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Issue 41, October 11, 2022

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CDC Science Clips: Volume 14, Issue 41, October 11, 2022

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

The report consists of these components:

  1. CDC Authored Publications
    The names of CDC authors are indicated in bold text.
    Articles published in the past 6-8 weeks authored by CDC or ATSDR staff.
    • Antimicrobial Resistance and Antibiotic Stewardship
      1. The importance of antimicrobial resistance in medical mycology
        Gow NA, Johnson C, Berman J, Coste AT, Cuomo CA, Perlin DS, Bicanic T, Harrison TS, Wiederhold N, Bromley M, Chiller T, Edgar K.
        Nat Commun. 2022 Sep 12;13(1):5352.
        Prior to the SARS-CoV-2 pandemic, antibiotic resistance was listed as the major global health care priority. Some analyses, including the O'Neill report, have predicted that deaths due to drug-resistant bacterial infections may eclipse the total number of cancer deaths by 2050. Although fungal infections remain in the shadow of public awareness, total attributable annual deaths are similar to, or exceeds, global mortalities due to malaria, tuberculosis or HIV. The impact of fungal infections has been exacerbated by the steady rise of antifungal drug resistant strains and species which reflects the widespread use of antifungals for prophylaxis and therapy, and in the case of azole resistance in Aspergillus, has been linked to the widespread agricultural use of antifungals. This review, based on a workshop hosted by the Medical Research Council and the University of Exeter, illuminates the problem of antifungal resistance and suggests how this growing threat might be mitigated.

    • Chronic Diseases and Conditions
      1. Lowering hemoglobin A1c level to less than 6.0% in people with type 2 diabetes may reduce major adverse cardiovascular events: a Bayesian's narrative
        Shao H, Guo J, Laiteerapong N, Tang S, Fonseca V, Shi L, Zhang P.
        Curr Med Res Opin. 2022 Sep 26:1-4.
        Whether lowering the hemoglobin A1c to <6.0% in patients with type 2 diabetes can reduce the risk of cardiovascular disease (CVD) remains under debate. The ACCORDION and the VADT studies both found reductions in the primary CVD composite associated with intensive glycemic control, though the difference is not statistically significant. However, the lack of significance is often overinterpreted as non-effective: a p-value >0.05 only implies that the study "failed to reject" the null hypothesis (i.e., lowering the A1c level to <6.0% results in no CVD benefit), which is different from concluding the null hypothesis being true. In this study, we used Bayesian analysis to reanalyze results from the ACCORDION and VADT-15 trials. Our results suggest achieving an A1c goal of <6.0% as compared to moderate control could result in a moderate risk reduction in MACE.

      2. Prescriptions for biologic therapy for treatment of Crohn's disease (CD) and ulcerative colitis (UC) have increased during the past two decades; however, trends are less clear regarding corticosteroid prescriptions in this context. We designed a cross-sectional study using the IQVIA Ambulatory Electronic Medical Records databases. Weighted linear regressions by age group were used to estimate annual percentage change from 2011 to 2020 in prescriptions for biologics and for corticosteroids among patients with or without biologic prescriptions within the same calendar year. Using 2019 data, we compared patient demographic and lifestyle risk factors using χ2 test for biologic prescriptions and corticosteroids with or without biologics prescriptions. There was an 11% (CD) and 16% (UC) annual increase in the percentage of patients prescribed biologics during the study period. The percentage of patients with biologics prescriptions prescribed corticosteroids decreased by 2% (CD) and 3% (UC) annually after 2015, while the percentage remained unchanged for corticosteroid prescriptions among patients without biologics. In 2019, differences in medication prescriptions existed by patient's demographic and lifestyle factors for patients with CD (n=52,892) and UC (n=52,280), including a higher percentage prescribed biologics among younger patients, men, those with fewer comorbidities, and current alcohol drinkers, and a higher percentage prescribed corticosteroids without biologics among women, those with more comorbidities, and a history of smoking. While medications continue to evolve during the biologic era, it is important to continue to monitor trends and differences in prescription patterns to assess progress toward optimizing treatment for patients with CD or UC. © American Federation for Medical Research 2022. No commercial re-use. See rights and permissions. Published by BMJ.

      3. An opportunity to better address hypertension in women: Self-measured blood pressure monitoring
        Wall HK, Streeter TE, Wright JS.
        J Womens Health (Larchmt). 2022 Sep 26.
        More than 56 million women in the United States have hypertension, including almost one in five women of reproductive age. The prevalence of hypertensive disorders of pregnancy is on the rise, putting more women at risk for adverse pregnancy-related outcomes and atherosclerotic cardiovascular disease later in life. Hypertension can be better detected and controlled in women throughout their life course by supporting self-measured blood pressure monitoring. In this study, we present some potential strategies for strengthening our nation's ability to address hypertension in women focusing on pregnancy-related considerations for self-measured blood pressure monitoring.

    • Communicable Diseases
      1. Examining geographical differences in the HIV care continuum among men who have sex with men in Mexico
        Algarin AB, Lara MV, Chapin-Bardales J, Baruch-Dominguez R, Sanchez TH, Hernandez-Avila M, Smith LR.
        AIDS Behav. 2022 Sep 26.
        We analyzed data collected by the Encuesta de Sexo Entre Hombres study from 15,233 Mexican men who have sex with men (MSM) between May-July 2017 to examine differences in the HIV care continuum. Data were stratified into 6 geographical regions. Prevalence ratios assessed associations between region and care outcomes. Among participants never testing HIV positive (n = 13,583), 66.1% had ever been tested and 43.0% in the past year. Among HIV-positive persons (n = 1,650), 83.9% reported counseling post-diagnosis, 61.9% timely linkage to care, 42.4% timely CD4/viral load results, 38.2% timely access to antiretroviral therapy (ART), and 87.7% were currently on ART. The Ciudad de México /Estado de México region had significantly superior care continuum outcomes in ever and recent HIV testing, linkage to care, CD4/viral load results, and current ART use. Understanding geographical variations in HIV care for MSM in Mexico is one important step to inform efforts for ending HIV/AIDS by 2030 in Latin America.

      2. Characterising persons diagnosed with HIV as either recent or long-term using a cross-sectional analysis of recent infection surveillance data collected in Malawi from September 2019 to March 2020
        Msukwa MT, MacLachlan EW, Gugsa ST, Theu J, Namakhoma I, Bangara F, Blair CL, Payne D, Curran KG, Arons M, Namachapa K, Wadonda N, Kabaghe AN, Dobbs T, Shanmugam V, Kim E, Auld A, Babaye Y, O'Malley G, Nyirenda R, Bello G.
        BMJ Open. 2022 Sep 23;12(9):e064707.
        OBJECTIVES: In Malawi, a recent infection testing algorithm (RITA) is used to characterise infections of persons newly diagnosed with HIV as recent or long term. This paper shares results from recent HIV infection surveillance and describes distribution and predictors. SETTING: Data from 155 health facilities in 11 districts in Malawi were pooled from September 2019 to March 2020. PARTICIPANTS: Eligible participants were ≥13 years, and newly diagnosed with HIV. Clients had RITA recent infections if the rapid test for recent infection (RTRI) test result was recent and viral load (VL) ≥1000 copies/mL; if VL was <1000 copies/mL the RTRI result was reclassified as long-term. Results were stratified by age, sex, pregnancy/breastfeeding status and district. RESULTS: 13 838 persons consented to RTRI testing and 12 703 had valid RTRI test results and VL results after excluding clients not newly HIV-positive, RTRI negative or missing data (n=1135). A total of 12 365 of the 12 703 were included in the analysis after excluding those whose RTRI results were reclassified as long term (n=338/784 or 43.1%). The remainder, 446/12 703 or 3.5%, met the definition of RITA recent infection. The highest percentage of recent infections was among breastfeeding women (crude OR (COR) 3.2; 95% CI 2.0 to 5.0), young people aged 15-24 years (COR 1.6; 95% CI 1.3 to 1.9) and persons who reported a negative HIV test within the past 12 months (COR 3.3; 95% CI 2.6 to 4.2). Factors associated with recent infection in multivariable analysis included being a non-pregnant female (adjusted OR (AOR) 1.4; 95% CI 1.2 to 1.8), a breastfeeding female (AOR 2.2; 95% CI 1.4 to 3.5), aged 15-24 years (AOR 1.6; 95% CI 1.3 to 1.9) and residents of Machinga (AOR 2.0; 95% CI 1.2 to 3.5) and Mzimba (AOR 2.4; 95% CI 1.3 to 4.5) districts. CONCLUSIONS: Malawi's recent HIV infection surveillance system demonstrated high uptake and identified sub-populations of new HIV diagnoses with a higher percentage of recent infections.

      3. Association of treated and untreated chronic hepatitis C with the incidence of active tuberculosis disease: a population-based cohort study
        Baliashvili D, Blumberg HM, Benkeser D, Kempker RR, Shadaker S, Averhoff F, Gvinjilia L, Adamashvili N, Magee M, Kamkamidze G, Zakalashvili M, Tsertsvadze T, Sharvadze L, Chincharauli M, Tukvadze N, Gandhi NR.
        Clin Infect Dis. 2022 Sep 22.
        BACKGROUND: Hepatitis C virus (HCV) infection causes dysregulation and suppression of immune pathways involved in the control of tuberculosis (TB) infection. However, data on the role of chronic hepatitis C as a risk factor for active TB are lacking. We sought to evaluate the association between HCV infection and the development of active TB. METHODS: We conducted a cohort study in Georgia among adults tested for HCV antibodies (January 2015 - September 2o2o) and followed longitudinally for the development of newly diagnosed active TB. Data were obtained from the Georgian National programs of hepatitis C and TB. The exposures of interest were untreated and treated HCV infection. Cox proportional hazards model was used to calculate adjusted hazards ratios. RESULTS: A total of 1,828,808 adults were included (median follow-up time: 26 months, IQR: 13-39 months). Active TB was diagnosed in 3,163 (0.17%) individuals after a median of 6 months follow-up (IQR: 1-18 months). The incidence rate per 100,000 person-years was 296 among persons with untreated HCV infection, 109 among those with treated HCV infection, and 65 among HCV-negative persons. In multivariable analysis, both untreated (aHR = 2.9, 95%CI: 2.4-3.4) and treated (aHR = 1.6, 95%CI: 1.4-2.0) HCV infection were associated with a higher hazard of active TB, compared to HCV-negative persons. CONCLUSIONS: Adults with HCV infection, particularly untreated individuals, were at higher risk of developing active TB disease. Screening for latent TB infection and active TB disease should be part of clinical evaluation of people with HCV infection, especially in high TB burden areas.

      4. Weight gain and metabolic effects in persons with HIV who switch to ART regimens containing integrase inhibitors or tenofovir alafenamide
        Palella FJ, Hou Q, Li J, Mahnken J, Carlson KJ, Durham M, Ward D, Fuhrer J, Tedaldi E, Novak R, Buchacz K.
        J Acquir Immune Defic Syndr. 2022 Sep 23.
        BACKGROUND: The timing and magnitude of antiretroviral therapy-associated weight change attributions are unclear. SETTING: HIV Outpatient Study participants. METHODS: We analyzed 2007-2018 records of virally suppressed (VS) persons without integrase inhibitor (INSTI) experience who switched to either INSTI- or another non-INSTI-based ART, and remained VS. We analyzed BMI changes using linear mixed models (LMM), INSTI-and tenofovir alafenamide (TAF) contributions to BMI change by LMM-estimated slopes, and BMI inflection points. RESULTS: Among 736 participants (5,316 person-years), 441 (60%) switched to INSTI-based ART; the remainder to non-INSTI-based ART. Mean follow-up was 7.15 years for INSTI recipients, 7.35 years for non-INSTI. Pre-switch, INSTI and non-INSTI groups had similar median BMI (26.3 versus 25.9 kg/m2, p=0.41). INSTI regimens included raltegravir (178), elvitegravir (112) and dolutegravir (143). Monthly BMI increases post-switch were greater with INSTI than non-INSTI (0.0525 versus 0.006, p<0.001). A BMI inflection point occurred eight months after switch among INSTI users; slopes were similar regardless of TAF use immediately post-switch. Among INSTI+TAF users, during eight months post-switch, 87% of BMI slope change was associated with INSTI use, 13% with TAF use; after eight months, estimated contributions were 27% and 73%, respectively. For non-INSTI+TAF, 84% of BMI gain was TAF-associated consistently post switch. Persons switching from TDF to TAF had greater BMI increases than others (p<0.001). CONCLUSION: Among VS persons who switched ART, INSTI and TAF use were independently associated with BMI increases. During eight months post-switch, BMI changes were greatest and most associated with INSTI use; afterward, gradual BMI gain was largely TAF-associated.

      5. OBJECTIVES: Gay, bisexual, and other men who have sex with men (MSM) are disproportionately affected by HIV. This study reports data on HIV testing program outcomes among MSM tested for HIV in non-healthcare settings in the United States. METHODS: We analyzed CDC's National HIV Prevention Program Monitoring and Evaluation data collected in 2019. Descriptive and multivariate robust Poisson regression analyses were conducted to summarize the patterns of HIV testing program outcomes (i.e., positivity, linkage to HIV medical care within 30 days of diagnosis, interview for partner services (PS), and PrEP awareness and referral) by demographic characteristics, HIV prevalence, and testing site type. RESULTS: A total of 123,251 HIV tests were conducted among MSM; of these, 1,773 (1.4%) were newly diagnosed with HIV. Among MSM newly diagnosed with HIV, 75% were linked to HIV medical care and 80% were interviewed for PS. Among MSM who tested HIV-negative, 63% were aware of PrEP and 47% of those who were eligible for PrEP were referred to PrEP providers. Referral or linkage to services varied by demographic characteristics or other factors. CONCLUSIONS: Linkage to HIV medical care and interview for PS among MSM newly diagnosed with HIV in non-healthcare settings were below national or funding program targets. The majority of MSM with risk factors for HIV infection were not referred to PrEP providers. Expanded efforts to address barriers to equitable access to services may help improve HIV-related outcomes among MSM and contribute to ending the HIV epidemic in the United States.

      6. Hepatitis B prevalence and risk factors in Punjab, India: A population-based serosurvey
        Shadaker S, Sood A, Averhoff F, Suryaprasad A, Kanchi S, Midha V, Kamili S, Nasrullah M, Trickey A, Garg R, Mittal P, Sharma SK, Vickerman P, Armstrong PA.
        J Clin Exp Hepatol. 2022 Sep-Oct;12(5):1310-1319.
        BACKGROUND: The prevalence of hepatitis B virus (HBV) infection in Punjab, India, is unknown. Understanding the statewide prevalence and epidemiology can help guide public health campaigns to reduce the burden of disease and promote elimination efforts. METHODS: A cross-sectional, population-based survey was conducted from October 2013 to April 2014 using a multistage stratified cluster sampling design. All members of selected households aged ≥5 years were eligible. Participants were surveyed for demographics and risk behaviors; serum samples were tested for total antibody to hepatitis B core (total anti-HBc), hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody (anti-HCV), and HCV RNA. HBsAg-positive specimens were tested for HBV genotype. RESULTS: A total of 5543 individuals participated in the survey and provided serum samples. The prevalence of total anti-HBc was 15.2% (95% confidence interval [95% CI]: 14.1-16.5) and HBsAg was 1.4% (95% CI: 1.0-1.9). Total anti-HBc positivity was associated with male sex (adjusted odds ratio [aOR] 1.46; 95% CI: 1.21-1.75), older age (aOR 3.31; 95% CI: 2.28-4.79 for ≥60 vs. 19-29 years), and living in a rural area (aOR 2.02; 95% CI: 1.62-2.51). Receipt of therapeutic injections in the past 6 months also increased risk (4-8 injections vs. none; aOR 1.39; 95% CI: 1.05-1.84). Among those positive for total anti-HBc, 10.4% (95% CI: 8.1-13.2) were also anti-HCV positive. CONCLUSION: Punjab has a substantial burden of HBV infection. Hepatitis B vaccination programs and interventions to minimize the use of therapeutic injections, particularly in rural areas, should be considered.

