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Issue 37, September 13, 2022

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CDC Science Clips: Volume 14, Issue 37, September 13, 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. Discovery of substituted benzyloxy-benzylamine inhibitors of acetyltransferase Eis and their anti-mycobacterial activity
        Pang AH, Green KD, Chandrika NT, Garzan A, Punetha A, Holbrook SY, Willby MJ, Posey JE, Tsodikov OV, Garneau-Tsodikova S.
        Eur J Med Chem. 2022 Aug 18;242:114698.
        A clinically significant mechanism of tuberculosis resistance to the aminoglycoside kanamycin (KAN) is its acetylation catalyzed by upregulated Mycobacterium tuberculosis (Mtb) acetyltransferase Eis. In search for inhibitors of Eis, we discovered an inhibitor with a substituted benzyloxy-benzylamine scaffold. A structure-activity relationship study of 38 compounds in this structural family yielded highly potent (IC(50) ∼ 1 μM) Eis inhibitors, which did not inhibit other acetyltransferases. Crystal structures of Eis in complexes with three of the inhibitors showed that the inhibitors were bound in the aminoglycoside binding site of Eis, consistent with the competitive mode of inhibition, as established by kinetics measurements. When tested in Mtb cultures, two inhibitors (47 and 55) completely abolished resistance to KAN of the highly KAN-resistant strain Mtb mc(2) 6230 K204, likely due to Eis inhibition as a major mechanism. Thirteen of the compounds were toxic even in the absence of KAN to Mtb and other mycobacteria, but not to non-mycobacteria or to mammalian cells. This, yet unidentified mechanism of toxicity, distinct from Eis inhibition, will merit future studies along with further development of these molecules as anti-mycobacterial agents.

      2. Antibiotic prescribing for acute gastroenteritis during ambulatory care visits-United States, 2006-2015
        Collins JP, King LM, Collier SA, Person J, Gerdes ME, Crim SM, Bartoces M, Fleming-Dutra KE, Friedman CR, Francois Watkins LK.
        Infect Control Hosp Epidemiol. 2022 Aug 26:1-10.
        OBJECTIVE: To describe national antibiotic prescribing for acute gastroenteritis (AGE). SETTING: Ambulatory care. METHODS: We included visits with diagnoses for bacterial and viral gastrointestinal infections from the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey (NAMCS/NHAMCS; 2006-2015) and the IBM Watson 2014 MarketScan Commercial Claims and Encounters Database. For NAMCS/NHAMCS, we calculated annual percentage estimates and 99% confidence intervals (CIs) of visits with antibiotics prescribed; sample sizes were too small to calculate estimates by pathogen. For MarketScan, we used Poisson regression to calculate the percentage of visits with antibiotics prescribed and 95% CIs, including by pathogen. RESULTS: We included 10,210 NAMCS/NHAMCS AGE visits; an estimated 13.3% (99% CI, 11.2%-15.4%) resulted in antibiotic prescriptions, most frequently fluoroquinolones (28.7%; 99% CI, 21.1%-36.3%), nitroimidazoles (20.2%; 99% CI, 14.0%-26.4%), and penicillins (18.9%; 99% CI, 11.6%-26.2%). In NAMCS/NHAMCS, antibiotic prescribing was least frequent in emergency departments (10.8%; 99% CI, 9.5%-12.1%). Among 1,868,465 MarketScan AGE visits, antibiotics were prescribed for 13.8% (95% CI, 13.7%-13.8%), most commonly for Yersinia (46.7%; 95% CI, 21.4%-71.9%), Campylobacter (44.8%; 95% CI, 41.5%-48.1%), Shigella (39.7%; 95% CI, 35.9%-43.6%), typhoid or paratyphoid fever (32.7%; (95% CI, 27.2%-38.3%), and nontyphoidal Salmonella (31.7%; 95% CI, 29.5%-33.9%). Antibiotics were prescribed for 12.3% (95% CI, 11.7%-13.0%) of visits for viral gastroenteritis. CONCLUSIONS: Overall, ∼13% of AGE visits resulted in antibiotic prescriptions. Antibiotics were unnecessarily prescribed for viral gastroenteritis and some bacterial infections for which antibiotics are not recommended. Antibiotic stewardship assessments and interventions for AGE are needed in ambulatory settings.

      3. Tinea, a dermatophyte fungal infection, is a common outpatient complaint that is easily misdiagnosed by visual inspection. Antifungal-drug-resistant tinea is an emerging global public health problem, with several cases reported in the United States. We analyzed data from a Spring 2022 web-based survey of healthcare provider attitudes and practices. Among 1500 healthcare providers, only 20.1% reported typically using diagnostic testing for tinea, and 19.5% reported clinical experience with drug-resistant tinea. Drug-resistant tinea may be more widespread than previously recognized. However, the low frequency of diagnostic testing indicates potential misunderstanding or misdiagnosis of drug-resistant tinea and missed opportunities to detect drug-resistant cases.

    • Chronic Diseases and Conditions
      1. Vitamin D status and prevalence of metabolic syndrome by race and Hispanic origin in U.S. adults: findings from 2007-2014 NHANES
        Ahluwalia N, Raghavan R, Zhang G, Talegawkar SA, Jacques PF.
        Am J Clin Nutr. 2022 Aug 29.
        BACKGROUND: Vitamin D status has been found to be inversely associated with metabolic syndrome (MetS) in some studies. Vitamin D status varies by race and ethnicity, and the association of MetS with Vitamin D status in U.S. adults and by race and Hispanic origin has not been evaluated extensively. OBJECTIVES: To examine the associations between Vitamin D status and MetS overall, and across race and Hispanic origin groups in a nationally representative sample of U.S. adults who participated in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2014. DESIGN: The total sample included 8,639 adults, 20 years of age and over. Serum Vitamin D was measured using a standardized liquid chromatography-tandem mass spectrometry method and was categorized using data driven tertiles. MetS was defined using measured waist circumference, triglycerides, HDL cholesterol, blood pressure, and fasting glucose. Multivariable logistic regression models were fitted (accounting for sociodemographic and lifestyle factors, dietary supplement use, and BMI) to examine the associations of serum Vitamin D with MetS among adults overall, and by race and Hispanic origin. RESULTS: Serum Vitamin D in the lowest tertile (≤ 56 nmol/L) was significantly associated with increased odds of MetS compared to the highest tertile (> 77.9 nmol/L); fully adjusted model OR: 1.85 and 95% CI: 1.51, 2.27. Inverse associations were noted for all race-Hispanic origin groups: non-Hispanic White (OR: 2.24; and 95% CI: 1.67, 3.01), non-Hispanic Black (OR: 1.56; and 95% CI: 1.06, 2.29) and Hispanic (OR: 1.48; and 95% CI: 1.03, 2.14) adults. CONCLUSIONS: Lower Vitamin D status was significantly associated with MetS among U.S. adults after adjusting for sociodemographic and lifestyle factors, dietary supplement use, and BMI. This finding was noted across all race and Hispanic origin groups, although the strength of the association varied being strongest for non-Hispanic White adults.

      2. Advancing the role of neuroimmunity and genetic susceptibility in Gulf War Illness
        Sullivan K, O'Callaghan JP.
        Brain Sci. 2022 Aug 12;12(8).
        Gulf War Illness (GWI) is a chronic multi-symptom disorder affecting as many as 30% of veterans of the 1991 Gulf War [...].

      3. The burden of living with cutaneous lupus erythematosus
        Drenkard C, Barbour KE, Greenlund KJ, Lim SS.
        Front Med (Lausanne). 2022 ;9:897987.
        Cutaneous lupus erythematosus (CLE) is a group of heterogeneous autoimmune disorders primarily affecting the skin. Patients with these conditions are mostly young women when they become sick and often suffer from recurrent skin symptoms or longstanding changes in their physical appearance. CLE disorders lead to different levels of morbidity and can impact profoundly patients' quality of life, particularly in the psychological and social health domains. This review provides a summary of recent research investigating the psychosocial burden of living with CLE and the intersect amongst the disease characteristics, patient factors, and social determinants of health. Furthermore, this review provides insight into patient care and research needs that remain unmet to improve the quality of life of patients living with CLE.

      4. Maternal urinary organophosphate ester metabolite concentrations and glucose tolerance during pregnancy: The HOME Study
        Yang W, Braun JM, Vuong AM, Percy Z, Xu Y, Xie C, Deka R, Calafat AM, Ospina M, Yolton K, Cecil KM, Lanphear BP, Chen A.
        Int J Hyg Environ Health. 2022 Aug 24;245:114026.
        BACKGROUND: Endocrine-disrupting chemicals may alter glucose homeostasis, especially during pregnancy. Biomonitoring studies suggest ubiquitous human exposure to organophosphate esters (OPEs), chemicals with endocrine-disrupting capabilities. Few studies have examined the association between maternal exposure to OPEs and blood glucose during pregnancy. METHODS: With data from 301 pregnant women in the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort in Cincinnati, Ohio, USA, we examined whether OPE concentrations were associated with changes in blood glucose. We quantified four OPE metabolites in maternal spot urine samples collected at 16- and 26-weeks pregnancy. We extracted results from the glucose challenge test (GCT) and oral glucose tolerance test (OGTT) via medical chart review. Women with GCT ≥ 140 mg/dL or any abnormal values in OGTT (≥ 95 mg/dL fasting glucose, ≥ 180 mg/dL 1-h glucose, ≥ 155 mg/dL 2-h glucose, ≥ 140 mg/dL 3-h glucose) were defined as having elevated glucose levels. We used linear regression and Bayesian Kernel Machine Regression (BKMR) to estimate the associations of individual OPE metabolites and OPE mixtures with blood glucose levels during pregnancy. We used modified Poisson regression to estimate the associations of OPE metabolite concentrations with elevated glucose levels. We further examined effect measure modification by maternal characteristics (age, pre-pregnancy body mass index [BMI], and race/ethnicity). RESULTS: Diphenyl phosphate (DPHP) had the highest geometric mean concentration of the urinary OPE metabolites (1.83 μg/L at 16 weeks, 1.24 μg/L at 26 weeks). Thirty women (10.0%) had elevated glucose levels. Individual OPE metabolites or their mixtures were not significantly associated with continuous GCT results. We did not observe effect measure modification by maternal age, pre-pregnancy BMI categories, or race/ethnicity. Compared with women in the 1st tertile of average DPHP of 16- and 26 weeks of pregnancy, women in the 3rd tertile tended to have a reduced risk of elevated glucose levels (RR = 0.41, 95% CI = 0.16-1.06, p for trend = 0.06). CONCLUSION: In this cohort, maternal urinary OPE metabolite concentrations were weakly associated with blood glucose levels during pregnancy.

    • Communicable Diseases
      1. Epidemiological and viral characteristics of undiagnosed HIV infections in Botswana
        Bhebhe L, Moyo S, Gaseitsiwe S, Pretorius-Holme M, Yankinda EK, Manyake K, Kgathi C, Mmalane M, Lebelonyane R, Gaolathe T, Bachanas P, Ussery F, Letebele M, Makhema J, Wirth KE, Lockman S, Essex M, Novitsky V, Ragonnet-Cronin M.
        BMC Infect Dis. 2022 Aug 28;22(1):710.
        BACKGROUND: HIV-1 is endemic in Botswana. The country's primary challenge is identifying people living with HIV who are unaware of their status. We evaluated factors associated with undiagnosed HIV infection using HIV-1 phylogenetic, behavioural, and demographic data. METHODS: As part of the Botswana Combination Prevention Project, 20% of households in 30 villages were tested for HIV and followed from 2013 to 2018. A total of 12,610 participants were enrolled, 3596 tested HIV-positive at enrolment, and 147 participants acquired HIV during the trial. Extensive socio-demographic and behavioural data were collected from participants and next-generation sequences were generated for HIV-positive cases. We compared three groups of participants: (1) those previously known to be HIV-positive at enrolment (n = 2995); (2) those newly diagnosed at enrolment (n = 601) and (3) those who tested HIV-negative at enrolment but tested HIV-positive during follow-up (n = 147). We searched for differences in demographic and behavioural factors between known and newly diagnosed group using logistic regression. We also compared the topology of each group in HIV-1 phylogenies and used a genetic diversity-based algorithm to classify infections as recent (< 1 year) or chronic (≥ 1 year). RESULTS: Being male (aOR = 2.23) and younger than 35 years old (aOR = 8.08) was associated with undiagnosed HIV infection (p < 0.001), as was inconsistent condom use (aOR = 1.76). Women were more likely to have undiagnosed infections if they were married, educated, and tested frequently. For men, being divorced increased their risk. The genetic diversity-based algorithm classified most incident infections as recent (75.0%), but almost none of known infections (2.0%). The estimated proportion of recent infections among new diagnoses was 37.0% (p < 0.001). CONCLUSION: Our results indicate that those with undiagnosed infections are likely to be young men and women who do not use condoms consistently. Among women, several factors were predictive: being married, educated, and testing frequently increased risk. Men at risk were more difficult to delineate. A sizeable proportion of undiagnosed infections were recent based on a genetic diversity-based classifier. In the era of "test and treat all", pre-exposure prophylaxis may be prioritized towards individuals who self-identify or who can be identified using these predictors in order to halt onward transmission in time.

      2. Optimising neonatal antiretroviral therapy using raltegravir: a qualitative analysis of healthcare workers' and caregivers' perspectives
        Katirayi L, Stecker C, Andifasi P, Mushavi A, Tiwari P, Jakazi C, Maphosa T, Thorsen V, Murandu M, Gombakomba G, Mungati M, Denoeud-Ndam L, Rivadeneira E, Weber R, Hrapcak S.
        BMJ Paediatr Open. 2022 ;6(1).
        Background In 2020, Zimbabwe adopted the WHO's recommendation to use raltegravir (RAL) granule-based regimens for treatment of neonates identified with HIV at the time of birth testing. This study explores the acceptability of RAL granules by caregivers and healthcare workers (HCWs). Methods Interviews were conducted with 15 caregivers and 12 HCWs from 8 health facilities in Zimbabwe participating in the introductory pilot of RAL granules treatment for newborns. Eligible caregivers included those who had administered RAL to their infant and attended either 8th or 28th day of life appointments. Caregivers of neonates recently initiated on RAL were selected through convenience sampling. Eligible HCWs who provided RAL preparation, administration instructions and support to caregivers of neonates on RAL for at least 3 months were recruited from the same facilities as the caregivers. Interview transcripts were coded and thematically analysed. Results Caregivers reported that their babies looked healthier after RAL initiation, with improved skin appearance and weight gain. Some caregivers wanted their child to remain on RAL beyond 28 days instead of switching regimens, as recommended by national guidelines. HCWs observed that RAL granules improved health outcomes compared with other regimens. HCWs reported challenges with caregivers understanding dosing instructions, measuring with a syringe, swirling and not shaking the medicine, discarding unused medication and following the changes in the dosing schedule and amount when RAL was initiated a few days after birth. HCWs stated that adequate counselling and repeat demonstrations were crucial to ensure that caregivers clearly understood RAL dosing and administration instructions. HCWs requested more standardised training targeting nurses with guidance on handling missed doses and clarification on mixing RAL granules with water and not breastmilk. Conclusion While feedback from caregivers and HCWs on RAL implementation was positive, barriers were also noted. Adequate training and sufficient instruction and support for caregivers would help to ensure that RAL granules are prepared, dosed and administered correctly. © Author(s) (or their employer(s)) 2022.

      3. Reinfection with severe acute respiratory syndrome coronavirus 2 among previously infected healthcare personnel and first responders
        Akinbami LJ, Biggerstaff BJ, Chan PA, McGibbon E, Pathela P, Petersen LR.
        Clin Infect Dis. 2022 Aug 24;75(1):e201-e207.
        BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus testing among first responders and healthcare personnel who participated in a May 2020-August 2020 serosurvey that assessed spike protein antibodies provided an opportunity to assess reinfection. METHODS: Serology survey data were merged with virus testing results from Rhode Island (1 March 2020-17 February 2021) and New York City (10 March 2020-14 December 2020). Participants with a positive virus test ≥14 days before their serology test were included. Reinfection was defined as a second positive SARS-CoV-2 test ≥90 days after the first positive test. The association between serostatus and reinfection was assessed with a proportional hazards model. RESULTS: Among 1572 previously infected persons, 40 (2.5%) were reinfected. Reinfection differed by serostatus: 8.4% among seronegative vs 1.9% among seropositive participants (P < .0001). Most reinfections occurred among Rhode Island nursing home and corrections personnel (n = 30) who were most frequently tested (mean 30.3 tests vs 4.6 for other Rhode Island and 2.3 for New York City participants). The adjusted hazard ratio (aHR) for reinfection in seropositive vs seronegative persons was 0.41 (95% confidence interval [CI], .20-.81). Exposure to a household member with coronavirus disease 2019 (COVID-19) before the serosurvey was also protective (aHR, 0.34; 95% CI, .13-.89). CONCLUSIONS: Reinfections were uncommon among previously infected persons over a 9-month period that preceded widespread variant circulation. Seropositivity decreased reinfection risk. Lower reinfection risk associated with exposure to a household member with COVID-19 may reflect subsequently reduced household transmission.

      4. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta outbreak among fully vaccinated nursing home residents likely initiated by a fully vaccinated staff member - Connecticut, July-August 2021
        Bart SM, Harizaj A, Pearson CL, Conteh T, Grogan E, Downing R, Kirking HL, Tate JE, Jernigan JA, Leung V.
        Clin Infect Dis. 2022 Aug 24;75(1):e909-e911.
        During July-August 2021, a coronavirus disease 2019 (COVID-19) outbreak involving 21 residents (all fully vaccinated) and 10 staff (9 fully vaccinated) occurred in a Connecticut nursing home. The outbreak was likely initiated by a fully vaccinated staff member and propagated by fully vaccinated persons. Prior COVID-19 was protective among vaccinated residents.

