected risk factors. Overall, 5.7% of women reported any type of violence during pregnancy. Emotional violence was most prevalent (5.4%), followed by physical violence (1.5%), and sexual violence (0.9%). Among women who reported any violence, 67.6% reported one type of violence, 26.5% reported two types, and 6.0% reported three types. Reporting any violence was highest among women using marijuana or illicit substances, experiencing pre-pregnancy physical violence, reporting depression, reporting an unwanted pregnancy, and experiencing relationship problems such as getting divorced, separated, or arguing frequently with their partner. There was no difference in report of discussions with prenatal care providers by experience of violence. The majority of women did not report experiencing violence, however among those who did emotional violence was most frequently reported. Assessment for IPV is important, and health care providers can play an important role in screening. Coordinated prevention efforts to reduce the occurrence of IPV and community-wide resources are needed to ensure that pregnant women receive needed services and protection. © 2022, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

    • Laboratory Sciences
      1. Evaluation of the effect of extended refrigerated storage of serum and plasma specimens on syphilis serologic test resultsexternal icon
        Sun Y, Shukla MR, Deutsch J, Cao W, Fakile Y, Kersh EN, Pereira LE.
        Diagn Microbiol Infect Dis. 2022 Feb;102(2):115588.
        The effect of extended refrigerated storage of 14 serum and plasma specimens on 5 syphilis serologic tests was evaluated for 16 weeks. Higher stability of nontreponemal and treponemal antibodies in serum was recorded compared to plasma. Described work may provide insights on refrigerated specimens' stability and suitability for syphilis tests.

      2. The sensitivity of the BinaxNOW coronavirus disease 2019 (COVID-19) Ag Card test (BinaxNOW) was 51.6% among asymptomatic healthcare employees relative to real-time reverse transcriptase polymerase chain reaction (rRT-PCR). The odds of a positive BinaxNOW test decreased as cycle threshold value increased. BinaxNOW could facilitate rapid detection and isolation of asymptomatically infected persons in some settings while rRT-PCR results are pending.

      3. Performance characteristics of the Abbott BinaxNOW SARS-COV-2 antigen test in comparison to real-time reverse transcriptase PCR and viral culture in community testing sites during November 2020external icon
        Almendares O, Prince-Guerra JL, Nolen LD, Gunn JK, Dale AP, Buono SA, Deutsch-Feldman M, Suppiah S, Hao L, Zeng Y, Stevens VA, Knipe K, Pompey J, Atherstone C, Bui DP, Powell T, Tamin A, Harcourt JL, Petway M, Bohannon C, Folster JM, MacNeil A, Salerno R, Kuhnert-Tallman W, Tate JE, Thornburg N, Kirking HL, Sheiban K, Kudrna J, Cullen T, Komatsu KK, Villanueva JM, Rose DA, Neatherlin JC, Anderson M, Rota PA, Honein MA, Bower WA.
        J Clin Microbiol. 2022 Jan 19;60(1):e0174221.
        Point-of-care antigen tests are an important tool for SARS-CoV-2 detection. Antigen tests are less sensitive than real-time reverse transcriptase PCR (rRT-PCR). Data on the performance of the BinaxNOW antigen test compared to rRT-PCR and viral culture by symptom and known exposure status, timing during disease, or exposure period and demographic variables are limited. During 3 to 17 November 2020, we collected paired upper respiratory swab specimens to test for SARS-CoV-2 by rRT-PCR and Abbott BinaxNOW antigen test at two community testing sites in Pima County, Arizona. We administered a questionnaire to capture symptoms, known exposure status, and previous SARS-CoV-2 test results. Specimens positive by either test were analyzed by viral culture. Previously we showed overall BinaxNOW sensitivity was 52.5%. Here, we showed BinaxNOW sensitivity increased to 65.7% among currently symptomatic individuals reporting a known exposure. BinaxNOW sensitivity was lower among participants with a known exposure and previously symptomatic (32.4%) or never symptomatic (47.1%) within 14 days of testing. Sensitivity was 71.1% in participants within a week of symptom onset. In participants with a known exposure, sensitivity was highest 8 to 10 days postexposure (75%). The positive predictive value for recovery of virus in cell culture was 56.7% for BinaxNOW-positive and 35.4% for rRT-PCR-positive specimens. Result reporting time was 2.5 h for BinaxNOW and 26 h for rRT-PCR. Point-of-care antigen tests have a shorter turnaround time than laboratory-based nucleic acid amplification tests, which allows for more rapid identification of infected individuals. Antigen test sensitivity limitations are important to consider when developing a testing program.