      7. Comparative assessment of severe acute respiratory syndrome coronavirus 2 variants in the ferret model
        Pulit-Penaloza JA, Belser JA, Sun X, Pappas C, Brock N, Kieran TJ, Ritter JM, Seixas JN, Jones J, Basu Thakur P, Pusch E, Wang L, Tumpey TM, Wentworth DE, Zhou B, Maines TR.
        mBio. 2022 Sep 22:e0242122.
        The continued spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in humans necessitates evaluation of variants for enhanced virulence and transmission. We used the ferret model to perform a comparative analysis of four SARS-CoV-2 strains, including an early pandemic isolate from the United States (WA1), and representatives of the Alpha, Beta, and Delta lineages. While Beta virus was not capable of pronounced replication in ferrets, WA1, Alpha, and Delta viruses productively replicated in the ferret upper respiratory tract, despite causing only mild disease with no overt histopathological changes. Strain-specific transmissibility was observed; WA1 and Delta viruses transmitted in a direct contact setting, whereas Delta virus was also capable of limited airborne transmission. Viral RNA was shed in exhaled air particles from all inoculated animals but was highest for Delta virus. Prior infection with SARS-CoV-2 offered varied protection against reinfection with either homologous or heterologous variants. Notable genomic variants in the spike protein were most frequently detected following WA1 and Delta virus infection. IMPORTANCE Continued surveillance and risk assessment of emerging SARS-CoV-2 variants are critical for pandemic response and preparedness. As such, in vivo evaluations are indispensable for early detection of variants with enhanced virulence and transmission. Here, we used the ferret model to compare the pathogenicity and transmissibility of an original SARS-CoV-2 isolate (USA-WA1/2020 [WA1]) to those of a panel of Alpha, Beta, and Delta variants, as well as to evaluate protection from homologous and heterologous reinfection. We observed strain-specific differences in replication kinetics in the ferret respiratory tract and virus load emitted into the air, revealing enhanced transmissibility of the Delta virus relative to previously detected strains. Prior infection with SARS-CoV-2 provided varied levels of protection from reinfection, with the Beta strain eliciting the lowest level of protection. Overall, we found that ferrets represent a useful model for comparative assessments of SARS-CoV-2 infection, transmission, and reinfection.

      8. Notes from the field: Norovirus outbreaks reported through norostat - 12 states, August 2012-July 2022
        Kambhampati AK, Wikswo ME, Barclay L, Vinjé J, Mirza SA.
        MMWR Morb Mortal Wkly Rep. 2022 Sep 23;71(38):1222-1224.

      9. Two cases of monkeypox-associated encephalomyelitis - Colorado and the District of Columbia, July-August 2022
        Pastula DM, Copeland MJ, Hannan MC, Rapaka S, Kitani T, Kleiner E, Showler A, Yuen C, Ferriman EM, House J, O'Brien S, Burakoff A, Gupta B, Money KM, Matthews E, Beckham JD, Chauhan L, Piquet AL, Kumar RN, Tornatore CS, Padgett K, O'Laughlin K, Mangla AT, Kumar PN, Tyler KL, O'Connor SM.
        MMWR Morb Mortal Wkly Rep. 2022 Sep 23;71(38):1212-1215.
        Monkeypox virus (MPXV) is an orthopoxvirus in the Poxviridae family. The current multinational monkeypox outbreak has now spread to 96 countries that have not historically reported monkeypox, with most cases occurring among gay, bisexual, and other men who have sex with men (1,2). The first monkeypox case in the United States associated with this outbreak was identified in May 2022 in Massachusetts (1); monkeypox has now been reported in all 50 states, the District of Columbia (DC), and one U.S. territory. MPXV is transmitted by close contact with infected persons or animals; infection results in a febrile illness followed by a diffuse vesiculopustular rash and lymphadenopathy. However, illness in the MPXV current Clade II outbreak has differed: the febrile prodrome is frequently absent or mild, and the rash often involves genital, anal, or oral regions (3,4). Although neuroinvasive disease has been previously reported with MPXV infection (5,6), it appears to be rare. This report describes two cases of encephalomyelitis in patients with monkeypox disease that occurred during the current U.S. outbreak. Although neurologic complications of acute MPXV infections are rare, suspected cases should be reported to state, tribal, local, or territorial health departments to improve understanding of the range of clinical manifestations of and treatment options for MPXV infections during the current outbreak.

      10. Clusters of rapid HIV transmission among gay, bisexual, and other men who have sex with men - United States, 2018-2021
        Perez SM, Panneer N, France AM, Carnes N, Curran KG, Denson DJ, Oster AM.
        MMWR Morb Mortal Wkly Rep. 2022 Sep 23;71(38):1201-1206.
        Gay, bisexual, and other men who have sex with men (MSM) accounted for 68% of new HIV diagnoses in the United States in 2020* (1). Despite advances in treatment and prevention, HIV transmission among MSM continues, in part because of stigma and barriers to accessing prevention and treatment services (2). HIV cluster detection and response, a core strategy of the Ending the HIV Epidemic in the United States initiative,(†) is an important tool for early identification and response to rapid HIV transmission, including among MSM. To better understand rapid HIV transmission among this population, CDC characterized large HIV molecular clusters detected using analysis of HIV-1 nucleotide sequence data from the National HIV Surveillance System (NHSS).(§) Among 38 such clusters first detected during 2018-2019 that had grown to include more than 25 persons by December 2021, 29 occurred primarily among MSM. Clusters primarily among MSM occurred in all geographic regions, and 97% involved multiple states. Clusters were heterogeneous in age, gender identity, and race and ethnicity and had rapid growth rates (median = nine persons added per year). The overall transmission rate at cluster detection was 22 transmission events per 100 person-years, more than six times that of previously estimated national transmission rates (3). Most clusters of rapid HIV transmission occur among MSM. Swift response to reach diverse persons and communities with early, tailored, and focused interventions is essential to reducing HIV transmission (4).

      11. Monkeypox in a young infant - Florida, 2022
        Saunders KE, Van Horn AN, Medlin HK, Carpenter A, Lee PA, Gutierrez L, Dillon J, Newman AP, Kimball A, McCormick DW, Stanek DR.
        MMWR Morb Mortal Wkly Rep. 2022 Sep 23;71(38):1220-1221.
        In August 2022, the Florida Department of Health (FDOH) was notified of a suspected case of monkeypox in an infant aged <2 months who was admitted to a Florida hospital with a rash and cellulitis. This case report highlights findings from the related epidemiologic investigation and describes the public health actions taken. This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.* This is the youngest patient with confirmed monkeypox infection in Florida to date.

      12. Modeling the probability of HIV infection over time in high-risk seronegative participants receiving placebo in five randomized double-blind placebo-controlled HIV pre-exposure prophylaxis trials: A patient-level pooled analysis
        Garcia-Cremades M, Hendrix CW, Jayachandran P, Strydom N, Jarlsberg L, Grant R, Celum CL, Martin M, Baeten JM, Marrazzo J, Anderson P, Choopanya K, Vanichseni S, Glidden DV, Savic RM.
        Pharmaceutics. 2022 Aug 27;14(9).
        The World Health Organization recommends pre-exposure prophylaxis (PrEP) for individuals at substantial risk of HIV infection. The aim of this analysis is to quantify the individual risk of HIV infection over time, using a large database of high-risk individuals (n = 5583). We used data from placebo recipients in five phase III PrEP trials: iPrEx, conducted in men who have sex with men and transgender women; VOICE, conducted in young women at high sexual risk; Partners PrEP, conducted in HIV serodiscordant heterosexual couples; TDF2, conducted in high-risk heterosexual men and women; and BTS, conducted in persons who inject drugs. The probability of HIV infection over time was estimated using NONMEM7.4. We identified predictors of HIV risk and found a substantial difference in the risk of infection among and within trial populations, with each study including a mix of low, moderate, and high-risk individuals (p &lt; 0.05). Persons who were female at birth were at a higher risk of HIV infection than people who were male at birth. Final models were integrated in a tool that can assess person-specific risk and simulate cumulative HIV risk over time. These models can be used to optimize future PrEP clinical trials by identifying potential participants at highest risk.

      13. Seroprevalence of SARS-CoV-2 antibodies in Bali Province: Indonesia shows underdetection of COVID-19 cases by routine surveillance
        Sawitri AA, Yuliyatni PC, Astuti PA, Ajis E, Prasetyowati EB, Husni , Morgan J, Mika J, Praptiningsih CY, Mangiri A, Mulyadi E, Noviyanti R, Trianty L, Hawley WA.
        PLOS Glob Public Health. 2022 ;2(8).
        The international tourist destination of Bali reported its first case of Coronavirus Disease 2019 or COVID-19 in March 2020. To better understand the extent of exposure of Bali's 4.3 million inhabitants to the COVID-19 virus, we performed two repeated cross-sectional serosurveys stratified by urban and rural areas. We used a highly specific multiplex assay that detects antibodies to three different viral antigens. We also assessed demographic and social risk factors and history of symptoms. Our results show that the virus was widespread in Bali by late 2020, with 16.73% (95% CI 12.22-21.12) of the population having been infected by that time. We saw no differences in seroprevalence between urban and rural areas, possibly due to extensive population mixing, and similar levels of seroprevalence by gender and among age groups, except for lower seroprevalence in the very young. We observed no difference in seroprevalence between our two closely spaced surveys. Individuals reporting symptoms in the past six months were about twice as likely to be seropositive as those not reporting symptoms. Based upon official statistics for laboratory diagnosed cases for the six months prior to the survey, we estimate that for every reported case an additional 52 cases, at least, were undetected. Our results support the hypothesis that by late 2020 the virus was widespread in Bali, but largely undetected by surveillance.

    • Disaster Preparedness and Emergency Services
      1. Developing a radiation-savvy public health workforce
        Salame-Alfie A, Whitcomb RC, Evans CL, Howard G, Gilstrap J, Gill A, Hardrick H.
        Environ Adv. 2022 Oct;9.
        In 2016 the United States Centers for Disease Control and Prevention (CDC) established a Nuclear/Radiological Training and Exercise Preparedness (TEP) Program to better prepare its workforce to respond to a nuclear/radiological incident. The TEP program is comprised of staff across CDC programs with a variety of specialties such as epidemiologists, clinicians, data managers, communicators, environmental health specialists, at risk population specialists and health physicists. Key TEP activities include the preparation of the CDC Nuclear/Radiological Incident Response and Recovery Annex that describes CDC's roles and responsibilities in the event of a nuclear/radiological incident; establishment of an Incident Management System (IMS) structure to reflect an agency-wide response consistent with CDC's All Hazards Plan; and completion of nuclear/radiological public health preparedness and response training and exercises. In addition to training sessions on the various radiation topics, the TEP program includes seminars on the various roles and responsibilities of the task forces defined in IMS during a response. The TEP program includes a range of discussion-based (seminars, workshops, tabletop exercises) and operations-based (drills and functional exercises) activities aimed at enhancing IMS staff capabilities and capacity to be prepared to respond to a nuclear/radiological incident. In summary, the CDC's Nuclear/Radiological TEP Program prepares knowledgeable, well-trained staff, or a radiation-savvy workforce, ready for a robust response to a nuclear/radiological emergency.

      2. Coping with oil spills: oil exposure and anxiety among residents of Gulf Coast states after the Deepwater Horizon Oil Spill
        Goldman ZE, Kaufman JA, Sharpe JD, Wolkin AF, Gribble MO.
        UCL Open Environ. 2022 ;4.
        In April 2010, a fatal explosion on the Deepwater Horizon drilling rig in the Gulf of Mexico resulted in the largest marine oil spill in history. This research describes the association of oil exposure with anxiety after the Deepwater Horizon Oil Spill and evaluates effect modification by self-mastery, emotional support and cleanup participation. To assess the impacts of the Deepwater Horizon Oil Spill, the Centers for Disease Control and Prevention (CDC) conducted the Gulf States Population Survey (GSPS), a random-digit-dial telephone cross-sectional survey completed between December 2010 and December 2011 with 38,361 responses in four different Gulf Coast states: Louisiana, Florida, Alabama and Mississippi. Anxiety severity was measured using the Generalised Anxiety Disorder (GAD) symptom inventory. We used Tobit regression to model underlying anxiety as a function of oil exposure and hypothesised effect modifiers, adjusting for socio-demographics. Latent anxiety was higher among those with direct contact with oil than among those who did not have direct contact with oil in confounder-adjusted models [β = 2.84, 95% confidence interval (CI): 0.78, 4.91]. Among individuals with direct contact with oil, there was no significant interaction between participating in cleanup activities and emotional support for anxiety (p = 0.20). However, among those with direct contact with oil, in confounder-adjusted models, participation in oil spill cleanup activities was associated with lower latent anxiety (β = -3.55, 95% CI: -6.15, -0.95). Oil contact was associated with greater anxiety, but this association appeared to be mitigated by cleanup participation.

    • Drug Safety
      1. Association of preconception mixtures of phenol and phthalate metabolites with birthweight among subfertile couples
        Zhang Y, Mustieles V, Williams PL, Souter I, Calafat AM, Demokritou M, Lee A, Vagios S, Hauser R, Messerlian C.
        Environ Epidemiol. 2022 31 Oct;6(5):E222.
        Background: Although parental preconception exposure to some phenols and phthalates have been associated with reduced birthweight, few studies have examined these chemicals as complex mixtures. Method(s): We included 384 mothers and 211 fathers (203 couples) who gave birth to 384 singletons from a prospective cohort of couples seeking fertility evaluation. Urinary concentrations of bisphenol A (BPA), parabens, and 11 phthalate metabolites including those of di(2-ethylhexyl) phthalate (DEHP) were examined. Birthweight was abstracted from delivery records. We used principal component analysis and Bayesian Kernel Machine Regression (BKMR) to examine maternal and paternal preconception mixtures in relation to singleton birthweight. We also fit couple-based BKMR with hierarchical variable selection to assess couples' joint mixtures in relation to birthweight. Result(s): PC scores of maternal and paternal preconception low molecular weight phthalates factor, and paternal preconception DEHP-BPA factor were associated with reduced birthweight. In BKMR models, we found that maternal preconception monoethyl phthalate and BPA concentrations, and paternal preconception mono-n-butyl phthalate concentrations were inversely associated with birthweight when the remaining mixture components were held at their median concentrations. In couple-based BKMR models, paternal preconception biomarkers contributed more to couples' joint effect on birthweight compared with maternal preconception biomarkers. A decreasing trend of birthweight was observed across quantiles of maternal, paternal, and couples' total preconception mixture concentrations, respectively. Conclusion(s): Results from this preconception cohort of subfertile couples suggest a complex interplay between paternal and maternal preconception exposure to mixtures of nonpersistent chemicals, with both parental windows of exposure jointly contributing to reduced birthweight. Copyright © 2022 Wolters Kluwer Health. All rights reserved.