      5. Multisystem inflammatory syndrome in adults after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) vaccination
        Belay ED, Godfred Cato S, Rao AK, Abrams J, Wyatt Wilson W, Lim S, Newton-Cheh C, Melgar M, DeCuir J, Webb B, Marquez P, Su JR, Meng L, Grome HN, Schlaudecker E, Talaat K, Edwards K, Barnett E, Campbell AP, Broder KR, Bamrah Morris S.
        Clin Infect Dis. 2022 Aug 24;75(1):e741-e748.
        BACKGROUND: Multisystem inflammatory syndrome in adults (MIS-A) was reported in association with the coronavirus disease 2019 (COVID-19) pandemic. MIS-A was included in the list of adverse events to be monitored as part of the emergency use authorizations issued for COVID-19 vaccines. METHODS: Reports of MIS-A patients received by the Centers for Disease Control and Prevention (CDC) after COVID-19 vaccines became available were assessed. Data collected on the patients included clinical and demographic characteristics and their vaccine status. The Vaccine Adverse Events Reporting System (VAERS) was also reviewed for possible cases of MIS-A. RESULTS: From 14 December 2020 to 30 April 2021, 20 patients who met the case definition for MIS-A were reported to CDC. Their median age was 35 years (range, 21-66 years), and 13 (65%) were male. Overall, 16 (80%) patients had a preceding COVID-19-like illness a median of 26 days (range 11-78 days) before MIS-A onset. All 20 patients had laboratory evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Seven MIS-A patients (35%) received COVID-19 vaccine a median of 10 days (range, 6-45 days) before MIS-A onset; 3 patients received a second dose of COVID-19 vaccine 4, 17, and 22 days before MIS-A onset. Patients with MIS-A predominantly had gastrointestinal and cardiac manifestations and hypotension or shock. CONCLUSIONS: Although 7 patients were reported to have received COVID-19 vaccine, all had evidence of prior SARS-CoV-2 infection. Given the widespread use of COVID-19 vaccines, the lack of reporting of MIS-A associated with vaccination alone, without evidence of underlying SARS-CoV-2 infection, is reassuring.

      6. BACKGROUND: Uptake of HIV pre-exposure prophylaxis (PrEP) has been increasing in the United States since its FDA approval in 2012; however, the COVID-19 pandemic may have affected this trend. Our objective was to assess the impact of COVID-19 on PrEP prescriptions in the United States. METHODS: We analyzed data from a national pharmacy database from January 2017 through March 2021 to fit an interrupted time-series model that predicted PrEP prescriptions and new PrEP users had the pandemic not occurred. Observed PrEP prescriptions and new users were compared with those predicted by the model. Main outcomes were weekly numbers of PrEP prescriptions and new PrEP users based on a previously developed algorithm. The impact of the COVID-19 pandemic was quantified by computing rate ratios and percentage decreases between the observed and predicted counts during 15/3/2020-31/3/2021. RESULTS: In the absence of the pandemic, our model predicted that there would have been 1 058 162 PrEP prescriptions during 15/3/2020-31/3/2021. We observed 825 239 PrEP prescriptions, a 22.0% reduction (95% CI: 19.1-24.8%) after the emergency declaration. The model predicted 167 720 new PrEP users during the same period; we observed 125 793 new PrEP users, a 25.0% reduction (95% CI: 20.9-28.9%). The COVID-19 impact was greater among younger persons and those with commercial insurance. The impact of the pandemic varied markedly across states. CONCLUSIONS: The COVID-19 pandemic disrupted an increasing trend in PrEP prescriptions in the United States, highlighting the need for innovative interventions to maintain access to HIV-prevention services during similar emergencies.


      8. Rifapentine with and without moxifloxacin for pulmonary tuberculosis in people with HIV (S31/A5349)
        Pettit AC, Phillips PP, Kurbatova E, Vernon A, Nahid P, Dawson R, Dooley KE, Sanne I, Waja Z, Mohapi L, Podany AT, Samaneka W, Savic RM, Johnson JL, Muzanyi G, Lalloo UG, Bryant K, Sizemore E, Scott N, Dorman SE, Chaisson RE, Swindells S.
        Clin Infect Dis. 2022 Aug 30.
        BACKGROUND: Tuberculosis (TB) Trials Consortium Study 31/AIDS Clinical Trials Group A5349, an international randomized open-label phase 3 non-inferiority trial showed that a 4-month daily regimen substituting rifapentine for rifampin and moxifloxacin for ethambutol had non-inferior efficacy and was safe for the treatment of drug-susceptible pulmonary TB (DS-PTB) compared with the standard 6-month regimen. We explored results among the pre-specified subgroup of people with HIV (PWH). METHODS: PWH and CD4 + counts ≥100 cells/μL were eligible if they were receiving or about to initiate efavirenz-based antiretroviral therapy (ART). Primary endpoints of TB disease-free survival 12 months post-randomization (efficacy) and ≥ grade 3 adverse events (AEs) on treatment (safety) were compared, using a 6.6% non-inferiority margin for efficacy. Randomization was stratified by site, pulmonary cavitation, and HIV-status. PWH were enrolled in a staged fashion, to support cautious evaluation of drug-drug interactions between rifapentine and efavirenz. RESULTS: 2,516 participants from 13 countries in sub-Saharan Africa, Asia, and the Americas were enrolled. Among 194 (8%) microbiologically eligible PWH, the median CD4 + count was 344 cells/μL (interquartile range: 223-455). The rifapentine-moxifloxacin regimen was non-inferior to control (absolute difference in unfavorable outcomes -7.4% [95% CI -20.8% to +6.0%]); the rifapentine regimen was not non-inferior to control (+7.5% [95% CI -7.3% to +22.4%]). Fewer AEs were reported in rifapentine-based regimens (15%) than the control regimen (21%). CONCLUSIONS: In people with HIV-associated DS-PTB with CD4 + counts ≥100 cells/μL on efavirenz-based ART, the 4-month daily rifapentine-moxifloxacin regimen was non-inferior to the 6-month control regimen and was safe.

      9. Primary and secondary attack rates by vaccination status after a SARS-CoV-2 B.1.617.2 (Delta) variant outbreak at a youth summer camp - Texas, June 2021
        Baker JM, Shah MM, O'Hegarty M, Pomeroy M, Keiser P, Ren P, Weaver SC, Maknojia S, Machado RR, Mitchell BM, McConnell A, Tate JE, Kirking HL.
        J Pediatric Infect Dis Soc. 2022 Aug 31.
        Children are capable of initiating COVID-19 transmission into households, but many questions remain about the impact of vaccination on transmission. Data from a COVID-19 Delta variant outbreak at an overnight camp in Texas during June 23-27, 2021 were analyzed. The camp had 451 attendees, including 364 youths aged <18 years and 87 adults. Detailed interviews were conducted with 92 (20.4%) of consenting attendees and 117 household members of interviewed attendees with COVID-19. Among 450 attendees with known case status, the attack rate was 41%, including 42% among youths; attack rates were lower among vaccinated (13%) than among unvaccinated youths (48%). The secondary attack rate was 51% among 115 household contacts of 55 interviewed index patients. Secondary infections occurred in 67% of unvaccinated household members and 33% of fully or partially vaccinated household members. Analyses suggested that household member vaccination and camp attendee masking at home protected against household transmission.

      10. Assessment of clinical and virological characteristics of SARS-CoV-2 infection among children aged 0 to 4 years and their household members
        Karron RA, Hetrich MK, Na YB, Knoll MD, Schappell E, Meece J, Hanson E, Tong S, Lee JS, Veguilla V, Dawood FS.
        JAMA Netw Open. 2022 Aug 1;5(8):e2227348.
        IMPORTANCE: Few studies have prospectively assessed SARS-CoV-2 community infection in children aged 0 to 4 years. Information about SARS-CoV-2 incidence and clinical and virological features in young children could help guide prevention and mitigation strategies. OBJECTIVE: To assess SARS-CoV-2 incidence, clinical and virological features, and symptoms in a prospective household cohort and to compare viral load by age group, symptoms, and SARS-CoV-2 lineage in young children, older children, and adults. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study enrolled 690 participants from 175 Maryland households with 1 or more children aged 0 to 4 years between November 24, 2020, and October 15, 2021. For 8 months after enrollment, participants completed weekly symptom questionnaires and submitted self-collected nasal swabs for SARS-CoV-2 qualitative real-time reverse transcriptase polymerase chain reaction (RT-PCR) testing, quantitative RT-PCR testing, and viral lineage determination. For the analyses, SARS-CoV-2 Alpha and Delta lineages were considered variants of interest or concern. Sera collected at enrollment and at approximately 4 months and 8 months after enrollment were assayed for SARS-CoV-2 spike and nucleocapsid protein antibodies. MAIN OUTCOMES AND MEASURES: Incidence, clinical and virological characteristics, and symptoms of SARS-CoV-2 infection by age group and correlations between (1) highest detected viral load and symptom frequency and (2) highest detected viral load and SARS-CoV-2 lineage. RESULTS: Among 690 participants (355 [51.4%] female and 335 [48.6%] male), 256 individuals (37.1%) were children aged 0 to 4 years, 100 (14.5%) were children aged 5 to 17 years, and 334 (48.4%) were adults aged 18 to 74 years. A total of 15 participants (2.2%) were Asian, 24 (3.5%) were Black, 603 (87.4%) were White, 43 (6.2%) were multiracial, and 5 (0.7%) were of other races; 33 participants (4.8%) were Hispanic, and 657 (95.2%) were non-Hispanic. Overall, 54 participants (7.8%) had SARS-CoV-2 infection during the surveillance period, including 22 of 256 children (8.6%) aged 0 to 4 years, 11 of 100 children (11.0%) aged 5 to 17 years, and 21 of 334 adults (6.3%). Incidence rates per 1000 person-weeks were 2.25 (95% CI, 1.28-3.65) infections among children aged 0 to 4 years, 3.48 (95% CI, 1.59-6.61) infections among children aged 5 to 17 years, and 1.08 (95% CI, 0.52-1.98) infections among adults. Children aged 0 to 17 years with SARS-CoV-2 infection were more frequently asymptomatic (11 of 30 individuals [36.7%]) compared with adults (3 of 21 individuals [14.3%]), with children aged 0 to 4 years most frequently asymptomatic (7 of 19 individuals [36.8%]). The highest detected viral load did not differ between asymptomatic vs symptomatic individuals overall (median [IQR], 2.8 [1.5-3.3] log10 copies/mL vs 2.8 [1.8-4.4] log10 copies/mL) or by age group (median [IQR] for ages 0-4 years, 2.7 [2.4-4.4] log10 copies/mL; ages 5-17 years: 2.4 [1.1-4.0] log10 copies/mL; ages 18-74 years: 2.9 [1.9-4.6] log10 copies/mL). The number of symptoms was significantly correlated with viral load among adults (R = 0.69; P < .001) but not children (ages 0-4 years: R = 0.02; P = .91; ages 5-17 years: R = 0.18; P = .58). The highest detected viral load was greater among those with Delta variant infections (median [IQR], 4.4 [3.9-5.1] log10 copies/mL) than those with infections from variants not of interest or concern (median [IQR], 1.9 [1.1-3.6] log10 copies/mL; P = .009) or those with Alpha variant infections (median [IQR], 2.6 [2.3-3.4] log10 copies/mL; P = .006). CONCLUSIONS AND RELEVANCE: In this study, SARS-CoV-2 infections were frequently asymptomatic among children aged 0 to 4 years; the presence and number of symptoms did not correlate with viral load. These findings suggest that symptom screening may be insufficient to prevent outbreaks involving young children.

      11. High-contact object and surface contamination in a household of persons with Monkeypox Virus Infection - Utah, June 2022
        Pfeiffer JA, Collingwood A, Rider LE, Minhaj FS, Matheny AM, Kling C, McCollum AM, Nolen LD, Morgan CN.
        MMWR Morb Mortal Wkly Rep. 2022 Aug 26;71(34):1092-1094.
        In May 2022, the Salt Lake County Health Department reported two real-time polymerase chain reaction (PCR)-confirmed travel-associated cases of monkeypox to the Utah Department of Health and Human Services (UDHHS). The two persons with monkeypox (patients A and B) lived together without other housemates. Both persons experienced prodromal symptoms (e.g., fatigue and body aches). Eight days after symptom onset, patient A experienced penile lesions; lesions spread to the lips, hands, legs, chest, and scalp by day 10. Patient B experienced prodromal symptoms 8 days after illness onset of patient A; patient B experienced a lesion on the foot which spread to the leg and finger by day 11. Although both patients had lesions in multiple anatomic areas, the overall number of lesions was small, and lesions varied in presentation from "pimple-like" or ulcerated, to characteristically well-circumscribed and centrally umbilicated. Both patients had mild illness. The time from symptom onset to resolution was approximately 30 days for patient A and approximately 22 days for patient B.

      12. Performance of HIV rapid testing algorithm in Nigeria: findings from a household-based Nigeria HIV/AIDS Indicator and Impact Survey (NAIIS)
        Patel HK, Ikpe S, Bronson M, Birhanu S, Abimiku A, Jahun I, Detorio M, Lupoli K, Yavo D, Bassey OO, Jelpe TD, Kagurusi B, Iriemenam NC, Patel D, Okoye MI, Dalhatu IT, Ohakanu S, Voetsch AC, Aliyu S, Ashefor G, Gambo A, Ikwulono GO, Nzelu C, Adewole IF, Swaminathan M, Parekh B.
        PLOS Glob Public Health. 2022 ;2(7).
        Background: The Nigeria AIDS Indicator and Impact Survey (NAIIS), a cross-sectional household survey, was conducted in 2018 with primary objectives to estimate HIV prevalence, HIV-1 incidence, and status of UNAIDS 90-90-90 cascade. We conducted retrospective analysis of the performance of HIV rapid tests and the national HIV testing algorithm used in Nigeria.

      13. OBJECTIVES: Older adults represent nearly half of people living with HIV in the United States. The objective of this analysis was to describe HIV testing, demographic characteristics, and risks of adults aged ≥50 years (older adults) reached in 2019 by HIV testing programs funded by the Centers for Disease Control and Prevention (CDC). METHODS: We collected data from 101 CDC-funded community-based organizations and 61 health departments. All funding recipients submitted deidentified program service data for 2019 through a secure online CDC-supported system. We used multivariable robust Poisson regression to assess the association between demographic and risk characteristics and the proportion of tests that resulted in a new diagnosis. We also assessed the proportion of people who received a positive test result, were linked to HIV medical care, and were interviewed for partner services. RESULTS: During 2019, among 2 452 507 CDC-funded HIV tests provided in the United States, 412 164 (16.8%) were provided to older adults. Among the 1059 (0.26% positivity) older adults with newly diagnosed HIV infection for whom we had data, 582 (68.4%) were linked to HIV medical care within 30 days of diagnosis and 494 (72.1%) were interviewed for partner services. Among the 2858 older adults with previously diagnosed HIV infection, 1321 (46.2%) reported not being in HIV medical care at the time of the test; of those with linkage data, 425 (49.9%) were linked to HIV medical care within 30 days of testing HIV positive. CONCLUSIONS: More rapid disease progression and higher morbidity and mortality rates among older adults suggest that services are needed to ensure early diagnosis, rapid linkage, and interview for partner services.

      14. Rotavirus strain trends in United States, 2009-2016: Results from the National Rotavirus Strain Surveillance System (NRSSS)
        Mijatovic-Rustempasic S, Jaimes J, Perkins C, Ward ML, Esona MD, Gautam R, Lewis J, Sturgeon M, Panjwani J, Bloom GA, Miller S, Reisdorf E, Riley AM, Pence MA, Dunn J, Selvarangan R, Jerris RC, DeGroat D, Parashar UD, Cortese MM, Bowen MD.
        Viruses. 2022 Aug 15;14(8).
        Before the introduction of vaccines, group A rotaviruses (RVA) were the leading cause of acute gastroenteritis in children worldwide. The National Rotavirus Strain Surveillance System (NRSSS) was established in 1996 by the Centers for Disease Control and Prevention (CDC) to perform passive RVA surveillance in the USA. We report the distribution of RVA genotypes collected through NRSSS during the 2009-2016 RVA seasons and retrospectively examine the genotypes detected through the NRSSS since 1996. During the 2009-2016 RVA seasons, 2134 RVA-positive fecal specimens were sent to the CDC for analysis of the VP7 and VP4 genes by RT-PCR genotyping assays and sequencing. During 2009-2011, RVA genotype G3P[8] dominated, while G12P[8] was the dominant genotype during 2012-2016. Vaccine strains were detected in 1.7% of specimens and uncommon/unusual strains, including equine-like G3P[8] strains, were found in 1.9%. Phylogenetic analyses showed limited VP7 and VP4 sequence variation within the common genotypes with 1-3 alleles/lineages identified per genotype. A review of 20 years of NRSSS surveillance showed two changes in genotype dominance, from G1P[8] to G3P[8] and then G3P[8] to G12P[8]. A better understanding of the long-term effects of vaccine use on epidemiological and evolutionary dynamics of circulating RVA strains requires continued surveillance.

    • Community Health Services
      1. The impact of community-based testing sites and gift incentives on COVID-19 testing uptake in Maryland, April 29 - May 9, 2021
        Turbyfill C, Thomas I, Agravat N, Prasher JM, Nett RJ, Stevens M, Ricaldi JN, Dunams TM, Brickhouse-Frazier L, Carter MD, Gebru Y, King A, May CS, Miller JD, Oguh C, Pullman A, Roman K, Rose C, Scherr R, Sidibe T, Soelaeman R, Weinstein J, Wilson T, Tran CH.
        Am J Health Promot. 2022 Aug 25:8901171221119796.
        PURPOSE: Information on incentives for COVID-19 testing is needed to understand effective practices that encourage testing uptake. We describe characteristics of those who received an incentive after performing a rapid antigen test. DESIGN: Cross-sectional descriptive analysis of survey data. SETTING: During April 29-May 9, 2021, COVID-19 rapid antigen testing was offered in 2 Maryland cities. SAMPLE: Convenience sample of 553 adults (≥18 years) who tested and received an incentive; 93% consented to survey. MEASURES: Survey questions assessed reasons for testing, testing history, barriers, and demographics. ANALYSIS: Robust Poisson regressions were used to determine characteristic differences based on testing history and between participants who would re-test in the future without an incentive vs participants who would not. RESULTS: The most common reasons for testing were the desire to be tested (n = 280; 54%) and convenience of location (n = 146; 28%). Those motivated by an incentive to test (n = 110; 21%) were 5.83 times as likely to state they would not test again without an incentive, compared to those with other reasons for testing (95% CI: 2.67-12.72, P < .001). CRITICAL LIMITATIONS: No comparative study group. CONCLUSION: Results indicate internal motivation and convenience were prominent factors supporting testing uptake. Incentives may increase community testing participation, particularly among people who have never tested. Keywords COVID-19, pandemic, incentives, health behavior, community testing.