      4. Epidemiologic, immunologic, and virus characteristics in patients with paired severe acute respiratory syndrome coronavirus 2 serology and reverse-transcription polymerase chain reaction testingexternal icon
        Shragai T, Smith-Jeffcoat SE, Koh M, Schechter MC, Rebolledo PA, Kasinathan V, Wang Y, Hoffman A, Miller H, Tejada-Strop A, Jain S, Tamin A, Harcourt JL, Thornburg NJ, Wong P, Medrzycki M, Folster JM, Semenova V, Steward-Clark E, Drobenuic J, Biedron C, Stewart RJ, da Silva J, Kirking HL, Tate JE.
        J Infect Dis. 2022 Jan 18;225(2):229-237.
        BACKGROUND: The natural history and clinical progression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections can be better understood using combined serological and reverse-transcription polymerase chain reaction (RT-PCR) testing. METHODS: Nasopharyngeal swabs and serum were collected at a single time-point from patients at an urban, public hospital during August-November 2020 and tested for SARS-CoV-2 using RT-PCR, viral culture, and anti-spike pan-immunoglobulin antibody testing. Participant demographics and symptoms were collected through interview. The χ 2 and Fisher exact tests were used to identify associations between RT-PCR and serology results with presence of viable virus and frequency of symptoms. RESULTS: Among 592 participants, 129 (21.8%) had evidence of SARS-CoV-2 infection by RT-PCR or serology. Presence of SARS-CoV-2 antibodies was strongly associated with lack of viable virus (P = .016). COVID-19 symptom frequency was similar for patients testing RT-PCR positive/seronegative and patients testing RT-PCR positive/seropositive. Patients testing RT-PCR positive/seronegative reported headaches, fatigue, diarrhea, and vomiting at rates not statistically significantly different from those testing RT-PCR negative/seropositive. CONCLUSIONS: While patients testing SARS-CoV-2 seropositive were unlikely to test positive for viable virus and were therefore at low risk for forward transmission, coronavirus disease 2019 (COVID-19) symptoms were common. Paired SARS-CoV-2 RT-PCR and antibody testing provides more nuanced understanding of patients' COVID-19 status.

      5. Influenza A virus (IAV), like other viruses, depends on the host cellular machinery for replication and production of progeny. The relationship between a virus and a host is complex, shaped by many spatial and temporal interactions between viral and host proteome, ultimately dictating disease outcome. Therefore, it is imperative to identify host-virus interactions as crucial determinants of disease pathogenies. Heterogeneous ribonucleoprotein A1 (hnRNPA1) is an RNA binding protein involved in the life cycle of many DNA and RNA viruses; however, its role in IAV remains undiscovered. Here we report that human hnRNPA1 physically interacts with the nucleoprotein (NP) of IAV in mammalian cells at different time points of the viral replication cycle. Temporal distribution studies identify hnRNPA1 and NP co-localize in the same cellular milieu in both nucleus and mitochondria in NP-transfected and IAV-infected mammalian cells. Interestingly, hnRNPA1 influenced NP gene expression and affected viral replication. Most importantly, hnRNPA1 knockdown caused a significant increase in NP expression and enhanced viral replication (93.82%) in IAV infected A549 cells. Conversely, hnRNPA1 overexpression reduced NP expression at the mRNA and protein levels and impeded virus replication by (60.70%), suggesting antagonistic function. Taken together, results from this study demonstrate that cellular hnRNPA1 plays a protective role in the host hitherto unknown and may hold potential as an antiviral target to develop host-based therapeutics against IAV. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

      6. Development and evaluation of a molecular hepatitis A virus assay for serum and stool specimensexternal icon
        Kozak RA, Rutherford C, Richard-Greenblatt M, Chau NY, Cabrera A, Biondi M, Borlang J, Day J, Osiowy C, Ramachandran S, Mayer N, Glaser L, Smieja M.
        Viruses. 2022 Jan 15;14(1).
        Hepatitis A virus (HAV) is an emerging public health concern and there is an urgent need for ways to rapidly identify cases so that outbreaks can be managed effectively. Conventional testing for HAV relies on anti-HAV IgM seropositivity. However, studies estimate that 10-30% of patients may not be diagnosed by serology. Molecular assays that can directly detect viral nucleic acids have the potential to improve diagnosis, which is key to prevent the spread of infections. In this study, we developed a real-time PCR (RT-PCR) assay to detect HAV RNA for the identification of acute HAV infection. Primers were designed to target the conserved 5'-untranslated region (5'-UTR) of HAV, and the assay was optimized on both the Qiagen Rotor-Gene and the BD MAX. We successfully detected HAV from patient serum and stool samples with moderate differences in sensitivity and specificity depending on the platform used. Our results highlight the clinical utility of using a molecular assay to detect HAV from various specimen types that can be implemented in hospitals to assist with diagnostics, treatment and prevention.

    • Maternal and Child Health

      1. Prevalence of critical congenital heart defects and select co-occurring congenital anomalies, 2014-2018: A U.S. population-based studyexternal icon
        Stallings EB, Isenburg JL, Aggarwal D, Lupo PJ, Oster ME, Shephard H, Liberman RF, Kirby RS, Nestoridi E, Hansen B, Shan X, Navarro Sanchez ML, Boyce A, Heinke D.
        Birth Defects Res. 2022 Jan 19.
        BACKGROUND: Critical congenital heart defects (CCHDs) are one of the most common types of birth defects and can lead to significant morbidity and mortality along with surgical or catheter interventions within the first year of life. This report updates previously published estimates of CCHD prevalence with the latest population-based surveillance data from 19 birth defect surveillance programs. METHODS: The U.S. population-based surveillance programs submitted data on identified cases of 12 CCHDs and co-occurring cardiovascular and chromosomal birth defects from 2014 to 2018. We estimated prevalence by program type and maternal and infant characteristics. Among nine programs with active case ascertainment that collect more than live births, we estimated the percentage of co-occurring cardiovascular and chromosomal birth defects for the 12 CCHDs. RESULTS: We identified 18,587 cases of CCHD among all participating programs. Overall CCHD prevalence was 19.6 per 10,000 live births among all 19 programs and 20.2 per 10,000 live births among active programs. Among maternal racial/ethnic groups, infants/fetuses born to American Indian/Alaska Native mothers showed the highest overall prevalence for all CCHDs (28.3 per 10,000) along with eight of the 12 individual CCHDs. Among 7,726 infants/fetuses with CCHD from active case ascertainment programs, 15.8% had at least one co-occurring chromosomal birth defect. CONCLUSION: Our study provides prevalence estimates for CCHDs by maternal and infant characteristics along with co-occurrence with cardiovascular and chromosomal birth defects among infants/fetuses with CCHD using one of the largest and most recent cohorts since the implementation of widespread CCHD screening. These data can provide a basis for future research to better understand risk factors for these defects.