    • Environmental Health
      1. Gestational per- and polyfluoroalkyl substances exposure and infant body mass index trajectory in the New Hampshire Birth Cohort Study
        Romano ME, Heggeseth BC, Gallagher LG, Botelho JC, Calafat AM, Gilbert-Diamond D, Karagas MR.
        Environ Res. 2022 Sep 23:114418.
        Perand polyfluoroalkyl substances (PFAS) are environmentally persistent, potential metabolic disruptors of concern for infants. Mothers participating in the New Hampshire Birth Cohort Study (NHBCS) provided a plasma sample during pregnancy to measure concentrations of seven PFAS, and infant weight and length were abstracted from well-child visits between birth and 12 months. Sex-specific growth patterns of child body mass index (BMI) were fit using a growth mixture model (GMM) and the relative risk ratios (RRR) and 95% Confidence Intervals (95% CI) for the association of maternal plasma PFAS with BMI growth patterns during infancy were estimated by using multinomial logistic model for the group probabilities in the GMM. Four growth patterns were identified: Group 1) a steep increase in BMI during the first 6 months, then a leveling off; Group 2) a gradual increase in BMI across the year; Group 3) a steep increase in BMI during months 1-3, then stable BMI; and Group 4) a gradual increase in BMI with plateau around 3 months (reference group). For boys, higher maternal pregnancy perfluorooctanoate concentrations were associated with a 60% decreased chance of being in group 3 as compared to group 4, after adjusting for potential confounding variables (RR = 0.4; 95% CI: 0.1, 0.9). For girls, higher maternal perfluorooctane sulfonate (PFOS) concentrations during pregnancy were associated with a higher likelihood of following the growth pattern of groups 2 (RRR = 2.5; 95% CI: 1.0, 6.1) and 3 (RRR = 2.8; 95% CI: 1.0, 7.6) as compared to group 4, adjusting for potential confounding variables. In this cohort, sex-specific associations of maternal plasma PFAS concentrations during pregnancy with growth patterns during the first year of life were observed, with greater BMI growth observed among infant girls born to mothers with higher pregnancy concentrations of PFOS.

      2. Natural history of pulmonary coccidioidomycosis: Further examination of the VA-Armed Forces database
        Shemuel J, Bays DJ, Thompson GR, Reef S, Snyder L, Freifeld AJ, Huppert M, Salkin D, Wilson MD, Galgiani JN.
        Med Mycol. 2022 Sep 27.
        There are still many limitations related to the understanding of the natural history of differing forms of coccidioidomycosis, including characterizing the spectrum of pulmonary disease. The historical Veterans Administration-Armed Forces database, recorded primarily before the advent of antifungal therapy, presents an opportunity to characterize the natural history of pulmonary CM. We performed a retrospective cohort study of 342 armed forces service members who were diagnosed with pulmonary CM at VA facilities between 1955-1958, followed to 1966, who did not receive antifungal therapy. Patients were grouped by predominant pulmonary finding on chest radiograph. The all-cause mortality was low for all patients (4.6%). Cavities had a median size of 3-3.9 cm (IQR: 2-2.9 cm - 4-4.9 cm), with heterogeneous wall thickness and no fluid level, while nodules had a median size of 1-1.19 cm (IQR 1-1.9 cm - 2-2.9 cm) and sharp borders. The majority of cavities were chronic (85.6%), and just under half were found incidentally. Median complement fixation titers in both the nodular and cavitary groups were negative, with higher titers in the cavitary group overall. This retrospective cohort study of non-disseminated coccidioidomycosis, the largest to date, sheds light on the natural history, serologic markers, and radiologic characteristics of this understudied disease. These findings have implications for the evaluation and management of CM. Coccidioidomycosis (CM), also known as San Joaquin Valley Fever, causes a variety of symptoms including pneumonia. This historical study investigates CM of the lungs in American soldiers with CM in the 1950s, prior to modern antifungals, to better understand the natural history. eng

      3. Outbreak of acute gastroenteritis among rafters and backpackers in the backcountry of Grand Canyon National Park, April-June 2022
        Dale AP, Miko S, Calderwood LE, King RF, Maurer M, Dyer L, Gebhardt M, Maurer W, Crosby S, Wikswo ME, Said MA, Mirza SA.
        MMWR Morb Mortal Wkly Rep. 2022 Sep 23;71(38):1207-1211.
        On May 11, 2022, the National Park Service (NPS) Office of Public Health (OPH) and Coconino County Health and Human Services (CCHHS) in Flagstaff, Arizona contacted CDC about a rising number of acute gastroenteritis cases among backcountry visitors to Grand Canyon National Park (Grand Canyon). The agencies reviewed illness report forms, assessed infection prevention and control (IPC) practices, and distributed a detailed survey to river rafters and hikers with backcountry permits (backpackers) who visited the Grand Canyon backcountry. During April 1-June 17, a total of 191 rafters and 31 backpackers reported symptoms consistent with acute gastroenteritis. Specimens from portable toilets used by nine river rafting trip groups were tested using real-time reverse transcription-polymerase chain reaction and test results were positive for norovirus. Norovirus-associated acute gastroenteritis is highly transmissible in settings with close person-to-person contact and decreased access to hand hygiene, such as backpacking or rafting. IPC assessments led to recommendations for regular disinfection of potable water spigots throughout the backcountry, promotion of proper handwashing with soap and water when possible, and separation of ill persons from those who are not ill. Prevention and control of acute gastroenteritis outbreaks in the backcountry requires rapid reporting of illnesses, implementing IPC guidelines for commercial outfitters and river rafting launch points, and minimizing interactions among rafting groups.

      4. Aflatoxin exposure is endemic in developing countries with warm, humid climates that promote toxigenic mold growth on crops and foodstuffs. Estimating human aflatoxin exposure is key to identifying and abating contamination sources. Serum aflatoxin B1 bound to albumin lysine (AFB1-lys) is a preferred exposure biomarker, but field sample collection, processing, transportation, and storage logistics are challenging. We validated an improved LC-MS/MS method for serum AFB1-lys and applied it to three field sampling challenges: transportation/storage (elevated temperature); collection/processing (hemolysis); and sample type substitution (heparinized plasma). Our new LC-MS/MS method had a LOD of 0.03 ng/mL, accuracy (mean spike recovery) of 112%, total imprecision (replicate pool measurements) ≤5% at ≥0.2 ng/mL, and results that were 95.1% similar (mean percentage similarity) to an established method. AFB1-lys in human serum spiked with serum from aflatoxin-dosed rats was stable for 14 days at both ambient (22.5 °C) and elevated (38 °C) temperatures. Simulated hemolysis (adding 0.25-3 mg hemoglobin) did not affect AFB1-lys accuracy at ≥0.5 ng/mL but caused 10-25% signal suppression. Heparinized plasma AFB1-lys was 99.0% similar to serum but interfered with albumin measurements (bromocresol green) causing spurious low bias. Further investigation is warranted, but our findings suggest that AFB1-lys is pre-analytically robust.

    • Epidemiology and Surveillance
      1. All-cause and cause-specific mortality rates for Kisumu County: a comparison with Kenya, low-and middle-income countries
        Waruiru W, Oramisi V, Sila A, Onyango D, Waruru A, Mwangome MN, Young PW, Muuo S, Nyagah LM, Ollongo J, Ngugi C, Rutherford GW.
        BMC Public Health. 2022 Sep 27;22(1):1828.
        BACKGROUND: Understanding the magnitude and causes of mortality at national and sub-national levels for countries is critical in facilitating evidence-based prioritization of public health response. We provide comparable cause of death data from Kisumu County, a high HIV and malaria-endemic county in Kenya, and compared them with Kenya and low-and-middle income countries (LMICs). METHODS: We analyzed data from a mortuary-based study at two of the largest hospital mortuaries in Kisumu. Mortality data through 2019 for Kenya and all LMICs were downloaded from the Global Health Data Exchange. We provided age-standardized rates for comparisons of all-cause and cause-specific mortality rates, and distribution of deaths by demographics and Global Burden of Disease (GBD) classifications. RESULTS: The all-cause age-standardized mortality rate (SMR) was significantly higher in Kisumu compared to Kenya and LMICs (1118 vs. 659 vs. 547 per 100,000 population, respectively). Among women, the all-cause SMR in Kisumu was almost twice that of Kenya and double the LMICs rate (1150 vs. 606 vs. 518 per 100,000 population respectively). Among men, the all-cause SMR in Kisumu was approximately one and a half times higher than in Kenya and nearly double that of LMICs (1089 vs. 713 vs. 574 per 100,000 population). In Kisumu and LMICs non-communicable diseases accounted for most (48.0 and 58.1% respectively) deaths, while in Kenya infectious diseases accounted for the majority (49.9%) of deaths. From age 10, mortality rates increased with age across all geographies. The age-specific mortality rate among those under 1 in Kisumu was nearly twice that of Kenya and LMICs (6058 vs. 3157 and 3485 per 100,000 population, respectively). Mortality from injuries among men was at least one and half times that of women in all geographies. CONCLUSION: There is a notable difference in the patterns of mortality rates across the three geographical areas. The double burden of mortality from GBD Group I and Group II diseases with high infant mortality in Kisumu can guide prioritization of public health interventions in the county. This study demonstrates the importance of establishing reliable vital registry systems at sub-national levels as the mortality dynamics and trends are not homogeneous.

      2. U.S. CDC support to international SARS-CoV-2 seroprevalence surveys, May 2020-February 2022
        Hamida AB, Charles M, Murrill C, Henao O, Gallagher K.
        PLOS Glob Public Health. 2022 Aug 5;2(8).
        SARS-CoV-2 seroprevalence surveys provide critical information to assess the burden of COVID-19, describe population immunity, and guide public health strategies. Early in the pandemic, most of these surveys were conducted within high-income countries, leaving significant knowledge gaps in low-and middle-income (LMI) countries. To address this gap, the U.S. Centers for Disease Control and Prevention (CDC) is supporting serosurveys internationally. We conducted a descriptive analysis of international serosurveys supported by CDC during May 12, 2020-February 28, 2022, using an internal tracker including data on the type of assistance provided, study design, population surveyed, laboratory testing performed, and status of implementation. Since the beginning of the pandemic, CDC has supported 72 serosurveys (77 serosurvey rounds) in 35 LMI countries by providing technical assistance (TA) on epidemiologic, statistical, and laboratory methods, financial assistance (FA), or both. Among these serosurvey rounds, the majority (61%) received both TA and FA from CDC, 30% received TA only, 3% received only FA, and 5% were part of informal reviews. Fifty-four percent of these serosurveys target the general population, 13% sample pregnant women, 7% sample healthcare workers, 7% sample other special populations (internally displaced persons, patients, students, and people living with HIV), and 18% assess multiple or other populations. These studies are in different stages of implementation, ranging from protocol development to dissemination of results. They are conducted under the leadership of local governments, who have ownership over the data, in collaboration with international partners. Thirty-four surveys rounds have completed data collection. CDC TA and FA of SARS-CoV-2 seroprevalence surveys will enhance the knowledge of the COVID-19 pandemic in almost three dozen LMI countries. Support for these surveys should account for current limitations with interpreting results, focusing efforts on prospective cohorts, identifying, and forecasting disease patterns over time, and helping understand antibody kinetics and correlates of protection.

      3. Developing sentinel surveillance for chlamydia and gonorrhea using test results from routine screening during pregnancy
        Lazenby GB, Korte JE, Pekar E, Peterman TA, Cope AB.
        Sex Transm Dis. 2022 Sep 26.
        BACKGROUND: Interpretation of case-based surveillance of chlamydia and gonorrhea is limited by the lack of negative tests for comparison. We sought to develop a sustainable electronic health record (EHR)-based approach to disease surveillance in a sentinel population of pregnant persons. METHODS: We conducted a one-year assessment of sexually transmitted infections (STIs) in persons receiving at least one pregnancy-related visit within our university medical center. Data were obtained using EHR analytic structured query language code (SQL). Patients were categorized by whether they had an STI test during pregnancy and if screened, by the STI test results (positive or negative). We assessed screening and positivity by demographic using bivariate analyses. Predictors of a positive STI test were determined using logistic regression. RESULTS: We identified 4,553 persons who received pregnancy care from January 1 to December 31, 2021. Seventy-six percent (n, 3483) of persons were screened for an STI during pregnancy. Those who identified as white or had private insurance were less likely to have a chlamydia test. Among persons screened, Trichomonas was the most commonly detected STI (5%, 141/2,698) followed by chlamydia (4%, 135/3,456), and gonorrhea (0.7% 24/3,468). Predictors of a positive STI test during pregnancy were Black race [adjusted odds ratio (aOR) 6.0 (95% Confidence Interval 4.2-8.7)], age ≤ 25 [aOR 2.5 (1.9-3.3)], and public insurance [aOR 1.6 (1.2-2.1)]. CONCLUSIONS: We demonstrated that EHRs can be utilized to assess gonorrhea and chlamydia positivity. These methods could potentially be applied in other jurisdictions to improve the understanding of national STI surveillance.

    • Food Safety
      1. Outbreak of foodborne botulism associated with a commercially produced multipack potato product, Colorado: September 2019
        Gayou N, Plumb ID, Edwards L, Pomeroy M, Herlihy RK, Johnson R, Pattison K, Dykes J, Gómez GA, Jervis RH.
        Foodborne Pathog Dis. 2022 Sep 23.
        During September 2019, public health authorities in El Paso County, Colorado, were notified of four patients who had presented to nearby hospitals with clinical features consistent with botulism, a paralytic illness caused by botulinum neurotoxin. One patient died soon after presentation; the other three patients required intensive care but recovered after receiving botulism antitoxin. Botulinum toxin type A was detected in serum from all patients. On further investigation, all four patients had shared a meal that included commercially prepared roasted potatoes from an individual package without refrigeration instructions that had been left unrefrigerated for 15 d. Storage of the product at ambient temperature likely allowed botulism spores to produce botulinum toxin, resulting in severe illness and death. The manufacturer improved labeling in response to this outbreak. Public health officials should consider unrefrigerated potato products as a potential source of botulism; clinicians should consider botulism as a possible cause of paralytic illness.

      2. Dietary and socioeconomic risk factors for fumonisin exposure among women of reproductive age in 18 municipalities in Guatemala from 2013 to 2014
        Garsow AV, Torres OR, Matute JA, Riley RT, Harris JR, Lamichhane AP, McCotter O, Kowalcyk BB.
        PLOS Glob Public Health. 2022 ;2(8).
        Fumonisin exposure is common in populations where maize is a dietary staple, such as in Guatemala, and has been associated with negative health outcomes including neural tube defects. The objective of this study was to estimate fumonisin B<sub>1</sub> (FB<sub>1</sub>) exposure among Guatemalan reproductive-age women and develop a better understanding of the dietary and sociodemographic risk factors for exposure. A cross-sectional study in 18 municipalities in Guatemala was conducted. Midwives and study nurses enrolled consenting women and collected individual and household demographic and socioeconomic data. A food frequency questionnaire was administered to estimate quantity and types of food products consumed. A urine sample was collected and urinary fumonisin B<sub>1</sub> (uFB<sub>1</sub>) concentration was measured. A univariable analysis was conducted to identify predictors of low/high uFB<sub>1</sub>. Multivariable logistic regression was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). In total, 775 women had analyzable urine samples. Higher uFB<sub>1</sub> levels were associated with speaking Mayan (OR = 2.33, 95% CI:1.44-3.77), less than high school education (OR = 1.61, 95% CI:1.12-2.30), increasing dietary proportion of maize-based foods (OR = 1.02, 95% CI:1.01-1.03), and consumption of tostadas (fried tortillas) (OR = 1.11, 95% CI:1.02-1.22). Lower uFB<sub>1</sub> levels were associated with consumption of highly processed maize-based foods (OR = 0.93, 95% CI:0.87-0.99). Tortillas were the most frequently consumed maize-based food among study participants and significantly associated with high uFB<sub>1</sub> exposure in the univariable but not multivariable analysis. Consumption of >4,750 grams/week of maize-based foods, >5,184 g/week of locally produced maize-based foods, and >110 servings/week of tortillas were also significantly associated with high uFB<sub>1</sub> exposure in univariable analysis. Populations with low socioeconomic status/education levels and high consumption of maize-based foods had higher fumonisin exposure. Interventions aimed at reducing the risk of exposure to mycotoxins through maize in Guatemala, including the increased consumption of non-maize-based foods, should be further explored.