      2. Declines in the utilization of hospital-based care during COVID-19 pandemic
        Kazakova SV, Baggs J, Parra G, Yusuf H, Romano SD, Ko JY, Harris AM, Wolford H, Rose A, Reddy SC, Jernigan JA.
        J Hosp Med. 2022 Aug 29.
        The disruptions of the coronavirus disease 2019 (COVID-19) pandemic impacted the delivery and utilization of healthcare services with potential long-term implications for population health and the hospital workforce. Using electronic health record data from over 700 US acute care hospitals, we documented changes in admissions to hospital service areas (inpatient, observation, emergency room [ER], and same-day surgery) during 2019-2020 and examined whether surges of COVID-19 hospitalizations corresponded with increased inpatient disease severity and death rate. We found that in 2020, hospitalizations declined by 50% in April, with greatest declines occurring in same-day surgery (-73%). The youngest patients (0-17) experienced largest declines in ER, observation, and same-day surgery admissions; inpatient admissions declined the most among the oldest patients (65+). Infectious disease admissions increased by 52%. The monthly measures of inpatient case mix index, length of stay, and non-COVID death rate were higher in all months in 2020 compared with respective months in 2019.

      3. "They are our eyes outside there in the community": Implementing enhanced training, management and monitoring of South Africa's ward-based primary healthcare outreach teams
        Mantell JE, Masvawure TB, Zech JM, Reidy W, Msukwa M, Glenshaw M, Grund J, Williams D, Pitt B, Rabkin M.
        PLoS One. 2022 ;17(8):e0266445.
        INTRODUCTION: In 2018, South Africa's National Department of Health provided additional resources for ward-based primary healthcare outreach teams (OT) with support from the U.S. President's Emergency Plan for AIDS Relief. The intervention package included a new training curriculum, enhanced staffing, revised management and supervisory structures, and more intensive monitoring and evaluation (M&E). The goal was to strengthen OT and their impact on both primary healthcare and HIV-specific services. We conducted a process evaluation of this intervention package during its second year and examined implementation successes and challenges. METHODS: We conducted a mixed-methods evaluation at 20 purposively selected facilities in Bojanala and City of Tshwane districts, including surveys with 222 community health workers (CHWs) and outreach team leaders (OTLs); key informant interviews and online surveys with 28 policy and program stakeholders; 70 in-depth interviews with health facility staff; 20 focus group discussions with 194 CHWs; 20 structured health facility assessments; directly-observed time-motion studies; and review of program documents. RESULTS: Most participants highlighted the hiring and training of CHWs and OTLs as a key implementation success because this had partially alleviated staffing shortages and helped clarify CHWs' and OTLs' responsibilities and supervisory structures. The new monitoring tools were welcomed for their potential to improve data collection and program tracking. However, participants highlighted many program challenges: short-lived gains in CHWs' knowledge and skills due to lack of ongoing training and mentoring; insufficient integration of OT into health facility management structures; persistent shortages of equipment, supplies, transportation, and workspace for CHWs; and insufficient remuneration for staff. CONCLUSION: Strengthening and expanding CHW programs, such as OT, requires intensive support and continuous investments. To sustain improvements in training, supervision, and job satisfaction, CHWs must be equipped with needed resources, provided with ongoing supportive supervision, and strengthened by optimized program management, monitoring and processes.

      4. Digital tools adopted by public health agencies to support COVID-19 case investigation and contact tracing, United States, 2020-2021
        Surio P, McLean JE, Jain A, Chughtai Z, Ruebush E, Lane JT, Ali H, Pina J.
        Public Health Rep. 2022 Aug 30:333549221116136.
        During the COVID-19 pandemic, public health agencies implemented an array of technologies and digital tools to support case investigation and contact tracing. Beginning in May 2020, the Association of State and Territorial Health Officials compiled information on digital tools used by its membership, which comprises 59 chief health officials from each of the 50 states, 5 US territories, 3 freely associated states, and the District of Columbia. This information was presented online through a publicly available technology and digital tools inventory. We describe the national landscape of digital tools implemented by public health agencies to support functions of the COVID-19 response from May 2020 through May 2021. We also discuss how public health officials and their informatics leadership referenced the information about the digital tools implemented by their peers to guide and refine their own implementation plans. We used a consensus-based approach through monthly discussions with partners to group digital tools into 5 categories: surveillance systems, case investigation, proximity technology/exposure notification, contact tracing, and symptom tracking/monitoring. The most commonly used tools included the National Electronic Disease Surveillance System Base System (NBS), Sara Alert, REDCap, and Maven. Some tools such as NBS, Sara Alert, REDCap, Salesforce, and Microsoft Dynamics were repurposed or adapted for >1 category. Having access to the publicly available technology and digital tools inventory provided public health officials and their informatics leadership with information on what tools other public health agencies were using and aided in decision making as they considered repurposing existing tools or adopting new ones.

      5. Current and emerging trends in diabetes care and education: 2021 National Practice and Workforce Survey
        Kavookjian J, Bzowyckyj AS, DiNardo MM, Kocurek B, Kolb LE, Noe D, Ryan D, Saunders MM, See M, Uelmen S.
        Sci Diabetes Self Manag Care. 2022 Aug 30:26350106221120787.
        PURPOSE: The purpose of the National Practice Survey is to understand current trends related to the diabetes care and education specialist's integration into the full care team beyond formal diabetes self-management education and support services. METHODS: The 2021 National Practice Survey (NPS2021) contained 61 questions for all respondents with an additional 56 questions pertaining to specific diabetes care and education segments. An anonymous survey was administered online to respondents who are diabetes care and education specialists or a part of the diabetes care team. Email lists were obtained from the Association of Diabetes Care & Education Specialists (ADCES) and the Certification Board for Diabetes Care and Education (CBDCE). Approximately 39,258 emails were sent, and 3357 were undeliverable, with 3797 surveys completed between February 9 to April 6, 2021, resulting in an 11% response rate. The response rate may have been affected by the COVID-19 public health emergency. RESULTS: Diabetes care and education specialists represent an interprofessional specialty of nurses, dietitians, physicians, pharmacists, health educators, and others. Many respondents reported holding either certification as a Certified Diabetes Care and Education Specialist (CDCES) or being Board Certified in Advanced Diabetes Management (BC-ADM). In addition, there appears to be a slight increase in those trained as a Lifestyle Coach to provide the National Diabetes Prevention Program (CDC Recognized National DPP) compared to NPS2017. Most respondents reported being Caucasian/White (84%), followed by Hispanic or Latinx (7%) and African American/Black and Asian/Asian American (at 4% each), like in previous surveys. Respondents reported diverse care delivery models, including traditional and nontraditional services, and expanded models of care such as population health/risk stratification models, the Chronic Care Model, Accountable Care Organizations, managed care, and others. CONCLUSION: The NPS2021 describes DCES workforce opportunities and challenges. Identifying and addressing those that impact the specialty's sustainability, diversity, and growth will guide strategies for the future workforce and their practice settings. Opportunities identified include embracing diabetes community care coordinators for person-centered delivery of care and education services and supporting frontline health care team members to increase competence and expertise in the prevention of type 2 diabetes, diabetes care, and education/support for related chronic diseases. In addition, as health care evolves, it creates opportunities for the DCESs to demonstrate a broader, key role as part of the diabetes care team.

    • Disaster Preparedness and Emergency Services
      1. Strains associated with two 2020 welder anthrax cases in the United States belong to separate lineages within Bacillus cereus sensu lato
        Carroll LM, Marston CK, Kolton CB, Gulvik CA, Gee JE, Weiner ZP, Kovac J.
        Pathogens. 2022 Jul 29;11(8).
        Anthrax-causing members of Bacillus cereus sensu lato (s.l.) pose a serious threat to public health. While most anthrax-causing strains resemble B. anthracis phenotypically, rare cases of anthrax-like illness caused by strains resembling "B. cereus" have been reported. Here, whole-genome sequencing was used to characterize three B. cereus s.l. isolates associated with two 2020 welder anthrax cases in the United States, which resembled "B. cereus" phenotypically. Comparison of the three genomes sequenced here to all publicly available, high-quality B. cereus s.l. genomes (n = 2890 total genomes) demonstrated that genomes associated with each case effectively belonged to separate species at the conventional 95% average nucleotide identity prokaryotic species threshold. Two PubMLST sequence type 78 (ST78) genomes affiliated with a case in Louisiana were most closely related to B. tropicus and possessed genes encoding the Bps exopolysaccharide capsule, as well as hemolysin BL (Hbl) and cytotoxin K (CytK). Comparatively, a ST108 genome associated with a case in Texas was most closely related to B. anthracis; however, like other anthrax-causing strains most closely related to B. anthracis, this genome did not possess Bps-, Hbl-, or CytK-encoding genes. Overall, results presented here provide insights into the evolution of anthrax-causing B. cereus s.l.

      2. The evolution of medical countermeasures for Ebola virus disease: Lessons learned and next steps
        Crozier I, Britson KA, Wolfe DN, Klena JD, Hensley LE, Lee JS, Wolfraim LA, Taylor KL, Higgs ES, Montgomery JM, Martins KA.
        Vaccines (Basel). 2022 Jul 29;10(8).
        The Ebola virus disease outbreak that occurred in Western Africa from 2013-2016, and subsequent smaller but increasingly frequent outbreaks of Ebola virus disease in recent years, spurred an unprecedented effort to develop and deploy effective vaccines, therapeutics, and diagnostics. This effort led to the U.S. regulatory approval of a diagnostic test, two vaccines, and two therapeutics for Ebola virus disease indications. Moreover, the establishment of fieldable diagnostic tests improved the speed with which patients can be diagnosed and public health resources mobilized. The United States government has played and continues to play a key role in funding and coordinating these medical countermeasure efforts. Here, we describe the coordinated U.S. government response to develop medical countermeasures for Ebola virus disease and we identify lessons learned that may improve future efforts to develop and deploy effective countermeasures against other filoviruses, such as Sudan virus and Marburg virus.

    • Disease Reservoirs and Vectors
      1. Preparation for post-hurricane mosquito control is essential for an effective emergency response to protect public health and promote recovery efforts. Effective pre-hurricane planning includes laying the groundwork for a successful reimbursement application to the Federal Emergency Management Agency. The critical and overlapping need to sustain funding for mosquito control programs is highlighted here in the context of both normal and emergency responses. Community support is an integral component of an effective integrated pest management program and is established over time with appropriate communication and engagement. Experienced mosquito control operators who are familiar with treatment areas are an essential component of successful operations. Here, practical advice is provided to plan, prepare, and implement a successful ground- and aerial-based mosquito control response.

    • Environmental Health
      1. Keep your water safe with resources from the Centers for Disease Control and Prevention
        Curtiss E, Hils J, Rokisky J.
        J Environ Health. 2022 ;84(10):42-43.

      2. The article discusses the Agency for Toxic Substances and Disease Registry's (ATSDR) activities for better understanding of hazardous substances and protection of public health in 2022. Topics covered include updating the public health assessment guidance manual (PGHAM), its basic components, and the new e-manual's six main sections. Also noted is the largest section Conducting Scientific Evaluations in the manual with its four subsections.

      3. Early life organophosphate ester exposures and bone health at age 12 years: The Health Outcomes and Measures of the Environment (HOME) study
        Kuiper JR, Vuong AM, Lanphear BP, Calafat AM, Ospina M, Cecil KM, Xu Y, Yolton K, Kalkwarf HJ, Braun JM, Chen A, Buckley JP.
        Sci Total Environ. 2022 Aug 25:158246.
        BACKGROUND: No human studies have evaluated early life organophosphate ester (OPE) exposures with bone health outcomes, despite evidence of osteotoxicity. OBJECTIVES: We assessed associations of urinary OPE metabolites measured across early life with areal bone mineral density (aBMD) and bone mineral content (BMC) at age 12 years. METHODS: Among 223 mother-child dyads enrolled in the Health Outcomes and Measures of the Environment (HOME) Study, we quantified concentrations of bis-2-chloroethyl phosphate (BCEP), bis-(1,3-dichloro-2-propyl) (BDCIPP), di-n-butyl phosphate (DnBP), and diphenyl phosphate (DPHP) in urine collected from mothers during pregnancy and children at ages 1, 2, 3, 5, and 8 years. At age 12 years, we performed dual energy x-ray absorptiometry and calculated aBMD and BMC z-scores at six skeletal sites. We estimated overall and sex-stratified BMD/BMC z-score differences per interquartile range (IQR) increase in OPE concentrations at multiple exposure timepoints: gestation (average) and 1-3 (average), 5, and 8 years. RESULTS: In adjusted models, overall associations of BCEP and BDCIPP with total hip and 1/3rd distal radius aBMD and BMC varied significantly by exposure timepoint, as did BDCIPP with whole body aBMD. For example, differences (95 % CI) in total hip aBMD z-score per IQR increase in BDCIPP were 0.33 (0.01, 0.64), -0.10 (-0.34, 0.14), -0.18 (-0.40, 0.05), and 0.14 (-0.09, 0.38) for concentrations during gestation and at 1-3, 5, and 8 years, respectively. Overall DnBP and DPHP associations were generally null at all timepoints. We observed sex-specific associations for some timepoints and skeletal sites. For example, an IQR increase in 8-year DPHP was associated with a 0.21 (0.05, 0.38) greater total hip aBMD z-score among females but -0.19 (-0.43, 0.05) lower z-score among males. DISCUSSION: Early life OPE exposures may be associated with sex- and exposure period-dependent alterations in early adolescent bone mineral accrual and strength.

    • Epidemiology and Surveillance
      1. Lessons learned for surveillance system strengthening through capacity building and partnership engagement in post-Ebola Guinea, 2015-2019
        Hemingway-Foday JJ, Diallo BI, Compaore S, Bah S, Keita S, Diallo IT, Martel LD, Standley CJ, Bah MB, Bah M, Camara D, Kaba AK, Keita L, Kone M, Reynolds E, Souare O, Stolka KB, Tchwenko S, Wone A, Worrell MC, MacDonald PD.
        Front Public Health. 2022 ;10:715356.
        The 2014-2016 Ebola outbreak in Guinea revealed systematic weaknesses in the existing disease surveillance system, which contributed to delayed detection, underreporting of cases, widespread transmission in Guinea and cross-border transmission to neighboring Sierra Leone and Liberia, leading to the largest Ebola epidemic ever recorded. Efforts to understand the epidemic's scale and distribution were hindered by problems with data completeness, accuracy, and reliability. In 2017, recognizing the importance and usefulness of surveillance data in making evidence-based decisions for the control of epidemic-prone diseases, the Guinean Ministry of Health (MoH) included surveillance strengthening as a priority activity in their post-Ebola transition plan and requested the support of partners to attain its objectives. The U.S. Centers for Disease Control and Prevention (US CDC) and four of its implementing partners-International Medical Corps, the International Organization for Migration, RTI International, and the World Health Organization-worked in collaboration with the Government of Guinea to strengthen the country's surveillance capacity, in alignment with the Global Health Security Agenda and International Health Regulations 2005 objectives for surveillance and reporting. This paper describes the main surveillance activities supported by US CDC and its partners between 2015 and 2019 and provides information on the strategies used and the impact of activities. It also discusses lessons learned for building sustainable capacity and infrastructure for disease surveillance and reporting in similar resource-limited settings.

      2. Modeling infection from SARS-CoV-2 wastewater concentrations: promise, limitations, and future directions
        Soller J, Jennings W, Schoen M, Boehm A, Wigginton K, Gonzalez R, Graham KE, McBride G, Kirby A, Mattioli M.
        J Water Health. 2022 Aug;20(8):1197-1211.
        Estimating total infection levels, including unreported and asymptomatic infections, is important for understanding community disease transmission. Wastewater can provide a pooled community sample to estimate total infections that is independent of case reporting biases toward individuals with moderate to severe symptoms and by test-seeking behavior and access. We derive three mechanistic models for estimating community infection levels from wastewater measurements based on a description of the processes that generate SARS-CoV-2 RNA signals in wastewater and accounting for the fecal strength of wastewater through endogenous microbial markers, daily flow, and per-capita wastewater generation estimates. The models are illustrated through two case studies of wastewater data collected during 2020-2021 in Virginia Beach, VA, and Santa Clara County, CA. Median simulated infection levels generally were higher than reported cases, but at times, were lower, suggesting a discrepancy between the reported cases and wastewater data, or inaccurate modeling results. Daily simulated infection estimates showed large ranges, in part due to dependence on highly variable clinical viral fecal shedding data. Overall, the wastewater-based mechanistic models are useful for normalization of wastewater measurements and for understanding wastewater-based surveillance data for public health decision-making but are currently limited by lack of robust SARS-CoV-2 fecal shedding data.

      3. Evaluation of accuracy and performance of self-reported HIV and antiretroviral therapy status in the Nigeria AIDS Indicator and Impact Survey (2018)
        Jahun I, Ehoche A, Bamidele M, Yakubu A, Bronson M, Dalhatu I, Greby S, Agbakwuru C, Baffa I, Iwara E, Alagi M, Asaolu O, Mukhtar A, Ikpeazu A, Nzelu C, Tapdiyel J, Bassey O, Abimiku A, Patel H, Parekh B, Aliyu S, Aliyu G, Charurat M, Swaminathan M.
        PLoS One. 2022 ;17(8):e0273748.
        BACKGROUND: Data on awareness of HIV status among people living with HIV (PLHIV) are critical to estimating progress toward epidemic control. To ascertain the accuracy of self-reported HIV status and antiretroviral drug (ARV) use in the Nigeria HIV/AIDS Indicator and Impact Survey (NAIIS), we compared self-reported HIV status with HIV rapid diagnostic test (RDT) results and self-reported ARV use with detectable blood ARV levels. METHODS: On the basis of responses and test results, participants were categorized by HIV status and ARV use. Self-reported HIV status and ARV use performance characteristics were determined by estimating sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Proportions and other analyses were weighted to account for complex survey design. RESULTS: During NAIIS, 186,405 participants consented for interview out of which 58,646 reported knowing their HIV status. Of the 959 (weighted, 1.5%) who self-reported being HIV-positive, 849 (92.1%) tested HIV positive and 64 (7.9%) tested HIV negative via RDT and polymerase chain reaction test for discordant positive results. Of the 849 who tested HIV positive, 743 (89.8%) reported using ARV and 72 (10.2%) reported not using ARV. Of 57,687 who self-reported being HIV negative, 686 (1.2%) tested HIV positive via RDT, with ARV biomarkers detected among 195 (25.1%). ARV was detected among 94.5% of those who self-reported using ARV and among 42.0% of those who self-reported not using ARV. Overall, self-reported HIV status had sensitivity of 52.7% (95% confidence interval [CI]: 49.4%-56.0%) with specificity of 99.9% (95% CI: 99.8%-99.9%). Self-reported ARV use had sensitivity of 95.2% (95% CI: 93.6%-96.7%) and specificity of 54.5% (95% CI: 48.8%-70.7%). CONCLUSIONS: Self-reported HIV status and ARV use screening tests were found to be low-validity measures during NAIIS. Laboratory tests to confirm self-reported information may be necessary to determine accurate HIV and clinical status for HIV studies in Nigeria.