      2. Pathogens associated with linear growth faltering in children with diarrhea and impact of antibiotic treatment: The Global Enteric Multicenter Studyexternal icon
        Nasrin D, Blackwelder WC, Sommerfelt H, Wu Y, Farag TH, Panchalingam S, Biswas K, Saha D, Jahangir Hossain M, Sow SO, Reiman RF, Sur D, Faruque AS, Zaidi AK, Sanogo D, Tamboura B, Onwuchekwa U, Manna B, Ramamurthy T, Kanungo S, Omore R, Ochieng JB, Oundo JO, Das SK, Ahmed S, Qureshi S, Quadri F, Adegbola RA, Antonio M, Mandomando I, Nhampossa T, Bassat Q, Roose A, O'Reilly CE, Mintz ED, Ramakrishnan U, Powell H, Liang Y, Nataro JP, Levine MM, Kotloff KL.
        J Infect Dis. 2021 Dec 20;224(12 Suppl 2):S848-s855.
        BACKGROUND: The association between childhood diarrheal disease and linear growth faltering in developing countries is well described. However, the impact attributed to specific pathogens has not been elucidated, nor has the impact of recommended antibiotic treatment. METHODS: The Global Enteric Multicenter Study enrolled children with moderate to severe diarrhea (MSD) seeking healthcare at 7 sites in sub-Saharan Africa and South Asia. At enrollment, we collected stool samples to identify enteropathogens. Length/height was measured at enrollment and follow-up, approximately 60 days later, to calculate change in height-for-age z scores (ΔHAZ). The association of pathogens with ΔHAZ was tested using linear mixed effects regression models. RESULTS: Among 8077 MSD cases analyzed, the proportion with stunting (HAZ below -1) increased from 59% at enrollment to 65% at follow-up (P < .0001). Pathogens significantly associated with linear growth decline included Cryptosporidium (P < .001), typical enteropathogenic Escherichia coli (P = .01), and untreated Shigella (P = .009) among infants (aged 0-11 months) and enterotoxigenic E. coli encoding heat-stable toxin (P < .001) and Cryptosporidium (P = .03) among toddlers (aged 12-23 months). Shigella-infected toddlers given antibiotics had improved linear growth (P = .02). CONCLUSIONS: Linear growth faltering among children aged 0-23 months with MSD is associated with specific pathogens and can be mitigated with targeted treatment strategies, as demonstrated for Shigella.

      3. Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) phenotypes are used to describe disease progression in affected individuals. However, considerable heterogeneity has been observed across and within these two phenotypes, suggesting a spectrum of severity rather than distinct conditions. Characterizing the phenotypes and subphenotypes aids researchers in the design of clinical studies and clinicians in providing anticipatory guidance to affected individuals and their families. Using data from the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet), we used K-means cluster analysis to group phenotypically similar males with pediatric-onset dystrophinopathy. We identified four dystrophinopathy clusters: Classical BMD, Classical DMD, late ambulatory DMD, and severe DMD. The clusters that we identified align with both 'classical' and 'non-classical' dystrophinopathy described in the literature. Individuals with dystrophinopathies have heterogenous clinical presentations that cluster into phenotypically similar groups. Use of clinically-derived phenotyping may provide a clearer understanding of disease trajectories, reduce variability in study results, and prevent exclusion of certain cohorts from analysis. Findings from studying subphenotypes may ultimately improve our ability to predict disease progression. © 2022 - IOS Press. All rights reserved.

      4. Strengthening the reporting of stillbirths globallyexternal icon
        Joos O, Swiney C, Sferrazza L.
        Lancet. 2022 Jan 8;399(10320):140-141.

      5. Measuring BMI change among children and adolescentsexternal icon
        Freedman DS, Goodwin Davies AJ, Phan TT, Cole FS, Pajor N, Rao S, Eneli I, Kompaniyets L, Lange SJ, Christakis DA, Forrest CB.
        Pediatr Obes. 2022 Jan 22:e12889.
        BACKGROUND: Weight control programs for children monitor BMI changes using BMI z-scores that adjust BMI for the sex and age of the child. It is, however, uncertain if BMIz is the best metric for assessing BMI change. OBJECTIVE: To identify which of 6 BMI metrics is optimal for assessing change. We considered a metric to be optimal if its short-term variability was consistent across the entire BMI distribution. SUBJECTS: 285 643 2- to 17-year-olds with BMI measured 3 times over a 10- to 14-month period. METHODS: We summarized each metric's variability using the within-child standard deviation. RESULTS: Most metrics' initial or mean value correlated with short-term variability (|r| ~ 0.3 to 0.5). The metric for which the within-child variability was largely independent (r = 0.13) of the metric's initial or mean value was the percentage of the 50th expressed on a log scale. However, changes in this metric between the first and last visits were highly (r ≥ 0.97) correlated with changes in %95th and %50th. CONCLUSIONS: Log %50 was the metric for which the short-term variability was largely independent of a child's BMI. Changes in log %50th, %95th, and %50th are strongly correlated.