    • Genetics and Genomics
      1. Efficient rescue of a newly classified Ebinur lake orthobunyavirus with GFP reporter and its application in rapid antiviral screening
        Ren N, Wang F, Zhao L, Wang S, Zhang G, Li J, Zhang B, Wang J, Bergeron E, Yuan Z, Xia H.
        Antiviral Res. 2022 Sep 21;207:105421.
        Orthobunyaviruses have been reported to cause severe diseases in humans or animals, posing a potential threat to human health and socio-economy. Ebinur lake virus (EBIV) is a newly classified orthobunyavirus, which can induce the histopathogenic change and even the high mortality of infected BALB/c mice. Therefore, it is needed to further study the viral replication and pathogenesis, and develop the therapies to cope with its potential infection to human or animals. Here, through the reverse genetics system, the recombinant EBIV of wild type (rEBIV/WT) and NP-conjugated-eGFP (rEBIV/eGFP/S) were rescued for the application of the high-content screening (HCS) of antiviral drug. The eGFP fluorescence signal of the rEBIV/eGFP/S was stable in the process of successive passage in BHK-21 cells (over 10 passages) and this recombinant virus could replicate in various cell lines. Compared to the wild type EBIV, the rEBIV/eGFP/S caused the smaller plaques (diameter around 1 mm on 3 dpi) and lower peak titers (10(5) PFU/mL), suggesting attenuation due to the eGFP insertion. Through the high-content screening (HCS) system, two antiviral compounds, ribavirin and favipiravir, which previously reported to have effect to some bunyavirus were tested firstly. Ribavirin showed an inhibitory effect on the rEBIV/eGFP/S (EC50 = 14.38 μM) as our expect, while favipiravir with no inhibitory effect even using high doses. Furthermore, Tyrphostin A9 (EC50 = 0.72 μM for rEBIV/eGFP/S, EC50 = 0.05 μM for EBIV-WT) and UNC0638 (EC50 = 1.26 μM for rEBIV/eGFP/S, EC50 = 1.10 μM for rEBIV/eGFP/S) were identified with strong antiviral effect against EBIV in vitro from 150 antiviral compounds. In addition, the time-of-addition assay indicated that Tyrphostin A9 worked in the stage of viral post-infection, and the UNC0638 in all pre-, co-, and post-infection stages. This robust reverse genetics system will facilitate the investigation into the studying of viral replication and assembly mechanisms, and the development of drug and vaccine for EBIV in the future.

      2. Vibrio tarriae sp. nov., a novel member of the Cholerae clade
        Islam MT, Liang K, Orata FD, Im MS, Alam M, Lee CC, Boucher YF.
        Int J Syst Evol Microbiol. 2022 Sep;72(9).
        A number of bacteria with close resemblance to Vibrio cholerae have been isolated over the years by the Centres for Disease Control and Prevention (CDC), which could not be assigned a proper taxonomic designation on the basis of the results from preliminary identification methods. Nine such isolates have been found to share 16S rRNA gene identity exceeding 99 % with V. cholerae, yet DNA-DNA hybridization (60.4-62.1 %) and average nucleotide identity values (94.4-95.1 %) were below the species cut-off, indicating a potentially novel species. Phylogenetic analysis of core genomes places this group of isolates in a monophyletic clade, within the 'Cholerae clade', but distinct from any other species. Extensive phenotypic characterization reveals unique biochemical properties that distinguish this novel species from V. cholerae. Comparative genomic analysis reveals a unique set of siderophore genes, indicating that iron acquisition strategies could be vital for the divergence of the novel species from a common ancestor with V. cholerae. On the basis of the genetic, phylogenetic and phenotypic differences observed, we propose that these isolates represent a novel species of the genus Vibrio, for which the name Vibrio tarriae sp. nov. is proposed. Strain 2521-89 (T) (= DSM 112461=CCUG 75318), isolated from lake water, is the type strain.

      3. The goals of the Association for Molecular Pathology Clinical Practice Committee's Pharmacogenomics (PGx) Working Group are to define the key attributes of pharmacogenetic alleles recommended for clinical testing and a minimum set of variants that should be included in clinical PGx genotyping assays. This article provides recommendations for a minimum panel of variant alleles (Tier 1) and an extended panel of variant alleles (Tier 2) that will aid clinical laboratories when designing assays for PGx testing. The Association for Molecular Pathology PGx Working Group considered the functional impact of the variant alleles, allele frequencies in multiethnic populations, the availability of reference materials, as well as other technical considerations for PGx testing when developing these recommendations. The ultimate goal of this Working Group is to promote standardization of PGx gene/allele testing across clinical laboratories. This article focuses on clinical TPMT and NUDT15 PGx testing, which may be applied to all thiopurine S-methyltransferase (TPMT) and nudix hydrolase 15 (NUDT15)-related medications. These recommendations are not to be interpreted as prescriptive, but to provide a reference guide.

      4. Characterization of reference materials for TPMT and NUDT15: A GeT-RM collaborative project
        Pratt VM, Wang WY, Boone EC, Broeckel U, Cody N, Edelmann L, Gaedigk A, Lynnes TC, Medeiros EB, Moyer AM, Mitchell MW, Scott SA, Starostik P, Turner A, Kalman LV.
        J Mol Diagn. 2022 Oct;24(10):1079-1088.
        Pharmacogenetic testing is increasingly provided by clinical and research laboratories; however, only a limited number of quality control and reference materials are currently available for many of the TPMT and NUDT15 variants included in clinical tests. To address this need, the Division of Laboratory Systems, Centers for Disease Control and Prevention-based Genetic Testing Reference Material (GeT-RM) coordination program, in collaboration with members of the pharmacogenetic testing and research communities and the Coriell Institute for Medical Research, has characterized 19 DNA samples derived from Coriell cell lines. DNA samples were distributed to four volunteer testing laboratories for genotyping using a variety of commercially available and laboratory developed tests and/or Sanger sequencing. Of the 12 samples characterized for TPMT, newly identified variants include TPMT∗2, ∗6, ∗12, ∗16, ∗21, ∗24, ∗32, ∗33, and ∗40; for the 7 NUDT15 reference material samples, newly identified variants are NUDT15∗2, ∗3, ∗4, ∗5, ∗6, and ∗9. In addition, a novel haplotype, TPMT∗46, was identified in this study. Preexisting data on an additional 11 Coriell samples, as well as some supplemental testing, were used to create comprehensive reference material panels for TPMT and NUDT15. These publicly available and well-characterized materials can be used to support the quality assurance and quality control programs of clinical laboratories performing clinical pharmacogenetic testing.

    • Global Health

    • Health Economics
      1. How much does the United States spend on respiratory diseases?
        Nurmagambetov TA.
        Am J Respir Crit Care Med. 2022 Sep 26.

      2. The economic burden of TB faced by patients and affected families in Papua New Guinea
        Aia P, Viney K, Kal M, Kisomb J, Yasi R, Wangchuk LZ, Islam T, Jadambaa N, Rehan R, Nishikori N, Labelle S, Ershova J.
        Int J Tuberc Lung Dis. 2022 Oct 1;26(10):934-941.
        BACKGROUND The costs associated with TB disease can be catastrophic for patients, affecting health and socioeconomic outcomes. Papua New Guinea (PNG) is a high TB burden country and the costs associated with TB are unknown.METHODS We undertook a national survey of TB patients to determine the magnitude of costs associated with TB in PNG, the proportion of households with catastrophic costs and cost drivers. We used a cluster sampling approach and recruited TB patients from health facilities. Descriptive statistics were used to analyse the costs and cost drivers and multivariate logistic regression to determine factors associated with catastrophic costs.RESULTS We interviewed 1,000 TB patients; 19 (1.9%) of them had multidrug-resistant TB (MDR-TB). Costs due to TB were attributable to income loss (64.4%), non-medical (29.9%) and medical (5.7%) expenses. Catastrophic costs were experienced by 33.9% (95% CI 31.0-36.9) of households and were associated with MDR-TB (aOR 4.47, 95% CI 1.21-16.50), hospitalization (aOR 3.94, 95% CI 2.69-5.77), being in the poorest (aOR 3.52, 95% CI 2.43-5.10) or middle wealth tertiles (aOR 1.51, 95% CI 1.03-2.21) or being employed (aOR 2.02, 95% CI 1.43-2.89).CONCLUSION The costs due to TB disease were catastrophic for one third of TB-affected households in PNG. Current support measures could be continued, while new cost mitigation interventions may be considered where needed.

    • Health Equity and Health Disparities
      1. Disparities in infant mortality by maternal race and Hispanic origin, 2017-2018
        Driscoll AK, Ely DM.
        Semin Perinatol. 2022 Aug 27:151656.
        Disparities in infant mortality by race and Hispanic origin groups continue to persist in the United States. Maternal and infant characteristics known to be associated with infant mortality vary by race and ethnicity. This report describes racial and ethnic disparities in infant mortality in the United States using the 2017-2018 cohort linked birth/infant death files from the National Vital Statistics System. Distributions of births and infant mortality rates are described by selected maternal and infant characteristics. Adjusted rates and rate ratios from logistic regression models, compared to unadjusted rates and ratios, show the extent to which race and Hispanic origin disparities would be attenuated if all groups had the same distributions of select maternal and infant factors. Results support the premise that the different distributions of several variables across racial/ethnic groups, most notably gestational age, account for a significant portion of the disparities in infant mortality between racial/ethnic groups.

      2. Ensuring equitable COVID-19 vaccine allocation in New Hampshire: The first eight months toward a new era
        Selembo TD, Talbot EA, Courtine CT, Daly ER, Hull TW, Durzy KJ.
        Vaccines (Basel). 2022 Aug 29;10(9).
        The global coronavirus disease 2019 (COVID-19) pandemic has been exacerbated by social vulnerabilities and racial disparities, resulting in disproportionate morbidity and mortality that require continued attention to strategies that ensure equitable vaccine allocation. The State of New Hampshire (NH) developed a transparent framework to guide COVID-19 vaccine allocation plans, of which one key component was the allocation of 10% of vaccine supply to disproportionately impacted and highly vulnerable populations, predominantly identified through a national vulnerability index. The process, operational approaches, ethical challenges, and unanticipated consequences resulted in many valuable lessons learned. Equitable allocation of this limited and critical pandemic countermeasure required public understanding and engagement, which was achieved through a publicly available framework that was flexible, resourced using public funds, and widely communicated. Broad partnerships were also critical to addressing disparities in the delivery of vaccine. The lessons learned and described here will facilitate more nimble and equitable jurisdictional responses in future public health emergencies.

    • Immunity and Immunization
      1. Co-administration of oral cholera vaccine with oral polio vaccine among Bangladeshi young children: A randomized controlled open label trial to assess interference
        Islam MT, Date K, Khan AI, Bhuiyan TR, Khan ZH, Ahmed S, Hossain M, Khaton F, Zaman K, McMillan NA, Anand A, An Q, Zhang C, Weldon WC, Yu A, Luby S, Qadri F.
        Clin Infect Dis. 2022 Sep 22.
        BACKGROUND: Cholera remains a public health threat for low- and middle-income countries, particularly in Asia and Africa. ShancholTM, an inactivated oral cholera vaccine (OCV) is currently in use globally. OCV and oral poliovirus vaccines (OPV) could be administered concomitantly but the immunogenicity and safety of coadministration among children aged 1-3 years is unknown. METHOD: We undertook an open-label, randomized, controlled, inequality trial in Dhaka city, Bangladesh. Healthy children aged 1-3 years were randomly assigned to one of the three groups: bivalent OPV (bOPV)-alone, OCV-alone, or combined bOPV + OCV and received vaccines on the day of enrollment and 28 days later. Blood samples were collected on the day of enrollment, day 28, and day 56. Serum poliovirus neutralizing antibodies and vibriocidal antibodies against V. cholerae O1 were assessed using microneutralization assays. RESULTS: A total of 579 children aged 1‒3 years were recruited, 193 children per group. More than 90% of the children completed visits at day 56. Few adverse events following immunization were recorded and were equivalent among study arms. On day 28, 60% (90% Confidence interval, 53%-67%) and 54% (46%-61%) of participants with co-administration of bOPV + OCV responded to polioviruses type 1 and 3 respectively, compared to 55% (47%-62%) and 46% (38%-53%) in the bOPV-only group. Additionally, >50% of participants showed a ≥4-fold increase in vibriocidal antibody titre responses on day 28, comparable to the responses observed in OCV-only arm. CONCLUSIONS: Co-administration of bOPV and OCV is safe and effective in children aged 1-3 years and can be cost-beneficial.

      2. Factors influencing the decision to receive seasonal influenza vaccination among US corporate non-healthcare workers
        Aguolu OG, Willebrand K, Elharake JA, Qureshi HM, Kiti MC, Liu CY, Restrepo Mesa A, Nelson K, Jenness S, Melegaro A, Ahmed F, Yildirim I, Malik FA, Lopman B, Omer SB.
        Hum Vaccin Immunother. 2022 Sep 22:2122379.
        Influenza causes significant mortality and morbidity in the United States (US). Employees are exposed to influenza at work and can spread it to others. The influenza vaccine is safe, effective, and prevents severe outcomes; however, coverage among US adults (50.2%) is below Healthy People 2030 target of 70%. These highlights need for more effective vaccination promotion interventions. Understanding predictors of vaccination acceptance could inform vaccine promotion messages, improve coverage, and reduce illness-related work absences. We aimed to identify factors influencing influenza vaccination among US non-healthcare workers. Using mixed-methods approach, we evaluated factors influencing influenza vaccination among employees in three US companies during April-June 2020. Survey questions were adapted from the WHO seasonal influenza survey. Most respondents (n = 454) were women (272, 59.9%), 20-39 years old (n = 250, 55.1%); white (n = 254, 56.0%); had a college degree (n = 431, 95.0%); and reported receiving influenza vaccine in preceding influenza season (n = 297, 65.4%). Logistic regression model was statistically significant, X (16, N = 450) = 31.6, p = .01. Education [(OR) = 0.3, 95%CI = 0.1-0.6)] and race (OR = 0.4, 95%CI = 0.2-0.8) were significant predictors of influenza vaccine acceptance among participants. The majority had favorable attitudes toward influenza vaccination and reported that physician recommendation would influence their vaccination decisions. Seven themes were identified in qualitative analysis: "Protecting others" (109, 24.0%), "Protecting self" (105, 23.1%), "Vaccine accessibility" (94, 20.7%), "Education/messaging" (71, 15.6%), "Policies/requirements" (15, 3.3%), "Reminders" (9, 2.0%), and "Incentives" (3, 0.7%). Our findings could facilitate the development of effective influenza vaccination promotion messages and programs for employers, and workplace vaccination programs for other diseases such as COVID-19, by public health authorities. Influenza causes significant mortality and morbidity in the United States (US).The US working-age group (18–64-year-old) bears a huge burden of influenza annually.Influenza vaccination coverage in the working-age group is low.Physicians and employers can influence vaccine acceptance of working adults.Employers can consider practical steps, e.g., incentivizing, or offering vaccine onsite. eng

      3. Challenges to COVID-19 vaccine introduction in the Democratic Republic of the Congo - a commentary
        Zola Matuvanga T, Doshi RH, Muya A, Cikomola A, Milabyo A, Nasaka P, Mitashi P, Muhindo-Mavoko H, Ahuka S, Nzaji M, Hoff NA, Perry R, Mukamba Musenga E.
        Hum Vaccin Immunother. 2022 Sep 27:2127272.
        COVID-19 vaccination in the Democratic Republic of the Congo (DRC) began in April 2021. A month later, most COVID-19 vaccine doses were reallocated to other African countries, due to low vaccine uptake and the realization that the doses would expire before use. Based on data available on 13 August 2022, 2.76% of the DRC population had been fully vaccinated with last dose of primary series of COVID-19 vaccine, placing the country second to last in Africa and in the last five in global COVID-19 vaccination coverage. The DRC's reliance on vaccine donations requires continuous adaptation of the vaccine deployment plan to match incoming COVID-19 vaccines shipments. Challenges in planning vaccine deployments, vaccinating priority populations, coordinating, and implementing the communications plan, disbursing funds, and conducting supervision of vaccination activities have contributed to low COVID-19 vaccine coverage. In addition, the spread of rumors through social media and by various community and religious leaders resulted in high levels of vaccine hesitancy. A strong risk communication and community engagement plan, coupled with innovative efforts to target the highest-risk populations are critical to increase vaccine uptake during the next phase of COVID-19 vaccine introduction.