    • Genetics and Genomics
      1. Genome sequences of 18 Salmonella enterica serotype Hadar strains collected from patients in the United States
        Webb HE, Kim JY, Tagg KA, de la Cruz F, Peñil-Celis A, Tolar B, Ellison Z, Schwensohn C, Brandenburg J, Nichols M, Folster JP.
        Microbiol Resour Announc. 2022 Aug 29:e0052222.
        Despite being linked to a number of recent poultry-associated outbreaks in the United States, few reference genomes are available for Salmonella enterica serotype Hadar. Here, we address this need by reporting 18 Salmonella Hadar genomes from samples collected from patients in the United States between 2014 and 2020.

      2. Molecular characterization of circulating Salmonella Typhi strains in an urban informal settlement in Kenya
        Ochieng C, Chen JC, Osita MP, Katz LS, Griswold T, Omballa V, Ng'eno E, Ouma A, Wamola N, Opiyo C, Achieng L, Munywoki PK, Hendriksen RS, Freeman M, Mikoleit M, Juma B, Bigogo G, Mintz E, Verani JR, Hunsperger E, Carleton HA.
        PLoS Negl Trop Dis. 2022 Aug 25;16(8):e0010704.
        A high burden of Salmonella enterica subspecies enterica serovar Typhi (S. Typhi) bacteremia has been reported from urban informal settlements in sub-Saharan Africa, yet little is known about the introduction of these strains to the region. Understanding regional differences in the predominant strains of S. Typhi can provide insight into the genomic epidemiology. We genetically characterized 310 S. Typhi isolates from typhoid fever surveillance conducted over a 12-year period (2007-2019) in Kibera, an urban informal settlement in Nairobi, Kenya, to assess the circulating strains, their antimicrobial resistance attributes, and how they relate to global S. Typhi isolates. Whole genome multi-locus sequence typing (wgMLST) identified 4 clades, with up to 303 pairwise allelic differences. The identified genotypes correlated with wgMLST clades. The predominant clade contained 290 (93.5%) isolates with a median of 14 allele differences (range 0-52) and consisted entirely of genotypes 4.3.1.1 and 4.3.1.2. Resistance determinants were identified exclusively in the predominant clade. Determinants associated with resistance to aminoglycosides were observed in 245 isolates (79.0%), sulphonamide in 243 isolates (78.4%), trimethoprim in 247 isolates (79.7%), tetracycline in 224 isolates (72.3%), chloramphenicol in 247 isolates (79.6%), β-lactams in 239 isolates (77.1%) and quinolones in 62 isolates (20.0%). Multidrug resistance (MDR) determinants (defined as determinants conferring resistance to ampicillin, chloramphenicol and cotrimoxazole) were found in 235 (75.8%) isolates. The prevalence of MDR associated genes was similar throughout the study period (2007-2012: 203, 76.3% vs 2013-2019: 32, 72.7%; Fisher's Exact Test: P = 0.5478, while the proportion of isolates harboring quinolone resistance determinants increased (2007-2012: 42, 15.8% and 2013-2019: 20, 45.5%; Fisher's Exact Test: P<0.0001) following a decline in S. Typhi in Kibera. Some isolates (49, 15.8%) harbored both MDR and quinolone resistance determinants. There were no determinants associated with resistance to cephalosporins or azithromycin detected among the isolates sequenced in this study. Plasmid markers were only identified in the main clade including IncHI1A and IncHI1B(R27) in 226 (72.9%) isolates, and IncQ1 in 238 (76.8%) isolates. Molecular clock analysis of global typhoid isolates and isolates from Kibera suggests that genotype 4.3.1 has been introduced multiple times in Kibera. Several genomes from Kibera formed a clade with genomes from Kenya, Malawi, South Africa, and Tanzania. The most recent common ancestor (MRCA) for these isolates was from around 1997. Another isolate from Kibera grouped with several isolates from Uganda, sharing a common ancestor from around 2009. In summary, S. Typhi in Kibera belong to four wgMLST clades one of which is frequently associated with MDR genes and this poses a challenge in treatment and control.

    • Health Economics
      1. Assessment of the costs of implementing COVID-19 vaccination clinics in 34 sites, United States, March 2021
        Yarnoff BO, Pike JJ, Athar HM, Bates LG, Tayebali ZA, Harris LQ, Jones-Jack NH, Washington ML, Cho BH.
        J Public Health Manag Pract. 2022 Aug 27.
        OBJECTIVES: To estimate the costs to implement public health department (PHD)-run COVID-19 vaccination clinics. DESIGN: Retrospectively reported data on COVID-19 vaccination clinic characteristics and resources used during a high-demand day in March 2021. These resources were combined with national average wages, supply costs, and facility costs to estimate the operational cost and start-up cost of clinics. SETTING: Thirty-four PHD-run COVID-19 vaccination clinics across 8 states and 1 metropolitan statistical area. PARTICIPANTS: Clinic managers at 34 PHD-run COVID-19 vaccination clinics. INTERVENTION: Large-scale COVID-19 vaccination clinics were implemented by public health agencies as part of the pandemic response. MAIN OUTCOMES MEASURED: Operational cost per day, operational cost per vaccination, start-up cost per clinic. RESULTS: Median operational cost per day for a clinic was $10 314 (range, $637-$95 163) and median cost per vaccination was $38 (range, $9-$206). There was a large range of operational costs across clinics. Clinics used an average of 99 total staff hours per 100 patients vaccinated. Median start-up cost per clinic was $15 348 (range, $1 409-$165 190). CONCLUSIONS: Results show that clinics require a large range of resources to meet the high throughput needs of the COVID-19 pandemic response. Estimating the costs of PHD-run vaccination clinics for the pandemic response is essential for ensuring that resources are available for clinic success. If clinics are not adequately supported, they may stop functioning, which would slow the pandemic response if no other setting or approach is possible.

    • Health Equity and Health Disparities
      1. Social vulnerability and rurality associated with higher severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-induced seroprevalence: A nationwide blood donor Study-United States, July 2020-June 2021
        Li Z, Lewis B, Berney K, Hallisey E, Williams AM, Whiteman A, Rivera-González LO, Clarke KE, Clayton HB, Tincher T, Opsomer JD, Busch MP, Gundlapalli AV, Jones JM.
        Clin Infect Dis. 2022 Aug 24;75(1):e133-e143.
        BACKGROUND: Most studies on health disparities during the coronavirus disease 2019 (COVID-19) pandemic focused on reported cases and deaths, which are influenced by testing availability and access to care. This study aimed to examine severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody seroprevalence in the United States and its associations with race/ethnicity, rurality, and social vulnerability over time. METHODS: This repeated cross-sectional study used data from blood donations in 50 states and Washington, DC, from July 2020 through June 2021. Donor zip codes were matched to counties and linked with Social Vulnerability Index (SVI) and urban-rural classification. SARS-CoV-2 antibody seroprevalences induced by infection and infection-vaccination combined were estimated. Association of infection-induced seropositivity with demographics, rurality, SVI, and its 4 themes were quantified using multivariate regression models. RESULTS: Weighted seroprevalence differed significantly by race/ethnicity and rurality, and increased with increasing social vulnerability. During the study period, infection-induced seroprevalence increased from 1.6% to 27.2% and 3.7% to 20.0% in rural and urban counties, respectively, while rural counties had lower combined infection- and vaccination-induced seroprevalence (80.0% vs 88.1%) in June 2021. Infection-induced seropositivity was associated with being Hispanic, non-Hispanic Black, and living in rural or more socially vulnerable counties, after adjusting for demographic and geographic covariates. CONCLUSIONS: The findings demonstrated increasing SARS-CoV-2 seroprevalence in the United States across all geographic, demographic, and social sectors. The study illustrated disparities by race-ethnicity, rurality, and social vulnerability. The findings identified areas for targeted vaccination strategies and can inform efforts to reduce inequities and prepare for future outbreaks.

      2. Investigating employment quality for population health and health equity: A perspective of power
        Fujishiro K, Ahonen EQ, Winkler M.
        Int J Environ Res Public Health. 2022 Aug 13;19(16).
        Employment quality (EQ) has gained increasing attention as a determinant of health, but the debate among occupational health researchers over the measurement of EQ poses a challenge to advancing the literature. This is especially problematic when the concept is used across social, cultural, and national borders, as EQ is shaped by power dynamics within sociopolitical and economic contexts that are specific to each society. Investigating EQ in context could help develop a clearer understanding as to why EQ is configured in certain ways, how best EQ could be measured, how EQ impacts health, and ultimately how EQ could be improved. In this paper, we propose that attention to social context-and in particular power-may help advance the research on EQ and health. We present an allegory, or a visual description, that articulates the power balance in the employer-worker relation as well as in the sociopolitical context in which the employer-worker relation takes place. We end by proposing specific approaches for occupational health researchers to incorporate a perspective of power in EQ research that may clarify the concept and measurement of EQ. A clearer recognition of EQ as a product of power in social context aligns with the research approach of addressing work as a social structural determinant of health.

      3. Neighbourhood socio-economic environment predicts adiposity and obesity risk in children under two
        Conrey SC, Burrell AR, Brokamp C, Burke RM, Couch SC, Niu L, Mattison CP, Piasecki A, Payne DC, Staat MA, Morrow AL.
        Pediatr Obes. 2022 .
        Background: Neighbourhood socio-economic environment (SEE) is associated with obesity in older children and adults, but little is known about this relationship in younger children. Breastfeeding is an important preventative of adiposity in childhood, but its relationship with neighbourhood SEE is unknown. Aims: We assessed differences in adiposity and obesity in children before age two by neighbourhood SEE, controlling for family socio-demographics and breastfeeding duration. Materials and Methods: Family socio-demographics, child body mass index z scores (BMIz), and breastfeeding duration were collected at periodic study visits from participants in PREVAIL (n = 245), a birth cohort in Cincinnati, OH. Addresses were assigned a Deprivation Index score, a validated measure of SEE, and dichotomized into highest SEE (least deprived quartile of scores) and not highest SEE (remaining quartiles). Longitudinal and Poisson models assessed differences in BMIz by SEE over the second year of life and obesity risk at age two, respectively (highest SEE, reference), while attenuation of obesity risk by breastfeeding duration was tested in mediation models. Results: Residing outside of the highest SEE neighbourhoods was associated with an increased BMIz of 0.04 (95%CI 0.02, 0.06) per month of life and increased obesity risk at age two (aRR: 3.7, 95%CI 1.2, 16.2), controlling for family socio-demographics. Breastfeeding duration attenuated >9% of the obesity risk attributable to SEE (mediated RR: 3.4, 95%CI 1.1, 14.8). Discussion: In the PREVAIL Cohort, residing outside of the highest SEE neighbourhoods predicted a significant increase in BMIz and obesity risk in children before age two, a relationship that was partially mediated by breastfeeding duration. Conclusion: Breastfeeding support may play an important role in reducing obesity rates in children in lower SEE neighbourhoods. © 2022 The Authors. Pediatric Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.

      4. Racial-ethnic disparities in adolescent sexual behaviours: the cross-sectional Youth Risk Behavior Survey, 2009-19
        Demissie Z, Ethier K, Williams K, Dunville R, Cavalier Y, Payne R, Underwood JM.
        Sex Health. 2022 Aug 3.
        BACKGROUND: There are notable disparities by race/ethnicity in the sexual health of US adolescents and young adults. Our objective was to examine change over time in racial-ethnic disparities in sexual behaviours among US high school students. METHODS: Data were analysed from six biennial cycles of the national Youth Risk Behavior Survey (2009-19), conducted among cross-sectional, nationally representative samples of 9th-12th grade students. Data were collected via self-administered questionnaires. Multivariable logistic regression models tested for linear trends by race/ethnicity (White, Black, Hispanic) and differences in these trends in: ever had sex, current sexual activity, having four or more lifetime sexual partners, and condomless sex. Prevalence ratios and risk differences by race/ethnicity for each cycle were used to calculate average percent change in the estimates to determine if health disparities changed over time. RESULTS: During 2009-19, prevalence estimates for ever had sex, current sexual activity, and having four or more lifetime sexual partners decreased overall and across all racial-ethnic groups. For condomless sex, prevalence estimates increased over time overall (38.9-45.7%) and for Black (37.6-51.8%) and White (36.7-44.2%) students, but not Hispanic (45.1-43.8%) students. Significant differences in trends by race/ethnicity were observed for all variables. Data suggest that racial-ethnic health disparities for sexual behaviours decreased over time, except for condomless sex. CONCLUSIONS: Although racial-ethnic gaps in sexual behaviours may be shrinking for many behaviours, work is still needed to achieve health equity in risks associated with HIV/AIDS, sexually transmitted infections, and pregnancy.

    • Immunity and Immunization
      1. BACKGROUND: Rotavirus vaccine performance appears worse in countries with high rotavirus genotype diversity. Evidence suggests diminished vaccine efficacy (VE) against G2P[4], which is heterotypic with existing monovalent rotavirus vaccine formulations. Most studies assessing genotype-specific VE have been underpowered and inconclusive. METHODS: We pooled individual-level data from ten Phase II and III clinical trials of rotavirus vaccine containing G1 and P[8] antigens (RV1) conducted between 2000 and 2012. We estimated VE against both any-severity and severe (Vesikari score ≥11) rotavirus gastroenteritis (RVGE) using binomial and multinomial logistic regression models for non-specific VE against any RVGE, genotype-specific VE, and RV1-typic VE against genotypes homotypic, partially heterotypic, or fully heterotypic with RV1 antigens. We adjusted models for concomitant oral poliovirus and RV1 vaccination and the country's designated child mortality stratum. RESULTS: Analysis included 87,644 infants from 22 countries in the Americas, Europe, Africa, and Asia. For VE against severe RVGE, non-specific VE was 91% (95% confidence interval (CI): 87-94%). Genotype-specific VE ranged from 96% (95% CI: 89-98%) against G1P[8] to 71% (43-85%) against G2P[4]. RV1-typic VE was 92% (95% CI: 84-96%) against partially heterotypic genotypes but 83% (67-91%) against fully heterotypic genotypes. For VE against any-severity RVGE, non-specific VE was 82% (95% CI: 75-87%). Genotype-specific VE ranged from 94% (95% CI: 86-97%) against G1P[8] to 63% (41-77%) against G2P[4]. RV1-typic VE was 83% (95% CI: 72-90%) against partially heterotypic genotypes but 63% (40-77%) against fully heterotypic genotypes. CONCLUSIONS: RV1 VE is comparatively diminished against fully heterotypic genotypes including G2P[4].

      2. Investigation of a severe acute respiratory syndrome coronavirus 2 Delta (B.1.617.2) variant outbreak among residents of a skilled nursing facility and vaccine effectiveness analysis: Maricopa County, Arizona, June-July 2021
        Dale AP, Almendares O, Howard BJ, Burnett E, Prasai S, Arons M, Collins J, Duffy N, Pandit U, Brady S, White JR, Garrett B, Kirking HL, Sunenshine R, Tate JE, Scott SE.
        Clin Infect Dis. 2022 Aug 24;75(1):e20-e26.
        BACKGROUND: Short-term rehabilitation units present unique infection control challenges because of high turnover and medically complex residents. In June 2021, the Maricopa County Department of Public Health was notified of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta outbreak in a skilled nursing facility short-term rehabilitation unit. We describe the outbreak and assess vaccine effectiveness (VE). METHODS: Facility electronic medical records were reviewed for residents who spent > 1 night on the affected unit between June 10 and July 23, 2021, to collect demographics, SARS-CoV-2 test results, underlying medical conditions, vaccination status, and clinical outcomes. Coronavirus disease 2019 VE estimates using Cox proportional hazards models were calculated. RESULTS: Forty (37%) of 109 short-stay rehabilitation unit residents who met inclusion criteria tested positive for SARS-CoV-2. SARS-CoV-2-positive case-patients were mostly male (58%) and White (78%) with a median age of 65 (range, 27-92) years; 11 (27%) were immunocompromised. Of residents, 39% (10 cases, 32 noncases) received 2 doses and 9% (4 cases, 6 noncases) received 1 dose of messenger RNA (mRNA) vaccine. Among nonimmunocompromised residents, adjusted 2-dose primary-series mRNA VE against symptomatic infection was 80% (95% confidence interval, 15-95). More cases were hospitalized (33%) or died (38%) than noncases (10% hospitalized; 16% died). CONCLUSIONS: In this large SARS-CoV-2 Delta outbreak in a high-turnover short-term rehabilitation unit, a low vaccination rate and medically complex resident population were noted alongside severe outcomes. VE of 2-dose primary-series mRNA vaccine against symptomatic infection was the highest in nonimmunocompromised residents. Health departments can use vaccine coverage data to prioritize facilities for assistance in preventing outbreaks.

      3. Characteristics of reported deaths among fully vaccinated persons with coronavirus disease 2019-United States, January-April 2021
        François Watkins LK, Mitruka K, Dorough L, Bressler SS, Kugeler KJ, Sadigh KS, Birhane MG, Nolen LD, Fischer M.
        Clin Infect Dis. 2022 Aug 24;75(1):e645-e652.
        BACKGROUND: Vaccines against coronavirus disease 2019 (COVID-19) are highly efficacious, but severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections do occur after vaccination. We characterized COVID-19 cases among fully vaccinated persons with an outcome of death. METHODS: We analyzed COVID-19 cases voluntarily reported to the Centers for Disease Control and Prevention by US health departments from 1 January to 30 April 2021. We included cases among US residents with a positive SARS-CoV-2 test result ≥14 days after completion of an authorized primary vaccine series and who had a known outcome (alive or dead) as of 31 May 2021. When available, specimens were sequenced for viral lineage and death certificates were reviewed for cause(s) of death. RESULTS: Of 8084 fully vaccinated persons with reported COVID-19 during the surveillance period, 245 (3.0%) died. Compared with patients who remained alive, those who died were older (median age, 82 vs 57 years;), more likely to reside in a long-term care facility (51% vs 18%), and more likely to have ≥1 underlying health condition associated with risk for severe disease (64% vs 24%) (all P < .01). Among 245 deaths, 191 (78%) were classified as COVID-19 related. Of 106 deaths with available death certificates, COVID-19 was listed for 81 deaths (77%). There were no differences in the type of vaccine administered or the most common viral lineage (B.1.1.7). CONCLUSIONS: COVID-19 deaths are rare in fully vaccinated persons, occurring most commonly in those with risk factors for severe disease, including older age and underlying health conditions. All eligible persons should be fully vaccinated against COVID-19 and follow other prevention measures to mitigate exposure risk.