    • Occupational Safety and Health
      1. Classification of rock and coal is one preliminary problem for fully automated or intelligent mining. It assists for the automated rib stability analysis and enables the shearer to adjust the drums without human intervention. In this paper, the classification of rock from coal on rib images has been studied with machine learning techniques. A database of rock and coal image has been created by filtering photographs taken by NIOSH researchers in gateroad during site visits and only the images with fresh areas of rock and coal on the rib were selected. Machine learning was conducted on patches with a determined size, which are smaller images randomly extracted from each rock or coal image. After training, the classifier was validated with the testing dataset and an accuracy score of 0.9 was obtained. The influence of patch size and classifier was also investigated. The trained classifier was then applied to classify rock and coal on a new rib image with three rock layers of different thicknesses and good agreement was achieved. © 2021, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

      2. Occupational risk factors for work disability following carpal tunnel syndrome: a pooled prospective studyexternal icon
        Harris-Adamson C, Eisen EA, Kapellusch J, Hegmann KT, Thiese MS, Dale AM, Evanoff B, Meyers AR, Bao S, Gerr F, Krause N, Rempel D.
        Occup Environ Med. 2022 Jan 24.
        BACKGROUND: Although recent studies have identified important risk factors associated with incident carpal tunnel syndrome (CTS), risk factors associated with its severity have not been well explored. OBJECTIVE: To examine the associations between personal, workplace psychosocial and biomechanical factors and incident work disability among workers with CTS. METHODS: Between 2001 and 2010 five research groups conducted coordinated prospective studies of CTS and related work disability among US workers from various industries. Workers with prevalent or incident CTS (N=372) were followed for up to 6.4 years. Incident work disability was measured as: (1) change in work pace or work quality, (2) lost time or (3) job change following the development of CTS. Psychosocial factors were assessed by questionnaire. Biomechanical exposures were assessed by observation and measurements and included force, repetition, duty cycle and posture. HRs were estimated using Cox models. RESULTS: Disability incidence rates per 100 person-years were 33.2 for changes in work pace or quality, 16.3 for lost time and 20.0 for job change. There was a near doubling of risk for job change among those in the upper tertile of the Hand Activity Level Scale (HR 2.17; 95% CI 1.17 to 4.01), total repetition rate (HR 1.75; 95% CI 1.02 to 3.02), % time spent in all hand exertions (HR 2.20; 95% CI 1.21 to 4.01) and a sixfold increase for high job strain. Sensitivity analyses indicated attenuation due to inclusion of the prevalent CTS cases. CONCLUSION: Personal, biomechanical and psychosocial job factors predicted CTS-related disability. Results suggest that prevention of severe disability requires a reduction of both biomechanical and organisational work stressors.

    • Parasitic Diseases
      1. Cross-border malaria in the triple border region between Brazil, Venezuela and Guyanaexternal icon
        Abdallah R, Louzada J, Carlson C, Ljolje D, Udhayakumar V, Oliveira-Ferreira J, Lucchi NW.
        Sci Rep. 2022 Jan 24;12(1):1200.
        The state of Roraima, in Brazil, has recently seen an increase in the number of reported Plasmodium falciparum infections believed to be imported from neighboring countries. The objective of this study was to determine the prevalence of Plasmodium species among patients attending malaria health posts in Roraima and quantify the infections attributable to imported malaria. This cross-sectional case study was carried out between March 2016 and September 2018. Study participants were recruited as they exited the malaria health post. Information about residence, occupation and travel history was collected using a questionnaire. A dried blood spot was collected and used for malaria diagnosis by PCR. A total of 1222 patients were enrolled. Of the 80% Plasmodium positive samples, 50% were P. falciparum, 34% P. vivax, 8% mixed P. falciparum/P. vivax and 0.2% mixed P. falciparum/P. ovale infections and 8% tested positive for Plasmodium, but the species could not be identified. 80% of the malaria patients likely acquired infections in Venezuela and the remaining 20% acquired in Guyana, Brazil, Suriname and French Guyana. 50% of the study participants reported to be working in a mine. Results from this study support the hypothesis that imported malaria contribute to the bulk of malaria diagnosed in Roraima. These findings are in keeping with previous findings and should be considered when developing malaria control interventions.

    • Physical Activity
      1. Estimated number of deaths prevented through increased physical activity among US adultsexternal icon
        Saint-Maurice PF, Graubard BI, Troiano RP, Berrigan D, Galuska DA, Fulton JE, Matthews CE.
        JAMA Intern Med. 2022 Jan 24.

      2. Sedentary behavior in U.S. adults: Fall 2019external icon
        Matthews CE, Carlson SA, Saint-Maurice PF, Patel S, Salerno EA, Loftfield E, Troiano RP, Fulton JE, Sampson JN, Tribby C, Keadle SK, Berrigan D.
        Med Sci Sports Exerc. 2021 Dec 1;53(12):2512-2519.
        PURPOSE: Higher levels of sedentary behavior are associated with early mortality, but the distribution of sedentary time by classes of behavior and demographic groups is poorly described in U.S. adults. To quantify the amount and sources of sedentary time in U.S. adults, we conducted a nationwide survey using a novel validated self-administered previous-day recall method and compared these values with a commonly used sitting time question. METHODS: Participants from the AmeriSpeak panel 20 to 75 yr of age (N = 2640) completed up to two activities completed over time in 24 h (ACT24) previous-day recalls. Recalls were conducted on randomly selected days in October and November 2019. Survey sample designs were applied to reflect the U.S. population. RESULTS: Mean age was 45.3 yr, 51% were female, 67% non-Hispanic White, and 37% had a body mass index of ≥30 kg·m-2. U.S. adults reported a mean 9.5 h·d-1 of sedentary time (95% confidence interval = 9.4, 9.7 h·d-1), which was 34% more than reported using a common surveillance measure (P < 0.01). Most daily sedentary time was accumulated in the leisure and work life domains, with leisure accounting for 47% (4.3 h·d-1, 95% confidence interval = 4.2, 4.5 h·d-1) of the total sedentary time. Eighty-two percent of leisure time was spent sedentary, mainly watching television/videos or engaged in Internet/computer use. CONCLUSIONS: U.S. adults appear to spend more time in sedentary behavior than previously thought, and the majority of this time is accumulated at work and in leisure time. Reducing sedentary screen time during leisure in favor of physically active could be an important intervention target in the effort to increase physical activity in U.S. adults.