      4. Long-term protection associated with COVID-19 vaccination and prior infection
        Tenforde MW, Link-Gelles R, Patel MM.
        Jama. 2022 Sep 26.

      5. Estimation of COVID-19 mRNA vaccine effectiveness against medically attended COVID-19 in pregnancy during periods of Delta and Omicron variant predominance in the United States
        Schrag SJ, Verani JR, Dixon BE, Page JM, Butterfield KA, Gaglani M, Vazquez-Benitez G, Zerbo O, Natarajan K, Ong TC, Lazariu V, Rao S, Beaver R, Ellington SR, Klein NP, Irving SA, Grannis SJ, Kiduko S, Barron MA, Midturi J, Dickerson M, Lewis N, Stockwell MS, Stenehjem E, Fadel WF, Link-Gelles R, Murthy K, Goddard K, Grisel N, Valvi NR, Fireman B, Arndorfer J, Konatham D, Ball S, Thompson MG, Naleway AL.
        JAMA Netw Open. 2022 Sep 1;5(9):e2233273.
        IMPORTANCE: Pregnant people are at high risk for severe COVID-19 but were excluded from mRNA vaccine trials; data on COVID-19 vaccine effectiveness (VE) are needed. OBJECTIVE: To evaluate the estimated effectiveness of mRNA vaccination against medically attended COVID-19 among pregnant people during Delta and Omicron predominance. DESIGN, SETTING, AND PARTICIPANTS: This test-negative, case-control study was conducted from June 2021 to June 2022 in a network of 306 hospitals and 164 emergency department and urgent care (ED/UC) facilities across 10 US states, including 4517 ED/UC encounters and 975 hospitalizations among pregnant people with COVID-19-like illness (CLI) who underwent SARS-CoV-2 molecular testing. EXPOSURES: Two doses (14-149 and ≥150 days prior) and 3 doses (7-119 and ≥120 days prior) of COVID-19 mRNA vaccine (≥1 dose received during pregnancy) vs unvaccinated. MAIN OUTCOMES AND MEASURES: Estimated VE against laboratory-confirmed COVID-19-associated ED/UC encounter or hospitalization, based on the adjusted odds ratio (aOR) for prior vaccination; VE was calculated as (1 - aOR) × 100%. RESULTS: Among 4517 eligible CLI-associated ED/UC encounters and 975 hospitalizations, 885 (19.6%) and 334 (34.3%) were SARS-CoV-2 positive, respectively; the median (IQR) patient age was 28 (24-32) years and 31 (26-35) years, 537 (12.0%) and 118 (12.0%) were non-Hispanic Black and 1189 (26.0%) and 240 (25.0%) were Hispanic. During Delta predominance, the estimated VE against COVID-19-associated ED/UC encounters was 84% (95% CI, 69% to 92%) for 2 doses within 14 to 149 days, 75% (95% CI, 5% to 93%) for 2 doses 150 or more days prior, and 81% (95% CI, 30% to 95%) for 3 doses 7 to 119 days prior; estimated VE against COVID-19-associated hospitalization was 99% (95% CI, 96% to 100%), 96% (95% CI, 86% to 99%), and 97% (95% CI, 79% to 100%), respectively. During Omicron predominance, for ED/UC encounters, the estimated VE of 2 doses within 14 to 149 days, 2 doses 150 or more days, 3 doses within 7 to 119 days, and 3 doses 120 or more days prior was 3% (95% CI, -49% to 37%), 42% (95% CI, -16% to 72%), 79% (95% CI, 59% to 89%), and -124% (95% CI, -414% to 2%), respectively; for hospitalization, estimated VE was 86% (95% CI, 41% to 97%), 64% (95% CI, -102% to 93%), 86% (95% CI, 28% to 97%), and -53% (95% CI, -1254% to 83%), respectively. CONCLUSIONS AND RELEVANCE: In this study, maternal mRNA COVID-19 vaccination, including booster dose, was associated with protection against medically attended COVID-19. VE estimates were higher against COVID-19-associated hospitalization than ED/UC visits and lower against the Omicron variant than the Delta variant. Protection waned over time, particularly during Omicron predominance.

      6. Outcomes at least 90 days since onset of myocarditis after mRNA COVID-19 vaccination in adolescents and young adults in the USA: a follow-up surveillance study
        Kracalik I, Oster ME, Broder KR, Cortese MM, Glover M, Shields K, Creech CB, Romanson B, Novosad S, Soslow J, Walter EB, Marquez P, Dendy JM, Woo J, Valderrama AL, Ramirez-Cardenas A, Assefa A, Campbell MJ, Su JR, Magill SS, Shay DK, Shimabukuro TT, Basavaraju SV.
        Lancet Child Adolesc Health. 2022 Sep 21.
        BACKGROUND: Data on medium-term outcomes in indivduals with myocarditis after mRNA COVID-19 vaccination are scarce. We aimed to assess clinical outcomes and quality of life at least 90 days since onset of myocarditis after mRNA COVID-19 vaccination in adolescents and young adults. METHODS: In this follow-up surveillance study, we conducted surveys in US individuals aged 12-29 years with myocarditis after mRNA COVID-19 vaccination, for whom a report had been filed to the Vaccine Adverse Event Reporting System between Jan 12 and Nov 5, 2021. A two-component survey was administered, one component to patients (or parents or guardians) and one component to health-care providers, to assess patient outcomes at least 90 days since myocarditis onset. Data collected were recovery status, cardiac testing, and functional status, and EuroQol health-related quality-of-life measures (dichotomised as no problems or any problems), and a weighted quality-of-life measure, ranging from 0 to 1 (full health). The EuroQol results were compared with published results in US populations (aged 18-24 years) from before and early on in the COVID-19 pandemic. FINDINGS: Between Aug 24, 2021, and Jan 12, 2022, we collected data for 519 (62%) of 836 eligible patients who were at least 90 days post-myocarditis onset: 126 patients via patient survey only, 162 patients via health-care provider survey only, and 231 patients via both surveys. Median patient age was 17 years (IQR 15-22); 457 (88%) patients were male and 61 (12%) were female. 320 (81%) of 393 patients with a health-care provider assessment were considered recovered from myocarditis by their health-care provider, although at the last health-care provider follow-up, 104 (26%) of 393 patients were prescribed daily medication related to myocarditis. Of 249 individuals who completed the quality-of-life portion of the patient survey, four (2%) reported problems with self-care, 13 (5%) with mobility, 49 (20%) with performing usual activities, 74 (30%) with pain, and 114 (46%) with depression. Mean weighted quality-of-life measure (0·91 [SD 0·13]) was similar to a pre-pandemic US population value (0·92 [0·13]) and significantly higher than an early pandemic US population value (0·75 [0·28]; p<0·0001). Most patients had improvements in cardiac diagnostic marker and testing data at follow-up, including normal or back-to-baseline troponin concentrations (181 [91%] of 200 patients with available data), echocardiograms (262 [94%] of 279 patients), electrocardiograms (240 [77%] of 311 patients), exercise stress testing (94 [90%] of 104 patients), and ambulatory rhythm monitoring (86 [90%] of 96 patients). An abnormality was noted among 81 (54%) of 151 patients with follow-up cardiac MRI; however, evidence of myocarditis suggested by the presence of both late gadolinium enhancement and oedema on cardiac MRI was uncommon (20 [13%] of 151 patients). At follow-up, most patients were cleared for all physical activity (268 [68%] of 393 patients). INTERPRETATION: After at least 90 days since onset of myocarditis after mRNA COVID-19 vaccination, most individuals in our cohort were considered recovered by health-care providers, and quality of life measures were comparable to those in pre-pandemic and early pandemic populations of a similar age. These findings might not be generalisable given the small sample size and further follow-up is needed for the subset of patients with atypical test results or not considered recovered. FUNDING: US Centers for Disease Control and Prevention.

      7. Enhanced immunogenicity of adjuvanted microparticulate HPV16 vaccines administered via the transdermal route
        Vo TP, Panicker G, Braz-Gomes K, Parenky AC, Rajbhandari I, Rajeevan MS, Unger ER, D'Souza MJ, Uddin MN.
        Pharmaceuticals (Basel). 2022 Sep 9;15(9).
        Human papillomavirus (HPV) causes cervical cancer among women and is associated with other anogenital cancers in men and women. Prophylactic particulate vaccines that are affordable, self-administered and efficacious could improve uptake of HPV vaccines world-wide. The goal of this research is to develop a microparticulate HPV16 vaccine for transdermal administration using AdminPatch(®) and assess its immunogenicity in a pre-clinical mouse model. HPV16 microparticles were prepared using a biocompatible polymer and characterized in terms of size, zeta potential, encapsulation efficiency and microparticle yield. Scanning and transmission electron microscopy were conducted to confirm particle image and to visualize the conformation of HPV16 vaccine particles released from microparticle formulation. In vivo studies performed to evaluate the potential of the microparticulate vaccine initiated a robust and sustained immune response. HPV16 IgG antibodies were significantly elevated in the microparticle group compared to antigen solutions administered by the transdermal route. Results show significant expansion of CD4+, CD45R, CD27 and CD62L cell populations in the vaccinated mice group, indicating the high efficacy of the microparticulate vaccine when administered via transdermal route. The findings of this study call attention to the use of minimally invasive, pain-free routes to deliver vaccine.

      8. Thrombosis and thromboembolism: Brighton collaboration case definition and guidelines for data collection, analysis, and presentation of immunization safety data
        Gollamudi J, Sartain SE, Navaei AH, Aneja S, Kaur Dhawan P, Tran D, Joshi J, Gidudu J, Gollamudi J, Chiappini E, Varricchio F, Law B, Munoz FM.
        Vaccine. 2022 Sep 20.
        This is a Brighton Collaboration case definition of thrombosis and thromboembolism to be used in the evaluation of adverse events following immunization, and for epidemiologic studies for the assessment of background incidence or hypothesis testing. The case definition was developed by a group of experts convened by the Coalition for Epidemic Preparedness Innovations (CEPI) in the context of active development of SARS-CoV-2 vaccines. The case definition format of the Brighton Collaboration was followed to develop a consensus definition and defined levels of certainty, after an exhaustive review of the literature and expert consultation. The document underwent peer review by the Brighton Collaboration Network and by selected expert reviewers prior to submission.

      9. Adjuvant effects of a new saponin analog VSA-1 on enhancing homologous and heterosubtypic protection by influenza virus vaccination
        Bhatnagar N, Kim KH, Subbiah J, Park BR, Wang P, Gill HS, Wang BZ, Kang SM.
        Vaccines (Basel). 2022 Aug 24;10(9).
        Adjuvants can increase the magnitude and durability of the immune response generated by the vaccine antigen. Aluminum salts (Alum) remain the main adjuvant licensed for human use. A few new adjuvants have been licensed for use in human vaccines since the 1990s. QS-21, a mixture of saponin compounds, was included in the AS01-adjuvanted Shingrix vaccine. Here, we investigated the adjuvant effects of VSA-1, a newly developed semisynthetic analog of QS-21, on promoting protection in mice after vaccination with the inactivated split virus vaccine. The adjuvant effects of VSA-1 on improving vaccine efficacy after prime immunization were evident as shown by significantly higher levels of hemagglutination-inhibiting antibody titers and enhanced homologous protection compared to those by QS-21 and Alum adjuvants. The adjuvant effects of VSA-1 on enhancing heterosubtypic protection after two doses of adjuvanted vaccination were comparable to those of QS-21. T cell immunity played an important role in conferring cross-protection by VSA-1-adjuvanted vaccination. Overall, the findings in this study suggest that VSA-1 exhibits desirable adjuvant properties and a unique pattern of innate and adaptive immune responses, contributing to improved homologous and heterosubtypic protection by inactivated split influenza vaccination in mice.

      10. Intent among parents to vaccinate children before pediatric COVID-19 vaccine recommendations, Minnesota and Los Angeles County, California-May-September 2021
        Suvada KA, Quan SF, Weaver MD, Sreedhara M, Czeisler M, Como-Sabetti K, Lynfield R, Grounder P, Traub E, Amoon A, Ladva CN, Howard ME, Czeisler CA, Rajaratnam SM, Ekwueme DU, Flannery B, Lane RI.
        Vaccines (Basel). 2022 Sep 1;10(9).
        Objectives: This study assessed the associations between parent intent to have their child receive the COVID-19 vaccination, and demographic factors and various child activities, including attendance at in-person education or childcare. Methods: Persons undergoing COVID-19 testing residing in Minnesota and Los Angeles County, California with children aged &lt;12 years completed anonymous internet-based surveys between 10 May and 6 September 2021 to assess factors associated with intention to vaccinate their child. Factors influencing the parents' decision to have their child attend in-person school or childcare were examined. Estimated adjusted odds rations (AORs, 95% CI) were computed between parents' intentions regarding children's COVID-19 vaccination and participation in school and extra-curricular activities using multinomial logistic regression. Results: Compared to parents intending to vaccinate their children (n = 4686 [77.2%]), those undecided (n = 874 [14.4%]) or without intention to vaccinate (n = 508 [8.4%]) tended to be younger, non-White, less educated, and themselves not vaccinated against COVID-19. Their children more commonly participated in sports (aOR:1.51 1.17-1.95) and in-person faith or community activities (aOR:4.71 3.62-6.11). A greater proportion of parents without intention to vaccinate (52.5%) indicated that they required no more information to make their decision in comparison to undecided parents (13.2%). They further indicated that additional information regarding vaccine safety and effectiveness would influence their decision. COVID-19 mitigation measures were the most common factors influencing parents' decision to have their child attend in-person class or childcare. Conclusions: Several demographic and socioeconomic factors are associated with parents' decision whether to vaccinate their &lt;12-year-old children for COVID-19. Child participation in in-person activities was associated with parents' intentions not to vaccinate. Tailored communications may be useful to inform parents' decisions regarding the safety and effectiveness of vaccination.