      4. Effect of repeat vaccination on immunogenicity of quadrivalent cell-culture and recombinant influenza vaccines among healthcare personnel aged 18-64 years: A randomized, open-label trial
        Gaglani M, Kim SS, Naleway AL, Levine MZ, Edwards L, Murthy K, Dunnigan K, Zunie T, Groom H, Ball S, Jeddy Z, Hunt D, Wesley MG, Sambhara S, Gangappa S, Grant L, Cao W, Liaini Gross F, Mishina M, Fry AM, Thompson MG, Dawood FS, Flannery B.
        Clin Infect Dis. 2022 Aug 29.
        BACKGROUND: Antibody responses to non-egg-based standard-dose cell-culture influenza vaccine (containing 15 µg hemagglutinin (HA)/component) and recombinant vaccine (containing 45 µg HA/component) during consecutive seasons have not been studied in the United States. METHODS: In a randomized trial of immunogenicity of quadrivalent influenza vaccines among healthcare personnel (HCP) aged 18-64 years over two consecutive seasons, HCP who received recombinant-hemagglutinin (RIV) or cell-culture-based vaccine (ccIIV) during the first season (Y1) were re-randomized the second season of 2019-2020 (Y2) to receive ccIIV or RIV, resulting in four ccIIV-RIV combinations. In Y2, hemagglutination inhibition (HI) antibody titers against reference cell-grown vaccine viruses were compared in each ccIIV-RIV group with titers among HCP randomized both seasons to receive egg-based, standard-dose inactivated influenza vaccine (IIV), using geometric mean titer (GMT) ratios of Y2-post-vaccination titers. RESULTS: Y2 data from 414 HCPs were analyzed per-protocol. Compared to 60 IIV/IIV recipients, 74 RIV/RIV and 106 ccIIV/RIV recipients showed significantly elevated GMT ratios (Bonferroni corrected P <.007) against all components except A (H3N2). Post-vaccination GMT ratios for ccIIV/ccIIV and RIV/ccIIV were not significantly elevated compared to IIV/IIV except for RIV/ccIIV against A(H1N1)pdm09. CONCLUSIONS: In adult HCPs, receipt of RIV two consecutive seasons or the second season was more immunogenic than consecutive egg-based IIV for three of the four components of quadrivalent vaccine. Immunogenicity of ccIIV/ccIIV was similar to that of IIV/IIV. Differences in hemagglutinin antigen content may play a role in immunogenicity of influenza vaccination in consecutive seasons.

      5. Contact-tracing outcomes among household contacts of fully vaccinated coronavirus disease 2019 (COVID-19) patients: San Francisco, California, 29 January-2 July 2021
        Sachdev DD, Chew Ng R, Sankaran M, Ernst A, Hernandez KT, Servellita V, Sotomayor-Gonzalez A, Stoltey J, Cohen SE, Nguyen TQ, Chiu CY, Philip S.
        Clin Infect Dis. 2022 Aug 24;75(1):e267-e275.
        BACKGROUND: The extent to which vaccinated persons diagnosed with coronavirus disease 2019 (COVID-19) can transmit to other vaccinated and unvaccinated persons is unclear. METHODS: Using data from the San Francisco Department of Public Health, this report describes outcomes of household contact tracing during 29 January-2 July 2021, where fully vaccinated patients with COVID-19 were the index case in the household. RESULTS: Among 248 fully vaccinated patients with breakthrough infections, 203 (82%) were symptomatic and 105 were identified as the index patient within their household. Among 179 named household contacts, 71 (40%) contacts tested, over half (56%) were fully vaccinated and the secondary attack rate was 28%. Overall transmission from a symptomatic fully vaccinated patient with breakthrough infection to household contacts was suspected in 14 of 105 (13%) of households. Viral genomic sequencing of samples from 44% of fully vaccinated patients showed that 82% of those sequenced were infected by a variant of concern or interest and 77% by a variant carrying mutation(s) associated with resistance to neutralizing antibodies. CONCLUSIONS: Transmission from fully vaccinated symptomatic index patients to vaccinated and unvaccinated household contacts can occur. Indoor face masking and timely testing of all household contacts should be considered when a household member receives a positive test result in order to identify and interrupt transmission chains.

      6. Neutralizing antibody response to pseudotype severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) differs between mRNA-1273 and BNT162b2 coronavirus disease 2019 (COVID-19) vaccines and by history of SARS-CoV-2 infection
        Tyner HL, Burgess JL, Grant L, Gaglani M, Kuntz JL, Naleway AL, Thornburg NJ, Caban-Martinez AJ, Yoon SK, Herring MK, Beitel SC, Blanton L, Nikolich-Zugich J, Thiese MS, Pleasants JF, Fowlkes AL, Lutrick K, Dunnigan K, Yoo YM, Rose S, Groom H, Meece J, Wesley MG, Schaefer-Solle N, Louzado-Feliciano P, Edwards LJ, Olsho LE, Thompson MG.
        Clin Infect Dis. 2022 Aug 24;75(1):e827-e837.
        BACKGROUND: Data on the development of neutralizing antibodies (nAbs) against SARS-CoV-2 after SARS-CoV-2 infection and after vaccination with mRNA COVID-19 vaccines are limited. METHODS: From a prospective cohort of 3975 adult essential and frontline workers tested weekly from August 2020 to March 2021 for SARS-CoV-2 infection by reverse transcription-polymerase chain reaction assay irrespective of symptoms, 497 participants had sera drawn after infection (170), vaccination (327), and after both infection and vaccination (50 from the infection population). Serum was collected after infection and each vaccine dose. Serum-neutralizing antibody titers against USA-WA1/2020-spike pseudotype virus were determined by the 50% inhibitory dilution. Geometric mean titers (GMTs) and corresponding fold increases were calculated using t tests and linear mixed-effects models. RESULTS: Among 170 unvaccinated participants with SARS-CoV-2 infection, 158 (93%) developed nAbs with a GMT of 1003 (95% confidence interval, 766-1315). Among 139 previously uninfected participants, 138 (99%) developed nAbs after mRNA vaccine dose 2 with a GMT of 3257 (2596-4052). GMT was higher among those receiving mRNA-1273 vaccine (GMT, 4698; 3186-6926) compared with BNT162b2 vaccine (GMT, 2309; 1825-2919). Among 32 participants with prior SARS-CoV-2 infection, GMT was 21 655 (14 766-31 756) after mRNA vaccine dose 1, without further increase after dose 2. CONCLUSIONS: A single dose of mRNA vaccine after SARS-CoV-2 infection resulted in the highest observed nAb response. Two doses of mRNA vaccine in previously uninfected participants resulted in higher nAbs to SARS-CoV-2 than after 1 dose of vaccine or SARS-CoV-2 infection alone. nAb response also differed by mRNA vaccine product.

      7. Prevention and control of seasonal influenza with vaccines: Recommendations of the Advisory Committee on Immunization Practices - United States, 2022-23 Influenza Season
        Grohskopf LA, Blanton LH, Ferdinands JM, Chung JR, Broder KR, Talbot HK, Morgan RL, Fry AM.
        MMWR Recomm Rep. 2022 Aug 26;71(1):1-28.
        THIS REPORT UPDATES THE 2021-22 RECOMMENDATIONS OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP) CONCERNING THE USE OF SEASONAL INFLUENZA VACCINES IN THE UNITED STATES: (MMWR Recomm Rep 2021;70[No. RR-5]:1-24). Routine annual influenza vaccination is recommended for all persons aged ≥6 months who do not have contraindications. For each recipient, a licensed and age-appropriate vaccine should be used. With the exception of vaccination for adults aged ≥65 years, ACIP makes no preferential recommendation for a specific vaccine when more than one licensed, recommended, and age-appropriate vaccine is available. All seasonal influenza vaccines expected to be available in the United States for the 2022-23 season are quadrivalent, containing hemagglutinin (HA) derived from one influenza A(H1N1)pdm09 virus, one influenza A(H3N2) virus, one influenza B/Victoria lineage virus, and one influenza B/Yamagata lineage virus. Inactivated influenza vaccines (IIV4s), recombinant influenza vaccine (RIV4), and live attenuated influenza vaccine (LAIV4) are expected to be available. Trivalent influenza vaccines are no longer available, but data that involve these vaccines are included for reference. INFLUENZA VACCINES MIGHT BE AVAILABLE AS EARLY AS JULY OR AUGUST, BUT FOR MOST PERSONS WHO NEED ONLY 1 DOSE OF INFLUENZA VACCINE FOR THE SEASON, VACCINATION SHOULD IDEALLY BE OFFERED DURING SEPTEMBER OR OCTOBER. HOWEVER, VACCINATION SHOULD CONTINUE AFTER OCTOBER AND THROUGHOUT THE SEASON AS LONG AS INFLUENZA VIRUSES ARE CIRCULATING AND UNEXPIRED VACCINE IS AVAILABLE. FOR MOST ADULTS (PARTICULARLY ADULTS AGED ≥65 YEARS) AND FOR PREGNANT PERSONS IN THE FIRST OR SECOND TRIMESTER, VACCINATION DURING JULY AND AUGUST SHOULD BE AVOIDED UNLESS THERE IS CONCERN THAT VACCINATION LATER IN THE SEASON MIGHT NOT BE POSSIBLE. CERTAIN CHILDREN AGED 6 MONTHS THROUGH 8 YEARS NEED 2 DOSES; THESE CHILDREN SHOULD RECEIVE THE FIRST DOSE AS SOON AS POSSIBLE AFTER VACCINE IS AVAILABLE, INCLUDING DURING JULY AND AUGUST. VACCINATION DURING JULY AND AUGUST CAN BE CONSIDERED FOR CHILDREN OF ANY AGE WHO NEED ONLY 1 DOSE FOR THE SEASON AND FOR PREGNANT PERSONS WHO ARE IN THE THIRD TRIMESTER IF VACCINE IS AVAILABLE DURING THOSE MONTHS: UPDATES DESCRIBED IN THIS REPORT REFLECT DISCUSSIONS DURING PUBLIC MEETINGS OF ACIP THAT WERE HELD ON OCTOBER 20, 2021; JANUARY 12, 2022; FEBRUARY 23, 2022; AND JUNE 22, 2022. PRIMARY UPDATES TO THIS REPORT INCLUDE THE FOLLOWING THREE TOPICS: 1) THE COMPOSITION OF 2022-23 U.S. SEASONAL INFLUENZA VACCINES; 2) UPDATES TO THE DESCRIPTION OF INFLUENZA VACCINES EXPECTED TO BE AVAILABLE FOR THE 2022-23 SEASON, INCLUDING ONE INFLUENZA VACCINE LABELING CHANGE THAT OCCURRED AFTER THE PUBLICATION OF THE 2021-22 ACIP INFLUENZA RECOMMENDATIONS; AND 3) UPDATES TO THE RECOMMENDATIONS CONCERNING VACCINATION OF ADULTS AGED ≥65 YEARS. FIRST, THE COMPOSITION OF 2022-23 U.S. INFLUENZA VACCINES INCLUDES UPDATES TO THE INFLUENZA A(H3N2) AND INFLUENZA B/VICTORIA LINEAGE COMPONENTS. U.S.-LICENSED INFLUENZA VACCINES WILL CONTAIN HA DERIVED FROM AN INFLUENZA A/VICTORIA/2570/2019 (H1N1)PDM09-LIKE VIRUS (FOR EGG-BASED VACCINES) OR AN INFLUENZA A/WISCONSIN/588/2019 (H1N1)PDM09-LIKE VIRUS (FOR CELL CULTURE-BASED OR RECOMBINANT VACCINES); AN INFLUENZA A/DARWIN/9/2021 (H3N2)-LIKE VIRUS (FOR EGG-BASED VACCINES) OR AN INFLUENZA A/DARWIN/6/2021 (H3N2)-LIKE VIRUS (FOR CELL CULTURE-BASED OR RECOMBINANT VACCINES); AN INFLUENZA B/AUSTRIA/1359417/2021 (VICTORIA LINEAGE)-LIKE VIRUS; AND AN INFLUENZA B/PHUKET/3073/2013 (YAMAGATA LINEAGE)-LIKE VIRUS. SECOND, THE APPROVED AGE INDICATION FOR THE CELL CULTURE-BASED INACTIVATED INFLUENZA VACCINE, FLUCELVAX QUADRIVALENT (CCIIV4), WAS CHANGED IN OCTOBER 2021 FROM ≥2 YEARS TO ≥6 MONTHS. THIRD, RECOMMENDATIONS FOR VACCINATION OF ADULTS AGED ≥65 YEARS HAVE BEEN MODIFIED. ACIP RECOMMENDS THAT ADULTS AGED ≥65 YEARS PREFERENTIALLY RECEIVE ANY ONE OF THE FOLLOWING HIGHER DOSE OR ADJUVANTED INFLUENZA VACCINES: QUADRIVALENT HIGH-DOSE INACTIVATED INFLUENZA VACCINE (HD-IIV4), QUADRIVALENT RECOMBINANT INFLUENZA VACCINE (RIV4), OR QUADRIVALENT ADJUVANTED INACTIVATED INFLUENZA VACCINE (AIIV4). IF NONE OF THESE THREE VACCINES IS AVAILABLE AT AN OPPORTUNITY FOR VACCINE ADMINISTRATION, THEN ANY OTHER AGE-APPROPRIATE INFLUENZA VACCINE SHOULD BE USED: THIS REPORT FOCUSES ON RECOMMENDATIONS FOR THE USE OF VACCINES FOR THE PREVENTION AND CONTROL OF SEASONAL INFLUENZA DURING THE 2022-23 INFLUENZA SEASON IN THE UNITED STATES. A BRIEF SUMMARY OF THE RECOMMENDATIONS AND A LINK TO THE MOST RECENT BACKGROUND DOCUMENT CONTAINING ADDITIONAL INFORMATION ARE AVAILABLE AT: https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/flu.html. These recommendations apply to U.S.-licensed influenza vaccines used according to Food and Drug Administration-licensed indications. Updates and other information are available from CDC's influenza website (https://www.cdc.gov/flu). Vaccination and health care providers should check this site periodically for additional information.

      8. Intradermal vaccination for monkeypox - benefits for individual and public health
        Brooks JT, Marks P, Goldstein RH, Walensky RP.
        N Engl J Med. 2022 Aug 31.

      9. Effectiveness of a COVID-19 vaccine rollout in a highly affected American Indian community, San Carlos Apache Tribe, December 2020-February 2021
        Le-Morawa N, Kunkel A, Darragh J, Reede D, Zhou N, Lees Y, Hoffman D, Dia L, Kitcheyan T, White M, Belknap I, Agathis N, Began V, Balajee SA.
        Public Health Rep. 2022 Aug 25:333549221120238.
        COVID-19 has disproportionately affected American Indian tribes, including the San Carlos Apache Tribe, which resides on 1.8 million acres in Arizona and has 16 788 official members. High vaccination rates among American Indian/Alaska Native people in the United States have been reported, but information on how individual tribes achieved these high rates is scarce. We describe the COVID-19 epidemiology and vaccine rollout in the San Carlos Apache Tribe using data extracted from electronic health records from the San Carlos Apache Healthcare Corporation (SCAHC). By mid-December 2020, 19% of the San Carlos Apache population had received a positive reverse transcription polymerase chain reaction test for SARS-CoV-2, the virus that causes COVID-19. The tribe prioritized for vaccination population groups with the highest risk for severe COVID-19 outcomes (eg, those aged ≥65 years, who had a 46% risk of hospitalization if infected vs 13% overall). SCAHC achieved high early COVID-19 vaccination rates in the San Carlos community relative to the state of Arizona (47.6 vs 25.2 doses per 100 population by February 27, 2021). These vaccination rates reflected several strategies that were implemented to achieve high COVID-19 vaccine access and uptake, including advance planning, departmental vaccine education sessions within SCAHC, radio and Facebook postings featuring tribal leaders in the Apache language, and pop-up community vaccine clinics. The San Carlos Apache Tribe's vaccine rollout strategy was an early success story and may provide a model for future vaccination campaigns in other tribal nations and rural communities in the United States.

      10. Progress towards the development of a universal influenza vaccine
        Wang WC, Sayedahmed EE, Sambhara S, Mittal SK.
        Viruses. 2022 Jul 30;14(8).
        Influenza viruses are responsible for millions of cases globally and significantly threaten public health. Since pandemic and zoonotic influenza viruses have emerged in the last 20 years and some of the viruses have resulted in high mortality in humans, a universal influenza vaccine is needed to provide comprehensive protection against a wide range of influenza viruses. Current seasonal influenza vaccines provide strain-specific protection and are less effective against mismatched strains. The rapid antigenic drift and shift in influenza viruses resulted in time-consuming surveillance and uncertainty in the vaccine protection efficacy. Most recent universal influenza vaccine studies target the conserved antigen domains of the viral surface glycoproteins and internal proteins to provide broader protection. Following the development of advanced vaccine technologies, several innovative strategies and vaccine platforms are being explored to generate robust cross-protective immunity. This review provides the latest progress in the development of universal influenza vaccines.