    • Substance Use and Abuse
      1. Cigarette smoking is associated with acrylamide exposure among the U.S. population: NHANES 2011-2016external icon
        Kenwood BM, Zhu W, Zhang L, Bhandari D, Blount BC.
        Environ Res. 2022 Jan 21:112774.
        2-carbamoylethyl mercapturic acid (2CaEMA, N-Acetyl-S-carbamoylethyl-L-cysteine) is a urinary metabolite and exposure biomarker of acrylamide, which is a harmful volatile organic compound found in cigarette smoke and in some foods. The goal of this study was to determine the association between cigarette smoking and urinary 2CaEMA concentrations among the U.S. population while considering potential dietary sources of acrylamide intake and demographics. We measured 2CaEMA concentrations in urine specimens collected during the National Health and Nutrition Examination Survey 2011-2012, 2013-2014, and 2015-2016 cycles from eligible participants 18 years and older (n = 5443) using liquid chromatography/tandem mass spectrometry. We developed multiple regression models with urinary 2CaEMA concentrations as the dependent variable and sex, age, race/Hispanic origin, reported primary sources of dietary acrylamide intake, and cigarette smoke exposure as independent variables. This study demonstrates that cigarette smoking is strongly associated with urinary 2CaEMA, suggests that cigarette smoking is likely a primary source of acrylamide exposure, and provides a baseline measure for 2CaEMA in the U.S. population.

      2. A qualitative study of service engagement and unmet needs among unstably housed people who inject drugs in Massachusettsexternal icon
        Hassan R, Roland KB, Hernandez B, Goldman L, Evans KN, Gaul Z, Agnew-Brune C, Buchacz K, Fukuda HD.
        J Subst Abuse Treat. 2022 Jan 16:108722.
        INTRODUCTION: People who inject drugs (PWID) are disproportionately affected by HIV in the United States, and HIV prevention and care services may be inaccessible to or underutilized by PWID. In 2018, the Massachusetts Department of Public Health (MDPH) and the Centers for Disease Control and Prevention (CDC) investigated an increase in HIV diagnoses primarily among unstably housed PWID in Lawrence and Lowell. METHODS: The response team interviewed 34 PWID in Lawrence and Lowell, with and without HIV, to inform effective response strategies. Qualitative interviews were recorded, transcribed, and coded. Interviews were transcribed verbatim and coded using a thematic analysis approach structured around pre-designated research questions related to service engagement (including harm reduction services, substance use disorder treatment, medical services, shelters, and other community services), unmet needs, and knowledge gaps regarding HIV prevention. RESULTS: Participants ranged in age from 20 to 54 years (median: 32); 21 of the 34 participants (62%) were male, and 21 were non-Hispanic white. Fifteen (44%) self-reported being HIV positive. All 34 participants had experienced homelessness in the past 12 months, and 29 (85%) had ever received services at syringe service programs (SSP). We identified five key themes: substance use as a barrier to accessing health and social services; experiences of trauma and mental illness as factors impacting substance use and utilization of services; unstable housing as a barrier to accessing services; negative perceptions of medication for opioid use disorder (MOUD); and the desire to be treated with dignity and respect by others. CONCLUSIONS: Findings highlight the need for well-resourced and integrated or linked service provision for PWID, which includes mental health services, housing, MOUD, harm reduction, and infectious disease prevention and care services. Co-locating and integrating low-barrier services at trusted community locations, such as SSPs, could increase service engagement and improve health outcomes for PWID. Further implementation science research may aid the development of effective strategies for services for PWID and build trusting relationships between service providers and PWID.

      3. INTRODUCTION: To examine population-level characteristics of support for - versus neutrality or opposition toward - cigarette pack warnings that use text and images to portray the negative health effects of smoking. METHODS: We used nationally representative cross-sectional data of U.S. adults age 18 and older from the 2020 Health Information National Trends Survey (n=3865). Frequencies and weighted proportions were calculated for neutrality toward, opposition to, and support for pictorial warnings across sociodemographics and other predictors. Weighted, multivariable logistic regression examined predictors of being neutral or opposed versus supportive of pictorial warnings. RESULTS: In 2020, an estimated 69.9% of U.S. adults supported pictorial warnings, 9.1% opposed, and 20.9% neither supported nor opposed them. In fully adjusted models, current smokers had almost twice the odds of being neutral or opposed to pictorial warnings as never smokers (OR=1.99, CI 1.12,3.52). Adults 75 years and older (vs. 18-34) (OR=0.55, CI 0.33,0.94) and those with children under 18 in their household (vs. no children) (OR=0.67, CI 0.46,0.98) were less likely to be neutral or opposed. CONCLUSIONS: In advance of the Food and Drug Administration's implementation of pictorial warnings on cigarette packages, nearly 70% of American adults support this policy. Disseminating information about the effectiveness of pictorial warnings may further strengthen support among current smokers who are less supportive than never smokers. Furthermore, framing messages around the benefits of pictorial warnings for protecting youth may increase public support. IMPLICATIONS: While public support for pictorial warnings on cigarette packages is high in the U.S., it may increase further after policy implementation and be strengthened by utilizing information campaigns that convey the evidence that pictorial warnings are an effective public health strategy.