      11. Norovirus infection in young Nicaraguan children induces durable and genotype-specific antibody immunity
        Brewer-Jensen PD, Reyes Y, Becker-Dreps S, González F, Mallory ML, Gutiérrez L, Zepeda O, Centeno E, Vielot N, Diez-Valcarce M, Vinjé J, Baric R, Lindesmith LC, Bucardo F.
        Viruses. 2022 Sep 16;14(9).
        There are significant challenges to the development of a pediatric norovirus vaccine, mainly due to the antigenic diversity among strains infecting young children. Characterizing human norovirus serotypes and understanding norovirus immunity in naïve children would provide key information for designing rational vaccine platforms. In this study, 26 Nicaraguan children experiencing their first norovirus acute gastroenteritis (AGE) episode during the first 18 months of life were investigated. We used a surrogate neutralization assay that measured antibodies blocking the binding of 13 different norovirus virus-like particles (VLPs) to histo-blood group antigens (HBGAs) in pre- and post-infection sera. To assess for asymptomatic norovirus infections, stools from asymptomatic children were collected monthly, screened for norovirus by RT-qPCR and genotyped by sequencing. Seroconversion of an HBGA-blocking antibody matched the infecting genotype in 25 (96%) of the 26 children. A subset of 13 (50%) and 4 (15%) of the 26 children experienced monotypic GII and GI seroconversion, respectively, strongly suggesting a type-specific response in naïve children, and 9 (35%) showed multitypic seroconversion. The most frequent pairing in multitypic seroconversion (8/12) were GII.4 Sydney and GII.12 noroviruses, both co-circulating at the time. Blocking antibody titers to these two genotypes did not correlate with each other, suggesting multiple exposure rather than cross-reactivity between genotypes. In addition, GII titers remained consistent for at least 19 months post-infection, demonstrating durable immunity. In conclusion, the first natural norovirus gastroenteritis episodes in these young children were dominated by a limited number of genotypes and induced responses of antibodies blocking binding of norovirus VLPs in a genotype-specific manner, suggesting that an effective pediatric norovirus vaccine likely needs to be multivalent and include globally dominant genotypes. The duration of protection from natural infections provides optimism for pediatric norovirus vaccines administered early in life.

    • Informatics
      1. Along with the rapid emergence of web surveys to address time-sensitive priority topics, various propensity score (PS)-based adjustment methods have been developed to improve population representativeness for nonprobability- or probability-sampled web surveys subject to selection bias. Conventional PS-based methods construct pseudo-weights for web samples using a higher-quality reference probability sample. The bias reduction, however, depends on the outcome and variables collected in both web and reference samples. A central issue is identifying variables for inclusion in PS-adjustment. In this paper, directed acyclic graph (DAG), a common graphical tool for causal studies but largely under-utilized in survey research, is used to examine and elucidate how different types of variables in the causal pathways impact the performance of PS-adjustment. While past literature generally recommends including all variables, our research demonstrates that only certain types of variables are needed in PS-adjustment. Our research is illustrated by NCHS' Research and Development Survey, a probability-sampled web survey with potential selection bias, PS-adjusted to the National Health Interview Survey, to estimate U.S. asthma prevalence. Findings in this paper can be used by National Statistics Offices to design questionnaires with variables that improve web-samples' population representativeness and to release more timely and accurate estimates for priority topics.

      2. Using a cloud-based machine learning classification tree analysis to understand the demographic characteristics associated with COVID-19 booster vaccination among adults in the United States
        Meng L, Fast HE, Saelee R, Zell E, Murthy BP, Murthy NC, Lu PJ, Shaw L, Harris L, Gibbs-Scharf L, Chorba T.
        Open Forum Infect Dis. 2022 Sep;9(9):ofac446.
        A tree model identified adults age ≤34 years, Johnson & Johnson primary series recipients, people from racial/ethnic minority groups, residents of nonlarge metro areas, and those living in socially vulnerable communities in the South as less likely to be boosted. These findings can guide clinical/public health outreach toward specific subpopulations.

    • Laboratory Sciences
      1. Detection of apparent early rabies infection by LN34 pan-lyssavirus real-time RT-PCR assay in Pennsylvania
        Dettinger L, Gigante CM, Sellard M, Seiders M, Patel P, Orciari LA, Yager P, Lute J, Regec A, Li Y, Xia D.
        Viruses. 2022 Aug 23;14(9).
        The Pennsylvania Department of Health Bureau of Laboratories (PABOL) tested 6855 animal samples for rabies using both the direct fluorescent antibody test (DFA) and LN34 pan-lyssavirus reverse transcriptase quantitative PCR (RT-qPCR) during 2017-2019. Only two samples (0.03%) were initially DFA negative but positive by LN34 RT-qPCR. Both cases were confirmed positive upon re-testing at PABOL and confirmatory testing at the Centers for Disease Control and Prevention by LN34 RT-qPCR and DFA. Rabies virus sequences from one sample were distinct from all positive samples processed at PABOL within two weeks, ruling out cross-contamination. Levels of rabies virus antigen and RNA were low in all brain structures tested, but were higher in brain stem and rostral spinal cord than in cerebellum, hippocampus or cortex. Taken together, the low level of rabies virus combined with higher abundance in more caudal brain structures suggest early infection. These cases highlight the increased sensitivity and ease of interpretation of LN34 RT-qPCR for low positive cases.

    • Maternal and Child Health
      1. Association between age of starting clean intermittent catheterization and current urinary continence in individuals with myelomeningocele
        Freeman KA, Liu T, Smith K, Castillo H, Castillo J, Joseph D, Wang Y, Tanaka S.
        J Pediatr Urol. 2022 Sep 5.
        INTRODUCTION: Patients with myelomeningocele often use clean intermittent catheterization (CIC) for renal preservation and to promote urinary continence. While starting CIC at an early age is associated with better renal outcomes, the impact of age of CIC initiation on continence outcomes has not been examined. OBJECTIVE: To examine whether earlier CIC initiation is associated with higher likelihood of current urinary continence for patients with myelomeningocele. STUDY DESIGN: Data of patients aged ≥5 years at last visit were obtained from 35 spina bifida clinics participating in the National Spina Bifida Patient Registry from 2013 to 2018. Sociodemographic characteristics, disease characteristics, and current bladder management strategies were collected. Via univariate and multiple logistic regression models, the latter conducted controlling for all variables associated with current continent status, associations between continence and sociodemographic factors, condition characteristics, and age CIC began (<3 years of age, 3-5 years, 6-11 years, ≥12 years) were analyzed. RESULTS: Data from 3510 individuals were included (mean age at last visit = 17.0 years, range 5.0-88.7). The sample was evenly distributed by sex (52% female); most individuals were non-Hispanic White (62.6%). The majority of patients (55.2%) started CIC before age 3 years. Continence varied markedly across those who never started CIC (0.6% of patients were continent) and those who started at any age (range 35.3-38.5%). Among those who started CIC, the magnitude of the association was not proportional to age CIC was started. Compared with those who started CIC at age 12 or older, estimated adjusted odds ratio of being continent ranged from 1.04 (6-11 years, 95% CI, 0.72-1.52) to 1.25 (<3 years, 95% CI, 0.89-1.76). DISCUSSION: Although CIC may be positively associated with achieving urinary continence in individuals with myelomeningocele, we could not demonstrate that younger age at CIC initiation increased the likelihood of achieving this goal. Limitations include lack of data on reason for starting CIC, urodynamic data, and the observational nature of data collection. CONCLUSIONS: Further study is needed addressing limitations of the current investigation to determine if urinary continence outcomes are influenced by the age of starting CIC among patients with myelomeningocele.

      2. Levels of neonatal care among birth facilities in 20 states and other jurisdictions: CDC levels of care assessment tool(SM) (CDC LOCATe(SM))
        Wilkers JL, DeSisto CL, Ewing AC, Madni SA, Beauregard JL, Brantley MD, Goodman DA.
        J Perinatol. 2022 Sep 22.
        OBJECTIVE: Describe discrepancies between facilities' self-reported level of neonatal care and Centers for Disease Control and Prevention Levels of Care Assessment Tool(SM) (CDC LOCATe(SM))-assessed level. STUDY DESIGN: CDC LOCATe(SM) data from 765 health facilities in the United States, including 17 states, one territory, one large multi-state hospital system, and one perinatal region within a state, was collected between 2016 and 2021 for this cross-sectional analysis. RESULT: Among 721 facilities that self-reported level of neonatal care, 33.1% had discrepancies between their self-reported level and their LOCATe(SM)-assessed level. Among facilities with discrepancies, 75.3% self-reported a higher level of neonatal care than their LOCATe(SM)-assessed level. The most common elements contributing to discrepancies were limited specialty and subspecialty staffing, such as neonatology or neonatal surgery. CONCLUSION: Results highlight opportunities for jurisdictions to engage with facilities, health systems, and partners about levels of neonatal care, and to collaborate to promote standardized systems of risk-appropriate care.

      3. Delayed entry into prenatal care among women with pre-pregnancy health conditions, National Birth Defects Prevention Study, 1997-2011
        Simeone RM, Reefhuis J, Jamieson DJ, Drews-Botsch CD, Lash TL, Fisher SC, Howley MM, Evans S, Howards PP.
        Prev Med. 2022 Sep 21:107272.
        First trimester entry into prenatal care is recommended for all women, and especially women with pre-pregnancy conditions. Our objective was to determine whether women with pre-pregnancy conditions were at lower risk of entry after the first trimester (delayed entry) into prenatal care than women without a pre-pregnancy health condition. We used data from 10,890 participants in the National Birth Defects Prevention Study who delivered liveborn infants without birth defects. Women reported pre-pregnancy conditions and timing of entry into prenatal care during a computer-assisted telephone interview. Multivariable logistic regression analyses were conducted to evaluate whether having a pre-pregnancy condition was associated with delayed entry into prenatal care compared to women without pre-pregnancy conditions. Approximately 13% of women reported delayed entry into prenatal care, and 18% of women reported a pre-pregnancy condition. Delayed entry into prenatal care was not associated with pre-pregnancy cardiometabolic or neurologic conditions. Women with thyroid conditions were less likely to report delayed entry into prenatal care (prevalence odds ratio (OR), 95% confidence interval (CI): 0.55 [0.32, 0.94]), but women with hematologic and respiratory conditions were more likely to report delayed entry into prenatal care (OR: 1.95 [1.00, 3.82] and 1.27 [0.95, 1.72], respectively), compared to those without any chronic conditions. Future research investigating the success of early prenatal care among women with thyroid conditions could identify ways to reduce delayed prenatal care among women with other pre-pregnancy conditions.

    • Occupational Safety and Health
      1. Accuracy of an estimated core temperature algorithm for agricultural workers
        Egbert J, Krenz J, Sampson PD, Jung J, Calkins M, Zhang K, Palmández P, Faestel P, Spector JT.
        Arch Environ Occup Health. 2022 ;77(10):809-818.
        There is a substantial burden of occupational health effects from heat exposure. We sought to assess the accuracy of estimated core body temperature (CBT(est)) derived from an algorithm that uses sequential heart rate and initializing CBT,(1) compared with gastrointestinal temperature measured using more invasive ingestible sensors (CBT(gi)), among outdoor agricultural workers. We analyzed CBT(est) and CBT(gi) data from Washington State, USA, pear and apple harvesters collected across one work shift in 2015 (13,413 observations, 35 participants) using Bland Altman methods. The mean (standard deviation, range) CBT(gi) was 37.7 (0.4, 36.5-39.4)°C. Overall CBT bias (limits of agreement) was -0.14 (±0.76)°C. Biases ranged from -0.006 to -0.75 °C. The algorithm, which does not require the use of ingestible sensors, may be a practical tool in research among groups of workers for evaluating the effectiveness of interventions to prevent adverse occupational heat health effects.

      2. Potential for exposure to particles and gases throughout vat photopolymerization additive manufacturing processes
        Bowers LN, Stefaniak AB, Knepp AK, LeBouf RF, Martin SB, Ranpara AC, Burns DA, Virji MA.
        Buildings. 2022 ;12(8).
        Vat photopolymerization (VP), a type of additive manufacturing process that cures resin to build objects, can emit potentially hazardous particles and gases. We evaluated two VP technologies, stereolithography (SLA) and digital light processing (DLP), in three separate environmental chambers to understand task-based impacts on indoor air quality. Airborne particles, total volatile organic compounds (TVOCs), and/or specific volatile organic compounds (VOCs) were monitored during each task to evaluate their exposure potential. Regardless of duration, all tasks released particles and organic gases, though concentrations varied between SLA and DLP processes and among tasks. Maximum particle concentrations reached 1200 #/cm3 and some aerosols contained potentially hazardous elements such as barium, chromium, and manganese. TVOC concentrations were highest for the isopropyl alcohol (IPA) rinsing, soaking, and drying post-processing tasks (up to 36.8 mg/m3), lowest for the resin pouring pre-printing, printing, and resin recovery post-printing tasks (up to 0.1 mg/m3), and intermediate for the curing post-processing task (up to 3 mg/m3). Individual VOCs included, among others, the potential occupational carcinogen acetaldehyde and the immune sensitizer 2-hydroxypropyl methacrylate (pouring, printing, recovery, and curing tasks). Careful consideration of all tasks is important for the development of strategies to minimize indoor air pollution and exposure potential from VP processes. © 2022 by the authors.

      3. The articles published as part of the Frontiers in Public Health research topic, "Investigating exposures and respiratory health in coffee workers" present research findings that better characterize exposures to diacetyl and 2,3-pentanedione and inform our understanding of the health risks posed by these exposures. Although various research groups and organizations have conducted risk assessments to derive occupational exposure limits (OELs) for diacetyl, differences in the data used and assumptions made in these efforts have resulted in a wide range of recommended OELs designed to protect human health. The primary drivers of these differences include the decision to use data from human or animal studies in conducting a quantitative risk assessment, and the application of uncertainty factors (UF) to derive an OEL. This Perspectives paper will discuss the practical implications of these decisions, and present additional commentary on the potential role that the recent investigation of human exposures to relatively low concentrations of α-diketones, specifically diacetyl and 2,3-pentanedione, may play in supporting qualitative or quantitative human health risk assessments.

      4. Editorial: Investigating exposures and respiratory health in coffee workers
        Virji MA, Cummings KJ, Cox-Ganser JM.
        Front Public Health. 2022 ;10:1026430.

      5. Barriers to SARS-CoV-2 testing among U.S. employers in the COVID-19 pandemic: A qualitative analysis conducted January through April 2021
        Caban-Martinez AJ, Parvanta C, Cabral N, Ball CK, Eastlake A, Levin JL, Moore K, Nessim D, Stracener E, Thiese MS, Schulte PA.
        Int J Environ Res Public Health. 2022 Sep 19;19(18).
        During the first year of the COVID-19 pandemic, U.S. companies were seeking ways to support their employees to return to the workplace. Nonetheless, the development of strategies to support the access, use, and interpretation of SARS-CoV-2 testing was challenging. In the present study, we explore, from the perspective of owners and company leadership, the barriers to SARS-CoV-2 testing among U.S. companies. Key informant interviews with company representatives were conducted during January-April 2021 about SARS-CoV-2 testing. A pre-interview survey assessed respondent socio-demographic and organizational characteristics. Interview sessions were transcribed, coded, and analyzed using MaxQDA. A total of twenty interviews were completed with at least two interviews conducted in each major U.S. industry sector. Ninety percent of participants represented companies in business &gt;10 years, comprising both small and large workforces. Using a grounded theory approach, six themes emerged: (1) access to and knowledge of SARS-CoV-2 tests; (2) strategies for symptomatic and asymptomatic testing of workers; (3) type/availability of personal protective equipment to mitigate coronavirus exposures; (4) return-to-work policies; (5) guidance and communication of SARS-CoV-2 Testing; and (6) use of contact tracing and SARS-CoV-2 vaccination. Various modifiable and non-modifiable challenges for SARS-CoV-2 testing among U.S. companies were identified and can inform work-related SARS-CoV-2 testing strategies.