    • Informatics
      1. Evaluating COVID-19 exposure notification effectiveness with SimAEN: A simulation tool designed for public health decision making
        Streilein W, Finklea L, Schuldt D, Schiefelbein MC, Yahalom R, Ali H, Norige A.
        Public Health Rep. 2022 Aug 30:333549221116361.
        OBJECTIVES: Exposure notification (EN) supplements traditional contact tracing by using proximity sensors in smartphones to record close contact between persons. This ledger is used to alert persons of potential SARS-CoV-2 exposure, so they can quarantine until their infection status is determined. We describe a model that estimates the impact of EN implementation on reducing the spread of SARS-CoV-2 and on the workload of public health officials, in combination with other key public health interventions such as traditional contact tracing, face mask wearing, and testing. METHODS: We created an agent-based model, Simulated Automated Exposure Notification (SimAEN), to explore the effectiveness of EN to slow the spread of SARS-CoV-2. We varied selected simulation variables, such as population adoption of EN and EN detector sensitivity configurations, to illustrate the potential effects of EN. We executed 20 simulations with SimAEN for each scenario and derived results for each simulation. RESULTS: When more sensitive versus more specific EN configurations were compared, the effective reproductive number, R(E), was minimally affected (a decrease <0.03). For scenarios with increasing levels of EN adoption, an increasing number of additional infected persons were identified through EN, and total infection counts in the simulated population decreased; R(E) values for this scenario decreased with increasing EN adoption (a decrease of 0.1 to 0.2 depending on the scenario). CONCLUSIONS: Estimates from SimAEN can help public health officials determine which levels of EN adoption in combination with other public health interventions can maximize prevention of COVID-19 while minimizing unnecessary quarantine in their jurisdiction.

    • Injury and Violence
      1. Return to learn ECHO: Telementoring for school personnel to help children return to school and learning after mild traumatic brain injury
        McAvoy K, Halstead M, Radecki L, Shah A, Emanuel A, Domain S, Daugherty J, Waltzman D.
        J Sch Health. 2022 .
        BACKGROUND: Return to learn (RTL) after mild traumatic brain injury (mTBI) presents unique challenges for school professionals. A multidisciplinary team approach is necessary yet training school professionals is logistically difficult. This paper describes an innovative pilot RTL program and its evaluation. METHODS: Utilizing the telehealth/telementoring program Project ECHO® (Extension for Community Healthcare Outcomes), this study utilized a multidisciplinary team of subject matter experts to deliver five 1-hour sessions across 5 cohorts of school-based professionals (total of 133 participants). The evaluation used a mixed-methods approach of post-session and post-program participant surveys and post-program participant focus groups. RESULTS: Participants who completed a post-program survey reported statistically significant improvements in essential aspects of RTL knowledge and self-efficacy. This included improvements in how to manage a student with an mTBI (44.8% to 86.9%), benefits of early return to school for students following mTBI (31.8% to 86.9%), and the importance of written RTL policies/procedures (55.1% to 97.1%). CONCLUSIONS: This study demonstrates that RTL training via a telementoring approach may be a positive and effective way to train school-based professionals and improve knowledge and self-efficacy, especially when attending face-to-face trainings are difficult. This model has the potential to produce programmatic and systematic improvements for RTL education. © 2022 The Authors. Journal of School Health published by Wiley Periodicals LLC on behalf of American School Health Association.

      2. Belt fit for children in vehicle seats with and without belt-positioning boosters
        West BA, Reed MP, Benedick A, De Leonardis D, Huey R, Sauber-Schatz E.
        Traffic Inj Prev. 2022 Aug 26:1-6.
        OBJECTIVE: The purpose of the current study is to use 3D technology to measure in-vehicle belt fit both with and without booster seats across different vehicles among a large, diverse sample of children and to compare belt fit with and without a booster. METHODS: Lap and shoulder belt fit were measured for 108 children ages 6-12 years sitting in the second-row, outboard seats of three vehicles from October 2017 to March 2018. Each child was measured with no booster, a backless booster, and a high-back (HB) booster in three different vehicles. Alternative high-back (HB HW) and backless boosters that could accommodate higher weights were used for children who were too large to fit in the standard boosters. Lap and torso belt scores were computed based on the belt location relative to skeletal landmarks. RESULTS: Both lap and torso belt fit scores were significantly different across vehicles when using the vehicle belt alone (no booster). In all vehicles, lap belt fit improved when using boosters compared with no booster among children ages 6-12 years in rear seats-with one exception of the HB HW booster in the minivan. Torso belt fit improved when using boosters compared with no booster in the sedan, and torso belt fit improved in the minivan and SUV with the use of HB and HB HW boosters when compared with no booster. CONCLUSIONS: Lap and torso belt fit for children ages 6-12 years in rear seats was substantially improved by using boosters. Parents and caregivers should continue to have their children use booster seats until vehicle seat belts fit properly which likely does not occur until children are 9-12 years old. Decision makers can consider strengthening child passenger restraint laws with booster seat provisions that require children who have outgrown car seats to use booster seats until at least age 9 to improve belt fit and reduce crash injuries and deaths.

    • Laboratory Sciences
      1. Volume-associated clinical and histopathological effects of intranasal instillation in Syrian hamsters: Considerations for infection and therapeutic studies
        Forero C, Ritter JM, Seixas JN, Coleman-McCray JD, Brake M, Condrey JA, Tansey C, Welch SR, Genzer SC, Spengler JR.
        Pathogens. 2022 Aug 10;11(8).
        Syrian hamsters are a key animal model of SARS-CoV-2 and other respiratory viruses and are useful for the evaluation of associated medical countermeasures. Delivery of an infectious agent or intervention to the respiratory tract mirrors natural routes of exposure and allows for the evaluation of clinically relevant therapeutic administration. The data to support instillation or inoculation volumes are important both for optimal experimental design and to minimize or avoid effects of diluent alone, which may compromise both data interpretation and animal welfare. Here we investigate four intranasal (IN) instillation volumes in hamsters (50, 100, 200, or 400 µL). The animals were monitored daily, and a subset were serially euthanized at one of four pre-determined time-points (1, 3, 7, and 14 days post-instillation). Weight, temperature, oxygen saturation, CBC, radiographs, and respiratory tissue histopathology were assessed to determine changes associated with instillation volume alone. With all the delivery volumes, we found no notable differences between instilled and non-instilled controls in all of the parameters assessed, except for histopathology. In the animals instilled with 200 or 400 µL, inflammation associated with foreign material was detected in the lower respiratory tract indicating that higher volumes may result in aspiration of nasal and/or oropharyngeal material in a subset of animals, resulting in IN instillation-associated histopathology.

    • Maternal and Child Health
      1. Clinical risk factors of adverse outcomes among women with COVID-19 in the pregnancy and postpartum period: A sequential, prospective meta-analysis
        Smith ER, Oakley E, Grandner GW, Rukundo G, Farooq F, Ferguson K, Baumann S, Waldorf KA, Afshar Y, Ahlberg M, Ahmadzia H, Akelo V, Aldrovandi G, Bevilacqua E, Bracero N, Brandt JS, Broutet N, Carrillo J, Conry J, Cosmi E, Crispi F, Crovetto F, Gil MD, Delgado-López C, Divakar H, Driscoll AJ, Favre G, Buhigas IF, Flaherman V, Gale C, Godwin CL, Gottlieb S, Gratacós E, He S, Hernandez O, Jones S, Joshi S, Kalafat E, Khagayi S, Knight M, Kotloff K, Lanzone A, Longo VL, Le Doare K, Lees C, Litman E, Lokken EM, Madhi SA, Magee LA, Martinez-Portilla RJ, Metz TD, Miller ES, Money D, Moungmaithong S, Mullins E, Nachega JB, Nunes MC, Onyango D, Panchaud A, Poon LC, Raiten D, Regan L, Sahota D, Sakowicz A, Sanin-Blair J, Stephansson O, Temmerman M, Thorson A, Thwin SS, Tippett Barr BA, Tolosa JE, Tug N, Valencia-Prado M, Visentin S, von Dadelszen P, Whitehead C, Wood M, Yang H, Zavala R, Tielsch JM.
        Am J Obstet Gynecol. 2022 Aug 23.
        OBJECTIVE: This sequential, prospective meta-analysis (sPMA) sought to identify risk factors among pregnant and postpartum women with COVID-19 for adverse outcomes related to: disease severity, maternal morbidities, neonatal mortality and morbidity, adverse birth outcomes. DATA SOURCES: We prospectively invited study investigators to join the sPMA via professional research networks beginning in March 2020. STUDY ELIGIBILITY CRITERIA: Eligible studies included those recruiting at least 25 consecutive cases of COVID-19 in pregnancy within a defined catchment area. STUDY APPRAISAL AND SYNTHESIS METHODS: We included individual patient data from 21 participating studies. Data quality was assessed, and harmonized variables for risk factors and outcomes were constructed. Duplicate cases were removed. Pooled estimates for the absolute and relative risk of adverse outcomes comparing those with and without each risk factor were generated using a two-stage meta-analysis. RESULTS: We collected data from 33 countries and territories, including 21,977 cases of SARS-CoV-2 infection in pregnancy or postpartum. We found that women with comorbidities (pre-existing diabetes, hypertension, cardiovascular disease) versus those without were at higher risk for COVID-19 severity and pregnancy health outcomes (fetal death, preterm birth, low birthweight). Participants with COVID-19 and HIV were 1.74 times (95% CI: 1.12, 2.71) more likely to be admitted to the ICU. Pregnant women who were underweight before pregnancy were at higher risk of ICU admission (RR 5.53, 95% CI: 2.27, 13.44), ventilation (RR 9.36, 95% CI: 3.87, 22.63), and pregnancy-related death (RR 14.10, 95% CI: 2.83, 70.36). Pre-pregnancy obesity was also a risk factor for severe COVID-19 outcomes including ICU admission (RR 1.81, 95% CI: 1.26,2.60), ventilation (RR 2.05, 95% CI: 1.20,3.51), any critical care (RR 1.89, 95% CI: 1.28,2.77), and pneumonia (RR 1.66, 95% CI: 1.18,2.33). Anemic pregnant women with COVID-19 also had increased risk of ICU admission (RR 1.63, 95% CI: 1.25, 2.11) and death (RR 2.36, 95% CI: 1.15, 4.81). CONCLUSION: We found that pregnant women with comorbidities including diabetes, hypertension, and cardiovascular disease were at increased risk for severe COVID-19-related outcomes, maternal morbidities, and adverse birth outcomes. We also identified several less commonly-known risk factors, including HIV infection, pre-pregnancy underweight, and anemia. Although pregnant women are already considered a high-risk population, special priority for prevention and treatment should be given to pregnant women with these additional risk factors.

      2. Provider perspectives: Identification and follow-up of infants who are deaf or hard of hearing
        Cree RA, Bitsko R, Grimm C, Nash A, Cahill E, Dunham E, Logan N, McKay SL, Martinez DR, Gaffney M.
        Am J Perinatol. 2022 Aug 29.
        OBJECTIVE: Without timely screening, diagnosis, and intervention, hearing loss can cause significant delays in a child's speech, language, social, and emotional development. In 2019, Texas had nearly twice the average rate of loss to follow-up (LFU) or loss to documentation (LTD; i.e., missing documentation of services received) among infants who did not pass their newborn hearing screening compared to the United States overall (51.1% vs. 27.5%). We aimed to identify factors contributing to LFU/LTD among infants who do not pass their newborn hearing screening in Texas. STUDY DESIGN: Data were collected through semi-structured qualitative interviews with 56 providers along the hearing care continuum, including hospital newborn hearing screening program staff, audiologists, primary care physicians, and early intervention (EI) program staff located in three rural and urban public health regions in Texas. Following recording and transcription of the interviews, we used qualitative data analysis software to analyze themes using a conventional content analysis approach. RESULTS: Frequently cited barriers included problems with family access to care, difficulty contacting patients, problems with communication between providers and referrals, lack of knowledge among providers and parents, and problems using the online reporting system. Providers in rural areas more often mentioned problems with family access to care and contacting families compared to providers in urban areas. CONCLUSION: These findings provide insight into strategies that public health professionals and health care providers can use to work together to help further increase the number of children identified early who may benefit from EI services.

      3. OBJECTIVES: As, cases of congenital syphilis (CS) and infectious syphilis among women more than doubled in Florida and across the nation during 2013-2019, we sought to understand what may be contributing to these increases in Florida. DESIGN: A two time-period observational study. SETTING: Pregnant women with reported syphilis infections and their pregnancy outcomes (2013-2014 and 2018-2019) in Florida. PARTICIPANTS: 1213 pregnant women with reported syphilis infections living in Florida and 341 infants meeting the CS case definition. OUTCOME MEASURES: We assessed what proportion of the increase in CS was from increases in maternal syphilis infections. We examined maternal demographics, infection characteristics and timing of diagnoses that could explain the increase in CS. Finally, we reviewed if changes in presentation or severity of CS cases occurred. RESULTS: During 2013-2014, 83 (21%) of 404 pregnant women with syphilis delivered babies with CS. During 2018-2019, 258 (32%) of 809 pregnant women with syphilis delivered babies with CS. Comparing CS prevention rates, it was determined that 65% of the increase in CS was due to the increases in maternal syphilis infections. The proportion of maternal cases staged as primary or secondary increased over time (7%-13%) (p<0.01) and reports of drug use became slightly more common (6%-10%) (p=0.02). During 2018-2019, women delivering CS infants were more likely to be reinfected during the same pregnancy (27 (10%) vs 5 (6%) p=0.23) and more had negative third trimester screening tests (43 (17%) vs 7 (8% p=0.07)). The percentage of infants with CS who had ≥1 sign or symptom increased from 35% to 40%, and the combined total of stillbirths and infant deaths increased from 5 to 26. CONCLUSIONS: Recently, more pregnant women are being infected with syphilis and a higher per cent are not being treated to prevent CS. The reasons for this finding are unclear.

      4. Interaction of maternal medication use with ambient heat exposure on congenital heart defects in the National Birth Defects Prevention Study
        Ou Y, Papadopoulos EA, Fisher SC, Browne ML, Lin Z, Soim A, Lu Y, Sheridan S, Reefhuis J, Langlois PH, Romitti PA, Bell EM, Feldkamp ML, Malik S, Lin S.
        Environ Res. 2022 Aug 27:114217.
        BACKGROUND: Maternal exposure to weather-related extreme heat events (EHEs) has been associated with congenital heart defects (CHDs) in offspring. Certain medications may affect an individual's physiologic responses to EHEs. We evaluated whether thermoregulation-related medications modified associations between maternal EHE exposure and CHDs. METHODS: We linked geocoded residence data from the U.S. National Birth Defects Prevention Study, a population-based case-control study, to summertime EHE exposures. An EHE was defined using the 90th percentile of daily maximum temperature (EHE90) for each of six climate regions during postconceptional weeks 3-8. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for associations between EHE90 and the risk of CHDs were estimated by strata of maternal thermoregulation-related medication use and climate region. Interaction effects were evaluated on multiplicative and additive scales. RESULTS: Over 45% of participants reported thermoregulation-related medication use during the critical period of cardiogenesis. Overall, these medications did not significantly modify the association between EHEs and CHDs. Still, medications that alter central thermoregulation increased aORs (95% CI) of EHE90 from 0.73 (0.41, 1.30) among non-users to 5.09 (1.20, 21.67) among users in the Southwest region, U.S. This effect modification was statistically significant on the multiplicative (P = 0.03) and additive scales, with an interaction contrast ratio (95% CI) of 1.64 (0.26, 3.02). CONCLUSION: No significant interaction was found for the maternal use of thermoregulation-related medications with EHEs on CHDs in general, while medications altering central thermoregulation significantly modified the association between EHEs and CHDs in Southwest U.S. This finding deserves further research.

      5. Optimizing vocabulary instruction for preschool children
        Madsen KM, Peters-Sanders LA, Kelley ES, Barker RM, Seven Y, Olsen WL, Soto-Boykin X, Goldstein H.
        J Early Interv. 2022 .
        A cluster randomized design was used to investigate the effects of the Story Friends vocabulary curriculum on learning of 84 preschoolers in 24 classrooms who were at risk for language difficulties. Children in the treatment condition received explicit vocabulary instruction of 36 words during small-group storybook listening centers with extended practice opportunities in the classroom and at home. Children in the comparison condition were exposed to the same words in stories without explicit instruction or extended practice. Children (n = 16) with average or above language skills from six treatment classrooms were included to examine the impact of extended practice. Children at risk in treatment classrooms learned significantly more words (52%) than children at risk in comparison classrooms (12%). Children not at risk learned vocabulary equal to children at risk. A tiered approach to implementing Story Friends appears feasible for enhancing the vocabulary learning of preschoolers with and without language delays. © 2022 SAGE Publications.

      6. Investigating the quality of HIV rapid testing practices in public antenatal health care facilities, South Africa
        Nsibande DF, Woldesenbet SA, Puren A, Barron P, Maduna VI, Lombard C, Cheyip M, Mogashoa M, Pillay Y, Magasana V, Ramraj T, Kufa T, Kindra G, Goga A, Chirinda W.
        PLoS One. 2022 ;17(8):e0268687.
        Monitoring HIV prevalence using antenatal HIV sentinel surveillance is important for efficient epidemic tracking, programme planning and resource allocation. HIV sentinel surveillance usually employs unlinked anonymous HIV testing which raises ethical, epidemiological and public health challenges in the current era of universal test and treat. The World Health Organization (WHO) recommends that countries should consider using routine prevention of mother-to-child transmission of HIV (PMTCT) data for surveillance. We audited antenatal care clinics to assess the quality of HIV rapid testing practices as the first step to assess whether South Africa is ready to utilize PMTCT programme data for antenatal HIV surveillance. In 2017, we conducted a cross-sectional survey in 360 randomly sampled antenatal care clinics using the adapted WHO Stepwise-Process-for-Improving-the-Quality-of-HIV-Rapid-Testing (SPI-RT) checklist. We calculated median percentage scores within a domain (domain-specific median score), and across all domains (overall median percentage scores). The latter was used to classify sites according to five implementation levels; (from 0:<40% to 4: 90% or higher). Of 346 (96.1%) facilities assessed, an overall median percentage score of 62.1% (inter-quartile range (IQR): 50.8-71.9%) was obtained. The lowest domain-specific median percentage scores were obtained under training/certification (35% IQR: 10.0-50.0%) and external quality assurance (12.5% IQR: 0.0-50.0%), respectively. The majority (89%) of sites had an overall median score at level 2 or below; of these, 37% required improvement in specific areas and 6.4% in all areas. Facilities in districts implementing the HIV Rapid Test Quality Improvement Initiative and supported by the President's Emergency Plan for AIDS Relief (PEPFAR) had significantly higher median overall scores (65.6% IQR: 53.9-74.2%) (P-value from rank sum test: <0.001) compared with non-PEPFAR-supported facilities (56.6% IQR:47.7-66.0%). We found sub-optimal implementation of HIV rapid testing practices. We recommend the expansion of the PEPFAR-funded Rapid Test Continuous Quality Improvement (RTCQI) support to all antenatal care testing sites.