    • Telehealth and Telemedicine
      1. In-person vs electronic directly observed therapy for tuberculosis treatment adherence: A randomized noninferiority trialexternal icon
        Burzynski J, Mangan JM, Lam CK, Macaraig M, Salerno MM, deCastro BR, Goswami ND, Lin CY, Schluger NW, Vernon A.
        JAMA Netw Open. 2022 Jan 4;5(1):e2144210.
        IMPORTANCE: Electronic directly observed therapy (DOT) is used increasingly as an alternative to in-person DOT for monitoring tuberculosis treatment. Evidence supporting its efficacy is limited. OBJECTIVE: To determine whether electronic DOT can attain a level of treatment observation as favorable as in-person DOT. DESIGN, SETTING, AND PARTICIPANTS: This was a 2-period crossover, noninferiority trial with initial randomization to electronic or in-person DOT at the time outpatient tuberculosis treatment began. The trial enrolled 216 participants with physician-suspected or bacteriologically confirmed tuberculosis from July 2017 to October 2019 in 4 clinics operated by the New York City Health Department. Data analysis was conducted between March 2020 and April 2021. INTERVENTIONS: Participants were asked to complete 20 medication doses using 1 DOT method, then switched methods for another 20 doses. With in-person therapy, participants chose clinic or community-based DOT; with electronic DOT, participants chose live video-conferencing or recorded videos. MAIN OUTCOMES AND MEASURES: Difference between the percentage of medication doses participants were observed to completely ingest with in-person DOT and with electronic DOT. Noninferiority was demonstrated if the upper 95% confidence limit of the difference was 10% or less. We estimated the percentage of completed doses using a logistic mixed effects model, run in 4 modes: modified intention-to-treat, per-protocol, per-protocol with 85% or more of doses conforming to the randomization assignment, and empirical. Confidence intervals were estimated by bootstrapping (with 1000 replicates). RESULTS: There were 173 participants in each crossover period (median age, 40 years [range, 16-86 years]; 140 [66%] men; 80 [37%] Asian and Pacific Islander, 43 [20%] Black, and 71 [33%] Hispanic individuals) evaluated with the model in the modified intention-to-treat analytic mode. The percentage of completed doses with in-person DOT was 87.2% (95% CI, 84.6%-89.9%) vs 89.8% (95% CI, 87.5%-92.1%) with electronic DOT. The percentage difference was -2.6% (95% CI, -4.8% to -0.3%), consistent with a conclusion of noninferiority. The 3 other analytic modes yielded equivalent conclusions, with percentage differences ranging from -4.9% to -1.9%. CONCLUSIONS AND RELEVANCE: In this trial, the percentage of completed doses under electronic DOT was noninferior to that under in-person DOT. This trial provides evidence supporting the efficacy of this digital adherence technology, and for the inclusion of electronic DOT in the standard of care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03266003.

      2. Strengthening ehealth systems to support universal health coverage in sub-Saharan Africaexternal icon
        Ojo A, Tolentino H, Yoon SS.
        Online J Public Health Inform. 2021 ;13(3):E17.
        The aim of universal health coverage (UHC) is to ensure that all individuals in a country have access to quality healthcare services and do not suffer financial hardship in using these services. However, progress toward attaining UHC has been slow, particularly in sub-Saharan Africa. The use of information and communication technologies for healthcare, known as eHealth, can facilitate access to quality healthcare at minimal cost. eHealth systems also provide the information needed to monitor progress toward UHC. However, in most countries, eHealth systems are sometimes non-functional and do not serve programmatic purposes. Therefore, it is crucial to implement strategies to strengthen eHealth systems to support UHC. This perspective piece proposes a conceptual framework for strengthening eHealth systems to attain UHC goals and to help guide UHC and eHealth strategy development.