      6. Injuries that happen at work lead to more opioid prescriptions and higher opioid costs
        Asfaw A, Quay B, Bushnell T, Pana-Cryan R.
        J Occup Environ Med. 2022 Sep 22.
        OBJECTIVES: To compare opioid prescription incidence, supply days, and cost associated with occupational injury and other injury-caused conditions. METHODS: We used Medical Expenditure Panel Survey (MEPS) data for 2010-2019. MEPS provides information on medical conditions and associated medical encounters, treatments, and treatment costs, as well as demographic, education, health, working status, income, and insurance coverage information. We used descriptive statistics and logistic and two-part regressions. RESULTS: Controlling for covariates and compared to other injury-caused conditions, occupational injury-caused conditions resulted in 33% higher odds of opioid prescribing, 32.8 more opioid prescription supply days, and $134 higher average cost. CONCLUSION: Occupational injuries were associated with higher opioid incidence and costs, and more opioid supply days. These findings point to the need to focus on making work safer and the role employers may play in supporting worker recovery from injury and opioid use disorders.

      7. Effects of whole-body vibration on reproductive physiology in a rat model of whole-body vibration
        Krajnak K, Waugh S, Welcome D, Xu XS, Warren C, McKinney W, Dong RG.
        J Toxicol Environ Health A. 2022 Sep 27:1-19.
        Findings from epidemiological studies suggest that occupational exposure to whole-body vibration (WBV) may increase the risk of miscarriage and contribute to a reduction in fertility rates in both men and women. However, workers exposed to WBV may also be exposed to other risk factors that contribute to reproductive dysfunction. The goal of this experiment was to examine the effects of WBV on reproductive physiology in a rat model. Male and female rats were exposed to WBV at the resonant frequency of the torso (31.5 Hz, 0.3 g amplitude) for 4 hr/day for 10 days. WBV exposure resulted in a significant reduction in number of developing follicles, and decrease in circulating estradiol concentrations, ovarian luteinizing hormone receptor protein levels, and marked changes in transcript levels for several factors involved in follicular development, cell cycle, and steroidogenesis. In males, WBV resulted in a significant reduction in spermatids and circulating prolactin levels, elevation in number of males having higher circulating testosterone concentrations, and marked alterations in levels of transcripts associated with oxidative stress, inflammation, and factors involved in regulating the cell cycle. Based upon these findings data indicate that occupational exposure to WBV contributes to adverse alterations in reproductive physiology in both genders that may lead to reduction in fertility.

      8. Health care personnel exposures to subsequently laboratory-confirmed monkeypox patients - Colorado, 2022
        Marshall KE, Barton M, Nichols J, de Perio MA, Kuhar DT, Spence-Davizon E, Barnes M, Herlihy RK, Czaja CA.
        MMWR Morb Mortal Wkly Rep. 2022 Sep 23;71(38):1216-1219.
        The risk for monkeypox transmission to health care personnel (HCP) caring for symptomatic patients is thought to be low but has not been thoroughly assessed in the context of the current global outbreak (1). Monkeypox typically spreads through close physical (often skin-to-skin) contact with lesions or scabs, body fluids, or respiratory secretions of a person with an active monkeypox infection. CDC currently recommends that HCP wear a gown, gloves, eye protection, and an N95 (or higher-level) respirator while caring for patients with suspected or confirmed monkeypox to protect themselves from infection(†) (1,2). The Colorado Department of Public Health and Environment (CDPHE) evaluated HCP exposures and personal protective equipment (PPE) use in health care settings during care of patients who subsequently received a diagnosis of Orthopoxvirus infection (presumptive monkeypox determined by a polymerase chain reaction [PCR] DNA assay) or monkeypox (real-time PCR assay and genetic sequencing performed by CDC). During May 1-July 31, 2022, a total of 313 HCP interacted with patients with subsequently diagnosed monkeypox infections while wearing various combinations of PPE; 23% wore all recommended PPE during their exposures. Twenty-eight percent of exposed HCP were considered to have had high- or intermediate-risk exposures and were therefore eligible to receive postexposure prophylaxis (PEP) with the JYNNEOS vaccine(§); among those, 48% (12% of all exposed HCP) received the vaccine. PPE use varied by facility type: HCP in sexually transmitted infection (STI) clinics and community health centers reported the highest adherence to recommended PPE use, and primary and urgent care settings reported the lowest adherence. No HCP developed a monkeypox infection during the 21 days after exposure. These results suggest that the risk for transmission of monkeypox in health care settings is low. Infection prevention training is important in all health care settings, and these findings can guide future updates to PPE recommendations and risk classification in health care settings.

    • Occupational Safety and Health - Mining
      1. Postexposure progression of pneumoconiosis among former Appalachian coal miners
        Hall NB, Blackley DJ, Markle T, Crum JB, Halldin CN, Laney AS.
        Am J Ind Med. 2022 Sep 26.
        BACKGROUND: The prevalence of pneumoconiosis among working United States underground coal miners has been increasing for the past two decades, with the highest rates of disease observed among miners in the central Appalachian states of Kentucky, Virginia, and West Virginia. Surveillance for this disease in the United States focuses on working coal miners, who continue to be occupationally exposed to dust. This study examines the radiographic evidence for postexposure progression of pneumoconiosis in a population of former coal miners no longer occupationally exposed to coal mine dust who were seen at a community radiology clinic in eastern Kentucky. METHODS: Data were obtained and analyzed from clinical records of former coal miners who had a clinic encounter during January 1, 2017-August 1, 2019, a recorded final year of employment, and ≥2 postemployment digital chest radiographs. Radiographs were classified according to the International Labour Office guidelines by at least two B Readers. A final summary pneumoconiosis severity score (range, 0-13), accounting for both small and large opacities, was assigned to each chest radiograph. Progression was defined as an increase in severity score between a miner's radiographs over time. RESULTS: Data for 130 former coal miners were analyzed. All miners were male and most (n = 114, 88%) had worked primarily in Kentucky. Information on race/ethnicity was not available. The most common job types were roof bolters (n = 51, 39%) and continuous miner operators (n = 46, 35%). Forty-one (31.5%) miners had evidence of radiographic disease progression after leaving the workforce, with a median of 3.6 years between first and latest postretirement radiograph. A total of 80 (62%) miners had evidence of pneumoconiosis on their latest radiograph, and two-thirds (n = 53) of these were classified as progressive massive fibrosis (PMF), the most severe form of the disease. CONCLUSIONS: Postexposure progression can occur in former coal miners, emphasizing the potential benefits of continued radiographic follow-up postemployment. In addition to participating in disease screening throughout their careers to detect pneumoconiosis early and facilitate intervention, radiographic follow-up of former coal miners can identify new or progressive radiographic findings even after workplace exposure to respirable coal mine dust ends. Identification of progressive pneumoconiosis in former miners has potential implications for clinical management and eligibility for disability compensation.

      2. Standing supports have been used in coal mines for decades to enhance roof support capability. Sometimes standing supports are used as a tool to resist the lateral movement of spalled ribs. Researchers from the National Institute for Occupational Safety and Health (NIOSH) are conducting a testing program for different types of standing supports (steel and timber) to investigate the effect of lateral loading on their vertical loading capacities and the factors affecting their lateral loading capacities. In this paper, the mine roof simulator (MRS), at the NIOSH Pittsburgh research facility, was used to determine the response of steel props to vertical and horizontal loadings. Finite element models (FEMs) were developed and verified using the tested steel props. To justify the testing program for testing standing supports with end-conditions of rock-like materials, the verified prop models were used to study the effect of a wide range of roof and floor materials (gray shale, shale, and claystone) on the critical buckling loads of the steel props. Also, several lateral loading scenarios were evaluated in which the steel props were laterally loaded at different heights. The critical buckling load for steel props setting up against a claystone roof and floor was found to be one-half of that shown by the MRS test where roof and floor platens are made of steel. Minimum prop performance was observed when the lateral load was applied at the mid-height of the steel prop, especially at small lateral displacement (less than 2 in). © 2022, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

    • Parasitic Diseases
      1. Safety of single-dose primaquine as a Plasmodium falciparum gametocytocide: a systematic review and meta-analysis of individual patient data
        Stepniewska K, Allen EN, Humphreys GS, Poirot E, Craig E, Kennon K, Yilma D, Bousema T, Guerin PJ, White NJ, Price RN, Raman J, Martensson A, Mwaiswelo RO, Bancone G, Bastiaens GJ, Bjorkman A, Brown JM, D'Alessandro U, Dicko AA, El-Sayed B, Elzaki SE, Eziefula AC, Gonçalves BP, Hamid MM, Kaneko A, Kariuki S, Khan W, Kwambai TK, Ley B, Ngasala BE, Nosten F, Okebe J, Samuels AM, Smit MR, Stone WJ, Sutanto I, Ter Kuile F, Tine RC, Tiono AB, Drakeley CJ, Gosling R, Stergachis A, Barnes KI, Chen I.
        BMC Med. 2022 Sep 16;20(1):350.
        BACKGROUND: In 2012, the World Health Organization (WHO) recommended single low-dose (SLD, 0.25 mg/kg) primaquine to be added as a Plasmodium (P.) falciparum gametocytocide to artemisinin-based combination therapy (ACT) without glucose-6-phosphate dehydrogenase (G6PD) testing, to accelerate malaria elimination efforts and avoid the spread of artemisinin resistance. Uptake of this recommendation has been relatively slow primarily due to safety concerns. METHODS: A systematic review and individual patient data (IPD) meta-analysis of single-dose (SD) primaquine studies for P. falciparum malaria were performed. Absolute and fractional changes in haemoglobin concentration within a week and adverse effects within 28 days of treatment initiation were characterised and compared between primaquine and no primaquine arms using random intercept models. RESULTS: Data comprised 20 studies that enrolled 6406 participants, of whom 5129 (80.1%) had received a single target dose of primaquine ranging between 0.0625 and 0.75 mg/kg. There was no effect of primaquine in G6PD-normal participants on haemoglobin concentrations. However, among 194 G6PD-deficient African participants, a 0.25 mg/kg primaquine target dose resulted in an additional 0.53 g/dL (95% CI 0.17-0.89) reduction in haemoglobin concentration by day 7, with a 0.27 (95% CI 0.19-0.34) g/dL haemoglobin drop estimated for every 0.1 mg/kg increase in primaquine dose. Baseline haemoglobin, young age, and hyperparasitaemia were the main determinants of becoming anaemic (Hb < 10 g/dL), with the nadir observed on ACT day 2 or 3, regardless of G6PD status and exposure to primaquine. Time to recovery from anaemia took longer in young children and those with baseline anaemia or hyperparasitaemia. Serious adverse haematological events after primaquine were few (9/3, 113, 0.3%) and transitory. One blood transfusion was reported in the primaquine arms, and there were no primaquine-related deaths. In controlled studies, the proportions with either haematological or any serious adverse event were similar between primaquine and no primaquine arms. CONCLUSIONS: Our results support the WHO recommendation to use 0.25 mg/kg of primaquine as a P. falciparum gametocytocide, including in G6PD-deficient individuals. Although primaquine is associated with a transient reduction in haemoglobin levels in G6PD-deficient individuals, haemoglobin levels at clinical presentation are the major determinants of anaemia in these patients. TRIAL REGISTRATION: PROSPERO, CRD42019128185.

      2. You cannot find what you are not looking for! detecting malaria outbreaks in Uganda: a case study
        Kwesiga B, Nabunya P, Riolexus Ario A, Kadobera D, Bulage L, Kabwama SN, Harris JR.
        Pan Afr Med J. 2022 ;41(Suppl 1):2.
        Malaria is the leading cause of morbidity and mortality in Uganda, with nearly half of the population becoming infected in any given year. Uganda relies on analyzing high-quality surveillance data to help detect outbreaks, determine which areas or population groups are most affected, and help target resources to where they are most needed. In March 2019, over 300 health facilities from different districts in Uganda reported substantially higher malaria cases than usual. In 13 districts, health facilities reported that the number of malaria cases was so high that they were experiencing stock outs of antimalarial drugs. Although seasonal increases in cases had been expected, districts reported that the number of cases being identified were overwhelming the capacity of the health facilities. Uganda´s National Malaria Control Division tasked a team of epidemiologists to investigate this unprecedented increase in malaria cases. National Malaria Control Division were interested in how malaria epidemiology had been changing in recent years, and whether they had missed something that would have predicted the situation they were facing in 2019. This case study describes the steps taken to conduct a descriptive analysis of routine malaria surveillance data and demonstrates how to detect malaria outbreaks using historical data. It is useful for training Field Epidemiologists and public health officers involved in analysis of surveillance data.

      3. Malaria outbreak facilitated by engagement in activities near swamps following increased rainfall and limited preventive measures: Oyam District, Uganda
        Katusiime M, Kabwama SN, Rukundo G, Kwesiga B, Bulage L, Rutazaana D, Ario AR, Harris J.
        PLOS Glob Public Health. 2022 ;2(8).
        In April 2019, the District Health Office of Oyam District, Uganda reported an upsurge in malaria cases exceeding expected epidemic thresholds, requiring outbreak response. We investigated the scope of outbreak and identified exposures for transmission to inform control measures. A confirmed case was a positive malaria rapid diagnostic test or malaria microscopy from 1 January-30 June 2019 in a resident or visitor of Acaba Sub-county, Oyam District. We reviewed medical records at health facilities to get case-patients. We conducted entomological and environmental assessments to determine vector density, and identify aquatic Anopheles habitats, conducted a case-control study to determine exposures associated with illness. Of 9,235 case-patients (AR = 33%), females (AR = 38%) were more affected than males (AR = 20%) (p<0.001). Children <18 years were more affected (AR = 37%) than adults (p<0.001). Among 83 case-patients and 83 asymptomatic controls, 65 (78%) case-patients and 33 (40%) controls engaged in activities <500m from a swamp (OR<sub>MH</sub> = 12, 95%CI 3.6-38); 18 (22%) case-patients and four (5%) controls lived <500m from rice irrigation sites (OR<sub>MH</sub> = 8.2, 95%CI 1.8-36); and 23 (28%) case-patients and four (5%) controls had water pools <100m from household for 3-5 days after rainfall (OR<sub>MH</sub> = 7.3, 95%CI 2.2-25). Twenty three (28%) case-patients and four (5%) controls did not sleep under bed nets the previous night (OR<sub>MH</sub> = 20, 95%CI 2.7-149); 68 (82%) case-patients and 43(52%) controls did not wear long-sleeved clothes during evenings (OR<sub>MH</sub> = 9.3, 95%CI 2.8-31). Indoor resting vector density was 4.7 female mosquitoes/household/night. All Anopheles aquatic habitats had Anopheles larvae. Weekly rainfall in 2019 was heavier (6.0+or-7.2 mm) than same period in 2018 (1.8+or-1.8 mm) (p = 0.006). This outbreak was facilitated by Anopheles aquatic habitats near homes created by human activities, following increased rainfall compounded by inadequate use of individual preventive measures. We recommended awareness on use of insecticide-treated bed nets, protective clothing, and avoiding creation of Anopheles aquatic habitats.