    • Nutritional Sciences
      1. BACKGROUND: High energy intake from non-nutrient dense sources correlates with poorer diet quality. OBJECTIVES: To, 1) estimate total energy intake, and energy from solid fats and added sugars, and combined (SOFAS), and identify their top food category sources for ages 2-18 years in 2015-2018, and 2) describe trends over time in 2009-2018. DESIGN: Data were from the National Health and Nutrition Examination Survey. Pairwise differences were examined using univariate t statistics (2015-2018, n=5,038), and trends by age, and over time (2009-2018, n=14,038) examined using orthogonal polynomials. RESULTS: In 2015-2018, SOFAS contributed (mean [SE], 30.0% [0.3%]) of total energy. Solid fats 16.1% [0.2%] and added sugars 13.8% [0.2%] each contributed >10%. The contribution of added sugars increased with age from 11.1% (2-3 years) to 14.4% (14-18 years), and was higher for all other race/Hispanic origins than Non-Hispanic Asians. Top five sources of energy were sweet bakery products, savory snacks, pizza, other mixed dishes, and unflavored milk, and for SOFAS also included soft drinks, other desserts, candy and snack bars. Total energy did not change between 2009-2018, but energy from SOFAS, and servings of solid fats, and added sugars declined. The contribution of unflavored milk to total energy declined for all ages and most race/Hispanic origins. Fruit drinks (all ages) and soft drinks (9-18 years) remained among top added sugars sources despite declines. The contribution of sweet bakery products to energy from SOFAS increased for most ages, and candy and snack bars to energy from added sugars. CONCLUSIONS: In 2015-2018, SOFAS contributed over 30% of total energy for ages 2-18 years, which doubled the Dietary Guidelines for Americans' recommended limit of 15%. Top five sources of total energy were similar to those of solid fats, and those of SOFAs similar to those of added sugars. These results may inform public health efforts for improving diet quality.

    • Occupational Safety and Health
      1. Decrements in lung function and respiratory abnormalities associated with exposure to diacetyl and 2,3-pentanedione in coffee production workers
        Virji MA, Fechter-Leggett ED, Groth CP, Liang X, Blackley BH, Stanton ML, LeBouf RF, Harvey RR, Bailey RL, Cummings KJ, Cox-Ganser JM.
        Front Public Health. 2022 ;10:966374.
        Coffee production workers are exposed to complex mixtures of gases, dust, and vapors, including the known respiratory toxins, diacetyl, and 2,3-pentanedione, which occur naturally during coffee roasting and are also present in flavorings used to flavor coffee. This study evaluated the associations of these two α-diketones with lung function measures in coffee production workers. Workers completed questionnaires, and their lung function was assessed by spirometry and impulse oscillometry (IOS). Personal exposures to diacetyl, 2,3-pentanedione, and their sum (Sum(DA+PD)) were assigned to participants, and metrics of the highest 95th percentile (P95), cumulative, and average exposure were calculated. Linear and logistic regression models for continuous and binary/polytomous outcomes, respectively, were used to explore exposure-response relationships adjusting for age, body mass index, tenure, height, sex, smoking status, race, or allergic status. Decrements in percent predicted forced expiratory volume in 1 second (ppFEV(1)) and forced vital capacity (ppFVC) were associated with the highest-P95 exposures to 2,3-pentanedione and Sum(DA+PD). Among flavoring workers, larger decrements in ppFEV(1) and ppFVC were associated with highest-P95 exposures to diacetyl, 2,3-pentanedione, and Sum(DA+PD). Abnormal FEV(1), FVC, and restrictive spirometric patterns were associated with the highest-P95, cumulative, and average exposures for all α-diketone metrics; some of these associations were also present among flavoring and non-flavoring workers. The combined category of small and peripheral airways plus small and large airways abnormalities on IOS had elevated odds for highest-P95 exposure to α-diketones. These results may be affected by the small sample size, few cases of abnormal spirometry, and the healthy worker effect. Associations between lung function abnormalities and exposure to α-diketones suggest it may be prudent to consider exposure controls in both flavoring and non-flavoring settings.

      2. Automated crude oil vapor inhalation exposure system
        McKinney W, Jackson MC, Law B, Fedan JS.
        Inhal Toxicol. 2022 Aug 25:1-10.
        Objective: Inhalation exposure systems are tools for delivering compounds (particles, vapors, and gases) under well-controlled conditions for toxicological testing. The objective of this project was to develop an automated computer-controlled system to expose small laboratory animals to precise concentrations of crude oil vapor (COV).Materials and Methods: Vapor from heated Deepwater Horizon surrogate oil was atomized into a fine mist then diluted with filtered air, then the air/droplet mixture was routed into an evaporation column with an high efficiency particulate air (HEPA) filter on its exit port. The HEPA filter was used to remove oil particles, thus ensuring only vapor would pass. The vapor was then introduced into a custom-built exposure chamber housing rats. A calibrated flame ionization detector was used to read the total volatile organic compounds (TVOC) in real time, and custom software was developed to automatically adjust the amount of oil entering the atomizer with a syringe pump. The software also controlled relative humidity and pressure inside the exposure chamber. Other exposure chamber environmental parameters, e.g. temperature and CO(2) levels, were monitored. Four specific components within the COV were monitored during each exposure: benzene, toluene, ethylbenzene, and xylenes.Results: The TVOC vapor concentration control algorithm maintained median concentrations to within ±2 ppm of the target concentration (300 ppm) of TVOC during exposures lasting 6 h. The system could reach 90% of the desired target in less than 15 min, and repeat exposures were consistent and reproducible.Conclusion: This exposure system provided a highly automated tool for conducting COV inhalation toxicology studies.

      3. Temporary and permanent auditory effects associated with occupational coexposure to low levels of noise and solvents
        Bohn V, Morata TC, Roggia S, Zucki F, Pouyatos B, Venet T, Krieg E, José MR, de Lacerda AB.
        Int J Environ Res Public Health. 2022 Aug 11;19(16).
        This study aimed to assess temporary and permanent auditory effects associated with occupational coexposure to low levels of noise and solvents. Cross-sectional study with 25 printing industry workers simultaneously exposed to low noise (&lt;80 dBA TWA) and low levels of solvents. The control group consisted of 29 industry workers without the selected exposures. Participants answered a questionnaire and underwent auditory tests. Auditory fatigue was measured by comparing the acoustic reflex threshold before and after the workday. Workers coexposed to solvents and noise showed significantly worse results in auditory tests in comparison with the participants in the control group. Auditory brainstem response results showed differences in III-V interpeak intervals (p = 0.046 in right ear; p = 0.039 in left ear). Mean dichotic digits scores (exposed = 89.5 ± 13.33; controls = 96.40 ± 4.46) were only different in the left ear (p = 0.054). The comparison of pre and postacoustic reflex testing indicated mean differences (p = 0.032) between the exposed (4.58 ± 6.8) and controls (0 ± 4.62) groups. This study provides evidence of a possible temporary effect (hearing fatigue) at the level of the acoustic reflex of the stapedius muscle. The permanent effects were identified mainly at the level of the high brainstem and in the auditory ability of binaural integration.

      4. Introduction: Using crew scheduling and injury incident data from a Fortune 500 manufacturing company, this study analyzed the effect of consecutive shifts and shifts near holidays on near misses and incidents. Methods: Logistic regressions were conducted with consecutive workdays, days near holidays, and time of shift as predictors of incident and near miss outcomes. Results: The logistic regression analysis indicated that working consecutive day shifts increases the probability of an incident occurring, with the fourth consecutive shift resulting in the most risk. The consecutive shift pattern did not replicate to employees working the night shift. However, the first and second shifts when transferring to a night schedule appear to have a greater chance of incident. Shifts near holidays did not have a significantly higher risk than other shifts. Practical application: The current research suggests that organizations can use similar analytic techniques to determine if shift scheduling might be related to increased risk and allocate resources to mitigate hazards during those peak probability shifts. © 2022 National Safety Council and Elsevier Ltd

      5. Notes from the field: Coccidioidomycosis outbreak among wildland firefighters - California, 2021
        Donnelly MA, Maffei D, Sondermeyer Cooksey GL, Ferguson TJ, Jain S, Vugia D, Materna BL, Kamali A.
        MMWR Morb Mortal Wkly Rep. 2022 Aug 26;71(34):1095-1096.

    • Parasitic Diseases
      1. Efficacy of artemether-lumefantrine and dihydroartemisinin-piperaquine for the treatment of uncomplicated plasmodium falciparum malaria among children in Western Kenya, 2016 to 2017
        Westercamp N, Owidhi M, Otieno K, Chebore W, Buff AM, Desai M, Kariuki S, Samuels AM.
        Antimicrob Agents Chemother. 2022 Aug 29:e0020722.
        Antimalarial resistance threatens global malaria control efforts. The World Health Organization (WHO) recommends routine antimalarial efficacy monitoring through a standardized therapeutic efficacy study (TES) protocol. From June 2016 to March 2017, children with uncomplicated P. falciparum mono-infection in Siaya County, Kenya were enrolled into a standardized TES and randomized (1:1 ratio) to a 3-day course of artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DP). Efficacy outcomes were measured at 28 and 42 days. A total of 340 children were enrolled. All but one child cleared parasites by day 3. PCR-corrected adequate clinical and parasitological response (ACPR) was 88.5% (95% CI: 80.9 to 93.3%) at day 28 for AL and 93.0% (95% CI: 86.9 to 96.4%) at day 42 for DP. There were 9.6 times (95% CI: 3.4 to 27.2) more reinfections in the AL arm compared to the DP arm at day 28, and 3.1 times (95% CI: 1.9 to 4.9) more reinfections at day 42. Both AL and DP were efficacious (per WHO 90% cutoff in the confidence interval) and well tolerated for the treatment of uncomplicated malaria in western Kenya, but AL efficacy appears to be waning. Further efficacy monitoring for AL, including pharmacokinetic studies, is recommended.

      2. INTRODUCTION: Malaria is a major public health burden in developing countries despite efforts made by several countries. This disease leads to high morbidity and mortality among Rwandans, particularly in the Southern Province where it was the sixth national cause of morality; at Munini hospital it is the first cause of mortality, but the associated factors remain unknown. In this study, we determined the factors associated with deaths among patients with severe malaria to come up with evidence-based interventions to prevent malaria and its factors. METHODS: A retrospective cross-sectional study was conducted on malaria patients who were treated at the Munini District Hospital from 2016 to 2017. Data were collected from the hospital records or registers relating to patients who were admitted with severe malaria. The odds ratio was estimated by bivariate logistic regression and multivariate hierarchical regression models for determining the associated factors of deaths. Data were analyzed using STATA/MP Version 14.1 and Epi-info with proportions. RESULTS: The study population were mostly women (n = 237, 59.1%), farmers (n = 313, 78.05%), aged 16-30 years (n = 107, 26.68%). Our results indicated that the majority of deaths were women (56.25%). Socio-economic and clinical determinants are important predictors of death among patients with severe malaria. Patients with coma had higher odds of dying (AOR = 7.31, 95% CI :3.33-16.1, p < 0.001) than those who were not. The possibility of mortality increased by almost four times in patients who delayed consultation by a day (AOR = 3.7, 95%CI:1.8-4.1; p < 0.001) compared to those who came in very early. Patients who had severe malaria in the dry season were at a lower risk of mortality (AOR = 0.23, 95%CI:0.08-0.64, p = 0.005) compared to those with severe malaria during the rainy season. CONCLUSION: Lack of health insurance, age of the patient, delayed diagnosis, coma, proximity and access to healthcare services, and weather conditions were the major factors associated with mortality among patients with severe malaria. Comprehensive, long-term, equity-based healthcare interventions and immediate care strategies are recommended.

      3. BACKGROUND: Primaquine is essential for the radical cure of Plasmodium vivax malaria, but it poses a potential danger of severe hemolysis in G6PD-deficient (G6PDd) patients. This study aimed to determine whether primaquine is safe in a population with high G6PD prevalence but lacking G6PD diagnosis capacity. METHODS: In Myanmar, 152 vivax patients were gender- and age-matched at 1:3 for G6PDd versus G6PD-normal (G6PDn). Their risk of acute hemolysis was followed for 28 days after treatment with the standard chloroquine and 14-day primaquine (0.25 mg/kg/day) regimen. RESULTS: Patients anemic and non-anemic at enrollment showed a rising and declining trend in the mean hemoglobin level, respectively. In males, the G6PDd group showed substantially larger magnitudes of hemoglobin reduction and lower hemoglobin nadir levels than the G6PDn group, but this trend was not evident in females. Almost 1/3 of the patients experienced clinically concerning declines in hemoglobin, with five requiring blood transfusion. CONCLUSIONS: The standard 14-day primaquine regimen carries a significant risk of acute hemolytic anemia (AHA) in vivax patients without G6PD testing in a population with a high prevalence of G6PD deficiency and anemia. G6PD testing would avoid most of the clinically significant Hb reductions and AHA in male patients.

    • Public Health Leadership and Management
      1. Lessons learned for public health workforce development: An evaluation of the Centers For Disease Control And Prevention's Laboratory Leadership Service Fellowship
        McColloch C, Davis M, Araujo A, Theodore S, Barkley J, Paek M, Henning T.
        Eval Program Plann. 2022 Aug 13;95:102147.
        The Centers for Disease Control and Prevention launched the Laboratory Leadership Service (LLS) Fellowship Program in July 2015 to develop public health laboratory (PHL) leaders who will improve PHL quality and safety. This article describes a retrospective, summative evaluation to determine the extent to which LLS has met its short-term goals for PHL workforce development. The evaluation relied on existing data from routine LLS data collection and reporting, supplemented with a new alumni survey. The purpose of the design was threefold: 1) to reduce data collection burden on program staff and participants, 2) to assess the value and limits of routine fellowship data for comprehensive public health workforce development program evaluation, and 3) to identify ways to improve LLS's routine data collections for program evaluation. We used descriptive statistics, qualitative analysis, and participatory methods (i.e., a data party) to analyze and interpret data. Results show LLS short-term outcome achievement and highlight opportunities for program improvement, particularly related to the design of certain training requirements and for future evaluations. Overall, the evaluation contributes to lessons learned for PHL workforce development efforts, including how routine data collections can contribute to comprehensive public health workforce development evaluations.

      2. Uganda National Institute of Public Health: Establishment and experiences, 2013-2021
        Ario AR, Makumbi I, Kadobera D, Bulage L, Ocom F, Kwesiga B, Jarvis DF, Nabatanzi S, Homsy J, Banage F, Brown V, Harris JR, Boore AL, Nelson LJ, Binder S, Mwebesa HG, Aceng JR.
        Glob Health Sci Pract. 2022 Aug 30;10(4).
        Uganda is an ecological hot spot with porous borders that lies in several infectious disease transmission belts, making it prone to disease outbreaks. To prepare and respond to these public health threats and emergencies in a coordinated manner, Uganda established the Uganda National Institute of Public Health (UNIPH) in 2013.Using a step-by-step process, Uganda's Ministry of Health (MOH) crafted a strategy with a vision, mission, goal, and strategic objectives, and identified value additions and key enablers for success. A regulatory impact assessment was then conducted to inform the drafting of principles of the bill for legislation on the Institute.Despite not yet attaining legal status, the UNIPH has already achieved faster, smarter, and more efficient and effective prevention, detection, and response to public health emergencies. Successes include a more coordinated multisectoral, disciplined, and organized response to emergencies; appropriate, timely, and complete information receipt and sharing; a functional national lab sample and results transportation network that has enabled detection and confirmation of public health events within 48 hours of alert; appropriate response to a confirmed public health event in 24-48 hours; and real-time surveillance of endemic- and epidemic-prone diseases.In this article, we document success stories, lessons learned, and challenges encountered during the unique staged process used to develop the components of the UNIPH. The creation of an integrated disease control center has proven to yield better collaboration and synergies between different arms of epidemic preparedness and response.

    • Substance Use and Abuse
      1. Kratom use categories and their associations with co-occurring substance use and mental health disorder symptoms during the COVID-19 pandemic
        Adzrago D, Obekpa EO, Suragh TA, John ER, Yeh PG, Gallardo KR, Wilkerson JM.
        Drug Alcohol Depend. 2022 Aug 19;239:109605.
        BACKGROUND: Kratom, a psychoactive substance, use is an evolving research area that needs more studies to augment the limited literature. Our study examines the association between kratom use categories and mental health and substance use disorders in the U.S. METHODS: We used the 2020 National Survey on Drug Use and Health data (N = 32,893), a cross-sectional survey data, on the U.S. population aged 12 years or older. We used STATA/SE version 16 to perform a multinomial logistic regression analysis to assess our study aims. RESULTS: Bisexuals, compared to heterosexuals, had higher risks of kratom use within the past 30 days (relative risk ratio [RRR]= 2.47, 95% CI= 1.07, 5.71). Major depressive episode was positively associated with kratom use more than 30 days ago (RRR= 2.04, 95% CI= 1.24, 3.34). This association was also observed for mild (RRR= 2.04, 95% CI= 1.38, 3.02), moderate (RRR= 2.25, 95% CI= 1.13, 4.51), or severe alcohol use disorder (RRR= 1.88, 95% CI= 1.05, 3.36); and mild (RRR= 1.98, 95% CI= 1.27, 3.11), moderate (RRR= 2.38, 95% CI= 1.27, 4.45), or severe marijuana use disorder (RRR= 2.13, 95% CI= 1.02, 4.47). Illicit drug other than marijuana use disorder was associated positively with kratom use more than 30 days ago (RRR= 2.81, 95% CI= 1.85, 4.26) and kratom use within the past 30 days (RRR= 5.48, 95% CI= 1.50, 20.02). CONCLUSIONS: Our findings suggested that identifying as bisexual, experiencing depression, alcohol use disorder, or illicit drug use disorder increased the risks of kratom use. There is a need to consider mental health and substance use disorders and sexual identity in kratom use interventions and policies geared toward reducing or preventing kratom use.