    • Zoonotic and Vectorborne Diseases
      1. Zika-associated birth defects reported in pregnancies with laboratory evidence of confirmed or possible Zika virus infection - U.S. Zika Pregnancy and Infant Registry, December 1, 2015-March 31, 2018external icon
        Roth NM, Reynolds MR, Lewis EL, Woodworth KR, Godfred-Cato S, Delaney A, Akosa A, Valencia-Prado M, Lash M, Elmore A, Langlois P, Khuwaja S, Tufa A, Ellis EM, Nestoridi E, Lyu C, Longcore ND, Piccardi M, Lind L, Starr S, Johnson L, Browne SE, Gosciminski M, Velasco PE, Johnson-Clarke F, Locklear A, Chan M, Fornoff J, Toews KE, Tonzel J, Marzec NS, Hale S, Nance AE, Willabus T, Contreras D, Adibhatla SN, Iguchi L, Potts E, Schiffman E, Lolley K, Stricklin B, Ludwig E, Garstang H, Marx M, Ferrell E, Moreno-Gorrin C, Signs K, Romitti P, Leedom V, Martin B, Castrodale L, Cook A, Fredette C, Denson L, Cronquist L, Nahabedian JF, Shinde N, Polen K, Gilboa SM, Martin SW, Cragan JD, Meaney-Delman D, Honein MA, Tong VT, Moore CA.
        MMWR Morb Mortal Wkly Rep. 2022 Jan 21;71(3):73-79.
        Zika virus infection during pregnancy can cause serious birth defects of the brain and eyes, including intracranial calcifications, cerebral or cortical atrophy, chorioretinal abnormalities, and optic nerve abnormalities (1,2). The frequency of these Zika-associated brain and eye defects, based on data from the U.S. Zika Pregnancy and Infant Registry (USZPIR), has been previously reported in aggregate (3,4). This report describes the frequency of individual Zika-associated brain and eye defects among infants from pregnancies with laboratory evidence of confirmed or possible Zika virus infection. Among 6,799 live-born infants in USZPIR born during December 1, 2015-March 31, 2018, 4.6% had any Zika-associated birth defect; in a subgroup of pregnancies with a positive nucleic acid amplification test (NAAT) for Zika virus infection, the percentage was 6.1% of live-born infants. The brain and eye defects most frequently reported included microcephaly, corpus callosum abnormalities, intracranial calcification, abnormal cortical gyral patterns, ventriculomegaly, cerebral or cortical atrophy, chorioretinal abnormalities, and optic nerve abnormalities. Among infants with any Zika-associated birth defect, one third had more than one defect reported. Certain brain and eye defects in an infant might prompt suspicion of prenatal Zika virus infection. These findings can help target surveillance efforts to the most common brain and eye defects associated with Zika virus infection during pregnancy should a Zika virus outbreak reemerge, and might provide a signal to the reemergence of Zika virus, particularly in geographic regions without ongoing comprehensive Zika virus surveillance.

      2. INTRODUCTION: Globally, traditional medicine is widely used to treat a variety of injuries and illnesses, including dog bites, and exposures that are risky for rabies. However, efficacy of most traditional remedies used for rabies prevention or treatment has not been demonstrated in controlled trials or proven in community-based surveys. METHODS: Six databases were searched including the terms rabies, traditional treatment, traditional remedy, traditional therapy, traditional medicine, and medicinal treatment to review traditional remedies used in the prevention and treatment of rabies. In addition, published literature of rabies transmission dynamics was used to estimate statistical likelihood of dog bite victims developing rabies to provide clarity as to why traditional healers have a high apparent success rate when preventing death from rabies in victims bitten by suspected rabid dogs. RESULTS: Literature review yielded 50 articles, including three controlled experiments, that described use of traditional remedies for rabies prevention and treatment. Traditional remedies for rabies ranged from plant- or animal-based products to spiritual rituals; however, only a few controlled mice trials were conducted, and none of these trials demonstrated efficacy in preventing or treating rabies. Risk of dying from rabies after a bite from a dog with unknown rabies status is low, 1.90% (0.05%-29.60%). Therefore, traditional healers had a 98.10% (70.40%-99.95%) apparent success rate in preventing death from suspected rabid dog bites despite inefficaciousness of herbal remedies. CONCLUSION: There was no universal plant species or route of administration that was consistently used for rabies prevention or treatment across countries. No traditional remedy was efficacious in the prevention or treatment of rabies in randomized controlled experiments. Understanding the cultural context under which traditional remedies are used may facilitate collaboration of traditional healers with the modern medical system to ensure timely and appropriate use of proven therapies for prevention and clinical management of rabies.

      3. Monoclonal antibodies to Cache Valley virus for serological diagnosisexternal icon
        Skinner B, Mikula S, Davis BS, Powers JA, Hughes HR, Calvert AE.
        PLoS Negl Trop Dis. 2022 Jan 24;16(1):e0010156.
        Cache Valley virus (CVV) is a mosquito-borne virus in the genus Orthobunyavirus, family Peribunyaviridae. It was first isolated from a Culiseta inorata mosquito in Cache Valley, Utah in 1956 and is known to circulate widely in the Americas. While only a handful of human cases have been reported since its discovery, it is the causative agent of fetal death and severe malformations in livestock. CVV has recently emerged as a potential viral pathogen causing severe disease in humans. Currently, the only serological assay available for diagnostic testing is plaque reduction neutralization test which takes several days to perform and requires biocontainment. To expand diagnostic capacity to detect CVV infections by immunoassays, 12 hybridoma clones secreting anti-CVV murine monoclonal antibodies (MAbs) were developed. All MAbs developed were found to be non-neutralizing and specific to the nucleoprotein of CVV. Cross-reactivity experiments with related orthobunyaviruses revealed several of the MAbs reacted with Tensaw, Fort Sherman, Tlacotalpan, Maguari, Playas, and Potosi viruses. Our data shows that MAbs CVV14, CVV15, CVV17, and CVV18 have high specific reactivity as a detector in an IgM antibody capture test with human sera.

      4. Assessing rodents as carriers of pathogenic Leptospira species in the U.S. Virgin Islands and their risk to animal and public healthexternal icon
        Hamond C, Browne AS, de Wilde LH, Hornsby RL, LeCount K, Anderson T, Stuber T, Cranford HM, Browne SK, Blanchard G, Horner D, Taylor ML, Evans M, Angeli NF, Roth J, Bisgard KM, Salzer JS, Schafer IJ, Ellis BR, Alt DP, Schlater L, Nally JE, Ellis EM.
        Sci Rep. 2022 Jan 21;12(1):1132.
        Leptospirosis is a global zoonotic disease caused by pathogenic bacteria of the genus Leptospira. We sought to determine if rodents in U.S. Virgin Islands (USVI) are carriers of Leptospira. In total, 140 rodents were sampled, including 112 Mus musculus and 28 Rattus rattus. A positive carrier status was identified for 64/140 (45.7%); 49 (35.0%) were positive by dark-field microscopy, 60 (42.9%) by culture, 63 (45.0%) by fluorescent antibody testing, and 61 (43.6%) by real-time polymerase chain reaction (rtPCR). Molecular typing indicated that 48 isolates were L. borgpetersenii and 3 were L. kirschneri; the remaining nine comprised mixed species. In the single culture-negative sample that was rtPCR positive, genotyping directly from the kidney identified L. interrogans. Serotyping of L. borgpetersenii isolates identified serogroup Ballum and L. kirschneri isolates as serogroup Icterohaemorrhagiae. These results demonstrate that rodents are significant Leptospira carriers and adds to understanding the ecoepidemiology of leptospirosis in USVI.