    • Physical Activity
      1. BMI and physical activity, military-aged U.S. Population 2015-2020
        Webber BJ, Bornstein DB, Deuster PA, O'Connor FG, Park S, Rose KM, Whitfield GP.
        Am J Prev Med. 2022 Sep 22.
        INTRODUCTION: Obesity and physical inactivity are considered possible U.S. national security threats because of their impact on military recruitment. The objectives of this study were to estimate the prevalence of (1) BMI eligibility for military entrance, (2) adequate physical activity participation among the BMI-eligible population, and (3) combined BMI eligibility and adequate physical activity. METHODS: This cross-sectional study of nonpregnant, military-aged civilians (aged 17-42 years) used objectively measured weight and height data and self-reported aerobic physical activity data from the 2015-2020 National Health and Nutrition Examination Survey. BMI eligibility was defined as 19.0-27.5 kg/m(2), per Department of Defense regulation. Adequate physical activity for entering initial military training was defined as ≥300 minutes/week of equivalent moderate-intensity aerobic physical activity from all domains, approximating U.S. Army guidance. Participants meeting both definitions were further classified as eligible and active. Analyses were conducted in 2021-2022. RESULTS: Of military-aged participants (unweighted n=5,964), 47.3% were eligible by BMI. Among BMI-eligible participants, 72.5% reported adequate physical activity. Taken together, 34.3% were both eligible and active. The prevalence of eligible and active status was higher among males, persons who were younger and non-Hispanic White, college graduates, and those with higher family income than among their counterparts. CONCLUSIONS: Among the military-aged U.S. population, slightly under half were eligible to enter the military on the basis of their BMI, and only 1 in 3 met BMI eligibility and were adequately physically active. Equitable promotion of healthy weight achievement and physical activity participation may improve military preparedness.

    • Reproductive Health
      1. Acceptability of an intravaginal ring for simultaneously preventing HIV infection and pregnancy: Qualitative findings of the Kisumu combined ring study, 2019
        McLellan-Lemal E, Deaton SR, Betts JE, Ondenge K, Mudhune V, O'Connor SM, Nyagol B, Thurman AR, Doncel GF, Allen SA, Heffron R, Mugo NR.
        Contemp Clin Trials. 2022 Sep 23:106935.
        Multipurpose prevention technology intravaginal rings (MPT IVRs) may offer a promising solution for addressing multiple women's sexual and reproductive health needs. We describe MPT IVR acceptability perspectives and examine user experiences of 25 cisgender women aged 18-3 years enrolled in a phase IIa randomized, partially blinded, placebo-controlled evaluation of tenofovir-based IVRs with and without contraceptive co-formulation. All took part in an individual, audio-recorded, semi-structured qualitative interview. A thematic analysis of transcribed interviews was completed in MaxQDA. Participants shared little or no knowledge of or experience with IVRs prior to joining the study. Four MPT IVR themes were identified: physical wellbeing, method reliability, personal management, and societal endorsement. Commonly cited of concern, but less described as being experienced, were physical discomforts (e.g., painful insertion/removal; inability to carry out daily activities/chores; foreign body sensation; expulsion; sexual interference, or debilitating side effects). Uncertainty regarding efficacy influenced perspectives about intended prevention benefits. Personal choices in managing reproduction and sexual behaviors had to be congruent with sociocultural values and norms for acceptance beyond the individual user level. Participants viewed broader community acceptance as likely to be mixed given community opposition to the use of modern family planning methods. They also shared concerns that IVR use could lead to infertility, especially among nulliparous women, or that it would encourage premarital sex or high-risk sexual behaviors among adolescent and young women. While a MPT IVR may not be suitable for all women, first-hand testimonials could help influence collective receptivity. Additional community acceptability research is needed. Clinical Trial Registration The study is registered at ClinicalTrials.gov under the identifier NCT03762382.

    • Substance Use and Abuse
      1. Increases in methamphetamine injection among treatment admissions in the U.S
        Jones CM, Han B, Seth P, Baldwin G, Compton WM.
        Addict Behav. 2022 Sep 17;136:107492.
        BACKGROUND: Prior research indicates rising methamphetamine use and harms in the U.S., potentially related to increases in methamphetamine injection. To date, research on trends and correlates of methamphetamine injection is limited. METHODS: Analysis of trends and correlates of methamphetamine injection among treatment admissions among persons aged ≥ 12 whose primary substance of use at admission is methamphetamine. Data are from the Treatment Episode Data Set. Analyses includes descriptive statistics, trend analyses, and multilevel multivariable logistic regression. RESULTS: Primary methamphetamine treatment admissions increased from 138,379 in 2010 to 201,021 in 2019. Among primary methamphetamine admissions, injection as the usual route of use increased from 24,821 (18.0 % of admissions) in 2010 to 55,951 (28.2 % of admissions) in 2019. Characteristics associated with increased adjusted odds of reporting methamphetamine injection included: males (aOR = 1.13, 95 % CI = 1.10-1.15); admission age 25-34 years (aOR = 1.23, 95 % CI = 1.19-1.28) and 35-44 years (aOR = 1.12, 95 % CI = 1.08-1.17) compared to age 18-24; dependent living (aOR = 1.33, 95 % CI = 1.29-1.37) and homelessness (aOR = 1.58, 95 % CI = 1.54-1.63) compared to independent living; part-time employment (aOR = 1.08, 95 % CI = 1.02-1.14), unemployment (aOR = 1.39, 95 % CI = 1.34-1.44) and not in labor force (aOR = 1.43, 95 % CI = 1.37-1.49) compared to full-time employment; one to ≥ four prior treatment admissions (aORs ranging from 1.19 to 1.94) compared to no prior admissions; also reporting use of cocaine (aOR = 1.10, 95 % CI = 1.05-1.16), heroin (aOR = 3.52, 95 % CI = 3.40-3.66), prescription opioids (aOR = 1.61, 95 % CI = 1.54-1.67), or benzodiazepines (aOR = 1.42, 95 % CI = 1.32-1.52) at treatment admission. CONCLUSIONS: Findings lend further evidence to a resurgence of methamphetamine use that is intertwined with the ongoing opioid crisis in the U.S. Efforts to expand evidence-based prevention, treatment, and response efforts, particularly to populations at highest risk, are urgently needed.

      2. Manipulation of menthol and nicotine content in cigarettes: Effects on smoking behavior and toxicant exposure in women menthol smokers
        Oncken C, Litt MD, Thurlow S, Mead-Morse EL, Wang L, Hatsukami DK.
        Nicotine Tob Res. 2022 Sep 26.
        BACKGROUND: The purpose of this study was to determine the effects on smoking and other outcomes of assigning cigarettes with reduced nicotine and/or no menthol to female menthol smokers. METHODS: Non-treatment seeking female menthol smokers (N=263) participated in a randomized controlled trial in which levels of menthol and nicotine in cigarettes were manipulated using experimental cigarettes. After a baseline period, participants were assigned to the following conditions for 6 weeks: 1) their own brand of cigarette (conventional nicotine with menthol); 2) a conventional nicotine cigarette with no menthol; 3) a cigarette with reduced nicotine (RNC) with menthol; or 4) a RNC cigarette and no menthol. Participants then returned to using their own brand and were followed for another 6 weeks. Outcomes included cigarettes smoked, biomarkers of exposure, and dependence measures. RESULTS: Results indicated that, after an initial increase, rates of smoking of all three experimental cigarettes were at or below baseline rates of smoking of one's own brand. Levels of biomarkers also decreased during the experimental phase, but rebounded somewhat after participants resumed smoking their own brand. There was evidence that overall amount of smoking decreased similarly among women switched to non-menthol and/or RNC cigarettes. CONCLUSIONS: These results suggest that no detrimental effect will occur in nicotine or toxicant exposure levels with a ban on characterizing menthol and/or a product standard on nicotine content in cigarettes. IMPLICATIONS: The implication of this work is that there would be no risk to women menthol smokers associated with regulations restricting nicotine and eliminating menthol in cigarettes.

      3. Availability and content of clinical guidance for tobacco use and dependence treatment - United States, 2000-2019
        VanFrank B, Uhd J, Savage TR, Shah JR, Twentyman E.
        Prev Med. 2022 Sep 22;164:107276.
        Evidence-based treatments for tobacco use and dependence can increase cessation success but remain underutilized. Health professional societies and voluntary health organizations (advising organizations) are uniquely positioned to influence the delivery of cessation treatments by providing clinical guidance for healthcare providers. This study aimed to review the guidance produced by these organizations for content and consistency with current evidence. Documents discussing healthcare providers' role in treatment of tobacco use and dependence produced by US-based advising organizations between 2000 and 2019 were identified in both peer-reviewed and grey (i.e., informally or non-commercially published) literature. Extraction of variables, defined in terms of healthcare provider role and endorsement of specific treatment(s), was completed by two independent reviewers. Review of 38 identified documents sponsored by 57 unique advising organizations revealed deficits in the direction of comprehensive care and incorporation of the most recent evidence for treatment of tobacco use and dependence. Documents endorsed: screening (74%), pharmacotherapy (68%), counseling (89%), or follow-up (37%). Few documents endorsed more recent evidence-based treatments including combination nicotine replacement therapy (18%), and text- (11%) and web-based (11%) interventions. Advising organizations have opportunities to address identified gaps and enhance clinical guidance to contribute toward expanding the provision of comprehensive tobacco cessation support.

    • Telehealth and Telemedicine
      1. Monitoring and evaluation platform for HEARTS in the Americas: improving population-based hypertension control programs in primary health care
        Prado P, Gamarra A, Rodriguez L, Brettler J, Farrell M, Girola ME, Malcolm T, Martinez R, Molina V, Moran AE, Neupane D, Rosende A, González YV, Mukhtar Q, Ordunez P.
        Rev Panam Salud Publica. 2022 ;46:e161.
        HEARTS in the Americas is the Pan American Health Organization flagship program to accelerate the reduction of the cardiovascular disease (CVD) burden by improving hypertension control and CVD secondary prevention in primary health care. A monitoring and evaluation (M&E) platform is needed for program implementation, benchmarking, and informing policy-makers. This paper describes the conceptual bases of the HEARTS M&E platform including software design principles, contextualization of data collection modules, data structure, reporting, and visualization. The District Health Information Software 2 (DHIS2) web-based platform was chosen to implement aggregate data entry of CVD outcome, process, and structural risk factor indicators. In addition, PowerBI was chosen for data visualization and dashboarding for the analysis of performance and trends above the health care facility level. The development of this new information platform was focused on primary health care facility data entry, timely data reporting, visualizations, and ultimately active use of data to drive decision-making for equitable program implementation and improved quality of care. Additionally, lessons learnt and programmatic considerations were assessed through the experience of the M&E software development. Building political will and support is essential to developing and deploying a flexible platform in multiple countries which is contextually specific to the needs of various stakeholders and levels of the health care system. The HEARTS M&E platform supports program implementation and reveals structural and managerial limitations and care gaps. The HEARTS M&E platform will be central to monitoring and driving further population-level improvements in CVD and other noncommunicable disease-related health.

    • Zoonotic and Vectorborne Diseases
      1. ICTV virus taxonomy profile: Hepeviridae 2022
        Purdy MA, Drexler JF, Meng XJ, Norder H, Okamoto H, Van der Poel WH, Reuter G, de Souza WM, Ulrich RG, Smith DB.
        J Gen Virol. 2022 Sep;103(9).
        The family Hepeviridae includes enterically transmitted small quasi-enveloped or non-enveloped positive-sense single-stranded RNA viruses infecting mammals and birds (subfamily Orthohepevirinae) or fish (Parahepevirinae). Hepatitis E virus (genus Paslahepevirus) is responsible for self-limiting acute hepatitis in humans; the infection may become chronic in immunocompromised individuals and extrahepatic manifestations have been described. Avian hepatitis E virus (genus Avihepevirus) causes hepatitis-splenomegaly syndrome in chickens. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Hepeviridae, which is available at www.ictv.global/report/hepeviridae.

      2. Detection of neutralizing antibodies against Zika virus in wild nonhuman primates in Rwanda
        Umuhoza T, Makio A, Hunsperger E, Mudakikwa A, Muvunyi R, Nziza J, Widdowson MA.
        J Wildl Dis. 2022 Sep 22.
        The range of nonhuman primate (NHP) species involved in Zika virus (ZIKV) sylvatic transmission is not known. We tested 97 NHP archived sera, collected from 2006 to 2016 in Rwandan National Parks, for neutralizing antibodies to ZIKV. Serum from one olive baboon (Papio anubis) was positive for ZIKV antibodies.

      3. Introduction: the Kenema District Surveillance team in Sierra Leone received notifications of patients with suspected Lassa fever on February 20th and March 2nd, 2019. On that day, an investigation started to confirm the diagnosis and search for additional cases. Methods: we used the Lassa fever surveillance case definition and collected demographic and exposure information from suspected cases through interviews and clinical records. Blood samples were collected from the cases to confirm the diagnosis. Active case finding was conducted in the community and health facility. Results: on February 10, 2019, an eight-year-old male developed a fever (&gt;39.5°C) and a sore throat. On February 18, 2019, he was admitted to a hospital and treated for malaria and pneumonia. On February 20, 2019, Lassa fever was suspected because the patient was bleeding from orifices and testing. On February 15, a 5-year-old female developed fever and headache and was treated with anti-malarial drugs. On February 26ththe high fever re-emerged with severe bleeding from the orifices. She was admitted and treated with antibiotics, confirmed for Lassa fever, and died on March 2, 2019. Conclusion: the two children had Lassa fever, and no additional cases were identified. We sensitized clinicians on suspicion of Lassa fever to improve early detection and treatment. © Umaru Sesay et al.

      4. Bovine polyomavirus-1 (Epsilonpolyomavirus bovis): An emerging fetal pathogen of cattle that causes renal lesions resembling polyomavirus-associated nephropathy of humans
        Giannitti F, da Silva Silveira C, Bullock H, Berón M, Fernández-Ciganda S, Benítez-Galeano MJ, Rodríguez-Osorio N, Silva-Flannery L, Perdomo Y, Cabrera A, Puentes R, Colina R, Ritter JM, Castells M.
        Viruses. 2022 Sep 14;14(9).
        Bovine polyomavirus-1 (BoPyV-1, Epsilonpolyomavirus bovis) is widespread in cattle and has been detected in commercialized beef at supermarkets in the USA and Germany. BoPyV-1 has been questioned as a probable zoonotic agent with documented increase in seropositivity in people exposed to cattle. However, to date, BoPyV-1 has not been causally associated with pathology or disease in any animal species, including humans. Here we describe and illustrate pathological findings in an aborted bovine fetus naturally infected with BoPyV-1, providing evidence of its pathogenicity and probable abortigenic potential. Our results indicate that: (i) BoPyV-1 can cause severe kidney lesions in cattle, including tubulointerstitial nephritis with cytopathic changes and necrosis in tubular epithelial cells, tubular and interstitial inflammation, and interstitial fibroplasia; (ii) lesions are at least partly attributable to active viral replication in renal tubular epithelial cells, which have abundant intranuclear viral inclusions; (iii) BoPyV-1 large T (LT) antigen, resulting from early viral gene expression, can be detected in infected renal tubular epithelial cells using a monoclonal antibody raised against Simian Virus-40 polyomavirus LT antigen; and (iv) there is productive BoPyV-1 replication and virion assembly in the nuclei of renal tubular epithelial cells, as demonstrated by the ultrastructural observation of abundant arrays of viral particles with typical polyomavirus morphology. Altogether, these lesions resemble the "cytopathic-inflammatory pathology pattern" proposed in the pathogenesis of Human polyomavirus-1-associated nephropathy in immunocompromised people and kidney allograft recipients. Additionally, we sequenced the complete genome of the BoPyV-1 infecting the fetus, which represents the first whole genome of a BoPyV-1 from the Southern Hemisphere. Lastly, the BoPyV-1 strain infecting this fetus was isolated, causing a cytopathic effect in Madin-Darby bovine kidney cells. We conclude that BoPyV-1 is pathogenic to the bovine fetus under natural circumstances. Further insights into the epidemiology, biology, clinical relevance, and zoonotic potential of BoPyV-1 are needed.


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