      2. Project ECHO interprofessional telementoring: Using a novel case-based approach for building the U.S Public Health Service clinical response in pain and substance use disorder
        Katzman JG, Bhatt S, Krishnasamy V, Mells LC, Rubel S, Tomedi L, Jacobsohn VC, Groves CR, Neubert CP.
        J Interprof Educ Pract. 2022 ;29.
        Background: The opioid overdose crisis is a US public health emergency that caused over an estimated 93,000 deaths in 2020. To build the clinical capacity of the Commissioned Corps of the US Public Health Service (USPHS), the US Centers for Disease Control and Prevention and Prevention (CDC) collaborated with Project ECHO in pain and substance use disorder (SUD). Purpose: The purpose of this article is to describe the evaluation results of an interprofessional telementoring program using novel clinical vignettes. Method: Interprofessional Project ECHO Pain faculty and the CDC recruited a diverse group of 163 USPHS clinical officers to join one (of two) 16-week, hour-long ECHO Opioid and Pain (OP) telementoring sessions. The structured curriculum included chronic pain, substance use, harm reduction and mental health-related didactics, as well as novel clinical vignettes. Discussion: During this OP telementoring training, novel clinical vignettes were used successfully to train USPHS officers in an interprofessional “all-teach, all-learn” team-based, interdisciplinary learning environment. Over 30% (n = 48) of the USPHS officers attended at least 9 of the 16 sessions. Cohort surveys demonstrated that participants (n = 26) self-reported significantly increased knowledge regarding chronic pain, SUD, and mental health issues when compared to baseline. Focus group participants (n = 41) noted increased self-efficacy in clinical skills and compassion regarding patient care. Conclusion: This interprofessional ECHO training using novel clinical vignettes demonstrates the potential to increase clinical response capacity in pain management and SUD treatment by improving both knowledge and self-efficacy among participants. © 2022

      3. Patient-level and county-level trends in nonfatal opioid-involved overdose emergency medical services encounters - 491 counties, United States, January 2018-March 2022
        Casillas SM, Pickens CM, Stokes EK, Walters J, Vivolo-Kantor A.
        MMWR Morb Mortal Wkly Rep. 2022 Aug 26;71(34):1073-1080.
        The number of nonfatal opioid-involved overdoses treated by health care providers has risen in the United States; the median number of emergency department (ED) visits for these overdoses was significantly higher during 2020 than during 2019 (1). ED visit data can underestimate nonfatal opioid-involved overdose incidence because, increasingly, persons experiencing a nonfatal opioid overdose are refusing transport to EDs by emergency medical services (EMS) (2). A study in Kentucky found that during a 6-month period, 19.8% of persons treated by EMS for an opioid overdose refused transport to an ED (2). Thus, EMS encounter data involving suspected nonfatal opioid-involved overdoses complement ED data and also allow for near real-time analysis (3). This report describes trends in rates of EMS encounters for nonfatal opioid-involved overdoses per 10,000 total EMS encounters (rates) by selected patient- and county-level characteristics during January 2018–March 2022 in 491 counties from 21 states using data from biospatial, Inc.* During this period, the nonfatal opioid-involved overdose rate increased, on average, 4.0% quarterly. Rates increased for both sexes and for most age groups. Rates were highest among non-Hispanic White (White) and non-Hispanic Native Hawaiian or other Pacific Islander (NH/OPI) persons, and increases were largest among non-Hispanic Black (Black), followed by Hispanic or Latino (Hispanic) persons. Rates increased in both urban and rural counties and for all quartiles of county-level characteristics (i.e., unemployment, education, and uninsured), except in counties with the lowest percentage of uninsured persons. Rates were highest and rate increases were largest in urban counties and counties with higher unemployment rates. This analysis of nonfatal opioid-involved overdose trends in EMS data highlights the utility of these data and the importance of addressing inequities that contribute to disproportionate overdose risk, such as through focused outreach to racial and ethnic minority groups, who disproportionately experience these inequities, and communities with higher levels of unemployment. EMS providers are in a unique position to engage in postoverdose response protocols and promote evidence-based overdose education and facilitate linkage to care and harm reduction services.†,§

      4. Background: Economic theory predicts that the excise tax structure influences the distribution of cigarette prices. Evidence shows that uniform specific excise tax structures exhibit the least price variability relative to other tax structures. The distribution of cigarette prices under different excise tax structures has never been examined for a group of African countries. Objectives: To examine the distribution of cigarette prices under different tax structures in nine African countries and to critically evaluate the effectiveness of African regional tax directives in promoting public health. Methods: Data from the Global Adult Tobacco Survey, conducted in eight African countries during 2012-2018, and data from the 2017 Gambia Tobacco Survey were used to construct survey-derived cigarette prices. The coefficients of variation and skewness of the price distribution were compared in the context of each country's cigarette excise tax structure. Results: The least price variability is found in countries with a uniform specific tax, or a mixed system with a minimum specific floor. Cigarette price variability is largest in countries with uniform ad valorem tax structures. Three of the four countries with ad valorem tax structures are in regional blocs, where the tax directives specify that they should implement an ad valorem structure. Conclusions: Regional tax directives that require the adoption of uniform specific excise taxes, or high minimum specific floors, could be an efficient way to get multiple African countries to adopt a tax structure that reduces substitution possibilities in response to excise tax increases. © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

      5. Substance misuse and condomless sex among transgender youth
        Schlissel AC, Carpenter R, Avripas S, Heim Viox M, Johns MM, Harper C, Michaels S, Dunville R.
        Transgend Health. 2022 Aug;7(4):314-322.
        PURPOSE: The purpose of this research is to explore the relationship between substance use and sexual risk behaviors among transgender youth. METHODS: Data from the transgender subsample of the Survey of Today's Adolescent Relationships and Transitions (n=1567) were analyzed to assess associations between substance misuse (binge drinking, prescription drug misuse, illicit drugs) and sexual risk behaviors (condom use during sex). Multivariate logistic regression models calculated adjusted odds ratios (AORs) for substance use by sexual risk behavior controlling for race/ethnicity, gender identity (transgender male, transgender female, genderqueer/gender nonconforming), age, sexual identity, and region. RESULTS: Among participants, lifetime marijuana use (AOR=0.45), cocaine use (AOR=0.46), prescription drug misuse (AOR=0.52), and injecting substances with a needle (AOR=0.45) were all associated with lower odds of reporting condom use during the last act of receptive anal sex. Similarly, marijuana use in the last 30 days (AOR=0.46), lifetime marijuana use (AOR=0.25), heroin use (AOR=0.29), methamphetamine use (AOR=0.32), misuse of prescription drugs (AOR=0.40), and injecting substances with a needle (AOR=0.17) were all associated with lower odds of reporting condom use during the last act of insertive anal sex. No associations between substance use and condom use during last act of receptive frontal (vaginal) sex were found. CONCLUSION: We found that transgender youth who reported any lifetime substance use were more likely to report condomless sex during receptive and insertive anal sex than those who did not report substance use. Significant differences exist among demographic groups, type of substance use, and sexual risk behaviors for respondents based on gender identity.

    • Telehealth and Telemedicine
      1. Telehealth and public health practice in the United States-before, during, and after the COVID-19 pandemic
        Neri AJ, Whitfield GP, Umeakunne ET, Hall JE, DeFrances CJ, Shah AB, Sandhu PK, Demeke HB, Board AR, Iqbal NJ, Martinez K, Harris AM, Strona FV.
        J Public Health Manag Pract. 2022 Aug 27.
        Telehealth is the use of electronic information and telecommunication technologies to provide care when the patient and the provider are not in the same room at the same time. Telehealth accounted for less than 1% of all Medicare Fee-for-Service outpatient visits in the United States in 2019 but grew to account for 46% of all visits in April 2020. Changes in reimbursement and licensure policies during the COVID-19 pandemic appeared to greatly facilitate this increased use. Telehealth will continue to account for a substantial portion of care provided in the United States and globally. A better understanding of telehealth approaches and their evidence base by public health practitioners may help improve their ability to collaborate with health care organizations to improve population health. The article summarizes the Centers for Disease Control and Prevention's (CDC's) approach to understanding the evidence base for telehealth in public health practice, possible applications for telehealth in public health practice, and CDC's use of telehealth to improve population health.

      2. IMPORTANCE: Federal emergency authorities were invoked during the COVID-19 pandemic to expand use of telehealth for new and continued care, including provision of medications for opioid use disorder (MOUD). OBJECTIVE: To examine receipt of telehealth services, MOUD (methadone, buprenorphine, and extended-release [ER] naltrexone) receipt and retention, and medically treated overdose before and during the COVID-19 pandemic. DESIGN, SETTING, AND PARTICIPANTS: This exploratory longitudinal cohort study used data from the US Centers for Medicare & Medicaid Services from September 2018 to February 2021. Two cohorts (before COVID-19 pandemic from September 2018 to February 2020 and during COVID-19 pandemic from September 2019 to February 2021) of Medicare fee-for-service beneficiaries 18 years and older with an International Statistical Classification of Diseases, Tenth Revision, Clinical Modification OUD diagnosis. EXPOSURES: Pre-COVID-19 pandemic vs COVID-19 pandemic cohort demographic characteristics, medical and substance use, and psychiatric comorbidities. MAIN OUTCOMES AND MEASURES: Receipt and retention of MOUD, receipt of OUD and behavioral health-related telehealth services, and experiencing medically treated overdose. RESULTS: The pre-COVID-19 pandemic cohort comprised 105 240 beneficiaries; of these, 61 152 (58.1%) were female, 71 152 (67.6%) were aged 45 to 74 years, and 82 822 (79.5%) non-Hispanic White. The COVID-19 pandemic cohort comprised 70 538 beneficiaries; of these, 40 257 (57.1%) were female, 46 793 (66.3%) were aged 45 to 74 years, and 55 510 (79.7%) were non-Hispanic White. During the study period, a larger percentage of beneficiaries in the pandemic cohort compared with the prepandemic cohort received OUD-related telehealth services (13 829 [19.6%] vs 593 [0.6%]; P < .001), behavioral health-related telehealth services (28 902 [41.0%] vs 1967 [1.9%]; P < .001), and MOUD (8854 [12.6%] vs 11 360 [10.8%]; P < .001). The percentage experiencing a medically treated overdose during the study period was similar (18.5% [19 491 of 105 240] in the prepandemic cohort vs 18.4% [13 004 of 70 538] in the pandemic cohort; P = .65). Receipt of OUD-related telehealth services in the pandemic cohort was associated with increased odds of MOUD retention (adjusted odds ratio [aOR], 1.27; 95% CI, 1.14-1.41) and lower odds of medically treated overdose (aOR, 0.67; 95% CI, 0.63-0.71). Among beneficiaries in the pandemic cohort, those receiving MOUD from opioid treatment programs only (aOR, 0.54; 95% CI, 0.47-0.63) and those receiving buprenorphine from pharmacies only (aOR, 0.91; 95% CI, 0.84-0.98) had lower odds of medically treated overdose compared with beneficiaries who did not receive MOUD. CONCLUSIONS AND RELEVANCE: Emergency authorities to expand use of telehealth and provide flexibilities for MOUD provision during the pandemic were used by Medicare beneficiaries initiating an episode of OUD-related care and were associated with improved retention in care and reduced odds of medically treated overdose. Strategies to expand provision of MOUD and increase retention in care are urgently needed.

    • Veterinary Medicine
      1. Coccidioidomycosis is a disease caused by the dimorphic fungi Coccidioides spp., which affects humans and a variety of animal species, including domestic dogs. In dogs, accurate diagnosis could provide a substantial improvement on the quality of canine life, as well as an advancement in the mapping of regions endemic for coccidioidomycosis. The purpose of this study was to compare immunodiagnostic assays for anti-Coccidioides antibody (Ab) detection in dogs' serum. Three commercially available immunodiagnostic assays (IMMY(®); Norman, OK, USA) were evaluated, including the sōna Coccidioides Ab Lateral Flow Assay (LFA), Coccidioides IDCF immunodiffusion assay (IDCF), and the Clarus Coccidioides Ab Enzyme Immunoassay (EIA). Assays were evaluated using 98 dog serum samples: 29 from dogs with coccidioidomycosis, 15 from dogs diagnosed with histoplasmosis, 10 from dogs diagnosed with blastomycosis, and 44 from dogs without a fungal disease. Using specimens from dogs with coccidioidomycosis, the IDCF had an accuracy of 92% (95% confidence interval [95% CI] = 85-96%), the EIA had an accuracy of 91% (95% CI = 83-96%), and the LFA displayed an accuracy of 82% (95% CI = 73-89%). Using Kappa analysis, the agreement between LFA and EIA was 0.59 (95% CI = 0.42-0.75), that between LFA and IDCF was 0.64 (95% CI = 0.48-0.79), and that between EIA and IDCF was 0.79 (95% CI = 0.64-0.90). Most cross-reactions were observed in dogs with histoplasmosis. Compared with EIA and IDCF, the LFA requires substantially less laboratory equipment and infrastructure and rapidly produces results, offering a substantial improvement for the initial screening of coccidioidomycosis in dogs.

      2. Review of CDC's suspension of and advance written approval process for dogs entering the United States from Egypt - May 2019-December 2020
        Latzer M, Pieracci EG, Altenburger A, Stauffer KE, Brown CM.
        MMWR Morb Mortal Wkly Rep. 2022 Aug 26;71(34):1081-1084.
        Dog-maintained rabies virus variant (DMRVV) was eliminated in the United States in 2007. During 2015–2019, three dogs with rabies were imported into the United States from Egypt, where DMRVV is endemic. CDC developed a risk mitigation strategy, in consultation with a diverse group of subject matter experts, that permitted 296 dogs to be imported from Egypt during May 10, 2019–December 31, 2020, minimizing the risk for future rabid dog importations. The broadly vetted risk mitigation strategy, which included serologic testing for rabies antibody titer, improved CDC’s ability to ensure that imported dogs from Egypt posed no public health risk in the United States. This strategy could be used to guide future policy decisions regarding dog importations.

    • Zoonotic and Vectorborne Diseases
      1. Salmonella typhimurium outbreak associated with exposure to pet hedgehogs, 2017-2020
        Fagan-Garcia K, Denich L, Tataryn J, Janicki R, Osch Ov, Kearney A, Misfeldt C, Nadon C, Gaulin C, Mah V, Raminderjeet S, Waltenburg M, Bijay A, Hanan S, Lowe AM.
        Can Commun Dis Rep. 2022 ;48(6):282-290.
        Background: In October 2020, an investigation began in Canada on an outbreak of Salmonella Typhimurium infections of the same strain as a concomitant outbreak in the United States (US) that was linked to pet hedgehogs. The objective of this article is to identify the source of the outbreak, determine if there was a link between the Canadian and US outbreaks and identify risk factors for infection to inform public health interventions.

      2. A recombinant rabies vaccine that prevents viral shedding in rabid common vampire bats (Desmodus rotundus)
        Cárdenas-Canales EM, Velasco-Villa A, Ellison JA, Satheshkumar PS, Osorio JE, Rocke TE.
        PLoS Negl Trop Dis. 2022 Aug 26;16(8):e0010699.
        Vampire bat transmitted rabies (VBR) is a continuing burden to public health and agricultural sectors in Latin America, despite decades-long efforts to control the disease by culling bat populations. Culling has been shown to disperse bats, leading to an increased spread of rabies. Thus, non-lethal strategies to control VBR, such as vaccination, are desired. Here, we evaluated the safety and efficacy of a viral-vectored recombinant mosaic glycoprotein rabies vaccine candidate (RCN-MoG) in vampire bats (Desmodus rotundus) of unknown history of rabies exposure captured in México and transported to the United States. Vaccination with RCN-MoG was demonstrated to be safe, even in pregnant females, as no evidence of lesions or adverse effects were observed. We detected rabies neutralizing antibodies in 28% (8/29) of seronegative bats post-vaccination. Survival proportions of adult bats after rabies virus (RABV) challenge ranged from 55-100% and were not significantly different among treatments, pre- or post-vaccination serostatus, and route of vaccination, while eight pups (1-2.5 months of age) used as naïve controls all succumbed to challenge (P<0.0001). Importantly, we found that vaccination with RCN-MoG appeared to block viral shedding, even when infection proved lethal. Using real-time PCR, we did not detect RABV nucleic acid in the saliva samples of 9/10 vaccinated bats that succumbed to rabies after challenge (one was inconclusive). In contrast, RABV nucleic acid was detected in saliva samples from 71% of unvaccinated bats (10/14 sampled, plus one inconclusive) that died of the disease, including pups. Low seroconversion rates post-vaccination and high survival of non-vaccinated bats, perhaps due to earlier natural exposure, limited our conclusions regarding vaccine efficacy. However, our findings suggest a potential transmission-blocking effect of vaccination with RCN-MoG that could provide a promising strategy for controlling VBR in Latin America beyond longstanding culling programs.

      3. Outbreak of Middle East Respiratory Syndrome Coronavirus in camels and probable spillover infection to humans in Kenya
        Ngere I, Hunsperger EA, Tong S, Oyugi J, Jaoko W, Harcourt JL, Thornburg NJ, Oyas H, Muturi M, Osoro EM, Gachohi J, Ombok C, Dawa J, Tao Y, Zhang J, Mwasi L, Ochieng C, Mwatondo A, Bodha B, Langat D, Herman-Roloff A, Njenga MK, Widdowson MA, Munyua PM.
        Viruses. 2022 Aug 9;14(8).
        The majority of Kenya's &gt; 3 million camels have antibodies against Middle East respiratory syndrome coronavirus (MERS-CoV), although human infection in Africa is rare. We enrolled 243 camels aged 0-24 months from 33 homesteads in Northern Kenya and followed them between April 2018 to March 2020. We collected and tested camel nasal swabs for MERS-CoV RNA by RT-PCR followed by virus isolation and whole genome sequencing of positive samples. We also documented illnesses (respiratory or other) among the camels. Human camel handlers were also swabbed, screened for respiratory signs, and samples were tested for MERS-CoV by RT-PCR. We recorded 68 illnesses among 58 camels, of which 76.5% (52/68) were respiratory signs and the majority of illnesses (73.5% or 50/68) were recorded in 2019. Overall, 124/4692 (2.6%) camel swabs collected from 83 (34.2%) calves in 15 (45.5%) homesteads between April-September 2019 screened positive, while 22 calves (26.5%) recorded reinfections (second positive swab following ≥ 2 consecutive negative tests). Sequencing revealed a distinct Clade C2 virus that lacked the signature ORF4b deletions of other Clade C viruses. Three previously reported human PCR positive cases clustered with the camel infections in time and place, strongly suggesting sporadic transmission to humans during intense camel outbreaks in Northern Kenya.


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