      5. A cross sectional sampling reveals novel coronaviruses in bat populations of Georgiaexternal icon
        Urushadze L, Babuadze G, Shi M, Escobar LE, Mauldin MR, Natradeze I, Machablishvili A, Kutateladze T, Imnadze P, Nakazawa Y, Velasco-Villa A.
        Viruses. 2021 Dec 31;14(1).
        Mammal-associated coronaviruses have a long evolutionary history across global bat populations, which makes them prone to be the most likely ancestral origins of coronavirus-associated epidemics and pandemics globally. Limited coronavirus research has occurred at the junction of Europe and Asia, thereby investigations in Georgia are critical to complete the coronavirus diversity map in the region. We conducted a cross-sectional coronavirus survey in bat populations at eight locations of Georgia, from July to October of 2014. We tested 188 anal swab samples, remains of previous pathogen discovery studies, for the presence of coronaviruses using end-point pan-coronavirus RT-PCR assays. Samples positive for a 440 bp amplicon were Sanger sequenced to infer coronavirus subgenus or species through phylogenetic reconstructions. Overall, we found a 24.5% positive rate, with 10.1% for Alphacoronavirus and 14.4% for Betacoronavirus. Albeit R. euryale, R. ferrumequinum, M. blythii and M. emarginatus were found infected with both CoV genera, we could not rule out CoV co-infection due to limitation of the sequencing method used and sample availability. Based on phylogenetic inferences and genetic distances at nucleotide and amino acid levels, we found one putative new subgenus and three new species of Alphacoronavirus, and two new species of Betacoronavirus.

      6. Multistate outbreak of Salmonella Typhimurium linked to pet hedgehogs, United States, 2018-2019external icon
        Hoff C, Nichols M, Gollarza L, Scheftel J, Adams J, Tagg KA, Francois Watkins L, Poissant T, Stapleton GS, Morningstar-Shaw B, Signs K, Bidol S, Donovan D, Basler C.
        Zoonoses Public Health. 2022 Jan 19.
        In December 2018, PulseNet, the national laboratory network for enteric disease surveillance, identified an increase in Salmonella Typhimurium isolates with an uncommon pulsed-field gel electrophoresis pattern which was previously isolated from hedgehogs. CDC, state, and local health partners interviewed patients with a questionnaire that focused on hedgehog exposures, conducted traceback of patients' hedgehog purchases, and collected hedgehog faecal pellets and environmental samples. Isolates in this outbreak were analysed using core-genome multi-locus sequence typing (cgMLST) and compared to sequence data from historic clinical isolates from a 2011-2013 outbreak of Salmonella Typhimurium illnesses linked to pet hedgehogs. Fifty-four illnesses in 23 states were identified between October 2018 and September 2019. Patients ranged from <1 to 95 years, and 65% were female. Eight patients were hospitalized. Eighty-one per cent (29/36) of patients interviewed reported contact with a hedgehog before becoming ill; of these, 21 (72%) reported owning a hedgehog. Analysis of 53 clinical, 11 hedgehog, and two hedgehog bedding isolates from this outbreak, seven hedgehog isolates obtained prior to this outbreak, and two clinical isolates from the 2011-2013 outbreak fell into three distinct groupings (37 isolates in Clade 1 [0-10 alleles], 28 isolates in Clade 2 [0-7 alleles], and eight isolates in Clade 3 [0-12 alleles]) and were collectively related within 0-31 alleles by cgMLST. Purchase information available from 20 patients showed hedgehogs were purchased from multiple breeders across nine states, a pet store, and through an online social media website; a single source of hedgehogs was not identified. This outbreak highlights the ability of genetic sequencing analysis to link historic and ongoing Salmonella illness outbreaks and demonstrates the strain of Salmonella linked to hedgehogs might continue to be a health risk to hedgehog owners unless measures are taken to prevent transmission.

      7. OBJECTIVE: We describe the epidemiology of live poultry-associated salmonellosis (LPAS) and investigate potential risk factors associated with hospitalization among adults aged ≥65 years in the United States during 2008-2017. LPAS is a public health concern in the United States, especially among people with increased risk for hospitalization, such as older adults. SAMPLE: We analysed data from people aged ≥65 years with non-typhoidal salmonellosis who reported live poultry contact within seven days prior to illness onset. PROCEDURE: We used logistic regression to estimate the odds of hospitalization associated with several risk factors including types of live poultry contact exposures. RESULTS: LPAS among older adults in this analysis resulted in high hospitalization rates. Salmonella Hadar infection was associated with increased hospitalization. Among older adults with LPAS, 109 individuals of 127 (86%) reported contact with live poultry at their or someone else's residence, and 85 of 105 with available information (81%) reported owning poultry. CONCLUSIONS AND CLINICAL RELEVANCE: Additional infection prevention information and education targeted at poultry-owning older adults are needed to prevent illness and hospitalization.


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